Tropical Diseases/Chapter 20

by Patrick Manson

CHAPTER XX

PLAGUE

Definition.— Plague is a specific, inoculable, and otherwise communicable epidemic disease common to man and many of the lower animals. It is characterized by fever, adenitis, a rapid course, a very high mortality, and the presence of a specific bacterium, Bacillus pestis, in the lymphatic glands, viscera, and blood. In a large proportion of cases buboes form in the groins, armpits, or neck.

Geographical distribution.— Though not necessarily confined to warm climates, in modern times plague, like leprosy, has practically become so. The hygienic conditions which advancing civilization has brought in its train have forced back these two diseases from Europe, where at one time they were even more prevalent than they are in their present tropical and sub-tropical haunts. Plague and leprosy are typical examples, of that large group of acute and chronic germ diseases whose spread depends on social and hygienic rather than on climatic conditions, and more especially on the verminous accompaniments of filth and overcrowding: conditions which nowadays are found, to an extent and an intensity sufficient to ensure the endemic prevalence or epidemic extension of these diseases, for the most part only in warm countries.

It is difficult to say what the pestis of the ancients may have been. Probably in many instances it was bubonic plague; doubtless the term was sometimes applied to other epidemic sicknesses attended with a large mortality.

The descriptions which have come down to us of these old-world epidemics are too vague for recognition. According to Hirsch, the first recognizable description of what is now understood by plague refers to its occurrence in Libya, Egypt, and Syria about the end of the third and the beginning of the second century before the Christian era. The next authentic account, and the first as regards Europe, refers to the great epidemic known as the plague of Justinian, which, in A.D. 542, starting from Egypt, spread to Europe and all over the Roman Empire, and which, lasting for fifty or sixty years, wrought the most frightful devastation wherever it reached, depopulating the towns and turning the country into a desert. From that time until 1841, when plague appeared for the last time in Constantinople, it recurred again and again in different parts of Europe, though latterly only in the south-eastern parts of the continent and in areas becoming gradually more circumscribed. In 1878-79 a small epidemic, which speedily died out, broke out in the Russian province of Astrakhan. With the latter exception and the limited epidemics at Oporto in 1899 and at Glasgow in 1901, and a few isolated and mostly imported cases at the large seaports, Europe has long enjoyed exemption from this worst of epidemic diseases. The plague, as a widespread epidemic, visited England for the last time in 1664-79, when, in 1664-65, upwards of 70,000 of the 460,000 inhabitants of the London of that day perished. In recent years and from time to time cases of plague have occurred in the Port of London in seamen from Eastern countries, and plague-infected rats are by no means uncommon in the docks of the metropolis, but with the exception of a limited epizootic in rats and rabbits and several fatal cases in man in 1910 in Suffolk there is no record of plague in England, apart from the cases occasionally seen in the seaports, since the seventeenth century.

Egypt, in former times a favourite haunt of the disease, until 1899 had been exempt since 1844, although several epidemics have since the latter date occurred in its neighbourhood in Tripoli (Benghasi) in 1856, in 1859, and in 1874; and on the Red Sea coast of Arabia (Assir) from 1853 to the present time. It is now known to be endemic in Uganda and in the hinterland of German East Africa. Many epidemics have occurred in Mesopotamia (last in 1892), in Turkestan (last in 1892), in India, in China, and in Mongolia. In India there were several outbreaks during the nineteenth century, but, with the exception of the current epidemic, they were of a localized rather than of a general character. One, beginning in Cutch in 1815, spread to Scinde and Gujerat, and continued till 1821. Epidemics have also occurred in Kumaon and Gharval on the southern slopes of the Himalayas in 1824, 1834-37, 1846-53, 1876, and 1884; also at Hansi in Delhi, 1828-29. In 1836 it appeared at Bareilly, Rohilcund, and at Pali in Rajputana, spreading to Jodhpore and to Marwar, and continuing till 1838. Probably plague is always present in some part of India, especially among the rude hill-peoples.

It is now known that plague has been endemic in the south-west of China, in the province of Yunnan, for many years. It is probable that the present extension of plague had its origin in that part of China. There it was seen by Rocher and others in 1878 and afterwards. It was particularly active in 1871-73, after the great Mohammedan rebel-lion. From Yunnan, probably following the trade route, it spread to Pakhoi on the Gulf of Tonquin, a severe epidemic occurring in 1883 in that and in neighbouring towns. In 1894 it had extended to Canton, where it killed, it is estimated, 60,000 in a population of 1,500,000 (?). Later in the spring of the same year it broke out in the British colony of Hong Kong, subsequently spreading to Macao, Swatow, Amoy, Foochow, Formosa, and probably to many other places in the southern provinces of the Chinese Empire, where, in one place after another, considering the wretched hygienic conditions and the poverty of the inhabitants, it is safe to prophesy that plague will continue epidemic for many years to come. Japan and the Philippines were both infected from China.

Having probably been imported from Hong Kong, appeared in 1896 at Bombay, and subsequently as a great epidemic spread to Calcutta, and to many other parts of India, where it still prevails. The mortality from the current epidemic is numbered in millions.

Soon after its appearance in India, plague became extensively epidemic in Mauritius, where it still prevails at certain seasons. Mombasa and British East Africa (including Nairobi), the West African colonies, Madagascar, Delagoa Bay, Cape Town, Port Elizabeth in Cape Colony, and Durban; also Sydney and Brisbane in Australia, and Alexandria in Egypt, have all been invaded.

Until its recent appearance in Brazil, the Argentine and other South American countries, in San Francisco and Mexico, plague had never invaded the western hemisphere.

Etiology. The micro-organism.— The proofs are now complete that the specific cause of plague is the cocco- bacillus which was discovered first by Kitasato and afterwards, independently, by Yersin during the Hong Kong epidemic in 1894. This microbe occurs in great profusion in the characteristic buboes —generally in pure culture, although towards the later stages it is often associated with the streptococci and staphylococci of suppuration. It is present, besides, in great abundance, in the spleen, intestines, lungs, kidneys, liver, and other viscera, and also, though in smaller numbers, in the blood. In the pneumonic type of the disease it is present in the sputum in enormous numbers. It occurs also in the urine and fæces; in the latter, though detectable by inoculation and by cultivation, the bacillus may be hard to find by direct observation. Towards the termination of rapidly fatal cases it may become so abundant in the blood as to be readily observed there with the microscope.

The plague bacterium (Fig. 66), as seen in smearings or scrapings from the pulp of the buboes, or from any of the inflamed lymphatic glands, or from the viscera, is a short, thick cocco-bacillus (1.5 to 2 μ and 0.5 to 0.7 μ) with rounded ends, very like that of chicken cholera. Gordon says it has one terminal flagellum. A capsule, according to the same observer, or the appearance of a capsule, can generally be made out, especially in those bacilli which are present in the blood. The bacillus is readily stained by aniline dyes, the extremities taking on a deeper colour than the interpolar part. It is usually decolorized by Gram.

Culture characters.—When sown on blood serum and kept at body temperature, in from twenty-four to forty-eight hours an abundant moist, yellowish-grey growth is formed without liquefaction of the culture medium. On agar, but better on

Fig. 66.—Bacillus of plague in chains showing polar staining. From a young culture in bouillon, x 1,000. (Muir and Ritchie.)

glycerine agar, the growths have a greyish-white appearance. In agar plate cultures they show a bluish translucence, the individual colonies being circular, with slightly irregular contours and a moist surface; on mannite neutral-red-bile-salt agar the colonies are bright red, but are colourless on a similar medium in which lactose is substituted. Litmus-milk and glucose-broth are rendered slightly acid, lactose-broth is unchanged. Young colonies are glass-like, but older colonies are thick at the centre and more opaque; they are singularly coherent and may be removed en bloc with a platinum needle. Stab cultures show after one or two days a fine dust-like line of growth. According to Yersin, when sown on gelatin the bacillus gives rise to white transparent colonies which, when examined in reflected light, present iridescent borders. In bouillon the cultures present a characteristic appearance the liquid remains clear, whilst a granular deposit takes place on the sides and bottom of the tube. Cultivated on brothin which clarified butter or coco-nut oil is floated, B.pestis presents characteristic stalactite growths which gradually fall off, forming a granular deposit. Examined with the microscope, these various cultures show chains of a short bacillus, presenting here and there large bulbous swellings. In gelatin the bacilli sometimes form fine threads, sometimes thick bundles made up of many laterally agglomerated bacteria. The bacillus does not produce spores.

