Cholera (278 Geographical Distribution and)

278 Geographical Distribution and Statistics. 293 Asiatic cholera (cholera asiatica), an acute infectious disease caused by the cholera vibrio. Clinically, it is accompanied in most cases by typical manifestations from the gastrointestinal tract; it is distinguished by high mortality. History. The name "cholera" is already found in Hippocrates; with this name, cholera nostras was designated. It was assumed that this disease was caused by enhanced secretion of bile (Greek chole-bile and rheo-to flow). English authors, who were the first to describe Asiatic cholera, gave it this name. In the Russian medical literature of the early 19th century, cholera appears under the names "spasmodic cholera" (cholera spasmodica), "Indian cholera", "Indian cholera morbus", "cholera disease" (cholera morbus), "dog's death" (incorrectly transformed by French authors from the local name mordezym into "mort de chien"). Movement of cholera epidemics. Cholera originates in India. Most researchers believe that in India, in the Ganges valley, cholera has existed since time immemorial. Since 1817, it has spread far beyond its endemic area. Gradually moving westward, in 1823 it first penetrated Europe (to Astrakhan). In total, there are 6 major epidemic waves worldwide. Chronologically, they are arranged in the order indicated in Table 1. Hirsch, up to 1875, counts 4 waves, Haeser-5 waves: 1816-23, 1826-37, 1840-50, 1852-60 and 1863-73. During the first epidemic of 1817-23, the spread of cholera from India eastward and southward was initially observed. The war that was taking place at that time between the English and the native rebels contributed to the spread of cholera. In August 1817, cholera raged in Jessore (North Bengal), where during 2 months more than 10,000 people died from it. By the end of September, it reached Calcutta. The English army stationed here, numbering 90,000 people, lost from cholera in a short time about 15,000 people. Table 1. Years Duration Distribution 1817-1823 1826-1837 1846-1862 1864-1875 1883-1896 1902-1926 6 years 11 years 17 years 12 years 13 years 25 years Asia, Africa, Europe (Astrakhan) Asia, Africa, Europe, America, Australia Asia, Africa, Europe, America Asia, Africa, Europe, America Asia, Africa, Europe, America Asia, Africa, Europe In 1818, cholera in Benares claimed 15,000 victims within 2 months. In 1819, cholera crossed the sea and reached Ceylon, and then Sumatra. In 1820, it penetrated the Philippines and China (Canton), in 1821 it captured Borneo, Java (more than 100,000 people died), Siam (in Bangkok about 40,000 people died), etc. At the same time, cholera advanced northwestward. In 1821, it reached Basra in Persia, where about half of the population perished, and in 1822 it reached Tabriz, capturing Baghdad and Erzurum. In June 1823, it spread in the Caucasus, and in September it penetrated Astrakhan. With this, the march of cholera into Europe stopped. The progress of the epidemic was very slow, which corresponded to the slowness of human movement at that time.

In 1826, a new intensification of cholera begins in India, gradually it covers Afghanistan, Bukhara (1827), Khiva (1828) and in 1829 reaches the Orenburg province. Another wave of it went through Persia, in 1830 it penetrated Baku and at the same time into Mesopotamia, and in 1831-into Mecca and Medina, where at that time more than 100,000 pilgrims were present. From Arabia, cholera moved to Syria and Egypt (in Alexandria and Cairo in the first few months up to 30,000 people died). From Egypt, cholera moved up the Nile, it bypassed the northern coast of Africa and penetrated deep into Africa, into Abyssinia and Sudan. In the east at this time, cholera reached Japan. From the Orenburg province, cholera began to spread through Russia. In 1830, the eastern provinces were affected by it, in 1831-the northern and western ones, then through Poland it penetrated Prussia and Austria-Hungary. It also penetrated Prussia through Riga, Mitau and Danzig. In 1832, it raged in Central Europe and spread to England (from Hamburg by sea), France (from England), Belgium, the Netherlands, the Balkan Peninsula. In the same year, it was brought by sea to Canada, the USA and Australia. In the summer of 1833, it raged in Mexico, in the winter of 1833-in Portugal and Spain. In 1834, it struck Sweden and Norway and penetrated Italy, where it developed strongly in 1836-37 (Naples, Rome). In 1837, cholera subsided, and from 1838 it completely disappeared in Europe. A new, third wave begins in 1845. It goes from India through Afghanistan, Meshhed (Persia), Tehran, Baghdad to Arabia. In November 1846, cholera caused enormous devastation among pilgrims in Mecca and Medina. Its path from Meshhed to Mecca, cholera covered in 10 months. Another path of this wave-through Kabul (Afghanistan) and Samarkand (September 1845), from where it penetrated the shores of the Caspian Sea (Astrakhan) and up the Volga-on the one hand, and on the other-along the caravan route to Orenburg and further through Russia. Along the Kura River, cholera penetrated Georgia, reached Trebizond, and in November 1847 appeared in Constantinople, from where it advanced through the Mediterranean Sea to Syria. From Turkey, cholera passed through Bulgaria and Romania. From Russia through Poland, cholera penetrated Prussia, Galicia, Bohemia, Hungary and Northern Germany (1848), from Hamburg-to England, then France (Paris, where it appeared in March 1849, losing about 10,000 people from cholera) and most Western European countries. At the end of 1848, it spread through North America. In 1849, it rages in North Africa, in Germany, Austria, the Netherlands, Belgium, France, Great Britain, Italy and Switzerland. In America it strikes, besides the USA, Canada and Mexico. In 1850, it penetrates the South American states: Colombia and Ecuador. In 1851, cholera subsided everywhere. In 1852, a new exacerbation of cholera begins (Haeser considers this the beginning of a new wave)-it takes on the character of an epidemic in India, Persia, Mesopotamia, Russia and Germany. Gradually covering a number of other countries, cholera raged in Europe, Asia, Africa and America until 1859 (in 1855 Brazil was affected). In 1860-1862, it almost ceased in Europe, Africa and America, but continued to rage in Asia (India, China, Japan, Persia, Afghanistan, Khiva, Turkestan, Mesopotamia, Arabia). An idea of the extent of cholera in some Western European countries in the previous 2 epidemics is given in Table 2 (countries are arranged from north to south): Table 3. Number of cases of illness and deaths from cholera in some Western European countries in the epidemics of 1831-38 and 1848-61. 1831-1838 1848-1861 Countries sick died sick died Sweden . . Norway Denmark . . Prussia Holland Belgium England . Austria . France. Italy . Spain Portugal [ \ 15,227 55,773 10,253 19,106 80,203 846 566 255 262 19,320 274,121 50,614 \ 8,114 32,647 4,821 7,984 30,924 344,360 111,722 67,134 17,949 25,803 3,794 10,598 312,036 230,725 49,941 236,744 In 1863, a new outbreak of cholera begins in India and its spread eastward and westward. It covers Hindustan, Indochina, the Sunda and Philippine Islands, Japan, and on the west, together with pilgrims, it penetrates Arabia. In 1865, it struck Egypt, Abyssinia, Algeria and Morocco. The development of communication routes-railways and steamships and the cutting of the Suez Canal-significantly accelerated the advance of cholera. From Egypt, where cholera was brought in May 1865 by pilgrims returning from Hejaz to Suez, it was by sea in an extremely short time (within a few weeks) brought to various ports of Southern Europe, in particular to Valencia, Marseille, Constantinople. It quickly spread through Italy, France, Spain, Turkey, Romania. In one year, cholera struck Asia, Africa, Europe and America, and cholera moved primarily along the routes of shipping lines. In 1866, cholera covered all European states (Prussia, during the war with Austria in 1866, lost more soldiers from cholera than from enemy fire). Into Russia, cholera penetrated during this epidemic through the western border-through Germany and Poland. The epidemic lasted until 1875. The fifth epidemic in 1883 was brought from India to Egypt, from where in the following year it was brought to the ports of France, Italy and Spain. In the east, it was brought to Japan. In 1886, it was brought to Argentina and Chile. In 1892, there was an intensification of it in Afghanistan and Persia, and from the latter through the Caspian Sea it penetrated Baku, from there to Astrakhan and along the Volga into the interior of Russia. In the west, it gave numerous introductions to port cities of Europe, Africa and America, but nowhere, except Hamburg and Egypt, did it develop into a major epidemic; at this time, the cholera vibrio had already been discovered by R. Koch and a system of rational struggle with cholera had been proposed. In 1896, cholera subsided everywhere. The number of deaths from cholera in 1892-95 in Western Europe is expressed in the following figures (Table 3, according to Prinzing): Table 3. Countries and cities Hamburg ....... Prussia ...... Galicia and Bukovina Belgium ....... Italy ....... France .......

