THE BOMBAY BACTERIOLOGICAL LABORATORY* THE PREPARATION AND USE OF ANTI-PLAGUE VACCINE* BOMBAY: PRINTED AT THE TIMES PRESS. 1907. Introduction. The Bombay Bacteriological Laboratory has had a short, though eventful, history. Originally started by Mr. Haffkine, the discoverer of anti-plague vaccine, on the 8th October 1896, a fortnight after plague had been officially declared to exist in Bombay the Laboratory has grown from a small institution to one of considerable dimensions. For long the Laboratory was known as the Plague Research Laboratory, but recently the name has been changed to the Bombay Bacteriological Labo- ratory, thus indicating the wider field of investigation and research which is now undertaken at this institution. While the Laboratory functions as a general research institute for the Bombay Presidency, plague research still remains its chief duty. Nor has the Laboratory played an unimportant part in the progress of our knowledge of plague. Mr. Haffkine here first elaborated and prepared his wonderful “ Plague Prophy- lactic, ” which has saved the lives of many thousands of human beings. Here, too, more recently the epoch-making discoveries in connection with the aetiology of plague were made by a Commission working on the facts and materials which had been accumulated after ten years of patient labour on the part of the staff of the Laboratory. These discoveries have given to sanitarians and administrators a firm foundation on which to build their schemes for combating and preventing the spread of plague. It is pleasing to know that while India has been sorely smitten by this fell disease, she has been the leader in advancing our knowledge of its cause and prevention, and that the Bombay Bacteriological Laboratory has played no small part in assisting her to attain this position. This pamphlet has been prepared for the use of those who are called upon to carry out measures for preventing the spread of plague in India. It has been written, as will be understood from what has been said above, aft er a prolonged and extensive experience of the disease now extending over ten years, the facts which it details, therefore, are put forward with some authority. when determining what Anti=Plague Measures to adopt. Plague may be defined as a rat disease ; not infrequently, . under favourable circumstances, it is communicated to man, generally by rat fleas. The disease among men might almost ! be said to be accidental, and certainly avoidable, if there were . a distance between rats and men. The association of men with rats is dependent partly on the mode of living of the for- mer and partly on the habits of the latter. If rats could be .got rid of, there would be no plague ; but if this is impossible, we have only two alternatives, —either to flee from the disease «. or to acquire protection against it by being inoculated with Haffkine’s vaccine. Anti-plague measures are of two kinds : (i) measures of permanent utility and (2) measures of temporary utility. (1) Measures of permanent utility are directed against those habits of rats and men which bring about the association of ;the one with the other. They deal with the erection of well- built houses, the separation of shops, warehouses, granaries, aand stables from human habitations ; the construction of con- crete floors and roofs of materials which cannot harbour rats. These measures affect the habits of rats. Measures which are .directed to improve the habits of men are such as teach him ' to live in a tidy manner, which prevent him from throwing waste food material out of the window of his dwelling or plac- ing it in any other place where it may be reached by rats. All these are measures of permanent utility in the fight against plague, but unfortunately such measures will take many years to carry out to completion ; nevertheless, in the meantime, they should not be neglected. (2) Measures of temporary utility can be grouped under the ! following three heads :—(a) Measures for protecting the people I in their homes from rats and their parasites ; such measures can be classed under the term ‘ Rat destruction.’ (b) Measures for removing the people from their homes in order that they may avoid infection from rats and their parasites, measures which are recognised under the term ‘ Evacuation.’ (c) Measures rendering the individual largely immune from attack and death from plague, measures classed under the term ‘ Inoculation.’ Let us consider for a moment the advantages and disad- vantages of each of these measures for dealing with plague. In the first place it should be noted that all these measures require to be carried out repeatedly ; they are only temporary measures. In this respect rat destruction and evacuation possess no advantage over inoculation. While, however, the first two measures can be carried out by the people themselves, the latter requires the employment of a special staff. (a) But to take each measure separately, let us consider first the advantages of rat destruction. Undoubtedly, if there were no rats there would be no plague. This measure strikes at the root of the evil, and has the great advantage that it interferes little with human comfort. Indians who have experienced a temporary freedom from rats have recognised the advantages of living without these pests, their absence insures less disturbance at night and less injury and loss of property. The disadvantage of rat destruction lies in the fact that to be successful this measure must have the complete co-operation of an entire community and the operations must be extensive and sustained. The poisoning of rats either by the use of chemical poisons or by the dissemination of bacterial disease among them has not proved as successful as was anticipated. No more efficient rat destroyer than plague itself has yet been discovered. The failure to keep down rats by poisoning them arises from the fact that the operations have, as a rule, only been temporarily carried out and can never be persistently maintained except at great cost. Trapping rats alive and then destroying them has yielded better results when daily practised. At least one trap for every 50 inhabitants in a town or village should be set every day. The rat infestation of Indian towns and villages is enormous. Rats are so prolific that it is possible to remove from a village, within a period of one year, a larger number of them than the total human population of the place without materially affecting the number of rats remaining alive in the village. In a village of, say, 2,000 inhabitants nothing less than 2,500 rats should be captured and destroyed within a period of one year if it is desired to effect a check on the spread of plague. The removal of any smaller number will do more harm than good, for, by removing adult immune rats which have sur- vived from previous epidemics and permitting their replace- ment by young susceptible rats, the disease among these animals will be more extensive and virulent, so that the epidemic among men will be proportionately more severe. (6) Evacuation to be effective must be carried out early and completely. It is generally useless to vacate a house after a death from plague has occurred in it. Even when evacuation is not practised, only 20 to 30 % of houses yield more than one case. In towns, especially, it must be remembered that infec- tion is frequently not acquired at home but in the workshop, office, or other place of resort. The greatest disadvantage of evacuation, however, arises from the increased chances of spreading the disease. Many prefer to go to live with friends in uninfected villages rather than submit to the discomforts of camp life. Infection is thus distributed, for man is an import- ant carrier of the infection. Evacuation too tends to increase the panic produced by the high mortality associated with the disease. (c) The advantage of inoculation lies in the fact that it is a measure of personal prophylaxis. It matters little who else does or does not co-operate in the measure, those inoculated at least are safe. It is a measure which can be easily and cheaply carried out once a year. A guarantee can be given that at least six times the saving of life will be effected among the inoculated as compared with the uninoculated. When in- oculation is more extensively adopted, an even greater saving of life may be obtained. Every case which is saved from the disease affords many less opportunities for the disease being imported into fresh localities by friends who would have come from other towns and villages to attend the funeral ceremonies. Moreover, inoculation instils into those who undergo the oper- ation that confidence which is so necessary in averting a panic. When the majority in a village are inoculated, the epidemic assumes such moderate proportions that it can be dealt with easily and it is possible to adopt measures to prevent the spread of infection to adjoining areas. Inoculation checks the spread of plague, directly by lessening the number of attacks and reducing the mortality from the disease, and V indirectly by quelling panic and thus reducing the chances of importing the disease into uninfected places. What may be effected by Inoculation with Anti=Plague Vaccine. Like vaccination against small-pox, inoculation reduces the chances of plague attack in the inoculated ; and those who are attacked recover more frequently and more easily if they have been inoculated previously. During- an epidemic there are about three times fewer at- tacks of plague in the inoculated ; and among- plague patients the number of deaths in those who have underg-one inocula- tion, is about half as compared with the mortality amongst the uninoculated patients. The final result is that during- the prevalence of plague the number of deaths in the inoculated is about one-sixth that amongst the uninoculated living in the same infected locality. For instance, in a village of 4,000 inhabitants where plague was sufficiently virulent to attack three persons in every hundred of the inhabitants, and where half the population had been inoculated, we would expect to find the 2,000 uninoculated people yielding about 60 cases with 45 deaths, while the 2,000 inoculated would have some 20 cases with 7 deaths. Better results than these are secured when a proportion of the people greater than one-half is inoculated ; and if all are operated on, the epidemic assumes trifling proportions, is easily dealt with and creates no panic. The following examples of the benefit accruing from inocu- lation in a community which has been attacked by plague have not been selected as i.lustrating the best results obtained by this measure but because of the thoroughness with which the inquiry was conducted aftsr the disease had subsided and because of the carefully kept records which were available in each instance. The fitst example offers an illustration of the number of lives that may be saved in a village community. Experience in Villages- A very virulent epidemic of plague was raging in the village ot Undhera in the Baroda State. The village was visited and a nominal roll of the inhabitants then living in each household was made and as near as possible one half of the inhabitants in each household were inoculated. It was found that there were 950 persons then alive in the village and of these 513 were there and then inoculated. No selection was made as to who was or was not to be inoculated other than that required to make the two groups of inoculated and uninoculated as comparable as possible in regard to age, sex and physical fitness. Plague continued in the village for 42 days after the inoculations were performed and affected 28 families. These families were composed of 71 inoculated and 64 not inoculated persons. The 71 inoculated had 8 attacks with 3 deaths, while the 64 not inoculated had 27 attacks with 26 deaths. If the inoculated had suffered to the same extent as their uninoculated relatives, they should have had 29 deaths instead of 3 only. Colonel Bannerman, who with others investigated the results of this experiment, writes : “I myself carried the census lists, and from it called out the inhabitants of the plague-infected houses by name, and I shall never forget the experiences of that day. One incident I particularly remember, the finding in two huts in succession that all the uninoculated had died and that only the inoculated members of the household came out to answer to their names. The attitude of the people was also very striking, for, when asked about the results of the experi- ment, they said that ‘ about fifty uninoculated had been attacked and they are all dead, while only a few inoculated have been ill, and they have all recovered.’ ” Further details of this very carefully conducted experiment will be found in a pamphlet entitled “The Plague Prophy- lactic,” by Colonel Bannerman, I.M.S., and printed at Govern- ment Central Press, Bombay. Price 3 Annas. The following table compiled by Major E. Wilkinson, I.M.S., late Chief Plague Medical Officer in the Punjab, is of interest in this connection. The figures refer to all villages where 10 per cent, or more of the inhabitants had been inoculated and where plague was present or subsequently appeared not later than four months afterwards. Popu- lation. Attacks. Deaths. Case-incidence per cent. Case-mortality per cent. Inoculated... 186,797 3.399 S14 1*8 23-9 Not inocu- lated 639,630 49.433 29.723 77 6cm By a simple calculation one can readily estimate that in these villages inoculation saved some eight thousand lives. Experience in Towns- The next example selected illustrates what saving of life can be effected in a town. The figures refer to a single chall or large building in Bombay City known as No. 201 Cattle Lines, Pilot Bundar. In this chall there lived 61 persons in ten rooms. The rooms were separated from one another by io-foot partitions, but the roof space w’as common to all the rooms. Inoculations had been done among the people of this neigh- bourhood two months previous to the outbreak of plague in the chall. When the epidemic was over, an investigation was made and all the inhabitants of the chall traced with the ex- ception of four. Only one of these four had been inoculated and it was reported that none of them had been attacked by plague. The result was found to be as follows :—24 inoculat- ed persons had among them 1 attack and no death ; while 37 not inoculated had 19 attacks with 12 deaths. If the inoculated had suffered to the same extent as those not inoculated, they should have had 12 cases with 8 deaths, instead of 1 case which recovered. Fuller details of this experience will be found in the above mentioned pamphlet “ The Plague Prophylactic *’ by Colonel Bannerman. In No. 1 Division of Bombay City, the Municipal labourers are housed in challs owned by the Municipality. In 1905 and 1906 a large number of these Municipal servants and their families were inoculated. The result of the inoculations was IO carefully observed and investigated by Dr. Turner, the Health Officer, and his subordinates. The following table shows the events among the inhabitants ot the Municipal challs : — Population. Plague Deaths. Percentage of Deaths. Inoctilafe/f .. 3.317 3 0-09 UniuocuKted 836 18 2’1 If the 3,317 inoculated had suffered to the same extent as the 838 uninoculated, they ought to have had 71 deaths instead of 3 only. The following shows the occurrences in two challs in which the Health Officer says “ the greatest number of plague deaths occur ed”:— Popidation. Plague Deaths. Percentage of Deaths. ■ Inoculated ... 376 Nil Nil Uninoculated '65 11 66 If the 376 inoculated had suffered to the same extent as the 163 uninoculated, they ought to have had 25 deaths, whereas they had none. The above example illustrates what can be done by a Municipality to save the lives of their employes. The ex- perience of Bombay is not unique in this respect. Experience of Public Employers of Labour. In Karachi the Health Officer of that city inoculated a large number of the menial staff of the Municipality with the follow- ing results:— Popu- lation Cases. Deaths. % of Cases to Population. % of Deaths 10 Population. Case Mortality. Inoculated ... ',245 22 4 1-76 0’J2 18*18 8 8-33 62-50 Experience of Private Employers of Labour. Private employers of labour have had a similar experience of inoculation. By having- their emp'oy^s inoculated, great saving in time, labour and worry was effected during the prevalence of plague. Thus Mr. Bazonji Dadabhoy, the manager of the Empress Mills, Nagpur, found that of 1,116 mill-hands who were inoculated, only six died of plague, whereas 2,663 uninoculated mill-hands had 179 deaths from that disease. Experience of Railway Companies. The advantages of inoculation have been demonstrated to Railway Companies in a crucial experiment carried out among the employes of the Southern Mahratta Railway Com- pany in 1896. The men and their families lived in the Railway challs, some little distance from the town of Hubli. They were carefully kept under observation. Among 1,260 who were inoculated 11 cases and 2 deaths occurred, whereas among 760 who were not inoculated 35 attacks and 21 deaths occurred, so that although the uninoculated were about two- thirds less numerous than the inoculated, yet they had three times as many attacks and ten times as many deaths from the disease. For particulars of this experiment see report of the Hon. E. L. Cappel, Esq., Collector of Dharwar, published by Government, No. 3569 of 1898. Experience of Military Authorities. Military and Police Officers have learned that inoculation can save many lives in the presence of plague. For example, Major G. S. Thomson, I.M.S., who was in charge of the 114th Mahrattas, reported in 1906 that the whole of the 114th Infantry including families and followers were inoculated making a total of 1,155 individuals. Only 1 man of this number suffered from plague ; he had a mild attack and recovered. Now about 700 yards distant, the 121 st Pioneers were living in exactly similar circumstances and surroundings, but they were not inoculated at the time when inoculation was resorted to, to check the disease. Three attacks and two deaths occurred within 3 days after the inoculations were completed and these cases closed the epidemic. Experience among the Police In 1905, 1,598 policemen were inoculated in the Khandesh district, and of these only 3 died of plague, while of 230 who remained! uninoculated, 4 died of the disease. If the inoculated policemen had been exposed to plague to the same extent as the uninoculated policemen and if they had not been protected by inoculation, they would have had 26 deaths in place of 3 only. Experience of the Jails Jail authorities have found that inoculation is the best way to combat the plague. Major Jackson, I. M. S., Acting Inspector-General of Prisons, Bombay Presidency, writing to the Thnes of India of 25th September 1905, gives his experience somewhat as follows : — “ In the early years of plague prevalence, strict segregation and disinfection of all arrivals and their clothing with isola- tion of every suspicious case of fever were resorted to. It was under these circumstances that inoculation came to be the resource of the Jail authorities who were harassed by the endless labour (attending measures of isolation, &c.) and beaten in the strife with plague, and who found that inocula- tion is as successful as the most rigorous segregation, evacuation and disinfection and very much less troublesome to everyone concerned.” From figures he showed that “ as inoculation has been more and more resorted to in the pri- sons, so the incidence of plague and death-rate has dimin- ished.” Thus in 1897 with a daily average population of 8,392, there were 48 cases of, and 27 deaths from, plague, while in 1904, with an average population of 8,166, there were only 8 cases with 5 deaths from that disease. In fact, as Major Jackson observes, plague has been banished from the prisons, and in importance has “ sunk to the level of measles.” A Popular Account of theMechanism by which Anti=Plague Vaccine effects a Saving of Life in the Presence of Plague. All are familiar with the fact that persons seldom suffer from two attacks of certain diseases, such as small-pox, typhoid fever and plague. One attack of the disease protects the patient from another attack of the same disease : nevertheless, the protection so acquired is not absolute ; some people have suffered from small-pox or typhoid or plague on more than one occasion, but such cases are very infrequent. Dr. Jenner was the first to show that protection from small- pox could be acquired by inoculating a person with a modified form of the disease known as cow-pox. This cow-pox was cultivated by him, and he injected persons with it, who were thereby protected from small-pox. The material he used is derived from the cow which in Latin is called vacca, hence Jenner’s prophylactic for small-pox came to be known as vaccine. The vaccine for small-pox used by Jenner and others is a living organism which when placed upon the abraded surface of the skin can grow and multiply and penetrate beneath the skin into the blood, and so bring about changes in the living cells of the body which ultimately protect the person from small-pox. It was soon found in connection with other diseases as typhoid fever and plague that a living vaccine was not neces- sary to bring about those changes in the body of a person which ultimately protect him from a particular disease, provided only that the products of the life of the organism which produce the disease are injected under the skin, so that they may enter the blood and reach the living cells of the body. The vaccine having gained an entrance to the blood, and having come in contact with the living cells of the body, stirs them up to produce an antidote to the poison of the disease, and protec- tion from the disease is thereby effected. With the discovery that dead vaccines could be effectively used to protect a person from a particular disease, a large number of vaccines were prepared for a variety of diseases, and it became necessary to distinguish one vaccine from another. This was effected by applying to the word vaccine the name of the disease against which each particular vaccine protected. Hence nowadays you hear of small-pox vaccine, anti-typhoid vaccine and anti-plague vaccine. It is with this latter anti- plague vaccine that we are concerned. Inasmuch as the small-pox vaccine is a living vaccine, and is only placed on the surface of the abraded skin to ultimately multiply and penetrate into the blood, the term vaccination was applied and confined to this method of administering and using a living vaccine. But since a dead vaccine like the anti-typhoid and anti-plague vaccine requires to be injected under the skin to enter the blood stream, the term ‘ inoculation ’ has been applied to this method of administering a dead vaccine. « Vaccines have recently been used not only to protect persons before they acquire the disease, i.e., used as prophylactic agents, but they have been used also as curative agents after the person has actually been attacked by the disease. The first person to use a vaccine in this way was Pasteur, whose famous treatment of Hydrophobia or Rabies is simply a treat- ment with anti-rabies vaccine. Sir Almroth Wright has devoted much study to this subject and has successfully used vaccines in the treatment of many diseases and has given the name Vaccine Therapy to this branch of modern medicine. It will now be possible to consider and answer certain questions frequently asked by those who are about to be inoculated. Should Anti=Plague Inoculation be carried out in the Presence of the Disease ? Will any Harm be done to those who have actually acquired Infection, although at the Time of Inoculation they show no Signs of the Disease ? Some will confront us with the a priori objection that it is plainly irrational to expect anything but harm to accrue from L the injection of bacteria and their toxines into a person who is already infected with the living* bacteria which are, of course, constantly producing- their poisons. It is possible to answer such critics in two ways ; on the one hand, they may be con- fronted with the favourable results of actual experiments which disprove their a priori assumption and, on the other hand, it would be possible to direct their attention to certain facts which a closer study of Vaccine Therapy has revealed, which show that the use of vaccine in septicaemic conditions is not the irrational procedure that it might at first sight appear. To refute the critics in this latter way would entail a familiarity with technical terms with which the majority of the readers of this pamphlet are unfamiliar, and it will therefore be necessary to confine attention to detailing- the results of experiments which disprove the assumption that harm is done when a person is inoculated with anti-plague vaccine while he is incubating the disease. It has already been pointed out that vaccines have been used with success in curing persons suffering from certain diseases, and Pasteur’s method of treating Hydrophobia was instanced. Sir Almroth Wright has obtained “ in very numerous cases conclusive evidence of an augmentation of the opsonic pow*er of the blood within an hour after the inoculation of tubercle vaccine, and also trustworthy witness of associated clinical improvement within that time in connection with the in- oculation of tubercle vaccine in an infection of the eye.”1 Sir Almroth Wright’s experience with tubercle vaccine is in conformity with the experience obtained in India in connection with the use of anti-plague vaccine. Inoculations with anti- plague vaccine have been carried out on a large scale in vafious parts of India, hundreds of thousands of persons having been operated upon. It has been found possible to compile the following table from the reports sent in from certain prisons and small villages where accurate statistics have been kept, showing the case-mortality in persons inoculat- ed during the incubation period of plague. 1 Lancet, August 24, JQ07, p. 493. Attacks. Deaths. Case-mortality r> . . , , , per cent. Cases which had plague actually evident at time of in icul ition, or which deve- loped it the same day ••• ••• • •• 43 31 48*8 Cases which developed plague oil 1 first day after inoculation ••• •• • • • 40 23 57*5 » 1 99 2nd day 40 23 55*o ) 9 • 19 3rd », 3S 21 55*3 1) 99 4th „ 37 IO 370 I > 99 5th ,, 37 IS . 4S-6 n 9 9 bill ,, 36 IO 3^5 9 • 9 9 7'h „ 39 >4 4^ 3 >» 9 9 Sth ,, 24 9 1 * 9 » 9th ,, 24 >5 62-5 9) 9 9 10th ,, 30 9 3° *0 Total within the first ten days after inoculation., * • • • • ••• ••• • • • Ut CO 172 4S*o4 Cases which developed plague sub- sequent ly ••• ••• ••4 ••• ... 56 6 230 40*6 Total plague cases among the inocn- lated ... •• • ... ... 924 402 43'5 Total plague cases among the uninocu- lated portion of 'he population dur- ing the same epidemics ... 5,079 3,726 / a We have here records of over 6,000 attacks of plague, with a case-mortality in the inoculated of 43*5 per cent, and in the uninoculated of 73 3 per cent. These figures show that on no occasion did the case-morta- lity of the inoculated even approach the figure obtained among* the uninoculated, namely, 73*3 percent. Moreover those who had svmptoms of plague at the time of inoculation, or developed them the same day, had a case-mortality of only 4S‘S per cent, which is considerably lower than that found among the uninoculated. We conclude that no harm will be done by inoculating persons in the midst of plague infection, provided the dose of the anti-plague vaccine used does not exceed that prescribed on the bottles sent cut from this Laboratory. J7 How long does the Protection conferred by Inoculation with Anti=plague Vaccine last ? To answer this question satisfactorily, some knowledge of the problems of immunity is necessary, but the following explanation may suffice for the present. The amount of protection conferred on an individual by inoculation depends on (a) the dose of vaccine used ; (b) the power the individual has of reacting to a certain dose of vaccine ; (c) the circumstances in which the individual is found at the time when he is subjected to infection ; (d) the dose of the infection which he receives. With such a number of vary- ing factors affecting the degree of immunity conferred by inoculation.it is impossible to lay down the exact peiicd for which protection lasts. Some statistics are available, however, to show that, while protection is most marked during the six months immediately following inoculauon, immunity is still marked at the end of one year, and the degree of protection remaining during the second year after inoculation is only slightly less than that of the first year, and even after five years some trace of protection remains. While this is so, it is very desirable that persons should be inoculated during each successive plague season so as to acquire as high a degree of protection as possible. Men have been inoculated thirty and forty times without injury of any sort, and many now undergo the operation each year as the epidemic season approaches. Does Inoculation give rise to any Disease, or does it in any Way affect the Health of those inoculated ? lo both of these questions an emphatic answer in the negative can be given. Apart from the fact that a sterile fluid, such as the an'i-plague vaccine is, could not possib'y give rise to any bacterial disease ; statistics which have been collected prove that inoculation in no way affects the health of those who undergo the operation. The Medical Officers of Prisons have a unique opportunity of watching the inoculated for months ar d even years after the operation, so that if any ill- effects followed they would certainly discover them. In the large jail at Yeravda 3,000 prisoners were inoculated in 1900. In 1901 some 2,000 more were done, and those remaining in prison from the previous year were re-inoculated. In 1903 about 1,800 more prisoners and in the following year 35 contact cases were inoculated. Out of this total of 6,835 inoculations not a single bad result followed the operation except in three cases—an enlarged gland in the axilla, which disappeared within a week. Major Jackson, referring to the extensive inoculations which have been carried on in all the jails in the Bombay Presidency, remarks : “ Now, if inoculation haJ the varied and terrible after- effects that its opponents declare, we would naturally expect to find an increased death-rate in those prisons in which inoculation has been steadily resorted to. But we find the contrary.” After quoting statistics, the Inspector-General concludes with the following- weighty sentence : “ These death- rates seem to me to conclusively prove that no ill-effects followed inoculation either by lowering the general vitality or by the production of any specific disease.” To get further evidence on this subject, two officers from the Laboratory visited the Thana Jail in November 1901. The prisoners were paraded and every alternate man, as they happened to have seated themselves, was inoculated. Two groups of 238 inoculated and 236 uninoculated were thus obtained, and a minute record of them kept for nearly 30 months. Every fortnight these men were weighed, as this is a well recognised index to the state of health of prisoners. Details as to adm ssion into hospital, the nature of their illness, and its duration and result were also recorded, so that a comprehensive history of each individual during his stay in jail was compiled. It was curious to watch the close equality in all these matters which appeared in the two groups as the Carbolising the Anti-plague Vaccine. Vacuumising the Bottles. fortnightly records arrived. The following* table, which sum- marises some of the results obtained, is instructive :— Number of prisoners on 6th November 1901 Average weight on 6 th Nov- ember 1901 Number of the above* remaining in jail on 17th April 1904 ... Average weight on 17th April 1904. Average increase of weight Inoculated. 238 Lbs. io6'o 79 Lbs. io8'8 ,, 28 Uninoculated. 236 Lbs. io8'4 69 Lbs. tto'3 V !’9 The Preparation of the Vaccine- Nature of the Vaccine- It may interest the readers of this pamphlet to know some- thing- of the method adopted for preparing- the anti-plague vaccine. Shortly, the vaccine may be described as a culture cf the plague bacillus whiJi, after growing in broth for a period of at least six weeks, is sterilised or killed, and to which -5 per cent, carbolic acid is added. The material is sent out in hermetically sealed glass bottles. Each bottle contains, as a rule, 20 cubic centimetres of the vaccine, and this quantity is sufficient for five full doses. The Preparation of the Medium in which the Germ is grown. The broth or sod in which the plague germs are cultivated is manufactured from goat’s flesh or wheat flour. To this hydrochloric acid is added and the mixture is placed in large ja s for three days surrounded by water kept at a temperature of 7o°C or i58’F. The insoluble albumen of the meat or flour is converted during this process into the soluble albuminoid bodies, known as peptones and propeptones. Caustic soda is then added to the acid liquid until it becomes neutral, and common salt is thus formed. The liquid is now diluted, boiled and filtered and placed in large glass flasks which are corked with cotton wool. The flasks are passed into a larg-e steriliser, where they are subjected to saturated steam at a pressure of two atmospheres ; a clear sterile amber-coloured liquid or broth is thus obtained, and this is the soil in which the plague germ is grown. The Isolation of the Plague Germ. The plague germ is isolated either from the blood or the bubo of a patient suffering from the disease. It is purified by growing it in test-tubes containing broth jelly, which is made by adding some sea-weecl called agar-agar, or “ Chini ghas,” 10 the liquid bro’.h. The germ is then thoroughly iden- tified as the plague bacillus by submitting it to a number of tests. Among the chief of these tests is the characteristic appearance known as “ Haffkine’s stalactites” presented by the growth of the organism in suitably prepared broth. This apoe trance has been photographed and is reproduced on plate IV. The Preparation and Sowing of the Seed Material- The plague germ, which has thus been carefully isolated and identified, is then cultivated in a Pasteur flask for a period of not more than fourteen days. A small quantity of the material contained in the Pasteur flask is transferred to several larger flasks, each containing one litre of the broth. In this way the seed is multiplied. This is effected in the sowing and lesting room, a photograph of which is reproduced on plate V. The Incubation and Development of the Plague Bacilli- Adjacent to the sowing and testing room is the Incubating room. Here the flasks, which have been sown with the plague germs, are placed in rows on long tables and are allowed to remain there in semi-darkness for a period of at least six weeks. During this period the plague germs multiply enor- mously, so that the broth, which was clear when brought into the room, soon turns turbid because of the vast increase in the number of plague germs it contains. Testing the Purity of the Vaccine- When required for use the flasks are again returned to the sowing and testing room. Here a sma l sample of the con- tents of each flask is carefully removed with aseptic precautions and is transferred to a broth jelly tube. After 24 to 48 hours the germs grow upon the surface of this tube. Now, just as the farmer recognises the nature of the crops growing in his fields by their distinctive characters, so the bacteriologist dis- tinguishes the appearances of his crops of germs. If the appearances indicate that plague germs alone are present in the tube, the flask fro n which the sample was taken is passed on for further manufacture and tests. Sterilisation of the Vaccine. Having- passed this test, the plague germs contained in the flasks are next killed by being subjected to a temperature of 55°C. or i3i°F. for 15 mintues, a process which is effected by submerging the flasks in hot water. The material contained in the flask is now sterile and contains no living organism of any sort. Carbolising the Vaccine. To prevent any possibility of any organism growing in the broth after this stage in the manufacture has been reached, carbolic acid is added to the extent of .5 per cent. This addition of carbolic acid is an important step in the manufacture of the vaccine, for it renders the broth an unsuitable medium for the growth of any sort of germ, and therefore ensures that no such disaster as that which took place at Mulkowal in 1903 can ever again occur. The Preparation of the Bottles in which the Vaccine is despatched. At this point it is necessary to leave for a moment the consi- deration of the further treatment of the vaccine and pass on to review the methods adopted for the preparation of the bottles in which the vaccine is despatched. The glass bottles used for this purpose have a peculiar shape, which is illustrated in Plate X. By means of an air-pump and other apparatus illustrated in Plate VIII, the bottles are vacuumised and sealed in this condition. They are then packed into iron boxes which are placed in large ovens, where they are exposed to a temperature of about i8o°C. for three and a half hours. Exposure to this heat is sufficient to destroy any bacteria which may be present in the bottles. The iron boxes, when removed from the ovens, are immediately sealed and the word “sterilised,” with the date, is stamped upon them. They are then taken to the decant- ing room, where the bottles are filled with the sterile car- bolised vaccine. Decanting the Vaccine. In the decanting- room the anti-plague vaccine passes into the hands of the decanters who have been specially trained. They must pass a series of tests in the method of decanting before they are allowed to undertake the routine work of filling the bottles. It is their duty to introduce into the flask, in an aseptic manner, a suitably bent glass tube and connections known as the syphon and filler. This piece of apparatus has previously been sterilised, and is placed beside the decanters in closed zinc boxes, from which they are re- moved from time to time as required. Within the bulbous metal filler there is a rubber diaphragm and a bent piece of metal tubing, called the “ breaker.” To fill the bottle, the long bristle-like neck is thrust through the rubber diaphragm, and the point thus impinges upon the breaker. With gentle pres- sure and a rotatory movement the point of the bottle breaks off within the filler. As soon as this occurs, the fluid vaccine rushes through the syphon into the bottle to replace the vacuum, which, as we have seen, was created in the bottle belore it was sterilised. When the flow into the bottle ceases, the long neck is withdrawn from the filler, the rubber dia- phragm closes behind the bottle, and so prevents the escape of the fluid contained within the filler. Thus it comes about that the bottles are filled without exposing the fluid to contact with unsterilised air. '1 he broken point is immediately sealed in a flame after withdrawing the bottle from the filler. Testing the Vaccine for Sterility. The bottles are now set aside for a week—a period which permits of the multiplication of any germ which might inad- vertently have gained entrance to the vaccine during the process of decanting. Two bottles are selected from the number (about 45) which are filled from each flask or “ brew”, and these are examined to ensure that the brew is sterile. The tests are carried out in two ways—aerobically and anae- robically. By the former method any germs which require the presence of oxygen for their development are discovered, while by the latter method such organisms as the tetanus bacillus, which can grow only in the absence of oxygen, are detected. Should these tests prove satisfactory, the brew is pronounced fit for use. The Sealing of the Bottles and Retention of a Sample of each in the Laboratory. The last stage in the process of preparation is now reached. A small portion of the contents of each bottle is driven into the long neck. The neck is then heated in a blow-pipe flame near the shoulder of the bottle ; the glass is thus melted, and the long neck is separated from the body of the bottle. In this operation the bottle and neck are simultaneously hermetically sealed. The neck contains a mp le of the vaccine which is sent out in the bottle, and this sample is retained in the Laboratory as an “ office copy/’ All the samples from the same brew are kept in a sheet of corrugated paper in the manner depicted in plate X. Should any suspicion arise as to the condition of the contents of a bottle, the sample contained in the long neck of the bottle, which has been filed in the Laboratory, can be tested. In this manner not only is the public safeguarded, but the Laboratory is protected against false charges. Although thousands of doses of anti-plague vaccine have now been issued since the above-described improvements in the prepar- ation of the vaccine have been introduced, it has never been proved that a single bottle has been issued from the Labora- tory. the contents of which were not sterile. Precautions taKen to avoid Contamination of the Vaccine by the Operator- While in this way it is now possible to ensure that none but sterile anti-plague vaccine leaves the Laboratory, the chances of the vaccine becoming contaminated in the hands of even an unskilled operator have been greatly minimised, if not com- pletely abolished. In the first place, the new type of bottle is better adapted for opening in an aseptic manner than the old bottle with a rubber cork was. There is no cork to drop on the ground and contaminate the vaccine by being- reinserted in the bottle. The bottle cannot be opened by accident or from curiosity without first sterilising- the neck. When it is once opened, it cannot be closed ag-ain, and there is, therefore, no temptation to keep any of the fluid for another day. '1 he pointed end is heated in a flame till it becomes sterile and hot. 1 hen with a jerk the cold fluid in the bottle is made to impinge on the hot glass, which, in consequence, cracks, and the bottle is thus readily opened. In the second place, the syringe is sterilised by using hot oil or vaseline at a temperature of i6o° C. A cheap and effective apparatus has been designed for this purpose, and is supplied to all who desire to use it. A picture of Ur. Kapadia’s lamp, as this apparatus is called, is illustrated in plate XII. Directions for sterilising- the syringe will be found in another part of this pamphlet. Ag-ain, special classes have been instituted for the training of men in the methods of carrying out inoculation, and the anti-plague vaccine is only supplied to those who are certified as competent to carry out the simple operation. How to indent for the AntUPlague Vaccine- No special indent forms are required, but the following" rules published by the Government of Bombay in Government Resolution, General Department (Plague), No. 1567-P. of 16th November 1907, must be complied with :— Rules, for the issue of Plague Prophylactic from the Bombay Bacteriological Laboratory, Parel, Bombay. In India- 1. Applications received from Government or other public officials and Medical Officers, of whose fitness to use the pro- phylactic there is no doubt, and from practitioners who have already been once supplied on the recommendation of Civil or Medical Authorities, will be complied with at once. 2. Applications from medical practitioners who have not been supplied before must be sent through the Chief Civil Authority, or Medical Officer of the place where they reside. In the event of the application being supported, it will be complied with. Subsequent applications may be submitted direct to the Laboratory, when they will be dealt with in the ordinary course, the applicant not being required to submit his application again through the Civil or Medical Authority. 3. Applications from firms of chemists or private indivi- duals not medical men cannot be accepted. The Resident Physician of a firm of chemists may be supplied with the prophylactic, and the requisition will be dealt with as a case of first application from a private medical practitioner. In this case the prophylactic will be supplied on the distinct understanding that it is required for bona fide personal use, e.g., inoculating his staff or patients, &c. In no circum- stances is the Resident Physician authorised to allow the prophylactic supplied to him to be used by anyone else. 4. Local Governments, Local Boards or Municipalities desiring that a stock of'-prophylactic should be available lor use in emergencies should arrange for the local Medical Store- Shows the Shape of the Bottle and the Method of filing Samples keeper, or Civil Surgeon, or Health Officer, to be supplied accordingly. Only medical men are to be entrusted with the custody of the prophylactic. 5. A charge of 5 anna per dose is made for the anti-plague vaccine supplied to applicants outside the Bombay Presidency, as well as independent Native States within the Presidency. There will be, in addition, a charge of 1 anna 3 pies to defray the cost of each bottle, which contains, as a rule, 5 doses, besides the charges for packing and freight. In the Bombay Presidency no charge is made to applicants for anti-plague vaccine, except the cost of bottles, packing and freight. Out of India- 6. British Colonial Governments. — Applications from Bri- tish Colonial Governments will be complied with at once without any previous reference to Government. The despatch of such consignments will be at once reported to Government for information. 7. Applications from British Consulates will be complied with without any previous reference being made to Govern- ment. A report will be made as above. 8. Applications from Foreign Consulates and Governments must in all cases have received the previous sanction of Government before being complied with, subsequent intima- tion being also sent of the actual despatch. 9. Applications from medical practitioners not in the service of the British Government, including medical mission- aries and foreigners in the employ of Foreign Governments or Consulates, will not be complied with unless supported by the British Consul of the place where the applicant is a resident. 10. The supplies to countries outside India are subject to the condition that Indian requirements are met first. Applicants for anti-plague vaccine out of India will be charged annas 2 per dose, bes des 1 anna 3 pies, the cost of e tch bottle containing five doses, packing and freight being extra. The Storage of the Vaccine. Officers indenting- for a supply of vaccine should invariably specify the number of doses required, not the number of bottles. The boitles should be stored in a cool dark place, and under these circumstances the material may be expected to retain its full efficiency for at least 18 months. After this period the old vaccine may be destroyed and a fresh supply will be sent in exchange free of charge, except for cost of bottles, packing and freight, on intimation being received of the amount so destroyed. Indents for fresh vaccine to replace old material in stock should have this fact noted on them to prevent error in preparing bills. A supply of fresh vaccine, to Colonial and Foreign Govern- ments or other bod'es outside India, which is to take the place of vaccine which has deteriorated through lapse of time, will be charged for at the same rate as an original supply. Equipment for an Inoculator. Rs. a. p. The following complete equipment for an Inoculator is generally required :— Some doses of anti-plague vaccine Two 20 c.c. Roux syringes complete @ Rs. 17 each .. 6 extra needles @ Re. 1 each ... 6 spare rubber plungers @ ans. 6 each T& spare glass barrels @ ans. 1 1 each ... 