The most favourable temperature for culture is from 36° to 39° C.

Intensification and attenuation of virus. —There can be no question that, both by artificial means and in a natural way, the virulence of the bacillus of plague is susceptible of modification. It has been remarked in Russia, in Persia, and in Calcutta that certain outbreaks of plague were preceded by a sporadic or epidemic febrile, sometimes afebrile, affection, in the course of which the lymphatic glands became enlarged and perhaps suppurated. Cases of this nature, in which a bacteriological examination proved that a cocco-bacillus was present in the blood and enlarged glands, are recorded by Drs. Cobb and Simpson. It is further known that in some instances the virulence and case-mortality of a plague epidemic show a tendency to decrease, the early cases being the most frequently and most rapidly fatal.

Recent observations in India have brought to light a form of chronic plague in rats, in which the specific bacterium, without seriously affecting the health of the animal, remains latent for long periods in abscesses in connection with spleen, liver, or abdominal lymphatics. Although thus latent, it is potentially virulent, proving lethal when cultures obtained from these abscesses are injected into other animals. These facts seem to indicate that under certain unknown natural conditions the virus tends to acquire increased potency, whilst in other circumstances its virulence tends to diminish.

This conjecture is countenanced by the results of experiment on animals. It has been shown that by passing the virus by inoculation from one guineapig to another the rate of its action becomes accelerated. On the other hand, Yersin remarks that, although it is difficult to start a gelatin-peptone cultivation, nevertheless, when obtained, such a cultivation at all events certain parts of such a cultivation will be found to be quite as lethal as virus derived directly from a bubo. He further observes that in such cultures a proportion of the colonies develop more rapidly than others; that if inoculation is made from these more rapidly developed colonies, virulence is found to be diminished; and that if these rapidly growing cultures are frequently repeated, in the long run they cease to be fatal to guineapigs, although they may still prove fatal to white mice.

These and other natural and experimental data indicate a very pronounced tendency to mutability as regards virulence on the part of the plague bacillus: a disposition which, in the future, may very well be turned to important practical account.

It would appear that the gravity of an attack of plague is not affected by the amount of virus introduced. Barber, using an ingenious apparatus, infected guineapigs, each with a single bacillus. The resulting disease was as fatal as that produced by an injection of 500 bacilli.

Experimental plague. Inoculation.— Intentional and unintentional experiments have proved the inoculability of plague in man. Whyte in 1802 communicated the disease to himself, and died of it. At Cairo, in 1835, two condemned criminals were inoculated from the blood of plague patients; they contracted the disease, but recovered. The value of these experiments, as proving inoculability, is somewhat depreciated by the circumstance that they were made in the presence of an epidemic of the disease. Ordinary methods of infection cannot be said, therefore, to have been absolutely excluded. For the same reason the cases of Aoyama and his assistant, who were believed to have contracted the disease from dissection wounds, cannot be held as proving that plague is inoculable in man. The deplorable accident in a Vienna laboratory, in October, 1898, by which fatal plague of a pneumonic type was acquired— in what way is not exactly known— from manipulations with plague cultures goes far to complete the little that was wanting in the chain of evidence that this disease is caused by the introduction of the specific bacillus into the human body. The unintentional experiment, in this instance at all events, was not vitiated by having been made in the presence of a plague epidemic.

There is no reason for supposing that man differs in this respect from the lower animals, many of which are exceedingly susceptible to inoculation. Mice, rats, guineapigs, and rabbits are invariably killed if successfully inoculated from the buboes*^[1] of plague patients. They present on dissection characteristic lesions with numerous bacilli in the lymphatic glands, blood, spleen, and other viscera. Guineapigs die in from two to five days after inoculation, mice in from one to three days. Calves and swine are susceptible to inoculation, and so are monkeys and many other animals.

In the case of the guineapig, within a few hours of the introduction of the virus a considerable amount of œdema is already apparent around the puncture, and the adjacent gland is perceptibly swollen. At the end of twenty-four hours the animal is very ill; its coat is rough and staring, and it refuses food. Presently it falls on its side and becomes convulsed, one fit following another with increasing frequency as death approaches. If the body is opened immediately after death a rosy-red sanguineous œdema is found at the point of inoculation, with hæmorrhagic inflammatory effusions around the nearest lymphatic gland, which is much swollen and full of bacilli. The intestines are hyperæmic; the adrenals, kidneys, and liver are red and swollen. The much enlarged spleen frequently presents an eruption of small whitish granulations resembling in appearance miliary tubercles. All the organs, and even any serous fluid that may be present in peritoneum or pleura, will be found to contain plague bacilli. In the blood, besides those free in the liquor sanguinis, bacilli are to be found in the mononuclear, though not, it is said, in the polynuclear leucocytes.

Feeding experiments.— Rats or mice fed on cultures of plague bacilli, or on fragments of the liver or spleen of animals dead of plague, acquire the disease, and generally die with the characteristic symptoms and lesions. Similarly, as has been shown by Simpson, pigs, calves, sheep, monkeys, hens, pigeons, turkeys, geese, and ducks are affected with plague when fed on plague material. The type of plague induced by feeding is the septicæmic. The disease thus induced may be either of an acute or of a chronic nature. When the latter, it may be ill defined and not easily recognized. Thus, pigs may show no marked signs of illness until a month after feeding on infective material, and then only a few days or hours before death. Susceptibility to plague of the animals of the farmyard, and the chronicity and ill- defined nature of the disease which not infrequently occurs among these animals, as well as in rats, are likely to be important factors in continuing the disease in those endemic centres where people, cattle, pigs, and poultry, in addition to the ordinary domestic vermin, are housed under the same roof, and even in the same room.

Rôle of the rat in plague.— Although small and circumscribed epidemics of plague may occur without the intervention of the rat (Hossack), there can be no doubt that in most epidemics of the bubonic form this ubiquitous rodent plays an important part, both in the introduction and in the spread of the infection. The species principally concerned are Mus decumanus and Mus norvegicus (the grey rat) and Mus rattus (the black rat). The bandicoot and musk rat are of little importance in these respects, although susceptible to the infection. In Bombay the epizootic appears first in the Mus decumanus community, Mus rattus—the more domestic species—being subsequently attacked. Later the disease appears in epidemic form in man. (Chart 5.)

The seasonal prevalence of bubonic plague in rats

Chart 5, Showing progress of plague in rats and mice. (After Glen Liston.)

is marked, and is not due to a periodicity in their reproduction, but is connected with periods in which fleas are most numerous.

The ancients were well aware of the connection between plague and the rat. In the Bible the rat is mentioned in association with the plague which broke out amongst the Philistines after they stole the Ark of the Covenant. The Greeks of Asia Minor worshipped a rat-killing Apollo who was reputed to bring and remove plague epidemics. Sambon describes a coin of Lucius Severus, struck at Pergamum in Asia Minor at the time of a great plague epidemic. On the obverse of the coin is the god of medicine, Æsculapius, having at his feet a dead rat and at his side a naked human figure in an attitude of terror or supplication. Mediæval literature likewise contains abundant proof that the association of rats with plague was well recognized even in the dark ages. Many modern observers also have remarked the great mortality among rats and other animals which generally precedes and accompanies outbreaks of plague in man. When writing about the mortality among rats during the recent Canton epidemic, Rennie remarks that the Chinese regarded this unusual and striking occurrence as a sure indication of an extension of the epidemic. From districts of the city where the plague had been raging for some, time the rats entirely disappeared, whilst they kept on dying in other quarters to which the disease afterwards spread. The rats, he says, would come out of their holes, in broad daylight even, and tumble about in a dazed condition and die. In a very short time one Chinese officer alone collected upwards of 22,000 dead rats.

Glen Liston states that in places in which plague epidemics keep recurring year after year the local rats acquire a considerable degree of immunity, and, moreover, that this immunity is transmitted hereditarily. Thus in plague-free towns in India— e.g. Madras and Dacca— plague-inoculated Mus rattus gave a mortality of 90 to 100 per cent.; in plague- stricken towns— e.g. Cawnpore and Poona— it was only 20 to 40 per cent.

Another observation, already referred to, which together with the foregoing may have important bearings on the spread of plague and the yearly recurrence of epidemics in the same place, is to the effect that in certain rats the disease may assume a chronic form, the bacillus becoming more or less latent in the lymphatic glands, at the same time being capable of resuscitation into active pathogenicity.

