From Big Medical Encyclopedia

CHOLERA. With about d e r and N and e:

History............... 3 6

Aetiology.............. 3 7

Epidemiology............ 38

Pathogeny............... 3 9

Pathological anatomy....... 40

Immunity.............. 41

Clinical picture......... 41

Diagnosis............... 43

Treatment................ 4 4

Forecast............... 4 5

Prevention............ 45

Cholera (cholera; Greek cholera, from chole bile + rheo to flow, expire) — the acute infectious disease which is characterized by a gastrointestinal tract disease, disturbance of a water salt metabolism and dehydration of an organism owing to a fluid loss and salts with excrements and emetic masses. Distinguish the classical cholera caused by a so-called classical biopitch of a vibrio of cholera and the cholera El-Tor caused by a biopitch El-Tor.

History. Cholera — the most ancient disease of the person, edge extended to many countries of the world and even continents and claimed millions of the human lives. The endemic center of cholera were basins of the Ganges Rivers and Brahmaputra in India. The combination of hot climate to abundance of rainfall, geographical features (the low area, a set of floodplains, channels and lakes) and social factors (dense population, intensive pollution of reservoirs excrements, use of a contaminated water for drink and domestic needs) defined rooting of this infection in this region.

Till 1960 six pandemics (see) cholera were known though they were practically not divided epidemic by the safe periods. The first pandemic of cholera which began in India in 1817 in the next 8 years was brought to Ceylon, Philippines, to China, Japan and Africa, then to Iraq, Syria and Iran and, at last, to the cities of the Caspian Basin of Russia (Astrakhan, Baku). The second pandemic of cholera (1828 — 1837) which also began in India extended to China from where caravan tracks — to Afghanistan and to Russia (Bukhara, Orenburg). Other way of penetration of cholera to Russia — through Iran from where it extended to the countries of the Middle East and Transcaucasia. In this pandemic cholera captured the majority of provinces of Russia, was delivered to Western Europe and North America. The third pandemic of cholera (1844 — 1864) began with epidemics in India, China, on Philippines, in Afghanistan and pi Iran in Transcaucasia extended through the countries of Central Asia. Penetration of cholera into Russia was connected with epidemic which burst in countries of Western Europe from where the infection was delivered also to North America. The fourth pandemic of cholera (1865 — 1875) began in India

and, moving ahead in east (China, Japan) and the western direction, reached Europe, Africa and America. Cholera in this pandemic got into Russia through Turkey and from the West — through Prussia. The fifth pandemic of cholera (1883 — 1896) which captured the same districts of Asia, the southern ports of Europe and America did not pass also Russia. The sixth pandemic of cholera (1900 — 1926) was characterized by the expressed second rise that is connected with wars (Balkan, World War I, and also with intervention and the civil war in Russia).

During the periods between the described pandemics and after 1926 in the nek-ry countries of Asia there was no year, free from epidemic rise in incidence. The existing statistical data are based hl. obr. on the accounting of the dead from cholera. So, in China in 1939 — 1940 more than 50 thousand people died of cholera. On ofitsa. to data, in 1919 — 1949 in India died of cholera apprx. 10 million people. After 1950 the expressed decrease in spread of cholera was outlined. If from 1919 to 1949, according to the generalized O. V. Ba-royan's (1970) data, 350 — 400 thousand people died of cholera annually, then during the period from 1950 to 1954 this figure made 77 thousand, and in the subsequent fifth anniversary — approximately on 40 thousand. Classical cholera remained only in the ancient endemic center (in India) and in the 70th 20 century was not shown by massive epidemics. Pandemic spread of cholera these years is connected with the new activator — a biopitch El-Tor. The expressed ability of a biopitch El-Tor to cause epidemics of cholera drew attention of specialists in 1937 when in Indonesia on the Lake Sulawesi there was an epidemic of cholera caused by the specified activator. The lethality at this epidemic made 50 — 60%.

The wide spread occurance of cholera El-Tor began in 1961, to-ry many researchers consider year of the beginning of the seventh pandemic of cholera. Assessing current situation, the Committee of WHO experts (1970) considered quite probable spread of cholera in the near future and emergence it in those parts of the world, in to-rykh it was absent for many years. Role of a biopitch El-Tor as etiol. a factor of cholera quickly increased; the number of the diseases caused by this activator reached scales of epidemics. So, in 1960 a biopitch El-Tor was revealed at 50%, and next year — more than at 80% of all patients with cholera. Even in India in the 70th 20 century a biopitch El-Tor held the prevailing position.

According to not complete official data, in 1961 epidemics of cholera were registered in 8 — 10 countries; in the next four years cholera captured 18 countries, and since 1965 prior to the beginning of 1970 — 39 countries of the world. Such bystry spread of cholera over many countries of the world was not noted in one of the previous pandemics. At the same time primary emergence of an infection in many countries did not come to the end with elimination of the epidemic center and formation of full epidemic wellbeing. Cholera took roots in the territory of these countries. The developing pandemic of cholera El-Tor captured also those countries where the disease or was not registered many years, or was absent throughout all history of the previous pandemics.

At first cholera El-Tor developed on the Lake Sulawesi, then in Macau and Hong Kong from where it was delivered in Saravak, and by the end of 1961 — to Philippines. In the next 4 years cholera El-Tor developed on the lake of Taiwan, got into the countries of Southeast Asia and then into South Korea. In 1964 epidemic of cholera El-Tor arose in the Southern Vietnam where ached apprx. 20 thousand people. By 1965 it reached Afghanistan and Iran, extending in the districts directly adjacent to borders of the USSR. Final having sat down. - zap. the epidemic flash in Karakalpak the ASSR and the Khorezm region of the Uzbek SSR was border of spread of cholera in the middle of 1965. Further development of a pandemic of cholera El-Tor is characterized by frequency of epidemic flashes in the countries of Southeast Asia, the Middle East and its penetration on the African continent. In 1970 the epidemic outbreaks of cholera El-Tor arose in Odessa, Kerch, Astrakhan.