6 spare pairs of washers @ ans. 2 each 1 Kapadia’s sterilising apparatus complete with lamp, stand, aluminium dish and thermometer graduated in degrees centigrade 1 spare thermometer ... ... ... ... ... 1 pair of pliers 1 pair of dissecting forceps i u m Jail, 34 6 2 1 o o o 4 6 12 o o o o o aluminipm dish for carbolic lotion 1 and one^unce aluminium measure ... i 20-ounce bottle for 1 in 20 carbolic lotion 9 o o o o i bottle containing 1 lb, methylated spirit 1 bottle containing 1 lb. pure carbolic acid ... 1 tin containing 9 ounces of vaseline 2 packets containing £lb. absorbent cotton in each... 2 towels ••• ••• ••• ••• r cake of soap 1 box of matches • • • • • • 1 enamel basin 2 certificate books • •• ••• • ••• 2 copying in< pencils @ ans. 10 per dozen ... 2 sheers carbon paper @ ans. 1 each I painted dea wood box with padlock and keys complete for packing these articles ... ... 280 This complete equipment can be supplied pro- perly packed and in portable form, cosc exclusive of anti-plague vaccine for ... ... 60 /£ o The whole equipment or any separate article in this list can be supplied at the prices quoted above. T3 4 12 2 4 /Z. **- 030 9 8 6 12 6 2 0 8 4 1 2 Repairs- Minor repairs to syringes are effected at the Laboratory free of charge. Disposal of used Bottles, 6c. The empty bottles, boxes and material used for packing- are not to be returned to the Laboratory. Those supplied to Government officials should be sold locally to the best advan- tage and the proceeds credited to Government in the local treasury in the same way as boxes and packing from the Medical Stores are dealt with. Telegrams should be addressed “ RESE \ R.CH,” and parcels, if sent by G. I. P. Railway, to be booked to Parel ; if sent by B. B. & C. I. Railway, to Elphinstone Road Station. Letters should be addressed to— The Director, Bombay Bacteriological Laboratory, Box 12. Parel, Bombay. Methods for effecting Payment for Articles supplied. The bills preferred by this Laboratory for articles supplied are of two kinds : — (1) Adjustment bills. (2) Cash bills. (1) Bibs for supplies furnished to Government officials are sent on adjustment forms in duplicate. The original copy, together with the receipt at the f. ot of the duplicate copy, should be signed by the receiving officer and returned to the Labora'ory on receipt of the goods. The duplicate copy of the bill may be retained by the indenting officer. Cash should never be sent in payment of these bills. The money will be recovered by book-adjustment made by the Accountant- General, Bombay. (2) Cash bills are presented to private practitioners, municipalities and others who have no book-adjustment with the Accountant-General. The bills should be adjusted either by money order or cheque. Government officials, when order- ing vaccine or other materials on behalf of municipalities or others, should invariably state for whom the material is required, so that the proper bills may be despatched. The Syringe complete and 2n separate parts. Knpaiia’s Sterilising Lamp How to proceed to carry out Inoculations. The influential leaders ofthe people, heads of castes, teachers of relig\on and village headmen, should be approached. The advantages of inoculation should be explained to them and their assistance solicited to persuade their less educated brothers to protect themselves from plague by inoculation. A number of people, ioo or more, should be assembled with their leaders in a local temple, courtyard, school-house, or other suitable enclosure. Those who volunteer should be in- oculated, while the remainder of the people look on. Nobody should be allowed to leave the meeting until all who are will- ing have been inoculated. The onlooking waiverers, having seen how simple and painless the operation is, frequently come forward and follow the example of their friends. If the meeting is allowed to disperse before all who are willing are inoculated, some will leave with exaggerated ideas of the painfulness of the operation. It is always a disadvantage to inoculate small numbers of people at a time. The Symptoms produced by Inoculation. The symptoms caused by inoculation commence, as a rule, in 3 to 5 hours, and consist chiefly of swelling and pain at the seat of inoculation and of a rise of temperature. Pain is much increased by the taking of alcohol, or on movement of the part, so this had better be avoided for 36 hours after operation. The fever is accompanied by the general discomfort usual to this condition, and no treatment of symptoms is required beyond taking some rest. General symptoms subside after 24 to 36 hours as a rule, but if not, a purge will give relief. The pain at the seat of inoculation lasts for 3 or 4 days, disappearing gradually, but a painless induration may remain for some little time. The fluid acts differently on various people, and a uniform reaction cannot be obtained, fever being almost absent in some cases. It is not known whether there is any relation between the presence of high temperature after inoculation and the degree of protection acquired thereafter by the individual, so an absence of reaction does not mean that the inoculation has not “ taken, ” as would be said in similar circumstances after vaccination for small-pox. What Dose of Vaccine to use under varying Conditions ? The usual dose for an adult man is 4 cubic centimetres (1 c.c. 17 minims), but the labels on the bottles must always be consulted on this point. The following table shows the doses to be given to persons in good health at various ages :— If the dose marked on the bottles is 4 c.c. then— To individuals of from 10 days to 1 year give o*2 c.c. or 1/25 of full dose. y» yy 1 to 2 years y y o-8 c. c. or 1/ 5 ,, y y 5) 2 to 5 years yy 1 *6 c. c. or 2/ 5 ,, y y y y 6 to 11 years y y 2‘4 c. c. or 3/ 5 ,, y y y y 12 to 15 years yy 3-2 c. c. or 4/ 5 ,, y y yy 16 to 50 years y y 4*o c.c. or full dose. If the dose marked on the bottle is other than 4 c.c., the amount to be given at various ages is to be calculated in the same proportion as above. Children stand the treatment well, and no fear need be felt in giving the doses above mentioned. Persons over 50 years of age should get J^th less for each decade above that age. Women of all ages over 14 years should get Jg-th ^ess than men of corresponding ages. Pregnant women may be inoculated up to the 7th month inclusive, without making any special reduction of dose. After the 7th month the dose should be given in two instalments separated by an interval of a week or so. Miscarriage has never been known to result from inoculation ; and the danger from plague to lying-in women is so great that a special effort should be made to induce pregnant women to be inoculated. Persons suffering- from fever should not be inoculated till 48 hours have elapsed after the fever has entirely subsided. With the exception of persons suffering- from fever and those obviously ill from any cause, all can be inoculated. No harm has ever been known to be produced by inoculation in the case of persons suffering- from chronic diseases as phthisis, rheu- matism, diabetes, etc. How to sterilise and fill the Syringe. The first step in the operation of inoculation is to sterilise the syringe and needle. For this purpose Kapadia’s sterilis- ing apparatus is conveniently used. The apparatus consists of a pot for heating oil or vaseline. The pot is placed on a block tin stand, which at the same time serves to protect the flame of a spirit lamp placed beneath from draughts of air. Methylated spirit is used in the lamp. Never pour in spirit while the lamp is alight. The oil for use in the cup may be olive, cocoanut, or any similar oil which has not an acid reaction, but vaseline is very convenient, as it becomes solid when cold, and does not spill when packed for travelling. Fit up the sterilising apparatus and light the spirit lamp. See that the thermometer is in good order and adjust it properly in the vaseline. Then take out the syringes and needles. 1. See that the needles are sharp, clean and patent. If these points are attended to, work is greatly facilitated, and the operation is much less painful. Place the needles in the vaseline. 2. See that the syringe is airtight. This is done by placing a finger over the nozzle and at the same time pushing home the piston ; if the syringe is working properly, resistance will be felt to the pressure against the piston and it will slip back when released, provided the finger has been retained firmly over the nozzle. The tightness of the plunger in the barrel can be regulated by the screw in the handle. 3- When the temperature of the vaseline has reached 90° C. fill up the syringe with the heated vaseline and empty it again into the pot. This is done to get rid of moisture in the syringe; at temperatures above ioo° C. any moisture is immediately converted into steam, and this causes the vaseline to crackle and splash and may, perhaps, fracture or burst the glass barrel. 4. Now wait till the temperature has reached 160° C. Then completely fill and empty the syringe twice with the hot vaseline. A temperature higher than 160° C. injures the india- rubber plunger, and a temperature lower than 1600 C. is not so efficient in effecting sterilisation. 5. With the dissecting forceps fish out a needle, which has been lying in the hot vaseline, and adjust it firmly to the nozzle of the syringe by means of the pliers, which should, previous to grasping the needle, have been dipped momentarily in the hot vaseline. 6. Now for the third time draw up and eject the hot vaseline from the syringe ; on this occasion with the needle in position. The syringe may now be carefully laid on one side preferably supported on the lid of the syringe box and allowed to cool. The needle should not be allowed to come in contact with any article or surface. 7. A bottle of anti-plague is then taken in hand. The number of the brew and the number of the bottle and dose to be used is noted. Examine the neck carefully for any cracks or flaws. By handling the bottle in the same way that the index of a clini- cal thermometer is shaken down, leakage, through such cracks, may be detected. Faulty bottles should invariably be re ected, and the contents thrown out. The bottle should then be well shaken, so as thoroughly to mix the sediment, which will be seen at the bottom of the bottle, with the fluid. The sediment consists of the dead bacteria, and is an essential part of the vaccine. 8. To open the bottle, hold the neck in a flame, turning the bottle round all the time so as to sterilise every part of the neck. When the glass is sufficiently heated, jerk up a little of the fluid, and the neck will crack. The tip may then be knocked off by a sharp blow from a pair of sterilised forceps. 9. Now take up the syringe, draw into it a small quantity of hot vaseline, and again eject it. While the needle is still hot, draw into the syringe two or three cubic centimetres of the anti-plague vaccine. Place the bottle on its side on the table. Then draw out the piston of the syringe to its full extent, and shake up the small quantity of the vaccine within the barrel of the syringe. Eject the contents of the syringe. This is done to get rid of some of the excess of vaseline which adheres to the interior of the syringe. 10. Again dip the needle in the hot vaseline, pass the point of the bottle through the flame, and then fill up the syringe. Get rid of excess of air by adjusting the piston. Note the graduation marks on the shaft of the piston, and read off four marks counting from the outside of the barrel of the syringe. Screw up the discs (to be found at the handle end of the shaft of the piston) to the point noted. The syringe is now ready to deliver 4 cubic centimetres or one dose of the vaccine. How to carry out the Operation of Inoculation ? The most convenient site for the operation is the back of the left upper arm about rnidw y between shoulder and elbow. The skin at this spot should be well scrubbed with 5 per cent, carbolic lotion (1 in 20). The skin being then puckered up between the thumb and fingers of the left hand, the needle should be pushed through the skin in a sloping direction, more or less parallel to the surface, carefully avoiding the big vessels and not penetrating the muscles, but taking care to enter the subcutaneous tissue. Then slowly inject the dose. Withdraw the needle of the syringe, and apply for a few seconds a pad of cotton wool dipped in 1 in 20 carbolic lotion. The next patient is operated on in the same way. The needle of the syringe is first dipped momentarily in the hot vaseline, which is kept at hand at a temperature of 160° C. fhe screw on the shaft of the piston is again adjusted to four spaces from the barrel of the syringe, each space being equal to one cubic centimetre. The arm of the patient is scrubbed with t in jo carbolic lotion. A drop or two of the vaccine should be ejected from the syringe to get rid of any oil or vaseline within the needle. The needle is then inserted, and the dose injected. ' • Between each operation the needle of the syringe is sterilised by dipping it into the hot vaseline. As only sterile fluid has been introduced into the syringe, if proper precautions have been taken to sterilise the needle between each operation, the interior of the syringe need not he sterilised between the tilling of each bottle. At the close of the operations the syringe should be thoroughly washed out with i in co carbolic lotion, and the needles should be covered with vaseline. Other Work carried out at the Laboratory. In addition to the preparation of anti-plague vaccine, the Laboratory functions as a Pathological Diagnosis Institute. Pathological specimens of all sorts are examined and reported on. Slide preparations made from blood, ulcers, etc., are stained and examined, serum sent in blood capsules is tested, sections from tumours are prepared, diseases occurring in ani- mals, such as plague in rats, rabies in dogs, anthrax in cattle, are reported on. Mosquitos, fleas, biting* flies and other in- sects are examined and identified. Snakes are gladly received and identified. Scientific apparatus, chemicals, stains, sera, etc., according to the subjoined list, are supplied at the rates specified. Stains in Solution. Rs. a. p- Bismarck Brown, solution, aqueous • • • ... per too C.C. I o o >» »» »» alcoholic • • • ••• 99 »> »> 3 o o Carbol Fuchsine ,, • •• • •• ••• 99 > > ,, i o G ,, Thionin ,, • •• ••• • • • ... 9 | > > ,, i 6 O Gabbet’s Blue ,, for tubercle bacilli ••• 3 • > i ,, i o o Gentian Violet ,, alcoholic saturated ••• 9 9 IO ,, o 5 3 Giemsa’s ,, ••• '••• • • • ••• 99 5o ,, l 11 o Gram’s Iodine ,, ••• ••• ••• 9 9 100 ,, i o o Leishman’s Stain ,, • • • • • • • • • ••• 3» 5° ,, i 6 o Methjene Blue Stock solution for Romanowski... ,, IOO >> I 2 o Eosine ,, ,, 99 9 9 99 ••• 99 >» ,, o 12 o Dry Stains. Fuchsine powder in 5 grammes bottle ... o 8 o Gentian Violet 99 9 9 IO 99 99 ... 1 8 o Leishman’s Stain 9 9 99 5 9 9 99 ... 5 12 o Bismarck Brown ... 99 M 5 9 9 99 ... o 6 o Dahlia 9 9 9 9 5 9 9 99 ... o IO o Eosine Extra B.A. ... 9 9 9 9 5 9 9 9 9 ... o IO o Methlene Blue Med. pure ,, IO 99 9 9 ... I 8 o Neutral Red ... 9 9 9 9 5 99 9 9 ... 2 o 0 Glassware. Micro slides, quality No. I ... ,, ,, hoilow ground ,, ,, cover glasses Test tuber, without rims Flasks without rims, too c.c. capacity »• ,, ,, 2-OC.C. ,, ,, ,, >> 50J c.c. ,, Drop bottles Staining Well with lid Watch glasses • •• ••• ••• Graduated pipette, i c.c. capacity Extra W.M. stoppered bottle for slides ,, ,, ,, ,, ,, cover glasses Stoppered bottles N.M., 4 oz. capacity ,, ,, ,, 8 ,, ,, ... ... Blood capsules • •• • ••• '»• ••• Sedimentation tubes Specimen tubes with corks for mosquitos Glass pipetres, long... ••• ••• ••• ••• n ,, tubing and rod ... ... Instruments. Copper stand for warm staining ... Surgical needles, straight • •• ••• •• Platinum needle • M ••• Test tubes brush • • • ••• ••• • • • Cornet forceps (cover slip holder) Scissors, straight or bent or flat .. Mouse tongs ... Pencil for writing on glass (blue, red or yellow) India-rubber Teats ... Sterile swab for diphtheria or other purposes.. Filter paper, 11 c. m., in packets of too ,, ,, 15 c> j> >> »» >> •• chardin Rs. a. P per gross 8 0 0 ,, doz. 1 8 1 0 ,, gross 6 0 O ,, doz. 0 12 O ,, each 0 4 0 99 *t 0 5 0 9 9 9 9 0 6 0 9 9 9 9 c 8 0 9 9 9 9 t 2 0 y y dOZ* 0 12 0 ,, each 0 12 0 per each pair 0 to 0 per each 0 12 0 i» 0 6 0 99 0 3 6 99 0 4 6 per doz. 0 4 0 99 Q 4 0 9 9 O 1 2 0 ,» per lb. per each per doz. per each I 99 9 T per pair per each > 9 per doz. per each per too ,, >» Cultures and Emulsions. Culture of Typhoid and other organisms Plague Culture Bouillon ... ... ••• Agir Tubes for Cultures ... ... ••• Broth Tubes, hermetically sealed 8 o 5 ° 1 8 o 12 0 1 2 6 o t o 2 4 o 8 6 4 3 o o o o o o o o o o o o • • • 1 0 0 • • 1 2 0 >• ••• 1 8 0 nosis each 1 0 0 9 9 0 to 0 99 1 0 0 doz. 3 0 0 1 9 3 0 0 Sera. Tetanus Antitoxin, Fluid • • • per each bottle of c«c. ... Rs. 3 a. 0 P- 0 » Dry ... y y y y y y y y i grm .. 3 0 0 Antistreptococcic Serum • • • «> yy y y yy IO c.c. i 14 0 Anti-Dysenteric ,, • • • V y y y y yy 20 c.c. 3 12 0 Veterinary Tuberculin y y yy yy y y 3 c.c. o I 2 0 ,, Mallein • • y y 9 y y y yy 3 c-c- 0 12 0 Acid, Acetic • • • Chemicals. ... • . • per oz. o 2 0 Alcohol, Absolute • • • ... • • • I IO 0 ,, Methylated ... • • • ... • • • „ lb. o s 0 ,, Methyl Merk’s Puriss ... ... yy yy 2 4 0 Cedarwood Oil for immersion • • • ... ,, OZ. I 0 0 Oil of Cloves • • • • •• yy yy 0 8 0 Canada Balsam in Xylol * • • • • • • • • • • • y y yy o 8 0 Dulcite... .. . yy lb. 38 0 0 Formalin ... • • • • • . yy yy 2 0 0 Grubler’s Peptone • • • yy yy 36 0 0 Glycerine Pure... • • • y y OZ* 0 8 0 Lactose ... • • • yy yy 0 4 0 Levulose ... ... ... yy 9 y I 4 0 Litmus Powder • ■ • ... yy lb. 1 4 0 ,, Granular ... • • • •• • yy yy I 0 0 Lysol ... ... ... • • • yy yy I 0 0 Sodium Taurocholate... ... yy yy 8 0 0 Xylol ... ... ... ... • • . • • • • •• j j ^ oz* 1 4 0 Other stains and apparatus can be obtained on giving two months’ notice. &C bo INDEX. A Page. Anti-plague Vaccine—What may be effected by inoculation with ... 7 ,, ,, A popular account of the mechanism by which—effects a saving of life in the presence of plague 13 Articles—MiscellaneouSj price of, supplied by the laboratory •••37—39 B Bottles. Disposal of—used ... 30 ,, Preparation of the—, for the vaccine ... 22 ,, Sealing of, and retention of a sample of each 24 C Carbolising the vaccine • •• •• • ••• ••• ••• 22 Contamination. Precautions taken to avoid — of the vaccine ... 24 D Decanting the vaccine 23 Development and incubation of the plague bacilli ... ... ... 21 Disease. Does inoculation give rise to any—or does it affect the healths of the inoculated 17 Disposal of bottles used ... ... 30 Dose of vaccine ... ... .... ... ... ... ... 32 Duration of period of protection ... ... ... ... ... ... 17 E Equipment for an inoculator ... ... ... ... 29 Experience among Police ... ... ... ... ... ... ... i2 ,, of the Jails ... ... ... ... ... 12 ,, of the Military Authorities n ,, of private employers of Labour 11 ,, of public employers of Labour 10 ,, in Towns 9 ,, in Villages ... ... 8 G Germ. Isolation of the—(plague) ... ... ... ... ••• 2° Growth of the germ (plague)—Preparation of the medium in which the—takes place ... . 20 Health of the inoculated. H Page. Does inoculation give rise to any disease, or does it affect the— ... 17 I Inoculation and development of the plague bacilli ... Indent. How to—for the vaccine .., India. How to indent for the vaccine in— ... India. *,, ,, out of— Inoculation, What may be effected by—with anti-plague vaccine... ,, Should it be carried out in the presence of the disease (plague) ,, Does it give rise to any disease or does it affect the health of the inoculated ,, Symptoms produced by'— „ How to carry out the operation of— Inoculations. How to proceed to carry out— ... Inoculator. Equipment for an— Isolation of the plague germ 21 26 26 27 7 14 17 31 35 3i 29 20 J Jails. Experience of inoculation in— ... ... 12 L Laboratory. Other work carried out at the— ... 37 ,, Prices of miscellaneous articles supplied by the— ...37—39 M Mechanism. A popular account of the—by which anti-plague vaccine effects a saving of life 13 Medium. Preparation of the—in which the germ is grown 20 Methods of effecting payment for articles supplied ' 30 Military authorities. Experience of—in anti-plague inoculation ... 11 N Nature of the vaccine ... ... ... ... ... ... ... 20 O Observations, preliminary, as to some facts which should be kept in mind when determining w hat-anti plague measures to adopt ... ... ... ... ... ... ... 3 Operation of inoculation. How to carry out the— 35 Other work carried out at the Laboratory 37 Payment. Methods of effecting— Period of protectien. Duration of— Plague. Should inoculation be carried on in the presence of— ,, bacilli. Development and incubation of— Police. Experience of inoculation among— Precautions taken to avoid contamination of the vaccine ... Preliminary observations as to some facts which should be kept in mind when determining what anti-plague measures to adopt ... ... ... Preparation of the bottles for vaccine ,, and sowing of the seed material ,, of the vaccine ... ... ... ... ... ... Prices of miscellaneous articles supplied by the Laboratory Private employers of Labour. Experience of— Public », ,, j» ••• ... Purity. Testing the—of the vaccine Page. 3o i7 14 21 12 24 3 22 21 20 37-39 11 % 10 21 Railway Companies. Experience of— ... Repairs to syringes Retention of sample of each bottle and sealing ot the bottles 11 29 24 Sample of contents of each bottle, retention of, and mode ing of bottles of seal- 24 Sealing of bottles and retention ot a sample of each ... ... «• . 24 Seed material. Preparation and sowing of the— ... ... 21 Sowing. Preparation of the seed material and — ... 21 Sterilisation of the vaccine ... ... 22 Sterility. Testing the vaccine for ... 23 Storage of the vaccine ... 2S Symptoms produced by inoculation ... ... 31 Syringe. How to sterilize and fill— 33 Syringes. Repairs to— ... ... 29 T Testing the purity of the vaccine .. ... • 21 Testing the vaccine for sterility ... ... ... 23 Towns. Experience in — of anti-plague inoculation .. ... ... 9 U Used bottles. Disposal of— 3° Vaccine. INDEX. V Carbolising the— Decanting the— ... Dose of— How to indent for the— Nature of the— Precautions taken to avoid contamination Preparation of the— * Sterilisation of the— Storage of the— Testing the purity of the— Testing the—for sterility « t> ?46 Reprinted (with Additions) from the British Mfdicai, Journal, August 6th, 1910. CATS AS PLAGUE PREVENTERS. LIEUTENANT-COLONEL ANDREW BUCHANAN, M.A., M.D. It is now about three years and a half since I first endeavoured to show that the best way to prevent plague in India is by keeping cats, and although considerable pro- gress has been made, and many people have now come to realize the advantage of keeping cats, there are still some who hesitate to give the keeping of cats first place in the list of preventive measures. I should like now to reply to some of the objections that have been made regarding the cat; secondly, to consider some of the circumstances which have tended to retard the proper appreciation of the cat; and thirdly, to give some additional evidence in favour of the cat, and particularly to draw attention to the very valuable evidence from Professor Koch, who for some years, quite independently, advocated the employment of cats for preventing plague, and also to the evidence which Dr. Gimlette has supplied from Malay. It has been stated that the Indian cat is not a sufficiently good rat killer to justify the expectation that cats will many ways in which the activities of the cat can be defeated. For example, a lady informed me that although there were two or three cats in her compound (the enclosure in which the bungalow and outhouses stand) still there were several rats. It was found that about fifty old packing cases were stored in one outhouse, and as most of these packing cases contained old books, papers, straw, or rubbish, the rats had made holes in many of them, and so were able to escape from the cats. When these boxes were cleared out and the rubbish was burned we heard no more about rats in that place. Occasionally we found that a person who had a cat in his own house would complain that rats were frequently coming in, but on making inquiries it would be found that there were many servants’ [412/10] Objections to the Cat. houses in which rats were abundant because there were no cats in them. It is particularly desirable that the servants should be made to keep cats. Early last year I made the following experiment: Eight cats and seventeen rats were let loose in a room with glass doors, so that we were able to watch the result. In a few minutes all the rats were killed; one small cat ended up with four dead rats in its mouth, another had three, and another had two. The cats were ordinary village cats, and had not been specially selected. The editor of the Indian Medical Gazette was among those who at first doubted whether plague could be prevented by cats, but after hearing the subject fully discussed at the Bombay Medical Congress he wrote as follows : “ Conversation with many men after the meeting con- vinced us that very many were coming round to Colonel A. Buchanan’s views that the cat is the natural enemy of the plague rat, and that it is one of the measures of plague prevention dictated by their Scriptures to Moham- medans and Hindus alike, and which will therefore be acceptable to all. We certainly agree that more attention should be paid to this simple method of prevention.” It is essential that a reasonable chance should be given to the cat. Where there are grain stores and mud walls more cats are required ; where there is little food for rats and the walls are built with stone and lime a smaller number of cats will suffice. Is Plague Infectious ? One writer has attempted to show that plague pneu- monia is common, and that this form of plague is directly infectious from person to person. If that view is correct, then rat destruction can only be partially successful, and the employment of cats would not necessarily check the disease. In order to prove that plague pneumonia is infectious directly from person to person it would be necessary to exclude the possibility of infection having taken place in the house in which the first case occurred, or by a flea which may have been concealed in the clothes of the person who was suffering from pneumonic plague. If plague pneumonia is common, and if pneu- monic cases are directly infective, we should expect to find epidemics among the attendants in a plague camp, but Browning Smith a few years ago drew attention to the prevalent opinion that one of the safest places during a plague epidemic is a plague camp, and that has been the experience of most medical men in India. Now we do occasionally hear of a nurse who has been attending on a plague patient getting an attack of plague, and Dr. Gimlette reports from Malay the case of a patient who was in hospital for rheumatism, volunteering to attend on a plague patient who had been brought to the hospital, and getting an attack of plague. But such cases can be explained on the supposition that a rat-flea had been concealed in the clothes of the first case. If the infection were conveyed direct we should expect to hear of a second, third, and fourth cases, but such an instance has not come to my notice. Ten years ago I accepted as a working theory—it was before the rat-flea theory had been proved—that plague pneumonia is directly infectious, but when a pneumonic case has beeD admitted to a plague hospital, or accidentally to the wards of a general hospital, I have always been agreeably surprised to find that no cases occurred among the hospital atten- dants. I do not say that direct infection never occurs, but I have never been able to find any clear and definite proof that it does occur. The point is one of great practical importance for many reasons, but all that we need concern ourselves with at present is that the commonly accepted view, that plague is mainly due to rats, is not upset by the statements of the writer referred to. ■ Is Plague Dying Out ? One reason why there has been so much delay in appreciating the value of the cat is the idea which is prevalent in many parts that plague is dying out; and the recent events in Nagpur may be referred to by way of illustration. The population of the city is about 120,000. In the year8 1903-4 there was a severe epidemic with a mortality of 14,374. In 1906 there was a mortality of 5,165, and after that for a period of three years there was an absence of severe epidemics. Eat-catching was carried out for some time with considerable vigour, and fre- quently about 500 rats were caught in one day. A census of cats taken last year showed that the per- centage of tamed cats to houses was only four—that is, one to twenty-five houses. The annual report of the municipality, which was issued about July, 1909, contained the words, “ plague, like all epidemics, appears to have exhausted itself.” A scheme for the introduction of kittens had been started, but it was too late. In August and September plague spread rapidly through the city and the mortality rose to the unprecedentedly high figure of 205 in one day, and 3,900 in one month. When, then, we see it stated that plague is dying out it would be advisable to inquire on what basis this opinion is founded. Eat destruction by traps and poison may succeed for a time, but the only permanent way to keep the numbers down in India, where there are, and for many centuries likely to be, so many houses with mud built walls, is by the employ- ment of cats. If the number of cats is sufficiently in- creased we can say for certain that plague is dying out. But plague might die out from one of two causes—one by a diminution in the number of rats, and the other by a diminution in the virulence of the plague germ. If the plague germ is less virulent we should expect to find the intensity of the symptoms less, but there was certainly not any diminution in the intensity of the symptoms, for it was the general opinion among the medical men in Nagpur that they had never seen, especially in the earlier days of the epidemic, so many cases die before there was time for the buboes to appear. Cats versus Inoculation. Probably nothing has more retarded progress in the acceptance of the cat theory in India than inoculation. It is now generally admitted that inoculation with Haffkine’s serum is a good thing. During the fifteen months prior to my departure from India, I inoculated close on 10.000 persons, and I could give many illustrations to show the great advantage ol inoculation. In’ Amraoti all the police- men were inoculated except one man, and that man was #the only policeman who died. The forest officer’s servant Kishen, Kishen’s wife, and their two children lived in the same house. Kishen and his wife were not inoculated, and both died; the children were inoculated, and neither took plague In Nagpur all the city police, a force of about 190, were inoculated except two men, and these two were the only men in the force who died from plague. In the Empress Mills, where over 5,000 hands are employed, we inoculated nearly all the workpeople. Among the uninoculated 90 died, whereas among the inoculated only 7 died, and most of these 7 were inoculated in the incu- bation period. Here are the results in eight houses in which some of the workpeople lived: There were 63 persons ; cases occurred in each of the eight houses ; of 36 persons who were inoculated, none died, while of the remaining 27 only 4 escaped. I could give many similar instances to show the great value of inoculation, and I fancy there are few men who have better reason for appreciating the greatness of Haffkine’s discovery than I have, but I think it is better to try and prevent plague by getting rid of rats. A firs engine is good for preventing a conflagration, but it is better to prevent the risk of a conflagration by getting rid of the inflammable materials. Haffkine himself is a strong advocate of rat destruction, and I had recently * an opportunity of discussing the subject at Berlin with Professor Koch, who said: “ You cannot stop plague by inoculation of man, for plague is a disease of rats, and if you want to get rid of plague you must attack the rat.” There are some who seem to think that we should rely mainly on inoculation, but my view is that if in the intervals between epidemics efforts are made to instruct the people in regard to the necessity for keeping cats, and if facilities are afforded for the distribution of cats, the necessity for inoculation would rapidly diminish. Prevention is better than cure, and distal prevention by rat destruction is better than proximal prevention by inoculation. I have inoculated as many as 523 persons in one day, and it is perhaps only when one has done large numbers of inoculations that we begin to realize fully what a difficult task it would be to inoculate the * This letter was written prior to the late Professor Koch’s fatal illness. enormous population of India—not once or twice, but every year when an epidemic comes. The Hon. W. Chitnavis, Chairman of the Nagpur Municipality, and also member of the Viceroy’s Council, in a letter written last month, says that “ the Nagpur people have come to realize the truth of your teaching, and I am sure they have even now showed ready keenness to possess cats. I know every time there is ‘ a breeding ’ of cats in my house I find that somebody steals them away. That in itself is a proof that cats are not despised, but that there is a demand for them.” Rat Destruction by Traps and Poison. Another thing which has tended to retard the due appreciation of the cat is the comparative success which has attended the efforts to remove rats by traps and poison. There are, however, many Hindus who object very strongly to the use of traps and poison, but even in the European quarter in Nagpur, where no such objection was met, it was found that, although rats could be cleared out by traps and poison, within a few weeks other rats would come in. It was only in those houses in which cats were kept that the rats could be kept permanently away. When plague began to spread in Nagpur we started what may be called the rat-hole inspection scheme. A number of inspectors were employed to go to each house, thoroughly inspect every nook and corner of the bungalows, and especially of the servants’ houses, and to lay poison at the rat holes. After a few days the rat holes would be closed up, and if new holes were found poison would be laid again. As an emergency scheme this was very successful, but it is expensive. Professor Koch’s Views Professor Koch has been for some years recommending the employment of cats for preventing plague, and in accordance with his suggestion the use of the cat is now being advocated by Kitasato in Japan. In the Public Health Reports of Japan (September, 1908), Kitasato gives a summary of Koch’s views, and the folio wing is an abbreviated extract from his report: “ The use of artificial methods like mechanical devices and poisonous drugs must prove laborious, expensive and at the same time comparatively inefficient; the limited powers of man are far inferior to the boundless resources of Nature. Examples: The lantana, a plant with pretty flowers, was introduced into the Hawaiian Islands, and after a few years caused great damage to agriculture. A small species of fly (Agromyza), which deposits its eggs within the seeds of the lantana, was introduced from Mexico, and in a few years the lantana showed signs of diminution. Second example: The sugar cane pest, a species of leaf hopper, in the Hawaiian Islands caused a loss amounting to several million dollars; an ant-like animal parasitic within the egg mass of the leaf hopper was introduced in 1904 and the sugar-cane pest was checked. Koch had experimented with the ichneumon of Egypt, the mongoose of India, and the common European ferret, but he found the cat most fitted for the task. The most useful things are often to be found among the most commonplace. An outline is given of a scheme for encouraging the keeping of cats, and attention is drawn to the necessity for providing holes, large enough to admit cats into rooms in which rats are likely to be found.” Professor Koch came to the conclusion that the cat is the best plague preventer in Africa, and his conclusion, taken with the fact that there is such a strong religious feeling, both among Mohammedans and Hindus, in favour •of keeping cats, must surely strengthen very considerably the grounds for holding the view that the cat is the best plague preventer in India. Cats in Malay Peninsula. Dr. Gimlette, in the Journal of Hygiene (April, 1909), refers to the fact that there has been very little plague in further India, and states that on this account con- siderable interest attaches to the small outbreaks which occur from time to time. “ The keeping of cats,” he says, “is a national convention which is common to other Mohammedan people, but in Malay the influence of folk- lore has an additional significance. The ancient super- stitious faith of the Malays before their conversion to Mohammedanism seems to survive in the everyday treat- ment of their cats. In 1907 plague broke out among a gang of imported Javanese coolies who had been working on the Duff Development Concession. There happened to be no cats on the company’s rubber estate, a fact which is interesting as giving negative support to Colonel Buchanan’s hypothesis.” Cats in Other Countries. It would be interesting to know how far the failure of plague to get a hold in other countries could be accounted for by the presence of cats. Kitasato had a census of cats taken in various parts of Japan, and found that the per- centage of cats to houses varied from 4 in Tokio to 49 in the Yamanashi district, where cats are kept specially to protect the silk industry from rats. Now in Tokio, after 4i million rats had been destroyed, it was found that rats were still numerous. At the Bombay Congress Professor Shiga informed me that plague could never get a hold at Yamanashi. I think, then, that inquiries conducted on these lines would afford valuable evidence as to why one country or part of a country should escape, while another suffers from repeated epidemics of plague. Since plague began, the medical inspection of ships coming from India is gradually developing into a sort of tyranny, arid the sooner people come to realize that a good supply of cats at the port towns and a few cats on Bhips are all that is required for preventing the spread of plague at seaports, the sooner will the discomfort which arises from the present system of inspection be abolished. Conclusion. Some time ago I ventured to predict that “ a few years hence we shall look on the neglect of the cat as one of the most extraordinary things in the whole history of our inquiries into plague and its prevention,” and already there are indications that this prophecy is beginning to come true, for we frequently hear people saying something like this: “ If plague is a disease of rats, it is only plain common sense to check it by keeping cats.” There are, however, still many parts of India where the value of the cat is not fully understood, and there is a tendency among some to think that plague is dying out. One of two courses is now open—one to trust to luck and to soothe our minds with the idea that plague is dying out; the other to leave nothing to chance, but to endeavour by every means to reduce the number of rats, and to impress on the people that of all the methods that have been employed for killing rats, and for keeping them away, there is none that can be compared with the rat-destroyer which has been provided by Nature—namely, the cat. [Extract from Editorial Comment.] THE PREVENTION OF PLAGUE Some 5ears ago Lieutenant’Colonel Buchanan, I.M.S., advocated the keeping of cats to exterminate rats to prevent the spread of plague. He has recently published a pamphlet on the subject and also a paper, which appeared in the Journal of August 6th, 1910. In this he stated that considerable progress had been made, and that many people had now come to realize the advantage of keeping cats. Undoubtedly the presence of large numbers of cats, especially if not too heavily fed, will keep down the numbers of rats in any given place . . . There is not the slightest doubt that the mere presence of a cat in a house tends to keep the mice away whether it catches them or not. This latter fact is one of the strongest points in favour of Lieutenant-Colonel Buchanan’s method, and one may rest assured that if several cats are wandering about a house at night no rats will come out and wander about as well. The smell of the cat, just as of the ferret, the rat’s deadly enemy, also seems to frighten them away. Plague has recently been carrying off so many people in India that every possible means should be tried to stamp it out. The policy that will ultimately lead to success should fulfil three conditions : (1) It should be efficient; (2) it should be available (or likely to be available in the near future); and (3) it should be acceptable—a very important thing for India. Inexpensiveness might be added to these requisites. Now the cat fulfils these conditions quite well, and as the native does not mind his cat killing rats though he dislikes doing so himself, there must be a very great gain in having such animals about. The late Professor Koch’s conclusion that the cat is the best plague preventer in Africa, taken in connexion with the fact that there is such a strong religious feeling amongst Mohammedans and Hindus in favour of keeping cats, must certainly strengthen Lieutenant- Colonel Buchanan’s view of the efficacy of the cat in India. We thoroughly agree with the dictum that the cat is useful in preventing plague, and that it should be introduced and propagated in parts of India where it is scanty or does not exist ... It is to be hoped that Lieutenant-Colonel Buchanan’s scheme will be given a fair chance in India and other places infected with plague. From the Times (London), August 8th, 1910.—“It is now well established that the rat is the chief or only source of the infective material of plague . . . The cat is so completely the natural enemy of the rat that any great abundance of both is impossible, and hence the encouragement of the former is the most certain method of reducing the number of the latter . . . He (Colonel Buchanan) quotes the late Professor Koch and Professor Kitasato as being in decided agreement with his views. He also attaches importance to the fact that the members of religions which object to the destruction of life, and who will not therefore kill rats themselves have no objection to keeping cats for the purpose . . . The sugges- tions made by Colonel Buchanan are simple and practical and manifestly deserve the attention of the authorities.” Indian Medical Gazette, May, 1909.—“ Colonel Buchanan deserves the very greatest credit for turning the attention of the public to the advantages and importance of the cat in the war against plague. There is no doubt that anyone who reads his pamphlet must admit that he has made out an exceedingly strong case and that he is in earnest . . . There is no doubt of the efficiency of the cat in India, and as Colonel Buchanan shows in the most interesting manner, the cat is acceptable to both Hindus and Mahommedans, being the only animal that is sacred or specially protected by both religions ... In Colonel Buchanan’s method of rat destruction we have a simple, cheap, and easily carried out means of tackling the rat problem ... it wrould appear to be the clear duty of the authorities to follow the example of the Japanese Government and give the measures advocated by Colonel Buchanan a fair opportunity of proving their worth.” Nagpur and Berar Times, May 2nd, 1909—“The best and cheapest solution of the problem therefore lies in keeping cats.” Englishman (Calcutta).—“A remarkably readable and in- structive pamphlet.” Pioneer (Allahabad), June 30th, 1908.—“The information afforded by Colonel Buchanan’s researches is of very marked interest, and much new and original matter is contained in the different chapters.” * - • • 3rm * Paper read before the Bombay Medical and Physical Society, September i 1900, SOME OBSERVATIONS ON PLAGUE AND ITS TREATMENT WITH LUSTIG'S SERUM /. $ ■ W c> By fo. Dr. N. H. CHOKSEY, In Charge, Arthur Road Hospital, crc. w - IScmkas: PRINTED AT THE “ TIMES OF INDIA ” PRESS. \ \jvCL \Y_jlj c*^- VAa(a. A A / 1/ Reprinted from Vol. IV, No. 5, of the Bombay Medical and Physical Society’s Transactions. SOME OBSERVATIONS ON PLAGUE AND ITS TREATMENT WITH LUSTIG’S SERUM. By Dr. N. H. Choksey, in charge, Arthur Road Hospital, etc. Mr. President and Gentlemen,—Your Secretary having kindly extended to me an invitation, through Lieut.-Col, Wilkins, to read a paper on the application of Lustig’s serum in plague, before this Society, I have with pleasure acceded to his request, inasmuch as I hold that no discussion on the subject would be without its due weight and value i-11 finally assigning to this serum its proper place in Sero-therapy. Before entering into the subject of the serum treatment, I would c^ave permission to preface a few general observations on the nature and types of plague, its mortality, and the influence of race, age and sex, etc., on the same,. All these have an important bearing on the results of the serum treatment. With this purpose I shall draw upon the records of the Arthur Road Hospital, which has received nearly 6,000 plague patients during the four epidemics of plague, about 4,000 of whom have been under my personal observation, and the rest under those of my various assistants, but under my general supervision. And I shall supplement these with some facts derived from the records of the Maratha and Modikhana Hospitals that receive—more especially the former—a better class of patients, belonging mostly to the labouring classes and mill-hands, than those admitted' in the institution under my charge,and who consist mainly of the lowest stratum of Hindu society,— the waifs and strays of the city, the ill-fed and the half-starved, picked up from the road-side or drawn from the alleys and bye-lanes where they do most congregate. The bulk of the following observations may, therefore, be assumed to be typical of plague as seen in its worst and most fatal aspects, and they do not apply to the better classes of Hindus, or to other communities, who suffer less in proportion to their numbers, and in whom the mortality is comparatively low. THE TYPES OF PLAGUE. For purposes of clinical observation, plague may be divided into the seven following types (1) Pestis Minor, (2) Pestis Ambulans, (3) Simple Bubonic Plague, (4) Septicsemic Plague, (5) Pneumonic Plague, (6) Cellulo-Cutaneous Plague, and (7) Non-typical forms of Plague, such as those associated with relapsing fever, malaria, small-pox, measles, cholera, phthisis, etc. The proportion in which these types occur in hospital practice is found from an analysis of ll.GOO cases of plague to be as follows:— (1) Pestis Minor... ... o-oo per cent, (2) Pestis Ambulans ... 0*50 (3) Simple Bubonic Plague ... ... 77-05 1} (4) Septicaemic Plague ... 14-25 If . (5) Pneumonic Plague ... 4-10 97 (G) Cellulo-Cutaneous Plague0 ... 