Rocher states that in Yunnan the mortality among the rats is particularly noticeable. Other animals also die, he says; oxen, sheep, deer, pigs, and dogs are all attacked at times, the dog less severely and less frequently than the others.

Pringle says that in Shurwal, Himalayas, where in 1864 plague was epidemic, the rats quitted the various villages in anticipation of the advent of the disease, and that the people, taught by experience, on seeing this exodus recognized it as a warning.

Clemow has pointed out the connection of Mongolian and Siberian plague epidemics with the occurrence of the disease in a species of marmot, called tarbagan (Arctomys bobac), common and much hunted in these regions. This animal can harbour the plague bacillus in its body without apparently suffering any ill effects during hibernation, thus constituting a more or less permanent reservoir of the plague virus.

Schurupoff reports the ground squirrel of the Caucasus (Spermophilus guttatus) as being extremely susceptible to plague infection, and as probably concerned in the spread of the disease in that region. In California the ground squirrel (Citellus beechyi), although it does not live near human habitations, infects rats that do, and thereby acts as an important reservoir of B. pestis. It has been ascertained that in this instance the flea, Hoplopsyllus anomalus, which infests both animals, acts as the carrier of the plague bacillus from one to the other, the infection being ultimately transmitted to man by the rat- fleas (see below).

These and many similar facts observed in Bombay, Sydney, Cape Town, and Hong Kong with regard to plague in the lower animals throw important light on one of the ways in which the disease is spread. They, together with the results of the several experiments already alluded to, have to be reckoned with in the future, more than they have been in the past, in devising schemes of quarantine and in attempts at stamping out the disease in already affected localities. The wholesale destruction of domestic vermin should go hand in hand with the isolation of plague-stricken patients.*^[2]

The role of the flea in plague.— Yersin placed in the same cage healthy and plague-inoculated mice. The latter died first; but later the originally healthy uninoculated mice also succumbed proving that plague is communicable either through the atmosphere, by contact, or by ectozoa.

Yersin's experiment has been successfully repeated again and again, on mice, rats, guineapigs, and monkeys, and with many modifications. The result has been indisputable confirmation of Yersin's results, and further proof that bubonic plague is not communicable from animal to animal by simple confact or by atmospheric convection, but that it is readily communicated by ectozoa, especially rat-fleas —principally Xenopsylla cheopis †^[3] (Fig. 67) which act as passive intermediaries and carriers of the bacillus. Zirolia and others have found that Bacillus pestis multiplies in the stomach of the flea, retaining its virulence for over twenty days and being passed out in the fæces; so that the flea serves not only as a carrier, but also as a multiplier of the germs.

Especially convincing are the experiments of the Indian Plague Commission,^[4] which clearly show that if fleas are excluded healthy rats will not contract the disease, even if kept in intimate association with plague-infected rats. Young rats may even be suckled by their plague-stricken mothers and remain healthy. But if fleas are introduced, whether naturally or intentionally, into the field of experiment, plague at once begins to spread from rat to rat, and with a rapidity in proportion to the number of fleas present. The Commission has shown further that an epizootic of rat plague may start without contact or even proximity of healthy and
Fig. 67.—Xenopsylla cheopis. infected animals. It suffices to transfer fleas from a plague animal on to a healthy animal, or to place the latter in a room in which plague rats have died recently and been subsequently removed. The fleas that have left the body of the dead rats, remaining in the room, convey the germs. The atmosphere of the room is not infective; for if the experimental animal be suspended in an open cage a few feet above the floor, it does not become infected. Nor is the animal infected if placed on the floor, if the precaution be taken to surround the cage with "tangle foot" so as to keep off the fleas. But if it be placed on the unguarded floor, either in its cage or allowed to run about, or even if it be suspended two inches above the floor—a distance not beyond the saltatory powers of the flea—it will become infected. The Commission obtained practically the same results in experiments with guineapigs in plague-infected houses. It is therefore no longer open to question that the important—probably the most important—agents in the development and perpetuation of plague epidemics are the rat, and the rat-flea, Xenopsylla cheopis, and other fleas, such as Ctenocephalus canis (Fig. 68), which is known to bite dog, man, and rat indifferently. This important conclusion is completely supported by the elaborate epidemiological observations of Ashburton Thompson in Sydney, who has shown that the rat-flea theory best explains the behaviour of epidemic plague—at all events in that city.

The flea communicates the plague bacillus either on its fouled mandibles, or by regurgitation of the contents of its stomach during the act of sucking, or by provoking scratching and consequent inoculation of the bacilli deposited in its fæces on the skin.

Fig. 68.—Ctenocephalus canis (female). C. J. Martin's observations on plague-infected fleas are of great interest. He found that a proportion of the fleas fed on plague-infected rats develop a peculiar pathological condition of stomach and œsophagus, these organs becoming blocked with blood-clot containing a pure culture of B. pestis. When such a flea feeds on a normal rat, part of the culture regurgitates and communicates infection; at the same time bacilli are passed in the fæces and may infect through any existing abrasion. He further observed that the "blocked" fleas died very rapidly if placed in a warm, dry atmosphere, apparently of thirst. (Figs. 69, 70.)

In temperate climates fleas are most numerous during the warmer seasons of the year; hence summer and autumn is the bubonic plague season in such climates. In warm climates bubonic plague is most prone to become epidemic at those times of the year in which temperature ranges between 10° and 30° C. temperatures favourable to the multiplication and activity of the flea. Temperatures over 30° C. are unfavourable to the flea, especially if the atmosphere is dry. Pneumonic plague, not being spread by the flea, is not influenced by temperature in this way (see p. 344).^[5]

Bionomics of the rat-flea.—In ordinary circumstances the rat-flea completes its developmental cycle in fourteen days to three weeks, but in warm, damp weather this may be shortened to ten days. The average life of a flea, apart from its host, is about ten days, but it is capable of remaining alive without food for two months, should the temperature of the

Fig. 69.—a, Flea viewed as a transparent object. The proventriculus and stomach contain a mass of plague culture. b, Flea's stomach obstructed by growth of plague culture.

ŒS., Distended œsophagus containing fresh blood; P.C., obstructing mass of plague culture.

air be low at the time. In tropical temperatures the insect can harbour the plague bacillus without feeding on blood for forty-five days.

Apart from the very serious danger arising from vermin affected with chronic plague, which may hang about a house for a long time, it would appear that the house itself does not retain the infection for any length of time. The Plague Commission has shown that floors of cow-dung if contaminated with Bacillus pestis do not remain very infective for more than forty-eight hours, and that floors of chunam cease to be infective in twenty-four hours.

Conditions favouring naturally acquired plague.—The most potent circumstances which predispose to the epidemic outbreak of plague are extreme filth and overcrowding. In such circumstances the virus, once introduced, tends to spread. These conditions, however, are not all-sufficient, for even in the filthiest and most crowded oriental towns, and without any apparent

Fig. 70.—Edge of a mass of plague culture from flea's stomach. Microphotograph x 1,000.

Figs. 69 and 70 illustrate the method of transmission of B. pestis by Ceratophyllus fasciatus. (By kind permission of Dr. C. J. Martin, "Journ. of Hyg." 3rd Plague Suppl., Jan., 1914.)

alteration in the habits or circumstances of the population, the disease, after having become epidemic, dies out spontaneously. It may be difficult to indicate the exact way or ways in which filth and overcrowding operate; but certain it is, as experience has shown, that in good sanitary conditions plague does not spread even if introduced, and that in opposite conditions it may for a time spread like wildfire.

Filth and overcrowding imply close proximity of the sick and the healthy; an atmosphere saturated with the emanations of the sick; a lowered tone of the general health; saturation of the soil and of the surrounding media with animal refuse; abundance of body vermin of all kinds, as well as of other vermin, such as rats and mice, which serve as multipliers of the virus; carelessness about personal cleanliness, about wounds of the hands and feet, about clothing, and about food, dishes, and water. One can understand how in such circumstances the germ has opportunities to multiply and spread.

Except in the case of the relatively rare pneumonic form, plague, though " catching," is not nearly so contagious as are scarlet fever, measles, or small-pox. Medical men, and even nurses, in clean airy hospitals rarely contract the disease, provided they have no open wounds and do not remain too long in close proximity to their patients. In cities the cleanly districts are generally spared. This was well exemplified in the recent epidemics at Canton and Hong Kong, where the airy, cleanly European quarters and the relatively clean, well-ventilated boat population were practically exempt, whilst the disease ran riot in the adjoining filthy, overcrowded native houses only a few yards away.