A culmination point of the seventh pandemic of cholera is 1971. If in 1970 in the world 45011 patients with cholera, then in 1971 — 171 329 patients, in 1972 — 69 141, in 1973 — 108 989, in 1974 - 108 665 and in 1975 — 87 566 patients were registered. In 1971 in the countries of Asia 102 083 cases of cholera are registered; the greatest incidence was noted in India, Indonesia, Bangladesh and on Philippines. In the countries of Africa it was registered 69 12 5 cases of cholera; at the same time the greatest incidence was in Ghana, Nigeria, Chad, Niger, Mali, Morocco, Cameroon, Upper Volta.

In 1971 cholera El-Tor is registered also in the nek-ry countries of Europe: Portugal, Spain, France, Sweden, etc. the concept that cholera El-Tor — a disease only developing countries, in to-rykh a dignity, - ptg Was seriously shaken. the standard of living of the population did not reach an optimum, isklyuchayushcheyu development of epidemic. Still more epidemic of cholera which arose in 1973 in Naples (Italy) — St. 400 cases of diseases shook this concept; epidemic was connected with consumption of the oysters got in coastal waters of the Mediterranean Sea.

In the next years epidemic rises in incidence of cholera El-Tor were observed in 36 — 48 countries: in 1976 66 804 patients, in 1977 were registered._ 58 661, in 1978 — 74 632 and in 1979._ 54 179.

The saved-up data characterizing features of cholera El-Tor do not keep within concepts of the modern epidemiology considering epidemic process as a series of passages of the activator from the carrier to the healthy person. At the same time the part of the ways of transfer bringing the activator to a human body is assigned to objects of the environment (water of open reservoirs, sewer dumpings). According to these settled representations of people is the only object supporting a continuity of epidemic process. This situation excludes existence (not vyuemenny preservation, but development and accumulation) of the causative agent of cholera El-Tor in the environment out of a human body. The analysis of an epidemic situation on the cholera which developed by 70th worldwide shows that the difference in terms of emergence of epidemics in these countries makes several days, and it is not enough for formation of the center and consecutive forward advance of cholera from the territory of one country on the territory another. It is theoretically possible to assume that once in the past the population of these countries (including those, in to-rykh throughout all their history did not arise cholera) was in one step infected, and at some unknown in a crust, time conditions in 1970 and then in 1971 in them in one step there were epidemics. Whether these unknown conditions are defined only by migratory processes, it is difficult to tell.

The epidemic situation on cholera in the world remains intense. In such countries of the world as India, Indonesia, Burma, Bangladesh, Malaysia, Philippines, Ghana, Cameroon, Niger, Nigeria, Senegal, etc., are observed I do not stop - shchiyeeya cholera with annual registration of patients from hundreds to several thousand people.

Etiology. The causative agent of cholera — a cholera vibrio of Vibrio cholerae Pacini 1854. Distinguish two biopitch: classical — Vibrio cholerae bio-var cholerae and El-Tor — Vibrio cholerae biovar eltor. Both biopitch make serological

group 01.

The causative agent of cholera is for the first time found by the ital. pathologist F. Patxi-t (and in 1854 in contents of intestines and a mucous membrane of a small bowel of the people who died from cholera in Florence. In 1883 in Egypt

R. Koch allocated a cholera vibrio in pure growth from excrements of patients with cholera and corpses of the dead from cholera and studied its properties. F. Gotschlich in 1906 at the quarantine station El-Tor (in Egypt, on the Sinai peninsula) allocated from intestines of pilgrims a vibrio on biol. to properties same, as well as allocated with R. Koch, but differing in hemolitic properties. Long time it was not considered as the causative agent of cholera. Only in 1962 in connection with the seventh pandemic of the cholera caused by a vibrio El-Tor it is recognized as the causative agent of cholera.

In different years researchers opened and described vibrioes, nek-ry of to-rykh on biochemical properties are similar to a cholera vibrio, but differ on somatic O-antigen (see Bacteria, antigens of bacteria; t. 5, additional materials) are also not causative agents of cholera. They were called choleroid vibrioes, and is later ON G-vibrioes (neagglyutini-ruyushchiyesya vibrioes). On the basis of similarity of structure of DNA and a community of many biol. characteristics they are also carried to a type of V. cholerae. Thus, the type of V. cholerae is divided on structure somatic About - an anti-gene into serogroups, from to-rykh the causative agent of cholera V.cholerae 01, and V. cholerae 02 is; 03; 04... to 060 and more can cause banal enterita and a gastroenteritis.

V. cholerae 01 is presented by serotypes (serovars) Ogava, Inab and Gikoshim. The cholera vibrio produces ekzoenterotoksin — choleragen, to-ry is received in pure form and represents protein with relative a pier. it is powerful (weighing) 84 000, consisting from 2 immunological of the differing fragments.

Animals under natural conditions have no cholera, at experimental infection rabbits suckers are most susceptible to a cholera infection.

A breeding ground of the causative agent of cholera — intestines of the person. Nevertheless he can endure a nek-ry span in the environment, and under favorable conditions and breed that El-Tor especially treats a biopitch. It is suggested that nek-ry atypical (not producing or poorly producing exotoxin — choleragen) vibrioes El-Tor are freely living microorganisms.

Cholera vibrioes represent small slightly curved or direct polymorphic sticks 1,5 — 3 microns long, 0,2 — 0,6 microns wide, and capsules do not form a dispute, have one polarly the located flagellum on length 2 — 3 times exceeding the size of a cell causing active mobility of a vibrio (see fig. to St. Vibrioes, volume 4, Art. 185). They are well painted with aniline paints, gramotritsatelna. Electronic microscopic examination showed the complex cellular texture of vibrioes characteristic of gram-negative bacteria. Cholera vibrioes — facultative anaerobes, well grow on usual mediums of alkalescent and alkali reaction, especially in the presence in them sodium chloride in concentration of 0,5 — 2%; optimum pH 7,6 — 8,2. Microbes grow at t ° 10 — 40 ° (a temperature optimum 35 — 38 °).