Holland ...... 1892. 1893. 1894. 1895. 8 060 8 739 .- 3 040 - 4 550 approx. 900 - In Hungary for 1892-95 years died from Ch. 5 276, in Romania-872 people.-The sixth epidemic in 1902 spread to China and Japan, on the west it passed through Persia into Arabia. Here it spread strongly among 400,000 pilgrims gathered in Hejaz. Cholera was brought to Egypt, where it reached enormous proportions (about 40,000 people died), from where it penetrated into Syria and Palestine. Simultaneously through Central Asia and Samarkand in 1904 it reached Baku and through Astrakhan along the Volga spread throughout Russia. Later it was brought to Germany (in 1905-212 cases and 85 deaths, in 1909-20 deaths), Austria (1905), Belgium (1909), Hungary, Italy, Bulgaria, Romania, Turkey, Greece, Southern France (1910), and nowhere did it spread widely anymore. The number of deaths from Ch. in some of these countries in 1910-12 is expressed in the following figures (Table 4): Table 4. Countries 1910. 1911. 1912. 302 252 268 | 6 145 3 271 1 41 44 During the Balkan War 1912-13 years a major local outbreak of Ch. was observed. It began in November 1912 in Constantinople and spread among both Turkish and Bulgarian armies and penetrated into Hungary, where in 1913 died from Ch. 722 people. The World War gave a new impetus to the development of Ch. It spread strongly in the Turkish, Russian (see below), Austrian armies, less so in the German army. Morbidity in the German army fronts in individual years was expressed in such indicators (Table 5; per 1,000 of strength): Table 5. Table Armies Years of war 1st 2nd 3rd 4th 0.04 1.30 0.03 0.61 0.20 4.4 0.01 0.02 0.21 9.2 0.01 0.01 0.03 1>° The number of cases in the Austrian army is shown in Table 6: Table 6. Years of war Sick Died 11th............ 49 082 28 372 5 146 12th............ | 3rd............ Together with the troops Ch. was also brought into the civilian population. For 1914-19 years in individual countries died from Ch. (Table 7): Duration Number of registered 1 Years of illness deaths 1823 . . . _g - 1 year 6 months 14 » 1 year 9 months 5 » 1 year 22 months * 392 553 743 2 589 843 895 006 822 648 2 167 673 559 2C5 236 715 1 032 864 331 501 385 985 ' 1 393 151 895 з 1829-1834 1847-1861 1855-1873 1892-1896 1902 ... 1904-1926 Total . . 5 537 358 2 140 558 ¹ No cases noted in 1851. ² No cases noted in 1906. ³ Deaths only for 1904-14. Countries 1914. Germany.............. 41 Hungary............... 1153 Italy....... ........! o France..............I 40 1915. 1916. 1917. 1918. 1919. 4 057 Individual cases continued to be registered for several more years in France. In Greece there was a small outbreak of Ch. in 1924 in connection with the return of refugees. In Poland cases of illness and deaths from Ch. were registered: in 1919-3 and 3 (first figure-cases, second figure-deaths), in 1920-57 and 31, in 1921-12 and 4, in 1922- 125 and 34. Later Ch. was not observed in Western Europe. Soon it also ceased in the USSR. In recent years it has been concentrated exclusively in Asia (see below). Cholera in Russia and the USSR. In Russia Ch. first appeared in 1823. The last cases were observed in 1926. During this period of 104 years Ch. was observed for 57 years. One can note during this time 8 epidemic waves of varying duration and intensity, as seen in Table 8. The first wave of Ch. in June 1823 moved from Persia to Transcaucasia, where it spread in Lankaran and Baku. From there it penetrated to Astrakhan and Krasny Yar. In Astrakhan from 10/IX to 4/XI 371 people fell ill and 182 died. Ch. did not go further. After 6 years it appears again in Russia. This time it penetrates through 2 paths. Through Bukhara (1827) and Khiva (1828) in 1829 it passes to Orenburg-%i Orenburg province, where by February 1830 3,590 fell ill and 885 died. In 1830 it through Resht (Persia) penetrates into Salyany (16/VI), Baku (17/VI), Derbent (1/VII) and Astrakhan (4/VII). In one month in Astrakhan 2,935 people died. The spread of Ch. in Russia was greatly facilitated by the then war between Russia and Turkey. Ch. severely struck the Russian army and with the returning troops it spread throughout Russia. Cholera also broke out among the Russian troops sent to the Bug to suppress the Polish uprising (November 1830). In total in 1830 Ch. struck 34 provinces, in the following, 1831-56 provinces. In Moscow Ch. first appeared in September 1830, in Petersburg-in June 1831. Ch. continued until 1833, in the following years individual cases were observed.-The third wave of Ch. begins in Russia in 1847. Penetrating through Afghanistan (1846) and Persia to the Caucasus (in October-in Salyany, in November-Baku, in December-Shemakha), Ch. in April 1847 captured Derbent, in May-Temir-Khan-Shura, in June-Georgievsk, Mozdok and Pyatigorsk, in July-Stavropol, Azov, Rostov n/D. and Astrakhan. Already in this year 36 provinces were captured by it, in the following-50. Ch. continued until 1861. The Ch. curve went unevenly by individual years. The most severe was 1848, when 1,742 thousand cases and 690 thousand deaths were registered. The beginning of the next epidemic in Russia refers to 1865. At the end of June of this year cases were discovered in Baltsky district of Podolsk province, where German colonists from Prussia arrived, where at that time there was already a cholera epidemic. In August Ch. was brought from Constantinople to Odessa. The strongest development cholera acquired in 1866, when it covered 49 provinces (209 thousand cases and 72 thousand deaths). After several years of calm Ch. again took large dimensions in 1871 and 1872. The epidemic ended in 1873.-In 1892 Ch. penetrated into Russia from Meshhed into Transcaspian region through the Russian-Persian border. The first case was officially registered on May 18 in the village of Kaakha on the Transcaspian railway. On May 26 the first cases appeared in Ashkhabad, from where the mass exodus of the population began. On June 1 the first case is noted in Baku, June 12-in Astrakhan, 14/VI-in Saratov, 23/VI-in Samara, 24/VI-in Simbirsk and Kazan. Ch. began to spread rapidly throughout the country. In Moscow the first case was registered on 9/VII, in Petersburg on 14/VII. The spread of Ch. was greatly facilitated by the famine of 1891-92, accompanied by large population movements. Ch. in this year struck 77 provinces with about 18,000 inhabited places, where about 620 thousand 'cases and about 300 thousand deaths were registered. The following years gave a gradual weakening of cholera, which completely ceased in 1896. In the current century the first epidemic of Ch. began in 1902 in the Far East. It was brought from Manchuria in June along the Sungari River into Amur region, and in July by water and by railway into Primorye region. Individual cases of imported nature were noted in Transbaikal region (27 people) and in Irkutsk province (9 people). In total in 149 populated places 2,167 cases and 1,393 deaths were noted. The cities affected were: Vladivostok, Nikolsk-Ussuriysk, Khabarovsk and Blagoveshchensk. This epidemic did not spread inland. In 1904 Ch. penetrates into Russia from Persia both by land through Tabriz (into Yerevan province) and Meshhed (through Merv and Ashkhabad to Baku), and along the Caspian coast. In Baku Ch. was registered on August 15, in Saratov-September 4, in Samara-September 19, later in Astrakhan (October 5) and Tsaritsyn (October 19). In total this year 13 provinces 467 populated places (including 20 cities) were affected, where 9,226 cases and 6,850 deaths were registered. In 1905 its dimensions significantly decreased, in 1906 no cholera cases were registered at all, but in 1907 a new outbreak began. It quickly covers the basins of the Volga, Don and Dnieper, penetrates into Moscow, Siberia and Central Asia, in the following year-into Petersburg and Arkhangelsk, spreads throughout the country and reaches its peak in 1910 (in 72 provinces 230 thousand cases and 110 thousand deaths). Further Ch. weakens, and in 1912 it almost completely disappears (in Astrakhan province and Odessa only 9 cases were registered). In 1913 a new rise of Ch. begins. Most authors explain it as being brought from Romania and Serbia. Ch. was concentrated mainly in Podolsk province (1,603 cases), but individual cases were observed in 6 more provinces (197 cases). In 1914 with the beginning of the World War Ch. receives further development. Already this year in the army 7,915 cases were registered, mainly on the southwestern front (7,768 people); among the civilian population in 15 provinces 1,800 cases were noted. In 1915 Ch. spreads strongly both in the army (on the south-western front 11,440, on the north-western front 8,871 cases) and among refugees and civilian population (in 57 provinces 43,976 cases). In the next 2 years it gradually subsides, but in 1918 in connection with the movement of refugees, demobilized and prisoners of war a new outbreak is observed-incomplete data for 35 provinces over 40 thousand cases.

A very large number of cases was observed this year in Petrograd (8,470 cases), significantly fewer in Moscow (1,137 cases). The Volga region, Voronezh, Kursk, and Tambov provinces were severely affected. In 1919 and 1920, cholera was widespread over a large territory, but it was characterized by relatively low intensity. In the following years, cholera quickly disappeared. For more than 10 years now, no cholera cases have been observed in the USSR.