The fact that plague can be communicated to the lower animals by feeding them on the tissues of plague patients and on cultures of the specific bacillus, suggests that the disease may be conveyed to man in food or drink. The bacillus is sometimes found in the intestinal contents of patients. It is also to be found in the urine. Water or food contaminated with sewage or fæcal matter may therefore be regarded as a possible medium of infection. Food contaminated by infected rats is likely also to be a source of danger. In the epidemic of 1902, in Hong Kong, plague bacilli were found in the intestinal contents and mucus of the mouth in about one-third of the plague-infected rats examined, and in the urine in about one-fifth of the cases (Simpson).

The bacilli do not, as a rule, penetrate the unbroken epidermis, as proved by the impunity with which post-mortem examinations in plague cases have often been made; but it seems not improbable that in a proportion of instances the plague germ is introduced through trifling wounds of the feet. It is conceivable that such germs as may be lying about on the ground, deposited there in the discharges of sick human beings or of plague-stricken animals, or perhaps growing there in natural culture, may be picked up in this way. The frequency with which the primary bubo, as will be pointed out, is located in the deep femoral glands favours this idea. One can understand, too, how lice, fleas, bugs, and perhaps flies might act as carriers of the virus from person to person, inserting it with their bites, or inducing scratching and superficial skin lesions, through which the virus obtains entrance.*^[6] Yersin found that the flies in his Hong Kong plague laboratory died in great numbers, their bodies being crowded with the specific bacillus; he injected bouillon containing a trituration of one of these flies into a guineapig, and the animal presently died with all the signs of plague. Sablonowski, who in 1884 in a measure anticipated the discovery of the bacillus by Kitasato and Yersin, remarked that during the Mesopotamian epidemic of that year a certain species of fly appeared and disappeared concurrently with the plague he considered that this insect was an active agent in spreading the disease.

That the plague bacillus does at times enter the body through the unbroken skin or mucous membrane is made highly probable (1) by the absence in the great majority of cases of human plague of evidence of an initial skin lesion; (2) by the success of experimental feeding of animals with plague tissues or cultures; (3) by the ease with which infection is conveyed through the air to man and other animals in pneumonic plague; and (4) by the certainty with which rats can be infected by simply smearing a plague culture on the shaven skin.

Age, sex, and occupation have very little influence in plague. The youngest children are susceptible; old age seems to be to a certain extent protective, the disease being rarer after 50 than during adolescence. Women, doubtless on account of their remaining much indoors in the tainted surroundings, are relatively more frequently attacked than men.

Geological constitution of soil appears to have no direct influence on plague.

Atmospheric temperatures if very high or very low seem to have a repressing effect. Thus, as a rule, epidemics in Egypt and Mesopotamia declined during the height of the very hot and dry summer, and in Europe during the extreme cold of winter. On the other hand, plague on more than one occasion has flourished during a Russian winter, and also, as in Hong Kong recently, during the heat of a tropical summer. On the whole, the evidence points to moderate temperatures— 50° to 80° F.— combined with a certain degree of dampness as being the principal atmospheric condition favouring epidemic outbreaks and recurrences. Manifestly any influence temperature may have is only an indirect one.

In large towns, and in some districts, in which plague recurs for several years in succession, there is a seasonal periodicity (which may not be the same in all places) of maximum and minimum prevalence.

Elevation, as regards sea-level, does not directly affect the general distribution of the disease. Indeed, mountain tribes, probably on account of their poverty and squalor, are peculiarly liable to epidemics. In houses the ground floor is more dangerous than are the upper storeys.

The duration of epidemics of plague is very variable. In large cities— Bombay, Hong Kong, Canton, for example— when fairly established the disease may not relax its grip for ten or more years. In smaller places it may disappear in a few months.

The extension of plague epidemics is peculiar, and in many respects resembles that of cholera. It follows trade routes. Sometimes it may spread rapidly from point to point; more generally it creeps slowly from one village to another, from one street or one house to another, Sometimes it skips a house, a village, or a district, to appear there later on. Particular houses, and even particular floors of houses, may be infected, whilst neighbouring ones remain free from the disease.

These and many other facts in the epidemiology of plague are probably to be explained by the connection of the disease with the rat - flea. When we have fuller information about the migrations of the rat, the breeding seasons of the rat-flea, the influence of food and temperature and other circumstances on these animals, it is reasonable to expect that our knowledge of the principles that underlie the transmission, the spread, and decline of plague will be more satisfactory than it is at present.

Symptoms. Incubation period.— Symptoms of plague begin to show themselves after an incubation period of from two to eight days. It is said that in certain very rare instances the incubation period may extend to as much as fifteen days. It is also said that in highly malignant epidemics the disease may declare itself within three or four hours from the time of exposure to infection.

Prodromal stage.— In a certain but small proportion of cases there is a prodromal stage characterized by physical and mental depression, anorexia, aching of the limbs, feelings of chilliness, giddiness, palpitations, and sometimes dull pains in the groin at the seat of the future bubo.

Stage of invasion.— Usually, the disease sets in somewhat suddenly with fever, extreme lassitude, frontal or, more rarely, occipital headache, aching of the limbs, vertigo, drowsiness or perhaps wakefulness, or troubled dreams. Rigor is rarely a marked feature; ore often the disease is heralded by feelings of chilliness. The face quickly acquires a peculiar expression, the features being drawn and haggard, the eyes bloodshot, sunken and staring, the pupils probably dilated sometimes the face wears an expression of fear or horror. The patient, when he can walk, drags himself about in a dreamy sort of way, or he staggers like a drunken man. There may be nausea and vomiting; in some instances there is diarrhœa.

Stage of fever.— The stage of invasion may last for a day or two without a serious rise of temperature occurring. Usually it is of much shorter duration; or it may be altogether wanting, the disease developing abruptly without definite rigor or other warning, the thermometer rising rapidly to 103° or 104°, or even to 107° F, with a corresponding acceleration of pulse and respiration. The rise of temperature is more gradual than is usual in malarial fevers. The skin is now dry and burning, the face is bloated, the eyes are still more injected, sunken and fixed, the hearing is dulled. The tongue is swollen and covered with a creamy fur, which rapidly dries and becomes brown or almost black; sordes form on the teeth and about the lips and nostrils. Thirst is intense, prostration extreme, the patient from utter weakness being hardly able to make himself heard. Sometimes the patient becomes delirious; more generally he sinks into a state of typhoid stupor and prostration, perhaps picking the bedclothes or trying to catch imaginary objects. The delirium is sometimes wildly furious, sometimes fatuous, sometimes of a low muttering type. Coma, convulsions— sometimes of a tetanic character— retention of urine, subsultus tendinum, and other nervous phenomena may occur. Vomiting is in certain cases very frequent: some are constipated, others have diarrhœa. The spleen and liver are usually both enlarged. Urine is scanty, but rarely contains more than a trace of albumin. The pulse, at first full and bounding, in the majority of cases rapidly loses tone, becoming small, frequent, fluttering, dicrotic, intermittent. In the later stages the heart may be dilated, the first sound being feeble or absent. In many cases, as death approaches, there may be some cyanosis.

Stage of adenitis.— In from about two-thirds to nine-tenths of the cases, some time between the first few hours and the fifth day, generally within twenty-four hours, the characteristic bubo or buboes develop. Usually (in 70 per cent.) the bubo forms in the groin, most frequently on the right side, affecting one or more of the femoral glands; less frequently (20 per cent.) it is the axillary glands, and still more rarely (10 per. cent.), and most commonly in children, it is the glands at the angle of the lower jaw that are affected. The buboes are usually single; in about one-eighth of the cases, however, they form simultaneously on both sides of the body. Very rarely are buboes formed in the popliteal or in the epitrochlear elbow glands, or in those at the root of the neck. Occasionally buboes occur simultaneously in different parts of the body.

The buboes vary considerably in size. In some instances they are not so large as a walnut; in others they attain the size of a goose's egg. Pain is often very severe; on the other hand, it is sometimes hardly complained of. Besides the enlargement of the gland, there is in most instances distinct infiltration of the surrounding connective tissue.

In a very small proportion of cases what are usually described as carbuncles, but which are in reality small patches of moist gangrenous skin that may gradually involve a large area, develop on different parts of the integument. These occur either in the early stage or late in the disease. Sometimes they slough and lead to extensive gangrene.

