Plague

PLAGUE. Plague (pestis) is an acute infectious disease manifesting in bubonic, pneumonic, septic, and less frequently, cutaneous and intestinal forms; plague sepsis can be either primary or terminate the aforementioned local forms of plague infection. The word 'plague' comes from the Arabic 'jumma', which means bean or bubo. History. The first reliable information about plague dates back to the 3rd century BC. The first detailed description of a plague epidemic, called the Justinian Plague, which struck Egypt, Syria, Asia Minor, Turkey, Persia, and Arabia and lasted for more than 50 years, was made in the 6th century. Subsequently, plague appeared repeatedly in various countries throughout the 7th–10th centuries, though without reaching significant development. In the 14th century, the plague, having started in China, engulfed the entire Old World and was known by the name 'Black Death'. In Europe alone, 25 million inhabitants perished from it out of a total of 105 million. Plague epidemics disappeared from Europe in the mid-19th century. Its largest foci have remained in Asia and Africa (see below). Etiology. In 1894, in Hong Kong, Yersin and Kitasato, while studying a plague epidemic, independently discovered the causative agent of the plague. The plague microbe, Bacillus pestis, belongs to the group of causative agents of hemorrhagic septicemia and is a short coccobacillus 0.5 to 1.5–2.0 µm in length with a thickness of 0.3–0.5 µm. Bacillus pestis, a facultative aerobe, can only grow slowly and sparsely with restricted access to oxygen; it is non-motile, Gram-negative, does not form spores, and has a capsule, which is clearly expressed especially in the organs of animals and humans and is occasionally detected in cultures at 37° (Rowland). In smears and sections from organs, Bacillus pestis stains best at the ends. This bipolar staining is so characteristic of the plague microbe that it gave grounds to call it the bipolar bacillus [see separate table (col. 631–632), fig. 1]. In shape, the typical plague microbe resembles a barrel, having a thicker middle with tapering, rounded ends. However, the morphology and dimensions of the plague bacillus are very variable: sometimes it is a small coccus, sometimes a large sphere, sometimes a short coccobacillus, sometimes a long thread, sometimes a thick and coarse rod [see separate table (col. 635–636), fig. 1 and 2]. Such polymorphism is very characteristic of the plague microbe and allows it to be distinguished from a number of similar bacteria. Also characteristic of the plague microbe is the varying intensity of its staining and the presence in the preparation, alongside typically stained specimens, of pale-stained microbes. In old cultures, especially in broth, the plague microbe forms small granules, which under suitable conditions turn into rods (Schultz). The plague microbe grows on ordinary nutrient media at pH 6.8–7.8 (optimum pH 7.0–7.2). The growth limit of the plague microbe is from +4.5° to +43.5°, with an optimum at 28–30°. Characteristic of the plague microbe is slow growth, within 2 days, on nutrient media. On agar, after 12–24 hours, the plague microbe forms a delicate film of the future colony, resembling a cambric handkerchief. Growth is visible under low magnification of a microscope and allows for early diagnosis. After 24–48 hours, delicate dew-like colonies form on the agar, transparent and translucent; the colonies are granular in the center and bay-like at the edge. Plague microbes are capable of forming R- and S-forms on nutrient media (see separate table, fig. 2 and 3) and a number of transitional RO- and SO-forms. Virulent strains usually originate from R-form colonies, and less virulent or completely non-virulent ones from S-forms. When streaked on agar, a viscous grayish film forms. When the plague microbe grows on agar with a 3% sodium chloride content (Hankin), atypical forms are produced. They have a certain differential diagnostic significance.

In broth, the growth of the plague microbe occurs on the walls and at the bottom of the vessel. On the surface of the broth, a rim forms at the wall of the test tube, then a film over the entire surface of the medium. From the film, processes ('stalactites') extend downwards. Such growth in broth is facilitated if indifferent substances, e.g., oil droplets, float on its surface (Haffkine). The plague microbe grows in broth in the form of chains of 3–6 or more elements. Of all types of broth for cultivating the plague bacillus, it is best to use Martin's broth. On gelatin, the plague microbe grows at 22° in the form of a colony of gray, later yellowish color; the center of the colony is elevated, granular, with edges in the form of a shiny, serrated border. At 24°, from the 6th day, the colonies produce processes into the depth of the gelatin. When grown by streaking, these processes resemble a brush. From the 7th day, the gelatin becomes cloudy, and from the 11th–13th day, it becomes slightly transparent and resembles agar. The gelatin does not liquefy. On blood serum and blood agar, the plague microbe grows well and quickly. On potato, growth is sparse in the form of a dry grayish-white film. The plague microbe does not coagulate milk and grows sparsely. Of the carbohydrates, it decomposes dextrose, levulose, galactose, maltose, arabinose, mannitol, and salicin with the formation of acid, but without gas; it does not decompose lactose, sucrose, rhamnose, raffinose, dextrin, starch, dulcitol, and adonitol. However, the relationship of plague bacilli to carbohydrates is not constant, and different strains react differently when grown in media with carbohydrates. Kurauchi provides a summary of the action of Bacillus pestis on carbohydrates, according to which some authors state that Bacillus pestis ferments dextrin, while others state it does not; the same uncertainty exists regarding dulcitol, xylose, sucrose, and even dextrose and lactose. The plague microbe reduces methylene blue (Schardinger's reaction), indigo, malachite green, and litmus, as well as, although more weakly, thionine, Janus green, and neutral red. Bacillus pestis in Martin's broth reveals a proteolytic enzyme (Gubarev); during prolonged growth on agar, it is capable of forming a pigment from smoky-gray to black and bluish-black (Preisz). Highly diluted emulsions of the plague microbe do not grow on agar. If sarcinae are inoculated onto the same agar, the growth of the plague microbe appears around the colonies of the latter (Bokalo, Vedishchev, Sabinin, et al.). Besides symbiosis, phenomena of antibiosis of the plague microbe with some bacteria are observed. Near the colonies of some microbes, colonies of the plague microbe do not develop. The plague microbe produces filterable forms that pass through bacterial filters. From these filterable forms, microorganisms of the usual appearance can grow again. Under the influence of a specific bacteriophage, the plague microbe is lysed, its broth cultures become clear, and when inoculated on solid media, characteristic taches vierges are formed. Under the influence of the bacteriophage, individual colonies of the plague microbe gradually lose their appearance, undergo glassy degeneration, and are subjected to lysis, revealing the Twort phenomenon (Pokrovskaya). The plague microbe does not form indole. It does not produce a toxin; the body of the plague microbe contains an endotoxin that is released upon the dissolution of the bacteria. The resistance of the plague microbe is not great; it does not withstand drying, sunlight, or even diffused light. In smears from organs, sputum, and blood, it dies within 24 hours when dried in an incubator, in 1–8 days in diffused light at room temperature, and in 19–20 days in a dark cabinet. In blood and pus smears on filter paper, wool, flannel, and linen, the plague microbe dies at 36–37° within 2–4 days, and at 8° it lasts for 3 days (Maassen), while according to some authors (Semikoz and Ashurova), on grain soiled with animal urine and feces, it lasts up to 27 days. In mouse skins, the plague microbe dies after 6 days (German Commission); in ferret skins, it is preserved for up to 8 days when dried, and up to 17 days in a humid atmosphere (Skshivan and Shchastny); in guinea pig skins, it is preserved for up to 17 days at room temperature in a dark place (Suknev). It should be noted that the lower the temperature and the slower the drying, the longer the bacilli remain viable. Fluctuations in humidity, as occurs in nature, significantly harm the viability of plague bacilli. In a liquid medium, a temperature of 50° kills the plague microbe within 40 minutes, 60° in 2–3 minutes (Gladin) and 40 minutes (Giaxa and Gosio), 70° immediately in a thin layer (Gladin), and in a thicker layer within 10 minutes (Abel); boiling kills the plague microbe instantly; dry heat at 80° within 60 minutes, and at 100° within 20–30 minutes. Pure cultures of plague bacilli withstand freezing at -20° for 40 days or more, and in frozen corpses, plague bacilli are preserved for up to a year (Shurupov).

Repeated freezing and thawing accelerate the death of the plague bacillus. The question of the viability of the plague bacillus on food substances is interesting. On sterilized food substances at room temperature, the plague microbe lives in milk for up to 81 days, on boiled vegetables for up to 15 days, on clarified butter for less than 2 days, on non-sterile vegetables for up to 8-10 days, and on the crust of black bread for 2-4 days (Gladin), in salted meat for 16 days after salting (Stadler). In soil poor in extraneous microbes, the plague microbe persists for up to 2 months (Gladin); in soil rich in extraneous microbes, it dies within the first few days. In water at a temperature of 16-19°, plague microbes are still detectable after 10 days under the action of diffused light (Gladin), in sewage water after 20 days (Abel), and in seawater up to the 47th day (Würtz and Bourges). Plague bacilli retain their viability for a long time in the bodies of insects and their excrement. In infected and starving fleas, the viability of plague bacteria is maintained at a temperature of 37° for up to 5 days, at 18-20° for up to 90 days, at a temperature of 0-15° for up to 396 days (Golov and Ioff); in the body of a bedbug for up to 147 days (Novikova and Lalazarov); in ticks Rhipicephalus schulzei Ol. from an empty ground squirrel nest for up to several weeks (Golov and Knyazevsky); in the tick Argas persicus for up to 110 days (Fadeeva). Borzenkov and Donskoy established that all stages of development of the tick Hyalomma volgense can contain viable and virulent plague bacilli for up to 11 days. Observations in India show that the number of rat fleas containing plague bacilli drops rapidly during the epidemic period: from 43% in the first 4 days of the epidemic to 9% after 12 days. At low temperatures, infected fleas can be found for up to 47 days; usually, they disappear by the 22nd-30th day. By excavating ground squirrel nests, Tumansky confirmed the presence of plague fleas 5 months after the end of an epizootic. Firsov, introducing laboratory-infected fleas placed in calico bags into a ground squirrel nest, established the persistence of plague bacilli for up to 224 days. Tinker and Stupnitsky found plague bacilli in a flea (N. setosa) from a ground squirrel nest 8 months after the end of an epizootic. In flea excrement, plague microbes persist for up to 5 months (Verzhbitsky), in bedbug excrement for about a month (Novikova and Lalazarov), in the excrement of Hyalomma volgense ticks for up to 11 days (Borzenkov and Donskoy). From the pus of an unopened bubo, it is sometimes possible to isolate plague bacilli on the 20th day of the disease (Zlatogorov); in the sputum of a pneumonic plague patient after 7 weeks (v. Vagedes), and in the pus of a pelvic abscess 2 1/2 months from the onset of the disease. In some cases, it was possible to cultivate plague bacilli from a suppurating bubo of a patient 4 months from the onset of the disease (Zinno). As a rule, plague microbes disappear quickly from suppurating buboes. In convalescents, they are not found either in the blood or in excretions (German Commission). However, Gotschlich and Kitasato sometimes obtained plague cultures from the blood and sputum of convalescents 6-19 days after the temperature dropped. Of even greater interest is the finding of plague bacilli in healthy people, among whom there are sometimes bacillus carriers. A case is described where a healthy woman infected 11 people with plague over 15 days; Wu Lien Teh reports two cases of bacillus carriage during an epidemic of pneumonic plague with the finding of plague bacilli in the sputum and nasal mucosa. Sometimes it was possible to find pathogenic plague bacilli in a non-inflamed gland in people who had been in the company of a plague patient (Leger and Baury). It has been established that plague bacilli multiply in corpses during the first hours after death, and upon the onset of putrefaction, they disappear relatively quickly at a suitable temperature. At low temperatures, plague bacilli can persist in corpses for an indefinitely long period. Thus, if at 35° plague bacilli in guinea pig corpses persist for up to 5 days, then at 0° they persist for up to 140 days (Zlatogorov); in rat corpses in winter, plague bacilli persist for 34 days, but in summer only for 4 days (Toyada); in the organs of a camel that died of plague, kept in a room refrigerator, plague bacilli remained alive for up to 18 months (Zlatogorov). From the oral mucosa of human corpses, it was possible to cultivate plague bacilli after 3 months (Ragga); in frozen human corpses, plague bacilli were found after a year (Shurupov). Regarding disinfectants, the plague microbe is not very resistant. Of primary practical importance in the disinfection of objects contaminated with plague bacilli are: mercuric chloride, carbolic acid, lysol, mineral acids, chlorinated lime, flowing steam, and boiling, as well as chloropicrin. Mercuric chloride (1:1,000) in a protein-free medium kills plague bacilli within 1-2 minutes; in material containing protein substances, the action of mercuric chloride is unreliable; 2-3% carbolic acid destroys plague bacilli within 1-3 minutes, a 1% solution within 5-10 minutes; 1% lysol kills plague bacilli within 5 minutes in pus on cover slips; the same solution kills plague bacilli in agar cultures in 30 minutes (Abel). Lime milk, added in an amount of up to 1% to a broth culture, kills plague bacilli within 2 hours (Abel), and mixed in equal amounts with feces, it kills the microbes in an hour (German Commission); according to Gladin, 1% lime milk killed plague bacilli on silk thread in 20 minutes, and in broth in 15 minutes. Sulfuric acid in a concentration of 1:2,000 kills the microbe in 5 minutes, and hydrochloric acid 1:1,000 in 30 minutes (German Commission); even in a mixture with feces, the plague microbe dies in 20 minutes under the action of 1:2,000 sulfuric acid. Acetic acid has a weak effect, which in a 1:200 solution does not kill the microbe after an hour. 10% sodium hydroxide kills in 10 minutes (Schultz), and a 0.5% solution at 60° kills in 20 minutes. Formalin is a weakly acting agent, killing plague bacilli on silk thread only in a 1% solution within 20 minutes, while a 1:1,000 solution did not kill the bacilli within an hour (Gladin). Plague bacilli in the sputum of plague patients are killed by 10% carbolic acid within 5 minutes; by 1:50 lysol in 20 minutes; by 1:1,000 mercuric chloride in 30 minutes; 1:500 in 20 minutes; by absolute alcohol (rectified or denatured) in 4 minutes (Wu Lien Teh). Ultraviolet rays kill plague bacilli in physiological saline after 6-10 minutes, in blood serum after 15 minutes, in broth and urine after 2 1/2 hours, and in milk after 3 hours (Galeotti). Pathogenicity. The plague bacillus causes spontaneous disease among a significant