I. Dobreytser.

Etiology. The causative agent of Asiatic cholera was discovered by R. Koch in 1883 and named by him Vibrio cholerae asiaticae. The cholera vibrio was found by Koch in the intestinal contents of cholera corpses, in the excretions of cholera patients, and in the water of a pond that served as the source of numerous cholera cases. The specific etiological significance of Koch's vibrio was subsequently confirmed by numerous studies, in particular by experiments on the artificial reproduction of the disease in humans by consuming cultures of the cholera vibrio (Pettenkofer and Emmerich, Metchnikoff). The cholera vibrio, in form, represents a short, slightly curved rod ("comma") (see separate table, fig. 1-3), is highly motile due to the presence of a single flagellum. In stained preparations (the best stain is Pfeiffer's aqueous fuchsin), the length of the cholera vibrio is about 1.5 μ, and the width is approximately 1/10 of its length. In addition to these typical morphological vibrios, long, thread-like forms, S-shaped curved, are also observed in old cultures; sometimes the vibrios swell and assume a club-shaped and spherical shape. The cholera vibrio is a strict aerobe, does not form spores, and grows well on ordinary nutrient media, especially in media with a strongly alkaline reaction. In broth, the vibrio multiplies rapidly, turbidifies the medium, and forms a delicate film on its surface; such rapid growth of vibrios with film formation is also observed in a 1% solution of peptone in water with the addition of 0.5% sodium chloride, alkalized with soda. On agar, cholera vibrios form after 18-24 hours of growth at 37° small, round, transparent colonies, slightly opalescing bluish in transmitted light. On agar plates, cholera colonies are easily distinguished by their external characteristics from the coarser, opaque, whitish colonies of the bacillus coli and other intestinal microbes. On gelatin plates when grown at 22°, cholera vibrios form after 24 hours small, light, transparent colonies with even edges and a "shagreen" surface, which can be easily verified when examining the colonies with slight magnification. After 48 hours of growth of cholera colonies on gelatin, the liquefaction of the gelatin by the growing microbes is clearly detected. As a solid selective medium for growing cholera vibrios, Diedonne's alkaline blood agar (pH=9.0-9.6) is used, which inhibits the growth of intestinal microbes, while cholera microbes develop luxuriantly. For preliminary enrichment with great success, inoculations into 1% peptone water with transfer after 8 hours to alkaline agar are used. With 1% Witte peptone, the medium of Ottolenghi in the first modification can also compete. Among solid media, the medium of Aronson is a very demonstrative medium for vibrios. The development of the cholera vibrio occurs best at +30-40° and ceases at temperatures below +8°, however, prolonged preservation of virulent cholera vibrios is possible in ice (for several months). Cholera vibrios are very sensitive to drying and die within a few hours when dried. In the animal organism, cholera vibrios can be preserved for a very long time, and under natural conditions no animal except humans is susceptible to cholera. Experimentally, a disease similar to human cholera can be reproduced only in monkeys (especially anthropoid), in young rabbits (Metchnikoff), and in susliks (Zabolotny). In the intestines of fish, crayfish, and flies, vibrios are preserved for a relatively long time. In the human organism, the multiplication and preservation of cholera vibrios occur in the intestine, from here the vibrios are excreted into the external environment with feces or vomit. The metabolic products of vibrios are quite numerous and varied. From gases, H₂S is formed; from acids-lactic acid, a number of volatile acids and amines; from enzymes-diastase, catalase, lipase, protease. Of particular interest is reductase, which together with indole is found in the so-called cholera redness (cholerarot) reaction of Buyvid (more correctly Buyvid-Pel) or the nitroso-indole test (Brieger, Sal'kovsky). A positive reaction is obtained upon adding a few drops of concentrated sulfuric or hydrochloric acid, since in peptone or broth culture indole and salts of nitrous acid are simultaneously formed due to the reduction of nitrates. For the nitroso-indole reaction, it is better to use the following nutrient medium: peptone-10 g, table salt-5 g, potassium nitrate-1 g, and distilled water-1 l (however, ordinary 1% peptone water or broth can also be used). Bacteriological examination is the basis of the anti-cholera measures system and is carried out either for diagnostic purposes (examination of patient excretions) or to establish the routes of infection transmission (examination of water, food products, etc.). The materials for diagnostic examination are the feces and vomit masses of patients or the intestinal contents of suspicious corpses. Bacteriological examination of excretions is carried out according to the following scheme: 1) Direct microscopic examination of dried, fixed smears from feces or intestinal contents after staining with a diluted solution of carbolic fuchsin (1:10). Conclusive is the detection of a large number of morphologically typical cholera vibrios (see separate table, fig. 3). 2) Inoculation into 1% peptone water (1 cm³ of the material under investigation per 50 cm³ of peptone solution) and simultaneously inoculation of 4-6 loops of the material onto Diedonne agar in Petri dishes with successive inoculations of 3-4 dishes with the same spreader. 3) After 5-8 hours of growth at 37° in peptone water, transfer of several loops of liquid carefully taken from the surface of the peptone inoculum (film) onto plate alkaline agar, or Diedonne agar, or Aronson's medium, or Wedder and van Dam's medium. The latter consists of a) agar-30 g, NaCl-5 g, Pept. W.-10 g, water-1 l; b) KOH-0.2, N-20 cm³, Merck's hemoglobin-1 g, glycine-120 mg. At the same time, microscopic examination of the peptone film for the presence of vibrios is performed. 4) After 8-16 hours of growth on plate agar-isolation of suspicious colonies onto slant agar with simultaneous examination of smears from suspicious colonies and setting up agglutination tests in a hanging drop when vibrios are found microscopically. 5) Final agglutination of the isolated cultures with specific cholera serum in tubes with successive dilutions of the serum to the maximum titer. Primary inoculations onto Diedonne plate agar after 8-16 hours are examined for the presence of suspicious colonies with their examination according to paragraphs 4 and 5. Examination of water is carried out as follows. To 1 l of water under investigation, 100 cm³ of a basic (10%) solution of peptone is added, the mixture is poured into flasks of 100 cm³ each, and after 8-24 hours of standing in an incubator at 37° it is examined according to the above scheme according to paragraphs 3, 4 and 5. The bacteriological examination method for the presence of cholera vibrios, described above, is characterized by high sensitivity and accuracy and allows the detection of cholera vibrios even with their minimal content in the material under investigation. Of particular importance in this is the accumulation of cholera microbes on the surface of peptone water, where they develop significantly faster and more intensely than other intestinal microbes. The use of the selective media of Diedonne and Wedder and van Dam, which, due to their strongly alkaline reaction, inhibit the development of all microbes except cholera, reduces the duration of the examination by 8-16 hours, which is of significant importance, especially when examining the first cases suspicious for cholera. A final conclusion about the cholera nature of the isolated vibrios is made on the basis of a positive agglutination reaction with specific cholera serum. However, in the course of cholera bacteriological analysis, significant difficulties sometimes arise, as it has been established that freshly isolated from feces cholera vibrios sometimes do not agglutinate with cholera serum and acquire the ability to agglutinate only after a series of transfers on artificial nutrient media. On the other hand, it has been established that in nature (water) there are numerous species of saprophytic vibrios, among which single-flagellated cholera-like vibrios (para-cholera vibrios) that do not agglutinate with cholera serum are also found. Morphologically and in growth on ordinary nutrient media (broth, peptone water, gelatin, agar, milk), they are indistinguishable from true cholera vibrios. On blood agar (according to Kraus), cholera-like vibrios give hemolysis just as cholera vibrios do; on liquid blood medium (according to Slesarevsky)-1% peptone water with defibrinated sheep blood-the non-agglutinating vibrios give hemolysis after 48 hours in 80%, while agglutinating cholera vibrios do not give hemolysis.