In myasopentonny broth and 1% to peptone water the microbe quickly breeds: in 3 — 4 hours on a surface there is opacification, and a bit later a gentle film. On an alkaline agar in 14 — 16 hours at t ° 37 ° the cholera vibrio forms smooth colonies of average size, transparent with a bluish shade, a surface of colonies wet, brilliant, a smooth edge.

The cholera vibrio forms an oxidase, decarboxylizes a lysine and ornithine and arginine does not decompose, splits glucose in aerobic and anaerobic conditions with formation of acid without gas that is characteristic of all sort Vibrio. Cholera vibrioes ferment also a mannitol, a maltose, sucrose, mannose, levulose, a galactose, starch and a dextrin, do not split pectine sugar, dulcite, raffinose, rhamnose, an inositol, salicin and sorbite; produce an indole from tryptophane and recover nitrates in nitrites. The cholera vibrio concerns to the I group on Heyberg (see Vibrioes) — decomposes sucrose and mannose and does not decompose pectine sugar. Having the expressed proteolytic activity, it liquefies to gelatin, casein, fibrin and other proteins. It develops a lecithinase, a lipase, RNA azu, a mucinase, a neuraminidase. Cholera vibrioes of a biopitch El-Tor with a growth in glyukozofosfatny broth of Clark, as a rule, form acetylmethylcarbinol while cholera vibrioes of a classical biopitch have no such ability. Nek-ry strains of a biopitch El-Tor lyse mutton and goat erythrocytes in a liquid medium.

The antigenic structure both the bio-varov causative agent of cholera is identical. They contain a thermostable somatic antigen 01. By method of double diffusion precipitation in gel in extract of a cholera vibrio 7 antigens — from and to 0 are revealed. It is most studied thermostable lipopolisakharidny and - the antigen of a cell wall defining serological specificity. This antigen has also properties of endotoxin and at parenteral administration causes development of antibodies, providing antibacterial immunity. Thermolabile flagellar N-antigen is identical at representatives of all serogroups of V. cholerae.

The cholera vibrio is sensitive to temperature increase: at

t'J 56 ° he perishes in 30 min., and at 1 ° 100 ° — instantly.

He transfers low temperatures rather well, remaining viable at t ° 1 — 4 ° not less than 4 — 6 weeks. High sensitivity to drying and a sunlight, to disinfecting substances, including to alcohol, solution carbolic to - you and especially to acids is noted.

The cholera vibrio is highly sensitive to the majority of antibiotics — to tetracyclines, a levomitse-gin, rifampicin; it is sensitive to erythromycin, aminoglycosides, ii about l at with intetiches to them penits of l of l of Ying of m

of a broad spectrum of activity, is a little less sensitive to tsefalosio-rina.

Morphological, cultural and biochemical characteristics of a cholera vibrio and neagglyu-tiniruyushchikhsya vibrioes are identical.

Identification of cholera vibrioes is based on definition of specific somatic 01 antigen and sensitivity to cholera phages: a classical biopitch — to a phage With, and a biopitch El-Tor — to a phage El-Tor. Biovara identify also on sensitivity to a nolimiksin (the classical biopitch — is sensitive, the biopitch El-Tor — is steady); hemagglutinations of chicken erythrocytes (the classical biopitch does not cause hemagglutination, El-Tor causes a biopitch); products acetylmethyl carbinol (the classical biopitch does not produce, El-Tor produces a biopitch more often).

Epidemiology. A source of an infection is the person — the patient and a vibriononositel. At cholera the vibriononositelstvo after the postponed disease is observed, the erased and atypical forms, and also a healthy vibriononositelstvo often meet (see Nositeljstvo of contagiums). It is necessary to consider also expressed resistance of vibrioes El-Tor to influence of adverse environmental factors.

A basis of emergence of epidemic outbreaks of cholera, on the developed views, as well as preservation of the activator in about a cue the period, continuous circulation defines it among the population. This circulation is represented or as direct transfer of the activator healthy from the patient, i.e. the disease is followed by further transmission of infection (perhaps in the absence of measures of isolation of the diseased), or in the form of emergence of the erased forms of a disease, and also the carriage which are links between clinically expressed forms or as the chain of carriers filling the period between two epidemic raising of a disease. On these representations, the activator can remain in the environment only temporarily, napr, in ice of the rivers, lakes.

However the data obtained during the studying of epidemics of cholera El-Tor in the 70th considerably expanded ideas of epidemic process at this infection. The beginning of outbreaks of cholera El-Tor occurs against the background of an obsemenennost vibrioes El-Tor of the open reservoirs contaminated by sewer dumpings. Attempts to specify the beginning of the developed epidemic situation by verification of medical documentation of hospitals and policlinics for the purpose of identification of the first patient with cholera, as well as mass serological researches for the purpose of detection of antibodies to vibrioes at suffering in the past from intestinal frustration, never gave positive takes.

The possibility of direct infection of the healthy person from the patient or the carrier (a so-called contact way), as is not excluded at any intestinal infection. However this mechanism of infection at well debugged system of identification and urgent hospitalization (isolation) of the diseased loses the leading value. At cholera El-Tor quite often in the settlement it is single-step or within several days (usually after the days off in summertime) the certain patients who were not communicating with each other are registered. But at inspection comes to light that infection of all diseased is connected with the open reservoirs (bathing, fishing) contaminated by drain waters. Existence of a vibrio, independent of the person, El-Tor is for the first time established by O. V. Baroyan's researches, P. N. Burgasova (1976), etc. According to them, in the Astrakhan Region in the open reservoir isolated from the dwelling of the person and his sewer dumpings within 2 years (term of observation) vibrioes El-Tor of a serotype Ogava (constantly were found at absence in the past of the diseases connected with this serotype). Also eloquently confirms a role of the environment mentioned above the outbreaks of cholera El-Tor in Naples (1973), caused by consumption of the oysters infected vibrionakhm El-Tor. P. N. Burgasov's data on finds of vibrioes El-Tor in aquatic organisms, about intensive reproduction of vibrioes at their direct entering into the contaminated river water or into bathing sewer waters give the grounds to claim that the environment (first of all, aquatic organisms of open reservoirs) can be not the place of temporary stay of vibrioes El-Tor, and the environment of their dwelling, reproduction and accumulation.