Figure 1. Tarbagan—Arctomys bobac Pall.

quantities of animals, the total number of which is more than four dozen; mainly in nature, rodents suffer from plague, from which plague most often passes to humans. Usually, under natural conditions, rodents and humans suffer from plague. Isolated cases of disease in camels, cats, and donkeys have been described (Deminsky, Klodnitsky, and others), although all these animals are little susceptible to experimental plague. Cattle and horses do not suffer from plague under natural conditions and react only with local phenomena and fever upon artificial inoculation with live microbes. In different countries, different rodents naturally suffer from plague and cause its endemicity. In Manchuria and Mongolia, the main carrier of plague is the tarbagan (Arctomys bobac Pall.) (Fig. 1) (Belyavsky, Pisemsky, Zabolotny, Barykin, and others). Findings in 1926 of spontaneously plague-infected jerboas, Alactaga mongolica (Kukushkin), in 1929 of a polecat, Putorius eversmanni Less. (Petrovsky), in 1927 of a vole, Microtus raddei (Skorodumov) force us to pay attention to these animals as well. Among the rodents of Manchuria and Mongolia susceptible to experimental plague infection, one must point out hamsters, Cricetulus furunculus (Suknev, Jettmar), the pika, Ochotona daurica (Jettmar, Suknev), Spermophilus eversmanni (Jettmar), etc. Different species of ground squirrels (Citellus pygmaeus Pall., C. fulvus Licht., C. rufescens, and others) can also be a source of plague (Deminsky). Citellus pygmaeus is of particular importance due to its wide distribution in densely populated steppe areas. Mice (Mus musculus Nordm.) also play an important role. Besides these animals, the gerbil (Rhombomys opimus, Gerbillus tamaricinus), the steppe lemming (Lagurus lagurus), the vole (Microtus socialis, M. arvalis), jerboas (Alactaga saliens), and hares suffer from plague. In India, the main carriers of plague are rats (Mus decumanus, Mus rattus, M. alexandrinus), as well as squirrels (Sciurus palmarum); in California, ground squirrels (Citellus beecheyi) and gophers (Callospermophilus chrysoideus); in Egypt and East Africa, mice (Arvicanthis niloticus) and rats (Rattus concha and others); in West Africa, field rats (Golunda campanae); in South Africa, ground squirrels (Geosciurus capensis), mice (Mastomys coucha, Rhabdomys pumilio and others), hares, and kangaroo-type rodents (Pedetes caffer Gal.). Rats in all countries often serve as the cause of port and ship plague epidemics. Among laboratory animals, guinea pigs are highly susceptible to plague infection, rabbits somewhat less so. Monkeys, according to experiments by the Russian and German commissions in Bombay, are "susceptible to plague. The picture and course of the disease in them resemble the disease in humans. In animals that have contracted plague, the disease can proceed in the form of an acute, subacute, and chronic process, and very often enlarged lymph nodes are found in animals. They are usually fused with the surrounding tissue, impregnated with serous-hemorrhagic exudate, and are in the stage of suppuration. In the acute form of plague, the presence of hemorrhages under the skin, on the mucous and serous membranes, and in many organs is characteristic. The blood and organs are overflowing with plague bacilli, which, settling in the organs and multiplying in the form of huge clusters, give rise to characteristic necrotic nodules (see separate table, Fig. 3), especially in the spleen, which takes on a mottled appearance. Similar nodes, sometimes of large size, are observed in the liver and lungs (see separate table, Fig. 4). In chronic cases of plague, the clinical picture of the disease consists mainly of local lesions and lesions of the lymph nodes closest to the entry gates in the form of suppurated buboes, sometimes caseously degenerated and necrotically altered. Internal organs are little affected. The virulence of the plague microbe in relation to different species of animals is different. It is maximal for rodents and lower for camels and some predatory animals. Its strength for rodents falls in the following sequence: tarbagan, ground squirrel, rat, mouse. In connection with this, chronic forms are rarely encountered in tarbagans and ground squirrels. Thus, only two cases of chronic plague have been described among tarbagans (Barykin, 1907; Suknev, 1923). Among rats and mice, chronic forms are encountered more often. Ground squirrels, rats, and mice, as well as hamsters, voles, and pikas, in a certain percentage of animals, do not become infected with experimental plague. The virulence of the plague microbe is relatively well preserved in cultures if these cultures are periodically passed through susceptible animals; a culture enhanced by passages through one species of animal increases its virulence in relation to other species as well. With prolonged cultivation of the plague microbe on artificial nutrient media without passages through animals, its virulence is weakened and even completely lost. Toxins. For a long time, the question of true toxin formation by the plague microbe was controversial. The majority assumed that the poison is bound to the bodies of bacteria and represents an endotoxin (Yersin and Roux), which, in the form of a nucleoprotein, was proposed for the immunization of animals (Lustig, Galeotti). At the present time, some recognize the ability of the plague microbe, along with endotoxin, to produce a true toxin, however, it is extremely unstable and requires an abundant influx of air and cultivation of cultures at room temperature (Markl). The toxin has not yet been obtained in pure form. Plague-like bacteria. Among bacteria pathogenic to animals, there are those similar to the plague microbe not only in their morphological features but sometimes in the clinical and pathological-anatomical picture of the disease. These can include: 1) a group of causative agents of bacillary enteritis, 2) a group of hemorrhagic septicemia, and 3) a group of capsular bacteria. Among rats, bacilli of the Gärtner type (see Paratyphoid) or bacilli of the Bacterium coli commune type (see) are especially often encountered, which are pathogenic for rabbits, mice, rats, and guinea pigs. Cultures of these microbes are easily distinguished from plague ones by their motility, the speed of their growth, the formation of smooth colonies, the absence of the polymorphism characteristic of plague bacilli, gas formation during the fermentation of sugars, and specific serological reactions. The causative agents of hemorrhagic septicemia, belonging to the Pasteurella group, while causing a plague-like disease (see Pasteurellosis) and forming a characteristic bipolar staining, differ from plague bacilli by the speed of growth, some peculiarities of growth on nutrient media (turbidity of the broth, formation of films), colonies from agar more similar to colonies of E. coli, less polymorphism, and finally, the absence of specific reactions with plague serum. Capsular bacteria (see) of the Friedländer or aerogenes type sometimes also cause plague-like diseases in rats (Anjezky, Toyama, and others) and can give bipolar staining, but differ from plague bacilli by their growth on nutrient media and the formation of capsules in cultures. Of the greatest interest for differential diagnosis is the causative agent of pseudotuberculosis (see) - Bac. pseudotuberculosis rodentium Pt., which, causing a plague-like disease in rodents, has also been isolated in humans and presents such great difficulties for diagnosis that some believe that in the composition of the culture of false tuberculosis 'there are undoubted features of a plague culture, in no way differing from the true Bac. pestis either in biochemical or biological properties' (Zlatogorov and Mogilevskaya). For differential diagnosis between plague and pseudotuberculosis bacilli, many media have been proposed: salt media, Bessonova's medium with rhamnose, nutrient-poor acidic agar (Bessonova), Gimmelfarb's medium with maltose, media with glycerin, etc. Cultures of pseudotuberculosis possess greater alkali-forming energy (Nikanorov) or greater reducing capacity. However, these media and reactions have only relative significance, since between the biochemical activity of the microbes of pseudotuberculosis and plague there is only a quantitative, but not a qualitative difference (for more details, see Pseudotuberculosis). Bac. tularense belongs to the plague-like ones. However, the causative agent of tularemia (see), while causing a disease similar in clinical form to the bubonic form of plague, differs sharply from the plague microbe in its morphological and biological properties. Infection of experimental animals with plague is carried out through the skin, mucous, and serous membranes. For diagnostic purposes, the cutaneous method (Austrian method of infection) is of great importance, allowing the detection of the plague microbe even in putrefied material or in material containing many extraneous microbes, such as: feces, pus, etc. The material is rubbed into freshly shaved or depilated skin of the abdomen. In the presence of virulent plague bacilli, the disease and death of the animal occur. A pure culture of plague is isolated from its organs. Besides the cutaneous method, infection is carried out subcutaneously or intraperitoneally, as well as through the mucous membranes of the eyes, mouth, nose, etc., or by spraying the material and inhalation by animals. With the cutaneous method, swelling and redness appear at the site of the rubbed material, accompanied by purulent-necrotic infiltration of the skin and subcutaneous tissue with bloody impregnation and edema of the surrounding tissue. Regional lymph nodes are enlarged and hemorrhagic. Internal organs have changes similar to those in subcutaneous infection.

Upon injection of material under the skin, autopsy reveals necrosis at the site of inoculation with gelatinous hemorrhagic edema of the subcutaneous tissue. Regional glands are enlarged, necrotized, and surrounded by infiltrated hemorrhagic connective tissue. On the serous membranes of the intestine, peritoneum, on the pericardium and epicardium, as well as on the pleura, there are sometimes numerous subserous ecchymoses. The spleen is enlarged and dotted with grayish miliary nodules of various sizes. Infection into the peritoneum causes the development of purulent peritonitis with abundant viscous exudate containing a huge number of plague bacilli. Upon inhalation of the material, primary pneumonia develops in animals, and upon ingestion of plague cadaveric material, bubonic, pulmonary, or intestinal forms of Plague develop, ending in septicemia. Upon infection through mucous membranes, septicemia or even primary pneumonia develops most often, especially when plague material is applied to the nasal mucosa (Bazarov). With the cutaneous method of infection, death occurs on the 4th-7th day, with subcutaneous on the 3rd-4th, less often 6th-7th day, with administration per os in 3-6 days, with intraperitoneal in 24-48 hours. Epidemiology. Plague under natural conditions is a disease of animals, from which it is transmitted to humans. It has been established in places where the rat has a definite epidemiological significance (India, port cities) that about three weeks before human illness, the beginning of illness is observed among domestic rats (Mus rattus), which in turn is preceded by two weeks by illness of gray rats—Mus decumanus (Fig. 2). In other foci, illness among humans is always preceded by an epizootic of a plague nature among local rodents, the main carriers and transmitters of Plague to humans (see above). Of course, not every epizootic among rodents leads to human illness, just as human illness cannot always be linked to the presence of an epizootic among rodents, which could have already ended by the time a plague epidemic among humans was detected. Depending on the lifestyle of the rodents and the nature of their contact with humans, two different forms of plague epidemics are observed—summer and winter. Gotschlich already pointed out that Plague, which is owed to rats, gives a bubonic form in summer, while in winter, epidemics of pulmonary Plague are observed; at the same time, with the onset of the cold period, bubonic Plague either ceases or turns into a pulmonary form, and pulmonary Plague ends with the onset of warm weather. This regularity has been repeatedly noticed in other places as well. Such a regularity is explained mainly by the conditions of human life in different periods of the year—in summer, people live more separately, and bubonic plague is caused by direct contact with infected animals or their insects. In case of its complication by secondary pneumonia, further transmission of the infection by droplet route does not have widespread distribution due to the instability. October November December January February March Human illnesses occur in some places undoubtedly through direct contact with sick Plague animals and their corpses, for example, when hunting gophers and marmots-tarbagans. Infection occurs when skinning gophers and tarbagans, as well as when butchering their carcasses and other manipulations. In addition, infection occurs through infected insects, mainly fleas.