The enzymes of cholera-like vibrios (catalase, lipase, diastase, oxidoreductase, and protease) are similar to the enzymes of cholera vibrios. The fermentation of sugars (sucrose, arabinose) can also be carried out by cholera-like vibrios (Ermol'eva). Most cholera-like vibrios contain arabinose, but there is also a group containing galactose, similar to many cholera vibrios (Linton). Cholera-like vibrios are generally less sensitive to antiseptics. According to the research of Okolov and Ermol'eva, the resistance of vibrios to the action of chlorine for half an hour at a dose of 0.5 mg of active chlorine per 1 liter of distilled water mostly indicates a water origin of the vibrios. Thus, the study of the biochemical properties of cholera-like vibrios has rather brought them closer to cholera vibrios than established signs of differentiation. The existing differences are of a quantitative nature and give wide fluctuations in connection with the age of cultures and changes in the composition of the medium. In general, cholera vibrios can be characterized as having more active enzymatic systems. Virulence and pathogenicity, determined on laboratory animals, also do not allow to separate cholera-like vibrios from cholera vibrios. Subcutaneous and intravenous injection of cholera-like vibrios into guinea pigs, rabbits, and ground squirrels causes septicemia with acute enteritis, i.e., the syndrome of experimental cholera in these animals. There are both highly virulent for animals cholera-like luminescent vibrios (Ermol'eva), and on the other hand, cholera vibrios with very weak virulence (Zlatogorov, Barykin, and Zakharov). Thus, the only differential sign that may have practical significance remains the agglutination reaction with specific cholera serum. However, the fundamental and practical significance of this immunobiological sign is strongly shaken. Experiments on immunization with cholera-like vibrios show that they can create immunity to cholera vibrio as well. Agglutinating cholera vibrios can be converted into non-agglutinating ones (Barykin, Zlatogorov, Frize, Vagrensheer, Stamm) and vice versa (Gorovits-Vlasova, Ermol'eva). Ermol'eva, by isolating a persistently non-agglutinating vibrio by passage through its own intestine, converted it into an agglutinating strain indistinguishable from the typical cholera vibrio. In recent years, Combiesco-Popeseo has attempted to isolate cholera-like vibrios based on their insensitivity to cholera bacteriophage, but in connection with the discovery of 6 types of cholera bacteriophages, this sign also cannot be considered reliable. Similarly, the latest methods—agglutination with trypanflavine, acid agglutination, and the speed of movement of vibrios in an electric field—allow to differentiate S and R forms of vibrios, but not to distinguish cholera vibrios from cholera-like ones (Popesco, Damboviceanu, Soru). By the action of cholera bacteriophage on cholera vibrio, it was possible to obtain stable variants (for more than a year) of vibrios with diverse cultural and serological properties (hemolyzing and non-agglutinating vibrios) and thereby prove the possibility of formation of cholera-like vibrios from cholera vibrios (Ermol'eva, Doorenbos). However, the genetic closeness of cholera and cholera-like vibrios resulting from these experiments does not yet resolve the question of the possibility of spontaneous transformation under natural conditions of cholera-like vibrios into a cholera vibrio capable of causing an epidemic outbreak of cholera. Epidemiological observations of cholera epidemics characterize them as imported exotic diseases with the initial source of infection in endemic foci of cholera in India. At the same time, sporadic diseases with the clinical picture of cholera can undoubtedly be caused by non-agglutinating, so-called cholera-like vibrios. Such diseases, indeed individual cases, have been studied and described by a number of authors (Khavkin, Zlatogorov, Savchenko and Voronina, Ermol'eva, Doorenbos). Ermol'eva also isolated in three cases from patients with the clinical picture of cholera (from feces and bile) luminescent cholera-like vibrios that agglutinate with the sera of patients. Bacilli carriage of cholera-like vibrios has also been described (Ermol'eva, Doorenbos). In 1934, Doorenbos proposed to divide vibrios into 2 groups on a new basis: the epidemic type cholera vibrio and the endemic type cholera vibrio, considering that the first is the virulent cholera vibrio, and the second is 'avirulent'. According to Doorenbos, the syndrome of Asiatic cholera can be caused by any vibrio, but epidemic cholera is caused only by an agglutinating vibrio. The main cause of transformation of a virulent virus into an 'avirulent' one is bacteriophage. When treated with bacteriophage, the epidemic virus in carriers immediately passes into the 'avirulent' endemic one. A special property of both types is their extreme reversibility. Thus, scientific data do not provide evidence that a vibrio that does not possess all the biological peculiarities of the cholera vibrio is not a cholera vibrio or is not related to Asiatic cholera. On the contrary, it becomes more and more probable to assume that the 'atypical vibrio' is nothing other than a modified cholera vibrio. To overcome practical difficulties in isolating non-agglutinating vibrios from suspicious patients, German authors recommend the mandatory use of Diedonne medium and gelatin plates in primary cultures, in addition to peptonic enrichment, because water vibrios, being present in the intestine in small quantities, are not detected in cultures on plates and multiply abundantly in the peptone film. In addition, it is recommended to test all typical colonies found on plates for agglutinability in order to increase the probability of finding agglutinable strains. Passages of non-agglutinating vibrios through bile often restore their agglutinability (Ermol'eva). Immunity and specific prevention of cholera. Introduction of small amounts of cholera vibrios to experimental animals (rabbits, guinea pigs) gives them resistance to subsequent injections of lethal doses of cholera vibrio. The study of the properties of such an immunized animal made it possible to establish that cholera vibrios introduced into the abdominal cavity of an immunized animal are completely destroyed there in a very short time, which can be easily verified by examining microscopically every 5 minutes the exudate extracted from the animal's abdomen with a Pasteur pipette (Pfeiffer-Isaev phenomenon), while a control, non-immunized animal dies as a result of multiplication of cholera vibrios introduced into the abdominal cavity. Subsequently, the presence of the same bactericidal properties was established in the blood serum of animals immunized by subcutaneous injection of live or killed cholera cultures. In addition to these so-called Pfeiffer bacteriolysins, agglutinating properties in relation to cholera vibrios were found in the serum of immunized animals (Gruber and Derhem), and Kraus showed the ability of immune sera to give a specific precipitate (sediment) with the filtrate of old cholera cultures. These properties of the serum of immunized laboratory animals were also established in the serum of people who had had cholera disease. Similar properties of the serum and R. Koch's statement about the absence of a soluble exotoxin in cholera microbes formed the basis of the views of most authors on the essence of cholera immunity. According to these views, in cholera immunity, we are talking about a state when the immune organism is able to quickly kill the cholera vibrios that have penetrated it, before they multiply enough to cause lethal intoxication by the products of decay of bacterial cells (Pfeiffer). A number of authors (Huppe, Ransom, Mechnikov, Rou, Salimbeni) attribute the poison of the cholera vibrio to exotoxins. Apparently, the toxic products of the vibrio belong to both types. Satisfactory results obtained in experiments on animals made it possible to transfer preventive subcutaneous immunization to humans, and among the various types of proposed vaccines (live, sensitized cultures, killed by various methods, filtrates of cultures, etc.), the Kolle vaccine became most widespread, in which cholera microbes are killed by heating to 58° for 1 hour. The study of sera of people immunized with the Kolle vaccine showed that, starting from the 4th day after the end of immunization, it is possible to establish the presence of specific bactericidal properties of the serum, reaching a maximum after 10 days. The effectiveness of subcutaneous cholera vaccination has been tested on extensive material in epidemiological observations in Russia (Zlatogorov, Zabolotny), during the Balkan War of 1912-1913 and the imperialist war of 1914-18 (Cantacuzene); the vaccine gave a decrease in morbidity among the vaccinated with triple immunization with sufficient doses by 8-10 times compared to the unvaccinated and significantly reduced mortality among the sick. The per os immunization proposed by Bezredka with tablets of killed cholera microbes proved to be ineffective and is currently abandoned.

The discovery of bacteriophage (see Bacteriophagy) in the excretions of cholera convalescents by d'Hérelle prompted him to attempt to use the cholera bacteriophage for the prevention of cholera epidemics and for combating cholera outbreaks. d'Hérelle published extremely favorable data on the rapid elimination of cholera epidemics by administering bacteriophage to the entire population of affected villages by adding it to drinking water. Recent studies have established the existence of 6 types of cholera bacteriophages (A, B, C, D, E, F), with cholera vibrios isolated from the intestine being lysed by only one of these types of phage (predominantly type A and E), and 10% of strains proving resistant to all types of bacteriophage (Pasricha de Monte). In view of this, bacteriophage prophylaxis of cholera requires further study. However, the use of bacteriophage for epidemic control purposes deserves comprehensive attention.

A. Ermolyeva.

Epidemiology of cholera. The appearance and spread of the first epidemics of cholera were explained by 'miasmas from the earth' (influence of Sydenham's teaching), 'development of gastro-neurotic constitution', influence of meteorological factors, etc. In the 1850s, it was believed that 'the cholera pathogen enters the human body in three ways, namely: through the respiratory organs, digestive organs, and through the skin' (official instruction for physicians of the Medical Department of War, 1847). Trizinger in 1851 suggested that cholera diseases have their specific cause, their special poison, capable of being reduced wherever it is introduced. Pettenkofer believed that the cholera poison has a certain relation to the soil. Depending on the porosity of the soil, its humidity, and the level of groundwater, the soil creates conditions (u) favorable for the cholera poison (x) to transform into an active poison (g). For the development of cholera, therefore, its introduction is not sufficient, but there must be local predisposition (örtliche Disposition). But the same soil is not always suitable for the development of the cholera poison. In addition to local predisposition, there is also seasonal predisposition (zeitliche Disposition). Later, Emmerich modified the localistic theory of Pettenkofer. He believed that cholera disease is the result of poisoning of the body by nitrous acid. For this, the cholera vibrio must have the ability to convert intestinal nitrates into nitrites. The cholera vibrio (z) acquires this ability (u) only in the soil and then it transforms into an active microbe (z). The teaching of Pettenkofer and his followers now has only historical interest. The discovery by R. Koch of the cholera vibrio (in Egypt in 1883) opened the way for a comprehensive study of the epidemiology of cholera and the fight against it. At present, the following epidemiological facts can be considered established: 1) The spread of cholera is possible only from a patient (taking into account the variety of clinical forms of cholera: from the mildest-atypical, outpatient cases to the most severe) or a healthy carrier of cholera vibrios. 2) Vibrios are excreted not only during the period of clinical illness, but also for a certain time after recovery. On average, the duration of such excretion can be considered about 3 weeks, but individual cases of longer preservation of vibrios in the intestines of cholera patients have been described: up to 56 days (Zlatogorov), 71 days (Vecheslov), 93 days (Tseydler), and even a year (Kulesha). 3) Cholera vibrios have been found during epidemics in completely healthy individuals. During the cholera epidemic of 1908-1909 in St. Petersburg, among 9,737 isolated individuals, vibrios were found in 577 (5.9%). During the cholera epidemic in Odessa in 1918, among 1,707 examined contacts of patients, cholera carriers were found in 155 people (9.1%). Of these, 56 subsequently became ill, and 99 remained completely healthy. The longer the contact of contacts with a patient or carrier, the more often carriage of vibrios develops among them. Carriage is more common among women and children. This has great epidemiological significance (women as housekeepers can more strongly contribute to the spread of infection, as do children, in whom cholera often proceeds atypically). According to data from the Odessa epidemic, cleansing from vibrios in healthy carriers proceeded as follows: in the 1st week they disappeared in 87%, in the 2nd-in 10.9%, in the 3rd-in 1.5%, in the 4th and 5th-in 0.6%. 4) The portal of entry for cholera infection is the mouth, through which it penetrates into the intestine. There are no other ways for vibrios to enter the body. 5) Cholera vibrios are excreted from the body mainly through the intestine with feces; they are comparatively rarely found in vomit. 6) Outside the human body, cholera vibrios are preserved for varying times depending on the environment and physical conditions. They are very sensitive to drying out. On a cover glass in the air, most of them die within 2 hours. With rapid drying and under the influence of the sun, they die sooner. Their preservation in dry dust and the transmission of infection with it is impossible. Vibrios are sensitive to heating. At boiling temperature they die instantly, at 80°-in 5 min., at 56°-in 1/2 hour. They tolerate low temperatures better (their preservation in ice has been proven). They are sensitive to disinfectants: in a 1% solution of phenol they die in 5 min., in a 1/2%-solution-in 10 min., in a very weak solution of mercuric chloride (1:2-3 million) they die in 5-10 min. (culture), in a solution of hydrochloric and sulfuric acid (1:10,000)-in a few seconds. Chlorine in a dilution of 1:1,000,000 in water kills them in 15 min., in feces, lime milk (1:4) kills them in 1 hour with frequent stirring. In distilled water they do not last longer than 24 hours, in river water under natural conditions for several weeks. Zlatogorov found them in raw Neva water after 19 days, and in boiled water after 37 days. In feces in sealed jars at a temperature of 3-8° they were found for 7 (Zlatogorov) and 9 (Kulesha) months, in cesspools up to 106 days. In the presence of putrefactive bacteria they die quickly. In putrefying feces they die in 1-3 days, in individual cases they survive up to 30 days. They can remain for a long time in feces on linen in the absence of light and drying (over 200 days). On food products, vibrios remain depending on humidity and reaction. On dry products they die quickly, on liquid ones, in the absence of an acidic reaction, they can live much longer, e.g. in sterilized milk for about 10 days (according to Zlatogorov-several months), in non-sterilized milk due to competition of the microorganisms present-only 1-2 days. In butter they can live up to 26 days, on potatoes-up to 2 weeks, on fresh cucumbers-up to 4 days, on the surface of grapes-for several hours, in sealed baskets on grapes sprinkled with cork-about 3 days. 7) Infection from a patient is possible either through direct contact with feces or objects contaminated by them (e.g. linen) or through water and food products. The transfer of vibrios by insects (e.g. flies) is also admitted. Infection through water is possible with direct entry of feces into a body of water (e.g. from ships), with seepage of sewage into it, with washing of linen, etc. Such 'water' epidemics are characterized by rapid development, uniform distribution of diseases among all using this water source, and rapid cessation of the epidemic as soon as the source is excluded from use. Contact epidemics are characterized by slow, sluggish, and prolonged course, uneven distribution of diseases in the given locality; it is often possible to prove the transmission of the disease from one house to another, from one family to another. Water epidemics in turn can turn into contact ones. A typical example of a water epidemic is the cholera epidemic in Hamburg in 1892. The first cases began in the port. For several weeks there were individual cases, on 26/VIII the epidemic spread throughout the city. By the end of August, the number of cases reached up to 1,000 per day. The water supply had no filters at that time, and water from the Elbe entered the water supply without purification. The river water could easily be contaminated by patients and carriers from numerous ships, during washing of linen, etc. The city of Altona, located near Hamburg and downstream on the Elbe, which had good filtered water, had almost no cases (see figure-Water infections). Similarly, in 1908-10, when cholera was raging in St. Petersburg, the nearby Tsarskoye Selo, which had good water supply and a properly organized system of waste removal, was spared by it. In practice, pure water epidemics are rare, usually epidemics are either contact or mixed. 8) The routes of cholera are the communication routes along which cholera is carried by moving people. From the delta of the Ganges, it was repeatedly spread throughout India by pilgrims. Similarly, by Muslim pilgrims it was repeatedly introduced into Hejaz (Mecca) and from there spread along their return route. The movement of cholera along waterways (e.g. from Astrakhan up the Volga) should be explained by the movement of ships. In the last years of its existence in the USSR (1919 and subsequent years), it moved mainly along railway communication routes. 9) The speed of cholera's movement from one locality to another depends on the speed of people's movement. In the first epidemic of cholera, it took 6 years to move from India to the borders of Europe. Subsequently, with the improvement of means of communication, the time for cholera's movement significantly decreased. The cutting of the Suez Canal sharply shortened the path of cholera (see above). 10) The duration of individual outbreaks is related to the measures taken. If they are insufficiently carried out, cholera in the same locality can recur for many years in a row.