Numerous observations of foreign and domestic researchers will not always be coordinated in assessment of terms and the epidemic importance of a vibriononositelstvo. To a certain extent this results from the fact that data of observations belong both to classical cholera, and to the cholera caused by a biopitch El-Tor. So, J1. V. Gromashevsky and G. M. Vayndrakh (1947) as a result of generalization of big material note that usually intestines of the person who had cholera are cleared of cholera vibrioes to

15 — to the 20th day from an onset of the illness and only in 1% of cases the activator comes to light after 1 month. Cases of a carriage within 8 — 9 months are extremely rare (one on several thousands of patients with cholera). Possibility of a long carriage healthy people of cholera vibrioes of JI. V. Gromashevsky calls into question. V. I. Yakovlev (1892 — 1894), S. data of I. Zlatogorov (1908 — 1911), G. S. Kulesha (1910), etc. will be coordinated with this judgment. As WHO experts of Barua and Tsvetanovich consider (D. Barua, V. of Cvjeta-novic, 1970), carriers of cholera vibrioes constitute the main danger of delivery of cholera to the countries where it was not registered earlier. It is supposed that carriers keep cholera vibrioes in the interepidemic period. However as a result of the unique experiment made in the territory of our country when on a vibriononositelstvo 3 million 800 thousand healthy people (and a number of the contingents was inspected even repeatedly) were inspected any carrier of cholera vibrioes was not revealed that contradicts conclusions of WHO experts.

Other data are obtained during the studying of this question in the 70th 20 century in the centers of cholera El-Tor. According to the materials generalized by Barua and Tsvetanovich (1970), the attitude of number of carriers towards number of patients fluctuates from 10:1 to 100:1. So striking distinction of data on the frequency of formation of a «healthy» carriage in the epidemic centers of cholera demands the additional and very reasoned check. However it is necessary to consider that the vibriononositel-stvo given about frequency given by Barua and Tsvetano-vich generally are based on materials of the researches conducted within the endemic centers of cholera where intensity of epidemic process is extremely high. It is possible also that the number of vibriononositel quite often joins patients with the erased forms of a disease. The main reasons for broad planting by the causative agent of cholera of big collectives and emergence in this regard of considerable number of patients with asymptomatic forms or healthy carriers in many countries, unsuccessful on cholera, is insufficiency and limitation of measures for fight against it. E.g., speaking about moderately severe diarrhea, Mondal and Zac (Mondal, R. Century of Sack, 1971) note that it has great epidemiological value as promotes preservation of the activator among the population, but does not represent a wedge, problems since often it is not distinguished and it is not treated.

The mechanism of transfer of the causative agent of cholera to the person, as well as the mechanism of transfer of other intestinal infections (see the Mechanism of transmission of infection), consists in penetration of cholera vibrioes in went. - kish. a path with the infected water or foodstuff. However also the possibility of infection at direct contact with the patient when the activator can be brought in a mouth by the hands contaminated by allocations of the patient with cholera or a vibriononositel and also transfer of causative agents of cholera flies is not excluded.

Because environmental factors are important elements of the mechanism of transfer of the activator from the patient (or the carrier) healthy, extent of its impact on vibrioes and resistance of the last has essential value. With other things being equal at a vibrio El-Tor ability to survival out of a human body, than at a vibrio of classical cholera is more expressed. Resistance of the activator depends on features of the habitat, in particular on an obsemenennost its other microflora, concentration in it of salts, carbohydrates and organic matters, and also on temperature and pH of the environment. Perniciously the disinfectants used in practice of fight against intestinal infections in usual concentration affect cholera vibrioes. Also the direct sunlight has the same effect. Researches of Barua with sotr. (1970) on studying of survival of cholera vibrioes on various foodstuff showed that attempts to allocate vibrioes from the most various vegetables and fruit bought in the markets located in the endemic centers of cholera were undertaken repeatedly, but unsuccessfully.

As for survival of a vibrio El-Tor on artificially inseminated products, its term at the room temperature in relation to meat and fish products, and also vegetables makes

2 — 5 days. These data are obtained on Philippines in 1964. By P. N. Burgasov's researches, etc.

(1971, 1976), carried out at the solution of a question of a possibility of export of vegetables and water-melons from the districts affected with cholera, it was established that at the daytime temperature

of air 26 — 30 ° and scattered sunlight the tomatoes and water-melons which are artificially inseminated by a vibrio El-Tor were free from it in the 8th hour. Concerning spread of cholera water of the open contaminated reservoirs (the rivers, lakes, the water area of ports and beaches), and also the damaged water supply systems and wells has the greatest danger.

Nablyudeni I behind survival of cholera vibrioes El-Tor in the open reservoirs contaminated by sewer dumpings confirm long survival of the activator in this environment that has serious epidemiological value. These terms are estimated several months, and at fall of temperature and freezing of a reservoir vibrioes can winter. Sewer dumpings of big cities are characterized by heating environments and neutral or alkali reaction, optimum for the activator, as a result of wide use by the population of hot water and detergents. According to P. N. Burgasov (1976), after single-step dumping into sewer system of the acids by the industrial enterprise which changed reaction of sewer waters to pH 5,8, vibrioes to-rykh on an extent of long time found in the tests of water getting below dumping of the city sewerage, were not found any more.