2-50 yy CO Non-typical and mixed Plague ... POO lO'J-OO yr Pestis Minor and Pestis Ambulans. Pestis Minor and Pestis Ambulans, however interesting they may be from an epidemiological point of. view, do not call for any special remarks. No cases of the former ever seek hospital aid, and in the latter they occasionally resort to hospitals if the buboes happen to suppurate—as they sometimes do—and relief is required. Simple Bubonic Plague. Simple Bubonic Plague forms 77*65 per cent, of all cases, and is by far the most important type of plague. It is characterised, as its name implies, by the development of buboes in various parts of the bodyr and runs a definite course extending, from 8 to 11 days. And any subsequent rises of temperature after the eleventh day are generally due to suppuration of buboes or other complications. The temperature curve, which practically consists-of 2 curves, with an apyrexial interval, which may extend from a few hours to twenty-four or even more in some cases, is very peculiar and is so unlike that of any other disease, that it is quite characteristic and it has an important bearing on the behaviour of the serum, as I shall point out later on. There is usually a steady rise of temperature, till the evening of the third or fourth day, followed by a drop of two, three or more degrees on the morning of the fourth or fifth day respectively. The first curve ends here. The second curve begins a few hours after, and generally on the evening of the same day the temperature rises sud- denly high, to the same extent as on the evening previous or even higher, and coincidently with this, all the symptoms become grave, and death generally supervenes after this secondary rise or reaction. If the * During the last epidemic (1899-’00) the proportion was 3-Cl per ccut., »,e., about one per cent, higher than the average. patient is however going to recover, the reaction is not so high ; or if high, it soon subsides, the temperature drops again the next morning and it goes down steadily by gradually decreasing morning remissions and evening exacerbations until the normal is reached on the morning of the 8th, 9th, 10th or 11th day. There are many deviations from this, as in every other disease that runs a well-defined periodic course, but it would take up too much of time to discuss them in detail. It would be quite enough to state here, that the prognosis of the case greatly depends upon the termination of the first curve. The later it is, the better for the patient, and vice versa. And it has been found that for the serum to be effective, the patient must receive a large dose before the termination of the first curve and the longer the injection is delayed, the less the chance of recovery. The timely use of the serum before the temperature falls, contributes to lessening the shock consequent on the fall, which sometimes is very rapid and great, and may vary from 4 to 7 degrees or more and moderates the secondary reaction which is so dangerous and so fatal a feature of plague. The buboes that develop in different parts of the body have great influence in determining the mortality in this type. An analysis of 9,500 cases of buboes shows that they exist in the following relative frequency :— Femoral Inguinal Axillary Multiple Cervical Parotid Other situations 30'87 per cent. 23-25 21-85 13-95 6-72 F68 1-68 » 100-00 The average mortality rate in Simple Bubonic Plague is 77*25 per cent., but in individual position of buboes it may vary from 70 to 81 per cent., as follows :— Axillary Cervical Inguinal Multiple Femoral Other situations Parotid Mortality. 8P29 per cent. 78-87 77-62 75-87 72-56 71-42 70-34 )} Tho abovo mortality rates are again considerably influenced for the worse by the development of secondary pneumonia, or the occurrence of acute a-dema of lungs—one of the most common causes of death in bubonic plague—and in the case of cervical and parotid buboes by extensive infiltrations, serous or hemorrhagic, in the tissues of the neck, pharynx and larynx. Axillary buboes, again, if accompanied with extensive infiltration, are more fatal than the average of 81 *29 per cent. Septic/emic Plague. Septicajmic plague is a type of plague in which the bacillus pestis gains a direct entrance into the blood, and in which the patient suc- cumbs before any buboes can develop. Its course is more rapid than that of simple bubonic plague, extending at the utmost to six or seven days—usually from three to four,—and if the patient survives after the sixth or seventh day, a bubo generally appears shortly before death. The temperature curve is also different to that of simple bubonic plague. The temperature, as a rule, rises sharply and sudden- ly to 104° to 106°, or even higher, on the evening of the first day, and drops to normal or subnormal the following morning: and these morning and evening remissions and exacerbations may continue until death supervenes. In some cases the temperature remains high after tho first rise, and the fluctuations between the mornings and evenings do not exceed a degree or so, whilst in other cases the tendency is to remain between 97° and 101°. There are no buboes in this type, and plague bacilli can be obtained in abundance from a drop of blood. If the patient’s resisting power is so great as to tide him over the first four or five days, buboes appear simultaneously on various parts of the body. Haemorrhages from the lungs, stomach, intestines and kidneys are very common in this type. The mortality rate in 1,502 •cases was found to be 89'62 per cent. Pneumonic Plague. This form of plague to which Major Childe, I.M.S., drew our attention in 1897 is the most fatal ; the mortality in 514 cases was found to be 96*69 per cent. It exists variably in different epidemics, and in no two does it appear in anything like a fixed ratio. Its duration is short, from four to seven days—usually about four to five,—and it is characterised by high fever, rapid and distressed breathing, absence of buboes ; localised lobular pneumonia in isolated groyish patches, distributed over one or more than one lobe, with haemorrhagic sputum, which may be frothy and copious, or scanty, and in small pellets of almost pure congealed blood, or at times it maybe totally absent. Almost pure cultures of plague bacilli can be easily obtained from the sputum, and it is obvious that it is not only therefore the most fatal, but also the most dangerous and highly infecting type of plague. Cellulo-Cutaneous Plague. In the clinical report on plague which I published in 1897, I described, under the heading of Cellulo-Cutaneous Necrosis, large necro- tic patches involving the skin and the subcutaneous cellular tissue. Their origin was then obscure, but I surmised that they originated in the small umbilicated blisters which are occasionally seen, and sometimes constitute the only external evidence of plague. Further observation during the last three epidemics has not only confirmed this, but has led to the knowledge that these necrotic cases form by themselves, not only a distinct type, but also a comparatively milder type of plague, and which I propose to call Cellulo-Cutaneous Plague. It is now an accepted belief that in most cases of plague one of the principal channels of: infection is through the skin. The bacilli, soon after they gain an entrance thus, are conveyed to the nearest lymphatic glands without leaving any trace at the point of entrance. In thi instance, however, they remain in situ, and proliferate, and give rise to the large advancing necroses. A blister with or without an umbilication, generally the former, forms at the point of infection. Its contents are at first serous, and perfectly clear : they may become, however, turbid and purulent, and even haemorrhagic. Suspended from the central umbili- cation is a core which reaches to the floor of the blister. The cuticle breaks, the contents are discharged, and a reddish, angry-looking circular patch remains. Within a few hours it becomes of a dark- greenish hue, cold to the touch, hard, and almost leathery, the margin being conterminous with the surrounding healthy skin. The patch then begins to enlarge and advances from the circumference, and its size increases day by day, until a line of demarcation forms. The necrosis appears to be tied down firmly in the centre, which appears depressed, the edges being elevated. Around the circumference a hard red, angry-looking and raised areola is formed, sometimes covered over with minute sericles. The necrosis might go on advancing till largo areas of the body surface may be involved, the largest hitherto seen covering nearly 80 square inches. The size may vary from an inch or 0 even leas in diameter to eight or twelve inches. Large necroses cover- ing the whole of the gluteal region, the entire calf of the leg, or the interscapular space, have been noticed, and they have been found also on the scalp, neck, face, chest, abdomen, loins, thigh, leg, dorsum of foot, vulva, scrotum, etc. After the line of demarcation has formed, removal of the necrosis is fairly easy, if the sloughs underneath have separated, and when the whole of any such necrosis is removed en masse by the knife or scissors, a large unhealthy-looking saucer-shaped depression is left, with long and irregular shreds of necrosed tissue, pus and blood, and which under appropriate treatment becomes healthy-looking within three or four days, and heals fairly rapidly by granulation, and without the aid of skin-grafting. If the necrosis goes on however steadily enlarging, and the line of demarcation does not form bv itself, it is possible to restrict its no grosser libel on plague than to characterise a piague case mnu. * __ the mildness or otherwise is not to be, and cannot be, determined when the patient comes under treatment, but after the disease has run a certain course, and I hold that it would be certainly bold of any one, however wide and varied his experience of plague may be, to declare a case mild within the first three or four days of illness. And if I have been credited with selecting mild cases, I cannot certainly lay claim to any such super-human prescience. In no disease is it easier to tell what patient is going to die, and in none more difiicult as to who is going to recover. Under these circumstances, I submit, the words, u selection” and “ mild” were hardly appropriate. The clinical phenomena that manifested themselves after the injection of serum, were :—moderation in the intensity and duration of fever, im- provement in the state of the circulation as shown by increase of arterial pressure, diminution in the size of, and lessening of pain in buboes, cessation in the progress of advancing lymphatic infection, clearing of the mental faculties, and a general improvement in the condition of the patient. In those cases, where it did not ultimately save the life of the patient, it produced great amelioration in his condition and prolonged life, and time after time patients in semi-comatose condition have been observed to improve to such an extent as to be scarcely recognizable. It was also noted that the effects of the serum were not so evident in cases of septicaemic, or pneumonic plague or in those cases that have a naturally very high rate of mortality. On the other hand, its value was quite apparent in those cases that have a comparatively lower mortality rate, and which was still further reduced by its use. and from the advancing margin of the necrosis. And a timely con- firmation of this local necrotic action of the bacillus pestis comes from Klein.0 In his introductory remarks, as President of the Section of Pathology at the Annual Meeting of the British Medical Association last month, he describes the share which microbes have iu determining inflammation, which, he says, is brought about (1) by the toxic products of the microbes, or (2) by the protoplasm of the microbes themselves. The diphtheria bacillus, the tubercle bacillus, the tetanus bacillus and the typhoid bacillus possess the pro- perty of setting up inflammatory phenomena, locally and generally, through the action of their toxic products. The tubercle bacillus, the and often been proved to exist in association with plague ; during the- epidemic of measles in 1898-99 several cases of plague with a distinctly measly rash were noted ; and during the present year small-pox and cholera have been observed associated with plague. Small-pox develop- ing in a case of plague and plague appearing during the progress o». small-pox have been noted, and latterly a mixture of plague (pneumonic as well as bubonic type) and cholera has also been observed. Plague has also been noted to be associated with acute venereal infection, and. some fatal cases with hard and soft chancres have been observed. MORTALITY IN PLAGUE AND THE INFLUENCE The observations on the above lines were intermittent on account of the supply of serum being limited, as well as irregular, and there were long intervals during which no serum was available. They extended from March to October 1898, and again from February to April 1899, during which period, 403 patients were treated, of whom 249 died and 184 recovered, the recovery rate being 38^21 per cent. During the same period 1,190 patients were under ordinary treatment, of whom only 233 recovered, the recovery rate being 19*5 per cent. The differ- ence, therefore, in favour of the serum treated cases was nearly double. The Maratha and Modikhana hospitals received during the above period 4,762 patients who had a recovery rate of 19'7 per cent. There is thus a remarkable coincidence in the recovery rate between the non-serum cases at the Arthur Road Hospital and all the cases at the two latter hospitals. If it be conceded that the type of the disease, and the nature of the cases admitted into these hospitals, were the same—as they actually were—to- what should we ascribe the enhanced recovery rate of the serum cases ? It could not be ascribed to the so-called “ selection ” cases or “ mild ” cases, for were it so, the recovery rate in the non-serum cases ought to have reached a vanishing point, whereas it was not lower than the average recovery rate of the other hospitals. It would be beside the purpose of this paper to enter into any lengthy argument on these points and to those interested in the subject I would refer to the able report of Dr. Polverini published last year, as it contains all the replies to any arguments that may be advanced. Preliminary Conclusions.. The following preliminary conclusions were deduced from the above observations :— 1. That the serum exerted a distinctly favourable influence on the course of plague. 2. That where it failed to avert death, if prolonged life, and temporarily ameliorated the condition of the patient. 3. That it did not exert much effect in those types of plague that are characterised by an extremely high mortality rate. 4. That its application therefore was mainly, though not exclusively, limited to the bubonic type of plague. 5. That there were limitations to its use in hospital practice, as about 50 per cent, of all admissions die within 48 hours, 20 per cent, recover naturally, and there remain about 30 per cent, that can be influenced by the serum treatment. 6. That its use would be more effective in private practice, as early cases would be treated, and that encouraging . results, giving a recovery rate of 59‘37 per cent, in 32 patients, have been obtained up to now. 7. That it exerts no deleterious influence on the patient, and could be injected into the healthy not only without any ill-effects, but with positive good, as it is capable of conferring immediate but temporary immunity against plague ; this immunity may last from 10 to 15 days. The Alternative Method. Some doubts having been expressed on the validity of the results of the above observations, and the conclusions they led to, and as it was anticipated that more accurate data would be available if no attempts were made to exclude any class of cases, and by treating every alternate patient in the order of admission into hospital, it was resolved to conduct a series of 1,000 observations,—500 cases to be treated with the serum and 500 alternately with them by ordinary treatment. There were certain objections and fallacies involved in this method, to which I drew attention before the observations were begun. Whilst discussing this method of treatment with Professor A. E. Wright of the Indian Plague Commission, I had the houor to draw his attention to the complex nature of the affection, and the number of wide and varied factors that contribute to influence its mortality rate and to point out by actual data furnished from the hospital records, how race, sex, age, the type of plague, the position of buboes, the date of illness at commencement of treatment, .and the general condition of the patient, including the state of his circulation, influenced plague mortality. I further contended that for any set or sets of observations on the alternate system, it is quite indispensable, in order to secure accurate results, to so arrange that a serum case and a control case should be,—if not identical, at any rate approxi- mately so, as regards the above important factors, and that so long as these did not equalise, so long would the results be the Jess accurate. Professor Wright had to admit the force of these contentions, but said that under the conditions prevailing in the Bomba}' hospitals it would not be feasible to have such exact controls, but the probabilities were that in a series of 1,000 cases, the conditions would fairly equalise. We shall see later on how this anticipation has been realised in actual practice. Moreover, it was also thought that the moribund and con- valescent patients would balance each other in either series. The observations on the alternate system extended from May 1899 to end of July 1900—June 1899 being excepted. During this period 484 cases were treated with the serum, and 484 were taken as controls and were under treatment by ordinary methods. The former had 155 recoveries, equivalent to a recovery rate of 32*03 per cent., whereas the latter had 99 recoveries, that is, a rate of 20*46 per cent. ; there was thus a difference of 11*57 per cent, in favour of the serum cases. It would take me too long to enter here into any detailed analysis of these 968 cases, and as my friends Drs. Polverini and Mayr have just completed a comprehensive report, which will soon be published, I would refer you to the same. All that I need state here is that the fallacies to which we drew attention before the alternate system was begun, appear themselves most glaringly in the results, and in fact Drs. Polverini and Mayr have been enabled by these very statistics of the alternate system to expose the errors incidental to such a system when dealing with such a complex disease like plague, and thus to confirm our prognostications. The factors to which I drew your attention above as likely to influence and vitiate the final results, have not become equal- ised in either series, and to take one instance alone, the serum cases included 139 moribund patients that died within 24 to 27 hours of ad- mission, and 29 convalescents that recovered, as against 147 moribunds, and 38 convalescents on the control side. If for purposes of argument we ignore the moribunds from our calculation, as they were bound to die under any case, and take stock of the convalescents only that tended to obscure the results, and eliminate the same from either series, the serum cases show a recovery rate of 27’70 per cent., whereas the controls have a rate of only 13*68 per cent, only, i. e., nearly half that of the serum cases. If both the moribunds and convalescents be ex- cluded the recovery rate for the serum cases would stand at 39'88 per cent., as against 20*41 per cent, in the controls. Or to put it in other words, the recovery rate is enhanced by 56 per cent, in all cases treated alternately: by 95 per cent, if the moribunds and convalescents be excluded and by over 100 per cent, if the convalescents alone be eli- minated. A curious confirmation of the beneficial effects of serum is demonstrated by the cellulo cutaneous type of plague, which occurred somewhat to a larger extent during the last epidemic. Thirty-nine cases of this type came under observation, and of these 18 received the serum treatment, and 21 were treated by ordinary methods. Of the former 9 died'and 9 recovered, the recovery rate being exactly 50 per cent., where- as of the latter 13 died and 8 recovered, the recovery rate being 39T0 per cent.; that is the difference between the recovery rates of the two sets of cases was 1T90 per cent.—about the same as the difference shown on the’total of all observations. And thus even this small series of a peculiar type of plague proves beyond a shadow of doubt the influence of serum in reducing the mortality rate. It may be added that during the above period, there were 38 cases- that could not be included in one series or the other on account of the difficulty of diagnosis during life, or rapid death when kept under ob- servation. All these cases were subsequently verified to be plague after death—and in only six that recovered out of them, the course of the affection left no doubt as to their nature. These were called extra cases and have remained totally unconnected with the above. The results of these observations have confirmed the preliminary conclusions above stated, and a great step in advance has been made by the further knowledge gained during this enquiry. That the in- fluence of the serum treatment is demonstrable as a whole in reducing the total mortality of a hospital, can be shown by a comparison with the records of other hospitals. The total mortality rate of the above 1,006 cases ( serum, control, and extra ) at the Arthur Road Hospital was 7415 per cent. During the same period the Maratha Hospital had 2,599 cases, and the mortality rate was 80’95 per cent. So that with less than half the number of patients treated with the serum, at the Arthur Road Hospital, the mortality rate of the institu- tion was 6’80 per cent. lower than that of the Maratha, that receives a certainly better class of patients,—that is to say, that if all the patients at the former had been treated with the serum, the difference in the mortality rate between the two institutions would have been over 13 per cent. Mode of Application of the Serum—General Treatment, Etc. I will not weary you with all the details that we had to work out for ourselves, and without any previous experience,as regards the applica- tion of the serum, the best method for the same, &c., &c. The results of our experience have been embodied in the accompanying copy of 16 3. Cleanse the skin thoroughly with soap and water, and carbolic, sublimate, or lysol lotion before injecting. 4. After withdrawing the needle, seal up the puncture with collo- dium and cotton wool. I 15 instructions prepared for private medical practitioners, to whom it is intended to issue tbe serum for use in private practice. I would only add that, subsequent to the date of the framing of these rules some further observations have been made, which tend to show that two or three large doses of the serum, injected early, and within short JC Y. General and Local Treatment. The following lines of general and local treatment are suggested for cases treated with the serum :—• 1. Stimulants :—Brandy or rum in doses varying from 2 drachms to half an ounce or more, and well diluted should be administered every 2 hours. The quantity of alcohol required for each case would depend upon the habits, and the general condition of the patient. 2. Nourishment:—Milk or milk and conjee should be given every 2 hours in quantities varying from 4 to 8 ounces. 3. Cardiac Remedies :—If the patient’s condition when first seen is very low, or if it becomes so in the course of treatment, and if the heart’s action is impaired as shown by a weak, thready, readily com- pressible pulse, or if the pulse is intermittent or fluttering and impercep- tible, cardiac remedies should be administered hypodermically in addi- tion to the serum injections ; but these should be used with great cau- tion and at intervals of 6 to 8 hours or longer. 4. Control of Temperature:—Avoid, as far as possible, any drug treatment. Ice-bag to the head, sponging or wet pack should be the means of reducing high temperatures. 5. Complications :—Treat all complications on general principles. fi. Local Treatment Avoid all irritating applications to the bubo ; apply ice over the same. The above facts comprise all the data we have at hand up to now on the influence of Lustig’s serum in the treatment of plague, and they have so far satisfied the authorities concerned that preparations have already been made to make it on a larger scale for the next epidemic, and it has now been determined to revert to the former method of treatment, but on a larger scale, i.e., to treat all, exclusive of the moribunds and convalescents. Comparison with Sero-Therapy in Diphtheria. The only disease in which sero-therapy has given encouraging results up to now is diphtheria. But for purposes of comparison, diphtheria and plague stand wide asunder. They are so dissimilar in their duration, fatality, and mode of death,—plague being by far the graver of the two, that comparison can only be instituted under large reservations. Dr. Alexander Anderson, of Sheffield, has given* some interesting data of mortality statistics in diphtheria, both before and after the introduction of the antitoxin treatment. The average mortality in the Metropolitan Asylums Board Hospitals during the past re-antitoxin period (1888 to 1894) was 30‘3 per cent, in 11,598 cases ; from 1895 to 1898, it became reduced under the antitoxin treatment to 18'4 per cent, in 20,382 cases—a reduction of 12 per cent. And I would put it to you, which is the greater achievement,—a re- duction of 12 per cent, mortality in a disease with a natural mortality of only 30 per cent., after over a decade of observation and research, or a reduction of 12 per cent, in a disease with a natural mortality rate of 80 per cent., within 3 years of the inception of sero-therapy in the same ? There could be but only one reply to this, and that is sufficiently obvious. In this connection I should like to quote a few remarks of Dr. Anderson’s on sero-therapy in diphtheria, which are so opposite to sero-therapy in plague and which mutatis mutandis, word for word might be made applicable to plague :— “ I am strongly of opinion,” says he, “ that antitoxin ought to be given in every case, however mild, unless it is seen too late for the remedy to be of any value. The objection urged against the use of antitoxin in mild cases, that by other methods of treatment 60 to 70 per cent, of cases will recover, and that there is therefore no necessity to give antitoxin in these sixty or seventy cases, does not seem to me to be sound reasoning. In any individual attack of diphtheria, we are dealing with an unknown quantity, with bacilli whose potentiality for mischief cannot be estimated. It does not follow that because a case appears mild at the onset it will remain mild, and that any time grave symptoms may supervene in an apparently mild attack. In judging of the severity of an attack of diphtheria, two factors have to be taken into consideration—(1) the susceptibility of the patient, and (2) the virulence of the organism. Of these factors in any individual patient we know next to nothing. The personal equation is too often lost sight of. One is often surprised to find symptoms of cardiac failure, nephritis and paralysis occur in cases where one would have least expected these complications. The cells of certain individuals are peculiarly susceptible to the diphtheria * Quarterly Medical Journal for Yorkshire and the adjoining Counties February, 1900. toxins, and as we cannot gauge the resisting power of any patient beforehand, we are not justified in withholding the antitoxin.” Would you not apply these remarks to plague, enhanced three-fold in their serious import and gravity, and would you not then realise what measure of success can attend the lot of one whose labours are cast in the field of plague therapy ? Criticisms. Like every other new method of treatment, Lustig’s serum has had to undergo criticism. We invite criticism in matters scientific, but at the same time we stipulate that the criticism should be intelligent, that it should be informing, and that it should be honest and straightforward. At the same time, if it does not fall within these requirements, we discard it. I have to say it with great regret that almost all the criticism levelled at the serum treatment lacks one essential element, viz., personal observation and personal interest; and that, instead of inquiring into the subject as a matter of scientific interest, the critics have been led away by a certain amount of prejudice and distrust engendered, no doubt, by the glowing expectations with which another serum was received in Bombay early in 1897, and its limited results and the failure of sero-therapy in other diseases. But the conditions under which we work our public plague hospitals, the material with which we have to deal, and the complex nature and rapidity of death that characterise plague, forbid any such glowing expectations. We have to be thankful for such small mercies as are vouchsafed to us by any line of therapeutics, and if we succeed in enhancing the recovery rate by 50 per cent, in all cases, as we do with Lustig’s serum, we should consider our labours amply repaid. Under such circumstances I trust you will agree with me when I say that if I dojiot attach any importance to certain criticism, directed without personal experience, and from a safe and respectful distance, I am perfectly justified in adopting the course. There have been some critics who have reared up a fetish, to which they ask us all to bow down in all humility. Armed with a micros- cope, a few tubes of agar, a box of paint aud a gas jet, with a rabbit or two thrown in, they consider themselves competent to solve all the mysteries of disease in our complex human organism. They look down upon clinical observation, and a clinician is to them a creature to be tolerated as an inevitable, but necessary nuisance, and whom they would readily cast aside if they could. A human being is much too large an object for their study, and with a rat or a rabbit, and perhaps occasionally a monkey they are well content. They are apt to apply bodily and without due reservation, the results of their observations on lower animals to man, forgetting, at the same time, the essential differences in the vital processes of the man and the brute. Protests have been frequently raised against this tendency on the part of bacteriologists, by bacteriologists themselves, and by none so emphatically as the members of the Indian Leprosy Commission that included such noted bacteriologists, as the late Professor Kanthack and the late Dr. Beaven Rake, and the late Major Barclay, I.M.S. They say:—“We regret that without in the least under- estimating the importance of bacteriological and animal experiments, the modern advance in these have led observers to take a one-sided view to the disregard of the evidence derived from clinical and epidemiological experience. The bacteriologist, in experimenting upon highly susceptible animals, easily runs the risk of arguing beyond his premises and of drawing conclusions from his experiments, which he applies without sufficient reserve to the natural mode of infection. We believe that it is quite impossible for bacteriology alone, without the aid of clinical and epidemiological observations, to deduce the setiology of an infectious disease.” And yet after all our clinical ex- perience of plague in Bombay, during four epidemics, we are calmly told that the clinician is not to be trusted to diagnose plague, and that his opinion and diagnosis do not count for much, so long as the bacteriolo- gist is not at hand with his paraphernalia. I do not wish to be misunderstood. I have the greatest respect for the bacteriologist and his valuable work, so long as he remains within his proper sphere ; but the moment he forgets himself, and oversteps functions that do not legally and equitably belong to him, he becomes an hindrance instead of a useful help, which I readily admit he most undoubtedly is, and it is against this tendency of the bacteriologist to trench upon and usurp the rights that justly belong to the clinician, that I beg most empha- tically to protest on this occasion. I have been led to make these remarks because some persons having no other weapon or argument against the serum treatment, have gravely advanced one, vis., that the better results of the serum treatment could be explained away by the fact of cases that were not plague, having been taken as such, and that no case should be considered as one of plague unless and until the examination of blood reveals the presence of the bacillus pestis. Now, those who advance these arguments forget that if there are any errors of diagnosis, they ou ght to "be on both the sides the serum as well as the control, for it is not human for any clinician to so contrive that all his diagnostic errors should fall under one category and not the other. If there were any errors on the serum side, the controls should have shared equally in the same. They also forget that, time after time, the most exact and pains- taking examination of the blood, both by the microscope and by culture, have failed to reveal the presence of the bacillus in the most undoubted cases, and even fatal cases of plague, and that it is only just prior to death that in many cases it may be detected. The Austrian Plague Commission, who made daily exhaustive investiga- tions into this matter extending seriatim over 150 cases, confirm this. If then bacteriology fails to help us at the most critical moment, and the clinician is not to be trusted to make proper diagnosis, to whom should we turn for guidance ? A false analogy has been introduced by some in this controversy. Because in every case of diphtheria, it is necessary to verify the diagnosis by bacteriological examination, ergo, they argue, the same should be done in plague. They obviously forget that unlike, as in diphtheria, there is no other disease that can be mistaken for plague, just as croup—a comparatively benign disease,—is often mistaken for diphtheria. In the absence, therefore, of any other disease in our whole nosology that can be mistaken for plague, I fail to see the neces- sity of imposing% bacteriological examination in every case, or dis- trusting the results in those cases in which it has not been done. No other affection presents the typical cardinal symptoms of plague which are evident, more or less, in every case, and during epidemic times there is no disease of which the diagnosis is so easy. And yet in spite of this evident fact, it is often regrettable to observe that woful want of common sense, that fatal hesitancy, and that perverse inability to look things squarely in the face, that characterise the diagnostic efforts of some, who ransack the heavens above and the earth below for some cause or causes, probable and improbable, of the clinical phenomena they see, whilst self-evident facts appeal to them mutely but in vain and indicate what course to pursue. To this and to this source alone, I am inclined to attribute the high mortality rate that is so often observed in privato practice, especially among the better classes of people. Much valuable time is thus lost, and what timely assistance could have done in the oarly stages, becomes unavailing later on. The essence of 2 a plague treatment by serum, lies in its immediate, early and free use, and every hour that is wasted in futile diagnostic antics or self-deception adds to the danger of the patient. It is said that whilst 2,000 units prove beneficial in a case of diphtheria on the first day, even 50,000 are powerless on the third or fourth day ; and so also in plague. A good dose on the first day and perhaps a second one on the day following would, I believe, eventually suffice to arrest the progress of the disease,- although it would not be possible to undo the mischief already done, and which no serum is capable of doing. Then again it has been said that the personal bias of the clinician has much to do with the results. Nothing could be further from the demonstrable facts. However much this aphorism may be applicable to fields of laboratory research and animal experiment, it does not bear upon clinical observation, for there could be no personal bias, in clinical medicine, and no observer can convert into plague a case that is not plague and vice versa. The question becomes narrowed down to only a single issue. Were the cases treated with the serum, plague or not plague ? If the former, then no personal bias could enter into the inquiry: if the latter, then it shows that no clinician, however wide or varied his experience is trustworthy. No physician is infallible, and I do not claim to be one. This much would I permit myself to say, that the greatest care and circumspection was exercised in eliminating all sources of errors consequent on faulty diagnosis, and all that skill, experience and constant and daily vigilance could do to secure accur- ate results was done. If after that there were any errors, I may add humanum est errare. And now I shall conclude this paper in the same words, with which I closed a recent communication to the Lancet. “We have no reason to be dissatisfied with the progress made within two years of its application. Neither the mode of its preparation, nor its applica- tion at the bedside have yet been finally determined, and it is only by further research, experiment, and prolonged clinical observation, that we shall be enabled to place it on a proper basis. So far as we have gone, we have been able to prove that the serum treatment is the only treatment that can in any way reduce the high mortality of plague, and we abide by our experience,” r / (No. 2, February 1907) "jot*:' FURTHER OBSERVATIONS ON THE USE OF ADRENALIN IN PLAGUE BY KHAN BAHADUB N. H. CHOK8Y, m.d Hon. Causd, Freiburg, Germany ; Special A eeistant Health Officer, Bombay Municipality, in charge of Arthur Road and Maratha Plague Hospitals, Bombay Calcutta THACKER, SPINK AND CO 1907 . ‘si.-. V ■ - ':-A v“. ----- v;:.. . .3 ' ^ &: .4-*^ k; i$J8N? :r is$" >&-**•;..' ■ ; •> FURTHER OBSERVATIONS ON THE USE OF ADRENALIN IN PLAGUE. By KHAN BAHADUR N. H. CIIOKSY, m.d., Hon. Causa, Freiburg Germany, Special Assistant Health Officer, Bombay Municipality, in charge of Arthur Road and Maratha Plague Hospitals, Bombay. In a previous communication to this journal * the pre- liminary observations with adrenalin were related. They indicated that adrenalin exerted a distinctly beneficial effect upon the circulation by increasing the pulse tension, remedying its irregularities and steadying and sustaining the action of the heart, until such time as the system was able to eliminate the toxins, and bring about recovery. The full measure of the effects of the drug could not, however, be demonstrated, inasmuch as it was tentatively employed and other drugs were simul- taneously used. Nor was it then possible to determine in what doses and with what frequency it could be exhibited, the limit of its usefulness as also of its tolerance and finally its ill-effects, if any, had to be established. Further observations were therefore undertaken at the Maratha Plague Hospital during 1905 when adrenalin was used throughout the whole period of the epidemic, and certain data having been obtained, its use was still furthur extended during the epidemic of 1906. It is the purpose of this article to summarize the results of the above observations. * Cardiac Failure in Plague and its Treatment, April, 1905. ■± The main object of the observations, 19U5, was to compare the effects of small, medium and large doses of adrenalin, to fix the limit of the safest single maximum dose, to determine the frequency of its administration, and to record its after or ill-effects. Correct records of the amount administered and its frequency were kept and the effect upon the circulation carefully noted. As during the height of the epidemic, Yersin-Roux antiplague serum was also employed, it was possible to institute comparison between those cases treated with the serum and adrenalin and those without. * And full confidence having yet to be established in its utility, it was determined to use it simultaneously, but in alternate doses with the stimulant injection previously described (strychnine, sparteine and atropine). In order to allow of facility in administration and exact dosage, it was pi-escribed in the following formula : — R Adrenalin solution ... ... m. 5 Normal salt solution ad ... 5* The initial dose of the above varied from one to three drachms every three or four hours according to the condition of the pulse. If there was no improvement, or if the pulse became steadily worse, the dose was increased from four to six drachms and the frequency to two hours. When so prescribed, it was not found practicable for various reasons to administer twelve doses in the 24 hours, and the daily average in grave cases therefore came to about ten doses, equivalent to about 300 minims of adrenalin solution. This maximum dose was kept up for three or four days, sometimes longer, and after the pulse exhibited sustained improvement, it was gradually reduced by one drachm at a time, and subsequently at longer intervals. The doses were gradually decreased as the patient’s condition improved, and in by far the largest number of cases it was entirely stopped by the end of the second week. Even after sustained improvement in the condition or the circula- tion, it was found that abrupt stoppage or too great a reduction in the dose was not safe. It soon reached unfavourably upon the pulse, necessitating increased dosage. The decrease should therefore be always gradual and its effects require careful watching. If the maximum dose failed to have any effect, the condition of the patient was practically hopeless. In those cases where the circulation did not improve, notwithstanding the disappearance of all acute symptoms and general amelioration, it had to be kept up, and some patients received adrenalin in small doses for periods extending from six to eight weeks without any apparent harm. In order to grasp fully the results obtained under the above method, it would be necessary to revert for a time to the results of the previous observations of 1904 which were as under :— Line of treatment. Number. Died. Recovered. Case mortality per cent. Stimulant, and cam- phor injections ... 324 268 56 82-7 Stimulant injections 4- adrenalin (by mouth) 598 416 182 69'5 Adrenalin only (mostly subcuta- neously) 70 47 23 67-7 The above statement indicates that adrenalin used by itself had greater influence in lowering the mortality than when employed simultaneously with the stimulant injection, and further that the combination of stimulant injection aud adrenalin showed better results than the older method of treatment by stimulant and camphor injections only. The results of the observations of 1905, may now be stated as follows :— Line of treatment. Number. Died. • Recovered. Case mortality per cent. Stimulant, injection + Adrenalin 1,038 810 228 78-0 Do do + Yersin-Roux serum 222 138 84 62T twenty-four men were inoculated, but this was not compulsory. The history of this vaccination is about as follows;— “The culture was carefully carried out and identified, and was known to be a pure culture of the cholera organism up to 24 hours before the time when the vaccination was made. A large number of tubes of cholera media were • inoculated from these pure cultures and placed in the incubator. On the following mornincr the cultures were each suspended in one cubic centimeter of saline solution, the whole mixed, and inoculations, as .was necessary, made imme- diately after the preparation of t he suspension, it is supposed that some one placed a 48-hour virulent plague culture among the cholera cul- tures, the blue pencil marks which designated the culture having been erased from the glass by handling. This view is supported by the fact that on the afternoon of the day of inoculation a 48-hour virulent culture was missed from the incubator. It was known certainly that one of the five plague cultures prepared two days pre- vious!)’, as was shown by Dr. Strong’s note-book, bad been removed from the incubator, but it was not until two days later, when lie wished to examine the opsonic index of live guinea-pigs, for each one of which a 48-hour richly-grown culture had been prepared, that the plague cul- ture was missed. “ It was proved by a technical committee of three physicians appointed by the Governor- General to investigate the matter that a 48-hou»* richly-grown plague culture spread over the entire surface of the entire slant resembled some of the cholera cultures so strongly that they were unable to identify or to pick out such a plague culture by its gross appearance when it was placed among a number of the cholera cul- tures of the strain employed. It was also shown that a hanging-drop preparation and the stained microscopic one made from the mixed suspension of all the cholera cultures contaminated with the plague one (as used for the human inoculations] did not reveal the suspicion that the fluid was contaminated with plague bacilli, since no bipolar staining organisms were visible and, evidently, the plague bacilli were in too small numbers or those present did not show any sufficiently distinctive morphology to separate them from the pleomorphic cholera organisms in the saline solution. Nevertheless, this same suspension, in which plague bacilli were not detected by microscopic examination, when injected subcutaneously into guinea-pigs and a monkey, caused, after several days, death from plague infection. It has not been ascertained who placed the plague culture among the cholera ones after all possible tests of the cholera culture had been made. An investigation of the entire matter was pursued by the Government pros- ecuting attorney at our request, and later the Governor-General, in order to satisfy public opinion, appointed a committee of eight, six Filipinos, one American and one Englishman, three of which committee constituted a technical committee, for investigation. “ While the serum division of this laboratory is also in charge of Dr. Strong, and while this division prepares our regular cholera vaccine, it must be clearly understood that the regular preparation of our cholera prophylactic had absolutely no connection with this matter and that the vaccine used by Dr. Strong on the day of the accident is entirely distinct from the pre- paration with which he is identified. The a—2 method used on the Inst, twenty-four prisoners is the one which is best known by the names of “Ferran” and “ Haffkine. ” It is perhaps unnecessary to add that the laboratory has pre- pared several million units of vaccine virus and several thousand doses of plague prophylactic which have been us< d (in addition to the cholera prophylactic) with good results and without • accident.” I. The study of vaccination against cholera, according to the method worked out in 1890-93, in the Paiis Pasteur Institute, began in India in April 1893, that is, some 13 years previous to the Manila accident. The procedure which was adopted for cultivating and inoculating the vaccines was described, with great detail, in a pamphlet published in Lahore, Punjab, in 1894, by Mr. E. H. Hankin, M.a., Chemical Examiner and Bacteriologist to the Government, Surgeon Lt.-Colonel Ch. H. Owen, Medical Adviser to the State of Patiala, and myself, under the title of “ Technique of Haffkine’s anti-cholera inoculation.” The pamphlet was reproduced in the Indian Medical Gazette, Calcutta, in June, 1894. A more detailed version of the same “ Technique” was published in the journal just mentioned two years later, in June 1896, by Lt.