In favourable cases, sooner or later, after or without the appearance of the bubo, the constitutional symptoms abate with the setting in of profuse perspiration. The tongue now begins to moisten, the pulse-rate and temperature to fall, and the mild delirium, if it has been present, to abate. The bubo, however, continues to enlarge and to soften. After a few days, if not incised, it bursts and discharges pus and sloughs sometimes very ill-smelling. In rare instances suppuration is delayed for weeks; whilst in some the bubo subsides after a few weeks, or perhaps months, without having broken down. Convalescence, when it occurs, sets in some time between the sixth and tenth day, although it may be delayed for a fortnight or three weeks. Occasionally a pysemic condition, with boils, abscesses, cellulitis, parotitis, or secondary adenitis, succeeds the primary fever. The sores left by the buboes and abscesses of plague are extremely indolent, and may take months to heal.

Hœmorrhages of different kinds are not an unusual feature of plague. Ecchymotic effusions of a purplish or dull-red tint, and varying in size from a hemp-seed to spots half an inch in diameter, are very often found scattered in greater or less profusion over the skin, especially on exposed parts of the body and at the sites of insect bites or of wounds. Larger patches of cutaneous hæmorrhagic effusion are rare. There may be bleeding from the nose, mouth, lungs, stomach, bowel, or kidneys. Hæmorrhages occur with marked frequency in certain epidemics; they are regarded as evidence of great malignity. Especially malignant are those epidemics in which hæmoptysis, or pneumonia, is a common occurrence.

Abortion almost invariably occurs in pregnant women; the fœtus sometimes shows signs of the disease.

Death may take place at any time in the course of plague. Usually it occurs between the third and fifth day, with symptoms of profound adynamia, heart failure, or perhaps from convulsions, from coma, from internal hæmorrhage, or, later, from exhaustion consequent upon prolonged fever or suppuration, or from secondary hæmorrhages.

On the other hand, in a certain proportion of cases convalescence sets in and proceeds more or less rapidly. Generally it is a tedious affair, being prolonged by suppuration, sloughing, and similar complications.

The foregoing description applies more especially to the ordinary bubonic (as it is called) type of the disease. Of late, certain other forms of plague have received individual recognition in consequence of their extreme virulence and, in the case of one of these forms, of its high degree of coimnunicability. These forms are called respectively septicœmic and pneumonic.

Scpticæmic plague, sometimes called pestis siderans.— In this type there is no special enlargement of the lymphatic glands apparent during life, although after death the glands throughout the body are found to be somewhat enlarged and congested. The high degree of virulence and rapid course of the disease depend on the entry of large numbers of the bacilli into the blood, where they can be readily found during life. The patient is prostrated from the outset ; he is pale and apathetic; there is no, or very little, febrile reaction (100° F.). Great weakness, delirium, picking of the bedclothes, stupor, and coma end in death on the first, second, or third day. Frequently in these cases there are hæmorrhages.

Pneumonic plague.— This type of the disease, which was carefully studied by Childe and others, is especially dangerous as well as deadly: dangerous because of the multitude of bacilli which are scattered about in the patient's expectoration,*^[7] and because the clinical symptoms are unlike those of typical plague, and are apt to be mistaken for some ordinary form of lung disease. The illness commences with rigor, malaise, intense headache, vomiting, general pains, fever, and intense prostration. Cough and dyspnœa set in, accompanied by a profuse watery blood-tinged sputum. The sputum is not viscid and rusty, as in ordinary pneumonia. Moist râles are audible at the bases of the lungs, the breathing becomes hurried, other symptoms rapidly become worse, delirium sets in, and the patient dies on the fourth or fifth day. This is the most fatal as well as the most infectious form of plague.

Abortive or larval plague (pestis minor, pestis anibulans).— Certain epidemics are distinguished by the large proportion of mild cases. In such, buboes form and suppurate or resolve, the associated constitutional symptoms being comparatively mild, or perhaps altogether wanting. In every epidemic there may be cases in which the patient is able to be about, having little if any fever, and apparently being little inconvenienced by the disease. Such cases, however, may collapse suddenly.

Epidemics of bubo with little or no constitutional symptoms, which precede and follow true plague, sometimes occur. The cases forming this group are of great importance in their bearing on the spread and prevention of the graver form of the disease.

Relapses, though rare, do occur, and are dangerous.

Mortality.— The case- mortality of bubonic plague varies in different epidemics. It is usually greatest at the beginning and height of the epidemic. Disregarding those mild epidemics just alluded to, the death-rate may be anything from 60 to 95 per cent, of those attacked. Much appears to depend on the social condition of the patient and the attention and nursing available. Thus in a recent Hong Kong epidemic, whilst the case-mortality among the indifferently fed, overcrowded, unwashed, and almost unnursed Chinese amounted to 93.4 per cent., it was only 77 per cent, among the Indians, 60 per cent, among the Japanese, and 18.2 per cent, among the Europeans, a gradation in general correspondence with the social and hygienic conditions of these different nationalities. In the South American epidemics and in the recent circumscribed epidemics in Europe the mortality was only about one-third of that obtaining in India and China. Pneumonic plague is invariably fatal in from three to four days.

Pathological anatomy and pathology.—After death from plague the surface of the body very frequently presents numerous ecchymotic spots or patches. The number and extent of these vary apparently, in different epidemics. Sometimes as in the Hong Kong epidemic of 1894 they are few and trifling, having their origin, as mentioned, principally in insect bites. In other epidemics, according to their historians, the cutaneous hæmorrhages have been both extensive and numerous; hence the name " black death " formerly applied to this disease. The characteristic buboes are generally apparent; occasionally there are also furuncles, pustules, and abscesses. Rigor mortis is usually moderate; sometimes post-mortem muscular contractions, like those of cholera, take place. Post-mortem rise of temperature is often observed. Decomposition is said to set in early.

The characteristic appearance in a necropsy of plague is that of engorgement and hæmorrhage, nearly every organ of the body participating more or less. There is also parenchymatous degeneration in most of the organs. The brain, spinal cord, and their meninges are markedly congested, and there may be an increase of subarachnoid and ventricular fluid. There are numerous and pronounced puncta cruenta on the brain sections; occasionally there may be considerable extravasations of blood into the substance of the brain (mesocephalon and medulla oblongata).

Ecchymoses are common in all serous surfaces; the contents of the different serous cavities may be sanguineous. Extensive hæmorrhages are occasionally found in the peritoneum, mediastinum, trachea, bowel, pelvis of kidney, ureter, bladder, or in the pleural cavities. The lung frequently shows evidences of bronchitis and hypostatic pneumonia; sometimes hæmorrhagic infarcts and abscesses are found. The right side of the heart and the great veins are usually distended with feebly coagulated or fluid blood. In pneumonic plague the superficial lymphatic glands are not enlarged; the pleural cavities contain bloodstained serum; the infected lungs are deeply congested and œdematous, and at a later stage pneumonic consolidation is found. The bronchi contain blood stained serum and the bronchial glands are swollen and hæmorrhagic.

The liver is congested and swollen, and its cells are degenerated. The spleen is enlarged to two or three times its normal size. The mucosa of the alimentary canal as a whole is congested, showing here and there punctate ecchymotic effusions and, occasionally, hæmorrhagic erosions, and even— especially about the ileo-cæcal valve— ulcerations.

Similarly the kidneys are congested, and may exhibit ecchymoses both on the surface and in the pelvis. The perirenal connective tissue also may be congested and infiltrated. The ureters and the mucous surface of the bladder are often found to be sprinkled with ecchymoses, in which cases the contained urine is generally bloody.

Evidence is invariably discoverable of serious implication of the lymphatic system. One, two, or many of the lymphatic glands are inflamed and swollen. Both in and around the glands there is much exudation with hæmorrhagic effusion, hyperplasia of the gland cells, and an enormous multiplication of bacteria. The glands of the groin, of the armpit, and of the neck are particularly affected. On dissection the superficial buboes are very often found to be connected with extensive, deep-seated adenitis extending either through the crural ring or down the neck, and involving the pelvic, the abdominal, or the mediastinal glands, as the case may be. Section of the affected glands will reveal any stage of inflammation from cellular hyperplasia to suppurative softening, according to the period of the disease at which death has occurred. In whatever stage death has taken place, there is always evidence of intense hyperæmia in, as well as around, these glands a hyperæmia which is specially characterized by a marked tendency to hæmorrhagic effusion. In the earlier stages of the adenitis the specific bacillus is found in the lymph spaces around the follicles; later, it is found in the follicles themselves, in the lymph spaces, and in the medullary cords (Aoyama).