Formation and development of epidemic of cholera, its scales are defined by presence of patients or vibriononositel, conditions of possible infection with their excrements of objects of the environment (water, foodstuff), a possibility of direct transfer of the activator from sick (carrier) healthy, and also effectiveness epidemiol. supervision and timeliness of carrying out anti-epidemic measures. Depending on dominance of these or those factors of transfer of contagiums the arising epidemics are peculiar as on dynamics of emergence and increase of diseases, and by efficiency of anti-epidemic actions. So, e.g., the waterway of spread of cholera is characterized sharp (within several days) by rise in incidence that leads to massive infection of the environment and substantial increase of risk of infection of people in this territory. It is natural that the exception of a water spreading factor of cholera (neutralization of water, prohibition to bathe in the reservoirs infected with the activator) stops rise in incidence, but there is «tail» of single diseases at the expense of other ways of transmission of infection.

El-Tor is idiosyncrasy of formation of the centers of cholera emergence of severe forms of a disease against the background of wellbeing on intestinal infections in this territory. And at previous bacterial. inspections of objects of the environment and patients with intestinal frustration causative agents of cholera were not found. Retrospective researches had intestinal infections also excluded cholera in their anamnesis.

During the outbreak of cholera of the 70th in our country patients of advanced ages prevailed, and diseases of children were an exception. In endemic districts of other countries of the world children are ill generally, and persons of the senior age groups have immunity to the cholera acquired during life in these districts.

Pathogeny. Cholera vibrioes get into a human body through a mouth together with the water contaminated by them or food. If they do not perish in acid medium of contents of a stomach, then come to a gleam of a small bowel where intensively breed owing to alkali reaction of the environment and high content of cleavage products of protein. Process of reproduction and destruction of cholera vibrioes is followed by allocation of a large amount of toxicants. So, the exotoxin of cholera vibrioes (choleragen) applied on a mucous membrane calls the whole cascade of biochemical changes in cells; the cycle of these changes is finally not studied. The major is activation in enterocytes of a small bowel of adenylatecyclase that leads cyclic

3-5 adenosinemonophosphates to increase of synthesis, level to-rogo determines the volume of secretion of intestinal juice (see Intestines). The leading link in a pathogeny of cholera is development of the acute isotonic dehydration (see Dehydration of an organism) which is followed by a degrowth of the circulating blood (ginovolemiy), hemodynamic disorders and disturbances of fabric metabolism. Gppovolempya, falling of the ABP and .metabolichesky acidosis lead to development of an acute renal failure, disturbance of cordial activity and function of other bodies, and also processes of a blood coagulation (increase in fibrinolitic and anticoagulating activity of blood). In addition to dehydration, an essential role is played by loss at vomiting and a diarrhea of the major electrolytes, first of all potassium (see the Hypopotassemia), and also sodium and chlorine. Loss of potassium at cholera can reach 1/3 of its contents in an organism and in case of insufficient completion leads it to dysfunction of a myocardium, defeat of renal tubules, and also paresis of intestines and sharp muscular weakness.

According to kliniko-pathogenetic classification of the cholera offered by V. I. Pokrovsky and

V. V. Maleev (1973) distinguish four degrees of dehydration of an organism, according to a fluid loss percentage of the weight (weight) of a body: The I degree — 1 — 3%; The II degree — 4 — 6%; The III degree — 7 — 9%; The IV degree — 10% and more. Dehydration

of the I degree does not cause noticeable fiziol. disturbances. Dehydration

of the II degree is followed by emergence of moderately expressed symptoms of dehydration. Dehydration

of the III degree is characterized by existence of all symptom complex of dehydration and a condition of unstable compensation of water and electrolytic balance. At dehydration

of the IV degree (the algidny period, algid) secondary changes of the major systems and thereof process of compensation of water and electrolytic balance considerably becomes complicated are noted; at the same time development of shock (see) with considerable reduction of volume of the circulating plasma, sharp disturbance of microcirculation (see), a fabric hypoxia (see) and a metabolic decompensated acidosis is typical (see). In the absence of adequate therapy dehydration and metabolic frustration become irreversible.

Various disease (one patients have a profuse diarrhea with all the effects called above, at others — inf. process is limited to a condition of a vibrio-nonositelstvo) it is impossible to explain only with influence of choleragen; apparently, the condition of local and general immunity of an organism of the patient is of great importance (see Immunity).

Pathological anatomy. The morphology of cholera was for the first time described by N. I. Pirogov in 1849. The clearest morfol. symptoms of a disease are defined at the dead in the algidny period. The sharp emaciation caused by quickly developing syndrome of dehydration is characteristic. Early and quickly there comes the cadaveric spasm (see. Postmortem changes), a cut remains within 3 — 4 days. Top and bottom extremities of a corpse are bent that gives it the peculiar look reminding a pose of the gladiator. Within the first hour after the death of the patient skeletal muscles can relax and be reduced that is followed by their twitchings. Skin is dry, flabby, wrinkled, especially on fingers («beef-steak hand»), sometimes (within the first hours after death) skin reminds goose. Skin color cyanotic with dark-purple livors mortis. A mucous membrane of lips dry, cyanochroic, the tip of a nose and auricles are cyanotic. The eyes which deeply sank down are half-open, the acting cheekbones, cheeks hollow. The stomach is pulled in. At necropsy of the patient with cholera there is no pungent smell since rotting occurs late. Hypodermic cellulose dry. Dryness and dark red color of skeletal muscles are characteristic. Serous covers are dryish with the injected vessels, often have an opaque shade and pink-yellow (Percykovy) color. On a serous cover of intestines the slizevidny sticky exudate forming the fine ends lasting between loops of small bowels is found. The small bowel flabby, is sharply stretched with reinforced heavy loops. The gleam of intestines and stomach contains a large amount of the colorless, pinkish or yellowish liquid with a characteristic smell having an appearance of rice water. A mucous membrane of a small bowel pale, with characteristic lack of an imbibition bile. Microscopically acute serous comes to light, seroznogemorragichesky enteritis is more rare (see), a sharp plethora of a mucous membrane, swelled submucosal and muscular layers. At serous and hemorrhagic enteritis in places on a mucosal surface of a cover, especially ileal gut, sites of an intensive hyperemia with small and larger zones of hemorrhages, small swelling of neyero-vy plaques are visible (group limf, follicles) and solitary limf, follicles, it is frequent with a nimbus of hemorrhages on the periphery. At acute serous enteritis a mucous membrane of a small bowel throughout bulked up, edematous, plethoric. When opening is made soon after the death of the patient, in the smears from a mucous membrane painted by divorced carbolic fuchsin (see) it is possible to find cholera vibrioes.