-Colonel (then Surgeon- Captain) Hare, i.M.s., the present Sanitary Commissioner of Eastern Bengal and Assam. In the issue of the same journal for November, 1896, in an article entitled “ Technique of Haffkine’s method of preparing fixed cholera vaccine,” the same officer described the method of transforming cholera virus into the vaccine strain. The extent to which the above technique rendered the operation safe, and the facility with which it was learned by non-specialists and by subordinates, may be gauged from the following facts. The inoculations were at first carried on by myself, and between 1893 and 1896 were intro- duced in over 100 towns and villages in the Indian Plains and the Himalayas. I prepared the vaccines in trains, while travelling from place to place, in the ordinary passenger carriages, and at Railway stations, while wait- ing for the arrival of trains; also in tents, in dak-bungalows ” and rest-houses ; in rooms placed at my disposal for a day or two in dwell- ing-houses and transformed for that time into “laboratories;” and sometimes (in Calcutta and Agra) in established laboratories, in which various work was carried on at the time by other workers. Between April 1893 and July 1895, 42,197 people, who received in all close on 70,000 injections, were inoculated under these conditions, and in 1896, a further 30,000 were so operated on. A large proportion of the inoculated lived under medical and adminis- trative supervision, so that any unusual effect of the inoculation could not have escaped notice. Thus, the operated on of 1893-95 comprised officers, non-commissioned officers and men belonging to 64 British and Indian Regiments; contract labourers of 45 tea plantations in the Brahmaputra and Surma Valleys of Assam ; inmates of nine civil jails; children of boarding and other schools, etc. In 1894 the Municipal Corporation of Calcutta, voted a grant to its Health Office for applying these inoculations experimentally. A Hindu Medical Inspector, Mr. Jonomanjoy Chovvdry, a was put on to this duty. He was assisted, in the preparation of the vaccines, l>y two other Hindu officers, Messrs. Jogendranath Dut.t and Sasi Bhusan Ghose, of the Calcutta Healtli Office. None of these doctors had been acquainted with bacteriological work before. Apart from the preparation of the cholera vaccine, which, after a period of instruction, they were left to carry on independently, they became soon engaged in a variety of other kindred work, notably in connection with infectious diseases affecting the © ponies, buffaloes and bullocks in tbe “gow- klmnas ” of the Municipal scavenging depart- ment; with outbreaks of rinderpest and other epizootics reported from Calcutta and Howrah ; and in connection with the then Health Officer’s studies of pustules and vaccine lymph, in the Municipal vaccine depot. Cholera inoculation m the busteesand suburbs of Calcutta, with cultures prepared in the Health Office, was carried on daily for two years, and the results were closely followed by various members of the Municipal Corporation. The number of persons inoculated was 7,690. About two-thirds of them underwent inoculation twice, at an interval of five days, so that the number of injections of vaccine per- formed was about 13,000. In 1896 anti-cholera inoculation was started at Purulia, on the Bengal-Nagpur Railway, At first Surgeon-Captain (now Major) J. C. Vaughan, i.m.s., Superintendent of the Campbell Medical School, Calcutta, then Deputy Sanitary Commissioner for the Chota Nagpur Circle, was in charge of the work. Two Hindu assistant- surgeons were appointed to operate under his orders. Surgeon-Captain Vaughan was, after a few months, ordered away to the Tirah campaign ; and from that time on, one of tbe assistant-surgeons, Gopal Cliunder Muker- jee, was left in independent charge, the other co-operating with him. In this depot the oper- ations were performed every day for eight and-a- half years, till the end of 1904; and the number of persons inoculated was as follows :— In 1896 • • • ... 4.413 „ 1897 • • • ... 10,95" „ 1898 • • • ... 4,296- „ 1899 • • • ... 2,388 „ 1900 • • • ... 13,291 1901 • • r ... 3,453 „ 1902 ... ... 3.144 „ 1903 , , ... 2,202 and 1904 • • • ... 1,623 In all . . . ... 45,760 The material for these inoculations was manu- factured, examined and used in an improvised laboratory, by workers who had had before no bacteriological training. The inoculated were almost exclusively coolies contracted for trans- port to Assam, and who were,, at the time of inoculation, and during their subsequent journey and service, under the supervision of Govern- ment and labour supply officials. The slightest mishap would have at once been known to the emigration authorities and reported upon. In none of the above operations has an unto- ward result at any time come to knowledge; and quite certainly no accident of any gravity has ever occurred. Anti-cholera vaccination has thus been demonstrated to be as free from danger as any method devised by man. II. Just as in vaccination against small-pox and inoculation against hydrophobia, as well as in Professor Kobe’s inoculation which the Manila laboratory has advocated and applied against plague, the vaccine used in anti-cholera inocula- tion is a live virus, and is not sterilized before injection. Nevertheless the details mentioned in the preceding paragraphs and referring to a long testing in India, indicate that the methods followed in the preparation and use of that vaccine render it, even in relatively inexperi- enced hands, safe from contamination, and eliminate sources of mishap. Again, neither in the anti-cholera vaccine, in the emulsion of spinal cords containing live hydrophobia virus, as used for anti-rabic inocula- tion, nor in the live virus of small-pox vaccine lymph, nor in any of the sera and drugs used in hypodermic injections in man and animals can contamination with harmful germs be detected with certainty by the microscope; but obviously this does not mean that either of the methods mentioned, now so extensively prac- tised, is insecure. In the anti-cholera inocula- tion, the examination by the microscope is an adjunct so important that, when applied in the way in which it has always been applied in India, an accident such as occurred in Manila is impossible; and an extraneous culture like that of plague would be detected immediately. Nevertheless, entire elimination of mishap is secured, obviously, not by microscopic examina- tion alone, but by an ensemble of operations of which some precede and others follow that examination, and by the general dispositions of the work. HI. In the aceident at Manila it is essential to note that the cholera vaccine did not get con- taminated by plague spontaneously. Such an eventuality may be treated as outside all prac- t.ical possibilities. Every bacteriologist of expe- rience will take on himself to say that the spon- taneous invasion of a bacterial culture by germs of cholera, plague, glanders, anthrax, diphtheria, tubercle and certain other specific microbes is not to be thought of any more than the spon- taneous contamination of such a culture with arsenic or strychnine. There are a few patho- genic species,—like those causing abscesses, for instance,—which are, upon occasions, found to contaminate cultures and other materials. In Manila a plague cultivation, presumably free from admixtures of any kind, was put by the operator into a watery suspension of cholera cultures, the latter probably being at the time quite pure and uncontaminated also. The accident became possible by the operator deviating, amongst other points, from the following two rules prescribed in the anti- cholera inoculation, viz., the contents of the culture tubes should not have been mixed ; and each tube, immediately before being used, should have been, apart from other examination, sub- mitted to an examination by the microscope. Under these circumstances a plague culture would have never passed for a cholera culture. It is not stated that the material injected into the men in Manila had been examined bj? the microscope ; but the Technical Committee of enquiry have found that when they mixed, in an experiment ad hoc, the contents of one cultiv- ation tube of plague with that of a large number of cultivation tubes of cholera (as had been actually done at the time of the human inoculation), and examined a drop of the mix- ture, the plague bacilli were overlooked under the microscope. Such a result is, of course, only too probable. IV. The details of the Manila accident reported by Ur. Freer tend to show that its occurrence did not stand in connection with the degree of perfection or deficiency which belong to cholera vaccination or to any bacteriological method as such. Tn all pharmacies and shops where collections • of drugs are kept, simple dispositions are adopted, on the responsibility of those in charge, for making it impossible for dangerous materials to get mixed with harmless ones. Obviously these measures had, at the time of the accident, not been in force at Manila ; and it must be presumed that some particular circumstances which existed at the time did not allow of the necessary dispositions being taken. It is, further, a practice with those in possession of materials of various kinds, partic- ularly harmful ones, to differentiate these by inscriptions or marks of identification. The first action of an apothecan7, when handling his phials, is to look at the label, independent of any other mode of examination,—chemical, physiological, or other,—which may be at his disposal for identifying the materials. The labelling of cultivation tubes is one of the articles of instruction mentioned in bacteriological text- books and lectures. In the pamphlet on the “Technique of the Anti-cholera Inoculation ” referred to above the procedure is enjoined on p. 8, paragraph 12, where it is stated : “ Mark the inoculation tubes unmistakeably, in order that the kind of vaccine they contain and the date of their inoculation shall be known.” The operator who omits to provide his preparations with clear inscriptions, or omits to take notice VS of them when using the preparations, renders obviously nugatory the whole of the safeguards, however perfect, which have been devised for preparing his materials in a pure condition. In Manila, where the tubes of vaccine for inoculation in man had to be incubated in the same box as tubes of virulent plague, and other persons than the vaccinator had access to the same incubator and to the same batches of tubes, it is stated that the inscription on the tube was not ascertained previous to using it. The accident was, therefore,- in every way of the same kind as would be incurred by a, pharmacist mixing up a poisonous substance with the drug which he is preparing; and it was preventable also in the same way as such accidents are prevented in pharmacies. y. The idea that the Indian method afforded no possibility of avoiding the accident appeal’s to have been based on the following' consider- .ations mentioned by Dr. Freer:—“While the method allows of everv test as regards the purity of the cultures up to 24 hours before their use, after this time (when many cultures are employed) no satisfactory test of their purity can be made and no test on animals can be carried on, since the cultures must be inoculated 24 hours after their preparation.” The accident was caused by the mixing up of a plague culture with the cholera vaccine at the very moment of using the latter. Obviously, no test applicable 24 hours or any longer interval before that moment, nor any test applicable a shorter period, even one hour, before, could have prevented the result of a confusion thus made. To avoid such a confusion,—once the general dispositions in force at the time permitted of its occurrence,—a tester tests were required applic- able at the moment of using the tubes. The most direct of such tests were those mentioned already, viz., (1), the reading of the inscriptions made for that purpose on the receptacles ; and (2), the examination under the microscope of the contents, in the manner prescribed for the anti- cholera inoculation. There were also certain other aids, but the special object of the present article does not seem to require entering into them. VI. The Manila Officers have gracefully recog- nized as conclusive the results of the Indian cholera vaccination studies, and have themselves contributed not a little to the subsequent inves- tigations on the matter. A few years ago, before introducing that vaccination in the Philippines, the very able director of the labor- atory there mode, in the Institute for Infec- tious Diseases in Berlin, a study of the vaccine used in these operations. The vaccine,—as described in the publications referred to higher up,—is a strain of cholera germs transformed into a virus of exalted, fixed potency, by culti- vating it, in accordance With certain rules, in the peritoneal cavity of the guinea-pig. The bacteriologists in Beilin compared this vaccine, from the point of view of its immunization properties, with the natural strains of cholera germs maintained b}7 cultivation in laboratories, and convinced themselves of the significance of the transformation imparted to the vaccine. Conseauently, in the Philippines, a strain has been adopted,—for preventive inoculation in man,—which is prepared and maintained in the way in which this is done in India; but instead of operating with that substance itself, they advocate the plan of leaving it to soak in water, at the temperature of the incubator, and using the resulting soluble extraction ;—a plan to which, as Dr. Freer mentions, it lias been objected at the last International Medical Congress in Berlin that the extraction might not have the protective effect which the vaccine itself had. The Manila officers are under the im- pression that one of the advantages of the watery extraction is that it is free from the possibility of misadventure which they have had with the vaccine. The same department of the Manila ins- titute that prepares the extraction of the cholera vaccine prepares also soluble products of other microbes, such as the toxine of diphtheria ; that of tetanus, of which the admixture of a few c.c.s would, of course, suffice to kill a horse ; probably, solutions of snake venoms for the preparation of anti-venene ; and so forth. If these micro- bial toxines and solutions, or, for the matter of that, any alkaloids or other drugs were to be so kept as to permit of their being inadvertently mixed with one another; if, before using them under such circumstances, the inscriptions on the receptacles were not ascertained ; physical differences of the contents overlooked; and the contents mixed together and used ; that is, if a concurrence of circumstances took place iden- tical <>n all points with that which they have had the misfortune of having at the time of the late accident,—the extraction of the cholera vaccine would obviously be exposed to the same possibility of misadventure as has occurred in the use of the vaccine. Of course, it is not suggested that the above is the condition prevailing normally in the Manila laboratory. The latter has, in a few years, and most deservedly, taken a place amongst the first class institutions of its kind in the world. It is only unavoidable now to make it clear that their accident has not been conditioned by the peculiarities of the anti-cholera vaccination method, as, they believe it has. VII. Referring to the facts mentioned in section 3 of Dr. Freer’s article (“ Subsequent experiments in the town of Angat In the prison we had and two among the ones vaccin- ated ”), — they do not unfortunately convey indications as to whether the extraction of the cholera vaccine confers on man the immunity against asiatic cholera as has been obtained with the vaccine. Such an indication would have been most welcome to me, but obviously Dr. Freer had no data yet for making any definite affirmation on the matter. In the case of the town of Angat, the number of non-vaccin- ated inhabitants, among whom 121 cases of cholera occurred, and the degree of exposure to infection, in the case of the vaccinated and of the non-vaccinated, have not been made known, and consequently a deduction from the figures given is impossible. In the Government prison in Bilibid, where one-half of the prisoners had been vaccinated and one-half not, after which event 18 cases of cholera occurred among the non-vaccinated and 2 among the vaccinated, the result would have been quite important, and, under requisite conditions, even conclusive ; but, presumably, between the time of vaccination and the date of the cholera occurrence, changes of which details are not related in the article had taken place in the composition of the prison population; for Dr. Freer states that no conclu- sion could be drawn from the facts related about that prison. It is to be hoped that the above explanations will not be viewed as implying any want of consideration for the Manila scientists, whose efforts, ever since the establishment of their laboratories, have enriched science with numerous contributions of a truly remarkable character. a—3 •r ;- BULL. SOC. VAUD. SC. NAT. XXXVI, 135 23 LA PESTE BUBONIQUE Conference academique faite a Lausanne le 12 decembre 1S99 PAR LE Dr Bruno GALLI-VALERIO, Professeur a l'Univorsite. Mesdames, Messieurs, / Si Thistorique de la peste a bubons est bien connu a partir du VIe siecle apres Jesus-Christ, on est bien loin cl’en savoir quel- que chose de precis avant cette epoque, car nous mauquons presque completement de descriptions exactes, qui nouspermet- tent de nous prononcer sur la nature de certaines epidemies in- cliquees comine peste dans les anciens livres. Le mot peste, que nous trouvons souvent dans la Bible par exemple, ne peut pas nous renseigner, car il etait applique a toute epidemie meurtriere. En effet Galien appelait peste : Toute maladie qui, se montrant sous forme epidemique dans unelocalite, frappe un grand nom- bre de sujets et determine une mortalite considerable. C’est a cause de cela, que Ton doit etre tres reserve avant de se prononcer sur la grande epidemie pcnnue dans l’histoire sous le nom de peste de Thucydicle. Cette epidemie eclata a Athenes 430 ans avant Jesus-Christ, au commencement de Pete, peu de temps apres que les Pelopone- siens avaient envahi l’Attique et devaste le pays. Kile etait ca- racterisee par une forte sensation de chaleur a la tete, rougeur et brulaison des yeux, respiration difficile, eternuements, voix rauque, toux tres forte. Suivaient des maux d’estomac avec vo- missements bilieux, hoquets violents. La surface de la peau etait rougeatre, avec de petites vesicules et des ulceres. Parfois on observait de la diarrhee. On notait gangrene des extremites et, le plus souvent, la mort. Sur cette description incomplete de Thucydide, de nombreux savants out essaye de poser un diagnostic de la maladie. Pour les uns (von Schonke et Osann) c’etait la peste bubo- nique, mais, comme Daremberg l’a le premier remarque, il man- que dans la description de Thucydide, preeisement les signes les plus caracteristiques de cette maladie. II est vrai que nouscon- naissons aujourd'hui des formes de peste ou bubons et charbons manquent tout a fait, mais il serait tres curieux que dans une epidemie si etendue on n’ait jamais observe des cas avec ces lesions. Pour d’autres cette maladie etait de la fievre jaune (Webster et Smith); de la meningite cerebro-spinale epidemi- que (Lefevre-Douville); du typhus exanthematique (Meister, Ochs, Wawruch, Corlieu); une sorte de typhus (Haser); de la scarlatine (Malfatti); de la variole (Willa); de la variole as- sociee au typhus (Daremberg); de la variole sevissant sur une population en etat d’ergotisme latent (Robert); une pneumonie (Haller); de l’influenza (Rittmann); une association deplusieurs maladies (Hirsch); une maladie aujourd’hui disparue. Avec Ebstein nous devons conclure que tout essai de se pro- noncer sur la nature de cette maladie, avec la description qui nous en reste, est une vue de Pesprit. Dans un livre d’Oribase, de 250 ans avant J.-C., Angelo Mai a decouvert une premiere description qui, avec beaucoup de probability, se rapporte a la peste. On y parle en effet de bubons pestilentiels que l’on observait en Lybie, en Egypte et en Syrie. Il est tres douteux, que l’on doive rapporter a la peste l’epi- demie dont parle Ovide, et qui aurait ete envoyee par Junon a Tile d’Egine, epidemie qui frappa les animaux d’abord et ensuite Thom me. C’est de cette meme epidemie que parle le Dante (Enfer, XXIX, vers. 58): Non credo die a veder maggior tristizia Fosse in Egina il popol tutto infermo, Quando fu l’aer si pien di malizia, Che gli animali, infin al picciol vermo Coscaron tutti. Le meme doute snbsiste par rapport a la grande epidemie qui de 160 a 186 apres J.-C. s'abattit sur l’Empire romain de l’Est a l’Ouest et qui est connue sous le nom de Festis Antoniniana. La premiere epidemie de peste en Europe sur laquelle il ue reste aucun doute, e’est celle du VIe siecle. Elle se developpa en Perse et en Asie-Mineure Pan 532 de notre ere, elle gagna de la la basseEgypte et les Lords de la Me- diterranee. Des descriptions qui nous en restent de Evagrius, Procope et Agathias, nous pouvons relever que les patients presentaient des bubons et des cliarbons, et qu’ils perissaient presque tous, par- ibis comme frappes d’un coup d’apoplexie. Cette grave epidemie, connue sous le nom de peste de Justi- nien, dura 50 a 60 ans, et Warnefried ecrit que les villes en fu- rent depeuplees, les pays changes en un desert, et que les ani- maux sauvages s’etablirent la ou l’homme avait demeure. A cette grande epidemie du VIe siecle, d’autres ont succede, mais nous ne possedons d’elles aucune relation interessante, et il faut arriver au XIVe siecle pour trouver une epidemie de la gravite de la peste de Justinien. C’est en 1334 qu’elle eclata en Chine, gagna les Indes, la Perse, la Russie et en 1347 PEurope entiere. D’apres Hecker, en trois ans elle tua 25000000 d’hommes sur 105000000 d’habi- tants que l’Europe comptait. Les statistiques dressees parordre de Clement VI, tixent a environ 43 000 000 le nombre des victi- mes pour le monde entier. La seule ville de Florence perdit 100000 personnes. De cette epidemie, connue sous le nom de peste noire ou mort noire, il nous est reste d’excellentes descriptions, entre autres celle de Boccace : « Au debut de la maladie, se manifestaient soit aux hommes soit aux femmes, a I'aine ou aux aisselles, des enflures qui pouvcdent atteindre les dimensions cVune pomme ou d'un ceuf et qu'on appelait des bubons. Puis apparaissaient sur les cuisses et sur toutes les parties du corps des taclies noires ou livides, chez les uns grandes et rares, chez les autres petites et nombreu- ses. Soit les bubons, soit les fetches etaient un indice stir demort. Le traitement ne servait a rien, pas plus les conseils des mede- cins, cque la vertu des medecines: au contraire, soit par la nature de la maladie, soit par Vignorance des medecins, qui ne la con- naissaient pas, non settlement il n’y en avait point qui gueris- saient, mais presque tous, le 3ejour cles Vapparition des symp- tomes indiques, succombaient. » Et cette epidemic fid d’autant plus grave cpie par Us rap- ports elle se communiquait des malades aux sains, avec la meme faciiitc avec laquelle lefeu se [trend aux choses s'eches. » Et non seidementlefait de frequenter des malades pouvait communique)- la maladie, mais simplement le fait d'avoir tou- che des habits ou autres objets ay ant appartenu aux patients. » Le XVe siecle fat aussi riche en epidemies et e’est en 1400 ou 1402 que ia peste envaliit pour la premiere fois l’lslande. L’etude des epidemies du XVe siecle permit aux medecins de distinguer nettement, des cette epoque, la peste bubonique du typhus exanthema ti que. Au XVL siecle, la peste devint endemique en Europe. A tout instant elle apparaissait par-ci par-la, et au XVIIe siecle elle eclate de nouveau sous la forme d’une grande epidemie. La ville de Londres perdit en 1665 plus de 68 000 personnes, la ville de Milan en fat ravagee; et Lausanne perdit en quelques mois, en 1613, plus de 2000 de ses habitants. Mais vers la fin du XVIL siecle, la peste sembla disparaitre petit a petit. Au XVIIP, elle demeura pres des frontieres orien- tales del’Europe, d’ou elle fit encore des invasions multiples. Ainsi, de 1707 a 1714, elle envahit successivement la Turquie, la Russie, la Prusse, le Danemark, PAutriche et la Baviere; en 1720, elle eclate a Marseille et en Provence, tuant 80 000 personnes; en 1743, a Messine, faisant 43 000 victimes. A la fin du XVIIP"e siecle, elle se cantonna encore en Asie, en Afrique et surtout en Egypte. L’Europe etait done constamment menacee, et en 1813 la peste apparut a Malte ou Pon observa des cas isoles jusqu’en 1815. Cette annee-la l’Europe occidentale fut bien menacee par une grave epidemie qui eclata a Noia, petite ville des Pouilles, sur les bords de PAdriatique. Void ce que Pietro Colletta ecrit sur cette epidemie : « L’avidite du gain y introduisit la peste avec des marchan- dises. Je ne sais pas si dies venaient de Dalmatic ou de Smyrne, parce que Vauteur de la ccntrcbancle succomba ou se caclia, pour eviter la peine et Vinfamie du grand crime commis. Le 23 nov. 1815 succomba Liborio cli Donna et le jour sui- vant, Pasqua Cappelli, sa femme, septuagenairesjres pauvres... La peste, encore meconnue, se repandit parmi les gens les plus miserables... Puis toutes les classes de la societe furent att mites. Les symptomes etaient effray ants : la face se clecolo- rait, devenait jaune, grip pee, les pupilles sc dilataient, la langue se oouvrait cVune couche blanche, to soif etait Ires vive,ily avait (les frissons et du clelire.. Ensuite apparaissaient des Imbons a Vaine on aux aisselles, le ventre et la poitrine se couvraient de charbons... les pestiferes mouraient en trots, cinq on sept jours et quelques-ims en peu d'heures. » Les mesures energiques prises par le general Mirabelli ont sauve l’Europe du fleau : la ville de Noia fut entouree par trois fosses, l’un a 60 pas. l’autre a 90 et le troisienie a 10 mille. Tous ces fosses etaient gardes p tr des sentinelles. De grands feux les signalaient pendant la nuit. Un malheureux qui essaya de les depasser, fut tue raide par plusieurs coups de fusil. Le 7 juin 1816, on observait a Noia le dernier cas de peste. En six mois et demi, il y avait eu 1438 cas avec 728 deeds. Plus d'un quart de la population fut atteint par le fleau! A l’epide- raie de Noia succederent les epidemics de 1820 aux Baleares, de 1841 a Constantinople. Sur les cotes d’Afrique, la peste disparaissait petit a petit en 1818-1819 au Maroc, en 1837 en Algerie et en Tunisie, en 1844 en Egypte. L’Europe, qui croyait eteints egalement les foyers d’Asie, 011- blia la peste, niais pas pour longtemps. En effet, en 1858, la nouvelle se repandit que la peste venait d’eclater en Tripolitaine, a Benghazi. C’est que les foyers asiati- ques etaient bien loin d’etre eteints. En effet, en 1853, la peste s’etait manifestee dans l’Assir, tout pres de la Mecque; en 1866, dans l’lrak-Arabi, on, a differen- tes reprises, elle devaitse montrer jusqu’en 1877 ; en 1863, dans le Kurdistan; en 1870-71, pres du lac Ourmiah, en Perse, et en 1876, elle gagnait le Khorazan et la ville de Recht, pres de la mer Caspienne. Les frontieres orientales de l’Europe etaient done de nouveau menacees et en effet, en 1878, la peste eclatait en Russie. C’est en septembre ou octobre de ladite annee que l’on ob- servait le premier cas & Wetlianka, pauvre village de pecheurs a 195 km. en amont d’Astrakan, sur la rive droite de la Volga. Ce village, avec une population de 1800 ames, laissait beaucoup a desirer sous le rapport de l’hygiene. Au premier abord, on se trompa dans le diagnostic : on con- sidera la maladie comrne du typhus exanthematique ou de la pestis nostras! Le l)r Doppner arrivait k ecrire que c’etait: soit un typhus du genre le plus aigu, soit une peste particulare, soit me ma- ladie intermediate entre le typhus et la peste! Jilt pourtant, un pauvre officier de sante, qui mourut victime du devoir, Troubeiloff, avait bien pose le diagnostic de la peste bubonique! L’incertitude du diagnostic permit a l’epidemie de se propager dans tous les environs. Nonobstant, les mesures energiques prises par le gouverne- ment russe permirent d’etoufferen quelques mois Pepidemie qui avait fait deja 400 victimes dans la contree et coute la somme de 2 000 000 de francs. De quel cote la peste etait-elle entree en Europe ? Suivant l’opinion de Hirsch, elle avait ete importee du Caucase par l’armee russe qui devait avoir eu des rapports avec les pestife- res de l’lrak-Arabi; pour Zuber et d’autres, elle avait ete im- portee de Recht. II est tres difficile de se prononcer sur les deux opinions, car il y a des raisons pour Pune et pour l’autre. La deuxieme semble pourtant la plus probable, vu le voisinage du foyer de Recht et surtout sil’on songe qu’en 1877, on avait ob- serve a Astrakan 250 cas d’une maladie qu’on avait appelee tievre a bubons et qui pouvait fort bien etre de la peste attenuee. Le foyer de Wetlianka eteint, on oublia encore une fois la peste. Mais en Asie, il y avait toujours des epidemies : le foyer de l’Assir s’etait rallume, de nouvelles epidemies se manifestaient en Perse. Dans la province clnnoise de Yunnan, la peste, eclatee en 1880, avait persiste sous forme endemique. Elle y apparaissait en general de mois en mois, pour presenter une aocalmie pendant les grandes chaleurs; mais tout a coup, en 1894, elle eclata brusquement dans le port de Packo'i et de cette ville elle se repandit rapidement a Hainan, Canton, Hong-Kong, Amoi. Elle fit 180 000 victimes a Canton, 12 000 a Hong-Koug. Au mois de juin 1896, arrivait Pannonce que la peste avait eclate a Bombay. Suivant Hankin, Simond et d’autres, elle y aurait ete importee par la voie de mer de Hong-Kong; suivant la mis- sion allemande, elle provint au contraire du Guhrwal et du Ku- maan, districts de PHimalaya, ou la peste existait depuis de lon- gues annees a l’etat endemique. Petit a petit, toutes les Incles lurent envahies, et la peste y a fait jusqu’a present 250000 victimes. C’est depuis les Indes etla Chine qu’elle irradie dans PAfgha- nistan, le Turkestan russe, a Madagascar, a Tile Maurice, a la Reunion, a Formose, a Djeddah, a la Mecque, a Mascate, a Alexandrie d’Fgypte, en Perse, dans les Straits-Setlements, a P Ann am, a Mozambique, au Paraguay et au Bresil,a Lourengo- Marques, en Algerie, en Mandchourie. L’Europe, a son tour, ne devait pas etre epargnee. Faisant abstraction de quelques cas isoles observes dans les hopitaux de Londres et de Trieste, deux foyers ont surtout emotionne le public : Vienne et Oporto, et on devrait y ajouter Astrakan. Le 22octobre 1898, le gouvernenient austro-hongrois communiquait aux autres gouvernements la note suivante : « Par suite June imprudence, le nomme Barish, gargon de labor at oire a Vinstitut bacteriologique, s’est infecte, a contracts une pneumonie pesteuse d laquelle it a succombe ie 18 octobre, apres avoir ete isole. Pendant sa maladie, il n’a ete en contact immediat qiCavec le Dr Muller qui le soignait, et avec deux in- firmieres nominees Pecha et Iiochegger. Ces trois personnes ont ete immediatement isolees dans le nouveau lazaret de VHopital Frangois-Joseph. Le Dr Muller et Vinfirmiere Pecha ont con- tracts une pneumonie pesteuse. Vinfirmiere Hochegger estres- iee en bonne sante. Pas de cas de maladie par mi les per sonnes qui se sont trouvees en contact avec les malades et qui toutes ont ete isolees. Des le debut, les mesures d'isolement les plus rigou- reuses ont ete prises; tout ce qui provenait des malades, effets, dejections, excretions a ete bride, de fagon a eviter toute 'infec- tion du sol, des canaux, etc. L'etat sanitaire de la population, huit jours apres le premier cas, quatre jours apres le premier deces, est absolument normal. 11 n\y a pour le moment ni foyer cpidcmique, ni danger cVepidemie. Telle etaitla communication claire, precise, du gouvernement autrichien. Vous savez le bruit qu’on a fait sur ce malheureux accident. A entendre certains journaux, l’Europe allait etre en- vahie par une epidemie de peste comme celle du XIVe siecle! On a ainsi detourne l’attention du public des foyers qui mena- gaient reellement PEurope pour signaler les inconvenients qui pourraient resulter des laboratoires bacteriologiques. Ceux-ci, disait-on, menagaient chaque jour l’Europe d’une epidemie de peste. On reclama, et dans certains pays on eut la faiblesse d’ac- corder, la destruction des cultures dangereuses, celles relatives a la peste en particular. Et on ne songea pas que jusqu’a pre- sent, les victimes de la raorve delaboratoire sont plus nombreu- ses que celles de la peste, et qu’a ce compte on devait empecher absolument toute culture bacteriologique. Tons ceux qui orient ainsi, disais-je l’annee derniere a la Societe de medecine, m’ont Pair de certains antivivisectionnistes qui reclament la lumiere, en meme temps que l’extinction des foyers qui peuvent la donner. « Vouloir empecher, ecrivait a cetegard M. Vallin, l’etudedes maladies pestilentielles dans les laboratoires, serait une mesure tellement stupide, qu’il est inutile d’insister. Qu’on laisse au moins aux savants le droit de se devouer pour la science et pour l’humanite. » Mais la peur atavique de la peste avait, l’annee derniere, fait perdre la tete a bien des personnes. Ce n’etaient pas les laboratoires de bacteriologie, mais l’lnde, qui devait nous apporter la peste. Un navire anglais, qui avait charge a Londres du grain des Indes destine au Portugal, parait avoir porte la peste a Oporto. Elle y eclata au mois de juin, mais ode ne fut reconnue offi- ciellement qu’au milieu d’aout. Deux mois s’etaient ainsi ecoules et la maladie avait eu le temps de se repandre dans une vide tres sale. Les mesures absurdes prises contre l’epidemie n’etaient certainement pas iaites pour lui opposer une barriere, et encore maintenant des cas de peste sont signales a Oporto. Telle est l’epidemie qui nous menace de tout pres et a celle-ci j'ajoute encore'maintenant cede d’Astrakan. Apres le resume historique des epidemies de peste jusqu’a nos jours, passons en revue les foyers de peste en Asie et en Afrique, foyers qui sont pour notre continent une menace per- petuelle. ds occupent, comme M. Tboinot le fait observer, une bande ininterrompue de l’Assir a la Chine, mais je ferai re- marquer que dans cette zone il est necessaire d’indiquer specia- lement quelques foyers qui sont absolument permanents, car la peste y est endemique Tels sont les districts de Guhrwal et Ivumaan dans l’lndoustan, infectes depuis 1844 et ou la peste, designee sous le nom de Mahamurre, apparait vers la fin de la saison des pluies. Tel est le Yunnan on lapeste estaussi endemiquo, peut-etre depuis 1S50, en tout cas depuis 1876. A ces foyers asiatiques, j’en ai ajoute un autre en 1897. Je l’avais fait en m’appuyant sur la relation sui- vante de deux medecins russes : MM. Beliawski et Reclietnikoff. « Presque chaque annee, vers la fin de Pete, a l’epoque de la secheresse on au commencement de Pautomne, sevit parmi les Arctomys bobac, rongeurs voisins de la marmot!e habitant sur- tout les steppes voisines du lac Baikal, une epidemie speciale a laquelle les indigenes donnent le nom de peste de sarbagan. Les animaux deviennent apathiques, se trainent peniblement et so laisspnt facilement prendre. Une tumeur rougeatre, tendue, se developpe au niveau des epaules. Les arctomys malades meu- rent tons, mais les loups et les chiens peuvent manger les cada- yres sans devenir malades a leur tour. Par contre, des qu’un homme touche a un animal malade ou mort, s’il le mange ou le depouille, il s’infecte. Une maladie speciale, de nature infec- tieuse,. se developpe chez lui et amene rapidement la mort. II y eut des moments ou des villages entiers perissaient a cause de cette maladie. Des que la maladie eclate, les tentes et les ma- lades sont abandonees et les habitants ne reviennent que pour ensevelir les morts et bruler le tout. Chez ces patients, apres une incubation de trois a douze jours, la temperature monte vice ; il y a cephalee violente, des vomissements et de la diarrhee, rare- ment de la constipation. Parfois il y a des expectorations san- guinolentes, apparition d’adenites axillaires ou inguinales dou- loureuses, apathie, prostration. La mort survient au bout de quelques jours en pleine connaissance. » « Vis a-vis de cette description qui repete presque exactement la symptomatologie de la peste bubonique, ecrivais-je, en 1897r je crois qu’il n’est pas errone d’admet'tre que la peste cVArc- tomys bobac c’est la peste bubonique, et comme telle, elle se transmet a l’homme en provoquant les graves epidemics obser- vees sur les bords du lac Baikal. VArctomys bobac & certaine- inent pris la place du rat comme agent de dissemination de la maladie. » J’ai eu la satisfaction, scientifique bien entendu, de voir mes idees appuyees, naturellement sans me citer, par M. Favre, de Tlnstitut d’hygiene de Karkow, qui croit aussi qu’on se trouve en presence d’un foyer de peste bubonique. Ce foyer represen- tera surtout un danger pour PEurope lorsque le Transsiberien sera acheve. L’Afrique est aussi le siege cl’un foyer de peste tres important. II a ete decouvert en 1898 par Koch et Zupitza k Kisiba, entre le Nil Kagera etle lac Victoria, l’Afrique allemande orientaleet l’Ouganda. Le bacille specifique de la peste a pu y etre observe sur des cadavres d’hommes et de rats. Les indigenes connaissent fort bien la maladie, qu’ils appellent Lobenga et Nubanga, et ils craignent tous les rats morts qu'ils savent etre les agents de dissemination du fleau. La peste existerait du reste depuis long- temps dans l’Ouganda. Ce foyer deviendra dangereux, lorsque le chemin de fer de Momb£ssa a LOuganda Laura mis en relations directes avec la ■cote orientale de LAfrique. C’est peut-etre de ce foyer inconnu que la peste a ete importee autrefois en Egypte. La peste bubonique n’estpas une maladie exclusive abhomme, mais une maladie qui frappe en merne temps l’bomme et certains animaux et qui se transmet des uns a l’autre. M. le Dr Simond a voulu trouver dans la Bible une premiere indication de ce fait, au Livre I, chap. VI de Samuel. Quant a moi, je n’y ai trouve que l’indication de souris qui gatent le pays et il me paraft qu’il faut une forte dose de bonne volonte pour trouver qu’on y parle de la peste des rats. Dans la description de la peste d’Atbenes, Thucydide parle d’oiseaux et de cliiens qui mouraient apres avoir mange des pestiferes. Ovide et Dante repetent la chose par rapport a bepi- clemie d’Egine, mais je crois que la premiere indication exacte de la presence de la peste chez les animaux, nous la trouvons dans la belle description de la peste de Florence au XIVe siecle, par Boccace. Voici ce qu’il en ecrit: « Je dis que la contagiosite de la peste fid June telle force que non seulement elle se transmettait cl'homme d homme, mais que des objets ay ant appartenu a un pestifere, touches par un animal d'espece dijferente de V homme, non seulement lui don- naient la maladie, mais le tuaient en tres peu de temps. J’ai pn constater la chose moi-meme , car deux pores, comme il est dans leurs habitudes, ay ant second et pris avec leurs dents des hardes ayant appartenu a un pauvre diable mort cle la peste et qu'on avait jetees sur la rue tres peu de temps apres, apres quelques contorsions, comme s'ils eussent pris du poison, tomberent morts sur les hardes qu'ils avaient si malencontreusement touchees » Hseser rapporte aussi qu’& Tournai, pendant bepidemie de 1349, il mourait des chiens, des rats et des souris. Suivant Skene, l’epidemie d’Edimbourg en 1568 avait ete precedee par la mort des poulets, des taupes et des ser- pents. Au XVII* siecle, Hodges ecrivait qu’il est mauvais signe, si les taupes et les rats commencent a mourir en grand nombre. Dans l’epidemie de Pali (Indes) en 1836 et dans celles de Guhrwal et Kumaan en 1851, on signalaaussi une grande mor- tality des rats. Les experiences et les observations faites pendant l’epidemie actuelle ont continue l’existence de la peste bubonique chez certains animaux. Rocher a ete le premier a affirmer qu’au Yunnan, l’epidemie de peste avait ete precedee d'une grande mortalite des cbiens, des rats et des pores. A Canton, deux ou trois semaines avant les premiers cas de peste chez l’homme et meme pendant l’epidemie, la mortalite des rats fut exceptionnelle, si bien que le peuple finit par re- garder ces animaux comme des messagers diaboliques et s’ef- forga de les chasser. Dans certains quartiers, on retrouva jusqu’a 22 000 cadavres de rats. Les Chinois savaient du reste fort bien que la meme maladie frappait les hommes et les rats et 1’astronome de Pekin affirma que le bon Dieu aurait pu faire mourir les 8/10 des hommes, mais qu’il se contentait des 4/J0, en remplagant les autres par des rats. J’ai deja cite le fait qu’aKisiba les habitants connaissent tres bien les rats pestiferes. Suivant Ogata, a Formose, on appelle la peste bubonique : maladie des rats. Le docteur Janson affirme qu’a Canton les pores etaient aussi frappes par la peste et qu’on en avait interclit l’abattage. Suivant lui, au Yunnan, les animaux atteints ont ete les rats, les souris, les pores, les chiens, les chevaux, les bovides. Au Tonkin, la peste bubonique aurait ete observee par Yersin sur les buffles et autres bovides, mais je crois que Janson s’est trompe, car je n’ai jamais trouve dans les travaux de Yersin une affirmation pareille. La peste bubonique spontanee a aussi ete observee chez les souris, le singe, le rat palmiste, les cobayes, et nous pouvons aujourd’hui ajouter a cette liste 1’Arctomys bobac. Meme des invertebres, la mouchc, pur exemple, ainsi que l’a demontre Yersin, succombent par la peste bubonique. Apres la decouverte de l’agent specifique de la peste bubo- nique, on a pu faire de nombreuses experiences pour determiner le degre de receptivite des divers animaux pour la maladie. Parmi les mammiferes, on a pu constater que les rats, les souris, les cobayes, les lapins, les singes, les chats, les mulots, les pores, les moutons, peuvent etre inlectes de peste bubo- nique. Pourtant, suivant les experiences de Di Mattei, les pores et les moutons ne contractent la maladie par voie experimentale que sous l’influence de fortes doses de virus et, en general, sous une forme legere. Wilm, a Hong-Ivong, a pu infecter un pore en lui dormant a manger la rate d’un pestifere et le pore suecomba de la peste au bout de quatre semaines. Par rapport aux bovides, les experiences de Gosione sont pas parvenues a la communication de la peste a ces animaux par voie experimentale, mais les experiences faites sont encore trop peu nombreuses pour pouvoir se prononcer d’une fagon absolue. La mission allemande a inocule des chevaux, des bovides, moutons, chevres, pores, chats, chiens, qui n’ont presente que des lesions locales. Parmi les oiseaux, tandis que De Giaxa, Gosio et Di Mattei, ont pu donner la peste aux pigeons soumis au jeune, tandis que London n’a pas eu de resultats ni sur les pigeons, ni sur les poulets, ni sur les pinsons, Di Mattei inoculait positivement les poulets et les moineaux. Parmi les vertebres a sang froid, Devell a infecte liana tem- poraria, Nuttale Pelias berus et Lacerta agilis gardes a 2(i°-28n, mais il a eclioue sur les grenouilles. Parmi les Invertebres, Yersin et Nuttale ont pu constater que les mouches succombent a l’infection avec les bacilles de la peste. Abordons la question de la contagiosite de la peste. Les an- ciens auteurs, les peu pies cliez lesquels la peste a ete souvent observee n’elevent aucun doute sur sa contagiosite. II y a du reste desfaits bien nombreux qui parlent pour la contagiosite. Le personnel medical, s’il ne prend des precautions, est souvent atteint par la maladie. Durant la campagne d’Egypte, l'armee frangaise, forte de 30 000 homines, en perdit 1429.de la peste et 2419 d’autres maladies, tandis que le personnel medical et ad- ministratif enregistrait pour ce qui le concernait 260 decesdela peste et 49 dus aux autres maladies. Dans l’epidemie de Wet- lianka, trois medecins sur quatre et quatre officiers de saute sur six out ete atteints. En 1835, en Egypte, deux condamnes a inert succombent a la peste, apres avoir revetu des chemises de pes- tiferes; trois autres sont inocules avec de la serosite des bubons et un seul echappe a l’infection. Cerruti inocule six Europeens pour les preserver de la peste et il communique la maladie a cinq. En 1802, Whyte se fric- tionne avec le pus des bubons et succombe a la peste. On a fait beaucoup de bruit, pour nier la contagiosite de la peste, sur le cas du Dr Desgenettes, medecin de l’armeefrangaise, qui,a St-Jean-d’Acre. s’inocule avec du pus de bubons sans con- tractor la maladie. Mais ce fait n’a absolument aucune valeur, car il s’agissait sans doute d’un cas de resistance particuliere individuelle, comme on en rencontre a tout moment. La conta- giosite est aussi prouvee par le fait qu’un simple fosse, comme a dit Desgenettes, peut preserver de la diffusion de la maladie. Boccace nous dit que pendant l’epidemie de Florence, au XIYe siecle, ceux qui voulaient se preserver de la maladie se barrica- daient dans des maisons isolees. Dans Flrak-Arabi, les habitants bouchaient les portes des maisons et lie sortaient pas pendant l’epidemie. L’exemple de la vi lie de Xoia, foyer tres dangereux de peste qui resta tout a fait isole, est aussi la pour demontrer la conta- giosite de la maladie. Les agents de contagion sont represents par riiomme et les animaux pestiferes.et par tous les objets qui out ete souilles par le virus de la peste. La contagion directe d’homme a homme n’a pas ete tres ac- centuee dans l’epidemie actuelle des Indes. Le Dr Muller, qui a pourtant constate nettement chez 14 pestiferes l’infection par des rapports avec ctes malades, n’a pas note souvent des cas de peste chez les personnes chargees de soigner les pestiferes et lui-meme affirme avoir examine de nombreux malades sans trop de precautions et cependantsans s’etre infecte. La contagion directe d’homme a homme est surtout a craindre dans les cas de pneumonie pesteuse. La contagion par l’intermediaire des souris et des rats pesti- feres est celle a laquelle on a attribue le role principal dans l’epidemie actuelle. Je vous ai dejii indique que les epidemies de peste bubo- nique sont souvent precedees ou accompagnees d’une grande mortalite des rats. La decouverte du bacille de la peste a per- mis de demontrer que ces animaux meurent reellement infectes de peste bubonique. Ljes rats pestiferes, en se repandant dans les habitations, ou en se faisant transporter au loin par des navi res, deviennent de puis- sants agents de dissemination de la maladie. Suivant Hankin, dans un recit de l’empereur Jehangir, il est deja question de I’action des rats dans la transmission de la peste. Ce sont surtout MM. Hankin et Simond qui insistent sur le role de ces animaux dans la contagion de la peste bubonique. Pour M. Simond ils joueraient meme le role principal. Suivant lui, si on cite des cas de peste chez l’komme sans epidemie con- comitante chez les rats, c’est que l’on n’a pas fait attention a la mortalite de ceux-ci, qui pent du reste avoir ete tres faible. 