If death has taken place at a very early stage of the disease, the swelling of the lymphatic glands may not be so evident ; but it is rare not to find some gland or glands characteristically affected. In those septicæmic and pneumonic cases in which the bubo is absent nearly all the lymphatic glands of the body are slightly enlarged, pink or dark red in colour. Sometimes the lymphatic trunks are also markedly implicated.

Diagnosis.— The occurrence of fever and adenitis during a plague epidemic must invariably be viewed with suspicion, and particularly if the fever rapidly assumes an adynamic character. In the early stages diagnosis may be very doubtful, especially in pneumonic plague, and in countries of high filarial endemicity and in which filarial adenitis is necessarily a common occurrence. The discovery of the bacillus in the glands, blood, sputum, or discharges is the only thoroughly reliable test. A small quantity of the suspected material should be spread on a slide, dried, fixed, and stained with an aniline dye. Should a cocco-bacillus be found with the characteristic bipolar staining, it should be cultivated by Haffkine's method in broth on which clarified butter (ghee) or coco-nut oil is floated. From the under-surface of the oil, if the bacillus be that of plague, stalactite-like growths of bacilli will form. When disturbed, the stalactite growths break off and fall in snow-like flakes to the bottom of the vessel. No other known bacillus behaves in this way. (See p. 325.) In case of doubt, animal inoculation should be had recourse to: a little of the virus from the patient or a culture is rubbed into a shaven area (1 in. square) on the abdomen of a white rat or a guineapig. B. pestis inoculated in this way kills the guineapig in seven days, the rat sooner.* ^[8] General prophylaxis.— The prophylaxis of plague, as of other infectious diseases, has to be considered from the standpoint of the community and also from that of the individual. As regards the former, it includes measures for preventing the introduction of the virus, for staying its spread if introduced, and for securing its destruction.

Quarantine.— Modern systems of land or sea quarantine directed against plague take cognizance of the facts that the incubation period of the disease may extend to ten days, and that plague affects certain of the lower animals as well as man. Ten days is the minimum period that should elapse between the time of departure from an infected place, between the date of the last death, or between the arrival of a ship or batch of travellers with cases of plague in progress among them, and the granting of free pratique. Moreover, as Kitasato has shown that the specific bacillus persists in the bodies of those who have recovered from plague for at least three weeks from the cessation of the active disease, convalescents should be isolated for a month before they are allowed to mingle with an uninfected community.

Although Kitasato has stated that the plague bacillus perishes in four days when dried on coverglasses and protected from sunlight, and in from three to four hours when exposed to sunlight, experience has shown that under certain conditions, as yet unknown, it will survive outside the body for a very much longer period.*^[9] There is a. considerable mass of evidence tending to show that clothes, skins,

recognizable. If the gland is itself inflamed it is almost diagnostic of plague; in which case the liver will be found of a yellow colour and sprinkled with innumerable pinky-white granules. The spleen is enlarged, congested, and occasionally granular. Serous or blood-stained serous effusions are present in 72 per cent, of such rats. If on Microscopical examination of scrapings from glands or spleen bipolar -staining bacilli are detected the case is probably plague. Too great stress must not be laid on bipolar staining, as this feature depends somewhat on the method of staining; it is best demonstrated by Leishman or eosin-azur stain. textile fabrics, and other similar materials may preserve the virus in an active state for several months. Such articles, therefore, coming from an infected district, more especially if there is any suspicion that they have been soiled by or have been in proximity to plague patients, should be destroyed or thoroughly disinfected.

In ships coming from an infected port the rats, mice, and such-like vermin should be destroyed, thrown overboard, and sunk before harbour is entered. The generation of sulphurous acid gas under pressure, especially the Clayton system, has been found useful for this purpose.

Kitasato found that bouillon cultures of the bacillus were killed in half an hour by a temperature of 80° C., and in a few minutes by steam at 100° C. Growth of the bacillus did not occur in cultures after exposure for one hour to a 1-per-cent. solution of carbolic acid. The bacilli are also killed by a three-hours' exposure to milk of lime. These facts serve as a guide to suitable disinfectants, of which the best and most practicable are steam, 1-in-1,000 corrosive sublimate in carbol-sulphuric acid, lysol, chloride of lime in 1-per-cent. solution, carbolic acid in 5-per-cent., formalin 2-per-cent.

On plague breaking out in a small -village community, so soon as the disease is recognized measures should be taken to prevent the inhabitants leaving the locality and in this way spreading the disease. There is little danger of this until the inhabitants become alarmed by a rapid extension of the disease. If possible, after the patients have been isolated in a special hospital, the village should be evacuated for a month, the inhabitants being accommodated in temporary huts close by, while the houses which the patients have occupied and those in their neighbourhood should be disinfected. The safest and most thorough form of disinfection is by fire, and in the case of an isolated village prompt destruction of the infected houses by fire is the surest method of stamping out the infection. The clothes and bedding of all patients should be burned. The dead, with as little delay as possible, should be buried in deep graves or cremated. Isolated observation camps should be organized, in which " suspects " and " contacts " may be segregated for a time equal at least to the incubation period of the disease. Rats and mice should be poisoned or otherwise destroyed, and their bodies burned. Besides such special measures, general sanitation should be scrupulously carried out. The diffusion of plague by railways must be carefully guarded against.

In the event of an outbreak in a town, it must be borne in mind— first, that there is an intimate connection between rat plague and human plague; second, that rat plague is conveyed to human beings, and, once established in human beings, is communicable to others and to rats by means of the expectoration, by the discharges from the bowels and by the urine, and by discharges from the buboes or glandular swellings; and third, that a plague in rats usually precedes plague in human beings. It is as important to know in what houses, areas, and quarters of the town the rats are infected as it is to know in which of these there are plague patients. In addition, therefore, to prompt notification of plague patients, a system designed to obtain information as to the occurrence of plague in rats should be instituted. It is not sufficient to carry on a general campaign against rats, and to burn all rats which have been poisoned or caught in traps, but it is necessary also daily to examine bacteriologically every rat so destroyed, in order to determine whether it is healthy or infected, and so to differentiate the healthy from the infected parts of the town. A ticket on the rat, giving the address from which it was brought, locates the street and house, and permits of action being taken at once. A house in which a plague rat is found is a plague- infected house, and if plague among the inmates is to be prevented the necessary preventive measures should be taken at once. These measures consist in the evacuation of the house until it has been disinfected and rendered rat-proof, and the disinfection of the clothes and belongings of the inmates.

For the detection of plague-infected houses, guineapigs, which do not harbour fleas as a rule, are now employed in Japan and India as convenient traps for rat-fleas. The guineapigs are turned loose in houses and warehouses, and rapidly succumb to the disease if plague fleas are present.

In India the compulsory inspection of all dead bodies prior to burial has been found a valuable measure for discovering infected houses and localities.

In all efforts to control the introduction and spread of plague, cases of pestis ambulans must be sought out and treated with as much respect as the more virulent forms of the disease.

It is very questionable if in practice any system of rigid quarantine, no matter how carefully devised and theoretically perfect, is ever absolutely protective. Its working is necessarily at the mercy of a large number of individuals, any one of whom, either from incompetence or from dishonesty, may permit its regulations to be broken through. Even if the introduction of plague by man could be prevented in this way, it is difficult to see how its introduction by rats or mice could be effectually guarded against. Quarantine may, and doubtless does, keep out a proportion of the infected, and to this extent it does some good; but it must be combined with careful general sanitation, with thorough disinfection, with the destruction of all discharges and fomites, with the speedy discovery and isolation of the sick, with the evacuation of infected houses and even of neighbourhoods, and with the wholesale destruction of vermin. These latter things English experience has shown to be far more effective than any system of quarantine; it was only in deference to Continental views that quarantine, in the ancient sense of the word, was practised in Great Britain against plague and yellow fever. A rational quarantine plus rational sanitary measures is what is wanted.