The recurrence of outbreaks can be explained by the fact that vibrios persisted in carriers and 'under favorable conditions caused an outbreak, partly because vibrios may overwinter. 11) Cholera epidemics are mostly observed in the summer (see below - statistics). This is explained by the easier contamination of water bodies in the summer (navigation), the presence of flies, etc., but winter outbreaks are also often observed. 12) Cholera is mainly observed among the poorest sections of the population living in the most unsanitary conditions. During the cholera of 1908-09 in St. Petersburg, among the sick men, the largest group consisted of laborers, day laborers, and other representatives of unskilled labor; among women - housewives, servants, laborers, and laundresses. During the cholera epidemic of 1892 in Hamburg, a close connection was established between the incidence of cholera and family income (see Infectious diseases, table 17). 13) Wars and famines, associated with the movement of large masses of people and worsening sanitary living conditions, usually served as a factor contributing to a sharp increase in cholera. 14) The incidence of cholera in individual populated areas is entirely related to their sanitary improvement. There are no areas 'immune' by their natural conditions to cholera. Properly organized water supply and removal of waste and refuse and a high sanitary culture of the population exclude even with the introduction of the possibility of an outbreak of cholera in a given area. Geographical distribution and statistics. The largest focus of cholera continues to be British India. While fluctuating in individual years, cholera in India shows no noticeable tendency to decrease (figs. 1 and 2). In the current century in India, in individual years (1900, 1906), up to 700-800 thousand deaths from cholera were recorded. By decades, the number of deaths from cholera in India was: in 1901-10 - 3,770,845, in 1911-20 - 3,683,736, in 1921-30 - 2,597,847. In total for 30 years (1901-30), over 10 million deaths from cholera were registered in India. It should be borne in mind that in India, as in other colonial countries, the medical organization is more than primitive, and official figures can hardly claim any exhaustive completeness. Large foci of cholera continue to be French India, Indochina (fig. 3), Siam, the Philippines (fig. 4). Cholera has not been eradicated in Japan, although the number of cases has decreased significantly in recent years (fig. 5). The same applies to Korea. In the Near East, large outbreaks of cholera have been observed in Iraq in recent years. From the countries bordering the USSR, besides Japan and Korea, cholera is observed in Iran, Afghanistan (no numerical data available; according to official information, there was an outbreak in 1930) and China. Only fragmentary information is available for the latter. Large epidemics of cholera in BENGAL from 1927 to 1934 (absolute figures by quarters of the year), covering a significant part of the country, were observed in 1926, 1932 and 1933. In 1932, for the first 9 months, cases of cholera were registered: in Shanghai over 3,500, in Amoy - 1,638, in Canton - 1,109, in Nanking - 1,516, etc. In the cities of Manchuria in 1932, up to August, 13,365 cases were registered.

Morbidity by age. In some epidemics, cholera affected the younger age groups extremely severely. This was the case, for example, in the 1892 epidemic in Hamburg (table 9). In thousands, MORBIDITY AND MORTALITY from CHOLERA in FRENCH INDOCHINA from 1912 to 1932 (absolute figures). Designations: sick deceased Table 9. Mortality from cholera by age groups in Hamburg in 1892 (per 10,000 people of corresponding age). Age Mortality Age Mortality 5-15 years .... 15-25 years .... 336.5 213.3 63.7 59.6 70 years and older 106.9 205.7 271.2 135.1 The case fatality rate for cholera averages about 50%. Materials from Hamburg epidemics give the following percentage of case fatality (table 10): Table 10. Case fatality rate in cholera in Hamburg. Years Sick Died Case fatality 1848-50..... 1853-57..... 1866 . . . . ... 1892-93...... 5,672 2,275 2,586 2,254 i 729 17,226 2,798 1,385 1,285 1,158 1,001 8,684 49.3 60.9 49.7 51.4 57.8 50.4 In St. Petersburg during the 1908-09 epidemic, of 16,635 sick, 7,273 died, i.e. 43.7%. In Odessa, the case fatality rate was 55.8 in 1918, 47.2 in 1919, 65.0 in 1920, 48.8 in 1921. The case fatality rate varies in different age groups. It is highest in the youngest and oldest age groups (table 11). Seasonality of cholera morbidity. Before the war in Russia, cholera usually developed in June, reached its peak in July or August, and stopped or significantly decreased in the winter months. An example can be the monthly distribution of cholera in Russia in 1892 (table 12). Table 11. Case fatality rate in cholera in St. Petersburg in 1900-09 by age. Age Case fatality Age Case fatality 0-6 months . . . 81.5 -35 years.... 38.7 6-12 months ... 77.8 -45 years .... 50.0 1- 5 years . . . 59.8 -55 years .... 58.3 6-10 years .... 36.1 -70 years .... 67.1 11-15 years .... 20.6 years and older . 70.9 16-25 years .... 26.4 ; Table 12. Monthly distribution of cases and deaths from cholera in RUSSIA in 1892 (absolute figures) Months European Russia Caucasus Siberia Central Asia sick died sick died sick died sick died March 3,201 90 299 137 673 65 252 214 April 91 10 107 2,857 1,853 46,625 60,604 28,852 9,087 May 4,331 3,280 73,356 55,471 8,642 2,142 2,069 38,271 June 22,256 7,782 8,213 11,203 3,582 833 3,463 5,859 July 28,22 2,896 1,624

MORBIDITY AND MORTALITY from CHOLERA in JAPAN from 1910 to 1932 (absolute figures) * o nl.no рй" Designations **^t _rs sick ^and deceased BEFORE 100 days sick deceased years when cholera was not present, l Figure 5. In 1919-20, many winter outbreaks of cholera were observed in the USSR.

i. dobreytser.