In a mucous membrane, iodslizi-ostomies and muscular layers of a small bowel are expressed hypostasis, hemorrhages, lymphoid and plaz-motsitarny infiltration meet. In cells intramural (a meyssnerova and an auerbakhova) neuroplexes (see Intestines, anatomy) swelling of cytoplasm, karioni-knoz, karioliz, a chromatolysis is noted (see the Kernel of a cell), in nek-ry cases destruction of nervous cells with proliferation of elements of a neuroglia — satellites, and also signs of a neyronofagiya is observed (see).

In a stomach the picture of serous or serous and hemorrhagic gastritis is observed (see). The gall bladder is stretched, in its gleam light watery bile («white bile») or muddy contents. The mucous membrane of a gall bladder is hyperemic, sometimes with small hemorrhages. In a parenchyma of a liver dystrophic changes are noted, sites of a focal necrosis, hemosiderosis (see), a hyperplasia star-shaped to a retik of loendoteliotsit (see the Liver, pathological anatomy), thrombophlebitis small, and sometimes and large veins sometimes are found (see Thrombophlebitis). At cholera also damage of a large intestine like diphtheritic colitis is possible (see). There can be inflammatory reactions of a mucous membrane of a throat, throat, bladder, vagina.

The spleen is usually reduced, especially in the algidny period, flabby, with the wrinkled capsule. Microscopically in it it is often possible to find a plethora, a hypoplasia limf, follicles, and also moderately expressed hemosiderosis.

Changes in kidneys are more various, in to-rykh it can be observed both an anemia, and a plethora, and also the moderated or expressed dystrophic changes of an epithelium, sometimes even a necrosis of an epithelium of gyrose tubules. Permeability of capillaries is increased, as a result of it in the capsule of renal balls and in a gleam of gyrose tubules granular proteinaceous weight accumulates. Intersticial fabric of marrow is edematous. Gleams of direct tubules and collective tubules are squeezed by edematous liquid.

Lungs dry, fallen down, in them the anemia and obezvo-

chewing is observed, against the background of to-rykh it is possible to find the centers of bronchial pneumonia and hypostasis. In intersticial tissue of lungs hemosiderin comes to light. Cardial cavities contain dark liquid blood and blood parcels. Owing to an eksikoz the amount of the liquid which is contained in a cavity of a pericardium decreases, or it absolutely is absent. A surface of a serous cover sticky, more often in an epicardium hemorrhages are found. In a myocardium are noted proteinaceous (granular) and fatty dystrophy. In the carrying-out system of heart as well as in neuroplexes of a small bowel, there are changes of nervous cells.

In a brain venous stagnation, serous treatment of a soft meninx with dnapedezy erythrocytes, increase in amount of liquid in ventricles, a degeneration of nervous cells, neuron an aphagia (see), hemorrhages come to light. In bark and subcrustal nodes nerivaskulyarny hypostasis with grains and threads curled up during the fixing a squirrel is noted. The nervous cells of a brain which bulked up, but also their pycnosis is possible (see). The hyperchromatosis of separate kernels is noted, nervous cells often meet the destroyed kernels and degranuliniy granularity of Nissl (see. Nervous cell).

Defeats of closed glands at cholera are studied insufficiently. In adrenal glands sites with serous treatment of a stroma, and in cortical substance — zones with the cells deprived of lipids are found. There are signs of decrease in neurosecretion in a back share of a hypophysis.

In EiacT. time it is everywhere noted iatomorfoz cholera (see the Pathomorphism), caused by early hospitalization of patients, timely performing dehydrational therapy, use of antibiotics and performing preventive vaccination (see below). In this regard, at necropsy of the patient who died of cholera symptoms of dehydration, the expressed «pose of the gladiator», dryness, flabbiness and rugosity of skin of fingers usually are not found. Changes of intestines are indistinctly expressed, however a hyperemia of a mucous membrane of a small bowel with small hemorrhages, stickiness of a peritoneum and weak symptoms of enteritis are observed.

At the dead from cholera El-Tor at the IV degree of dehydration on opening it is possible to reveal a hyperemia of a mucous membrane of a stomach with punctulate and large hemorrhages. The small bowel is stretched muddy (milk) or colourless and d a bone yu, sometimes by N of an i [about m p on yushchy rice water or because of impurity of the blood having an appearance of meat slops. The serous cover of a small bowel is hyperemic, the mucous membrane which bulked up pink color with the dot or larger hemorrhages which are quite often surrounding in the form of nimbuses of an iyeyerova of a plaque. Sometimes the mucous membrane of a small bowel is covered with a scaly plaque. Mucous membrane of a large intestine pale. Mesenteric limf, the nodes which bulked up giperplazirovana. At gistol. a research superficial gastritis with desquamation of an epithelium is found. In a mucous membrane of a small bowel I am marked out intens an ivn des by kVA a mation of an epithelium I fibers, especially in their apical departments. At this epithelium of basal departments of crypts it is kept. The quantity of scyphoid cells of an epithelium of a mucous membrane is increased, On separate fibers sites of a necrosis are found. The stroma of fibers densely of an infiltrirovan lymphocytes and plasmocytes, is not enough segmentoyaderny leukocytes. As well as at other intestinal infections, damages of a mucous membrane have focal character. The leading value in diagnosis results have bacterial. researches.