Figure 2. Dependence of human plague on the epizootic curve in rats (Bombay, 1905-1906). Calculation in percentages in relation to the annual average (0-annual average).

resistance of the plague microbe to the action of light and heat; in winter, however, secondary plague pneumonia spreads rapidly by droplet infection among the closely living population, causing an outbreak of the pneumonic form of Plague. The bubonic form of Plague spreads slowly, does not produce large rises in the epidemic curve, and is often localized in specific districts, quarters, and even houses. Pneumonic plague spreads rapidly, produces a high rise in cases, and is easily carried to remote places. The mechanism of the emergence of summer and winter epidemics is not always the same; sometimes the emergence of winter pneumonic outbreaks of Plague is not connected with bubonic cases of the summer period, but depends exclusively on the lifestyle of rodents. For example, mice (Mus musculus) in the summer time live far from human dwellings, finding favorable conditions in nature for feeding and reproduction. In winter, mice, in search of food and for protection from the cold, migrate from the fields to populated areas where grain products are stored. As a result, mice come into close contact with humans. In the presence of an epizootic among mice, a winter outbreak of Plague occurs among people. In remote and isolated small settlements, where the first cases of bubonic Plague, complicated by secondary pneumonia, are observed, an outbreak of pneumonic Plague may begin. In the epidemiology of Plague, it has been established since 1897, when Ogata, through experiments on mice, established the presence of plague bacilli in rat fleas. Simond showed in 1898 that the transmission of plague from rat to rat occurs through the mediation of fleas. Subsequently, these observations were repeatedly confirmed, and at the present time, the role of fleas as transmitters of Plague from animal to animal and from animals to humans is not subject to doubt. Among rat fleas, Xenopsylla cheopis is of particular importance, being widespread not only among rats in India, but also among rats and other animals in other places (Japan, Formosa, Australia, Egypt, Algeria, Tunisia, North and South America, and Europe - Genoa, Marseille, Hamburg, the southeast of the USSR); another species of rat flea (Ceratophyllus fasciatus) is also significantly widespread. Several species of fleas are found on the gopher, of which Ceratophyllus tesquorum, Frontopsylla semura, Neopsylla setoza, Ctenophthalmus pollex, and others are more common. Under natural conditions, plague bacilli were found in Ceratophyllus tesquorum and Neopsylla setoza (Konovalova et al.), Ceratophyllus silantiewi (tarbagan flea; Suknev). Fleas of humans and other animals were found on the gopher, and gopher fleas bite humans. The mutual exchange of fleas of Indian rats with various animals (cats, rabbits, antelopes, etc.) and humans complements the picture of the importance of fleas in the epidemiology of Plague. Plague bacilli can not only live in the organism of the flea but also multiply there (Indian Commission), causing a peculiar blockage of the proventriculus, which leads to the regurgitation of the contents of the proventriculus during repeated attempts to suck blood and the possible introduction of microbes into the bite site. The mechanism of infection from the fleas of rodents and humans is not exhausted by the possibility of a flea bite. Plague microbes can live for a long time in the feces of fleas. Rubbing crushed fleas and their feces into the places of scratches and bites also leads to the infection of humans and animals. Animals can become infected by devouring their fleas. In plague-stricken rodents, cervical buboes are most often observed, because fleas are most often found on the back of the neck, and partly due to the devouring of fleas, sniffing of corpses, licking of places bitten by fleas, etc. Many deny the eating of corpses as an epidemiological factor even in rats (Indian Commission), believing that the infection of rats occurs mainly through fleas. In some places (India), it has been proven that the disease of rats is preceded by a maximum of flea reproduction and that years characterized by large flea reproduction produce a large epizootic among rats, which then causes an epidemic of Plague among people. In some places in India, it was established that during the absence of Plague, one could find on average up to 2 fleas on each rat; with an increase in the average number of fleas to 12-20 and more, an outbreak of Plague was observed among rodents. However, not all authors attach great importance to the flea factor in the spread of plague. Toyama, for example, on the basis of his experiments, considers the main factor of Plague transmission among rats to be the devouring of corpses of dead rats by healthy ones; other authors (Pearse, Hossack, and Crake) could not explain the diseases in Calcutta, Madras, and other places by the presence of fleas. It should be noted that the multiplication of plague microbes also occurs in the stomach of P. irritans, and it is possible to infect experimental animals with the bites of these fleas, although with greater difficulty than with rat fleas (Indian Commission). As for other insects of animals and humans, it has been established that tarbagan lice (Suknev), human head lice (Herzog), and body lice (Swellengrebel, Suknev), as well as gopher ticks (Rhipicephalus schulzei Ol.) (Golov and Knyazevsky) contain plague bacilli under natural conditions; however, the role of these insects in the epidemiology of Plague is limited, because lice easily and quickly die themselves from plague infection, and ticks rarely move to humans. It is important to note that rodents and their ectoparasites (fleas) play a greater epidemiological role the worse the sanitary-hygienic living conditions of the population are. The dirty dwellings of the poor in India, built of bamboo and leaves, serve as a lure and a convenient place for the nesting of rats, which leads to closer contact of the population with rats and their fleas. In multi-story buildings, cases of Plague among people are localized among the poor in basements and lower floors, sharply decreasing or being absent in the upper ones due to the reduction of rats. Thus, in India, among the lower Hindu castes, the incidence reaches 53.7‰, among Brahmins this figure drops to 20.7‰, and among Europeans it is equal to 0.8‰. In areas where mice play an epidemiological role in Plague, it is noted that the first cases among people more often begin in houses located on the outskirts of the settlement, closer to the field, from where mice come with the onset of cold weather. Rats have special importance in the spread of plague by ships, which has been repeatedly observed for the ports of Asia, Europe, and America. For example, in the port of Hamburg from 1903 to 1912, plague rats were identified on 45 ships. The main role in the spread of Plague by ships belongs to M. rattus (in 97.2%) and only an insignificant role is assigned to M. decumanus (2.8%). The constant storage of the Plague virus by rodents in certain territories depends on various conditions. In particular, Plague among rats is maintained, besides insects and the devouring of plague corpses, by the presence of chronic forms of Plague among these rodents (Gottshlich). Kolle and Martini experimentally observed "chronic forms" in rats in the form of suppuration of the bronchial glands, dense induration of the lungs, and encapsulated foci in the submaxillary glands containing plague bacilli for months. Hunter observed a large number of rats with chronic plague in Hong Kong; sometimes plague bacilli were found in rats without visible changes in organs (Raynaud). Chronic forms of plague were also confirmed in gophers, tarbagans, mice, hamsters, jerboas, etc. Undoubtedly, the percentage of immune individuals among adult rodents is higher than among young ones (McCoy), which explains the periodicity of plague epizootics among rats, gophers, tarbagans, and other animals. A very important moment ensuring the preservation of Plague among rodents is the presence of hibernation in some rodents. Dujardin-Beaumetz and Mosny established that hibernating marmots infected with Plague sometimes die on the 115th day with the presence of plague bacilli in the organs and blood and in the absence of a reaction to them in the organs. Outbreaks of Plague among gophers depend on their lifestyle. Thus, in the steppes of Western Kazakhstan, Plague among rodents is observed only in the southern parts. It turned out that gophers (C. pygmaeus) in the northern regions wake up from hibernation 2-3 weeks later than gophers in the southern regions, mate later, produce offspring later (susceptible to Plague), and go into hibernation earlier (Rall, Flegontova, and Sheikina). In former times, great importance was attached to the spread of Plague with goods, things, and especially clothing. In individual cases, the introduction of this kind of Plague into remote places was observed, for example, in 1899 in Buenos Aires from Oporto (Havelburg); nevertheless, this moment cannot be given great importance, keeping in mind the insignificant resistance of the plague microbe to drying, the action of light, etc. The transmission of infection by goods, clothing, etc., occurs in the presence of infected rodents and their fleas. Among goods, grain products (wheat, rye, oats, and rice) most of all present the possibility of the introduction of Plague (as places of the greatest accumulation of rodents). As for humans as a source of contagion, their role in bubonic Plague is quite limited, because the contents of ruptured buboes are not very contagious. Cases of the bubonic form of Plague among people, connected with each other, can be explained only by the role of insects. This possibility of transmission of Plague by insects from person to person depends on the presence of septicemia in the last stage of the infection.

In the pneumonic form of plague, rodents and their ectoparasites do not play a role; here, man himself acts as the agent, transmitting the infection either by direct contact or by droplet route. The role of the excreta and urine of a sick person is insignificant (Indian Commission). The perfection of modern means of communication and the liveliness of connections between countries contribute to the spread of plague. In former times, the routes followed by Mohammedan pilgrims served as the arteries along which plague was brought into Europe, and sea routes, along which merchants followed with their goods, gave the opportunity to carry plague to very remote places on the globe. In the epidemic of 1910–11 in Manchuria, railway and water routes of communication made it possible to widely disseminate pneumonic plague, which entailed officially more than 40,000 fatal cases, with a significant number of plague cases localized along the Chinese Eastern Railway. In the epidemiology of plague, one should also note the role of domestic animals, of which cats and dogs can be indirect carriers of plague. They can bring sick rodents with their insects into human dwellings. Cats, in addition, while suffering from plague, although rarely, are capable of directly infecting people. Dogs are little sensitive to plague contagion. Only very large doses of the plague microbe cause infection in dogs (Albrecht and Ghon et al.), but their excreta contain, after consuming plague-infected animals, fully virulent plague bacilli. However, the epidemiological role of cats and dogs is very limited, and only isolated cases of human disease have been observed that were connected with cats and dogs. Individual outbreaks caused by the consumption of meat from plague-infected camels have been described (Nikanorov et al.). Besides the ectoparasites of rodents and humans—fleas, lice, and ticks—some other insects may have a relation to the spread of plague in nature. The long-term storage of the plague microbe in the body of the bedbug and its excreta has already been indicated. Yersin as early as 1894 found plague microbes in the flies of his laboratory, and Nuttall established that house flies, when eating plague material, die from plague infection. Fly larvae that have developed on a plague-infected corpse contain plague bacilli, but pupae are mostly free from plague bacteria, and if flies develop from pupae containing plague microbes, they die within 12–24 hours (Gosio). With the help of flies (Stomoxys and Musca), it was possible to experimentally infect animals (Wayson). Some found plague bacilli in the proboscis and stomach of mosquitoes that had drunk the blood of the sick (Bon-nardiere and Xanthopulides), however, experiments on the transmission of plague to animals through mosquitoes were negative (Flu, Hunter). The English Commission observed under experimental conditions the transfer of plague through Stegomyia fasciata. Ants eat the corpses of dead rats and contain virulent plague bacilli, and the injection of ant secretions leads to plague infection in rats and mice (Hankin). Plague microbes pass through beetles and cockroaches alive and virulent (Giuseppe Cao), and infected cockroaches, although in a small percentage, die from plague (Barber). Earthworms for the most part die from plague infection, and a 70-day stay of plague microbes in the body of earthworms does not lead to their weakening (Fukuhara). Among other epidemiological factors, one should note the influence of climate and seasons, with climatic conditions affecting the epidemic curve partly directly, partly indirectly. The direct influence on the nature of the epidemic is manifested in the fact that in summer bubonic plague is observed, and in winter pneumonic plague (see above). In addition, in a hot climate during the hot season, the plague microbe easily dies due to its instability, and this leads to the fact that plague epidemics develop in a more temperate climate or on a high plateau with moderate temperature in hot countries. To the direct influence of climatic conditions, one should also attribute the increase in the number of cases of pneumonic plague in the coldest winter days (Petrov), which is explained, as already indicated, by the greater crowding of people in these days, and partly by their lower resistance to infection. Bubonic plague also shows a jump in the curve after cold days in places where mice play the role of carriers of infection, because in cold weather mice are found in greater numbers in the living parts of premises. The indirect influence of climate is manifested in the reduction of the period of wakefulness of hibernating rodents in a colder climate, which reduces the chances for the development of significant epizootics among them and hinders the transition of the epizootic to humans; furthermore, in cold periods of time, the reproduction of fleas slows down, which further reduces the possibility of the transition of diseases from rodents to humans. A hot climate and a dry, hot season, in turn, have an influence on the epidemic curve, reducing the number of fleas, which die in these conditions. All these moments are reflected in the corresponding way on the epidemic curve in plague, which is most common in conditions of a temperate climate and moderate temperature limits. All people, regardless of racial and national characteristics, are susceptible to plague. Occupation and profession sometimes have significance, as they increase the chances of infection. A special frequency of plague cases has been noted among tarbagan hunters, as well as bakers. In the latter, this is explained by easier and more frequent contact with rats and their excreta. A usually lower percentage (5%, according to Sticker) of cases in children under 5 years of age is noted, which depends not on lower susceptibility, but on less contact with infectious material, although epidemics have been described where the percentage of cases among children rose to 26. Poor sanitary-hygienic living conditions contribute to the emergence and spread of the epidemic.