Pathological anatomy. External examination of cholera patients who died in the algid stage reveals a characteristic emaciation, especially of the face; the cheeks and eyes are deeply sunken. The general integuments are somewhat cyanotic. This emaciation is of an acute nature and is associated with disturbances in water metabolism, partly due to fluid loss from diarrhea and vomiting, and partly due to the influx of blood to the internal organs. Also striking is the pronounced relief of the body and limb musculature and the rigor mortis of this musculature: the deceased appears as if he were an athlete, though he was not in reality. The corpse often retains the pose of a gladiator, when the rigor mortis of the musculature is combined with some bending of the limbs and tightly clenched fists. These phenomena of pronounced and early rigor mortis are characteristic, however, not only for cholera, but also for all sudden deaths occurring after severe convulsions or at the moment of extraordinary physical, resp. psycho-physical exertions. The tissues of the corpse are very poor in water. The blood in the vessels is very dark, thickened. The serous membranes are either dry or, what is more characteristic, covered with a thin slimy coating, like a soapy lubricant. From the hands, touching such surfaces, thin semi-transparent threads stretch. This phenomenon of "saponification" of the serous membranes, especially of the peritoneum and pleura, is apparently connected with the sharp thickening of the usual physiological fluid in the same cavities, i.e., it reflects the same phenomena of anhydremia as the blood. Anhydremia is also evidenced by the sharp increase in the number of red blood cells in the peripheral blood. From the side of the small intestine, the most acute serous-desquamative, often serous-hemorrhagic catarrh is found. The intestinal wall, especially of the jejunum, is pink, swollen, with small hemorrhages [see separate table (pp. 271-272), Fig. 4]. Similar changes are often observed in the large intestine, although the changes in the latter are more characteristic of cholera typhoid (see below). On microscopic examination, massive desquamation of the intestinal epithelium is found, both of the villi and of the Lieberkühn's glands. Pirogov compared such denuded villi with "withered dandelion heads". From the side of the nerve ganglia of the intestines, degenerative changes are noted. The contents of the small intestine are quite abundant and have the appearance of liquid rice broth, either completely white or pinkish in color. Pigmentation with bile pigments is often completely absent. On bacterioscopic examination, among the masses of epithelial cells, masses of cholera vibrios are found in the form of "schools of fish". Often, however, in the most acute cases, bacterioscopic examination gives a completely negative result, which is probably explained by the rapid bacteriolysis even during life. Vibrios are also found in the depths of the intestinal glands, as well as in the stroma or lymphatic vessels of the mucous membrane. The gallbladder is usually dilated, the mucous membrane is in a state of catarrh, and the bile itself is turbid, light (Kulesha). Bacteriocholia is a fairly constant phenomenon, and the hematogenous route of vibrio entry is most probable (through the general blood flow to the liver with subsequent excretion into the bile duct system and then into the bladder). Experimental data also speak for hematogenous bacteriocholia: the introduction of vibrios or their endotoxins into the blood causes the appearance of vibrios, resp. endotoxins, in the duodenum and jejunum within the next few hours. The possibility of penetration into the general bloodstream is also evidenced by the finding of vibrios in internal organs, e.g., in the brain, spleen, as well as in the meconium of fetuses of mothers who died from cholera. On the basis of the same facts, the entire mechanism of the development of intestinal phenomena should probably be considered not as a direct consequence of the entry, multiplication, and bacteriolysis of vibrios in the intestine, but as a result of the excretion of vibrios into the intestine (through the liver) with the subsequent release of endotoxins and the development of local and general phenomena upon absorption of the endotoxin. From the side of other organs, degenerative-necrobiotic changes are described in the ganglion cells of the brain and spinal cord (F. Ya. Chistovich). In the kidneys - a picture of necrotic nephrosis and various degenerative changes. In algid cholera, the spleen is not enlarged, it is often diminished and its capsule is wrinkled. This is probably also explained by the loss of water, i.e., the decrease in the mass of blood in the organ. The lymph nodes of the mesentery, partly retroperitoneal, are somewhat enlarged. - In cholera typhoid, the anatomical picture of cholera is completely different. Lesions are observed mainly in the large intestine in the form of their diphtheritic inflammation (similar to dysentery). Similar changes are possible in the stomach, in the gallbladder. There is an indication that this kind of picture is caused by an allergic reaction of the intestine (stomach, gallbladder) to repeated contact with cholera endotoxin. The diphtheritic changes of the mucous membranes subsequently give extensive ulcerative fields, scar changes. The picture is often complicated by marantic edema, general exhaustion.

I. Davydovsky.

Clinical picture of cholera. The duration of the incubation period in Ch. is on average 2-5 days. It should be noted that factors that lower local resistance, such as dietary errors and previous stomach and intestinal ailments, favor the development of infection. It has been repeatedly observed that patients with enteritis or dysentery during an epidemic became victims of Ch. in the first place. Clinically, all cases of the disease can be divided into four groups depending on severity: 1) choleric diarrhea, 2) cholera morbus, 3) algid, or asphyctic cholera, 4) fulminating Ch. 1) Choleric diarrhea is difficult to distinguish from ordinary mild diarrhea. Usually at night, the patient begins with moderate diarrhea, with 5-6 loose stools per day, the stool is fecal, liquid, quite abundant, of normal color. Abdominal pain, nausea and vomiting are absent. The general condition suffers little, sometimes a feeling of weakness appears, but rarely forcing the patient to bed. The duration of choleric diarrhea is 2-3 days, then the patient recovers or there is a transition to algid Ch., i.e., the diarrhea represents a prodromal stage of severe Ch. Naturally, such cases can be accurately recognized only with the help of bacteriological research. 2) Cholera morbus runs more severely than the previous form. Here there are already signs of intoxication characteristic of Ch. The disease begins with diarrhea, rapidly develops a decline in strength, loss of appetite, nausea and vomiting of colorless, cloudy fluid appear, sometimes containing an admixture of mucus. The excretions, at first, are fecal, liquid, soon take on the consistency and color of rice water or even cloudy water. The amount of urine decreases, protein is found in it. On the first day, the temperature may be subfebrile, but after 1-2 days it drops to normal. In many patients, a weak pulse and painful cramps in the calves are noted. All these phenomena continue for 5-6 days, then diarrhea and vomiting cease, the patient recovers or severe typical cholera develops. 3) Algid, or asphyctic Ch. The initial symptoms may appear in the form of the mentioned choleric diarrhea or cholera morbus, but the attack of the disease often develops suddenly, immediately, and in a severe form. Frequent stool appears, the excretions quickly lose their normal color, become grayish, watery, resembling milk serum, and when containing a large amount of mucus flakes, they resemble rice water. In very severe cases, blood is mixed with the intestinal excretions, they have the appearance of meat slops. The number of loose stools rarely exceeds 20-30 per day. It is characteristic that patients do not complain of pain and sensitivity of the abdomen on palpation. In microscopic examination of the flakes floating in the excretions, mucus, leukocytes, a huge amount of intestinal epithelium and numerous cholera vibrios are found. Diarrhea is always accompanied by vomiting, and the vomit masses do not differ in appearance from the intestinal excretions. Patients weaken, they are tormented by severe thirst, but every sip of liquid is immediately thrown up by vomiting. The appearing frequent hiccups is an unfavorable symptom. With the intensification of diarrhea and vomiting, algid, or asphyctic state develops rapidly, sometimes even after 12-24 hours, on the basis of endotoxin poisoning. The algid state is characterized by the development of collapse in the presence of acute gastroenteritis. The patient's external appearance changes sharply, cheeks sink in, the nose sharpens, eyes sink deeply, surrounded by dark circles, lips are cyanotic (facies cholerica). The skin is pale, with a cyanotic tint, cold to the touch, loses elasticity, raised folds do not smooth out for a long time. The bluish tint and wrinkles are especially pronounced on the fingers of the hands ('laundress's hands') [see separate table (pp. 271-272), Fig. 5]. The voice becomes hoarse, soundless (vox cholerica). Urine output decreases and may soon cease, the temperature in the axilla falls below normal, sometimes to 32-30°; it should be noted that in the first 1-2 days of the disease it can reach 38-39° (initial fever). The pulse quickly weakens, the second tone on the aorta is not heard due to a sharp drop in blood pressure. Heart activity decreases both due to muscle degeneration on the basis of toxemia and due to a sharp thickening of the blood (see Anhydremia). Patients are particularly troubled by painful tonic cramps, appearing mainly in the calves, sometimes in the thigh muscles and in the fingers of the hands and feet; they represent one of the symptoms of intoxication. Shortness of breath is striking, the number of breaths is often 40-50 per minute. At first, patients are restless, toss in bed, complain of tightness in the chest and lack of air, suffer from insomnia; later excitement gives way to apathy and drowsiness, but consciousness is lost only shortly before death. Blood examination reveals an increase in concentration, an increase in the number of red blood cells and leukocytes, the latter number can reach 20,000. The number of neutrophils is increased, eosinophils are usually absent. The described algid, or asphyctic stage develops on the basis of poisoning with cholera endotoxins and partly due to the loss of the body of a large amount of fluid. In cases with a fatal course, a stage then follows, characterized by extreme circulatory disorders. Diarrhea and vomiting become less frequent, or even cease, while cyanosis rapidly progresses. A sharp blueness of the face, hands, feet appears, sometimes the entire surface of the skin becomes dark purple, the pulse is absent, the corneas become dry and cloudy. This period is always short, after a few hours death occurs with signs of deep coma. When the algid period passes into the stage of recovery, the pulse improves or, if it was absent, reappears, cyanosis begins to disappear, shortness of breath passes, skin elasticity is restored, the voice acquires sonority. The temperature rises, reaching normal. Excretions are less frequent, lose their watery character, become mucous, then fecal with an admixture of mucus, often at this time they are foul-smelling. Vomiting disappears, but later than other symptoms and only slowly and gradually; even several days after vomiting ceases, patients complain of severe nausea. Urine output is restored, sometimes abundant diuresis appears immediately. In the urine, protein, hyaline and granular cylinders disappear, kidney function becomes normal. Despite the severe illness suffered, recovery occurs quickly, after 8-10 days, and usually without consequences. Vibrios are not found in most patients after 2 weeks. The period of convalescence does not always proceed smoothly, after a few days symptoms of the disease may return (relapse), of which the most constant are vomiting and anuria; diarrhea usually does not relapse. After severe algid phenomena, the patient is often threatened with the development of cholera typhoid. Immediately after the acute period of Ch. or in the stage of recovery, symptoms appear resembling status typhosus. The patient becomes apathetic, sleepy, speaks indistinctly, with difficulty answers questions, sometimes delirious. A flush appears on the cheeks, the conjunctiva are injected, the tongue is dry, covered with a dark coating. The temperature rises, sometimes significantly, the pulse is full, often slowed down. Deep and slowed breathing is especially characteristic of this stage. From the side of the gastrointestinal tract, persistent nausea, vomiting and often liquid, foul-smelling fecal stool are noted. The amount of urine decreases, anuria may even occur. During cholera typhoid, skin lesions in the form of urticaria, scarlatina- and rashes similar to measles are often observed, sometimes hemorrhagic exanthems, usually disappearing after a few days. These erythemas, it should be thought, are of toxic origin. In some patients, cholera typhoid is complicated by diphtheritic lesions of the large intestine, on the surface of which changes similar to dysenteric are found. The causative agents of dysentery are absent in these cases. Such patients have frequent, foul-smelling, bloody stools with an admixture of dark brown clots. Such diphtheritic changes can also be observed on the mucous membrane of the pharynx, larynx, bladder and vagina. In general, the duration of cholera typhoid is from 1 to 3-4 weeks. The prognosis is usually unfavorable, death occurs in a deep comatose state. The essence of typhoid is not clarified; it is assumed that the cause is the development of a mixed infection causing secondary changes in tissues weakened by cholera endotoxin. The participation of the kidneys in the clinical picture of Ch. and in particular cholera typhoid is not entirely clear. The causes of such a serious symptom as anuria are not exactly known. It should be considered certain that in the presence of anuria, changes in the kidneys are sometimes not found, and, on the other hand, diuresis may be sufficient despite severe degeneration of the renal epithelium. Oliguria and anuria, in addition to cholera nephrosis, can be caused by other reasons. In these cases, the thickening of the blood, the drop in blood pressure and possibly, as Munk thinks, the influence of the nervous apparatus regulating the secretory activity of the renal epithelium are of importance.