11 ajoute que si la peste n’atteint pas les maisons des riches, c’est qu’elles sont blindees contre l’invasion des rats. Mais M. Simond va encore plus loin : il aurait decouvert le moyen par lequel les rats infectent l’homme. Il affirme, que c’est par les piqures des puces des rats et des souris pestiferes qui passent sur l’homme. M. Simond aurait trouve chez des pestiferes (1 : 20) des phlyc- tenes contenant le bacille de la peste, phlyctenes qui seraient dus a la piqure de ces puces et qui seraient ainsi la porte d’en- tree du virus. Il aurait en outre observe que ces puces portees sur le cliien et sur l’homme les attaquent immediatement. La supposition de M. Simond n’a rien de bien extraordinaire. On saitdepuis plusieurs annees, que differentes maladies parasi- taires peuvent etre transmises par des piqures d’insectes. Au surplus nous savons que deja en 1897 Ogata avait trouve le ba- cille dans les puces et avait deja pu donner la peste a des rats en leur inoculant des puces sous la peau. Simond de meme affirme d’avoir tue des souris avec des puces pestiferees. Mais j’aurais bien aime que cet observateur ait etudie beaucoup mieux cette importante question, avant de lancer une affirma- tion si absolue, comme si la puce du rat fut l’unique moyen de transmission de la peste a l’homme. Pour vous demontrer avec combien peu d’esprit scientifique il a procede, je vous dirai qu’il n’a pas su reconnaitre avec quelle espece de puce il avaiteu affaire et il fait une deplorable confu- sion entre les puces du rat, du chat et de l’homme. Or tout le monde sait que presque cbaque espece animate a sa puce parti- culiere qui ne l’abandonne, sauf de rares exceptions, que pour passer sur un autre individu de la memo espece, et si elle se porte sur une espece differente, elle n’y reste pas longtemps. Sur les rats et sur les souris vit surtout Typhlopsylla musculi,. jusqu’a present non signalee sur l’homme. En manipulant une souris qui etait morte, plusieurs de ses puces ont passe sur moi, mais je n’en ai pas ete pique. Je viens de repeter l’experience en portant sur mon corps des puces de souris et en les tixant sous une cloche de verre ou en les laissant tout a fait libres. Bien que ces puces fussent res- tees a jeun de 24 a 48 heures, elles ne m’ont pas pique et elles ont quitte mon corps des qu’elles ont pu le faire. Cette espece ne semble done pas piquer l’homme. L’autre espece Pulex fas- ciatus est plus rare; je ne l’ai trouvee qu’une seule fois, sur le surmulot. Les medecins de la mission allemande aux Indes n’ont paa trouve sur les pestiferes de traces d’une transmission par les piqures de puces. La merae chose a ete constatee a Oporto par les medecins italiens. L’affirmation que la peste ne se rencontre pas dans les maisons des riches parce qu’elles sont blindees contre les rats, ne me parait pas non plus en rapport avec son affirmation de la trans- mission par les puces, car, meme dans les maisons des riches, on trouve, sinon des rats, des souris qui presen tent la meme puce et, chose plus interessante encore, tandis que le bacille de la peste s’attenue en passant du rat au rat, il augmente de viru- lence en passant sur les souris. Celles-ci devraient done agir plus encore pour la transmission de la maladie. En resume, les rats peuvent bien, avec les souris, entrer en jeu dans la transmission de la peste. Le role que M. Simoncl veut faire jouer aux puces qui habitent ces animaux demeure douteux. J’ajouterai qu’il faut bien se garder d’attribuer aux rats un role presque exclusif dans la dissemination de la peste, comme quelques-uns veulent le faire. On risquerait de distraire l’atten- tion d’autres causes tres importantes tel les que la transmission directe de l’homme a 1’homrae ou celle qui a lieu par les objets. Il parait en effet que les rats manquaient totalement en Angle- terre, en 1347, nn moment de la peste noire. 11s n’y auraient ete introduits qu’an XVIe siecle. Les mouches peuvent jouer dans la contagion mi certain role. Le I)r Fabricius qui pratiqua dans le canton de Vaud au XVII“ siecle signale les mouches parmi les vehicules possibles de la peste. Dans notre siecle, Hawser a attire sur elles l’attention dans l’epidemie de Benghazi. Les Turcs appellent cette ville le Royaume des mouches. Le Dr Yersin constata pendant l’epidemie de H,ong-Kong, que les mouches pouvaient s’infecter de peste et devemr un agent de contagion. L’inoculation qu’il tit d’une de ces mouches a un cobaye, lui donna la peste bubonique. M. Nuttall a continue le fait par voie experiinentale. II dit que si les mouches infectees vivent plusieurs jours, elles peuvent aller deposer des bacilles sur nos aliments. M. Han kin a observe aux Indes la dissemination par des fourmis, Monomoriwn vastcttor, qui ont depece des cadavres de rats pestiferes. L’inoculation de ces fourmis a des rats les tuait en 12 heures de peste bubonique. Les punaises peuvent aussi etre des agents de contagion, car Nuttall, plagant des pu- naises sur des rats pestiferes et les inoculant ensuite a des rats sains, a pu les tuer avec toutes les lesions de la peste bubonique. J’ajoute que'tres piobablement d’autres insectes parasites peuvent entrer en jeu. Ainsi il ne faut pas exclure l’infection possible par la puce de l’homme, certainement plus probable que celle par la puce de la souris, ou des rats, ou meme par les moustiques, bien que Muller n’ait pas pu constater des cas de transmission clus a ces insectes. L’air ne joue pas un role dans la dissemination de cette ma- ladie, car les bacilles de la peste sont tres vite tues par la des- sication et par l’ensoleillement. La dissemination par Pair peut done entrer en compte pour un petit espace, une chambre par exeniple, mais pas pour l’exterieur. En 17 ans, Tholozan iPa jamais observe en Orient le transport de la peste par l’atmos- phere. Si Ton a observe, dans de certaines epidemies, des cas de peste plus nombreux au voisinage des lazarets, ce n’est pas l’air qu’il faut incriminer, mais les rapports plus frequents avec le personnel charge du soin des inalacles. L’eau ne parait pas non plus jouer un role important dans la dissemination de la peste. Ilodges a signale le fait que dans l’epidemie de Londres, en 1665, sur 10000 personnes qui s’etaient refugiees sur des navires, sur la Tamise, pas une seule ne con- tracta la maladie. Un fait analogue a ete observe a Malte en 1S13: Pas un seul cas de peste ne fut observe abord des navires dansle port de La Vallette. A Canton, 80000 Chinois habitaient sur des bateaux et parmi eux on n'observa aucun cas de peste. Le bacille de la peste peut pourtant se trouver parfois dans les eaux. Wilm affirme Pavoir trouve dans troispuits a Hong Kong. Hankin l’a trouve dans un marais qui recevait les matieres excrementielles d’un village indou et il affirme que Pepidemie cessa des que l’on eut desinfecte soigneusement ce marais. Ce sont surtout les vetements des pestiferes qui jouent un role important dans la dissemination de la peste. En 1720, Mead ecrivait que les vetements contiennent la quintescence raeme de la contagion. II parait que dans les vetements, dans les hardes, surtout par le fait d’etre soustrait a Paction de la lumiere et de la dessication par Pair, le virus de la peste conserve longtemps toute sa virulence. Ce virus demeure surtout longtemps actif, si la temperature se maintient vers 8° a 10° et si les vetements sont humides. Trincavelli rapporte que des cordes qui avaient servi a enterrer des pestiferes donnerent la peste a l’homme apres vingt ans. A Breslau, on aurait observe un fait analogue avec des hardes de pestiferes. Ces affirmations sont sans aucun doute tres exagerees, mais il est certain que le virus de la peste, dans les conditions susindiquees peut rester actif pendant des semaines. Hankin Pa trouve actif apres trente- ■ six jours. Les peaux des animaux pestiferes peuvent etre dange- reuses, si elles sont a l’etat frais, mais elles ne le sont que tres peu si elles ont ete salees et plus du tout si elles ont ete tannees. Voyons maintenant par quelles voies le virus de la peste peut penetrer dans l’organisme. Les lesions cutanees sont une porte d’entree excellente. Suivant Netter, cette voie a ete signalee pour la premiere fois par un medecin genevois, Gosse, pendant la peste de la Moree. Le medecin japonais Aoyama ayant remarque aHong-Kong que les Chinois qui marchaient nu-pieds avaient ordinairement des bubons a la region inguinale, a suppose qu’ils s’infectaient le plus souvent par des blessures aux pieds. Plusieurs medecins et gargons d’amphitheatre ont contracts la peste pendant Pepi- demie actuelle d’Orient a la suite de piqures anatomiques. Du reste Pefficacite de cette voie est prouvee par les resultats posi- 2 tifsdes inoculations chez los animaux. La transmission par les puces ou autres insectes parasites se rattache au fond aussi k cettc voie d’infection. La mission allemande la considere comme la plus frequente. La contagion par les voies digestives a ete fortement appuyee par Wilm. Pour lui, la plus grande partie des pestiferes s’etaient infectes en avalant des aliments et des liquides souilles de virus. Bandi et Stagnitta affirment que, a Oporto, les observations cliniques et anatomopathologiques confirinent que la peste se propage surtout par la voie gastro-intestinale. Cette voie n’est cependant pas consideree comme frequente par la plupart des observateurs. bien que la medecine experimentale ait demontre la possibilite de donner la peste aux animaux par ingestion du virus. Ainsi Hankin, Lustig, Galeotti, ont infecte des animaux par voie diges- tive. Bandi et Stagnitta ont fait avaler a 47 cobayes des aliments charges de virus de la peste et tons ont succombe. Bandi. repe- tant les experiences de Batzaroff pour produire chez les animaux la pneumonie pesteuse primitive, nie l’infection directe par les voies respiratoires et aftirme que dans la plus grande partie des cas l’infection primitive est une gastro-enterite pesteuse. La voie de i’appareil respiratoire est cependant celle qui est admise comme la plus frequente par la majorite des observa- teurs. Signalee par Wyssokowitz et Zabolotny, puis par la mission allemande qui la considere comme rare, elle entrerait en jeu pour determiner la pneumonie pesteuse primitive chez rhomme. C’est a cette forme d’infection que Ton doit rapporter le cas du Dr Miiller de Vienne qui s’infecta en disinfectant la chambre de Barish. ^experimentation aurait demontre la pos- sibilite de creer chez les animaux une pneumonie pesteuse pri- mitive. De Giaxa et Gosio placent une trace de virus dans la trachee des cobayes et ceux-ci succombent en deux jours par pneumonie pesteuse. Sous la direction de Roux, Batzaroff a fait aussi des expe- riences a cet egard. En portant du virus de la peste sur la mu- queuse nasale des cobayes, des rats et des lapins, sans la leser, il a pu les tuer par pneumonie pesteuse primitive. L’infection avait lieu par cette voie, meme avec un virus tres attenue qui ne tuait plus par inoculation sous-cutanee et meme avec un virus desseche depuis 40 jours. La mortality. etait du 100%. Au cours de ces experiences, il a pu demontrer que toutes les autres muqueuses se pretent fort bien a ce role de porte d’entree. Deja, du reste, De Giaxa et Gosio avaient demontre qu’il suffit d’ir- riter la conjonctive des cobayes avec de l’ammoniaque et d’y deposer une trace de culture pour voir les animaux succomber en cinq jours a la peste. La mission allemande a signale une autre voie d’infection, celle des amygdales. Elle a ete constatee dans une autopsi \ Y a-t-il des causes capables de predisposer a l’infection par le virus de la peste buboniqueV Une des conditions essentielles de l’infection, c’est la salete associee a la misere. La poor’s pelague de Hodges en 1665 est restee encore telle aujourd’hui. A Canton et a Hong-Kong, Rennie a observe que la plus grande partie des malades etaient parmi les femmes, les petites lilies, les enfants, c’est-a-dire parmi ceux qui vivent sur- tout renfermes dans des maisons malpropres comme les maisons chinoises, ou les fenetres manquent souvent et ou les pores vi- vent dans la meme chambre que les bommes. II existe a Canton un contraste frappant entre la letalite des indigenes et celle de la colonie etrangere qui passa saine et sauve a travers l’epi- demie. M. Yrersin affirme que les conditions de malproprete de la ville chinoise etaient telles, que le seul remede eut ete de la b ruler. Les memes faits ont ete constates aux Indes. Le D1’ Muller, de la mission autrichienne, a fait l’interessante observation que les musulmans et les cliretiens indigenes ne sont presque pas frappes vis-a-vis de la forte mortality qui s’observe chez les Inclous. Or ces clerniers sont des vegetariens mal nourris et chetifs, tandis que les autres sont des mangeurs de viande bien nourris et soli des. M. Hankin a voulu nier les rapports entre la salete et la peste et, pour prouver sa these, il cite le fait de l’immunite clont jouis- sent les vagabonds mendiants, qui vivent toujours au grand air, et il ajoute: « L’immunite de ces gens qui vivent au grand air contraste avec la susceptibilite a la contagion de Brahmanes de Saara qui, en depit d’usages de proprete meticuleux, ne savent pas appre- cier l’utilite de la ventilation. » Or desirez-vous avoir un exemple de la proprete meticuleuse des Brahmanes? C’est M. Hankin lui-meme qui nous le donne en citant un Brahmane qui. avec sa femme, sa belle-mere, ses six enfants, un buttle et trois bullions, vivaient pele-mele sur la raeme litiere, toutes portes et fenetres closes! Si c’est Hi de la proprete meticuleuse, je mo demande ce que peut bien etre la salete ! D'autres exemples, du reste, ne nous manquent pas pour prouver l’influence de la malproprete et de I’encombrement sur le developpement de la peste. Parmi les agents de police de Bombay, ceux qui habitaient dans de nouvelles maisons, bien propres etaerees, ont eu quatre hommes atteints contre 151 pour ceux qui demeuraient dans les anciennes casernes. De ‘plus, l’histoire de toutes les epidermis de peste nous les montre en rapports in times avec la guerre et la famine, par con- sequent avec la misere. Boccace nous dit que dans l’epidetnie de Florence, au XIVe siecle, les pauvres succombaient par milliers. La peste de Milan, en 1630, fut precedee par la guerre et la famine. (Jolletta affirme qu’a Noia, la peste fit d'abord des ra- vages parmi les classes miserables. A Oporto, la peste frappe presque exclusivement des ouvriers entasses dans des maisons infectes. Dans un interessant rapport sur la peste des Indes, M. Lustig ecrit: « Actuellement, la famine y fait des ravages et a celle-ci sont associes la peste et le cholera. » B n’y a done pas de doute : misere, inanisation, encombre- ment, malproprete, voila les puissants allies du bacille de la peste bubonique. Un autre agent qui entre en jeu, comme il entre en jeu dans toutes les epidemies, c’est la peur qui agit comme un puissant predisposant. La peur, en effet — comme la medecine experimentale l a demontre, — affaiblit les moyens de defense de l’organisme contre les agents pathogenes. Dans toutes les epidemies, on a remarque l’influence du choc moral sur le developpemont des infections. C’est au fait de ne pas avoir eu peur que le celebre medecin de Nimegue, Isbrand de Diemerbroock, attribue en grande partie d’avoir passe indemne a travers la grande epi- demie qui frappa cette ville en 1636 et 1637. Plusieurs personnes, ecrit-il, ctaient surprises et se deman- daient comment je pouvais me garantir, moi qui entrais indiffe- remment dans toutes sortes de maisons infectees et qui visitais tous les malades. Cela les rendait attentives d ma conduite dont je vais donner ici le detail, afin qu’elle soit comme et profitc d tout le monde. Je fctisais tons mes efforts pour me mettre au-dessus des passions et pour me rendre intrepide. Je ne connaissciis ni le peril, ni la mort, ni quoi que ce soit; je regardais d’un osil in- different les maisons infectees et celles qui ne V etaient pas. J’en ttsais de meme d Vegard des malades ; je visitais avec autant de plaisir tin pauvre par charite qiCun riche qui me pay ait mes visites. Si quelquefois je in’ apercevais que la tristesse commengait a, s'emparer de mon dme, alorsje me redonnais du courage et je chcissais la rnelancolie avec trots on quatre verres de vin. Passons maintenant a Petude de Pagent specifique qui deter- mine la peste. Les anciens n’avaient pas beaucoup de peine a trouver la cause de la maladie: c'etait en general un dieu quelconque qui Penvoyait comme punition a l’humanite. Ainsi Boccace explique la peste noire comme la consequence de phenomenes astronomiques ou comme une juste punition envoyee aux homines par le bon Dieu. Symon de Covina en fait une consequence de perturbations dans les phenomenes astronomiques, tels que cometes, con jonc- tions de Saturne, Mars et Jupiter. Mais tous ces agents patho- genes etaient trop eloignes pour satisfaire le public qui desirait s’en venger, et on trouva tout de suite que les Juifs etaient les agents de la peste qu’ils repandaient avec des poisons. Aucune occasion plus favorable ne pouvait se presenter pour s’en debar- rasser et, comme les antisemites nationalistes d’aujourd’hui, on se mit a la besogne. Durant Pepidemie du XIV° siecle, plus de 50000 Juifs furent massacres. A chaque apparition nouvelle de peste, les massacres recommen§aient. Puis au XVIIe siecle tous deviennent suspects, tout le monde est soupQonne de repandre la peste. II suffisait de voir un mal- heureux se frotter contre un mur, s’arreter pour regarder une porte, pour qu’on le considerat comme un agent de dissemina- tion de la peste. Aussi rieii n’est plus triste a cet egard que ce qui se passa a Milan, dans Pepidemie de 1630, car ici les magistrals se firent les complices du peuple pour torturer et condamner a mort tous les malheureux soupgonnes d’etre les agents de dissemination de la peste. L'annee precedente, Philippe IV d’Espagne avait annonce au gouverneur de la Lombardie que quatre Fran^ais, soup^onnes de repandre des onguents pestiferes, avaient quitte Madrid. Des que la peste eclata, on vit ces homines partout. Un jour on les avait vus frotter les bancs d’une eglise, un autre jour les murs des maisons. On fit une grande procession et comme il est na- turel par le fait d’une grande agglomeration, les cas de peste doublerent. Les miserables avaient passe par la et avaient pro- fits de l’occasion pour semer au milieu de lafouleleurs poisons, dont on connaissait rnerne la formule : Ils etaient prepares avec c]es crapauds et des serpents, de la salive et du pus de bubons. On ne soupgonna.it pas seulement son voisin, em it Ripamonti, mais on doutait de Vami, de Vhote ; on craignait Le mari, la femme, le pere, le fils, le frere, la sceur; chose triste a dire, la table, le lit, etaient craints comme des guet-apens, comme des endroits empoisonnes. Les juges se preterent a ce jeu abominable et il en resulta le proces des untori, c’est-a-dire des personnes qui etaient censees oindre les maisons pour propager la peste. Et les juges, tout a fait convaincus de l’innocence des malheureux que le public leur avait designes, les condamnerent a la torture et a lamort dans les supplices. La decouverte de l’agent specifique de la peste ne devait etre faite qu’en 1894, lors de Pepidemie de Hong-Ivong, par Kitasato et Yersin. C’est un bacille tres petit, parfois a peine plus long que large, parfois quatre a cinq fois plus long que large, surtout dans les anciennes cultures. Dans les milieux de culture, il donne des formes comme des coques, parfois il est dispose en chainettes. Dans les cultures anciennes, on trouve des formes devolution raccourcies, rondes, en massue, en Clostridium. On y trouve des exemplaires legerement mobiles, mais la plupart sont immobiles. Oe bacille ne presente ni capsule, ni spores. On peut le colorer avec toutes les couleurs d’aniline, mais il ne prend pas le Gram. Une fois colore, il apparait comme un bacille a espace clair, c’est-A,-dire que les extremites seules sont colorees, tandis que la partie centrale est tout a fait incolore, s’il provient du sang, des bubons ou des cultures anciennes, tandis qu’il se colore uniformement lorsqu’il est fourni par des cultures fraiclies ou par des bubons au debut de leur developpement. On peut le cultiver sur tous les milieux de culture, a des tern- peratures de 10° a 37°, mais & cette derniere temperature il perd vite son pouvoir d’accroissement et j’ai de la sorte perdu completement des cultures. Sur plaques de gelatine, il donne des colonies blanches ou blanc-jaunatres, rondes, qui ne liquefient pas et qui se rappro- chent parfois par leur forme de celles du colibaciLie. Par pi- qure dans la gelatine, il donne une serie de petites colonies en profondeur et une plaque en surface. Parfois on y observe des ramifications, corame dans les cultures du charbon. Cultive sur agar, il donne des colonies blanches qui se fondent entre el les. Sur pomme de terre, il ne donne qu’une faible couche d’un blanc jaunatre. Sur les carottes cuites, son cleveloppement est a peine visible. Dans le bouillon, on obtient, dans la plupart des cas, un depot aufond et des grumeaux le long des parois de l’eprouvette, tandis que le bouillon reste clair, mais parfois tout le bouillon est trouble. Il cultive faiblement dans le lait et, excepte Wilm, personne iva vu la coagulation de ce milieu. Il ne fait pas fermenter le sucre et ne donne pas d’indol. Il est agglutine par le serum des pestiferes. Dans les cultures, ce bacille produit une substance toxique qui est surtout tres adherente au corps du bacille meme et par consequent plus abondante dans les vieilles cultures ou les ba- cilles sont maceres tandis que dans les cultures simplement filtrees il n’y en a pas. On pent la precipiter par du sulfate dammoniaque et on obtient une poudre qui a la dose d’un quart de milligramme, tue une souris en quelques heures. Cette toxine est tres peu resistante : Un chautfage a 70° peut en detruire une partie notable. Les cultures du bacille de la peste presentent la meme virulence que le virus pris sur les pestiferes, et determinent chez les ani- maux tous les symptomes de la peste. Les animaux succombent de quelques heures a quelques jours apres l’injection, et presentent cedeme au point d’inoculation, si I’injection a eu lieu par la voie cutanee, hemorragies dans les differents organes, tumefaction de la rate et du foie, congestion des capsules surrenales, serosites dans la plevre et le peritoine, broncho-pneumonie pesteuse primitive, ou pseudotubercules de pneumonie secondaire,lesionsdegastro-enterite pesteuse. Le ba- cille se trouve clans le sang, ganglions, serosites du peritoine et de la plevre, foyers pulmonaires, foie, rate. Chez les personnes atteintes de peste, les parties du corps dans lesquelles on trouve le bacille de la peste sont les sui- vantes: 1° Dans les ganglions, soit lorsqu’il y a des bubons, soit lors- qu’il n’y a pas de tumefaction visible. Lorsqu’ils entrent en pleine suppuration, il est tres difficile 5, cleceler, car il est rem- place presque tout a fait par des staphylocoques et des strepto- coques. 2° Dans le sang. Les observateurs sont tres partages sur la presence du bacille dans le sang. Suivant Yersin, on ne I’y ren- contre que dans les cas tres graves et rapidement mortels. La mission autrichienne l’a trouve 55 fois sur 122 cas, les Italiens 6 fois sur 15 ; Wilm dans le 77 °/u des cas. En general, suivant Netter, on le trouve dans le sang dans le tiers des cas. Suivant Kitasato on peut le cultiver du sang, meine trois semaines apres guerison. 3° Dans tous les organes, et dans les foyers de pneumonie pesteuse oil il est ti es abondant. 4° Dans les crachats des pestiferes atteints de pneumonie. 11s en sont remplis, et il y est a l’etat pur ou associe a d’autres bac- teries. 5° Dans les feces. Wilm et Kitasato affirrnent de I’y avoir sou- vent trouve a Hong-Kong (38 fois sur 45 suivant Wilm); Ga- leotti et Polverini ont eu quatre cas de peste intestinale avec de nombreux bacilles dans les feces. La mission allemande ne l'a jamais trouve dans les feces. 6° Dans les vomissements. Wilm l’aurait trouve IS fois sur 20 observations. 7° Dans les urines. Wilm affirme de l’avoir trouve 40 fois sur 40 observations, tanclis que la mission allemande ne l'a trouve que cleux fois. 8° Dans la salive, oil Wilm l'a trouve 14 fois sur 16, rnals il n’y a pas ete rencontre par la mission allemande. 9° Dans les sueurset sur l’enduit saburral de la langue, oil il a ete sign ale par Wilm. En dehors de l’organisme, dans le milieu exterieur, il a ete rarement observe. Kitasato l’a trouve dans la poussiere cl’une chambre de pestiferes; Yersin a 4-5 metres de profondeur dans le sol d’une maison de pestiferes, mais il n’etait plus virulent; Wilm dans deux puits a Hong-Kong, Hankin dans un niarais aux Indes. Etudions la resistance du bacille de la peste aux differents agents de destruction : II est a remarquer, en regie generale, qu'il parait presenter un degre de resistance tres faible, chose etonnante si nous pen- sons que dans les conditions naturelles il parait conserver long- temps sa virulence en dehors de Porganisme. M. Metchnikoff suppose Pexistence d’une forme de resistance de ce bacille, forme qui, jusq’a present n’aurait pas ete rencontree. D’autre part, si nous pensons que Baizaroff a pu donner la pneumonie pesteuse a des animaux en deposant sur lamuqueuse du nez des cultures qui lie donnaient plus la peste par inoculation, on peut suppo- ser que la voie dhutroduction peut redonner la virulence et la propriete de se multiplier a des formes tres affaiblies du bacille de la peste. Kitasato, a constate que les cultures exposees a la dessication sont tuees en quatre jours a 20°-30°; sous les rayons du soleil en 3-4 heures. L’air, la lumiere, n’agissent qu’associes a une temperature de 30"-35°. La mission allemande a constate qu’aux Indes, avec des temperatures de 29°-31° il est detruiten 4 jours. Dans nos climats, au contraire, il se conserve jusqu’a 30 jours, mais apres 18 jours il a perdu beaucoup de sa virulenee. Loffler, sur des fils de soie places dans l’obcurite a la temperature de la chambre, les a gardes vivants 56 jours. Par le chauffage a sec le bacille de la peste est tue en 1 heure a 100". En milieu hu- mide, suivant Kitasato, il est tue en 30 minutes a 80° et en quelques minutes a 100°. Toptschieff les a tues dans des tubes capillaires par un chauffage de 4 minutes a 58° et dans des- eprouvettes par un chauffage de 8 minutes. Des recherches d’Abel, il resulte qu'il est tue en 1 minute a 100°; en 5 a 80", en 10 a 70°, en plus de 10 a 60°. A une tempe- rature de 50° ii est parfois tue en 30-40 minutes, mais pas- toujours. Parmi les differents antiseptiques essayes, je signalerai le su- blime, le meilleur suivant la mission allemande, qui le tue en 2 minutes en solution 1 %0; l’acide phenique 5 % qui le tue ne 10 minutes; la creoline 5 °/„ qui le tue en 5 minutes; la formal- dehyde ‘/go qui le tue en 2-60 minutes; le lait de chaux 1 °/o qui le tue en 30 minutes; le chlorure de chaux 1 °/0 qui le tue en 2 minutes. Des recherches cle De Giaxa et Gosio, il resulte que le sel de ■cuisine peut en empecher le developpement et en attenuer la virulence. Le bacille de la peste bubonique, place dans l’enu distillee, y resiste 20 jours (Wilrn), dans l’eau de boisson 16 jours (Wilm), 10 48 jours (Kasanski); dans l’eau de mer 6 jours (Wilm), dans 1’urine de l’homme 62 iours (Kasanski), dans le lait 26 jours (Kasanski), sur les graines humides 10 jours (Bandi et Sta- gnitta). Par rapport a la persistance des bacilles dans les cadavres cnsevelis, les recherches de Yokote et de Klein, faites sur des animaux, demontrent qu'ils y persistent 20-30 jours. Plus elevee ■est la temperature et plus forte la putrefaction, moins resistant est le bacille de la peste dans les cadavres. Schottelius, experi- mentant avec des rats, aurait constate que les bacilles emigrent tres vite dans le sol, jusqu’a 20 cm. de distance. Passons maintenant a l’exposition des symptomes, du diag- nostic et du traitement de la peste bubonique. La peste bubonique a une incubation de 36 heures a 10 jours -et une moyenne de 1 jours. Apres cette periode d’incubation, qui n’est caracterisee par aucun symptome, la maladie eclate hrusquement, avec frisson, fievre, vomissements, cephalee, douleurs a l’epigastre et aux reins. La temperature monte tres vite a 40°-41°. La figure est pale, les yeux injectes, insomnie, delire, pouls tres frequent et tres faible. Langue a pointe rouge et le reste couvert par un enduit epais. jaunatre. Apparaissent des bubons a la region de Paine, de l’aisselle ou an cou. Sur 24 cadavres, Wyssokowitz et Zabolotny ont trouve les bubons 10 fois a. Paine, 4 a l’aisselle et 4 au cou. Suivant Yer- sin, ils siegent a Paine dans le 75 % des cas et a Paisselle dans le 10 °/0. Ces ganglions peuvent etre douloureux des le premier jour, ou bien ne se manifester qu’au deuxieme ou troisieme jour. Si les cas se terminent rapidement par la mort, les gan- glions restent durs, douloureux, entoures d’une zone cedema- teuse. Dans d’autres cas, ils peuvent etre resorbes. Mais le plus souvent ils atteignent la dimension d’un oeuf de poule et le septieme on hui tie me jour ils suppurent. II en resulte des ulce- res profonds, qui ont beaucoup de peine a guerir. L’intelligence se perd petit a petit, on peut observer des con- vulsions. La respiration est acceleree, bruyante, et il y a de l’cedeme pulmonaire ou des foyers de pneumonie secondaire. Souvent on observe de la diarrhee, mais parfois de la cons- tipation. L’urine est peu abondante, albumineuse dans la plus grande partie des cas. Sur la peau peuvent apparaitre des petecliies, des phlycte- nes qui s’ulcerent rapidement et donnent des charbons. La mort, qui s’observe dans le 64, 77, 95 % des cas cliez les indigenes, dans le 37-39 °j0 des cas cliez les Europeens, arrive en general dans le coma. Parfois on observe des cas tres legers, avec guerison en 8-10 jours. La forme que je viens de decrire est la forme pour ainsi dire classique de la peste bubonique, mais dans toutes les epidemies on observe de tres nombreuses varietes, dont quelques-unes tres importantes a connaitre. Une premiere variete est la forme septicemique, a debut tres violent, fievre a 41°-42°, courbature, delire suivi de coma. La mort survient en 24 heures a 2-3 jours. Elle est souvent accompagnee d’hemorragies, et il n’y a pas de bubons. C’est avec cette forme que la peste avait debute en Orient au XIVU siecle, et Boccuce ecrivait deja que le saignement du nez etait signe inevitable de mort. La seconde forme est une forme pulmonaire primitive ou pneumonie pesteuse. Deja observee dans les differentes epide- mies. elle a ete bien etudiee seulement dans l’epidemie actuelle. C’est le merite de Childe d’avoir attire l’attention sur cette forme dans l’epidemie de Bombay de 1897. Elle debute comme une pneumonie, avec frisson, fievre 39°-40°, cephalee, vomissements, sans acceleration de la respiration et sans dyspnee. Les crachats, sauf derares exceptions, ne sontpas visqueux ni rouilles, mais muqueux et roses et si on les examine au microscope on les trouve remplis de bacilles pesteux, seuls ou associes au pneumocoque et au streptocoque. Parfois toux et crachats font defaut. Cette forme reclou table, a cause de la grande infectiosite des crachats, tue en 3-5 jours. La petite epidemie de Vienne a ete caracterisee par cette forme et on La observee aussi en Egypte et a Oporto. La mortality est de 90 %. La troisieme forme est la forme abdomiuale, caracterisee par frisson, fievre, vomissements, ballonnement du ventre, diarrhee et suivie des symptomes generaux de la peste. Elle parait plus rare que les autres formes. Le diagnostic rapicle de la peste est de la derniere importance, car, comme nous le verrons sous peu, c’est sur un diagnostic imme- diatement pose que l’on peut esperer d’appliquer les regies pro- phyla ctiques avec resultat. Si la peste se presente dans la forme classique, avec tous les symptomes indiques, le diagnostic ne pourra pas etre douteux. II pourra etre confirme par l’examen microscopique et la cul- ture du liquide sereux qui provient de la zone empatee qui en- toure les ganglions. La mission allemande a eu de la sorte neuf resultats positifs sur onze examens. Le diagnostic devient plus difficile dans les formes septice- miques et loudroyantes de la peste oil le bubon manque. La confusion est alors possible avec le paludisme, la fievre typhoide, le typhus exanthematique, la fievre recurrente. C’est surtout la violence du debut, la prostration tres forte, le pouts tres frequent et tres faible qui peuvent mettre sur la voie du diagnostic. Dans ces cas, l’examen et les cultures du sang peuvent donner des indications favorables pour le diagnostic, mais il faudra faire de nombreuses preparations. On confirmera le diagnostic bacteriologique, soit en inoculant a des rats et a des souris de fortes doses de sang suspect, soit les cultures des qu’elles seront developpees. Le diagnostic de la pneumonie pesteuse est tres important, vu le grand danger de sa contagion. Les statistiques de Bombay, avant le travail de Childe, incliquaient toutes les pneumonies pesteuses primitives comme des affections pulmonaires ordi- naires. Le Dr Muller a Vienne considera d’abord la pneumonie de Barisli comme une pneumonie grippale. Pour le diagnostic, ce qu’il y a de plus sur, c’est de pratiquer l’examen bacteriolo- gique des crachats. Le pouvoir agglutinant du serum des pestiferes pourrait-il nous servir pour le diagnostic de la peste V Suivant Wyssokowitch et Zabolotny, une reaction bien tranche peut seule avoir nne valeur. Leumann auiait constate 1’agglutination 39 fois sur 40 cas cleja au cinquieme jour de la maladie. Mais les cas les plus difficiles a diagnostiquer, ce sont les cas de peste ambulante, caracterises par une fievretres legere, avec endure des ganglions. Ils sont surtout frequents au debut et a la tin des |pideinies. Simpson et Cobb a Calcutta auraient trouve dans le sang de six malades atteints de cette forme le bacille de la peste, mais la chose n’a pas ete confirmee. Quoi qu’il en soit, dans ces cas, I’examen bacteriologique sera le seul qui pourra permettre un diagnostic sur, mais au lieu de porter sur le sang il devrait porter sur les ganglions, car, meme s’il n’y a pas de bubon, les ganglions contiennent toujours du bacille (Yersin). Les lesions anatomo-pathologiques des pestiferes ne nous arreteront pas longtemps. S’il v a bubon, on trouve qu’il est le plus souvent forme par plusieurs ganglions reunis en pa- quet; et il est entoure d’une zone d’cedeme du tissu conjonctif. Soit le bubon, soit le liquide de l’oedeme, contiennent de nom- breux bacilles specifiques. Les autres glandes lympathiques sont aussi tumefiees, mais ne sont pas plus riches en bacilles quo le sang lui-meme. La rate et le foie presentent une forte tumefaction et contiennent des bacilles en assez grande quantite. Dans certains cas, il v a des lesions de broncho-pneumonie a foyers isoles, d’aspect muqueux et dans lesquels on note de nombreux bacilles, bacilles qu’on trouve aussi dans les ganglions bronchiques tumefies. Dans l’appareil digestif, on peut rencontrer des lesions de gastro-enterite. La recherche des bacilles, sur le cadavre ou sur le pesti- fere, peut se faire, soit par l’examen direct, soit par les cultures, soit par des inoculations sur les rats et les souris. La gelatine, mais preferablemeut l’agar ou le bouillon a 3?', donnent de bons resultats pour les cultures. Hankin recommande l’agar avec 2,5-3,5 % de sel ou 2 % de iodure ou bromure de potassium, car sur ce milieu les formes cl’involution caracteristiques du bacille de la peste se develop- pent tres vite. Pour inoculer une souris ou un rat, il suffit de charger une anse de platine avec un pen de virus, et de l’introduire dans une boutonniere de la peau de la cuisse ou bien de porter le virus sur la muqueuse du nez. Les animaux meurent en 2-4 jours avec de nombreux bacilles dans le sang et dans la rate. Le traitement de la peste bubonique a ete absolument nul jusqu’a ces derniers temps. Pour soigner la peste, ecrivait Boc- cacej il n'y avail ni conseil de medecin, ni vertu de medecines. On employait des exorcismes et le plus souvent on abandon- nait les malades ou on les bouchait dans leurs maisons. Je ne ferai que de citer les essais d’opoterapie que les peuples du lac Baikal pratiquent contre la peste de Sarbagane: 11s donnent a manger aux malades les capsules surrenales des Arctomys, mais sans resultat. C’est la decouverte du bacille specifique qui devait nous mettre sur le chemin pour decouvrir un remede contre la peste bubonique, et si la serotherapie n’a pas donne les resultats que l’on attendait d’elle, il n’est pas dit qu’elle ne puisse nous en donner sous peu de bicn meilleurs. C’est le merite de MM. Yersin, Calemett et Borrel, d’avoir introduit dans la pratique cette methode. Ces savants, apres avoir demontre qu’en vaccinant des lapins avec des cultures de B. pestis chauffees a 58° pendant une beure on pouvait en tirer un serum preventif et curatif, essayerent la meme chose sur le cheval. Le premier cheval a ete soumis a des inoculations de cultures vivantes et virulentes du bacille. A la premiere inoculation, la reaction a ete tres forte et tres longue. La deuxieme inoculation, apres 20 jours, donna aussi une reaction tres forte, mais decourte duree. Alors ils firent des injections a des intervalles plus rap- proches. Apres six semaines, le serum de ce cheval etait deja suffisam- ment actif pour preserver et curer des cobayes et des souris ino- cules de peste. Mais Limmunisation avec des cultures vivantes et virulentes presentait un grand danger pour la dissemination de la.peste. On l’a remplacee par Limmunisation avec des cultures tuees par le chauffage a 70° pendant une demi-heure. Malheureusement le serum obtenu par cette seconde methode est beaucoup moins actif. D’autres bacteriologistes ont essaye de preparer le serum an- tipesteux, en vaccinant des chevaux avec des substances toxiques produites par les bacilles. Roux a isole une toxine qui tue les souris a la dose de '/io cl. c. ; Markl une qui les tue a la close de V800 ; Wernicke aussi une toxine tres active. Mais ces experimentateurs, soit en vaccinant avec la toxine, soit avec celle-ci associee au corps des bacilles tues, n’ont pas pu obtenir un serum bien actif.. Roux prepare maintenant le serum avec des inoculations de doses enormes de toxine et de corps de bacilles tues par la chaleur. MM. Lustig et Galeotti, au contraire, ont prepare une toxine qui pourrait servir tres bien pour immuniser les clievaux. Ils laissent une culture en contact pendant 12-24 beures avec une solution de potasse caustique 0,75 %. Ils traitent alors le me- lange par Tackle acetique ou chlorhydrique. Ils obtiennent de la sorte une toxine qui tue les animaux a la dose de 5-8 mg., par 100 gr. du poids du corps et immunise assez rapidement les chevaux. Ilexiste maintenant a Bombay un institut ou Ton pre- pare le serum avec cette derniere methode. Voyons quels ont eteles resultats curatifs des serums antipesteux. En 1897, Yersin appliquait a Amo'i son serum. Sur 26malacles traites, il compta 24 guerisons ! On s’empressa de proclamer que grace au serum antipesteux, la mortality de la peste etait tombee du 90% au 7,6 °/0! M. Yersin passa faire ses inoculations aux Indes, mais ici les resultats ne furent pas si favorablcs. La mortalite des traites fut du 34 %. ANah-Trang. les inocules presentment une mortalite du 42 %. La mission allemande, tout en ayant constate Taction preven- tive et curative du serum Yersin sur les animaux, declare no pas pouvoir se prononcer par rapport a Thomme. La mission autrichienne a ete du meme avis et le Dr Muller qui en faisait partie, et qui mourut de la peste a Vienne, refusa de se faire traiter par le serum. Les medecins anglais aux Indes sont tres scepti- ques a son egard. La mission russe a eu des resultats pen satis- faisants. Les medecins italiens, de retour cTOporto, ecrivent quo la serotherapie par le serum Yersin y a donne des resultats ne- gates et Terni ajoute que, meme par la voie experimentale, le serum lui a donne des resultats absolument nuls. Le Dr Clenow aux Indes n’a eu aucun resultat, et suivant lui, ce serum est un liquide indifferent qui n'est pas clangereux, mais qui n’a aucune action! Quelles sont les causes de ces echecs ? D’abord il faut noter que le resultat primitif d’Amo'i, si favo- rable, cloit etre attribue au fait que la peste y etait alors beau- coup moins grave qu’aux Indes et, en outre, on ne pouvait pas comparer la mortalite des inocules avec celle qu’on avait obser- vee Iiong-Kong. Aux Indes, les formes de pneumonie pesteuse primitive et de septicemie sont tres frequentes. Or contre ces formes, les resultats de la serotherapie sont tres douteux. L’in- tirmiere Pecha a Vienne, traitee par le serum, est morte comme le Dr Muller qui n’avait pas voulu etre traite. Batzaroff, dans ses recherches sur la pneumonie pesteuse des animaux, n’a pas non plus obtenu de resultats favorables par la serotherapie et il condiut que la meme chose doit arriver chez Lhomme. Yersin fait aussi entrer en jeu, comme cause des echecs, le fait d’avoir employe du serum de chevaux insuffisamment vaccines. II faut, en effet, un an a un an et demi pour obtenir d’un clieval un serum efficace. En outre, les resultats sont defavora- bles si la serotherapie n’est pas appliquee des le debut de l’in- fection. Suivant Calmette, en outre, une seule injection ne suffit pas, il faut en faire plusieurs par jour. De la sorte il aurait, a Oporto, reduit la mortalite de 43,5 % a 13%. Le serum prepare par la methode Lustig-Galeotti a ete applique aux Indes, sur une eehelle assez vaste. A l’hopital Arthur-Iioad, les traites presentment une mortalite de 57,1 %, les non-traites de 83 %. Sur 104 autres malades traites, la mor- talite a ete du 45,2 %. Avec ce serum, on a pu guerir aussi trois cas de septicemie, mais jamais la pneumonie pesteuse. La com- mission de sante de Bombay le considere comme le seul serum curatif. Clenow pourtant, meme avec ce serum, n’a pas eu de resultats favorables. Les deux methodes me paraissent donner a peu pres les memes resultats. Nous sommes loin des resultats que i’on esperait apres l’experience d’Amoi. En principe, ecrit avec beaucoup d’a propos Metchnikoff, la serotherapie antipesteuse doit etre consideree comme une ques- tion resolue, mais dans la pratique il faut tdcher d’obtenir des serums beaucoup plus actifs que ceux qui ont ete employes jusqiCa present. Suivant Roux, le defaut de tous ces serums est d'etre antito- xiques et non antiinfectieux, e’est-a-dire agissant uniquement sur la toxine et non sur le bacille lui-meme. Quant a moi, j’ajouterai que les resultats obtenus ne sont pas du tout a dedaigner, car e’est toujours quelque chose d’avoir diminue quelque peu la mortalite par peste bubonique. Mais la lutte contre la peste bubonique doit etre engagee plus par les mesures prophylactiques que par le traitement, car a la prophylaxie tons peuvent et doivent contribuer. Abortions en premier lieu l’etude de la prophylaxie dans les siecles passes. La prophylaxie de la peste dans les siecles passes a ete un melange de mesures absurdes et de mesures bien congues. La superstition, la haine de race et de religion ont joue le plus grand role dans la prophylaxie des siecles passes et em- peche l’appiication des bonnes mesures qui etaient par-ci par-la recommandees. Durant la peste de Florence du XIVe siecle, Boccace nous inclique les mesures prophylactiques que Lon avait adoptees : on avait cree des deputes de sante •charges de nettoyer la ville et de donner des conseils pour se preserver de la peste. On interdit a tout malade cl’entrer dans la ville. On fit des processions et des prieres a Dieu. Le public, pour se preserver de la peste, abandonnait les infirmes et les maisons, systeme adopte encore aujourd’hui au lac Baikal et dans le district de Guhrwal. Quelques-uns se renfermaient dans des maisons isolees, pour y vivre separes de tous en mangeant et en buvant moderement. D’autres, au contraire, jugeaient que boire et s’amuser etait le meilleur preservatif contre la peste, et passaient toute la journee au cabaret. D’autres prenaient le juste milieu: ils ne limitaient pas trop I’alimentation, ne s’amusaient pas exeessivement, ne s’enfer- maient pas, mais ils se promenaient en portant dans leurs mains des fleurs, des herbes odorantes, differentes sortes d’epiceries, qu’ils portaient souvent au nez. Bien d’autres enfin, jugeant qu’il n’y avait de meilleur moyen que de s’enfuir, quittaient la ville et allaient s’etablir a la cam- pagne. Mais Boccace observe que dans toutes ces categories de personnes, on observait des cas de peste. Toujours au XIVC siecle, la republique de Venise creait les provediteurs de sante et la pratique des quarantaines. A cote de ga, on brulait des Juifs et on faisait des processions, des pelerinages et des flagellations. M. Porquet nous dit que dans les epidemies de peste de Nor- mandie aux XIVe et XVI0 siecles, on isolait ou abandonnait les raalades, on fermait ou gardaita vue les maisons des pestiferes. On donnait les sacrements avec de petites verges de bois ou des pincettes, les medecins portaient des habillements speciaux. On faisait beaucoup de pelerinages et de processions, dont le cler^e proclamait la souveraine efficacite. Au XVI” siecle en France, une ordonnance du 1G novembre 1510 imposait de signaler par une botte de paille toute maison oil se trouvait un pestifere et de laisser ce signalement deux mois sous peine d’une amende tres severe. Ceux qui demar- quaient les maisons avaient le poing coupe. Au siecle suivanty on fonda les hopitaux St Louis, St Marcel et Ste Anne, affectes- exclusivement aux pestiferes. Les convalescents de peste ne pouvaifnt sortir qu’avec un baton blanc. II existait des parfu- meurs et des aereurs jures, charges de desinfecter toutes les- maisons des pestiferes, mais ils n’avaient a leur disposition que des pastilles kites avec differentes substances aromatiques- auxquelles on ajoutait du soufre et du cinabre, et que l’on jetait en plus ou moins grande quantite sur des charbons ardents. La tenue des foires etait prohibee en temps de peste. A Milan, en 1630, on chercha aussi a prendre des mesures- propbjdactiques contre la peste. Tadino et Settala, medecins du tribunal de sante, proposerent avant l’explosion de la peste dans la ville, de defendre aux ha- bitants d’acheter toute sorte d’objets chez les soldatsqui devaient arriver des endroits infectes. Mais la proposition fut, repousseer car, comme Tadino l’ecrit, le president du tribunal de santer homme tres bon, ne pouvait pas croire qu’il put y avoir mortality de milliers de personnes pour des rapports avec des soldats et leurs objetsl Une fois la peste entree dans le ducbe de Milan, on envoya Tadino pour la reconnaitre, et il ecrit que les habitants, a la campagne, semblaient des creatures sauvages qui s’echappaient des maisons en portant dans leurs mains du romarin, de la menthe ou un flacon de vinaigre. On crea des ofticiers de sante- pour visiter les maisons des pestiferes, un corps d’infirmiers pour le transport des malades, infirmiers qui portaient une clochette pour avertir le public de s’eloigner d’eux s’il ne voulait pas s’infecter, un lazaret pour y transporter tous les pestiferes. Mais le public, convaincu que la peste etait disseminee par des miserables, forga les juges a en condatnner plusieurs a la mort, organisa des processions, et apres celles-ci la mortalite monta a plus de 3500 par jour ! Au siecle passe, on n’etait pas plus avance. M.Morax cite le fait qu’en 1720, sur avis du conseil de sante de Lausanne, le magnifique seigneur baillival de cette ville ordonne qu’on ne fera plus d’huile de noix et on ne distillera plus de genievre, parce que les noix et les grains de genievre sont de bons preser- vatifs contre la peste. On ajoutait pourtant a cela des quaran- taines pour les marchandises et on taisait parfumer les lettres provenant de l’etranger. Mais il est interessant de voir comment le corps medical se comportait dans les siecles passes pour se preserver de la peste: En 1619, a Paris, ecrit Fournier, pendant une des plus graves epidemies de peste, les medecins appeles aupres des malades ne les approchaient qu’avec terreur et paraissaient preoccupes sur- tout d’assurer leur propre conservation : Charles De Lorme, medecin de Louis XIII, avail invente un costume special qu’adop- terent aussitot la plupart de ses confreres. Par-dessus leurs ve- tements, ils portaient une chemise dont Petoffe avait ete trempee dans une composition dans laquelle entraient des sues, des huiles et sept poudres differentes. Ils s’enveloppaient en outre dans un habit de maroquin, que le mauvais air penetre tres difficilement, prenaient dans la bouche une gousse d’ail, se met- taient de la rue dans le nez, de l’encens dans les oreilles, cou- vraient leurs yeux de besides, et montes sur une mule, allaient visiter leurs clients en cet equipage. Cet habit etait encore em- ploye au siecle passe. Isbrand de Diemerbroock, dont je vous ai deja parle, outre qiril n’avait pas peur, avait d’autres specifiques pour se preser- ver de la peste: Pour ma nourriture, ecrit-il, fusais de viandes qui fussentde bon sue et de facile digestion, evitant avec grand soin celles qui m’avaientparu contraires ehez les autres, comme pour lepour- ceau, les harengs, etc. Je buvais de la Mere ordinaire de Ni- megue et du vin blanc leger, dont je prenais jusqiCd m’egayer, sans que ma tete en fut jamais troublee. Je me tenais Vestomac libre, et Veconomic des organes reglee avec autant d''attention et de soin qu'il etait en mon pouvoir. Une fois ou deux la semaine, en me mettant au lit, j’avalais une ou deux de mes pilules contre la peste. II n’oubliait pas non plus de se recommander au Seigneur, et de macher quelques grains de cardamome, de la theriaque, du dioscordium, de Pecorce d’orange et de la racine d’aune conhtes avec un verre de vin d’absinthe. Mais son preservatif par excel- lence, e’etait une bonne pipe de tabac ! J’ai toujours regarde cette plante comma le meilleur preser- vatif contrela peste. Ce n'est pas tant le raisonnement que ma propre experience qui m’en out convaincu, et je ne pense pas qu’on en ait trance nn plus sur jusqu’a present, pourvu que ce soit du bon tabac en corde, bien mur. Mais )es pauvres medecins, qu'on appelait semeurs depeste, etaient bien a plaindre. Merae s'ils eussent voulu prendre de bonnes mesures contre la peste, le people les en aurait empeches. Encore an siecle passe, on fut menace d’une emeute k Paris, parce.qu’on voulait remplacer par des conduites le long des maisons les gargouilles versant l’eau des toits au milieu des chaussees! 