V. Suknev.

Geographical distribution. The main foci of plague are located in the colonial and semi-colonial countries of Asia and Africa. The organization of medical aid in these countries is extremely primitive; therefore, official information on the number of illnesses and deaths from plague in them can hardly claim to be exhaustively complete. Below are the figures for registered cases of illness and death from plague for 1923–1932, based on official data published by the League of Nations. I. Asia. The world's largest foci of plague are concentrated in Asia. The number of registered cases of plague is given in Table 1. In East Asia, the largest foci of plague are located in China, in particular in Manchuria. The numerical data here are extremely scarce and do not give an idea of the scale of the plague. In the current century, the largest outbreak of plague in Manchuria was observed in 1910–1911 (about 44,000 people died). In 1920–1921, 4,529 deaths from plague were registered in the territory of the Chinese Eastern Railway, of which 4,179 were Chinese and 350 were Russians (in particular, 1,748 died in Harbin, 1,137 at Manchuria station, and about 1,000 in the Jalainur mines). In recent years, plague has been observed repeatedly in North and South Manchuria, as well as in Mongolia. In 1927, over 500 cases of plague were noted in the vicinity of Chengchiatun. In 1928, in the same area along the railway line in villages located between Chengchiatun and Chengchiatien, more than 1,200 people died from plague. The epidemic recurred in 1929 (over 400 cases) and in 1930 (more than 120 deaths). In September 1931, 18 people died in the Kaifeng area. In the province of Shanxi, plague epidemics were observed in 1917, 1919, 1925, and subsequent years. In 1928, about 4,000 people died from plague; in 1931, about 3,000 people. In total, more than 20,000 people died in the Shaanxi and Shanxi region in 1931. In recent years, plague has had a strong spread in the province of Fujian (southeast China), where 1,250 cases of plague were registered in 1931. In Japan, plague has been observed since 1897. The largest outbreaks were observed in Osaka (in 1907, 561 cases of illness and 509 deaths). In recent years, isolated cases have been noted. On Formosa, plague was observed from 1896 to 1917 (the largest outbreak was in 1904—4,500 illnesses and 3,374 deaths); since then, there have been no cases of plague. In Hong Kong (an island south of Canton; population in 1931 was 853,000), plague has been registered since 1894. The largest outbreaks were observed in 1908 (1,073 illnesses), 1912 (1,817), 1914 (2,146), and 1922 (1,181). The sequence of plague infection in individual ports of the Far East can be seen in Table 3. British India continues to remain the largest focus of plague to this day. If one sums the number of deaths from plague by five-year periods since 1898 (the beginning of registration), the following figures are obtained (Table 2) (the "plague year" in India, taking into account the movement of the monthly curve, is calculated from July 1 to June 30). The greatest number of deaths was registered in 1903–04 (1,138,451), 1904–05 (1,328,249), 1906–07 (1,286,513), 1910–11 (792,348), and 1917–18 (820,292). By individual provinces, plague is distributed unevenly. The second focus of plague after British India in terms of the number of victims is the Dutch East Indies. On Java, plague has been observed since 1911. It was first noted in the eastern port of Surabaya, where it was brought by rats arriving with a shipment of rice from British India. With shipments of rice, along with rats, the plague penetrated into the interior of the island. In some years (1925), the number of deaths amounted to 34.4 per 100,000 population. In addition to the countries listed in Table 1, in South Asia, plague is registered in Portuguese India, the Straits Settlements, the Malay Islands, and Singapore. Of the countries bordering the USSR in the east, there is no information about plague in the Mongolian Republic, where plague outbreaks are observed from time to time. In the Middle East, in addition to the countries listed in Table 1, plague was observed in Palestine (in 1922—64 cases, in 1923—15, and in 1924—2). II. Africa. In Africa, there are a number of foci of plague where it recurs from year to year (Table 4). In Northeast Africa, the largest of such foci is Egypt, where plague is scattered throughout the country. In port cities, it is observed annually here in Alexandria, Port Said, and Suez. In Northeast Africa, plague was also observed in Italian Somaliland (in 1924—84 cases). In Northwest Africa, in addition to the countries listed in Table 4, plague is observed in Tripoli (1921—24 illnesses, 1930—12, 1931—20). In West Africa, the largest focus is Senegal (French West Africa). Plague is also observed on the Gold Coast (in 1924, 322 illnesses and 272 deaths), in Gambia (1930), and Dahomey (1929). In Equatorial Africa, in addition to the listed countries, plague is observed in Nyasaland (1921, 1923, 1924), and in South Africa on Reunion (1927). In all foci in Africa, the plague does not yet have a tendency to decrease. Plague epidemics in colonial and semi-colonial (like China) countries serve as one of the vivid illustrations of the ruthless exploitation of these countries by European imperialists, the difficult economic and cultural situation of the working population in them, the lack of elementary care for the health of the population, and the systematic struggle against the plague. III. America. In North America, plague is observed in California (USA). Isolated illnesses were noted in Mexico (1922 and 1923). In South America, there are several foci of plague where it recurs from year to year. The largest of them are in Peru and Ecuador. Likewise, plague is registered annually in Argentina and Brazil. Isolated cases in individual years were observed in Bolivia (1923 and 1924), Venezuela (1923), Hawaii (1922 and 1923), Paraguay (1923), Uruguay (1923 and 1929), and Chile (1924 and 1926). The number of registered cases for some of these countries is given in Table 5. IV. Europe. The number of registered cases of plague for individual countries in Europe is given in Table 6. In Greece, cases of plague were observed [in the Kyrgyz steppes (Novaya Kazanka) and the Jambeytinsky district of the Ural region; 334 illnesses], in 1913 (Ural region, Astrakhan province, and the Kyrgyz steppe; 541 illnesses). In Transbaikalia, the plague is associated with epizootics among tarbagans.

From 1903 to 1926, isolated small outbreaks were also observed, with a total of 124 cases registered over 24 years. In 1921, an outbreak of plague was imported from Harbin into the Primorsky Region of the Far East. Cases were observed in Nikolsk-Ussuriysky and Vladivostok. In Turkestan, plague was observed in 1908 (in the Naryn Uyezd, Semirechye Region), in 1912–13 (in the Merv Uyezd on the border with Persia), in 1921 (in the Serakhs area on the border with Persia), and in 1924 (the village of Ak-Kamysh, Amu-Darya Region). In Transcaucasia, plague was observed in Azerbaijan: in 1913 in the village of Turkian (6 cases) and the village of Chikhirly (50 cases). In general, during the period of Soviet power, plague in the USSR has never spread beyond the two indicated regions (the southeastern steppe of the Caspian areas and the area of Transbaikalia bordering China). The isolated outbreaks that occurred during these years were quickly liquidated thanks to a widely established network of anti-plague institutions.

I. Dobreytser.

Pathological anatomy. From a pathological-anatomical point of view, two independent forms of plague are distinguished: bubonic and pneumonic. A third form, plague sepsis, is associated with them. Bubonic plague. A primary affect on the skin in the form of a primary phlyctena, pustule, plague carbuncle, and lymphangitis is usually absent. In bubonic plague, inflammatory processes in the external and internal lymph nodes predominate. As a rule, one group of lymph nodes is affected (less often one node), and the disease of this group is called a primary plague bubo. The localization of the primary plague bubo is connected with the site of infection entry. Primary buboes are most often located in the inguinal region (75%), then in the upper triangle of the thigh [see separate table (cols. 631-632), fig. 4], in the axillary, submandibular regions, or (especially in children) on the neck. Primary buboes sometimes reach the size of an adult's fist, e.g., inguinal ones. Sometimes they are insignificant and difficult to palpate. The skin over the primary bubo is tense, shiny, and dark red or dark blue in color. In a primary bubo, it is impossible to palpate individual lymph nodes; it appears as a whole packet. This is explained by the fact that the entire conglomerate of affected lymph nodes is covered by a general edema, spreading to the skin, subcutaneous tissue, fascia, and muscles, and gradually passing into inflammatory infiltration of the surrounding tissue. With severe edema, the corresponding part of the body is thickened compared to the normal state. When the bubo is localized on the lower limb, its flexion in the hip joint is observed. In acutely progressing bubonic plague, the bubo is covered with hemorrhages; the surrounding connective tissue is also infiltrated with erythrocytes and impregnated with edematous fluid. The primary bubo has a dense consistency, and the parenchyma of the lymph nodes swells in a brain-like manner. Due to the presence of necrotic yellow areas, the cross-section surface appears mottled and marbled. In cases of protracted bubonic plague, necrotic sequestra appear in the center of the swollen and hemorrhagic lymph nodes (4th-6th day), turning into cavities filled with thick purulent mass with necrotic tissue debris. With an even slower course of bubonic plague (8th-9th day), the primary bubo turns into a purulent cavity, and the changes in the surrounding tissue slowly undergo regression. In primary inguinal bubo, a whole chain of enlarged lymph nodes is found, located along the iliac vessels, as well as retroperitoneally along the spine up to the thoracic cavity. These lymph nodes, enlarged and infected from the primary bubo, are called primary buboes of the 2nd order. When a large number of plague bacteria enter the bloodstream, a new type of lymph node infection arises, namely secondary, metastatic from the blood, which leads to the formation of secondary buboes. Secondary buboes develop in all areas of the body, regardless of the location of the primary bubo. They are no larger than a hazelnut, moderately dense, and uniformly hyperemic. Subsequently, they undergo brain-like swelling, and small hemorrhagic foci appear in them. Microscopic changes in plague polyadenitis are diverse and depend on the location of the node and the stage of development of the pathological process. A combination of necrosis, hemorrhages, and leukocytic and bacillary infiltrations is noted in them. In the primary bubo, necrosis predominates. Karyolysis and karyorrhexis are observed, resembling in intensity the disintegration of nuclear substance in glanders (Albrecht and Ghon). On the periphery, hemorrhages, cellular and bacillary infiltrations predominate. In the capillaries and small vessels of the lymph nodes, especially at the site of the greatest accumulation of plague bacilli, there is a dilation of blood vessels and the transformation of their walls into homogeneous shiny strands and fibers that stain sharply with eosin (fibrinoid change). Staining for fibrin, according to Weigert, is negative. The same peculiarly coagulated mass is found in the lumen of the vessels, along their periphery, and among the adenoid tissue infiltrated with purulent cells and necrotic. Here, it is a matter of tissue necrosis and the coagulation of liquid masses under the influence of plague bacilli and their toxins. In the periglandular tissue, there are hemorrhages and a huge accumulation of plague bacilli and leukocytes, due to which the boundary between the lymph nodes and the surrounding tissue, which is in a stage of acute phlegmonous inflammation, is erased. Lymph vessels are dilated and contain a huge number of plague bacilli, sometimes an almost pure culture. The microscopic picture in primary buboes of the 2nd order is diverse and depends on the amount of plague bacilli, the speed of invasion, and the duration of the infection. In them, changes are localized in the area of the sinuses and the surrounding lymphadenoid tissue. Bacillary infiltration is in the foreground. Changes in the periglandular tissue are less intense. Secondary buboes give a different microscopic picture. Hyperemia predominates if the general infection has lasted for a short time; plague bacilli are found in the blood of dilated blood vessels in greater or lesser quantities, the capsule of the lymph nodes remains well preserved, and the lymphadenoid tissue is in a stage of brain-like hyperplasia. With a prolonged infection, microscopic changes characteristic of primary buboes can occur in secondary buboes. The spleen is more often enlarged (up to 22x17x6 cm), the capsule is tense, with hemorrhages. The pulp is red or dark red, slightly dry, finely granulated, the scraping is small, and the follicles do not noticeably protrude. In septic and mixed infections, these signs are absent. Histologically, the following are characteristic: hyperemia and hemorrhage in the pulp, an abundant number of leukocytes and plague bacilli in the pulp, and desquamation, proliferation, and degeneration of the endothelium in the venous sinuses. In the arteries of the Malpighian corpuscles and trabeculae, there are changes analogous to the changes in the vessels of the primary buboes. Sometimes there are small necroses in the pulp around the vessels with a huge number of plague bacilli (Albrecht, Ghon). In the serous cavities of the pleura, pericardium, and peritoneum, there is an accumulation of fluid that does not reach large sizes; on the parietal and visceral layers, there is hyperemia and hemorrhages ranging from pinpoint to the formation of extensive hemorrhages and hematomas in the mesentery and retroperitoneal tissue. In parenchymatous organs (heart, liver, kidneys), there is severe albuminous clouding or fine-droplet fatty degeneration and hemorrhages. In the liver and kidneys, there are sometimes numerous foci of metastatic necrosis around small arteries with a huge number of plague bacilli, in addition to a peculiar coagulation of the vascular loops of the glomeruli and hyaline thrombi; in the dilated renal pelves and ureters, there are accumulations of fresh clotted blood. The mucous membrane of the larynx, trachea, and bronchi is hyperemic, swollen, and hemorrhages are frequent on it. Almost all lymphatic follicles of the mucous membranes of the respiratory tract are swollen. Secondary metastatic bronchopneumonias are observed, according to Choksy's statistics, from 1% to 3.5%. They apparently can occur in every case of ordinary bubonic plague. Secondary bronchopneumonic foci are characterized by multiplicity and their peripheral location; their size ranges from an oat grain to a hazelnut. They sometimes have an infarct-like appearance. The pleura over the foci in the lungs is clouded, with sharp injection of vessels, dotted with numerous petechiae, or covered with yellowish films. Bronchopneumonic foci are of a delicate yellowish or reddish-gray color, non-granular, and on the cut surface, there is a viscous, turbid mass. The periphery of the foci is colored dark red with sharp edema of the lung tissue. Histomorphologically, the following are noted: dilation of the alveolar cavities, accumulation of leukocytes, mononuclear cells, desquamated epithelium, a small amount of fibrin, a homogeneous or granular protein mass, or a large number of erythrocytes and plague bacilli in them. In the capillaries and small vessels, there is a large number of plague bacilli. Aspiration bronchopneumonias occur in the severe form of necrotizing angina, with necrotic disintegration of the follicles of the root of the tongue or the posterior wall of the pharynx (Albrecht and Ghon). In such cases, purulent bronchitis is often observed. Histological examination reveals a mottled composition of exudate with plague bacilli and necrosis in the alveoli. In the digestive tract, starting from the oral cavity, no special changes are noted in bubonic plague, except for those associated with circulatory disorders. It should be noted that multiple petechiae and hemorrhagic erosions form on the gastric mucosa; in the small intestine, swelling of the solitary follicles and Peyer's patches and the formation of superficial defects are found. The exception is those relatively rare cases when the upper digestive tract serves as the portal of entry for the infection or when changes are observed here as sequential lesions in the presence of primary cervical plague buboes. In such cases, phenomena of fresh hemorrhagic inflammation of varying degrees are observed on the tonsils and on the lymph follicles of the entire posterior wall of the pharynx: swelling, hemorrhagic infarction, ulcer formation, and severe edema (plague angina).