Similar phenomena are observed, for example, in renal colic, which often cause reflex anuria. The development of necrotic nephrosis should be considered characteristic for the cholera kidney. In such cases, protein (up to 5-10/00), hyaline, granular, and especially epithelial cylinders, renal epithelium, leukocytes, and often even erythrocytes are found in the urine. Cylindruria is more pronounced after the immediately preceding period of anuria. In the stage of recovery, these changes almost always disappear without a trace. 4) Fulminating cholera is characterized by rapid development of severe intoxication, with diarrhea and vomiting being expressed to a slight degree or even absent. In the latter case, they speak of cholera sicca (dry cholera). Patients die after 1-2 days with symptoms of cyanosis, fall in blood pressure, and hypothermia. Complications. Regarding kidney damage, it has already been said. From the side of the lungs, complications occur with catarrhal, and less frequently with lobar pneumonia, which in clinical terms present no peculiarities, except that in the algid period they can occur with subnormal temperature. The already mentioned diphtheritic lesions of the mucous membranes can be accompanied by bleeding. Often in cholera patients, the development of purulent parotitis and phlegmon is observed. As a sequential disease, mental disorders are mentioned. Combinations of X. with typhoid fever, paratyphoid, and especially often with dysentery are described. Diagnosis. Mild forms of X. in clinical terms present nothing characteristic and can be accurately recognized only bacteriologically. From this it follows that during a cholera epidemic, every case, even of mild diarrhea, should be considered suspicious in relation to X. With typical progression, recognition is not difficult if X. has taken on epidemic spread. Such signs are characteristic as the rapid development of algid state in the presence of rice-like stools and vomiting and the absence of painful phenomena from the abdominal organs. The diagnosis is substantially reinforced by epidemiological data, which during an epidemic have even decisive importance. Completely accurate recognition is established bacteriologically. It is necessary to especially resort to bacteriological analysis when the first or sporadic cases of X. appear, since there are a number of diseases clinically very similar to the typical form of X. Some cases of local X. (cholera nostras) in clinical course do not differ from Asian X., but the absence of cholera vibrios in the stools, especially upon repeated examination, gives the right to exclude the latter disease. The cholera-like form of tropical malaria clinically very closely resembles algid X.; recognition is not difficult due to the presence of malaria parasites in the blood. Collapse, vomiting, and rice-like stools are also observed in acute arsenic poisoning, but it differs in that it is accompanied by severe pains in the abdominal region. From what has been said, it is clear that both cases suspicious for X. and those running with characteristic clinical signs of this disease should be subjected to bacteriological examination, by means of which the final and accurate diagnosis is established. It should be borne in mind that bacteriological examination of the stools of undoubted cases of X. sometimes gives a negative result. This happens in patients with cholera sicca, when cholera microbes may be absent in the contents of the rectum due to paralysis of the intestinal musculature, and at the same time are found upon section in the small intestines. It is not possible to use the agglutination reaction with the patient's serum for the diagnosis of X., because agglutinins in cholera patients are not formed constantly or in insufficient quantities. Prognosis. Sequential diseases after transferred, even severe X., are rarely observed. In some, protracted disorders of the intestine develop, more often manifesting in the form of diarrhea. In the vast majority of cases in those who have had cholera, complete recovery is noted. In general, mortality depends on the nature of the epidemic and ranges from 30% to 60%, although in reality it is lower, since mild cases escape registration. Cholera diarrhea and cholera give a favorable prognosis if they do not pass into the algid form. In the algid form, usually 50-60% die, cholera typhoid gives 80-90% mortality. The prognosis also depends on age - there are few chances of recovery in severe X. for the elderly and children under 5 years. Treatment. Specific therapy of X. has not given favorable results. In 1908 and 1909, Russian authors Stülern and Tushinsky applied the Bern serum against X. and observed marked improvement in the general condition and shortening of the illness. However, the high mortality rate obtained (29.9) does not give the right to consider this serum a valid means. Most clinicians who applied variously prepared sera against X. could not note a specific influence on the course of the illness. To specific therapeutic means should also be attributed the bacteriophage, virulent for the cholera vibrio. Experiments with treatment with this means were carried out by d'Hérelle in 1927 in India. The results were very good, mortality in the treated was 8.5%, while in the control it reached 60%. The bacteriophage was administered to patients repeatedly per os. Similar treatment experiments were conducted by other authors, but the results were contradictory, so it is still premature to judge the validity of the method. - Drug treatment. In the treatment of X., one should promote as soon as possible the excretion of the toxin from the body and at the same time support the weakening activity of the heart, protect from loss of heat and compensate for the loss of fluid. Prescription of means that delay diarrhea is indicated only in mild X., when there are no symptoms of toxemia. In such cases, tincture of opium is prescribed with the aim of giving rest to the inflamed organ. In the toxic form, this means is inappropriate, it delays the diarrhea, promoting the excretion of poisonous products. Some authors are satisfied with the treatment of severe X. with high enemas of a heated 1% solution of tannin, proposed by Cantani in 1884. This method, according to the observations of V. Stefanovsky in Odessa, gives no noticeable effect. Besides, the procedure itself is very tiring and distressing for seriously ill patients. The meaning of prescribing these enemas is unclear, since only in rare cases does the liquid in small amounts penetrate above the Bauhinian valve. In severe X., even in the algid stage, the best results are obtained from infusions of physiological salt solution, which were first applied in 1831 by the English physician Latta. This method was widely used in the Hamburg epidemic of 1892. Intravenous infusions of a solution heated to 40° often give a striking immediate effect: patients without a pulse, cyanotic, resembling a corpse, after a short time recover, sit in bed, ask for food, a pulse appears, cyanosis disappears. However, the improvement does not last long, after a few hours the previous state sets in. This is explained in part by the fact that physiological solution is corpus alienum for the blood and is very quickly removed from it. More stable and lasting results are given by subcutaneous infusions, but they act more slowly, after several hours. Therefore, in severe cases, both intravenous and subcutaneous infusions should be done simultaneously, in milder course of the illness or when improvement has already occurred - only subcutaneous. The introduced liquid dilutes the concentration of cholera toxin, promotes its excretion, increases blood pressure and warms the patient. Experience has shown that it is necessary to infuse 2-3 times a day, each time 1-2 liters; it is advisable to add to the liquid introduced under the skin 1 cm³ of adrenaline 1:1,000. The infusions give more stable improvement if hot baths (38-40°) with sequential sweating and continuous warming of the patient by means of hot-water bottles are applied simultaneously. It is very important to begin treatment no later than 12 hours after the onset of the disease, before the beginning of the algid period, and one should not forget that among therapeutic procedures, those that deliver to the body the heat it needs are especially effective. Hot baths are quite indicated, they cause dilation of the narrowed skin vessels and disappearance of cyanosis, increase body temperature by 1-2° and besides represent the best means for calming convulsions. Baths also influence urination, after them urine often appears. When getting out of the bath, the patient is wrapped in a sheet and woolen blanket and if there is no vomiting, hot drinks (tea) are prescribed, trying to induce profuse sweating. With sweat, part of the toxins is removed, the excretion of which in cholera patients is difficult due to kidney damage. Doctors unanimously note improvement in well-being after baths, and decrease in diarrhea and vomiting. Baths are done repeatedly, 3-4 times a day. - Of individual symptoms, frequent and painful convulsions deserve attention, which quickly, although temporarily, cease not only after baths but also with rubbing, best with talcum powder. To maintain the activity of the heart, subcutaneous injections of adrenaline are indicated, as already said.