11s devaient bien se garder de poser au debut d’une epidemie le diagnostic de peste. Le peuple menacait deles tuer. Le medecin L. Settala, qui bt le diagnostic cle la peste a Milan en 1630, faillit etre assomme. Tous ceux qui osaient parler de peste etaient insultes. Bien des medecins s’allierent du reste au peuple, et ils trouvaient cliaque jour un nouveau nom pour appeler un cas de peste qu’ils etaient charges de soigner. On cachait les malades, on corrompait les officiers de sante. On accusa Tadino et Settala d’avoir repandu le bruit de peste pour gagner de l’argent sur la peau du public. Et plus la peste faisait de progres, plus on s’acharnait a la nier: e’etaient des fievres malignes, des fievres pestilentielles. Pour convaincre le public, on fut force de promener dans les rues de Milan un char avec les caclavres d’une famille de pestiferes. D’aborcl done, ecrit a cet egard Manzoni, ce u'etait pas de la peste, absolument pas, cVaucune fcicon, clefendu meme cVen prononcer le nom. Vais des fievres pestilentielles; Videe est ad- mise en biais dans un adjectif. Puis ce n'est pas de la peste veritable, et pourtant e'en est, mais dans un certain sens; ce n’est pas precisement de la peste, mais line chose d laquelle on ne sait pas trouver un autre nom. Enfin, c’estlapeste sans aucun doute, et sans discussion, mais on y ajoute dejd line autre idee, Videe de Vempoisonnement, du malefice, idee qui altere et con- fond Video, exprimee par le mot que Von ne peut plus cacher. Mais devons-nous nous etonner de ca V Ne vous ai-je dit qu'a Wetlianka on trouva, en 1S78, le nom de pestis nostras, et on considera la maladie comme quelque chose entre la peste et le typhus ? N’avons-nous pas assiste au spectacle ecceurant du peuple de Oporto attaquant le Dr Jorge qui eut le merite de denoncer la peste ? Et en Russie, a propos des cas de Kolobovna, 17 medeeins les considerent comme des cas de peste, pour sept ils se rapproclient beaucoup de la peste! C’est de la peste, raais il lie faut pas le dire! Les siecles passent, rnais chez les homines restent les traces de l’ancienne superstition. Mais passons maintenant a l’etude de la prophylaxie actuelle. Deja au debut de notre siecle,a Noia, on nous donne Pexeinple d’une bonne prophylaxie : le foyer infecte est rigoureusement isole; on fait tuer les animaux soupconnes de pouvoir repandre la peste; on bride les objetsinfectes ; on cree des hopitaux dhso- lement pour les intirmes et les convalescents, des lazarets d'observation. Tous les commerces sont defendus, les eglises fermees. Des mesures analogues furent prises a Wetlianka en 1878: Loris Melikoff ecrivait: Toutes les maisons infectees ont ete brulees. La prophylaxie de la peste, en Europe, vise aujourd’hui deux points : 1° Proteger l’Europe de l’invasion de la peste d’Asie, d’Afri- que, d’Amerique. 2" Proteger les differents pays de PEurope contre la peste qui s’est manifestee dans un de ceux-ci : Bien qu’un foyer de peste existe deja en Europe, le premier point n’est certainement pas a abandonner, car de ce cote-la nous pouvons craindre une invasion plus grave que celle qui pourrait provenir d’Oporto. La defense de PEurope vis-a-vis de Pimportation d’Orient, est representee par une triple ligne : lrc ligne: Empecher Pembarquement et le depart des lieux infectes, des contamines, des malades ou des suspects et desin- fection de.tout ce qui pent transporter les germes. 2C ligne: Lazarets et postes d’observation dans le golfe Per- si jiie, la mer Rouge, et du cote de la Perse et du Turkestan russe. 3e ligne: Lazarets dans tous les ports de la Mediterranee, de l’Ocean et de la mer Noire et Caspienne. La premiere ligne est confiee au gouvernement anglais, qui fait visiter par une commission medicale les personnes qui s’em- barquent pour PEurope, et retient tous les suspects, les linges et les vetements souilles. La deuxieme ligne de defense coraprend, comme j’ai dit, la surveillance de l’importation de la peste par la voie de terre et de mer. La voie de terre est celle du Turkestan russe, des frontieres orientates de la Perse et de la frontiere siberienne. C’est & la Russie et a la Perse qu'incombe le devoir de bien surveiller cette ligne d’invasion. De ce cote, ou les populations sont clair- semees, les cordons sanitaires peuvent encore donner de bons resultats et, en effet, ils ont bien servi en 1897 quand la peste s’etait declaree dans le Belougistan et 1’Afghanistan. Le dan- ger d’importation par le Turkestan est augmente depuis la cons- truction de la ligne de chemin de fer qui, de Batoum sur la mer Noire, par Tiflis, va a Bakou sur la mer Caspienne, et se pro- longe de l’autre cote jusqu’a Samarcande. Des postes d’obser- vation doivent done etre entretenus sur ces frontieres. Par rap- port a la frontiere siberienne, le chemin de fer nous menace de l’importation de la peste du Baikal et de Mongolie. Ici encore, c’est le gouvernement russe qui doit s’occuper d’installer des postes d’observation le long de la ligne, et il clevra se rappeler du danger que peut representer l’importation des peaux d'Arc- tomys bobac, importation qu’il serait bon d’interdire. Par la voie de mer, la peste peut etre importee en Europe par le golfe Persique et la mer Rouge. Du cote du golfe Persique, comme M. Proust le fait remarquer avec raison, tout est a faire. Le seul lazaret qui existe de ce cote est celui de Bassorah qui, malheureusement, est a 80 km. de la mer ! En outre il n’existait, pour ainsi dire, que sur le papier. \ oici; en effet, dans quelles conditions il se trouvait en 1897 : C’etait une bicoque avec cinq ebambres non meublees. Les personnes en quarantaine etaient forcees d’engager un cuisinier si elles ne voulaient pas mourir de faim. Les sains etaient sepa- res des suspects par une natte de 50 cm. de baut. Le-linge sale etait porte en ville pour y etre lave. Les differentes pieces de l’etuve a disinfection etaient dispersees §a et la dans le lazaret. Heureusement qu’on nous rapporte que maintenant 1 ordre regne au lazaret de Bassorah! Mais il persiste toujours l’inconvenient de son mauvais empla- cement. On avait propose de choisir Eaou, au fond du golfe 1 ersique, mais les Angl iis refuserent ■, on proposa 1 lie d Otmuz ou de Kichim, k Pentree clu golfe Persique, mais a son tour la Perse ret'usa ; on s’adressa alors a la presqu’ile cle Djack, mais la France s’y opposa! Pour demontrer le gachis qui regne de ce cote, il me suffira de vous dire que le sultan de Maskate avait pris en 1898 cPex- cellentes mesures contre l’importation de la peste, mais les am- bassadeurs des puissances europeennes demanclerent de s’y soustraire, puis tous les Europeens, puis les notables indigenes, cle sorte que le sultan, indigne, supprima toutes les mesures. Si les puissances europeennes faisaient moins de conferences contre les maladies exotiques, mais respectaient mieux les con- clusions de celles qui out eu lieu,l’Europe serait mieux protegee ■contre la peste et le cholera. Du cote de la mer Rouge, a Pancienne quarantaine de 24 heures •que les navires provenant des ports contamines d’Orient devaient faire a Suez, on a substitue la visite medicale. La conference de Yenise trouvait insuffisants pour cette visite, quatre medecins. Souvent il n’y en a qu'un, qui doit visiter les passagers et l’equi- page des navires, desinfecter, surveiller les malades du lazaret ■des sources de Moise place a 20 km. de Suez. M. Proust demande qu’on installe clu moins dans la Mediter- ranee a 1-2 km. de Port-Said, trois chalands destines a recevoir, Pun les inclividus tombes malades durant le trajet du canal, l’autre les suspects, le troisieme avecle materiel et les etuves de -disinfection. La troisieme ligne est representee par les lazarets dans les ports (mer Caspienne, mer Noire, Mediterranee, Ocean). Il en existe, mais il pourrait en exister beaucoup plus et de ■mieux organises. Void les mesures qu’on doit y prendre vis-a-vis des navires provenant des ports infectes: Si les navires sont infectes, c’est-a-dire s’ils ont des cas de peste a borcl, les malades seront immediatement debarques et isoles, les autres personnes seront clebarquees et soumises a une observation on a une surveillance qui ne depassera pas les dix jours. On desinfectera tous les objets consideres comme conta- mines. On devrait y ajouter la destruction des rats et des souris dans la cale des navires. Les navires suspects, c’est-a-dire qui n’ont pas eu de cas a bord depuis douze jours, seront soumis a une visite medicale, a la disinfection des objets consideres comme contamines, desinfec- Gi2 tion de toutes les parties du navire qui ont ete liabitees par des- pestiferes. II est recommande de soumettre a une surveillance de dix jours, a dater de l’arrivee, les passagers et l’equipage. Les navires qui n’ont point presente de cas seront admis a la libre pratique immediate. On pourra faire une visite medicale et une disinfection, et soumettre equipages et passagers a une surveillance de dix jours, a partir du jour de depart du port con tarn in 6. Une question sur laquelle il faut bien attirer l’attention aw point de vue de la prophylaxie, est celle du pelerinage a la Mecque..Chaque annee, il y a environ 150000 musulmans qui, des differentes parties de l’Asie, de la peninsule balkanique et de l’Afrique, se portent a la ville sainte, ou ils vivent dans des- conditions d’extreme malproprete. Ils doivent done etre bien surveilles pour leur empecher d’etre les agents de propagation a l’Europe de la peste bubonique. Malheureusement, la ou la question religieuse s’en mele, il est bien difficile d’obtenir quelque chose au point de vue de la pro- phylaxie. On a eu beaucoup de peine a faire adopter par le gouvernement turc quelques mesures protectrices a Djeddah. Les softas affirment que la peste nous est envoyee par Allah,, et qu’il faut la prendre. « Mais la pluie aussi est envoyee par Allah, a observe Abdul-Mejid, et pourtant vous sortez avee des- pa rapluies ! » Il parait quo cette phrase de l’oncle du sultan a eu quelque influence sur les mesures prises en Arabie. Si un foyer de peste se manifeste en Europe, les gouverne- ments signataires de la conference de Venise doivent immedia- tement avertir les autres pays, et ceux-ci ne prendront des- mesures que vis-a-vis des personnes de la circonscription conta- minee. Les pays non contamines, pourront defendre Limportation des linges de corps, hardes, vetements usages, chiffons, peaux frai- ches. Par rapport aux peaux tannees, les recherches de De Giaxa et Gosioont demontre que les bacilles y sont detruits par le fait du tannage . Aux frontieres de terre, l’hygiene moderne n’admet plus de- quarantaines, qui ne representent que des entraves au com- merce, et n’empechent nullement a la peste de passer. On ne- fera que la visite des voyageurs, et s’il y en a presentant des- symptomes suspects, ils seront retenus. Des que les voyageurs provenant d’un lieu infecte seront arrives a destination, ils seront sounds a une surveillance de dix jours, a compter du jour de depart de Pendroit contamine. Lemedecin doit les visiter an moins unefois par jour, et des qu'il y a un suspect, avertir immediatement les autorites. II taudra en meme temps desin- fecter les bagages, si cette operation n’a pas ete operee ii la sta- tion de frontiere. Examinons maintenant quellos sont les mesures a prendre sur place, des que la peste s’est manifestee. Les premiers cas de peste seront immediatement declares. Pour aucune raison on ne doit cbercher a les cacher. Les pestiferes seront immediatement isoles dans des liopitaux speciaux. Tous ceux qui out eu des rapports avec les malades seront sounds a une surveillance au minimum de dix jours a partir de la cons- tatation du cas de peste et de la disinfection. Cette desinfection devra etre tres rigoureuse : ies objets de pen de valeur seront b rules, les autres passes a l’etuve a vapeur. On desinfectera les crachats, vomissements, dejections, urines, pus des pestiferes. La desinfection de la mafson sera des plus soignee. Si l’on se trouve en presence de buttes, on ne devra pas hesiter devant la destruction par le feu. Par exemple, Yersin, dans l’Annam, a fait batir un nouveau village a deux kilometres de Nah-Trang, y a transports la popu- lation apres un sejour de quinze jours dans un lazaret et il a bride l’aneien village avec defense d’y batir avant une annee. Dans nos pays, il faudra s’en tenir a la desinfection par la formaline et le sublime. Les medecins et les infirmiers doivent se rappeler des grands dangers qu’ils peuvent courir s’lis oublient les pre- cautions de desinfection. A Hong-Kong, sur sept medecins japo- nais, trois contracterent la peste et un mourut, tandis que des onze medecins anglais qui usaient des precautions hygieniques, pas un seul n’eut a souffrir. La destruction des rats et des souris doit etre poursuivie par tous les moyens dont on pent disposer: cultures de B. typhi murium, substances toxiques, acide carbonique, inondation des caves et des egouts. Preserver les habitations contre leur pene- tration. Il faudra bien avertir le public du danger qu’il y a a toucher des rats et des souris morts, en temps d’epidemie de peste. Tous les rats et les souris morts seront brides. Les cadavres des homines pestiferes seront ensevelis avec les precautions recommandees pour les autres infections. La cre- mation rendra d’excellents services. Les cordons sanitaires sont absolument a repousser dans nos contrees. Ils n’ont d’autre resultat que de suspendre tout com- merce et toute industrie, rendre plus forte la misere, et augmen- ter de la sorte la receptivite pour la peste. Mais une question tres importante pour la prophylaxie, est celle des vaccinations preventives. Dans toutes les epidemies des siecles passes, on avait remar- que que*les individus gueris de la peste etaient immunises con- tre elle, ou bien, s’ils la contractaient encore, ils presentaient une forme legere. Par analogie avec la variolisation contre la variole, on songea a inoculer la peste, dans l’idee de donner une forme legere capable de preserver des atteintes graves spon- tanees. Ce fut surtout Cerruti qui essaya cette methode en Egypte: sur six inocules, cinq succomberent a la peste. Mais la decou- verte de l’agent specifique de la maladie ouvrait le chemin a la vaccination preventive. Le serum antipesteux donne de meilleurs resultats comme preservatif que comme curatif. Yersin, dans un foyer de peste, a inocule 500 personnes et parmi celles-ci, 5 seulement contracterent la maladie. Simond en a inocule 1160, et parmi celles-ci, 9 seulement furent atteintes de peste. A Nah-Trang, tous les inocules echapperent a la peste. A Oporto, Calmette n’aurait pas observe de cas de peste. chez les vaccines avec le serum Yersin. Mais cette immunite ne dure que 14 jours, et il faut repeter la vaccination apres cette periode. Des resultats analogues ont ete obtenus par le serum I ustig- Galeotti. Mais un vaccin beaucoup plus simple a preparer, et qui a ete applique sur une vaste echelle aux Indes, est le vaccin Haff- kine. Ce vaccin est prepare de ia faqon suivante: On place dans un ballon deux litres de bouillon et on y ajoute un morceau de beurre. Le bouillon est sterilise et ensemeuce avec le bacille de la peste. Pendant un mois on le laisse a l’etuve et on l’agite de temps en temps pour precipiter la culture au fond. A la tin du mois on y ajoute %> % d’acide phenique, on distribue dans des tubes scelles et on chauffe une heure a 70". Ces cultures consti- tuent le vaccin qu’on inocule sous la peau, a la dose de 3-3 % c. c. chez l’adulte; 2-2 % c. c. cliez la femme; 1 c. c. eliez l’enfant age de plus de dix ans; 0,1-0,3 c. c. aux petits enfants. Cette inoculation determine frissons, fievre a 39"-40o, malaise general, souvent tumefaction des ganglions pendant 12-24 heures. Des experiences faites aux Indes, il resulte que ce vaccin pre- serve dela peste la plus grande partie des personnes inoculees, et, si elles contractent la maladie, celle-ci evolutionne d’une fagon legere. A Lower-Daman, les inocules ont presente une morta- lite de 1,6 °fa et les non inocules de 24,6 °/0. L’immunite est plus longue que celle conferee par le serum; mais elle n’arrive pas quand meme a l’annee. La mission allemande s’est prononcee d’une fagon tres favo- rable a cette methode. Terni a pu constater que le serum des individus ainsi vaccines, acquiert des proprietes bactericides tres notables pour le bacille de la peste; il suffit de quelques gouttes de ce sang pour empecher le developpement des cultu- res du JB. pestis. Nous possedons done dans le serum antipesteux et surtout dans le vaccin de Haffkine deux moyens qui peuvent nous ren- dre d’excellents services pour la prophvlaxie de la peste. Je suis pourtant bien loin d’accepter l’idee d’Haffkine, que les vaccina- tions doivent constituer toute la prophylaxie de la peste. Elies seront appliquees a cote des autres mesures prophylactiques que je vous ai indiquees. M. Calmette a cherche a perfectionner la methode de Haff- kine pour la rendre moins dangereuse. Dans ce but, a Oporto, il a associe l’inoculation du vaccin de Haffkine avec celle du serum. De la sorte il a supprime les accidents locaux qui s’ob- servent avec le premier. Terni et Bandi proposent un vaccin prepare de la fagon sui- vante : On inocule avec des cultures de peste des cobayes en injectant de 350-500 gr. dans l’abdomen, on recolte l’exsudat peritoneal, on le dilue avec de la solution physiologique, on le sterilise successivement a 50°-52fi et on y ajoute du carbonate de soude et de l’acide plienique. Ce vaccin a la dose de 2-2 ^ c. c. ne produirait pas les phenomenes reactifs du vaccin de Haff- kine. M. Lustig, a son tour, preconise maintenantun vaccin prepare avec une nucleoproteide obtenue des cultures du bacille de la peste. Elle peut etre obtenue en grande quantite en quelques jours. 11 faut faire trois vaccinations, debutant avec trois milli- grammes. 11 n’y a pas de troubles et Pimmunite dure deux mois. Les experiences stir les singes out ete favorables. Les expe- riences sur l’liomme manquent encore. Pour resumer, nous posseclons centre la pcste des moyens de combat que nous ne possedons pas contre bien d’autres mala- dies. La peste, en outre, ne donne pas les explosions meurtrieres du cholera, elle ne se propage pas a distance avec la meme vi- tesse que ce dernier qui suit la voie hydrique. La zone de diffu- sibilite de la peste est bien plus limitee que cclle d’autres mala- dies se propageant par Pair et par l’eau. Les convalescents de peste sont loin d’etre si dangereux que les convalescents du cholera. Malheureusement, il y a des medecins qui vous disent qu’il n’y a rien il faire contre la peste et qu'on doit se croiser les bras. Et ils vous citent l’Inde et la phrase de M. Yersin, prononcee peut-etre dans un moment cl’idees noires : Ilfautreconnaitre la faillite de toutes les mesures sanitaires adoptees contre Vepide- mic actuelle. C’est contre ces idees que je crois devoir reagir. Voyons. Mes- dames et Messieurs, comment les mesures prophylactiques ont ete appliquees aux Indes, a.vant de declarer qu’elles ont fait faillite. Des le debut de Pepidemie, le gouverneraent anglais avait tout dispose pour engager la lutte cl’une fagon rationnelle. Mais il s’est immediatement heurte a de tels prejuges, a de telles emeutes, qu’il a du y renoncer presque completement. Voigi ce que nous en dit M. Lustig qui a passe quelques mois sur les lieux: « Les comites crees pour pro ceder a la disinfection et d Viso- lement ont provoque Vinsurrection et plusieurs cles membres ont ete victimes des emeutiers. Et pourtant toutes les mesures prises par les comites etaient arrangees de la sorte qu’elles ne pussent pas offenser les sentiments religieux des habitants. On a du laisser aux proprietciires des mciisons le soin de desinfecter les habitations, aux indigenes le soin de declarer les cas de peste! Les nombreuses castes ont leurs hopitaux desservis par des me- decins indigenes. Le pestifere entre rarement seal dans les hd- pitaux; il est le plus souvent accompagne par les parents qui Vassistent dans sa malcidie, et dans ce but, ils restent, demi-nus, assis sur son lit ou couches par terre, littcralement converts de mouchcs qui se nourrissent du pus des buhons ou des crachais des pcstifercs. Lesol de ces hopitaux est en terre, il s'in fd.tr e de virus et tons y marchent nu-pieds. Toutes les mesures hygicni- ques sont appliquees trop tard, et memo tr'es mat congues. On ne s’inquiete pas de savoir si tine substance est reellement un anti- septique on non. On Vapplique quand meme. Les Parsis morts cle peste , sont deposes dans la. tour du silence. Les vautours et les corbeaux, emportent les morceaux de chair, et M. Lustig les a vus porter ces lambeaux dans les maisons. Les Indous brulent leurs cadavres, mais avant de les binder, ils les charrient a travers toute la ville. La combustion est tout a fait incomplete, et on voit les corbeaux porter des lambeaux de chair sur des promenades publiques. Les musulmans ensevelissent leurs pestiferes a la surface du sol, et leurs cimetieres en sont sursatures. II n'y a presque pas de cabinets d’aisance, les animaux vivent dans la merne chambre que les homines, et a cela s’ajoute la fa- mine, qui maintient le terrain favorable a Taction du bacille de la peste. La ou Ton a pu appliquer les mesures propliylactiques avec energie, comme a Hardenar, Tepidemie a ete arretee. Je regrette d’avoir du faire passer devant vos yeux un spec- tacle si triste, mais c’etait necessaire pour vous demontrer que si la peste fait des ravages aux Indes, ce n’est pas qu’elle echappe aux mesures propliylactiques, c’est qu’elles ne peuvent pas y etre appliquees. Mais en Europe, a de rares exceptions pres, on n’est pas dans des conditions pareilles. Des mesures energiques peuvent y etre immediatement prises pour enrayer Tepidemie. Je ne change pas les idees que j’exprimais en 1897 : La peste nepeut pas faire de grands ravages en Europe. Si la peste se maintient a Oporto, c’est que cette ville est une des plus insalubres. Le long du Douro, il y a des millions de metres cubes de matieres en putrefaction provenant des egouts. Dans certains quartiers, les ouvriers couchent par centaines dans des maisons infectes. Et nonobstant ga, nonobstant que la peste ait ete reconnue deux mois apres son explosion, nonobs- tant les absurdes mesures propliylactiques appliquees, el le y reste cantonnee, elle n’y donne qu’un nombre si limite de cas, qu’a peine on peut parler d’epidemie. Une epidemie de cholera, a l’heure qu’il est, aurait deja envahi tout le Portugal, l’Espagne et bonne partie de l’Europe. Tel est, Mesdames et Messieurs, l’etat de nos connaissances sur la peste. Nous pouvons Tattendre sans craintes. Tous nous devons contribuer a aider les pouvoirs publics dans la lutte qu’ils peuvent etre appeles k engager contre elle. Etdeja, avant qu’elle soit la, le terrain pourra lui etre rendu defavorable, en amelio- rant les conditions de l’hygiene des villes. Je serai heureux, si pour ma part, j’aurai quelque peu contri- bue a vous tranquilliser it l’egard de cette maladie, et k faire disparaitre la peur atavique que le simple nom de peste reveille chez plusieurs de vous. BIBLIOGRAPHIE Abba. — Rivista d’igiene e sanita pubblica, 1899, p. 341. Abel. — Centralblatt fur Bakteriologie, XXI, 1897, p. 497. Albrecht. — Semaine medicale, 1897, p. 211. Albrecht u. Ghan. — Gent. f. Bakt., XXVI, 1899, p. 362. Bandi. — Revue d’Hygiene, 1899, p. 797. Bandi e Stagnitta. — Revue d’Hygifene, 1898, p. 848. Bandi e Stagnitta. — Riv. d’ig. e san., 1899, p. 922. Batzaroff. — Annales Pasteur. 1899, p. 385. Beliavski. — Revue d’Hygiene, 1895, p. 941. Berliner Pestconferenz. — Deutsche med. Woch., 1899, p. 765. Bitter. — Zeitsch. f. Hyg., XXX, 1899, p. 448. Bizzozero. — Riv. d’ig. e san. pub., 1899, p. 809. Beinarowitsch. — Cent. f. Bakt., XXV, 1899, p. 937. Boccaccio. — II decameron., Milan, 1880. Calmette. — Revue d’Hygiene, 1899, p. 963. Catterina. —Atti 1st. Veneto, VIII, 1897, p. 1602. Clenow. — Cent. f. Bakt., XXVI, 1899. p. 374. Colletta. — Storia del reame di Napoli, Milan, 1861, vol. II, p. 193. Costa. — Sem. med., 1899, p. 300. Devell. — Cent. f. Bakt., XXII, 1897, p. 382. De Giaxa e Gosio. — Annali ig. sperim., 1897, VII, p. 261. Di Mattel — Riv. ig. e sanita pub., 1899, p. 693. Ebstein. — Die Pest des Thukydides, Stuttgart, 1899. Favre. — Zeitsch. f. Ilyg., 1899, p. 359. Fauvel. — Rev. d’Hyg., 1879, p. 8. Faxjvel. — Rev. d’Hyg., 1879, p. 89. Gabritchewsky. — Cent. f. Bakt., XXIH, 1898, p. 510. Galli-Valerio. —- Der Hausarzt, 1897. Galli-Valerio. - Giornale R. Soc. it. d’igiene, 1897, Nos 3, 4, 5. Galeotti. — Riv. d’ig. e san. pub., 1899, p. 784 Gladin. — Cent. f. Bakt., XXIV, 1898, p. 588. Gosio. — Policlinico, 1897, N. 12. Gotschlich. — Sem. med., 1897, p. 432. Hankin. — Cent. f. Bakt., XXIV, 1898, p. 587. Hankin. — Annales Pasteur, 1898, p. 705. Hankin. — Cent. f. Bakt., 1897, XXII, p. 437. Hankin u. Leumann. — Cent. f. Bakt., XXII, 1897, p. 438. Jans on. — Archiv. f. Wiss. und prakt. Thierheilkunde, 1895, XXI, p. 451. Kasanski. — Cent. f. Bakt., XXIII, 1898, p. 25. Kitasato. — Preliminary notice on the Bacillus of the bubonic plague, Hong-Kong, 1894, July. Koch. — Cent. f. Bakt., XXIV, 1898, p. 98. Kolle. — Semaine med., 1897, p. 76. London. — Cent. f. Bakt., XXV, 1899, p. 779. Loriga. — Riv. d’ig. e san. pub., 1899, p. 453. Lowson. — Cent. f. Bakt., XXI, 1897, p. 609. Lustig. — Riv. ig. e san. pub., 1897, p. 738. Lustig. — Arch. it. de biol., XXVIII, 1897, p. 307. Lustig. — Riv. ig. e san. pub., 1898, p. 484. Lustig. — Riv. ig. e san. pub , 1899, p. 105. Lustig. — Riv. ig. e san. pub., 1899, p. 495. Lustig. — Riv. ig. e san. pub., 1899, p. 720. Lustig. — Riv. ig. e san. pub, 1899, p. 913. Lustig e Galeotti. — Arch. it. de biol., XXXVIII, 1897, p. 327. Manzoni. — I promessi sposi, Torino, 1829. Manzoni. — Storia della colonna infame, Milan. Mahe. — Memoire sur les epidemies de peste bubonique. Paris, 1886. Markl. — Cent. f. Bakt., XXIV, 1898, p. 641. Matignon. — Annales d’Hyg. pub., 1898, p. 227. Mervyn-Gordon. — Cent. f. Bakt., 1897, p. 170. Morax. — Statistique medicale du canton de Vaud, Lausanne, 1899. Muller. — Cent. f. Bakt., XXVI, 1899, p. 300. Nadeschda-Schultz. — Cent. f. Bakt., XXIII, 1898, p. 594. Netter. — Sem. mbd., 1895, p. 69. Netter. — La Peste, Paris, 1899. Nuttall. — Cent. f. Bakt., XXII, p. 87. Ogata. — Cent. f. Bakt., XXI, 1897, N°s 20, 21. Pecclard. — Journal des connaiss. medicates, 1884, p. 333. Pick. — Sem. mbd., 1898, p. 433. Pick. — Sem. med., 1898, p. 448. Porquet. — Rev. d’Hyg., 1899, p. 330. Proust. — Rev. d’Hyg., 1899, p. 149. Reciietnikow. — Rev. d’Hyg., 1895, p. 941. Rennie. — British, med. journal, 1894, p. 615. Ripamonti. — De peste que fuit anno 1630, Mediolani, 1640. Rouk. — Sem. med., 1897, p. 27. Riureanu. — La peste, thbse de Paris, 1897. Simond. — Annales Pasteur, 1898, p. 625. Schilling. — Munchner med. Woch. 1898, N° 45. Schneider. — Rev. d’Hvg., 1896, p. 240. Schultz. — Sem. med., 1899, p. 89. Terni. — Riv. ig. e san. pub , 1899, p. 784. Ti-iolozan. — Rev. d’Hyg., 1887, p. 1019. Toptschieff. — Cent. f. Bakt., XXIII, 1898, p. 730. Vallin. — Rev. d’Hyg., 1897, p. 256 Vallin. — Rev. d’Hyg., 1885, p. 603. Van der Stricht. — Sem. med., 1897, p. 114. Wyssokowitz et Zabolotny. — Annales Pasteur, 1897, p. 663. Wernicke. — Cent. f. Bakt,., XXIV, 1898, p. 859. Zabolotny. — Annales Pasteur, 1899, p. 833. Zettnow. — Zeitsch. I. Hyg., 1896, XXI, p. 165. Zuber. — Rev. d’Hyg., 1879, p. 937. Zupitza. — Zeitsch. f. Hyg., XXXII, 1899, p. 268. Yamagiva. — Virchow’s Archiv., 149 Bd., p. 121,1897. Yersin. — Sem. med., 1896, p. 420. Yersin. — Annales Pasteur, 1894, p. 662. Yersin. — Annales Pasteur, 1899, p. 251. Yersin, Calmette et Borrel. — Annales Pasteur, 1895, p. 589. Yokote. — Cent. f. Bakt., XXIII, 1898. p. 1030. Notes, reglements, etc., parus dans la Revue d’Hygiene, Semaine medicale, Rivista d’igiene e sanita pubblica, etc. ♦ f PS : \\ o V. IS l The Part Played by the Fleas of Rats and Mice in the Transmission of Bubonic Plague BY DR. BRUNO GALLI-VALERIO Professor at the University of Lausanne, Switzerland 'r. Translated by P. FALCKE Reprinted from “The Journal of Tropical Medicint Feb. 1, 1902 (Belilios Prize.) ILontum JOHN BALE, SONS & DANIELSSON, Ltd. 83-89, Great Titchfield Street, Oxford Street, W. 1902 : : MASSON ET O, fiDITEURS 120, Boulevard Saint-Germain, Paris (O’). THE PART PLAYED BY THE FLEAS OF RATS AND MICE IN THE TRANSMISSION OF BUBONIC PLAGUE. The part played by certain insects and arachnides in the transmission of various parasitic diseases of man and beast is well known. It will suffice to recall the important role the mosquito plays in the transmission of the malaria of human beings and birds, of yellow fever, and of the fila- riasis of men and dogs; the role of the Tse-tse fly in the transmission of nagana; of ticks in the trans- mission of malaria of cattle and dogs; and the part played by flies and other dipterae in the transmission of anthrax, &c. These facts probably induced Dr. Simond* to open up the question of the transmission of bubonic plague to man from rats and mice through the instrumen- tality of the fleas of these animals. Ogata t had previously, in 1897, conveyed plague to mice by inoculating them with triturated fleas col- lected from plague-infected rats. M. Simond con- firmed the presence of a bacillus, morphologically similar to the plague bacillus, in the fleas taken from By Dr. Bruno Galli-Valerio. A Critical Note. Professor at the University of Lausanne, Switzerland (Translated, by P. Falclce.) * Annates Pasteur, 1898, No. 10, p. 625. f Centralbl. fur Baht., 1897, xxi., Nos. 20, 21, p. 769. rats suffering from plague. Of three mice inocu- lated with these fleas pounded up in a few drops of water, one only succumbed to bubonic plague. M. Simond, besides, observed the death of one rat and one mouse placed in a cage with a rat that had died of plague, to which he had previously added fleas from a cat (!); whereas of seven rats placed in a cage with a rat that had died of plague, but which exhibited no fleas, none of the seven showed symp- toms of plague. In consequence of these observations, M. Simond’s .attention was arrested by initial bullse observed on persons suffering from plague (one case in every twenty), and in which he found the plague bacillus. According to M. Simond these blebs were due to the bites of fleas of rats and mice. The mode of infection, according to M. Simond, is supposed to be as follows : “ The sting (sic /) steeped with blood cannot for long maintain its power of infection. The flea in these cases would be useless except at the moment when it leaves the plague-stricken animal. But it is feasible to suppose that during suction the flea deposits its dejecta, consisting of a tiny drop of digested blood, on the place where it is perched. In cases where this fluid is a culture of plague bacilli it is feasible to conjecture that it may infect the person through the perforation made by the sting.” From these facts M. Simond draws the following conclusions : “ While recognising that this hypothesis has not the value of a demonstrated fact, we are of belief that the various forms of ‘ spontaneous ’ plague in men and animals generally take place by one single mode of infection—intracutaneous parasitic inoculation.” M. Simond’s work made some sensation, but in- stead of being enquired into his views were accepted as they stood, and above all by the French, who had no hesitation in affirming that the transmission .of plague from rats and mice to man took place through the intermediation of fleas, and that this was the most important means of transmission of the disease. Before attacking M. Simond’s theory, we will first consider what publications have appeared subse- quently, having for their object the support of the theory of the transmission of plague by fleas. There is, first of all, an article by M. Loir, Director of the Pasteur Institute at Tunis. J He commences as follows: “ It has now been demonstrated that the flea is the principal intermediary of the plague between a rat and man.” A curious affirmation, when M. Simond himself had declared that his theory had not the value of a demonstrated fact ! Starting with such premises it is easy to arrive at conclusions favourable to M. Simond’s theory. In discussing this affirmation M. Loir explains why a certain immunity as regards plague is noticed in persons working with oil. The presence of oil on the skin drives the fleas away. This is how M. Loir and his assistants made their experiments: “We shut up a rat in a cage and afterwards placed it for twenty-four hours in a house in Tunis in which we knew by experience that fleas swarmed, inasmuch as, during a medical visit to a street porter living in this house, I had removed thirty-seven fleas from my garments in the evening. At the end of twenty-four hours the rat was swarming with these insects. We placed two small cages within this cage, one con- taining an ordinary rat, the other a rat previously dipped in olive oil; we then killed the first rat and left its body in the large cage at an equal distance from the two small cages. On the following day, of course, not a single flea was to be seen on the dead body. The rat that had been placed in the first of the small cages was covered with fleas, but the rat dipped in olive oil had not a single one.” M. Loir Q concludes from this experiment that it is perhaps < jfy '.' (Q this distaste of the rats for oil to which the immunity • of all workers in oil-factories is due, a circumstance that has been remarked in all epidemics of plague. X Revue Scientifique, 1900, No. 13, March, p. 395. Another work supporting M. Simond’s views is by Dr. Ashburton Thompson,§ Government medical officer at Sydney. During the epidemic in this city Dr. Thompson observed the blebs described by Simond in six cases; a small proportion, he observes, in relation to the great number of cases examined. In one of these pustules he found a bacillus, similar to B. pestis, in small numbers. Dr. Thompson then examined fleas taken from plague rats, and in one flea he found B. pestis, which proved destructive to guinea pigs. Of nine specimens of fleas he found on the rats he had examined to find out the species, two were P. serraticeps and the others P. fasciatus. In consequence of these facts Dr. Thompson thinks he is entitled to conclude that the transmission of plague from rats and mice by the intermediation of fleas must be very frequent. During the same epidemic Dr. Tidswell,|| Bacterio- logist to the city of Sydney, also pronounced favour- ably in support of M. Simond’s theory. He gave plague to rats by inoculating triturated fleas taken from plague rats; and he observed that at the time the quays of the city were covered by dead rats, that the fleas swarmed into the streets to such a degree that the labourers were obliged to tie the bottom of their trousers with string round their feet, in order to protect themselves from the onslaughts of these vermin. Let us now undertake a critical study of these articles. Dr. Nuttalllf is the first to throw doubts on M. Simond’s affirmations, for he observed that the bac- teria passing through the body of fleas and other insects often succumbed. In conclusion he observes: § Journal of Hygiene, vol. i., 1901, p. 153. || Journal of the Sanitary Institute, 1901, p. 509-578; Resume cles la Rev. cVHyg., 1901, p. 553. ^1 “On the Role of Insects, Arachnides and Myriapods as Carriers in the Spread of Bacterial and Parasitic Diseases of Man and Animals.” Johns Boykins Hospital Reports, vol. viii., 1899. “ What we want in this respect is more facts and fewer opinions, and the facts can only be gathered by further experimental research. Without having any knowledge of the work of Dr. Nuttall, which the author only sent to me after my article had been published, I also submitted a study which was critical and, to a certain degree, experi- mental on M. Simond’s theory,** and it is to a great degree the contents of these investigations which, in addition to the new facts and the new criticisms, I shall give here. In the first place the initial blebs, of which M. Simond has spoken as a point of entry by the bites of fleas, has been observed by him in too restricted a number to convince us that this mode of infection is the most frequent. This rarity forcibly struck Dr. Thompson, who notes how small the proportion of cases of blebs are in comparison to the cases examined, and of the six cases examined only one contained B. pestis. It is true that M. Simond, to explain the affair, evolves the theory that if the flea inoculates a very active virus the bleb will not be produced, though the in- fection is conveyed. But as M. Simond admits that the infection does not take place by direct inocula- tion, but by means of the bacilli passed through the digestive tract of the fleas, and as, according to the experience of Nuttall, these bacilli in most cases are attenuated, if not dead, it appears to me that if the indicated mode of infection were frequent blebs also should be much more common. M. Simond, in expounding his theory, has taken no trouble to find out if the fleas that live on rats and mice are of the same species as those that live on man. This is what he says: “ The flea commonly met with on the wall rat (India) is of medium size, of a greyish colour, with a spot the colour of dregs of wine on the lateral aspect of the abdomen; this ** Centralb. fur Bakt., 1900, xxvii., No. 1, p. 1, and xxviii., No. 4, p. 842. spot is nothing but the stomach filled with blood, seen in consequence of transparency.” “ We are not aware if this flea is a different variety from the ordinary fleas of men and domestic animals (sic). At the same time we have convinced ourselves experimentally that, transmitted to persons or dogs, they immediately attack them.” Such a confusion of the forty-eight species of common fleas is not adapted to inspire great confi- dence in the author’s experience. Indeed, how can we positively assert that the flea in question imme- diately bites man and the dog if we do not even understand what flea is in question; and a little time after, to make confusion more confounded, M. Simoncl records experiments made with fleas taken from the cat. A deplorable analogous confusion is exhibited in M. Loir’s work, who classes all the fleas together and tries to show that there is only one species. The first question to settle is the zoology of the fleas, and then discuss the question whether the specimens found on rats and mice can attack man. I set to work to ascertain the nature of these para- sites and find that the fleas met with on rats and mice under normal circumstances are TyphlojDsylla musculi and Pulex fasciatus. The first mention made in literature, and this after the appearance of my work, is by Dr. Thompson, who asserts that among fleas collected on rats there were two from which he obtained P. serraticeps. This specimen is a flea of the carnivora and is very frequent on dogs and cats. It sometimes passes on to man, and Railliet as well as myself have also found it on the rabbit. In order to confirm which species besides Pulex irritans bite man, this being man’s particular flea, I made some experiments on myself, and when per- mitted on other persons. Here are the results : — - Typihlopsylla musculi.—In one case in which I was invaded by numerous fleas of this species coming from a white mouse I did not receive a single bite, and all the fleas quickly left me. Some of these fleas, placed expressly on my body and left free or under glass bells, never bit me although fasting. Pulex fasciatus. What I have reported of T. musculi stands good for this species. P. serraticeps.—This species, as is known to numerous observers, bites man. I have myself found it on human beings. Placed on my body under a glass bell it immediately bit me. P. goniocephalus.—This specimen, conveyed from the rabbit to my bod)q did not bite me. P. avium.—A species which, according to M. Lucet, may bite man, being placed on the body of a colleague and myself caused no wound although it had been kept fasting a long time. I may remark that the specimen employed for this experiment emanated from a Ghelidon urbica. P. erinacei.—I was invaded by numerous fleas of this species. I placed some hundreds under a glass bell on to my body. Although I had not felt any bites from those that had been free on my body, yet those under the glass bell bit me slightly. They remained only a short time on my body. The experiments quoted are not of absolute value as they were mostly made on myelf and not on several persons, but their value is increased by the fact that I was bitten by different species, such as P. irritans, P. serraticeps and P. erinacei. From these experiments it appears that P. fas- ciatus and T. musculi' do not seem to bite man. There remains P. serraticeps, which Thompson affirms he twice gathered off rats. Put P. serraticeps must be very uncommon on rats. I have examined numerous rats without ever finding a specimen. Nobody, with the exception of Dr. Thompson, has quoted it as being found on this animal. On rabbits, where it was found by M. Railliet and myself, it is scarce, and M. Railliet’s efforts to acclimatise this species on a rabbit by introducing a number into the hutch were unsuccessful. Dr. Thompson’s observa- tion therefore palpably relates to a rare case, an accidental case, and we cannot rely on this observa- tion for the purpose of considering this flea as the ordinary medium for transmitting plague from rats to man. Dr. Tidswell, as M. Vail in admits, shows that he has a certain partiality for this almost exclusive mode of infection by means of the bites of fleas, but gives absolutely no facts to support his theory. In fact he failed to give plague to rats placed in cages separated by large-holed lattice work from other cages in which there were plague-stricken rats, or .even by placing healthy rats in dirty cages where other rats had died from plague. Quite recently Kolleff has also asserted that he could not succeed in giving plague to healthy rats placed in cages containing numerous fleas from off plague-infected rats, although he could positively affirm the fact that these fleas went onto the rats in the cages. He con- cludes that if the transmission of plague from rat to rat by means of fleabites exists it has not been proved. We know that Simond only had the death of one rat and one mouse placed in a cage with fleas from a cat originally taken from a plague rat. If trans- mission is so difficult from rat to rat, why, on the other hand, should it be so frequent from rats and mice to man, who is not as a general rule attacked by mouse and rat fleas. Dr. Tidswell tells us that the abundant fleas on the quays at Sydney, probably from dead rats, attacked men’s legs. But these fleas were not examined to ascertain if they were mouse and rat fleas; we are not informed if they bit the men or not, and we are not told if these men, invaded in this fashion, were more attacked by plague than others. Concerning these matters M. Yallin, though in favour of M. Simond’s theory, writes: “ At the same time Dr. Tidswell has not furnished us with sufficient details concerning his experiences, and has not supported the numerous assertions in his work by proofs.” ft Zeitschrift f. Hyg. u, infect., xxxvi., p. 397, To al] this I must add that neither the German Commission nor Mr. SchoteliusJ| in India, nor dur- ing the epidemics at Oporto, Glasgow, or Naples, has the transmission of plague to man been traced to the fleas of rats and mice. In opposition also to the as- sertion that this mode of transmission is the most frequent and almost exclusive (even taking into ac- count the great facility with which plague is trans- mitted to man by the Arctomys bobac, on which, as far as I know, there are no fleas), is the fact noted by Edington,§§ that at the Cape the rats that died of plague did not succumb to bubonic plague, but to a disease due to a bacillus analogous to B. pestis, which is non-pathogenic to guinea-pigs and pathogenic to pigeons. The facility also with which it is possible to arrest an epidemic of plague where hygienic conditions are good, and isolation properly carried out, speaks against this theory. If M. Simond’s hypothesis were correct, one might almost fold one’s arms in consequence of the difficulty of preventing the diffusion of infected fleas, which, according to Tidswell, were met with in millions where rats had died of plague. In conclusion, instead of asserting—as is too often the case—as an established fact that plague is trans- mitted to man by the bites of fleas of rats and mice, and that this is the most frequent and im- portant means of infection, it requires to be demon- strated, not only that the fleas convey plague from rats and mice to man, but from rat to rat. The question can only be solved in one way, namely, by conveying to the bodies of human beings rats’ and mice fleas that have lived on plague rats. If this experiment is, as I believe, considered to be necessary, I place myself entirely at the disposal of the committee to undergo it. \\ Hyg. Rundsch., 1900. §.