The absence of lesions in the mesenteric lymph nodes with changes characteristic of primary buboes argues against the primary gastrointestinal form of Plague. Changes in the central nervous system consist of edema of the pia mater of the brain and the substance of the brain itself. Hemorrhages are more often encountered on the inner surface of the dura mater. Sharp hyperemia of the brain substance is observed. The sympathetic ganglia of the abdominal cavity are often altered. Histologically, the formation of hyaline thrombi in their vessels, edema of the interstitial tissue, leukocytic infiltration, and necrosis with plague bacilli have been traced. In the ganglionic cells of the sympathetic nodes, there are hydropic changes and karyolysis (Shirokogorov). Some cases of sudden death are dependent on the lesion of the celiac ganglion. On the skin (cutaneous Plague in the narrow sense of the word), besides primary phlyctenae, pustules, and carbuncles, multiple hemorrhages are observed; the latter, however, are not of such a size as to justify the name 'Black Death' which was given to Plague in the Middle Ages. Much more often, secondary skin lesions are observed in the form of carbuncles at the site of the primary buboes, pustules resembling smallpox pustules in their distribution, and pemphigoid vesicles, in the serous or purulent contents of which and in the tissue, upon microscopic examination [see separate table (col. 631-632), fig. 5], plague bacilli and leukocytic and bacillary infiltrations are discovered. Pulmonary Plague. Here, the primary localization of the plague infection in the lungs is meant. The main type of primary plague pneumonia is lobular. The lobar type, which causes much discussion, i.e., hepatization of the entire lobe of the lung, as in croupous pneumonia, is not encountered in primary pulmonary Plague (Wu Lien Teh et al.). Lobular bronchopneumonias are encountered in one lobe or simultaneously in several lobes, giving a type of lobar or pseudolobar pneumonia. Finally, septicemia is observed as a special form in the respiratory form of infection (pulmonary type—Wu Lien Teh). Defenders of the tonsillar theory (Kulesha) consider plague pneumonia to be of hematogenous origin, but the majority insist on the respiratory form of infection, arising from the lower, deep part of the respiratory tract. Lobular bronchopneumonias are more often located subpleurally, less often centrally: they have a wedge-shaped or rounded form. The former, located peripherally, are more sharply demarcated. Sometimes smaller foci are encountered, of a paler color and difficult to define (acinous and miliary necroses). The color of the lobular foci is red or delicate gray-red. The cut surface is non-granular; a grayish-yellow or reddish-gray mucous turbid mass is scraped off, containing leukocytes, parts of elastic fibers, epithelial cells, and plague bacilli. The affected lobes are moderately enlarged, slightly emphysematous; the unaffected ones, e.g., the lower ones, are sharply hyperemic, edematous, dense, and give the impression of lobar red hepatization. Similar areas of small size are encountered between foci of gray or red hepatization, from which a picture of different stages of hepatization arises in one and the same lobe of the lung. According to a summary table (Cannel, Kulesha, Tsurumi, Wu Lien Teh), covering 123 cases of plague pneumonia, one lobe of the lung was affected in 58 cases, several lobes in 65 cases, the right upper in 51 cases, the right middle in 10 cases, the right lower in 60 cases, the left upper in 43 cases, and the left lower in 56 cases. Histological changes are different depending on the stage of the infection. In the very earliest stage (Jettmar's case), numerous plague bacilli were discovered around the bronchioles, in the lymphatic spaces of the interstitial tissue, and under the pleura. The vessels are hyperemic. In the alveoli, there is serous exudate with a large quantity of plague bacilli, which makes it look like a bacterial emulsion (Kulesha), where involutional forms of bacteria are almost absent. Further, the exudate becomes serous-hemorrhagic; fibrin is almost absent. Macroscopically, this stage corresponds to red hepatization in croupous inflammation. Subsequently, the alveoli expand strongly, the number of neutrophils increases; nevertheless, the stage of gray hepatization does not reach a full degree, because there is a fairly large admixture of erythrocytes. The quantity of plague bacilli decreases, involutional forms are encountered more often, and in some alveoli they disappear completely (bacteriolysis). In other parts, the exudate contains only a huge quantity of plague bacilli, and the cellular content in the alveoli is small ('bacterial hepatization' - Tsurumi). The alveolar septa are turned into a shiny, structureless network of varying thickness, in places almost disappeared (fibrinoid change). Similar changes are observed in the walls of small vessels, or hyaline thrombi are encountered in them. Staining for fibrin, according to Weigert, gives a negative result in these areas. In such areas, the exudate consists of a necrotized granular mass; hemorrhages are frequent. In later stages, the quantity of plague bacilli increases around the vessels and in the blood. The bronchioles are also dilated, their walls are necrotized. The mucosa of the trachea and bronchi is hyperemic; in their lumen is a frothy, bloody exudate. Their mucous membrane is in a stage of catarrhal inflammation; in some cases, necrosis of the epithelium is observed. In the epithelium, the submucosal layer, and in the glands, right up to the cartilaginous rings, surrounding and penetrating the blood vessels, there is a large quantity of plague bacilli. Microscopic changes in the upper respiratory tract are insignificant. Hyperemia of the mucosa of the tongue, pharynx, and larynx is observed; hemorrhages are rare. Kulesha notes necrosis and ulceration of the tonsils; microscopically, there is an accumulation of plague bacilli in their crypts; the changes in the tonsils themselves, according to Kulesha, resemble the changes in cutaneous plague pustules. The peritracheal and bronchopulmonary lymph nodes are enlarged, of an uneven red color; periglandular changes are less pronounced than in bubonic Plague. Histologically, the following are noted in them: hyperplasia of the sinus cells, accumulation of mononuclear cells, hemorrhages, necroses, and a large accumulation of plague bacilli. By their changes, the nodes resemble primary buboes of the second order. In the pleural cavities, a small quantity of serous-hemorrhagic exudate is encountered. On both layers of the pleura, at the site of the bronchopneumonic foci in the lungs, there are delicate fibrinous films or thick fibrinous deposits (Wu Lien Teh), and hemorrhages, which are encountered in large quantities also in places free from pneumonic changes. The visceral layer of the pleura is sometimes colored a bright red, with a well-distinguishable network of minute vessels. Rarely, the pleuritic exudate is of a purulent character (Kulesha), which is encountered in mixed infections and in pulmonary tuberculosis. Pericarditis is encountered extremely rarely. On the inner side of the pericardium and on the epicardium, there are multiple petechiae. The heart is usually dilated, especially the auricles. Dürck describes verrucous endocarditis of the mitral valve in mixed infection. In the heart muscle, there is sharp cloudy swelling or fine-droplet fatty degeneration. The spleen is often more or less enlarged, sometimes slightly, or in size no larger than normal; its consistency is denser than in other infections. The pulp is often of a reddish, almost pinkish color (Shirokogorov, Wu Lien Teh). The trabeculae do not stand out noticeably; the follicles are either indistinguishable or of small size, their periphery is red. Hemorrhages are encountered under the capsule and in the pulp. Rarely, small anemic infarcts have been observed (Dürck, Strong, Wu Lien Teh). Histologically, plague bacilli were discovered in large or small quantities in the pulp; proliferation of the endothelium and pulp cells is noted. In Jettmar's case, plague bacilli were absent in the spleen. In the digestive organs and in the kidneys, no specific changes are discovered in primary pulmonary Plague, with the exception of acute parenchymatous degenerations, fine-droplet fatty degeneration, focal necroses, hyperemias, and petechial hemorrhages, which are generally characteristic of acute infection. In the vessels of the organs, there is a small quantity of plague bacilli. Plague sepsis. Cases of plague sepsis proceed under the guise of a general disease with the character of hemorrhagic septicemia, both in bubonic and in primary pulmonary Plague. Here, the tonsillar theory of the origin of plague sepsis acquires great importance. On the other hand, focal phenomena may be completely absent (pulmonary type—Wu Lien Teh). In plague sepsis, the signs of bubonic or pulmonary Plague may acquire a secondary character. The bacteremia often observed in Plague does not yet mean sepsis; it may appear even shortly before death. In the pathological-anatomical picture of plague sepsis, the changes specific to Plague are erased. Phenomena of septic hemorrhage and jaundice are expressed; focal alterative (hyperergic) changes are noted in the parenchymatous organs (necroses, degenerative fatty degeneration), or, more rarely, vulgar pyemic abscesses are observed, often described as specific changes in Plague.

In all cases, there is a significant enlargement of the spleen with a septic character, sometimes infarcts, a moderate enlargement of the entire lymphatic apparatus (often the mesenteric and retroperitoneal lymph nodes) with the formation of hematomas in the wall of the abdominal cavity, and the formation of defects (ulcers) on the mucous membrane of the pharynx, and in the intestines—the cecum and rectum (e.g., in the pulmonary type), which were often mistaken for the intestinal form of plague (Vysokovich, Zabolotny). A sharp edema of the pia mater of the brain is noted. In all cases of sepsis, a greater or lesser number of plague bacilli are noted in the blood and vessels. Cases of sudden death are often associated with plague sepsis. Both in the bubonic and in the pulmonary form of plague, rigor mortis sets in quickly and remains for a long time, with the exception of cases of mixed or septic infection. Skeletal muscles are described as either moist or dry, dark, pale, and bright red, which often depends on the conditions of preservation of the corpse. Edema of the trunk and limbs on the corpse was registered by the Indian Commission. The skin of the corpse sometimes has a cyanotic color. Cases of chronic plague ("plague marasmus") lead to severe emaciation of the corpse; in prolonged cases of the bubonic form of plague, deep necroses are noted on the skin of the corpses at the site of the primary buboes, pustules, and carbuncles.