Essential changes in idea of a pathogeny and patomorfologiya of cholera resulted from implementation in the medical practician at an aspiratsponny biopsy (see) mucous membrane went. - kish. path. By means of this method Shprints (Sprinz, 1962), V. I. Pokrovsky and

N. B. Shalygina (1972), Juice (J. W. Fresh, 1974) with sotr. it was established. that the epithelium of a mucous membrane of a small bowel not only is not exposed to desquamation, but also essential damage. In the first days of a disease enterocytes look bulked up, but keep the main morfol. properties. The most characteristic is staz also the plethora of capillaries, expansion limf, sine and vessels, sharp swelling of basal membranes. Cells of an endothelium of capillaries on a bigger extent of a vakuolizirovana, basal membranes of vessels and an epithelium of a mucous membrane do not come to light or have an appearance of a wide indistinct strip. In own plate, both in fibers, and in the field of crypts, sharp serous hypostasis is noted. Expressiveness of hypostasis and swelling of basal membranes does not depend on degree of dehydration of an organism, however rather accurately correlates with character of excrements. So, on 6 — the 7th day of a disease at patients with the poluoformlen-ny or issued chair almost completely is absent hypostasis of a mucous membrane of a small bowel and much more accurately basal membranes come to light; at persons with the proceeding diarrhea the mucous membrane looks almost also, as well as on 1 — the 2nd day of a disease.

At a biopsy of a mucous membrane of a stomach acute catarral and exudative or catarral and hemorrhagic process with a paralytic trichangiectasia, plasmorrhagias, hypostasis and very moderate inflammatory infiltration is noted. Sharp vacuolation, and sometimes and death of obkladonny cells is observed. Swelling of an endothelium of capillaries and basal membranes is expressed also sharply, as well as in a small bowel. The large intestine is surprised much less, than a fenny gut and a stomach. In the first days of a disease hypostasis and hypersecretion of the flooded slime in sigmoid and a rectum are noted.

The cholera vibrio is found in a small bowel, a stomach and in a large intestine, both in patients with cholera, and in vibriononositel. Most often it is located in close proximity to fibers of a mucous membrane, is more rare in a gleam of crypts, but it is never found in fabric. Often vibrioes come to light morphologically in late terms of a disease (12 — the 20th day) when already repeatedly carried out bacterial. the analysis a calla yielded negative takes.

Results asiiratsionnop the biopsies and changes found in intestines on opening are not always comparable. The Asiiratsionny biopsy allows to receive for a research only sites of tissue of mucous membrane of initial departments went. - kish. a path (a stomach, a duodenum) therefore owing to, as a rule, focal defeat of a small bowel at cholera material can be taken from not affected area. In this regard to speak on the basis of data of an asii-ratsionny biopsy on absence at cholera of an inflammation in everything went. - kish. a path there are no bases.

Immunity. The postponed disease leaves behind otno-with an ita of l no resistant che-sky immunity of a vidospetsifa. The acquired immunity to cholera created by vaccination (see below) is short and does not prevent formation in poriononositelstvo.

Clinical picture. Most of clinical physicians [M. I. Afanasyev and II. B. Vaks; S. I. Zlatogorov, N. K. Rosenberg, G. P. Rudnev,

11. K. M at with Aba ev, R. L. PoHitzer, etc.] allocated various wedge, forms and options of a course of cholera however offered by them to classification in insufficient degree reflected the leading link in a pathogeny of a disease — degree of dehydration (degidrata-days) of an organism of the patient, a cut defines a wedge, displays of a disease, its result and tactics of treatment. As it was stated above, distinguish a wedge, the course of cholera with dehydration of I, II, III and IV degrees and a vibrio-nonositelstvo. A wedge, the course of classical cholera and cholera El-Tor is similar, though has nek-ry features (see below).

The incubation interval fluctuates from several hours to 5 days, 2 — 3 days are more often. It is shorter at persons with hron. diseases went. - kish. a path, especially at an achlorhydria (see) and after a resection of a stomach. At vaccinated it can be extended up to 9 — 10 days. The disease begins with a prodromal stage in the form of an indisposition, weakness, dizziness, an easy fever, sometimes temperature increase to 37 — 38 ° more often. The first clinically expressed symptom of cholera is the diarrhea, to-ry begins preferential in night or morning hours; if the disease progresses, then vomiting joins the speeded-up chair.

At patients with cholera with dehydration of the I degree gradual development of symptoms is usually noted. Almost in 1/3 cases of an excrement have kashitseobrazny character. A chair usually to 3 times a day. However even when its frequency reaches 10 times a day, an excrement not plentiful. Accession of vomiting is observed less than at a half of patients; usually it arises to 3 times a day. The initial fluid loss does not exceed 3% of body weight of the patient. Thereof symptoms of dehydration and disturbance of a hemodynamics are a little expressed (see Dehydration of an organism). The similar easy course of cholera is observed in a crust, time more than at a half of patients.

At cholera with dehydration of the II degree the acute onset of the illness is characteristic; only at a small part of patients the prodromal phenomena are possible. Excrements quickly become watery and at a half of patients remind rice water — rather turbid-white liquid with floating flakes, have no smell of an is-nrazhneniye. A chair —

from 3 to 20 and more times a day. At each defecation 300 — 500 ml of excrements (sometimes can be allocated up to 1 l). Defecation painless. At the same time there is plentiful vomiting, frequent the fountain. Sometimes vomiting precedes a diarrhea. Suddenness of vomiting, absence of the previous nausea is characteristic. In the beginning emetic masses may contain the remains of food, impurity of bile, however they become watery soon and also remind by the form rice water. Accession of vomiting even more accelerates development of dehydration; the fluid loss reaches 4 — 6% of body weight. Patients feel the increasing muscular weakness, pains and convulsive twitchings in sural and masseters. Quite often there are dizziness, faints. Patients are pale, the Crocq's disease (see), mucous membranes dry can be observed. Because of dryness of a mucous membrane of a throat and a throat the voice is weakened, at nek-ry patients hoarse. At a part of patients decrease in turgor of skin, especially on hands, tachycardia (see), moderate hypotension (see Hypotension arterial), an oliguria is noted (see).