§ Ccnircdb. fiir Bakt., xxix., No. 23, 1901, p. 889. Lessons to be Learnt from Professor Bruno Galli-Valerio’s Paper. The article in this issue of the Journal, by Dr. Bruno Galli-Valerio, should be studied carefully as an object lesson in scientific investigation. Dr. Galli-Valerio has not succeeded in showing, in fact he makes no pretension to do so, how plague is trans- mitted to man, nor even that the rat plays an im- portant, or any part, in the conveyance of plague .from man to animals. His article, however, is a clear exposition of our knowledge of the relations of rats to man as regards plague infection, and he demonstrates conclusively at what a fine point of scientific precision the investigation has arrived. After discussing several plausible theories, show- ing where they are weak and where they are scien- tifically valueless, he brings us by his processes of reasoning to this point, namely, that to prove the theory of the power of infected rat-fleas to transmit the disease to man, man must suffer himself to be bitten by infected fleas. This of course is, has been, and will remain the halting point in many investiga- tions of the kind; and, as in several recorded instances we find men willing to submit themselves to be experimented upon, so in this instance, Dr. Galli-Valerio is willing to become the subject of ex- periment, if such is considered necessary. But important although these points may be, it is not on that account we wish to direct attention to this article. It is because Professor Galli-Valerio has given us information in regard to plague in a direc- tion other than clinical and bacteriological. These have been the aspects of plague which have been dealt with by writers and observers well nigh exclu- sively, ever since 1894, when the modern pandemic declared itself in Hong Kong. It is now eight years since Aoyama, Cantlie, Kitar sato, Lowson and Yersin, gave us definite informa- tion concerning the signs and symptoms, the anatomical characters, the bacteriology, and even the serum-therapy of bubonic plague, and beyond the discovery of pneumonic plague by Childe in 1896, and important work by Haffkine and Hankin in India, subsequent investigators have practically been treading the same ground. They have given us stacks of literature—clinical, pathological, and statistical—but the additions to our knowledge of plague have been mostly details. The various foreign scientific expeditions to India were disappointing, they but reiterated what was already definitely known, and for the most part wasted both time and money. Reports on plague may be necessary for Governments, but the men employed in drawing them up have often to spend their time and intellect on scientifically useless work. Valuable men, capable of a better and higher order of work, are chained to the slavery of routine to no purpose, and are compelled to do work which their training and capabilities pronounce to be unworthy of their attention. Dr. Galli-Valerio’s paper, as Dr. Manson says in his comments on the paper, “ shows on what a slender basis of fact a catching theory may be founded, and how it may gain popularity and even acceptance.” According to Manson, the paper also indicates “ the disinclination for workers in plague to step outside the well-worn ruts of the clinical observations and the bacteriology of the disease; for, except for two or three inconclusive experiments, nothing has been done to exploit the rat-flea theory.” The cause, the origin, or the mode of diffusion of disease, after the clinical facts and the bacteriology of the disease are known, should be the work which scientific investigators should take up, not as a side issue, but as the kernel of the question. The pro- phylaxis naturally follows upon the discoverv of the cause or of the means of transmission. Dr. Galli-Valerio’s paper will serve as a guide in future to medical practitioners who wish to investigate the causes of disease, and there is no medical man, how- ever isolated, who cannot devote his attention to the elucidation of the cause of disease on the lines laid down by the writer of the article in question. REVUE D’HYGIENE ET DE POLICE SANITAIRE l EXTRAIT MASSON ET O, tiDlTEURS 150, Boulevard Snint-Germain, Paris RECHERCHES EXPERIMENTALES SUR LE ROLE DES PARASITES DU RAT DANS LA TRANSMISSION DE LA PESTE par M. J.-Constantin GAUTHIER Charge du laboratoire du Service sanitaire de Marseille et A. RAYBAUD Chef du laboratoire des cliniques a I’Ecole de medecine de Marseille EXTRAIT DB LA « REVUE d’hVGIENK » (MAI 1903) PARIS MASSON ET Cie, EDITED RS LIBRA I RES DE l’aCADEMIE DE MED E CINE 120, boulevard Saint-Germain V ! / EXTRAIT DE LA « REVUE D’HYGlfiNE ET I)E POLICE SANITAIRE »» Tome XXV, n° f>, 20 mai 19Q3. PARIS, MASSON & Cio, EDITEURS RECH ERCHES EXPERIMEXTALES SUR LE ROLE DES PARASITES DU RAT DANS LA TRANSMISSION DE LA PESTE 1 Par MM. les Docteurs J.-Constantin GAUTHIER Charge da laboratoire du Service sanitaire de Marseille et A. RAYBAUD Chef du laboratoire des cliniqnes a l’Ecole de medecinc de Marseille La theorie de Simond sor la transmission parasitaire de la peste de rat a rat et du rat a l’homme a ete, des le principe, adoptee tres generalement par les auteurs frangais et aussi par quelques savants etrangers. On a fait observer cependant que nulle etude de controle n’etait venue confirmer les experiences si coniines 2. Ces dernieres out etd, d’aulre part, avec leurs conclusions, soumises a une criti- que severe dans quelques pays voisins. Mais les donnees experi- mentales sur lesquelles s’appuie la refutation de la theorie en cause semblent insuffisantes. Les recherches dediagnostic qui nous son ten certains cas deman- dees portent sur des animaux toujours suspects et generalement parasites; elles necessitent un dispositif special contre tout danger de propagation. Nous Iron van t ainsi dans des conditions pafticu- lierement favorables pour verifier sur ses points principaux la theorie de Simond, nous n’avons pas cru devoir negliger cette op- port unite. 1. Une analyse de ce travail a ete presentee a l’Academie de Medecinc, par M. le professenr Rroust, Inspecteur general des Services sanitaires. [Hull. Acad. Mid., 16 decembre 1902.) 2. Annates de ITnsiitnt Pasteur, octobre 1898, p. 074. Ije probleme comporlail plusieurs donnees exp6rimentales pou- vant etre, cn somme, ramenees a ces deux chefs : 1° La peste se transmet-elle de rat a rat par la piqure de cer- tains insectes parasites ? 2" Ces insectes altaquenl-ils t’homme dans des conditions ana- logues d cedes qui, par hypotliese, realisent la contagion d'animal a animal ? I.*— Transmission de la Peste de rat a rat. D’apres noire experience, les parasites qui se rencontrent d’une faqon courante cliez le rat sont soit des insectes de la famille des pulicid6s, soit certains types d'acariens. De tres rares pediculides, trouves parfois aussi, ne nous paraissent pas devoir entrer en ligne de compte. Essais de transmission par les puces. Pour nos experiences sur les puces, nous nous sommes eftorces de nous placer dans des conditions aussi voisines que possible de ce qui doit se passer en pratique. Recueillant en bloc on certain nombre de puces sur des rats captures sains, nous avons parasite artificiellement a lour aide des animaux de laboratoire prealable- rnent inocules de cultures pures. Nous avons chercbe ensuite a produire l’infestation parasitaire ct l’infection consecutive d’ani- maux neufs. Nous avons adopte un dispositif experimental qui permet d’eli- miner toute cause de transmission autre que le passage des para- sites d’un animal a 1’autre et qui, en outre, donne uue securite parfaite au cours de ces manipulations justement regardees comine delicates, meme par les adversaires de la th^orie de Simond. Nous avons employe line cage cylindrique en fils de fer, de 20 centimetres de diametre environ, divisee au milieu par une cloi- son verticale formee de deux grilles metalliques eloign^es de 2 cen- timetres. L’animal inocule 6tant place dans Tun des compartiments, l’animal sain, inlroduit apres sa mort dans l’autre, n’a aucun con- tact avec le cadavre, la double cloison rempccbant meme de passer le museau dans la partie voisine. Parcontre, les puces peuventsauter d’un cote a l’autre de la cage et nous avons, dans chaque expe- rience, constate leor emigration rapide. 11 esl de toute n6cessite d’empecher que les puces puissent sortir de la cage a experiences et transporter sm* le personnel et sur les animaux du laboratoire le dangereux contage dont elles sont char- gees. Pour cela, nous enfermons notre cage metallique dans un grand bocal en verre, ferine d’un bouclion de liege convert de paraf- tine pour obturer les orilices et soigneusement lute sur ses bords. La cage interieure doit dre assez haute et altleurer sousle bouclion qui lui sert ainsi de couvercle, pour que les rats ne puissent pas, en grimpant contre les parois, passer d’un compartiment a l’autre. Deux tubes de verre de grand diametre, traversant le bouclion, s’ouvrent sur les deux coinpartiments de la cage ; par ces chemi- nees, on peut introduire les aliments, les puces neuves el les rats eux-memes, sans qu’il y ait jamais de communication entre l’inte- rieur et l’exterieur ; il suftit de placer les animaux ou les objets entre deux tampons de coton dont le premier, qui servait aupara- vant de bouclion tombe avec eux dans la cage, l’autre restant pour obturer par derriere l’orifice du tube. Deux autres tubes de plus petit diametre et egalement bouches a l’ouate permettent de faire l’ad'ation du bocal en les branchant sur un aspirateur ou unesouf- flerie quelconques. Pour retirer, en cours d’experience, le premier cadavre, on peut introduire par la cheminee de verre une longue pince enveloppee d'un linge, imbibe de solution de sublime, formant tente; des I’ori- lice, le rat est enveloppe dans ce linge et le tout est immediatement plonge dans une solution alcoolique de sublime qui tuerait toute puce egaree. L’experience achevee, il suftit de verser quelques centimetres cubes d’etber dans l’interieur du bocal pour tuer toutes les puces restantes. On desinfecte ensuite aisement tout le systeme en rem- plissant le bocal de solution antiseptique. Dans de telles conditions, on peut, en y portant une stride atten- tion, effectuer ces recherches de transmission par les puces sans craindre de propager la peste autour de soi. Experience A. — Le 1G seplembre 1902, un rat blanc est inocule, par injection sous-cutanee, avec une culture de peste liumaine. Une dizaine de puces, recnei 1 lies sur des rats sains captures a bord de divers navires, sont placees sur I’animal en experience quelques heures a pres 1’inoculation. Ce rat meurl le troisieme jour. On introduit, dans le compartiment voisin de la cage, un nouveau rat sain. Le radavre du premier n’est retire qu’au bout d’une dizaine d’lieures, quand toutes les puces sem- blent avoir emigre sur le rat neuf el apparaissent a plusieurs reprises a la surface de ses poils. Ge second rat meurt au bout de sept jours. Les puces restanles sont tuees. L’autopsio du premier rat montrait line reaction inllammaloire intense .au point d'inoculation, des adenites multiples, uno infiltration diffuse du tissu sous-cutane, mais une infection generale discrete ; les frottis de foie et de rate ne contenaient pas de bacillcs neltement caracteristiques ; ccpendant, les ensemencements du sang du coeur et de la pulpe de foie donnaient une culture typique de bacillcs pesleux. A l’autopsio du deuxieme rat, nous conslalions une septicemie beaucoup plus massive. Le tissu cellulaire sous-cutane etait hyperemie et les gan- glions inguinaux engorges a gauche. Les frottis de rate, de foie et de poumon presenlaient en grand nombre des bacillcs pesteux morpholo- giquement typiques. Les lubes ensemences avec le sang du coeur, la pulpe de foie et l’urine recueillie aseptiquement danslavessie donnerent des cultures pures de peste. Experience B. — Le 27 seplembre, un rat blanc est inocule avec une culture de peste tres virulente; quelques heures plus tard, on pro- jette dans sa cage une vingtaine de puces recueillies sur des rats de navires. L’animal inocule succombe en 48 heures. Un rat blanc neuf est introduit dans le compartiment voisin, quelques heures avant qu’on retire le cadavre du premier animal. Ce second rat meurt au bout de S jours. L’autopsie du premier animal montrait les signes habituels de l’in- feclion pesteuse experimentale, verifiee par ensemencement positif du sang du coeur et de la pulpe de foie. A l’aulopsic du deuxieme, on relevait une injection diffuse du tissu cellulaire sous-cutane, sans adenites. Les frottis de foie montraient quel- ques rares bacilles ; Lensemencement de la pulpe du foie donna des cul- tures impures, mais la culture obtenue avec le sang du coeur fournit des formes bien typiques de peste. Experience C. — Le 3 oclobre, un rat blanc inocule de peste est parasite a l’aide d’une vingtaine de puces recueillies sur des rats sains pris en ville ou sur divers navires. Ce rat succombe en 3G heures; comme dans les experiences prccedentes, on introduit un rat blanc sain dans le second compartiment de la cage. Ce dernier meurt au bout de li jours. L’autopsie du premier rat revelait une septicemic typique avec bacillcs dans les frottis de foie et cultures pures obtenues par ensemencement de la pulpe du foie et du sang du coeur. L’autopsie du deuxieme rat donnait des frottis d’organes depourvus de bacilles, mais, dans les cultures ensemencees avec le sang du coeur et la pulpe du foie, il so developpa du bacille pesleux typique. Dans les experiences qui suivent, nous n’avons pas pris la pre- caution de separer l’aniinal neuf du cadavre iufecte. Quoique la transmission par simple contact ait ete signalee coniine possible, 11011s avons ete amenes a la tenir pour nulle dans les cas de sepli- cemie chez les animaux non parasites, tels quo se trouvaient les rats et souris de notre laboraloire. Nous n’avons jamais reussi a contagionner ces animaux en nous bornant a les placer dans un nieine bocal avec des rats blancs infectes etnon parasites. Dans ces conditions, nous considerons ces dernieres observations comme aussi rigoureusement probantes que les premieres. Experience D. — Le 29 juin 1902, six puces, rccueillies sue des rats d’egoul captures en ville, soul placees surun rat blanc inocule de peste. Cel animal succombe 30 lieures apres l’inoculation. Aussi to l apres sa mort, on introduit dans le meme bocal un rat blanc neuf; le cadavre du premier n’est retire qu’apres une quinzaine d’heures pour permellre aux puces d’emigrer sur l’animal sain. Celni-ci succombe 10 jours plus lard. A l’autopsie du premier rat, nous avons constate une septicemic inten-e, avec bacilles dans les frottis d’organes et cultures pures par ensemencement du sang du coeur et de la pulpe du foie. Le second rat etait egalement infecte. II exislait une congestion diffuse du lissu cellulaire sous-cutane; les frottis d’organes montraicnt des bacilles typiques, quoique un peu moins abondants que dans les frottis du premier rat ; les cultures ensemencees avec le sang du coeur et la pulpe du foie elaient caracteristiques. Experience E. — A la suite de l’une des experiences precedents (B), nous avons place une souris blanche dans la cage ou etait mort le second rat, avant de detruire les puces. Cette souris blanche mourul en 24 lieures et I’ensemencemenl du sang du coeur donna des cultures de peste typiques l. An cours des experiences ci-dessus exposees, nous ne nous sommes pas attaches a saisir sur le fait lc passage du bacille de Yersin dans I’organisme des puces. D’autres auteurs out, precise ce point avant nous 2. Mais, chemin faisant, nous avons parfois examine en 1. Nous n’avons fait qu’une experience sur des souris, ear ces animaux nous paraissent peu utilisables dans ces essais, en raison de lour habiletc a detruire les puces. En etlet, dans des circonstances differentes, nous eiimes I’occasion de placer six puces de chien sur une souris blanche inoculee; apres sa mort une souris neuve fut i ntrodu i Le dans le bocal; mais el le reussit rapidement a se debarrasser des parasites et demeura indemne. 2. G. Zirolia. // Policlinico, Suppl. seltim., 12 avril 1902., p. 739. No tons en passant que nous avons eu plusieurs fois I’occasion dc constater sur les animaux en experience, l’existence de taches hematiques qui mouchc- laient leur pelage; Zirolia a demontre que les puces laissent ces traces au cours dc la succion, cn remplissant et vidant a plusieurs reprises lour tube digestif du sang de leur bote. froltis ou ensemence des puces reeueillies sur des aniniaux septi- cemies. Tousles frotlis operas avec des insectes recemment recueil- lis presentaient des bacilles pesteux morphologiquement typiques. Dans deux cas, ou nous avons mis en culture des insectes tubs depuis peu, il s’est developpe du bacille de Yersin caracteristique. Dans Tun des cas, ce bacille s’est niolitre depourvu de virulence, fait bien explicable apres le passage d’un insecte d’aussi f'aible volume qu’une puce dans des solutions antiseptiques, dont Tem- ploi est pourtant necessaire pour detruire les germes existant sur son tegument externe. Dans Tautre cas, la culture obtenue tuait la souris en 48 heures. Les resultats absolument concordants de cette serie d’experiences, nous permettent de conclure que les puces du rat sont capables, d’une facon constante, de transmettre la peste d’animal a animal, rat ou souris. L’animal inocule par les puces succombe en o a 10 join's avec une septicemie pesteuse generalisee. One souris est meme morte exceptionnellement en 24 heures, deja seplicemiee. Dans un cas, l’animal infecte par Tintermediaire des puces nous a montre une infection plus massive que le rat inocule; dans les autres, Tinfection etait moins intense chez les animaux inocules par les puces. Enfin, a I’occasion, il nous a meme ete donne de me tire en Evidence le bacille pesteux dans son passage a travel's Torganisme de la puce. Essais de transmission par les Acariens parasites du rat. Outre les puces, on trouve sur les rats de ville et de navires, sou vent en assez grande abondance, d’autres parasites du groupe des Acariens. Ces parasites, tres petils et tres agiles, out ete sou- mis a l’examen de M. le D1' Bordas, chef des travaux zoologiques a la Faculte des Sciences de Marseille, qui a bien voulu en faire la determination. Ils appartiennent a la fatnille des Gamasides, du genre Hxmomyson; ce sont des Hczmomyson musculi (Megnin). Leur nombre parfois tres considerable, nous a fait penser que l’etude de leur role eventuel dans la contagion devait etre 1’objet de quelques recherches experimenlales, analogues a cedes insti- tuees pour les pulicides. Ces acariens ne sautanl pas coniine les puces, il est plus facile de sc proteger contre leur issue du bocal a experiences; une coucbe assez epaisse de vaseline ala partie superieure du bocal et un bain de sublimb autour de ce recipient suffisent a eviter tout exode. Dans ces recherehes nous n’avons pas non plus pris la precaution de separer les animaux; nous avons deja indique a propos des experiences sur les puces que celle condition ne nous paraissait pas indispensable. Experience F. — Le 29 juio, une souris blanche inoculee de pesle est chargee d’une dizaine d’acariens pris sur un rat d’egout capture en ville. Le lendemain, deux souris saines sont placees aupres de la souris inoculee. Celle-ci meurt sept jours apres l’inoculation, de septicemic pesteuse, verifiee par l’examen des frottis d’organes etle developpement de cultures typiques. Les animaux sains, sur lesquels on a pu voir passer quelques acariens, demeurent en bonne sante et, en les sacrifiant dix-huit jours aprbs la mort de la premiere souris, on peut constater l’absence complete d’in- fection. Experience G. — Le 10 aoiit, un rat blanc est inocule sous la peau avec une culture de peste. Apres 48 heures, lorsque l’animal parait deja malade et moins capable de se defendre contre les parasites, on place sur lui 8 acariens, pris sur un rat d’egout capture en ville. Le rat en experience meurt 36 heures plus tard, de septicemie pesteuse, verifiee par les frottis et les ensemencements d’organes. Un rat blanc neuf est place pendant toute la nuit aupres du cadavre. II demeure sain et apres l’avoir sacrifie au bout de 20 jours, on peut verifier a I’autopsie l’absence complete d’infeclion. Experience H. — Le 11 seplembre, un rat blanc, inocule de pesLe est parasite d’une trentaine d’acariens recueillis sur des rals d’egout captures en ville. Ce rat meurt au bout de quatre jours de septicemie pesteuse, verifiee bacteriologiquement a l’autopsie. Un rat blanc sain, laisse quelques heures aupres du cadavre est con- serve ensuite en observation pendant 23 jours ; sacrifie au bout de ce temps, on le trouve indemne de toute infection. 11 etait cependant encore porteur de 28 acariens. Un de ces parasites avait ete rec-ueilli sur le cadavre du premier rat de cette experience, lav6 a l’alcool absolu et ecrase pour fournir des frottis et des ensemencements. Ni a l’examen direct, ni en cul- ture, nous n’avons retrouve chez ce parasite le bacille pesteux. La meme constatation negative a et6 faite sur plusieurs parasites de ce genre recueillis chez un rat de navire ayant succombe a la pesle sponlanee et dont les puces out, par contre, fourni des cultures vi- rulentes de bacille de Yersin. Nous pouvons conclure de ces experiences que les acariens para - sites des rats ne semblent pas capables de s’infecter sur un animal se trouvant dans des conditions ordinaires de septicemic et lie peu- vent ensuite vehiculer le contage sur un nouvel bote. Dans ces essais, nousn’avions pas separe nos animaux et l’absence de transmission montrerait deja que le contact seul ne pent suliire a determiner l’infection pesteuse. Nous avons cependant entrepris d’autres experiences pour eludier ce mode de contagion deja revoque cn doute par Simond. Ess'ais de transmission par simple contact. Nous avons multiplie ces essais en plaqant frequeinment des animaux sains dans le ineme bocal oil nous enferniions les rats ou les souris inocules au cours de recherches diagnostiques ou syste- rnatiques. Dans aucun cas, nous n’avons vu l’animal non parasite, simplement expose au contact d’un congenere pesteux, s’infecler a son tour. Nous ne relaterons pas tous ces divers essais au nombre d une vingtaine, tous identiques et negatifs. Nous indiquerons seu- lement, dans leur detail, les experiences les plus lypiques. Experience J. — Une souris blauche saine est placee, du 18 au 30 sep- tembre, en contacL successif avec six souris peheuses. Gelles-ci inoculees par lots de deux, sont remplacees de quatre en quatre jours, au fur et ii mesure qu’elles succombenta l’infection veriliee bacteriologiquement. La souris ainsi exposee est ensuite conservee en observation pendant un mods ; elle demeure en bonne sanleetapres Favoir sacrifiee, on cons- tate qu’elle est saine. Experience I(. — Le 19 novembre, on place simultanement, dans un ineme bocal, trois rats adultes, inocules de pesle par injection sous- cutanee et une rate blanche avec deux petils, ages de six a huit semai- nes, encore en cours d’allaitement. Les animaux inocules meurent successivement en deux et trois jours ile septic^mie typique. Un des cadavres est retire le troisiemc jour pour l’examen bacteriologique mais les deux auLres sont laisses en place jusqu’au 27 novembre. JVIalgre co contact prolonge, la rate et les deux jeunes rats sont restes slrictement indemnes. Ces deux experiences, coniirmant nos autres observations et ren- dues plus rigoureuses par la longue duree du contact avec des animaux septicemies ou avec leurs cadavres, par le nombre des animaux inocules mis successivement ou simultanement en expe- rience, par la receplivite parliculiere des jeunes sounds au second essai. semblcnt montrer avec evidence que le simple contact ne suffit pas a trausmettre rinfection d’un animal atteint de septicemic pesteuse a mi animal sain. 11. — Les Puces du rat piquent-elles l’homme ? D’apres les etudes experimentales qui font l’objet de la premiere partie de ce travail, nous etions autorises a admettre que les puces transmettent la septicemie pesteuse d’un animal a l’autre. Nous avons du rechercher ensuile si ces memes puces du rat peuvent piquer l’homme dans des conditions paraissant analogues a celles qui realisent la contagion entre animaux. Suivant ton jours la meme methode que dans les experiences de transmission, nous avons recneilli, telles quelles, des puces chez des rats gris captures. Apres nous etre assures de l’absence de toute infection chez l’liote, nous placions les parasites, tenus a jeun depuis quelques heures, sur le bras ou la jarnbe du sujet. Experience I. — Une puce recueillie sur un rat capture eu ville est placee, apr6s 6 heures de jeune, sur l’avant-bras du sujet A qu’elle ue pique pas. Experience II. — 2 insectes de meme origine, jeunant depuis 24 h., sont places sur l’avant-bras du sujet B, qui se sent piquer mais ne presente que des marques douteuses. Apres Fexperience, on voit nellement, par transparence, le contenu de 1’abdomen de la puce colore en rouge. Un des insectes s’echappe, 1'autre fournit un froltis rutilant ou les globules sanguins ont leur aspect carac- terislique apres coloration par l'eosine. Experience III. — Une puce, de provenance analogue, a jeun depuis 24 heures, est placee sans soccfes sur l’avant-bras du sujet C, dans un manchon de toile gommee. Une demi-heure apres, ce meme insecte est place sur l’avant-bras de B, avec le meme dispositif. Au bout de 10 m. environ, Linsecte se met tres visiblement a piquer el d6jecte bientot sur le bras de grosses goutles de sang rutilant. Les traces de piqures sont peu visibles. La puce s’echappe et se peril. Experience IV. — 2 autres puces, se trouvant dans les memes condi- tions de jeune, sont encore placces sur l’avant-bras de B, qui se sent piquer et n’offre pourlant que des marques douteuses, bien que l’un el 1’autre insecte dcrases se montrent nettement gorges de sang frais, reconnaissable a i’examen microscopique. Experience V. — 3 puces de rat d’egoul, laissees a jeun depuis 48 h , sont placees sur l’avant-bras de C. Elle se posent et piquent immedia- tement; avec la loupe on les voit rougir et se gonller. La piqure a ete nettement ressenlie et l’on observe trois marques bien distinctes, Un 6chantillon s’echappe, les deux autres peuvcnt elre determines, ce sont des pulex fusciatus. Experience VI. — 1 insccte de memo origine, a jean depuis 36 h., est place sur l’avanl-bras de G, sous un cylindre de verre. La puce pique a plusieurs reprises, laissant trois marques bien neltes; lorsqu’on la retire une demi-beure apres, son estomac est vu bien dessine en brun fonce. L’insecte est alors transport^ sur l’avant-bras de B ; il se place et parait piquer, sans laisser de trace bien visible ; il est tue au cours de ces manipulations. L’eslomac est extrail par dissection a la loupe et son conlenu franche- ment rutilant est etale sur lames. La coloration a 1’eosine montre Ires distinctement des hematies. Experience VII. — Sur un rat capture dans la cour du laboratoire on trouve trois pulex fasciatus etune puce non pectinee se differenciant. de p. irritans. (Nous reviendrons dans la suite sur les caracteres de cette variete.) Ces 4 insectes sont mis en experience apres 24 lieures de jeune ; places sur l’avant-bras de A, ils piquent tous pendant un temps assez court, laissant une seule marque punctiforme, sans areole pe- ripherique ni petechies. La puce non pectinee meurt dans la nuit, les Irois fasciatus sont conserves en lubes respectivemenl 2, 4, 8 jours fai- sant cheque jour 1 ou 2 repas, dont la duree augment&nt progressive- merit varie entre 2 et 9 minutes. Les traumatismes, forcement exerces au cours de ces manipulations successive^, ont cause la mort des in- sectes. Les piqures qui, dans les premiers jours, ne laissaient que des traces a peine perceptibles, determinaient ensuile sur la peau des petechies tres nettes et prurigineuses dans tous les points on avaient ete placees les puces. Experience VIII. — Un pulex fasciatus a jeun depuis 24 beures, place a la region interne de la jambe de B, fait ainsi plusieurs repas dans la journee, — quatre applications, quatre piqures; puis est tue accidentellement. Experience IX. — Un pulex fasciatus de petite taille, trouve avec cinq autres sur une souris de maison, est nourri depuis le 26 novembre jusqu’au 16 decembre par repas quotidiens ou bi-quolidiens d’une duree de 2 a 6 minutes en movenne et de treize minutes au maximum. Dans l’lnlervalle, l’insecte est conserve a l’abri du froid dans un tube de verre place dans la poche d’un vetement porte le jour seulemenl. Nourri d’or- dinaire sur l’avant-bras de C, il prend de temps en temps san> difficulty un repas sur une seconde personne (sujet D). Les marques de piqures ne sont pas constantes; lorsqu’elles apparaissent ce n’est qu’au bout de quelques minutes; elles sont plus accentuees sur la peau du sujet D que sur C; elles sont toujours fort peu prurigineuses. On voit qu'en soinme, de 9 experiences effecluees a 1’aide de 16 puces, un seul essai, lente apres 6 lieures de jeune seulemenl. de Einsecle, est reste entierement negatif (sujet A) L Or, des puces de meme provenance mais apres un jeune plus long, piquerent tres nettement le sujet B. De meme, dans la troisieme experience, nous voyons un eclian- tillon qui a refuse de piquer C, attaquer une demi-heure apres le sujet B. Celui-ci, gargon du laboratoire, est d’ailleurs, des divers sujets experiments, celui qui olTrc l’apparence de la plus vigou- reuse saute. A part ces deux echecs, run total, l’autre partiel, ne porlant quo sur deux des 10 insectes mis en experience, toutes les tentatives out. reussi. Les sujets dedaignes une fois ont pu etre piques dans la suite. Tous les repas offer ts ont ete effectues avec plein succes ; le meme insecte a pu, assez souvent, piquer plusieurs fois son bote humain dans une meme journee. La puce de l’experience IX a sur- vecu 20 jours malgre son regime exclusivement humain. Une parlie seulement des puces mises en experience ont ete de- terminees an cours de ces essais. Nous avons releve sept pulex fasciatus et une puce non pectinee. Dans plusieurs cas, I’insecte s’etant ecbappe on avant immediatement servi a des preparations bistologiques cette determination fut impossible. Nous n’avons pas cru, d’ailleurs, qu’il y eut a prendre l’enquete entomologique comme base et principe de notre etude, le point principal etant de prouver que les puces qui vivent communement en parasites sur le rat sont capables de piquer Thomme. Mais il nous a semble que la determination zoologique des para- sites de ces rongeurs n’est pas sans interet et nous l’avons prati- quee, au cours de nos recherches, sur 300 ecliantillons environ. Varietes de puces trouvees au cours (Vexperiences sur les rats. — Les puces n’existent d’ordinaire qu’en nombre limite sur le rat sain ; on en trouve souvent deux ou trois, parfois aucunc; dans d’autres cas ces insectes existent en nombre considerable 2. 1. II n’est peut-etro pas inutile de noter que le sujet A subissait a ce moment un traitemont intensif par des injections sous-cutanees de sels dc rminine. 2. Un rat, qui nous fut apporte au laboratoire par M. le D1' Dupuy (med. san. mar.) et qui fut 1’occasion initiale dTine scric de nos recherches etait litteralemcul convert de parasites. Sur un autre, nous avons recueilli 1G0 puces, dont 158 appartenaient a la memo cspece, lyphlopsylla musculi. La faulie parasitaire, dans nos observations, a etc trouvee ires diflerente cliez los rats pris a terre et clicz eenx des navi res. Chez les rats de terre ot quelques souris, nous trouvons, sur 52 ecliantillons : P iilex fascia lus 45 Puces non pectinees nutres rjuc p. irritans. 3 Tvp 11 lopsylla musculi 2 Pulex serraliceps' 2 Cliez les rats de navires, de provenances d’ailleurs Ires diverses, nous avons trouve, sur 250 ecliantillons : Pulex irritans type 2 Puces non pectinees nutres que p. irritans.. (H Typlilopsylla musculi 178 Pulex fasciatus „ G Nous avons rencontre sur un rat de navire deux puces de riiomme; mais nous 11’avons pu reussir a infester des rats blancs avec ce type (Pulex irritans), tandis que nous faisions vivre facilement sur ces memos aniinaux les especes trouv6es communement cliez le rat gris. Les autres puces non pectinees que nous avons rencontrees et qui appartiennent a line seule variete, ressemblent grandement a la puce de I’liommc dans scs principaux traits, en particulier I’absence de peignes, la forme de la t6te et de l’antenne, les for- mules respectives des segments du tarse, aux difif6rent.es pattes. Elies nous out paru s’en ecarter toujours notablement par leur taille qui est beaucoup moindre, par leur couleur plus pale, par l'absence de la strie foncee qui, cliez Pulex irritans, accuse le sommet de la fosselte antennale et enfm par la forme de l’amiature g6nitale. Ce type de puces, par ces caracteres, se rapproche beau- coup de la variete decrite par Taschenberg sous le 110111 de Pulex pallidus. Ces puces, dans nos reclierches etaient assez speciales aux rats des navires; nous nous sommes assures qu’elles pouvaient niclier et accomplir tout leur developpement sur ces animaux. conclusions Nos experiences nous permettent, croyons-nous, de r6pondre d’une fagon precise a la double question que nousposions au debut de ce travail. La transmission parasiiaire de la paste estpossible. Nous Taverns vue se faire do rat a rat par 1'inter media ire des puces do cos ani- maux, mais non par les aoariens dont iIs sont parfois infesles. Elio n’est pas realisee par le simple contact d’animal a animal quand tout parasite est exclu de Texperience. Les puces ainsi mises en cause dans la propagation des epizoo- ties doivent etre redoutees comme agents possiJ>Ies de transmission trds fort, munies d’oeillets, reunies dans un carton disposd specia c” a cet ell'et. El le esl acconipagnee d'un texte explicatifredige en ti ois a g (francais, allemand, anglais). Prix de la collection (port en sus). | L. Marbtheux, imprimeur, 1, rue Cassctlo. ..>0.*. Paris. A PRELIMINARY NOTE ON THE EPIDEMIC OF BUBONIC PLAGUE AT SAN JUAN. BY I. GONZALEZ MARTINEZ. M.D., SAN JUAN, PORTO RICO. Director of the Bacteriological Laboratory of the Service of Sanitation of Porto Rico. REPRINTED FROM THE MEDICAL RECORD July 13, 1912 WILLIAM WOOD & COMPANY NEW YORK LIBRARY - T1 DD IIM'V.' imoo—«—o——y———m>m unuty un w— a cet efl'et. Elle est accompagngc d’un textc expiicatifredig^en trois langil (fran^ais, alleraand, anglais). Prix de la collection (port, en sus). 250 SAN JUAN. By I. GONZALEZ MARTINEZ, M.D., DIRECTOR OF THE BACTERIOLOGICAL LABORATORY OF THE SERVICE OF SANITATION OF PORTO RICO. On the afternoon of June 15 Dr. Frias com- municated confidentially to our Laboratory Assist- ant Mr. Loubriel that he had seen two cases that showed symptoms that made him suspect bu- bonic plague. Mr. Loubriel immediately advised Dr. Watson, the acting director of sanitation, as to the confidential information he had received, and this latter made an examination of the patients and ordered the necessary quarantine measures. On the morning of the 16th the director and chiefs of divisions' of the department got together and, realizing the seriousness of the sanitary prob- lem to be solved, decided on the importance and necessity of a correct bacteriological diagnosis. To proceed with more rapidity we divided the work, commissioning Dr. Hernandez, assistant bacteriolo- gist of the laboratory, to perform the autopsy of Pedro Colon, one of the cases, who died in less than 60 hours, apparently of a grave septicemia. We took to our charge the delicate work of collecting specimens and making the bacteriological examina- tions in the case of Miguel Llanos, a patient who Copyright, William Wood & Company. pital. When we began the work, two hours after the meeting, we found Llanos adynamic, with high fever, and an enormous bubo in the left inguinal region. There was' no erosion whatever in the cor- responding extremity, nor the least lesion on the scrotum or penis. The patient stated that on pre- vious occasions he had had similar attacks with swelling of that group of lymphatic glands, and this made some of the physicians who examined him think that we might be dealing with a filarial adenolymphangitis. We, who had had the opportunity of s'eeing sev- eral cases of plague in Oporto during the first half of the year 1900, held him as suspicious, and taking all the precautions necessary to avoid disseminating the bacillus hidden in the ganglia, after painting the part with tincture of iodine, we punctured asep- tically the ganglion, and aspirated several drops of the ganglionar and periganglionar juices, with which we prepared s'everal smears, inoculated glycerin agar and simple agar test tubes, and in- jected a guinea-pig. The post-mortem examination of Colon, per- formed by Dr. Hernandez and by Dr. Belaval, health officer of San Juan, revealed, according to their re- port, the characteristic lesions of a grave pneumonia. They prepared smears from the lungs, spleen, and liver, also made cultures in simple agar and gly- cerine-agar test-tubes and inoculated two guinea- pigs. The microscopical examination of the s'mears did not throw sufficient light to clear the diagnosis, as the autopsy was made nearly 24 hours after the death of the subject and the bacteria of the cadav- eric flora covered almost entirely the microscopic fields. Under such circumstances it was difficult to form a definite opinion, and the case was re- garded as negative. However, when on the fol- lowing day we examined with more care the same smears, we found, mixed with the putrefactive bac- teria, and scattered among them, a short thick bacil- lus, with rounded ends, which was Gram negative and had the polar staining characteristics of Bacillus pestis. In this case the cultures were negative becaus'e of the reasons above mentioned, and the experimental inoculation was also unsuccessful, the guinea-pig dying of a rapid septicemia. But if this case, even though suspicious, had lost, because of the above-mentioned reasons, its diag- nostic importance from the bacteriological point of view, in its relations to an official declaration of an epidemic disease, the case of Miguel Llanos ofifered the best guarantee for a correct solution of the bac- teriological diagnosis and the subsequent sanitary problem. The microscopic examination of the smears showed the exclusive presence of a cocco- bacillus with the following morphological character- istics: a short, thick bacillus, microns in length by 0-75 to I in width, with rounded ends, more deeply stained toward the poles than at the center when subjected to the action of the aniline dyes and specially to the diluted carbol-thionine and carbol- methylene-blue of Kiihne. Their mode of taking the stains gives' them a “dumbbell” appearance and one is likely to confound them with a diplococcus. Said bacillus grew slowly in the cultures of simple agar and glycerin-agar, the characteristic colonies not being visible to the naked eye until after being ex- posed to the temperature of the room for 36 hours. With the object in view of hastening the diag- nosis, now that the examination of the smears' had made us suspect that the bacterium we were trying to isolate was the Bacillus pestis of Yersin, we did not wait for the spontaneous death of the guinea-pig, which already exhibited symptoms of a grave dis- order, but killed it and made our examination at once. The anatomopathological les'ions of the guinea-pig were those characteristic of the plague: a large sized bubo in the lymphatic gland corre- sponding to the leg in which it was inoculated; notable infarcts of the spleen and liver, pneumonic foci, very much enlarged suprarenal capsules, con- siderable increase in volume of both kidneys, a peri- toneal exudate, and capillary hemorrhages in the infarcted ganglia and the viscera. We found both in the ganglionar juices, the sanguinolent s'erosity of the peritoneum, and in the juice from the spleen and liver, the same germ that we had found in Miguel Llanos, in the subcutaneous gelatiniform edema of the guinea-pig, and in the pathological sections of a human bubo. Doubt was now im- possible, and we therefore sent to the director of health without further delay a preliminary report of our work. The official declaration of the existence of such an epidemic, which is one of the three great plagues of humanity and the most fatal of all pestilential diseases, could not and should not be made without having for a base the results of a careful bac- teriological examination. Now, this being a work whose technical direction we had assumed wholly, it can be understood that we had to bear the weight of all the responsibility which came with it. We knew that after our report, and using it as a support, sanitary measures would be taken which would cause mental uneasiness in the homes of the city, would greatly interfere with the Island and foreign trade, and would spread a panic all over the island. This would be a serious state of affairs, and it is not strange, therefore, that we felt it necessary to proceed with much caution. There could, however, be no doubt that the bacillus which we had found in our case and later in similar cases, was none other than the Bacillus pestis of Yersin. Among the bacteria pathogenic for man, this is the only one that possesses all the characteristics al- ready described ; it is true that the chancroid bacillus (bacillus of Ducrey) simulates it in shape and stain- ing properties and is sometimes found in venereal buboes, but it is, nevertheless, true that said microbe cannot be cultivated in ordinary culture media, nor is it pathogenic to laboratory animals. The origin of this outbreak is still obscure. We suppose that the plague was introduced from Vene- zuela, not directly but in an indirect manner, by means of a port which is not in quarantine, without any human epidemic, and the ships from there would not therefore be subjected to “deratisation” in the port of origin or while unloading at San Juan. It is true that the investigations made to determine if there had been any increase in the death rate of rats previous to the explosion of the epidemic have shown that two or three months be- fore any human cases were noted there had been an abnormal death rate among these rodents in several warehouses of the “Marina,” possibly be- cause from that date the epizootic had been making ravages among them. Perhaps the first human cas'es were unnoticed or were confused with other grave and fatal diseases, due to a lack of careful examination of the patients. This is almost positively so, though not proven. With regard to the epizootic of plague among the rats, we have proven beyond doubt its existence in the Mus decumanus and the Mus rattus, and the bacteriological examinations which are now being made in the special Plague Laboratory which has been established, will show to what extent the epi- demic has invaded them. It has been said that the cases of plague which have so far occurred have been of a benign type, but* this is erroneous, as' among the 26 positive cases there were, up to June 29, 17 deaths, which shows a mortality of 65.3 per cent. Of these 17 deaths, 14 occurred at San Juan, one in Arroyo, one in Caro- lina, and one in Loiza. Of the 14 at San Juan, one was of pneumonic type and another of the septi- cemic variety. In a civilized community the gravity of an epi- demic cannot be judged by the number of cases. The sanitary organization and the intellectual ca- pacity of the people must be borne in mind; and in this respect the Department of Health of the Island and the inhabitants' of San Juan, united by the same idea of defense of the community, have worked with extraordinary activity, heroic energy, and ad- mirable skill. That is the reason why we shall not see repeated in Porto Rico the frightful mortality of India. San Juan, Porto Rico, June 29, 1912. A COMPOSrrt FAO-SlUILt MEDICAL RECORD A Weekly Journal of Medicine and Surgery WILLIAM WOOD AMO COMPANY. Publlshore. 61 Fifth Avenue New Tort*. 55.00 Per Annum. Published at New York Every Saturday Single Copies, 15c. # ORIGINAL ARTICLES. Iladlum for the Treatment of Cancer and Lupus. By William J Morton. M t> . Now York Cutaneous Tuberculin Vaccination In the Diagnosis of Tuberculosis, By William J Butler M D . Chicago Prevention of Death During Anesthesia by Chloroform and Ether B> Robert Reyburn. AM.. M.D.. Washington. D C What Shall We Do with Far Advanced Cancer of the Large Bowel? By R C Coffey. M.D.. Portland. Oro Sanitation of the Canal Zone. By Colonel William C. Corgas. M D, Vaginal Implantation of Adcnwarcl* noma of the Uterus. Blood Metasta* ele In Recurrent Carcinoma. By Ceo. W Kean. M.D. Boston. Mass Pci a lion of Accidents to Functional Nervous Diseases and Psychoses. Medicolegal Considerations. By Al- fred Gordon. M.D.. Philadelphia. Pa. 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Repriuted from The Indian Medical Gazette, Vol. XLIV PLAGUE PNEUMONIA: ITS BEARING ON RECENT CONTROVERSIES AND EXIST- ING PREVENTIVE MEASURES ALSO A PERSONAL STATEMENT PAPER READ BEFORE THE MEDICAL SECTION OF THE ASIATIC SOCIETY OF BENGAL 1909 (No. 8, August 1909) By W. A. HOSSACK, m.d., d.f.h Reprinted from The Indian Medical Gazette, Vol. XLIV PLAGUE PNEUMONIA: ITS BEAM RECENT CONTROVERSIES AND EXIST- ING PREVENTIVE MEASURES* ALSO A PERSONAL STATEMENT. By W. A. HOSSACK, m.d., d.p.h. Captain Gill’s recent paper(l) is one of the greatest interest and importance, not only from its bearinor on recent controversies as to the n causation of plague, but also in relation to certain proposals that have lately been made as to the adoption of practical preventive measures. Captain Gill, in his introductory remarks, found- ing his opinion apparently on the fact that the Plague Commission make practically no reference to plague pneumonia and possibly also on Browning Smith’s dictum(2) that plague pneumonia is something accidental and unusual, puts forward the idea that plague pneumonia is generally reckoned “ a curious variety of the disease which, on account of its rarity, is of * (Paper read before the Medical Section of the Asiatic Society of Bengal, May 1909.) (No. S, Aug. 1909). but little practicable importance”. He also holds that it has received very little attention or study. Let me assure him that this is not alto- gether so. In a recent discussion on the causation of plague which followed a paper read by me before the Society of Tropical Medicine and Hygiene(3) pneumonia was given a prominent place, and most of those who took part in the discussion agreed with the views that I have from time to time put forward in the last few years. Dr. Cantlie pointed out that plague, as found in Glasgow, Liverpool and the Gold Coast, was almost entirely pneumonic, and summed up by stating that, owing to the amount of attention devoted to rats and fleas, we had neglected the human factor in plague and that there was evidence to show that this was much more important than had been generally allowed. Dr. H. G. Waters, speaking of the Punjab, confirmed Dr. Cantlie’s opinion about pneumonic plague being often passed on from man to man. He had seen towns where the whole epidemic was pneumonic, and rats were hardly if at all affected. Browning Smith in 1006, though he thought that pneumonia was accidental and unusual, had to admit that pneumonic epidemics occur, buthe holds that they tend to remain localized, unless they pass into bubonic epidemics. Elliot(4) describes an acute outbreak in Nasik due to direct human infection, and it is notable that both pneumonic and bubonic cases occur in the outbreak ; he adds that he has seen many such outbreaks. The significance of this will be more evident when I treat of the general cahracter of plague as a septicaemia. He sums up thus : “ it has been my lot to work through eight epidemics and I am firmly convinced that human intercourse plays a great part in spread- ing the disease Allchen Gi 11(5) in the same special plague number of this journal has a most thoughtful and well-balanced paper. He disagrees with the view that plague is primarily a disease of the rat and only accidentally of man. The part played by man is of equal importance to the role of the rat. Referring to 14 infected villages in Jhelum, he states “ in most cases it will be clear on enquiry that rat infection has occurred from man.” In this paper his position is clear and definite, but in his second and recent paper he makes a special note that his conclusions are tentative and ad interim lie clearly recognises that pneumonia is an integral part of plague, that it is common and as such plays a considerable part in the spread of the disease. He indicates that the influence of this form of the disease has been underrated, as also has the part played by direct human infection. Mitra,(6) as I have pointed out more than once in previous papers, has recorded that the first epidemic in Cashmere, amounting to 1,374 cases, was practically entirely pneumonic, though the original imported case was bubonic. No mortality amongst rats was observed. As far back as 1899 I was struck with the frequency of lung symptoms in plague, and in 1900, I made a special investigation as to their character and frequency in a series of cases, observed not in hospital for we had none, but in their own homes. The results of that investiga- tion were published in the Lancet, Nov. 24th, 1900, and shewed that out of 194 cases directly observed by me, no less than32*4 percent, shewed respiratory symptoms. Of these, 62 per cent. were primary pneumonia ; in 25 percent, it was doubtful whether the pneumonia was primary or secondary, and in only 13 per cent, was it clearly secondary to the bubo. I record that of the total 2,237 cases investigated in my district, about 30 per cent, were pneu- monic, or rather shewed signs of lung impli- cation. Since 1900 plague pneumonia has formed a varying but alwa}7s considerable proportion of the total cases in Calcutta ; but, in the absence of special investigation, it is impossible to obtain reliable figures, as will be evident from my definition of plague pneumonia which follows. Since Major Childe drew up his des- cription of plague pneumonia in 1899 there has prevailed a general impression that the pneu- monia of plague is one of a very definite type not easily overlooked and easily distinguishable from pneumonia due to other causes. My expe- rience in Calcutta has been very different and I have come to regard plague pneumonia not as an aberrant and rare type of a disease which is local rather than generalized, with buboes marking the site of skin infection, but as a fre- quent and occasionally a predominant expression of a disease which is essentially a septicaemia. Theoretical Considerations. — The bacillus pestis is a member of the pasteurella group, or the salmonella group as it is termed by the Germans, a group the essential characteristic of which is that they produce a septicaemia. The bubo in plague, I maintain, is as a rule as little an indication of the site of primary infection as is the ulceration of Pyers’ patches in typhoid or the thickening and inflammation of the cover- ings of the spinal cord in epidemic cerebro- spinal meningitis, or the deposits in the lung in many cases of phthisis. It is now known and ;> recognized that in all the diseases mentioned ZD we are dealing not with a lesion marking the site of entry of the bacillus or coccus, but with general bacteraemic diseases which have,however, their selective site for manifestations, Pyers’ patches in typhoid, the meninges in epidemic cerebro-spinal and the lung in phthisis, the respective channels being the intestine leading from the gall bladder, the nasopharynx lead- ing from the buccal cavity and in many cases, at all events, the lacteals leading from the in- testines. In all three diseases it is admitted that the human factor of infection is a very important one and in cerebrospinal meningitis it is admitted to be almost the only one. Is it then a strange conception to regard plague in the same light as a general septicsemic disease with a peculiar tendency to attack the lymphatic system and in its more acute manifestations to show deposits and lesions in the lungs, as is characteristic of most of the septicaemias ? Definition of Plague Pneumonia.