S. M. M. Mogapov.

Pathogenesis. Plague bacilli penetrate the organism through the skin, mucous membranes of the mouth, nasopharynx, respiratory tract, and gastrointestinal tract. Depending on the site of penetration of the plague bacilli, it is customary to distinguish the following forms of plague: cutaneous, bubonic, pulmonary, septic, and intestinal. The development of the disease process proceeds as follows. Having penetrated the skin or mucous membrane, plague bacilli cause a local disease in the form of the cutaneous form of plague or local lesions of the mucous membranes (angina pestica). Usually, following the skin lesion, the plague bacillus penetrates along the lymphatic vessels into the nearby lymph nodes, which increase in size. In this case, we will have a primary cutaneous ulcer and secondarily a bubo, and the disease may be complicated by the further penetration of plague bacilli into higher-lying nodes, producing a tertiary bubo, or the microbes penetrate into the blood, are carried to the lungs, and cause pneumonia as a process of the third order; finally, the plague bacilli, before penetrating into the lungs or after the lesion of the lung, multiply in the blood, causing septicemia of the third or fourth order. Most often, however, the plague microbe leaves no trace in the skin and mucous membranes at the site of the portal of entry and immediately penetrates along the lymphatic vessels to the nodes, causing the formation of a primary bubo, followed by a secondary bubo of the affected higher-lying node, or secondary pneumonia, or secondary or tertiary septicemia. Upon reaching the mucous membranes, especially of the nasopharynx and upper respiratory tract, the plague microbe penetrates into the lung tissue without prior lesion of the mucous membranes or nodes, causing primary pneumonia of a plague nature. By what route—aspiration, lymphatic, or hematogenous—the plague microbe enters the lungs has not yet been clarified, but the lymphogenous route is more likely. However, the aspiration route cannot be excluded (Strong). The hematogenous route of infection (Kulesha) is apparently unlikely (Jettmar). Having entered the lung tissue, the plague microbe is expelled with droplets of sputum during coughing, sneezing, and talking and serves as the cause of primary pneumonia upon entering the respiratory tract and the nasopharyngeal mucosa of healthy people. The intestinal form of plague is most often a secondary process, but in rodents, upon ingestion of plague material, a primary intestinal form can also develop. Each form of plague disease, in the case of a fatal outcome, ends in sepsis. The hemorrhages and necrotic nodes characteristic of the plague process are the result of the action of the plague toxin. The characteristic symptoms from the cardiovascular and nervous systems, consisting of pulse disturbances and severe nervous phenomena, must be explained by the action of the plague toxin. Clinical picture. The cutaneous form of plague develops at the site of penetration of plague bacilli into the organism upon a bite or the rubbing into skin wounds of a crushed infected insect or its feces, as well as upon the entry of plague microbes by any other route onto damaged skin or mucosa. A plague lesion of the skin begins with a spot, at the site of which a vesicle (phlyctena) soon forms, ranging in size from a pea to a hazelnut. The phlyctena is filled with grayish or yellowish contents, sometimes with an admixture of blood, and is surrounded by a rim of bright red skin. In case of recovery, rapid resorption of the vesicle occurs, followed by the formation of a scab with subsequent healing of the skin without a scar (Shirokogorov); in other cases, the vesicle turns into a pustule or even a carbuncle with deep infiltration of the underlying tissue. The pustule, and even more so the carbuncle, upon breakdown, produces an ulcer. The dried ulcer forms a black necrotic scab, resembling an anthrax carbuncle, and heals with the formation of a scar. Cutaneous lesions of the primary order are extremely rare; thus, in the Odessa epidemic of 1910, they were noted only twice out of 147 cases, while in other cases, the number of cutaneous lesions reaches 10%. From the pustule or carbuncle, cords of inflamed lymphatic vessels sometimes extend, reddened and indurated to the touch, with subsequent secondary involvement of regional nodes. In some cases, the appearance of phlyctenae, pustules, and carbuncles is observed as a secondary phenomenon with a primary bubo. Only in rare cases do significant skin lesions develop, which heal slowly or lead to marasmus with a fatal outcome, or the disease may end in death from septicemia before other symptoms have time to develop. Mortality in the cutaneous form of plague in the presence of complications ranges from 40-50% to 60%. The bubonic form of plague most often develops as a primary process without prior skin lesion. Such primary buboes, representing a lesion of the lymph nodes, appear simultaneously with fever, and sometimes even precede it. Sometimes, however, buboes are discovered late—on the 4th-8th, or even the 17th day of fever (Müller). The bubo, painful to the touch, represents a cluster of inflamed lymph nodes fused together, and as the bubo increases in size, the skin over it becomes tense, smooth, takes on a dark red color, and becomes hot. Along with this, the connective tissue is involved in the inflammatory process. The bubo, fusing with the skin, becomes immobile. Usually, the bubo increases over 5-6 days (Dorizo and Isakovich), and then either undergoes regression or softens, suppurates, and opens on the 8th-10th day. Scarring at the site of the bubo ends in 3-4 weeks. The suppurative process is accompanied by a decrease in temperature. The resulting necrotic ulcer sometimes does not heal for a long time and leads to plague cachexia, especially in cases complicated by staphylococcal or streptococcal infection. On the skin covering the bubo, there may be hemorrhages of greater or lesser size. The size of the bubo ranges from a small nut to an orange, and the swelling is sometimes visible to the naked eye. In adults, the inguinal and femoral nodes are more often affected, in children—the cervical ones. In the contents of the bubo, as well as in the edematous fluid of the surrounding tissue, there is a mass of plague bacilli. With the onset of the suppurative process, they gradually disappear; in other cases, they can persist for weeks in the bubo, even one that has suppurated (see above). Secondary involvement of nodes should be distinguished from primary; secondary buboes are multiple, rarely suppurate, are less painful, and undergo the process of regression faster (within 1-2 weeks). As already noted, in bubonic plague, not only secondary involvement of nodes can occur, but also secondary pneumonia, and before death, 24-48 hours prior, septicemia. Pulmonary plague (primary) begins without precursors, suddenly. Chills, malaise, headache, and an increase in temperature to 37.5° appear, which after 2-3 hours rises to 38° and some tenths, and after a few more hours reaches 40° and higher, at which levels it most often remains until death (Fig. 3). Weakness increases, restlessness, agitation, and pains in various places appear, nausea and vomiting occur. Consciousness sometimes remains intact, but more often it is more or less clouded, and delirium appears, sometimes quiet, sometimes restless and violent. A painful cough appears, accompanied by the expectoration of a small amount of mucous, colorless sputum, which soon becomes abundant, liquid, foamy, and colored most often bright red from an admixture of blood. Cough and sputum can sometimes be insignificant or even completely absent. With the further development of pulmonary plague, dyspnea [50-75 breaths per minute (Müller)] and cyanosis occur. The pulse quickens to 100 and higher per minute, becomes weak, and irregularities appear. In plague pneumonia, the severity of the infection does not correspond to the slight findings of auscultation and percussion. Primary pneumonia most often affects the lower lobe of the right lung and has the character of pseudolobar pneumonia. Other lobes of both the right and left lung are not excluded. Figure 3. In the case of a central location of the focus in the lung, dullness is difficult to ascertain or is not detected at all if the focus is small. Sometimes a clear tympanic tone is detected upon percussion. Breathing is sometimes vesicular, sometimes bronchial, sometimes indeterminate, and is accompanied by various rales. Microscopic examination of sputum, its culture, and the infection of animals with it allow for a correct diagnosis. Pneumonia in plague can be a secondary phenomenon, joining other forms of plague: bubonic, intestinal, and septic. Secondary pneumonia has a catarrhal lobular character, proceeds more slowly than primary pseudolobar pneumonia, and rarely results in recovery. In secondary pneumonia, unlike primary, the middle lobe of the right lung or the upper lobes of the lungs are involved in the disease process, and multiple foci are also observed. The intestinal form of plague is rare and can be primary or secondary. The primary form, although very rare (Wilm, Galeotti), is characterized by elevated temperature and symptoms from the gastrointestinal tract resembling cholerine: nausea, vomiting, rice-water stools initially, with blood streaks later. In the stools, there are sometimes significant quantities of plague bacilli.

Occasionally observed are: irritation of the peritoneum, likely from inflammatory processes in the iliac lymphatic glands, hemorrhages in the mucosa of the stomach and intestines. The primary intestinal form of Plague can develop upon ingestion of food containing plague bacilli (meat of infected animals), which has been proven experimentally (Muller, Poech); the secondary form develops upon swallowing sputum by a plague pneumonic patient (Albrecht, Ghon). The septic form is more often the final stage of every fatal case of Plague in any of its forms, although cases of early transient bacteremia have been observed in bubonic Plague. As a primary form of Plague, septicemia is encountered relatively rarely. Both primary and secondary septic forms of Plague almost always end in death. The septic form of Plague begins immediately with chills and high fever (39-41°), which persists until death, sometimes showing remissions in the mornings. With it, hemorrhages from the intestines, kidneys, and bloody vomiting are encountered. Upon examination of the blood, a significant quantity of plague bacilli is found. Plague sepsis sometimes proceeds fulminantly, ending in death a few hours after the onset of the disease. The incubation period for Plague is 2-3, rarely 5 days. The International Sanitary Convention of 1926 established the period of observation and isolation for suspected Plague at 6 days. The onset of Plague usually begins suddenly, and only as an exception have prodromal phenomena been observed in the form of general malaise and feeling of being unwell. The onset of the disease is characterized by chills, headache, dizziness, weakness, and a certain stupor of the patient. In the case of bubonic Plague, already from the very beginning, tenderness is sometimes noted at the site of the emerging bubo. In typical cases, the appearance of the patient is quite characteristic—facial features become sunken, the nose sharpens, the complexion changes, taking on a red or earthy hue, and sometimes becomes cyanotic. The eyes are wide open, pupils dilated, the conjunctiva is bloodshot. The patient is sometimes agitated and has the appearance of a drunkard, sometimes lethargic and indifferent. Rarely, a delirious state is observed: sometimes restless, even violent, sometimes quiet and passive. Sometimes the patient retains consciousness until death. The temperature rises rapidly to 39.5-41° and stays at these figures until death or shows remissions in the early morning hours. In cases of recovery, the fever resolves by lysis after 6-9 days and then subsides. A new rise in temperature indicates either the appearance of secondary plague phenomena (buboes, pneumonia, sepsis) or the suppuration of a bubo, caused by streptococci, staphylococci, etc. The skin of plague patients is dry and hot. On the skin, one can often detect petechiae and hemorrhages, either single or multiple, which gave reason in olden times to call Plague the "Black Death." Herpes labialis is not encountered in Plague. In severe cases, bedsores and gangrene are possible. From the nervous system, characteristic signs of intoxication appear early, such as: headache, dizziness, unsteady gait, clouding of consciousness up to deep hibernation and stupor, delirium, monotonous slowed speech, respiratory disorders, and sometimes even phenomena of meningism. Regarding cardiovascular activity, the discrepancy between pulse rate and temperature draws attention. In the very first days of the disease, the pulse is about 120-130, later 140-150 beats per minute. Blood pressure falls rapidly, the pulse becomes frequent, thready, arrhythmic, sometimes paradoxical, and is very difficult to palpate, so that one has to count the number of heartbeats by auscultation of the heart. During the recovery period, the pulse remains weak, frequent, and of low tension for a long time. The heart is very sensitive to plague intoxication; heart sounds are muffled, especially the first, which sometimes disappears completely; the second sound, especially in cases of involvement of the inguinal, iliac, and lumbar glands (Muller), is often accentuated. As for the respiratory tract, it does not present any special changes; bronchitis is a fairly frequent phenomenon. Pain in the side appears upon involvement of the pleura in the pathological process, especially when plague bacilli are localized in the bronchial glands. Phenomena from the digestive organs are insignificant, with the exception of the intestinal form of Plague. Appetite is sometimes absent, sometimes increased; thirst is an almost constant symptom. Nausea and vomiting are rarely severe, sometimes completely absent; before death, sometimes painful hiccups are observed. Stool is sometimes regular, sometimes delayed or frequent. In the feces, there is occasionally an admixture of blood and mucus. Lips are dry, sometimes cracked, often cyanotic. The tongue is covered with a gray-white coating, swollen, and trembles when protruded. The mucous membranes of the mouth, pharynx, soft palate, and epiglottis, as well as the tonsils, are often hyperemic. The spleen is enlarged, the liver is occasionally slightly enlarged and sensitive to pressure. In cases of involvement of the portal lymphatic glands, mild jaundice is observed. Plague bacilli have been found in the bile. Regarding urine, sometimes polyuria occurs, and in fatal outcomes in the last days, sometimes complete anuria. Urine is often saturated, contains an admixture of blood and a small amount of protein, the reaction is acidic, and the diazo reaction is negative. In the sediment, there is a large number of hyaline and granular casts, less often epithelial and blood casts, and even more rarely waxy casts. Leukocytes and erythrocytes are encountered. The genital organs usually do not present any changes; with inguinal buboes in men, edema of the scrotum is sometimes observed, and in women, of the labia majora. Uterine bleeding is often observed, and menstruation intensifies. Pregnancy is most often either interrupted by miscarriage or the children are born dead. The blood does not present any special changes: erythrocytes are normal, leukocytes are increased up to 45 thousand (Poech) and even up to 200 thousand (Aoyama) at the expense of polynuclear cells. Regarding the eyes, a characteristic sign of Plague draws attention: conjunctivitis, sometimes with hemorrhages; occasionally, keratitis and even panophthalmitis are encountered. No special changes are observed in the other sense organs. The corpses of the deceased often assume bizarre postures, which is explained partly by the rapid death that caught the patient in various positions during a delirious state, and also likely by convulsive phenomena in the pre-death period. Course and outcome. According to the severity of the disease, they distinguish pestis minor—mild cases of Plague, pestis ambulans—more severe cases, pestis bubonica and pestis pneumonica—severely proceeding diseases (Choksy), and finally pestis siderans (s. fulminans)—fulminant. Usually, the duration of the disease is from 3-5 to 6-8 days; from the 6th day, the prognosis quoad vitam improves. In other, rarer cases, the disease is prolonged due to secondary complications, exhaustion sets in, and patients perish with phenomena of plague marasmus. Cases of death on the 252nd day from the onset of the disease have been observed, with plague bacilli discovered in the spleen and axillary glands (Albrecht, Ghon). In milder cases, the disease proceeds with low temperature, insignificant phenomena from the lymphatic glands, and ends within 2-3 days. Patients work, and sometimes do not even consult doctors. Such mild forms are recognized only retrospectively. It is undoubted that in the past, epidemics of tularemia were mistaken for pestis minor or p. ambulans. Fulminant forms of Plague end within a few hours with a fatal outcome. Cases of death 3 hours after the onset of the disease have been described (Weir). In uncomplicated Plague, recovery even from severe forms occurs quickly. In other cases, however, the convalescent exhibits weakness, drowsiness, and slight excitability of the cardiovascular and respiratory apparatus for a long time. Complications can be caused by both plague bacilli and extraneous microbes. Complications of any of the primary forms of Plague can manifest as involvement of the lymphatic glands (secondary buboes), lungs (secondary pneumonia), intestines, and skin, as well as general sepsis. To this should be added plague meningitis, which can develop early and even be an independent form. Secondary infection with streptococci or staphylococci worsens the prognosis, since, for example, the combination of the plague microbe with a streptococcus or B. Friedlanderi sharply increases the virulent properties of the former. A particularly frequent complication in Plague is the suppuration of glands caused by pyogenic microbes, which can end in pyemia. Secondary infections with Fraenkel's diplococcus, B. Friedlanderi, streptococcus, staphylococcus, influenza bacillus, etc., can cause pneumonia, nephritis, paralysis, deafness, purulent inflammation of the ear, parotitis, skin and muscle abscesses, etc. In Plague, relapses are sometimes observed, even several weeks after recovery, and relapses proceed unfavorably. Cases of recurrent Plague disease are also observed, which usually proceed mildly. The lethality in the pulmonary form of Plague reaches almost 100%. Only isolated cases of recovery from primary pulmonary Plague (serum treatment) and a negligible number of cases of recovery from secondary pneumonia have been described. The septic form of Plague is also almost absolutely fatal. The most favorable form for prognosis is the cutaneous form of Plague, and somewhat less so is the bubonic form. In different epidemics and under different conditions, the lethality from bubonic Plague fluctuates from 23.6% (Odessa, 1910) to 95%. The prognosis depends on the form of the disease, the severity of the course, and complications.