Destruction of vermin and other measures in anticipation of the introduction of plague virus.— Considering the well-established facts that rats are specially susceptible to plague, that in many epidemics they have been attacked weeks before, the disease has shown itself in man, that their habits bring them into intimate association with man, there can be no doubt that these rodents play a very important part in the diffusion of the introduced virus. This being the case, it is reasonable to believe that if the rats were destroyed the risk from the introduction of a case of plague, whether by man, rat, or fomites, would be very much reduced in any community in which this measure had been carried out. The responsible authorities of all towns and villages in active communication with plague centres should, in anticipation of the possible advent of the infection, see to the destruction of all rats in their districts, and this in addition to instituting the ordinary measures for dealing with overcrowding, food and water supply, domestic and municipal cleanliness. The destruction of rats is a cheap measure in comparison with those adopted in India and elsewhere, which have so signally failed to arrest epidemic plague. The campaign against rats is usually carried on by the employment of rat-traps and rat-catchers, and the laying down, under precautionary conditions, of poisons such as arsenic and phosphorus. As no one method is satisfactory, it is usual to employ several at the same time. The pumping of SO 2 gas under pressure is useful for ships full of cargo and for warehouses with goods in them. So long as the sulphurous acid gas is dry, and is not used on damp articles, no damage is done to merchandise. Care has, however, to be taken with damp things, as they may get slightly discoloured.

Where possible houses and warehouses should be made rat-proof, not an easy measure considering the burrowing and climbing habits of the rat. Mus decumanus can penetrate ordinary lime mortar or soft brick, but is stopped by cement and concrete. Its burrows may attain a depth of 18 in. Mus rattusis not so active in this respect. Simpson re-commends that walls should be at least 6 in. thick when made of hard brick or concrete, and that they should extend to not less than 18 in. below the level of the ground floor, and that the latter should be made of concrete 3 in. thick, covered with J in. of cement. All ventilators should be protected with iron gratings, and all openings around wires and pipes cemented. The mooring cables of ships should be shielded in such a way as to prevent egress or ingress of rats, and all gangways should be taken up at night or when not in use.

Attempts have been made to set up an epidemic among the rats which should not be communicable to man. For this purpose the bacillus discovered by Danysz was recommended by him. But the method employed viz. inoculating a few rats with the bacillus and then allowing them to escape, in the hope that when they sickened they would be eaten by other rats, which would in their turn be taken ill, and an epidemic be thus set up has not been successful. Experiments on these lines have failed. The Danysz bacillus was, however, found to be useful in Cape Town and elsewhere for the destruction of rats when a system introduced by Professor Simpson was adopted, and bread soaked in the cultures was distributed and laid down in the same way as is usually done with biscuits on which rat poison is spread. By distributing thousands of doses an excellent result was obtained, and rats which were examined in the localities where the Danysz bacillus had been used in this way were found to have died from the disease induced by this organism. Rats which had migrated were also found to have died of the same cause in localities other than those in which the cultures were placed. An important point in the success attending these operations was found by Dr.R. W. Dodgson to be the raising and maintenance of the virulence of the cultures. Those sent out from the Pasteur laboratory after a fortnight's voyage were found to be useless, and consequently required to be exalted in virulence by a series of passages through healthy rats.*^[10] Personal prophylaxis.— As regards the individual, all unnecessary visits either to plague patients or to plague neighbourhoods should be avoided and, if possible, prevented. The attendants on the sick ought especially to take care that the ventilation of the sick-room is thorough, that cubic space is abundant, and that the utmost cleanliness is practised. Nurses must not hang over patients unnecessarily; they must also be careful to seal up and cover any wounds, no matter how trifling, they may have on their hands; they must go into the open air frequently, and not remain in the wards too many hours at a stretch; they must employ disinfectants freely on themselves and on the excreta of their patients, and use a disinfectant mouth-wash from time to time; they must be careful to wash hands and face before eating, and they must never partake of food or drink in the ward or sick-room. By carefully observing these common-sense precautions, the risk in nursing plague patients is very much reduced, and is certainly very much less than that attending the nursing of cases of typhus or diphtheria. To obviate risk from wounds and to prevent the access of fleas and similar suctorial insects, those engaged on plague duties should wear boots and have the legs protected by trousers tied tightly round the ankles or, better, by putties. Leather gloves are advisable if there is much handling of furniture or of anything likely to abrade the skin. Hospital work is only dangerous when patients are allowed to lie in their dirty flea-, louse-, or bug-infested clothing, when disinfectants are not properly used, and when attendants are careless, stupid, or rash, or where the wards, in the matter of light and ventilation, are by their construction ill adapted for plague cases, and where a number of pneumonic cases are crowded into a single apartment. Cats or dogs should not be allowed near plague patients.

The attendants on pneumonic cases should provide themselves with masks of muslin, three or four fold, and changed when at all damp, and also with goggles to protect the eyes. In Mukden a mask of absorbent cotton-wool (16 by 12 cm.) enclosed in muslin, and retained in position by a many-tailed gauze bandage, together with goggles, rubber gloves, and cotton uniform, proved thoroughly effective.

Haffkine's inoculations.— Early in the Bombay epidemic Haffkine introduced a system of prophylactic inoculation which is of proved value, both in reducing the number attacked with plague to the extent of from 77 to 85 per cent., and also in diminishing the mortality in those attacked by 80 per cent.*^[11]

It consists essentially in the subcutaneous injection of six-weeks-old cultures of plague bacilli incubated at 25°-30° C. and killed by heat 65° C. for one hour; carbolic acid, 0.5 per cent., is then added. The reaction is at times severe, but until quite recently no grave accident had occurred. The figures are not so favourable for Mauritius, where inoculations reduced the plague incidence to. the extent of 45 per cent, only, and the mortality in those inoculated to 32.9 per cent. The Indian Plague Commission reports strongly in favour of these inoculations. All plague laboratory workers and all who are likely to be exposed to plague infection should receive them. The protection they confer lasts about twenty months. In the report of the Bombay Bacteriological Laboratory, 1911, Glen Liston states that in the inoculated the incidence of plague was 8 per 1,000 of the population concerned, whereas it was 34 per 1,000 in the uninoculated in the same communities; the case-mortality in the inoculated was 39-5 per 1,000 attacked, in the uninoculated 78 per 1,000. The best results were obtained from a two-months' growth which had been stored about eighteen months. The prophylactic needs great care in its preparation. Its storage in hermetically sealed bottles should be insisted upon, and every bottle ought to be tested before use.

Lustig's injectiods.— Lustig and Galcotti have introduced a method of preventive inoculation which apparently obviates many of the drawbacks of Haffkine's. They dissolve agar-agar plate cultures of Bacillus pestis in 1-per-cent. solution of caustic potash, precipitate the nucleo-proteins so dissolved by weak acetic or hydrochloric acid, collect the precipitate, wash and dry it in vacua. This substance, apparently, can be kept for an indefinite time. The dose for a man is about 3 mg. Before injecting it subcutaneously, it is dissolved in a convenient quantity of 0.5-per-cent. solution of carbonate of soda. Its injection is followed by marked local and general reaction, and in the case of the lower animals by at least temporary immunity from plague. Favourable results have been obtained in man.

Klein advocated a prophylactic prepared by drying plague spleens at 47° C. over sulphuric acid. Ten to 15 mg. of this protects rats against virulent plague injections.

Strong prepared a vaccine by prolonged subcultivation of plague bacilli, or by cultivation on unfavourable media. Using the resulting living bacteria, he inoculated forty -two criminals. Beyond local and general reaction no harm ensued.

Other forms of antiplague vaccine have been introduced, but, so far, Haffkine's holds the field.

Treatment.— Hitherto the treatment of plague has been mainly symptomatic. In attempting to relieve symptoms the asthenic tendencies of the disease must ever be borne in mind, and depressant remedies of all kinds carefully avoided.