—It is rather unfortunate that Captain Hill gives no clinical description of the cases that he calls plague pneumonia and leaves one in doubt as to whether they were all Childe’s typical form or the vague, indefinite, and easily overlooked form which I have described. In Calcutta Childe’s pneumonia is extremely rare, so that it is evident- ly important for future observers to note which type is concerned, and it is to be hoped that Captain Hill will give us more detailed informa- tion on the point, particularly with reference to acute wholly pneumonic outbreaks.* Two or * In the discussion Major O’Kinealy described how in the Darjeeling pneumonic epidemic, the most careful physical examination failed to reveal definite signs of pneumonia in some of the cases. G three wholly pueuraonic outbreaks have been traced to Calcutta, notably one reported by Justice in Barisal, but the cases I have seen per- sonally occurred as part of acute outbreaks of septic and bubonic plague; that is to sa}% some cases in the same house had buboes, some had pneumonia, some had buboes and pneumonia, and some had neither. Considering the impor- tance of the subject and the fact that the article seems to have been overlooked b}^ Captain Hill, I may perhaps recapitulate the description of plague pneumonia or rather lung implication as observed by me in 1900. “ Lung Symptoms in Plague.—The main facts pointing to a case being plague pneumonia, in addition to its generally septic character, which has already been sufficiently described under general symptoms are as follows. Cough may be very slight and occasional. The breathing, taking into consideration the high temperature, is little hurried or laboured, and the ordinary pneumonic disproportion of pulse and respira- tion rate is reversed. The pulse is the rapid feeble pulse of sepsis already described, prob- ably 120 per minute. The sputum, like the cough, tends to be very scanty and occasionally so much so that in very many of my cases there was no opportunity of seeing it. As a rule, it is clear and mucoid, very like bronchitic sputum. Occasionally it may be faintly muco-purulent. Rusty sputum I have only seen once, and it was welcome as I had just shewn the case to a medical sceptic who on the strength of a first expectoration, bronchitic in character, had de- clared the case to be simple bronchitis. The rusty sputum came only after forced coughing. Blood in the sputum 1 have seen twice. In one case there was a history of almost haemorrhage from the lung. Prune-juice sputum 1 have never seen.” “ Physical signs.—Very frequently on the first day or two of illness it will be found impossible to make out anything abnormal in the chest Then will be found probably in one or both apices small patches, some two inches in diameter, with bronchial breathing and increased vocal resonance and a few line moist rales. Dullness on percussion, as a rule, is very faint, if made out at all. The rest of the lung will probably be normal, but an occasional rale or rhonchus may be made out. All the signs given may be very faint and over a very small area, but if present at all, however faintly, the}' may be taken, as far as my experience goes, as almost inevitably indi- cating a fatal result. So often has it been only after repeated examinations that such patcli has been found, and so liable is it to be overlooked, that I am inclined to call any case pneumonia as soon as I find cough present and to assume that the patch has either been overlooked or else is too deep in the lung to cause definite physical signs. The result of post-mortem examination as recorded by Major Childe, Captain Evans, and others in their reports supports that view, patches of from the size of a walnut to that of a pea being described. Of course, at times the patches are widely distributed over the lungs and may form a consolidated mass over the greater part of one lobe giving clear physical signs, but in my experience this is not common. Other observers, while agreeing for the most part with my description, lay less stress on the paucity of physical signs and describe the sputum rather differently. Thus Major Lyons, I.M.S., says: “ the expectoration is diagnostic from that of ordinary broncho-pneumonia, it being less viscid from the first and early becomes profuse and watery and generally tinged with blood or red- dish from admixture of blood Major Childe makes it “ loose and free, coming up with the slightest cough, looking more like serum than mucus, and it was slightly pink, not rusty yellow at all.” “ It is not always as described ”, it may be “ much less profuse ”, “ and in some cases tbe presence of blood is a marked feature ”, Captain Thompson makes it “ seromucoid, scanty, and occasionally tinged with blood”. Dr. McCabe Dallas describes it similarly. All, however, note the comparative absence of dysp- noea. I have described a form in the epidemic of 1899 where the general symptoms were very mild, rather bronchitic in character, and only the excessive pulse-rate and the unexpected fatal termination give the clue, but in the epidemic of 1900 such cases were not common. The duration of these cases may be up to ten days.’’ Frequency of Plague Pneumonia in Bom- bay.—The few figures that are to be found are so variable that it is difficult to come to any conclu- sion. Lamb makes it rare, less than three per cent.; while Dr. Petrie, on the authority of Dr. Choksy, estimates it at 1 per cent., but Dr. Choksy about a year ago admitted that it had been underestimated. There have been so many important alterations in original estimates in Bombay that probably it were wise to wait for further and more detailed information. Dr. Choks}7 in his last paper at the Congress made no statement as to its frequency. A Personal Statement.—The most common criticism I have met with even from friendly critics is to the effect that while my work may be useful why is it all destructive, why is none of it constructive ? I beg to submit that it has been constructive to a considerable extent. The most recent criticism of my work, that of Dr. Petrief?) in his reply to my last paper, is to suggest that it is academic and negative, that it is unsupported by personal observations and hence my criticisms are of little value. My reply to this is to recapitulate the follow- ing positive work, all based on careful observ- ations and, where it was possible, to make these experiments. In 1900 I established the fact that plague pneumonia and lung implication is common in Calcutta.(8) In 1902 I established simultaneity of infection in badly infected houses, the preponderance of single case houses, and the comparative uselessness of disinfec- tion.(9) In 1906-7 I worked out the rats of Calcutta and so was able to establish that any house species can convey plague.(10) In July 1906 I inaugurated the study of pulicides ; the subject was so absolutely new that I had to coin the word pulicide for the occasional 1) I estab- lished that tar acid or higher phenol disinfect- ants were the most suitable and reliable puli- cides. Captain Saigol, after omitting all men- tion of my work in his first paper of July 1907, claims my submersion method as his own in his second paper. (Indian Medical Gazette, Aug. 1908, p. 291.) In 1907-8 I established that the flea conditions of Calcutta were such as to ex- clude flea infection as a factor of any importance, and also established experimentally the fact that the rat-flea for practical purposes does not bite man.(12) Of course, in establishing some of these items I have had the assist- ance of my colleagues. It has been suggested to me that I have approached the subject of the rat-flea theory in a non-scientihc spirit and have, in short, in ray criticisms presumed on the fact that ultimate proof of the theory was impracticable. What better answer to this can I have than the fact that work on pulicides originated from me ? Where I am now defin- itely negative, I was then only doubtful, so I tentatively accepted the theory and set to work to translate it into practical action; devising a method of establishing the relative value of pylicides. Dr. Petrie, in his reply already referred to, conveys the impression that I lay great stress on feeding as one of the chief modes of natural infection in rats. All I have said in this connection is “ that there is too much evidence in favour of food transmission of infection in connection with rats to allow of this method of propagation, being dismissed as of no importance” (Cal. Plague Rep., 1907, p. vii). What I have put forward strongly is that, there are many modes of plague infection; the mode I have laid special stress on is direct infection in pneumonic or lung-affected cases. “ Etiology and Epidemiology of Plague— I wish to call vour attention to the fact that the 4/ Advisory Committee deny all responsibility for the Etiology and Epidemiology of Plague and the statements therein, particularly No. 3 of the general conclusions, “ all plague in man is due to bites of infected rat-fleas.”(13) The neces- sity for calling attention to these facts arises from the attitude of the Bombay Medical Con- gress. Major Lamb there read a paper which was simply a recapitulation of the “ Etiology and Epidemiology of Plague ” and reiterated his eight general conclusions including No. 3. I gather that the Congress accepted these conclu- sions and that most of the members who took part in the discussion still continue to accept them as the findings of the Plague Commission. Whether at the time this pamphlet was pub- lished, the conclusions were a fair summary of the views then held by the Commission is a question with which I have no concern. The important fact remains that the Commission deny all responsibility for the “ Etiology and Epi- demiology of Plague” and the conclusions there given, and I have had to apologize to the Com- mission for my error in imputing to them those conclusions. It will be evident from what has just been said that there is prevalent in India a good deal of misunderstanding about the present position of the rat-flea theory of plague and that my recent paper has failed in its purpose so far as India goes. It is now beginning to be ac- cepted at home that there has been a tendency on the part of the Commission to lay undue emphasis on positive evidence in favour of their theory and to neglect negative evidence, with the result that their conclusions are exaggerated and unreliable. Perhaps I may recapitulate briefly some of the main facts which have led to doubt being cast on the views of the Plague Commission. Verjbitski, in anticipation of the work of the Commission, carried out a very lengthy and elaborate scheme of experiments in which he demonstrated beyond all doubt that plague can be transmitted to animals by infected fleas and bugs. His experiments were on a grand scale similar to those of the Commis- sion and little if at all inferior in sheer weight of numbers. They were equally successful, but the point is that they were carried out without a single Pulex Cheopis for the good reason that it was not available. He used the bed-bug (Cimex lectularius) and three species of fleas ; Pulex irritans, the human flea, Typhlopsylla felis, the dog-flea, and Ctenocephalus musculi, the common rat-tiea of Russia. (14) His results with the bed-bug have been confirmed by Jardanski and Kladnitski.(15) The result is that the rat-flea of the East, Pulex Cheopis, has to be regarded not as the sole insect or arthropod carrier of plague, as put forward by Lamb, but as one of a goodly company. What militates still further against its claim to special recognition is the fact that with the exception of Ct. musculi, it is the only one of the company that will not bite man freely ; in fact, unstarved it will practically not bite man at all, and even starved, only occasion- ally. This is confirmed by the Commission themselves in their last report.(16) From over 696 starved fleas they only obtained 11 bites. Selection of Evidence by the Plague Commis- sion.—I do not propose to recapitulate my own observations; 1 will merely say that in most of the points in which I was able to check by personal observation the statements of the Commission, I was unable to corroborate their findings. One point which I have not been able to check owing to the absence of a plague laboratory, has been the limited amount of septicaemia in man and the very limited amount of infection in the excretions and dejecta of septicsemic cases. This investigation was carried out by the Commission on a series of 72 septicsemic cases. It is generally under- stood that septicsemic plague is plague in which the infection is so acute and overpowering that the tissues have no opportunity of re-acting, and they are cases which show neither buboes nor pneumonia. I now learn from Dr. Choksy’s last paper before the Congress that every one of these septicsemic cases had buboes except two. We are left with two alternative conclusions, either true septicaemic plague as known in Calcutta and other parts of India is unknown in Bombay, or they were unfortunate in the type of septicemic cases under observation and therefore conclusions from the experiments carried out cannot be accepted. Practical Conclusions.—It may be asked what is the use of this controversial rigmarole, as some may call it, in what way does it help forward at all the cause of plague prevention ? In this way, The rat-flea theory has got such a hold of plague workers in India that it tinges all their ideas and suggestions and is responsible for such wild proposals as those that have called for severe comment in a leading article in the December number of the Journal of Tropical Medicine. This suggestion is that kerosine oil emulsion is all that is wanted in the treatment of plague houses, on the ground that kerosine kills fleas well and that, though it has little bactericidal power, this is not necessary, as in the infected excreta and secretions of animals natural disinfection occurs. The sooner it is generally recognized that plague is not largely a local disease caused by the bites of the infected fleas, but a general septicaemic disease that is fostered by insanitation and is conveyed in many different ways and channels, the sooner we will reach sound and practical preventive measures. To accept the rat-flea theory in its entirety, it is necessary to premise that pneu- monia and septicaemia are very rare in man. I maintain that there is a large body of reliable evidence against this presumption. References. (1) Gill—“ Note on the Epidemiology of Pneumonic Plague.” Indian Medical Gazette, April 1909, p. 135. (2) Browning Smith—“ The Spread of|Plague.” Indian Medical Gazette—July 1906, p. 249 (plague number). (3) Hossack,“The Present Position of the Rat Flea Theory of Plague.” Trans. Society of Tropical Medicine and Hygiene, January 1909. 4) Elliot—“ How does plague spread ?” Plague Number, ante cit, p. 279. (5) Grill—“ How plague is spread ? ” Plague Number, ante cit, p. 287. 16) Mitra—“Plague in Cashmere.” Indian Medical Gazette, April 1907, p. 133. (7) Petrie—Transactions Society of Tropical Medicine and Hygiene, January 1909, p. 98. (8 & 9) Hossack—“ The Diagnosis of Plague.” Lancet, November 24th, 1900. (10) Hossack—'“ The Rats of Calcutta.” Memoir of Indian Museum, Vol. I, No. I, 1907 ; also “Aids to the Identification of Rats connected with Plague in India,” Pamphlet 1907. (11) Hossack—“ Note on Results of Disinfection in Calcutta,” 1902 Pamphlet. (12) Hossack—“ Some recent Developments in the Study of Plague.” Calcutta Medical Journal, May 1908, also Calcutta Plague Report, 1907. (13) Charles—“Discussion.” Trans. Society of Tropical Medicine and Hygiene, January 1909, p. 108. (14) Verjbitski—Journal of Hygiene, Vol. VIII, p. 185, &c. (15) Jardanski and Kladnitskie, Ann. Past. Inst., May 1908 from Epitome—Brit. Medical Journal, De- cember 5th, 1908. (16) Plague Commission, Journal of Hygiene, Vol. VIII, May 1908, pp. 249—253. MEDICAL SECTION OF THE ASIATIC SOCIETY OF BENGAL. [Discussion on Dr. Hossack’s Paper on Plague Pneumonia, May 1909.] Lieut.-Colonel Harris said that if the pres- ence of cough was to be taken as evidence of pneu- monia, as Dr. Hossack did, then the latter disease must be present in nearly every case of typhoid. The late Major Evans found plague pneumonia was not a broncho-pneumonia, and the speaker would not class cases with slight broncho-pneu- monia as primary pneumonic plague. In his experience plague pneumonia was always fatal. The haemorrhagic prune juice sputum was a marked feature of the disease. Dr. Pearce said that plague pneumonia formed an appreciable, hut unknown, proportion of plague cases, having formed much less than 10 percent, in Bombay in 1897. It was extremely fatal and also contagious, while bubonic plague was not infectious. He did not agree with Dr. Hossnck in considering that plague was spread by human beings, as the house incidence was onl}7- 1’2 cases in Calcutta. If pneumonic plague was common, whole families would frequently die of it, which was not the case. Pneumonia may occur as a late complication in plague as in other infectious diseases. Lieut.-Colonel Green did not agree with Dr. Hossack in thinking that bubos in plague were a sign of general septicaemia and not connected with a local infection. In cases of accidental inoculation the primary bubo occurred in rela- tion to the site of infection. He did not con- sider the presence of cough as an indication of the presence of pneumonia in plague. Major Vaughan had exceptional opportunities of studying plague at the Campbell Hospital, where plague pneumonia was associated with sero-sanguineous rather thin sputum. More severe haemorrhage like haernoptosis also occur- red. There were patches of consolidation and haemorrhages into the lungs, while the physical signs were less marked than in lobar pneumonia, only high pitched resonance being present some- times. The mortality was 100 per cent. Major W. D. Sutherland had seen plague in A kola in the Central Provinces in 1901, and in 1,500 fatal cases only four plague pneumonias had been reported, two in one house and two in another, no other persons living in the houses. It began with high fever, but the phy- sical signs were slight. It was always fatal. Dr. G. C. Chat ter jee was house physician when plague began in Calcutta and saw the late Major Evans’ post-mortems, in which small patches of consolidation were found in the centre of the lungs with haemorrhages, its characters being distinct from ordinary pneumo- •nia. Sections of the lung were also characteris- tic, being almost full of plague bacilli with very few cells. Dr. Hossack in reply referred to the following paragraph from a former paper on the subject as summarising his views :— The figures as to the frequency of pneumonia may possibly be challenged, but as to its excessive mortality all are agreed. The leading and most diagnostic point about this variety is that, while the general symptoms of the disease are exceptionally grave and exceptionally rapidly developed, the local lung symptoms and the results of physical examination are so very slightly marked that they can often be detected only after a most careful examination. The disease, in short, is of an intensely septic type and the lungs show little of the signs of consolidation of ordinary pneumonia as a rule. In fact, many of the cases which I have called pneumonic might by another observer have been called septicaemic. In this connexion it may be noted that the returns for the Medical College Hospital, Calcutta, for 1898 showed that out of 98 cases 10 were pneumonic, 20 were septi- cemic, and in four cases there were both buboes and pneumonia*—that is to say, that 30 per cent, of the total cases were non-bubonic. My figures for the epidemic of 1900 are 193 cases with 44 cases uon-bubonic, but only 11 of these 44 were septiciemic. In reality the number of septicsemic cases should be even less, as I know that in some of them in a second examination I made out lung symptoms,but in the rush of work no record * Captain C. H. Evans, Plague Commissioner's It : port, vol, i, p. 244. was made. The presumption from these figures is that Captain Evans, who compiled those returns, would have made some of my pneumonic cases septicsemic and vice versd, but, at all events, this fact is brought out clearly, that in Calcutta the proportion of non-bubonic cases is very high. The precise designation is a matter of secondary importance, particulatly as in his very valu- able pat hological report Captain Evans gives his opinion that plague pneumonia is due to infection from the blood rather than from the air passages—that is to say, that the pneumonia is simply the expression of a septicaemia. d—3 • V PBSTE ATYPIQUE PAR MM. R. JACQUES MEDECIN DES SERVICES MARITIMES MEDECIN DE LA SANTIS A MARSEILLE J-C. GAUTHIER CHARGE DE COURS A I.’ECOLE DE MEDECINE DE MARSEILLE MEDECIN DE LA SANTE Extrait de La Presse medicate (N° S3, 3 Juillet 190P 1901 COUHTE EPIDEMIE DE PESTE ATYPIQUE PAR MM. R. JACQUES / J.-C. GAUTHIER MEDECIN DES SERVICES MARITIMES MEDECIN DE LA SANT^ A MARSEILLE CHARGE DE COURS A L’ECOLE DE MEDECINE DE MARSEILLE MEDECIN DE LA SANTE Extrait de La Presse medicate (N° 53, 3 Juillet 1901' PARIS G. NAUD, Editeur 3, RUE RACINE, 3 DE PESTE ATYPIQUE M. le professeur Proust, dans le rapport qu’il deposait a PAcademie de Medecine en son nora et en celui de M. Faivre, donnait dernierement la relation de la courte epidemie observee a bord du vapeur francais N. et au lazaret des lies du Frioul, pres Mar- seille *. Quelques particularites de cet episode nous ontparu anoter comme une contribution, peut-6tre utile, au diagnostic de la peste. C’est la une question bien a l’ordre du jour et qui, tres simple souvent a resoudre, ne laissepas, comme on le rappelait ici il y a quelques 1. Bulletin de I’Academiede medecine, 1901, 26 Mars. jours, de presenter parfois de reelles diffi- cultesl. i Le 28 Aout 1900, mouillait au lazaret du Frioul le vapeur iVvenant de Constantinople, • et l’autorite du bord y signalait Lexistence de quelques cas presentant les symptdmes de l’infection pesteuse. Deux personnes sembla- blement atteintes avaient ete deja debarquees quelques jours auparavant a Clazomene. Les malades se trouvant a bord a l’arrivee a Marseille etaient : le medecin, l’officier d’administration et un chaulTeur du navire. Les mesures de rigueur en pareil cas furent aussitdt prises par la direction sanitaire : le navire fut isole avec son equipage, les passa- gers mis en observation dans les batiments du grand lazaret, tandis que les malades etaient transposes au petit lazaret de Rato- neau dont les circonstances nous amenerent successivement Fun et l’autre a diriger le service. M. Pellissier, interne des hdpitaux, nous fut adjoint sur sa demande. Rappelons d’abord, d’apres la relation de 1. (i La peste a Alexandrie ». La Presse Medicale, 1901. M. Bigot, medecin du navire, quels avaient ete les debuts de cette petite epidemie nau- tique. Le 22 Aoiit, dans le port de Constantinople apparaissait a bord un premier cas suspect chez un indigene de Kharpout embarque a Alexandrette, Nicham A. Le malade, avec une temperature de 39°8 et un pouls battant 113, ofTrait un visage vultueux, la peau seche, la langue jaunatre et, au niveau de l’aine gauche, un peu au-dessus de l arcade de Fallope, un ganglion gros comme une noisette, doulou- reux, mobile sous le doigt; dans l’aisselle du m6me c6te, un chapelet de petits ganglions durs et mobiles, douloureux. Le malade est isole, et uneponction dans l’atmosphere cellu- leuse periganglionnaire permet a MM. Rew- fick bey et Haim bey, assistants a l’lnstitut imperial de bacteriologie, a qui cet echantil- lon est soumis, de faire le diagnostic de peste. (Ce diagnostic fut depuis confirme par M. Nicolle, directeur de l lnstitut). Presque en m6me temps, un autre cas se declarait a bord. C’etait un garcon de service, Albert A..., chez qui, dans l’apres-midi du 23, apres deux jours de prodromes, on decouvrait, au-dessus et au-dessous de l’arcade crurale droite, deux ganglions peu volumineux adhe- rents a la peau et entoures d une gangue de periadenite. Ce malade, au moment oil il est debarque le lendemain au lazaret de Clazo- mene, presente un etat general grave et tous les signes d une suppuration imminente des deux adenites l. A peine le navire avait-il quitte Constanti- nople, le 24 Aoiit, pour rentrer a Marseille que M. B... se sentait lui-meme atteint de symptdmes generaux graves : vomissements incessants, cephalee intolerable, vertiges, symptomes dont la signification est bientbt precisee par Lapparition dans l’aine et l’ais- selle droites de ganglions douloureux. Le malade sfinjecte lui-meme en deux fois 50 centimetres cubes de serum antipes- teux. Le navire etant arrive sur rade de Mar- 1. Des renseignements ulterieurs, il resulte que 1’un ei l’autre malade ont gueri sans suppurations de leurs ade- nites. seille, M. B... est debarque au Lazaret du Frioul. 28 Aoiit. Le thermometre marque 38°7 le jour de l’arrivee. Le lendemain, il mar- que 39°,6; mais les jours suivants, le trace presente des oscillations considerables allant ffeneralement de 37°5 dans la matinee a 40° O ou 40°5 dans l’apres-midi. (Y. le trace.) Le 4 Septembre, on voit apparaitre une teinte verdatre de tout le tegument, laquelle s’accentue de plus en plus les jours suivants jusqu'a donner au malade la patine du bronze florentin. Urines legerement albumineuses. Le 9 septembre, apparaissent en meme temps de la depression circulatoire et du ballonnement du ventre qui devient doulou- reux; le facies se grippe, la temperature est au-dessous de la normale, autant de symptb- mes qui, corrobores par les oscillations ther- miques a forme d’infection purulente des jours precedents, font penser a la suppura- tion d’un ganglion profondement situe au voisinage du peritoine. Cette hypothese devient de plus en plus probable avec l’appa- rition d’une legere tumeur dans la fosse iliaque gauche. On se dispose aintervenir chi- rurgicalement, touten maintenant le malade sous l’influence des injections repet^es de serum de Yersin et de serum artificiel, quand subitement, le 16 septembre, la tumeur iliaque s’affaisse, le meteorisme disparait et le malade emet une abondante quantite d’urine. Celle-ci, fortement teintee envert, presente un depot epais dans lequel le microscope decele beaucoup de globules de pus et de tres nombreux bacilles a espace clair. Ces urines offrent nettement les reactions caracteris- tiques de la pyoxanthine et clu pigment vert fluorescent, faiblement celles de la pyocya- nine, ce qui fait conclure qu’un adeno-phle- gmon avec infection mixte par un bacille chro- mogene s’est rompu dans layessie, mettant en liberte les pigments qui donnaient precedem- ment au malade une teinte si speciale. Le sang puise dans une veine contient en abon- dance des microorganismes varies et un certain nombre de bacilles a espace clair, mais les cultures et inoculations en restent nega- tives. Le malade esttoujours en hypothermie, et une issue fatale est a craindre; on continue les injections de serum artificiel et de serum de Yersin; bains chauds, toniques, cardiaques et quinine par voie hypodermique. A partir du lendemain, 17 Septembre, la teinte est plus claire, la temperature remonte a la normale en meme temps que l’etat general devient meilleur; le malade ne tarde pas a entrer en pleine convalescence, mais il a presente depuis lors de frequents acces de fievre, lesquels semblent avoir depuis quelque temps definitivement cede au traitement qui- nique l. M. B... avait recu a bord les soins de M. de M..., commissaire du navire. Celui-ci, apres quelques prodromes vagues, entre au lazaret dans unetat general mauvais : nausees, vomissements, cephalee intense, inappetence, et avec une adenite axillaire droite, doulou- reuse, petite, ne tendant pas a la suppuration. Le malade presente les m6mes symptdmes jus- qu’au 4 Septembre, puis se remet rapidement. Entre temps, decedait presque subitement a bord un chauffeur qui ne s’etait plaint que de vagues symptomes, ne presentait pas d’ade- nite et avait refuse de s’aliter. L’autopsie, qui fut pratiquee, ne permit pas par les lesions ma- croscopiques constatees d’etablir avec preci- sion aucun diagnostic retrospectif. A signaler cependant la teinte asphyxique generalisee a tout le tissu cellulaire et aux teguments, don- nant a tout le corps une couleur uniformement noiratre. Rate grosse, diffluente. Etat poisseux du sang. II n’existait aucune augmentation 1. Observations recueillies par M. Pellissier. perceptible du volume des ganglions super- ficiels on profonds. Des echantillons furent preleves dans les differents organes pour l’examen bacteriologique. Les frottis du foie et de la rate presentent en tres grande abon- dance un microorganisme ayant tous les caracteres morphologiques et les reactions colorantes du bacille de Yersin. Les ganglions d’un rat inocule par simple piqure sous- cutanee et qui meurt le sixieme jour donnent des frottis aussi typiques. Mais nous n’ob- tinmes pas les cultures nettement caracteris- tiques1, M. le professeur Rietsch etM. Trous- 1. L’importance des associations microbiennes develop- pees pendant le delai que nous dumes mettre a l’expertise des prelevements faits k l’autopsie, la perte rapide de la virulence, ne permirent-ils pas d’obtenir des cultures pures de bacille pesteux? Yoici du moins oe que nous observames dans nos tentatives d’isolement. Ge fut, avec une grande regularite, l’alternance de cultures en bouil- lons tres floconneux et un peu troubles, donnant de courtes cbainettes bacillaires decolorees par le Gram; et sur plaques de gelatine, de petites colonies non lique- fiantes, rondes, bumides, n’ayant aucunement l’aspect macroscopique des colonies de Yersin, bien qu’elles fus- sent composees de coccobacilles microscopiquement typi- ques. Sur gelose, en quelques heures, on obtenait une culture trop grosse et trop vigoureuse. Toute virulence etait perdue pour les souris, rats, cobayes par voie nasale ou sous-cutanee. saint qui examinerent nos preparations, eurent l’obligeance de poursuivre nos reclier- ches, interrompues de lorce majeure, et n’iso- lerent pas davantage les cultures typiques du B. de Yersin. Les frottis de visceres humains et les gan- glions de rat etaient d’ailleurs nets a ce point, qu’a leur aide seule, M. le professeur Cal- mette formulait quelque temps apres le in6me diagnostic bacteriologique de peste pose par l’unde nous, comme il l’avait ete a Constanti- nople. Ajoutons que M. Nicolle, ainsi qu’il veut bien nous l’ecrire, constata l’apparence carac- teristique des cultures. Et pourtant l’infection en cours, dont la nature pesteuse etait soulignee ainsi a chaque etape, continuait a offrir quelques particula- rity bien speciales que les deux courtes observations suivantes mettent assez en lu- miere. Observation I. —Le chauffeur Car., remar- quablement vigoureux, a presente anterieure- ment plusieurs atteintes de paludisme; au moment de l’arriveedu navire a Marseille, ilse plaignaitde cephalalgie etde courbatureetpre- sentait une adenite axillaire gauche, de la gros- seur d’un oeuf de pigeon, avec peri-adenite et empatement de laisselle. Le jour de l’entrce au lazaret, la temperature atteint 41°2 et reste stationnaire jusqu’au lendemain, soit vingt- quatre heures apres l’injection de serum. Le malade est tres abattu, facies terreux. Une prise de serosite dans l’atmosphere ganglion- naire ne donne qu’un resultat negatif en Irottis, cultures et inoculations. Mais le sang de la veine tue tardivement un rat que l au- topsie demontre inlecte par des bacilles a espace clair, plus larges et plus longs que le bacille typique, ne prenant pas le Gram et loca- lises aux ganglions et a la rate. Une elevation de temperature se produit quarante-huit heures apres les in jections de serum antipes- teux, le 5et le 14 Septembre. Au moment du dernier acces (40°), on preleve du sang qui, examine, presente des amibes de Laveran, tres nettes, mais point de bacilles visibles. Sort du lazaret le 29 Septembre. Nouvel acces palustre le meme jour. Observation II. — D... J... a eu, un mois auparavant, au retour de l’lndo-Chine, un der- nier acces franchement palustre. En service au lazaret depuis le 28 Aoiit, il fait le ler Sep- tembre l’autopsie que nous venons de relater. II presente le soir m6me une elevation de temperature (38°5) qui parait devoir 6tre rapportee a l’infection palustre preexistante et subit le meme jour Linjection de 20 centi- metres cubes de serum antipesteux; l’injec- tion est repetee le 3 Septembre. Le 5, appa- rition de malaises et de courbatures intenses; le 8 se montre une adenite inguinale droite du volume d’une olive, presque indolore, avec empatement de l’aine. Les jours suivants, poly- adenite s'etendant aux deux aines et a l’aisselle gauche, dypsnee; acces de fievre le 11 (38°5) et le 13 (38°2). Le 15, l’examen du sang decele l’existence de nombreux bacilles a espaces clairs, de forme plutot allongee, ne prenant pas le Gram. On ne trouve pas d’amibes de Laveran a cet examen d’ailleurs pratique dans une periode d’apyrexie. La convalescence est lente ; asthenie cardio- vasculaire persistante. C’est le premier cas interieur. On a sans doute releve deja les deux memes faits saillants dans chacune des deux observations qui precedent : presence dans le sang de bacilles, complication de palu- disme. Le premier de ces faits est en contradic- tion avec ce qui a ete observe par les auteurs qui ont fixe dans ces dernieres annees 1’ana- tomo-pathologie microscopique de la peste ; ils ne signalent, en effet, la presence des ba- cilles dans le sang qu’en des cas rares et tres graves. Le bacille trouve par M. Kitasato dans le liquide sanguin nous parait etre hors de cause, puisque ce savant lui attribue comme carac- tere de se colorer par le Gram, ce qui n’est pas le cas ici; les essais d’isolement operes chez les malades deja satures d’ailleurs de se- rum ayant ete negatifs, il nous serait difficile d’affirmer plus positivement l’identite de ces elements deja modifies. Nous nous contenterons done d’indiquer que dans certains cas realisant le tableau de la peste attenuee, on trouve dans le sang, en assez grand nombre, des bacilles ayant une morphologie et des reactions colorantes tres analogues, sinon identiques, a celles du ba- cille de Yersin. Mais peut-6tre la raison de cette particula- rite doit-elle etre chercliee dans la nature du terrain, autant que dans celle du germe, et, precisement dans la coexistence du paludisme que Ton vient de noter et que nous signale- rons plus bas chez un malade encore. Ne faut-il pas soupconner sous l’influence de 1’impregnation malarienne, une mise en defaut de la protection phagocytaire a la porte d’entree, et un certain degre d’infection san- guine par unbacille d’ailleurs moyenneraent vi- rulent ; puis la fonction de defense se repre- nant sous Taction du traitement specifique, se multipliant avec la polyadenite qui tend a se generalise!'1 ? II semble d’ailleurs que, si Tinfestation 1. Chez le malade Car..., ou 1’infection baeillaire du sang ne put etre revelee que par l’inoculalion, l’adenite etait unique, mais tres developpee. C’etait de la micro- polyadenite chez le malade J..., oil l’examen direct des preparations du sang montrait de nombreux bacilles. La reaction ganglionnaire manquait totalement par contre chez le malade qui succomba. anterieure du sang par les protozoaires du paludisme a grandement favorise l’invasion par les cocco-bacilles, ceux-ci Font ensuite largement rendu aux premiers, d’ou des ac- ces palustres a apparence de rechute. Et alors on pense a une grande similitude entre ces formes cliniques et celle si bien etudiee par M. Thiroux a la Reunion, et dont M. Roux a confirme a son tour la nature pesteuse. Si les lesions lymphangitiques ont £te ici moins manifestes, nous retrouvons en revanche la virulence attenuee pour Fhomme et pour les rongeurs, la marclie trainante a rechute, les connexions avec le paludisme, parallelement auquel cette affection reparait subitement a la Reunion. Tour a tour decrite sous les noms de : fievre de Bombay, fievre intermittente, remittente, continue, pernicieuse, bilieuse, fievre de famine, fievre a rechute bilieuse, hmphite grave, et causant a Bourbon de rares deces chaque annee, elle tue a Maurice plu- sieurs milliers de personnes en quelques mois l. 1. Nous rapprocherons simplement ces faits de celui De ces formes d’infection si souvent de crites sans 6tre identifies avant l’ere du mi- croscope, la derniere dc nos observations que voici ne pourrait-elle etre donnee comme une •esquisse ? Observation III. — D... G... a presente au cours de sejours reiteres aux colonies des ma- nifestations non douteuses de paludisme, mais les derniers acces remontent a huit ans; il a subi le ier septembre la vaccination par le serum de Yersin et prend le service du laza- ret de Ratoneau le 7 du meme mois. Le 17, une douleur assez vive a l’aisselle droite fait decouvrir l’existence d’un ganglion de la gros- seur d’une noisette. La temperature atteint a peine 38°, les pbenomenes generaux sont assez peu accuses : anorexie, langue jaune, dysenterie. Les jours suivants, adenites multiples aux deux aisselles et aux aines, dyspnee amenant a pratiquer une injection intra-veineuse de signale par M. Metin, d’apres Stevenson, que 1’inoculation Hafkinienne a paru a l’ile Maurice preserver du paludisme des personnes qui en avaient souffert depuis des mois entiers. 20 centimetres cubes cle serum. Au huitieme jour, retour de la fievre, qui afi'ecte la forme remittente atteignant le soir entre 38°5 et 39°. L’examen du sang pratique a ce moment revele l’existence d’amibes de Laveran, et le traitement quinique institue fait disparaitre rapidement ces phenomenes febriles, tandis que la polyadenite persiste longtemps avec des retours de dysenterie. C’est le dernier cas observe, ce qui porte a huit le chiffre total de ceux releves en cours de route ou au lazaret du Frioul. De ce nombre, cinq ont ete observes par nous, parmi les- quels trois etaient compliques de manifesta- tions palustres. II parait probable que pour chacun de ces trois derniers cas il s’est agi d’un reveil de microbisme latent plutot que d’une inocula- tion tres recente des protozoaires de la mala- ria. En eflfet, les moustiques captures parmi ceux qui tourmenterent constamment le per- sonnel interne, examines par M. Troussaint, etaient uniquement des echantillons de culex pipiens; et le paludisme n’ajamais ete observe sur les rochers du Frioul1. Trois des ma- lades en question avaient eu anterieurement des manifestations palustres certaines. Pour vn quatrieme (D... B...), qui n’a presente ces accidents qu’a une epoque ulterieure, mais apres avoir frequente dans l’intervalle une region suspecte, il venait au moment de son atteinte pesteuse de visiter toute la c6te de Syrie, oil se trouvent reunies, toutes les con- ditions du paludisme. Nous n’en croyons pas moins que les rnous- tiques d’une facon generale aient pu jouer un rdle assez actif dans l’extension de la maladie ; et il est grand temps de nous demander com- ment a pu naitre et se propager l’epidemie qui nous occupe. L’origine premiere ? Il serait difficile de l’indiquer de maniere positive. D une part, l’indigene Nisham A., qui fut le premier at- teint, venait d une region ou la peste n’avait 1. L’un de nous a repris au printemps l’examen des. generations nouvellement ecloses. Nous avons toujours constate non les longues baguettes maxillaires des ano- pheles, mais les palpes en courts moignons des culex P, ou quelque autre variete al’abri du soupcon. point ete signalee : d’autre part, si ce malade parait nettement avoir ete l’agent de contami- nation pour M. B..., et consecutivement pour l’officier qui donna ses soins a ce dernier, la connexite est moins aisee a etablir entre ces cas et ceux des deux chauffeurs. M. le direc- teur de la sante, fait remarquer au cours de son enquete qu’un grand nombre de rats avaient ete jetes a la mer dans deux voyages precedents. « II est fort probable, dit M. Catelan, que l’epidemie a eu pour origine la migration des rats contagionnes dans une des relaches aux ports de l’Egypte ou de la Syrie, ou les cas de peste avaient ete constates au cours des mois precedents ». Quel qu’ait ete d’ailleurs le point de depart, la transmission d’homme a homme semble difficile a mettre en doute pour un certain nombre de cas; et pour ne parler que de ce que nousavons observe au lazaret, ou les para- sites ordinaires des habitations et de la literie n’ont jamais ete signales, non plus que les rats, dont on n’a point trouve de cadavres, nous ne voyons guere a incriminer que les culex comme cause des deux cas interieurs. La forme septic^mique que rev^tait plutot l’in- fection se pr^tait bien, on en conviendra d’ailleurs, a ce mode de transmission. Si les exemples n’en ont pas ete plus nombreux c’est, pensons-nous, que le germe en voie d’attenuation n’a plus trouve de sujets mis en etat de moindre resistance par la malaria; et sans doute ne s’en est-il fallu que de quelques anopheles pour que nous voyions s’etablir de facon plus durable une de ces formes mixtes auxquelles conviendrait le nom de pesto- malarienne, qui n’a fait que s’ebaucher sous nos yeux. ★ En ce qui concerne la therapeutique et la prophylaxie, ainsi que l’indiquait M. le pro- fesseur Proust dans son rapport al’Academie, Faction curatiye du serum antipesteux employe a haute dose nous a paru indeniable (le seul cas termine par la mort est celui qui n’a pu etre traite par le serum). Nous avons constate la se- dation des douleurs ganglionnaires et l’abaisse- ment de Facme-thermique due a Finfection spe- cifique. Quand une elevation de la temperature a ete notee apres l’injection pratiquee en apy- rexie, nous avons pu deux fois etablir bacte- riologiquement que cette poussee febrile etait fonction d’une complication palustre. Si nous observances d’ailleurs assez regulierement l’apparition de l’acces malarien dans les heures qui suivaient chez certains de nos ma- lades l’injection de serum antipesteux, nous sommes tres portes ay voir simplement le cas particulier de ce fait general, assez connu, que 1’efFet immediat d’une serotherapie quel- conque est souvent la determination de l’acces chez les sujets en puissance de paludisme. II nous a paru d’ailleurs dans un cas -de haute gravite (M. B.), avec infections secon- daires multiples, que l’emploi de serum artifi- ciel etait une ressource non negligeable. L’injection intra-veineuse de serum anti- pesteux suivant la technique indiquee par M. Calmette est aisee et nous a semble ne devoir offrir aucun inconvenient, aseptique- ment et soigneusement conduite. Au point de vue preventif, le caractere plutot attenue de l’epidemie regnante et l’atypie clinique n’ont permis qu’un emploi tres restreint cle la vaccination; le personnel s’y est generalement refuse. II est a craindre que l’on ne trouve a cet egard une resistance * regrettable au debut d’une epidemie. Netter, Mauson, citent les cas de Cob et Simpson dans l’lnde quinous paraissent tres analogues a ceux-ci, et oil un cocco-bacille existait dans le sang. La nature pesteuse en fut tres dis— cutee et ces cas n’en furent pas moins suivis d’une epidemie aussi severe que legitime. A propos de quoi Manson fait remarquer que rien ne permet de prevoir ce que deviendra peut-etre a bref delai la virulence d’une epi- demie pesteuse a un instant donne. Le fait observe par nous d’une infection d’ailleurs tres legere au seizieme jour apres la vaccination serait en plein accord avec ce que M. Yersin a constate touchant la duree de protection certaine conferee par l’injectionde serum, laquelle ne depassait pas dix jours. M. Pellissier, interne des hopitaux, avait subi quarante-liuit heures avant son isolement la vaccination halkinienne a l’aide de cultures prepares par M. le professeur Rietsch, et a vingt-quatre heures de distance, l’inoculation de serum Yersin. II n’a eprouve aucune reac- tion penible et a joui constamment d’une sante parfaite. L’experience est plut6t rassurante quant aux dangers d’importation du mime genre par voie maritime; la serie aurait, ce semble, les plus grandes chances de s’eteindre dans les lazarets. Celui de Ratoneau, bien isole sur un promontoire du petit archipel du Frioul, realise les conditions les plus heu- reuses. De meme, les mesures d’hygiene et de di- sinfection employees contre toute maladie infectieuse paraissent devoir se montrer plei- nement efficaces a etouffer un foyer urbain avant que la contagion ait pu se transmettre aux rats : ce dernier point, comme on le sait, modifie singulierement le pronostic d’une epi- demic et sa duree Mais il faut de toute neces- sity que Ton soit assure de la declaration par le medecin traitant de tout cas suspect, afin que l’expertise bacteriologique immediate en puisse itre faite. II n’est pas hors de propos d’ajouter que dans les cas oil la region serait infestee de moustiques, il y aurait lieu d’employer contre ces insectes les mesures qui ont un succes si complet dans la prophylaxie du paludisme en . ltalie. ★ * ■¥■ Telles sont les quelques notes recueillies au cours de notre periode d’isolement. Nous n’ignorons pas qu’elles sont loin de remplir toujours le cadre qui serait celui d’une etude au laboratoire; les exigences et les incidents du service d’un lazaret s’y pr^tent parfois assez mal. Nous gardant de tirer des conclu- sions trop hatives, nous avons cru devoir apporter neanmoins ces faits peu nombreux mais obeissant, on l’a remarque, a une regie de position qui leur donne quelque valeur logique. Ainsi relies entre eux, ils tracent assez nettement une ou deux directions prin- cipals de recherches, que nous voulions seu- lement signaler, a savoir : la determination des associations morbides oil entrerait 1’agent pesteux et de leur expression clinique; la verification de l’hypothese oil ce micro-orga- nisme avec des modifications de sa virulence offrirait parfois des variations dans ses carac- teres biologiques et ses modes de transmis- sibilite. Paris. — L. Maretheux, imp., 1, rue Cassette.