It should be borne in mind that at the beginning of an epidemic, a comparatively low mortality rate is sometimes observed, which reaches maximum figures at the height of the outbreak, only to decrease again towards the end (14.28% in Bombay). Mortality from plague does not depend on sex, but is related to age, yielding the highest figures for the age of 50-60 years. The younger the age, the lower the mortality. Diagnosis. Timely diagnosis, especially of the first cases of plague, is of enormous social and state importance, since the earliest possible localization of the infection and the prevention of an outbreak depend on it. When recognizing plague, it is necessary to rely on the above-mentioned characteristic clinical symptoms of plague, confirming the diagnosis with bacteriological examination. For bacteriological examination, depending on the clinical form of plague, one takes the contents of skin vesicles, pustules or ulcers, juice from a bubo (by puncture with a syringe needle or by incision), sputum, blood, or feces. Microscopic finding of characteristic bipolar polymorphic bacilli allows one to suspect plague infection and make a preliminary diagnosis. Usually, during microscopic examination of plague material, a huge number of characteristic microbes are easily found. Exceptions are cases of suppurating buboes, cases of recovery or chronic cases, as well as feces and blood, where it is not always easy to detect the presence of plague bacilli. Inoculation of material onto agar and broth is mandatory in all cases, regardless of a positive or negative microscopic examination. Characteristic growth on broth, typical colonies on agar, and corresponding microscopy data make the diagnosis of plague highly probable. It becomes indisputable upon obtaining a pure culture that agglutinates to the titer with specific anti-plague serum and causes typical experimental infection in animals. Guinea pigs, as well as mice, gophers, and other rodents, are most often used for infection. Infection is performed subcutaneously or intraperitoneally if the material is assumed to be free of extraneous microbes. In case of suspected contamination of the material with extraneous microbes, it is necessary, along with subcutaneous and intraperitoneal infection, to perform rubbing of the material into 1-2 animals on a freshly shaved surface of the abdomen (Austrian method). This allows, even with heavily contaminated material, to obtain plague infection in the animal and, consequently, to isolate a pure culture of plague. A characteristic pathological anatomical picture in animals that have died from the infection, obtaining a pure culture upon inoculation from organs and blood, and the agglutination reaction ensure the correctness of the final diagnosis. In addition to the clinical picture of the disease and bacteriological examination, epidemiological analysis of the disease comes to the aid. The detection of bipolar bacilli with a little-suspicious clinical picture of the disease in an area free of plague, in people who have not had contact with plague patients and plague foci, excludes the plague nature of the disease. Conversely, the finding of bipolar bacilli, even with an uncharacteristic clinical picture, is extremely suspicious in patients in an endemic plague focus; the establishment of a connection of this case with a plague patient or with animals suspected of having plague makes the microscopic diagnosis of plague highly probable. Nevertheless, even in these cases, the final diagnosis is established only upon obtaining a pure typical culture of plague. Serological reactions for early recognition of plague have no practical significance, since specific agglutinins, precipitins, and complement-fixing substances appear in the blood of patients only from the 7th day. They can be used for recognizing protracted cases. The serum of patients agglutinates plague bacilli in a dilution of 1:50, rarely 1:100. Treatment. At present, drug treatment of plague is reduced to the use of symptomatic agents. To support cardiac activity, camphor, caffeine, digitalis preparations, strophanthin, etc., are used. Some (Rai Bahadur Kailaschander, Anderson) recommend the use of adrenaline. Eusol, formalin, iodine, and salvarsan, yatren, as well as other arsenic preparations, have not yielded positive results. For bubonic plague, warming compresses with the use of ointments (ichthyol, etc.) and subsequent opening of the bubo in case of its suppuration are recommended. In general, pharmaceutical agents are powerless in the treatment of plague. Even less success should be expected from surgical intervention, which consists of extirpation of buboes. This operation may even accelerate the onset of septicemia. Specific treatment of plague in the form of saline and glycerin vaccines from the bodies of plague microbes has not yielded convincing results and has now been abandoned. Specific anti-plague sera are currently widely used, but so far without good results, therefore their effectiveness is disputed by many. At present, anti-plague serum is prepared by the Pasteur Institute in Paris, the Institute of Infectious Diseases in Bern, the Institute of Microbiology and Epidemiology in Saratov, the Oswaldo Cruz Institute in Brazil, and in institutes in India, Japan, and other places. The following sera are most commonly used: Parisian, Lustig's and Galeotti's, and Markl's. The Parisian serum is obtained from horses immunized with increasing doses, first of killed plague bacilli, and then with live cultures subcutaneously and intravenously. Immunization ends with the injection of filtrates of old broth cultures containing the suspected toxin. Immunization lasts from 8 months to 1 1/2 years, is tolerated quite difficultly by animals, and is brought up to the injection of 8-12 agar cultures of live plague bacilli. The serum is bactericidal and contains agglutinins, precipitins, bacteriolysins, opsonins, bacteriotropic substances, and, according to some, antitoxins. The antitoxic serum of Lustig and Galeotti is obtained from horses immunized with nucleoprotein (a product of the dissolution of plague bacterial bodies in weak alkali with subsequent precipitation with 1/2% acetic acid). Markl prepared an antitoxic serum by immunizing horses and goats with increasing doses of broth containing dissolved plague bacillus toxin. In addition to these sera, there are sera prepared by the Oswaldo Cruz Institute and other South American institutes. The method of obtaining these sera is a modification of one of the above-mentioned basic methods. Kikuchi obtained serum from rabbits by immunizing them with plague aggressins; Terni and Bandi immunized mules and oxen with peritoneal exudate of plague-infected guinea pigs or bubo juice. Using the indications of Schutze regarding the greater prophylactic power of vaccines obtained from capsular cultures of the plague bacillus grown at 37°, Zhukov-Verezhnikov prepared a serum in Saratov by immunizing a horse with the capsular fraction of the plague bacillus. In addition to these sera, there were attempts to obtain sera from sheep and calves (Naidu, Anderson), which proved to be sufficiently effective. Serum for the treatment of patients is administered subcutaneously, intramuscularly, and even better intravenously in amounts of 100 to 200 cm³ at one time; injections are repeated every 6-12-24 hours. The earlier serum treatment is applied, the better the effect obtained. According to Yersin's data, mortality from serum treatment is reduced from 80% to 7.6%, according to the Russian Commission - from 80% to 40%. According to other data, the serum provides almost no therapeutic effect. In particular, the German Commission explains the success of serum treatment by the fact that it is used in mild patients admitted to hospitals in the first days of the disease. Thus, Bannerman and Terni, comparing the effect of various sera in Bombay (Parisian, Lustig's, Terni, Brazilian), find that the mortality of untreated patients only slightly exceeds the mortality of treated ones. Along with this, the observations of some authors, although on small material, note a positive effect from the use of sera, especially intravenously. Thus, Calmette and Salimbeni, using the Parisian serum in Oporto, obtained a mortality rate of 14.78%, while in untreated patients it reached 63.72%; at the same time, three patients with the pulmonary form of plague were cured. Lustig's serum reduced mortality in Bombay from 79.1%, 80.5%, and 79.5% to 56.4%, 61.8%, and 68.0% (Choksy), and according to other data from 79-80% to 69-63% (data of the Indian Commission). In any case, the use of serum, being the only promising therapeutic agent, should be recommended for the treatment of plague patients, especially intravenously and in large doses, calculated up to 350-500 cm³ in total. For the first time, bacteriophage was used by d'Herelle as a therapeutic agent for plague. D'Herelle obtained a cure in four patients with bubonic plague. Further experiments with the use of bacteriophage for plague by other authors, with few exceptions, did not justify the hopes placed on it, and some even came to the conclusion that bacteriophage not only does not help but even inhibits the action of the serum and reduces the number of recoveries from plague when treated with serum alone (Naidu, Avari, et al.). Prophylaxis.