During the earlier stages, when headache and perhaps high fever are urgent, much relief may be obtained from ice-bags to the head and neck. If it be deemed advisable to attempt to lower the temperature, sponging of the body every hour with warm water is a much safer measure than the employment of such antipyretics as antipyrin and similar drugs. Vomiting, according to Lowson, is usually relieved by a full dose of calomel followed by a saline. If this does not succeed, or if diarrhœa be present, he recommends ice pills and an effervescing mixture containing morphia and hydrocyanic acid. Sinapisms to the epigastrium are also useful. Later, when the pulse begins to fail, the same authority recommends strychnia, with or without carbonate of ammonia, in preference to digitalis or strophanthus. Strychnia, he says, should be used as a routine treatment, and commenced early in the disease. In collapse, stimulants of various kinds, including strong ammonia to the nostrils and ether hypodermically, are indicated; they sometimes succeed in resuscitating a sinking patient. Given with judgment, Lowson found that morphia was by far the best hypnotic. At the commencement ⅛ to ½ gr. hypodermically relieves suffering and procures sleep; later, ⅛ gr. suffices. Hyoscine (1/200 to 1/75 gr.) or chloral (20 gr.) and bromide of potassium (30 gr.) are of service for the same purpose. Diarrhœa, if urgent, is best treated by intestinal antiseptics, as salol in 10-gr. doses every four hours. The buboes in the early stage may be treated with applications of glycerin and belladonna. Should they become red and inflamed they must be poulticed and, on softening occurring, incised and dressed with iodoform. Indolent bubonic swellings should be treated with iodine liniment. Feeding and stimulation are to be conducted on ordinary principles. In the Manchurian epidemic intravenous injections of salvarsan were tried without effect.

Serum-therapy.— Yersin, Calmette, and Borrel have shown that intravenous, intraperitoneal, and subcutaneous injections of gelatin cultures of plague bacillus mixed with a little bouillon and heated for one hour to 58° C., if employed in doses just short of producing a fatal issue, and repeated three or four times at intervals of fifteen days, render rabbits immune to the plague bacillus. The heating kills the bacillus but does not destroy its toxins, which at first give rise to a very smart but, with each repetition of the injection, diminishing reaction. They further found that the serum of an immunized animal, if injected into an unprotected rabbit, exercised both an immunizing and a therapeutic influence. An unprotected rabbit was inoculated with a virulent culture of the bacillus, and twelve hours afterwards with the serum. The progress of the disease, which would otherwise have certainly proved fatal, was at once arrested, and. the animal recovered. They then immunized a horse by intravenous injections of living virulent cultures. After several injections made at intervals (the second after twenty days), they found that reaction, from being intense, became shorter and less pronounced, and that the serum of the animal was now both preventive and curative of inoculated plague in rabbits, guineapigs, and mice. At the Lister Institute an antimicrobic serum is prepared by injection of dead and afterwards of living bacilli into horses, and in which antitoxic bodies are produced as well by immunization against the nucl co-proteins of B. pestis.

Accounts had led us to infer that the value of Yersin's discovery was practically established for man. Of 26 cases of plague in China treated with his antipest serum, 24 were reported to have recovered. Further experience in India, Hong Kong, and elsewhere has not confirmed these brilliant results, the serum treatment of plague both by Yersin's and by a number of other sera having so far proved a complete failure, and at the best but modifying the course of the disease and prolonging life.* ^[12]

FLEAS

These minute ectoparasites are now of considerable importance to the student of Tropical Medicine in view of the part they play in the spread of plague, and possibly of other diseases.

They are active parasites of mammals and birds; some suck blood indiscriminately, but the majority restrict themselves to one definite host.

In one family (Sarcopysllidœ) the females eventually attach themselves to heir host as fixed parasites, embedding themselves in its skin when pregnant; to this category belongs the "chigger."

The flea in its external structure is composed of a head, thorax, and abdomen.

CTBNOCEPHALUS. CHIATOPSYLLI'S. PVGIOPSYLLA. H HOPLOPSYLLUS.

• q &

Q * 2 l i 0.1 I! CO S The head is small compared with the abdomen, and is conical in shape; a comb of teeth is found sometimes on the cheek, or on the lower edge of the head. Eyes maybe present or absent. The head is provided with short antennae lodged in definite grooves. The mouth is furnished with appendages, maxillæ and palps, which conceal the other parts.

The thorax is composed of three segments, which are quite independent. Each consists of a dorsal arc carrying one or more belts of bristles. In some species the pronotum, or tergum of the first thoracic segment, carries a comb on its posterior edge.

The three pairs of legs are composed of a number of segments, the coxa being especially long and broad. The number and character of the bristles of the joints of the legs are used for distinguishing species.

{{smaller|The abdomen is composed of ten segments; on the ninth the tergum is in a great part occupied by a pitted sensory plate called the pygidium. In the male the sides of the tergum form large claspers. A large bristle or bristles project over and beyond the pygidium on the seventh segment, and are known as antepygidial bristles. There is a large and complex penis.

The female flea is larger than the male. The curved receptaculum seminis is a conspicuous object in the female.

The eggs are dropped by the female casually, and hatch in three or four days in summer time.

The larva lives in dust, is an active footless maggot, of a whitish colour, and is sparsely hairy. When full grown it spins a cocoon and pupates. The duration of the pupal stage depends on the temperature.

1. * The pus from a bubo is not always infective. Inoculation made with such may fail. Apparently the bacteria of suppuration may kill out the Bacillus pestis.
2. * It is stated that the handling of a rat newly dead of plague is fraught with danger, whereas a rat that has been dead for some time and is cold and stiff may be touched with impunity; and it is surmised that the fleas of the newly dead rat are still in its fur, and quit it for the body of the manipulator, carrying on their probosces the bacilli of the disease, which they introduce when they proceed to feed on their new host. "When a rat has been dead for some time and the body is cold, the fleas have already forsaken it; hence the impunity with which the rat itself may be handled, but the danger of the locality in which it died and where the hungry infected fleas are awaiting an opportunity for a meal. The fact that the glands of the legs are usually the first to become implicated in the majority of cases of plague suggests that the virus is generally introduced through the skin of the feet or legs, which are just those parts most likely to be attacked by a flea picked up in walking across the floor of a room in which plague-stricken rats or other animals have died.
3. † This is the rat-flea in the tropics. Ceratophyllus fasciatus, which attacks men as well as rats, is the rat-flea in temperate climates. Plague epizootics occur in mice, but are not associated with plague in man. Ctenopsylla wusculi does not readily feed on man.
4. Journal of Hygiene, vol. vi., No. 4, April, 1906.
5. Though it is possible to transmit plague experimentally by means of the human flea, Pulex irritans, yet this flea plays little or no part in the spread of plague at the present day.
6. * The origin of the epidemic of plague at Saraitschikow, in the Ural Province, Russia, in which 415 persons lost their lives, may be accounted for in this way. A rich Cossack died, presumably of plague. After his funeral his clothes were distributed.
7. * smaller|During the epidemic of pneumonic plague in Manchuria from October, 1910, to March, 1911, R. P. Strong and Teague exposed 82 agar plates at distances varying from 5 cm. to 2 metres in front of the faces of plague patients for a period of two minutes. In 39 instances the patient did not cough, and only 1 of the plates yielded plague bacilli. In 35 instances the patient coughed; the corresponding plates yielded plague cultures in 15 instances, the growths having originated in the invisible spray.}} The vitality of the plague bacillus outside the body depends in great measure on the rate of evaporation, that is to say, on the temperature and hygrometric conditions of the air. Thus in Harbin the bacillus retained its vitality for long periods when the thermometer stood at— 9° C. and the water deficit equalled about 0.3 mm. of mercury. In India, where evaporation goes on much more rapidly at temperatures perhaps of 30° C. and water deficit of 9.5 mm. of mercury, pneumonic plague is much rarer, amounting to only 3 per cent, of the total cases. In Manchuria there were only two or three cases of bubonic plague in a total of some 50,000 deaths. The initial case of this epidemic is said to have been that of a tarbagan hunter, who contracted his infection in skinning one of these animals. Domestic animals, donkeys and dogs were attacked during the epidemic and contributed to its spread.
8. * Post-mortem indications of plague in the rat.— Before rats suspected of being plague-infected are handled, they should be immersed in disinfectant to destroy ectoparasites. The lymphatic glands should be first exposed. If the rat is infected, subcutaneous injection around the glands is generally
9. * Schurupoff found seven-year-old cultures of B. pestis to be still alive. He examined 17 plague corpses a year after death; from 6 of them he recovered the plague bacillus.
10. * Danysz's bacillus rapidly loses its virulence when grown on the ordinary culture media, but retains it if grown on eggalbumin media, killing rats in from seven to nine days.
11. * For a description of Haffkine's methods see Brit. Med. Journ. June 12th, 1897.
12. * Connor (1913) Has reported the apparent recovery of three patients to whom intravenous injections of iodine (1 part) and distilled water (60 parts) were frequently administered. If this be so, the method is worthy of further trial on a more extensive scale. Recently, Rama Iyer had five recoveries in six cases treated by intravenous injection of tincture of iodine; 7-10 minims were injected the first day twice, twice the second day, and afterwards once a day.