It must be admitted that the indicated treatment for Cholera gives unsatisfactory results, with mortality rarely being below 30%. We do not have a better therapy. - The treatment of choleric typhoid presents an ungrateful task. The enormous mortality (80-90%) with all methods of treatment clearly indicates their ineffectiveness. Baths at 35-36° are prescribed, which improve the condition of patients. Feeding cholera patients becomes possible only after vomiting has ceased. With the existing diarrhea, liquid food is given, and patients at first willingly accept only ice water, later tea, lemonade, soda or Seltzer water, and especially Ac. citricum cum Natrio bicarbonieo. Later one can move on to jelly, black coffee, semolina porridge, crackers, and butter. Milk is not tolerated for a long time, causing nausea and vomiting. Several days after the diarrhea ceases, one can move on to minced meat, but only after the symptoms of nephrosis have disappeared. The nephrotic process in Cholera contraindicates the prescription of meat, as it is rarely observed in a pure form, and erythrocytes are usually found in the urine, indicating changes of a nephritic character as well.

V. Stefanekiy.

Fight against cholera. For a long time, one of the most important measures against the importation of Ch. was considered to be the establishment of quarantines: cities were cordoned off, cordon chains were set up between individual districts and between states. In Russia, the first cholera quarantine was established in 1829 in Orenburg, in 1830 Moscow, Kharkov and other cities were cordoned off, in 1831 St. Petersburg was surrounded by a double cordon of troops, etc. Similar quarantine measures were also carried out in Western Europe. In 1865, the English authorities organized a strict quarantine in Gibraltar; Ch. nevertheless penetrated there. Italy in 1884 implemented the strictest quarantine measures both on land borders and in coastal cities; this did not save it from Ch. The quarantine measures taken in many places in Germany in 1892 in connection with Ch. in Hamburg also proved futile. The first international sanitary conferences, convened to discuss anti-cholera measures, spoke in favor of the advisability of quarantines (e.g. the International Conference of 1866 in Constantinople). Only the Rome Sanitary Conference of 1885 stated that 'land quarantines and sanitary cordons are useless'. In the International Sanitary Convention of 1926, the main measures for the fight against Ch. are provided for in the following articles: Articles 1-5 - on notifications (immediate notification to other governments and the International Office of Public Health of the first unquestionable case of Ch.; simultaneously - providing detailed information about the locality and time of its appearance, about the number of cases, about the number of bacillus carriers, if any were found, about the measures taken; subsequent reports on the course of the epidemic and measures taken). Articles 13-14 - on measures in ports and upon the departure of vessels (not allowing persons showing symptoms of Ch. to board ships; ensuring that drinking water and food products brought on board are of good quality and that water brought on board as ballast is, if necessary, disinfected). Articles 17-20 - on goods and baggage (disinfection can be applied to recently used underwear, rags, clothing, bedding; fish, shells and fresh vegetables may be prohibited from import unless they have been subjected to operations capable of destroying the cholera vibrio). Articles 29-34 - on measures in ports and at sea borders: vessels arriving in ports and at sea borders are considered infected if there is a case of Ch. on board or if there was a case of Ch. during the 5 days preceding the vessel's arrival in port. They are considered suspicious if there was a case of Ch. at the time of departure or during the voyage, but there was no case during the 5 days before arrival. Infected vessels are subject to the following regime: a) medical examination, b) the sick are immediately taken ashore and isolated, c) the crew and passengers may be disembarked and held in observation or subjected to observation for a period not exceeding 5 days, counting from the time of the vessel's arrival. However, persons who provide proof that they have been immunized against Ch. by vaccination performed less than 6 months and more than 6 days ago may be subjected to observation but not to observation. Used bedding, dirty underwear, etc., as well as parts of the vessel in which the sick were located, are disinfected. The crew and passengers of suspicious vessels may be subjected to observation, which should not exceed 5 days from the time of the vessel's arrival. It is recommended to apply specific vaccination on as wide a scale as possible in cholera foci and to provide certain advantages with regard to restrictive measures to persons who agree to undergo this vaccination (see also Conventions, Port). Articles 58-66 - on measures at land borders (observation at land borders is not established; only persons showing symptoms of the disease can be detained at borders; if necessary, parts of borders may be closed, with places specified through which movement across the border is permitted; sanitary stations are set up at these places; travelers coming from affected districts may be subjected to medical observation, which, counting from the time of arrival, will not exceed five days). Approximately the same measures are also provided for in the legislation of the USSR ('Rules for the Sanitary Protection of the Borders of the USSR Union', 1932). As for measures to prevent Ch. within the country, they basically consist of carrying out general sanitary measures, first of all - the organization of central water supply [with filtration, and if necessary - disinfection (chlorination, ozonation)] and sewerage and the proper disposal of garbage and refuse. Where there is no central water supply, it is necessary in the event of a threat of cholera to provide the population with boiled water. All open bodies of water are taken under special sanitary supervision. The properly organized sanitary-food supervision (markets and bazaars, public catering establishments, etc.) is of enormous importance. A serious measure is the fight against flies. The implementation of personal preventive measures (washing hands before eating and after using the toilet, paying attention to drinking water and food) and sanitary propaganda are one of the most effective measures for the prevention of Ch. Special attention is paid to transport - railway and water (supply of passengers with boiled water and high-quality food products, disinfection of excreta, isolation facilities for suspicious cases), as well as to moving population groups (preventive vaccinations, see below). In places threatened by Ch., as well as upon the appearance of the first cases, mass preventive vaccinations must be carried out. According to the instruction of the People's Commissariat of Health (dated 10/X 1932) 'in the presence or threat of Ch., mass vaccinations against it should as a rule cover the entire population of the affected or threatened populated locality or district, with the most threatened professional groups and groups dangerous in terms of the spread of disease being vaccinated first, such as: medical personnel, sewer workers, workers and employees of water supply, food enterprises, laundries, workers and employees of transport, etc.; this also includes organized population groups moving along railway and water routes, especially settlers, seasonal workers, etc., and moreover both those moving from unfavorable areas to favorable ones and vice versa'. The diagnosis of cholera is made under laboratory control (the first cases of the disease must be subject to mandatory laboratory examination). Objects for examination can be the excreta of the sick, clothing stained with excreta (while they are still not dry), and in the case of death of a suspicious sick person - parts of the intestine with contents, taken during autopsy. In the absence of a laboratory at the site of the disease, the said objects are sent for examination to the nearest laboratory, with certain rules being observed, namely: the container for sending objects must not contain the slightest traces of disinfectants or acids. The container (made of thick glass; zinc, tin and other cans are not suitable, as the solder contains acid), as well as the cork with which it is covered, are previously sterilized by boiling for 20-30 minutes in a 1% soda solution. A well-fitting cork is covered on top with parchment paper or a cow's bladder and is tightly tied with twine. For sending excreta, mucopurulent flakes, clots and tissue fragments are taken from them, and the liquid part of the excreta is also taken. Pieces containing undried excreta are cut from the clothing with scissors. From the corpse, three sections of the small intestine are taken, tied in situ on the corpse on both sides. The length of each section is about 15 cm. One section must be near the cecum. The sections are placed in the vessel in which they will be sent without adding any liquid. With each object, information is provided indicating: 1) what is being sent, 2) the name and surname of the sick (or deceased) person, 3) their age, 4) where and when they arrived, 5) when they fell ill (or died), 6) when the material was taken, 7) a brief description of the disease or autopsy results. Objects for examination are sent by special messenger. Sometimes it is necessary to send water from a suspicious water source for bacteriological examination. If water is taken from a water supply, the faucet opening is first burned and water from the pipe is run for 5 minutes, after which the water is taken. To take a sample from a natural source, a previously boiled vessel is lowered on a rope to which a weight is attached into the body of water; after taking the sample, it is immediately closed with a boiled cork and immediately tied with parchment paper or a cow's bladder. For examination, at least 1 liter of water should be sent from each source. The water must be delivered to the laboratory no later than 1-2 days after it is taken. A person sick with Ch. must be hospitalized. In the medical institution where cholera patients are housed, a strict regime must be observed. The excreta and vomit of the sick, as well as objects contaminated by them, are subject to current disinfection.

A persistent fight is being waged against flies. The personnel must wash their hands as often as possible (each time after contact with the patient and his excretions), change gowns frequently, and is strictly forbidden from eating and smoking in the room where patients are located. The patient is considered safe for others after two negative results of research on feces for cholera vibrios. The first research is conducted no earlier than 5 days after clinical recovery from Cholera. In case of impossibility of research, the separation of patients, according to the rules of the People's Commissariat of Health, is terminated no earlier than 7 days after the end of clinical symptoms of the disease. Those who have come into contact with cholera patients are isolated, and according to the said rules, their separation from healthy people is terminated after a single negative result of research on feces for cholera vibrios, but not earlier than 5 days from the day of contact with the patient. For the transportation of cholera patients, special transport is allocated, which is subjected to thorough disinfection after EACH patient.