In 1897, at the 10th International Sanitary Conference, a uniform system of measures against plague was adopted for the first time; at the conferences of 1903 and 1912 in Paris, international sanitary conventions were concluded concerning the prevention of and the fight against plague. The International Sanitary Conference of 1926 again reviewed these measures and established a procedure for notifying neighboring states about the appearance of plague on the territory of any country (see Conventions). The most important measures for combating plague are provided for by the following articles of the International Sanitary Convention of 1926: Articles 1-5 on the procedure for notifications (immediate communication to other governments and the International Office of Public Hygiene regarding the first undoubted case of plague; providing detailed information on the time of the appearance of plague, the number of its cases, and the existence of plague or unusual mortality among rodents, and on the measures taken; subsequent reports on the course of the epidemic); Article 6 on the systematic examination of rodents in ports and districts affected by plague; Articles 13-14 on measures in ports and at the departure of ships (prohibiting the boarding of ships by persons presenting symptoms of plague; preventing the entry of rats on board in the event of plague); Articles 17-20 on goods and baggage (disinfestation and, if necessary, disinfection of recently used underwear, rags, clothing, and bedding; unloading of goods arriving from an affected district that may contain plague-infected rats, only on the condition that precautions necessary to prevent rats from escaping and to destroy them are taken); Articles 24-28 on measures in ports and at maritime borders (see Conventions, Port, Ship Hygiene); Articles 58-66 on measures at land borders (at borders, only persons presenting symptoms of plague may be detained; by way of exception, persons who have been in contact with patients with pneumonic plague may be detained for observation for a period not exceeding 7 days, counting from the time of arrival; travelers arriving from affected districts may be subjected to observation upon arrival at their destination for no longer than 6 days). One of the main preventive measures is the elimination of the causes of plague disease among humans. Therefore, an important preventive measure is the systematic examination of rodents and the earliest possible recognition of plague epizootics among them. Planned extermination of rodents, especially in endemic (enzootic) foci of plague and in ports, must be carried out through constant examination of rats, as well as mice. In the event that plague-infected rodents are discovered in any locality, it is necessary to prohibit commercial hunting for them in that area and to take measures for their extermination. As a result of extermination work, the epidemiological chain between the rodent and the human is broken, which should lead in the coming years to the elimination of the conditions causing the endemicity of plague. The following year, the same places are again subjected to clearing of gophers, as a result of which complete extermination of gophers should be achieved. The gassing of gopher burrows is carried out with chloropicrin, which is introduced in an amount of 1.5 g on cotton balls with long sticks into the depth of the burrow, the outer opening of which is then filled in. The extermination of mice is carried out by using various baits with poisonous chemical substances, mainly derivatives of arsenic. The bacteriological method of extermination has not yet become widespread. The extermination of mice is not achieved by the use of baits alone. It is necessary to apply for this purpose, in addition to the use of chemical and bacteriological baits, a complex of measures consisting of: 1) the destruction of mice in residential premises, barns, stacks, etc., by chloropicrin gassing; 2) their destruction by physical methods: traps, snares, etc.; 3) the destruction of weeds in yards and around settlements as places of accumulation and protection for mice; 4) the trenching of barns, grain and hay reserves with ditches to prevent mice from accessing food products; 5) the sanitary-hygienic maintenance of dwellings, storerooms, basements, etc., with the aim of protecting food products from access by rodents, which are deprived of food and do not find favorable conditions for life in human dwellings; and finally 6) the plugging of gassed mouse burrows with broken glass or other objects. In ports, the main attention must be paid to the extermination of rats both in port premises and on ships arriving at the port according to the rules set forth in the article on deratization (see). Furthermore, as a preventive measure, while permitting hunting for rodents in places free from epizootics, it is necessary to regulate it with certain conditions that reduce the danger of infection from rodents. In addition to the timely detection of an epizootic and the prohibition of hunting in affected territories, it is necessary to permit hunting for gophers and marmots only until a certain date, namely, before the young emerge from the parental burrows and disperse across the steppe into burrows infected with plague. With the dispersal of the young across the steppe, an epizootic among rodents usually begins, since the young, representing a susceptible population of the steppe, upon coming into contact with infected burrows, contract the infection, which develops into an epizootic of greater or lesser degree. Usually, the dispersal of the young ends in the South-East of the RSFSR at the beginning of June, by which date hunting is usually permitted. Furthermore, hunting for rodents should be permitted only to organized groups of the population that are easily accounted for, are under medical observation, and are well instructed regarding measures of personal prophylaxis against plague. The skinning of caught animals must be carried out by specific persons in a specific place, having special clothing and disinfectant agents. It is useful when skinning to smear the hands with a 10-20% calomel ointment (Suknev), and the carcasses of animals, if they are not subjected to a rendering process, must be buried deep in the ground. Extensive sanitary-educational work among the population of districts endemic for plague is also one of the most important measures for preventing plague among the population. The extermination of rodents must be combined with measures aimed at worsening the living conditions of rodents in a given area; these conditions arise in connection with the development of agricultural and industrial enterprises emerging in endemic districts. The construction of railways, irrigation of the area, the development of vegetable gardens, orchards, arable land, etc., accompanied by an increase in the population, lead to the disappearance of such rodents as gophers and tarbagans. The use of specific vaccinations represents one of the preventive measures. True, vaccination, due to the significant reaction in the vaccinated, the relatively small effectiveness of the vaccinations, and the rarity of plague disease among humans, has not become widespread and is recommended only for rodent hunters and for medical personnel working on plague. For vaccination, Haffkine's vaccine, the vaccine according to Kolle, or the nucleoprotein of Lustig and Galeotti is used. Haffkine's vaccine is a 6-week-old broth culture of the plague bacillus killed at 65° for 1 hour, used twice in doses from 0.5 to 1.5 cm³ with an interval of 3-5 days; for children, the dose is reduced to 0.1-1.0 cm³. Kolle's vaccine is prepared from 2-day-old agar cultures of plague bacilli, washed off with physiological saline and killed at 65° for 1 hour. The suspension of plague microbes is diluted with physiological saline at a rate of 2 billion bacterial bodies per 1 cm³ and is used three times in increasing doses of 0.5, 1.0, and 1.5 cm³ subcutaneously with a 3-5-day interval. For children, the dose is correspondingly smaller. The above-described nucleoprotein of Lustig and Galeotti, dissolved in physiological saline, is used subcutaneously at a rate of 2-3 mg of dry substance three times with a 3-5-day interval. Some have proposed avirulent live plague bacilli for the immunization of animals (Kolle and Otto), as well as humans (Strong), but this method of immunization has not yet become widespread, as it does not guarantee against an increase in the virulence of the bacilli in the body of the vaccinated people. Also not widespread are vaccinations with Besredka's endotoxin, which is a centrifugate of a suspension of killed, dried, and ground cultures of the plague microbe, extracted with distilled water, as well as the Terni-Bandi vaccine, which is peritoneal exudate of plague-infected guinea pigs inactivated by heating. Immunization with live bacteria from the hemorrhagic septicemia group, proposed by Konstantsov for mice, and then by Kolle and Otto for rats and guinea pigs, also did not have success; only MacConkey obtained immunity against plague by means of bacteria and filtrates of cultures of B. pseudotuberculosis rodentium. Encouraging results are obtained with the use of vaccines from plague bacilli grown at 37° and having a clearly expressed capsule. The capsular antigen is thermolabile, becomes haptenized at 100° for 15 minutes, and is completely destroyed by the action of this temperature for an hour. The effect of immunization with vaccines of the plague bacillus grown at 37° is increased by 1.5, or even 2 times compared with vaccines of microbes grown at 26° (Schutze).

When using vaccines, a local reaction is observed—redness, swelling, pain, and sometimes enlargement and tenderness of the corresponding lymph nodes, as well as a general reaction—headache, increased temperature, and malaise, which occurs especially when using the Haffkine vaccine. After 2-3 days, the reaction passes. Contraindications: acute febrile and gastrointestinal diseases, nephritis, heart disease, tuberculosis. Immunity after vaccinations sets in after 7-10 days and lasts from 4 to 6 months, and vaccinations during the incubation period apparently do not cause a negative reaction and do not worsen the course of the disease. To demonstrate the significance of Haffkine's vaccinations, a convincing experiment in the city of Hubli (India) is cited. There, in 1898, out of 48,000 inhabitants, 38,712 people were vaccinated, and during the epidemic, 13.2% of the unvaccinated died from plague and only 1.3% of the vaccinated; mortality among the vaccinated was 7 times lower compared to the unvaccinated, despite the fact that the number of unvaccinated kept decreasing and by the end of the epidemic only 600 people remained. Other data also confirm a decrease among the vaccinated in morbidity (from 44.7% to 19.6%), mortality (from 30.9% to 7.8%), and case fatality (out of 100 sick, 69 among the unvaccinated and 40 among the vaccinated). The number of vaccinations has a significant influence on morbidity and mortality from plague—three-dose vaccinations protect better than two- or one-dose ones. At present, the definitely expressed protective effect of the Haffkine vaccine is recognized by everyone, although it does not provide an absolute guarantee against plague, since a certain percentage (about 8) of the vaccinated fall ill fatally. Regarding the effect of the Kolle vaccine, as well as that of Lustig and Galeotti, there are not enough verified facts based on impeccable statistics. Some authors did not see a beneficial effect from the use of the Kolle vaccine (Seyffarth), others observed their more favorable effect (Oldt), and still others, after using the vaccine according to Kolle or Lustig and Galeotti, noted the cessation of diseases in a given locality, which could also be interpreted as a spontaneous cessation of the epidemic. The use of sera for prophylactic purposes has greater success than for therapeutic ones. Thus, Yersin, having performed 500 prophylactic vaccinations with Parisian serum, observed the disease in only 5, of whom two died. Other authors also observed a positive effect from the use of serum for prophylactic purposes in persons exposed to the danger of contracting plague. True, its use in cases of infection with pneumonic plague is little effective, but in bubonic plague, the prophylactic effect of the serum apparently takes place. For prophylactic purposes, from 20 to 50 cm³ of serum is injected subcutaneously or intramuscularly. After the use of sera, phenomena of serum sickness may develop, sometimes in a severe form. A disadvantage of this passive method of immunization is the disappearance of immunity after 2-2.5 weeks. The fight against plague and preventive measures in case of its appearance in modern conditions consist of the following points: isolation of the patient and people who have been in contact with him, disinfection and disinsection of clothing, premises, and excreta of the patient and those in contact, observation of the residents of a given settlement, and sometimes quarantine of the population and the cessation of all types of transport communication with the affected territory. The greatest danger in terms of spreading the contagion is presented by patients with pneumonic plague, who must be isolated separately from patients with the bubonic form; the latter, being not dangerous in the first period of the disease in the absence of opened buboes, can become a source of further infections upon suppuration and opening of the buboes, as well as in the last hours of life, when septicemia sets in, and upon complication with secondary plague pneumonia. These moments must be kept in mind, and at the slightest suspicion of secondary pneumonia, a stricter regimen should be applied, separating such patients from others with the bubonic form of plague. For visiting patients and caring for them, it is necessary to have a special suit in the form of a jumpsuit, boots, a kerchief and a hood for the head, rubber gloves, and when visiting pneumonic patients, it is necessary to wear protective goggles and a light mask made of gauze with a layer of cotton wool (Fig. 4), covering the mouth and nose. After visiting patients, masks and the suit are disinfected with a 1:1000 solution of sublimate or a 3% solution of carbolic acid. Before placing patients in the isolation ward, it is necessary to carry out their sanitary processing—change their clothing and linen and wash them with a warm solution of sublimate. For the care of patients, special personnel must be assigned, living separately from all others and well instructed in the care of plague patients. Isolation of those in contact.

Figure 4. Modern suit for plague.

Those who have been in contact must be isolated with varying degrees of strictness depending on the form of the disease. Those who have been in contact with a pneumonic plague patient must be isolated individually to avoid intra-isolation infections. Those who have been in contact with bubonic patients can be subjected to group isolation, since the danger of infection for the isolated is small, and furthermore, in case of the emergence of diseases among them, the possibility of infection within the isolation ward is excluded if, upon placement into it, the isolated were subjected to sanitary processing. Families of those in contact should be subjected to observation, i.e., daily medical examination with three-time daily measurement of temperature, as with the isolated. Isolation and observation are appointed for a period of 6 days from the moment of sanitary processing of the isolated. The premises and all things where the patient lived must be subjected to disinsection and disinfection, likewise, the premises and things of those in contact are disinfected. At present, the best method is the gas chlorpicrinization method, consisting of the evaporation of 10-30 cm³ of chlorpicrin per 1 m³ of the premises, depending on its airtightness. In an extreme case, one has to resort to fumigation with sulfur for disinsection and wet disinfection with solutions of carbolic acid or sublimate, sprayed with atomizers. All excreta of patients (sputum, urine, feces) are collected in vessels and disinfected on the spot with a solution of carbolic acid or other disinfectants. Corpses of the deceased, after their disinfection with a solution of sublimate or carbolic acid, are wrapped in sublimate sheets or blankets, placed in a tight coffin, at the bottom of which there is a layer of chlorinated lime, covered from above with a layer of chlorinated lime, and the coffin is tightly nailed shut. The coffin is lowered into a grave at least 2 m deep, covered with chlorinated lime, and buried. It is better to subject the coffin with the plague corpse to burning on a pyre of logs 2 m long with transverse inserts, forming a cage of firewood 1 m high. The corpse, doused with oil or kerosene, easily burns within 2-3 hours. Carts and stretchers that were used for transporting and carrying plague patients and their corpses must be disinfected. Upon the appearance of plague diseases in a settlement, all residents of this village are subjected to observation, daily examination by medical personnel with measurement of temperature in suspicious cases. If the settlement is large and there is little medical personnel, then the public should be involved in helping the medical personnel by organizing an institute of sanitary inspectors, to whose care 10-20 households are entrusted, about the health of the residents of which they must report twice daily to the medical personnel, who immediately examine the suspicious and take measures to isolate the plague-stricken. In case of significant spread of the infection in a given settlement or in a territory including several settlements, a quarantine is established, i.e., departure from the settlement or the affected territory is prohibited until the end of the epidemic; at the same time, railway stations and piers in the affected territory stop the sale of tickets and the boarding of passengers, and the receipt of cargo is also stopped, especially that which could be a carrier of plague—furs, grain products, fodder, etc., in which there may be plague-infected rodents. Departure from the infected area may be permitted after serving a 6-day quarantine in a special facility under the supervision of medical personnel with preliminary sanitary processing of the quarantined person and disinfection of his belongings. In case of a threat of plague from a neighboring state, the threatened country takes measures to protect its borders, where a medical examination of all those crossing the border is established, and, if necessary, their quarantine for a period of 6 days. However, such restrictive measures are in practice applied only in case of extreme necessity. Measures in ports and for the inspection of arriving sea vessels—see Conventions, Port, etc. Measures of personal prophylaxis consist of avoiding contact with infected animals and people, as well as with objects that could be a source of contagion. The nursing staff must not eat in the plague hospital, but must live in separate premises from the patients, having individual rooms. It is especially necessary to take measures for protection against insects: fleas, lice, bedbugs, and flies. When caring for patients, one must watch for the integrity of the skin, since abrasions and wounds can serve as entry gates for the plague infection.

V. Suknev.