At patients with dehydration of the III degree plentiful watery excrements (regarding cases the number of defecations does not give in to calculation) and vomiting (at 1/3 patients — to 15 — 20 times a day) are observed. The fluid loss makes 7 — 9% of body weight of the patient. Quickly the weakness which is often replaced by an adynamia (see) develops. Patients are disturbed by unquenchable thirst, quite often they become excited, irritable, complain of nagging pains and spasms in muscles, is more often than sural. Body temperature, edges at the beginning of a disease could be raised, progressively decreases and almost at 1/3 patients reaches subnormal figures. Features are pointed, eyeballs sink down, quite often eyes are surrounded with circles of cyanochroic coloring (a symptom of «dark glasses»). At most of patients decrease in turgor of skin is observed, it is preferential on extremities, quite often rugosity and its skladchatost. The xeroderma and mucous membranes, a Crocq's disease is expressed. The speech in a whisper, hoarseness and hoarseness of a voice is characteristic of most of patients. Tachycardia, weakening of pulse, the expressed hypotension, an oliguria is noted.

Cholera with dehydration of the IV degree is the most severe form of a disease, to-ruyu it is accepted to call algidy in connection with decrease in body temperature. It was considered to be what algid develops only after more or less long enteritis and a gastroenteritis. However during epidemics of cholera El-Tor dekompensirovanny dehydration at certain patients developed promptly during the first

2 — 3 hours, and at the majority — during 12 hours of a disease. Therefore in several hours from the beginning of a disease repeated plentiful watery excrements and vomiting can stop. The fluid loss makes 10% and more than a body weight of the patient. Into the forefront disturbances of a hemodynamics (see) and the phenomena of dehydration act. Skin is cold to the touch and covered with a clammy sweat, the Crocq's disease, at a part of patients — the general cyanosis with violet-gray coloring is noted. Skin loses elasticity, is wrinkled. Rugosity of hands — «beef-steak hands» is especially characteristic. The skin collected pleated sometimes does not finish within an hour. The face of the patient which grew thin his lines are pointed, the eyes which sank down, the symptom of «dark glasses», expression of suffering (facies chole-rica) appears. Myotonia are long; the periods of relaxation can be not expressed and therefore extremities adopt the forced provision. At spasms of fingers and hands the spasm in the form of «obstetrical hand» is observed. Convulsive reduction of muscles of an abdominal wall can be observed that leads to pain, clonic spasms of a diaphragm cause a painful hiccups. At most of patients pulse is not defined. Cardiac sounds are hardly listened, cordial reductions very frequent, arrhythmic. Breath is speeded up, then becomes superficial, arrhythmic. Patients have feeling of suffocation. The meteorism (see) as a result paresis of intestines is often noted; oliguria, perekhodyashchaya in an anury. Body temperature in axillary hollows lower than 36 °. Consciousness at patients with cholera is long remains clear. A soporous state (see Devocalization) or even a cholera hlorgidropenichesky coma (see) develop only shortly before death and are caused by accumulation of a large number of nedookislen-ny products of exchange in an organism and falloff of anti-toxic function of a liver.

Sometimes at patients with cholera with dehydration of the IV degree fulminant disease with the sudden beginning, rapid development of dehydration (can be in the first 1 — 4 hour from the moment of a disease), with symptoms of an encephalomeningitis is observed.

El-Tor is feature of a course of cholera a bigger variety a wedge, manifestations: more frequent disease with dehydration

of the I—II degree and in the form of a vibriononosi-telstvo; temperature increase is more often observed, almost at a half of patients the aching abdominal pains, morbidity in epigastriums or in okolopunochny area are noted.

In former epidemics the so-called dry cholera proceeding without diarrhea and vomiting was registered. Similar disease met at the exhausted persons more often and usually terminated letalno within several hours at the phenomena of cardiopulmonary insufficiency. Absence of a diarrhea and vomiting in this case, apparently, is explained early by the come lot of smooth muscles of l. - a whale. path.

In the centers of cholera the asymptomatic vibriononositelstvo when the activator is allocated comes to light, and it is especially frequent at the persons who were in contact with patients with cholera.

V. I. Pokrovsky, V. V. Maleev (1978) consider that identification at vibriononositel at the corresponding inspection gistomorfo l. and immunol. changes in an organism confirms a sub clinical current inf. process that is observed also at a bacteriocarrier of other pathogenic microbes of intestinal group.

The diagnosis is established on the basis of data epidemiol. the anamnesis (e.g., contact with patients with cholera, the use of not decontaminated water from open reservoirs), a wedge, the pictures ii of results of laboratory researches.

Changes of blood, first of all, are connected with dehydration. At dehydration of the I extent of change are very moderate: reduction of number of erythrocytes and a hemoglobin content at preservation of an invariable color indicator, ROE it is moderately accelerated, the leukocytosis or a leukopenia are possible. At dehydration of the II degree the leukocytosis is observed 21/2 times more often and reaches 10-103 and above in 1 mkl blood. At dehydration of the III—IV degree the hemoglobin content and erythrocytes is also, as a rule, reduced. The leukocytosis is observed more often and reaches 15-103 — 20-103 in 1 mkl. Increase in number of leukocytes happens at the expense of neutrophils, at a relative monocytopenia, a lymphocytopenia and an aneosinophilia. The shift of a blood count is characteristic to the left.

At initial degrees of dehydration (I and II degree) the pachemia usually is absent; on the contrary, at a part of patients compensatory Lucia of a gemoda is observed — relative density and viscosity of blood are a little reduced (1,0225 — 1,0217 g! ml and 4,0 respectively). At a considerable part of patients with dehydration of the III degree relative density of blood, an index of a hematocrit and viscosity of blood also are on the upper bound of norm; at dehydration of the IV degree a pachemia — the most characteristic sign (density of plasma reaches 1.045 — 1,050 g! ml, index of a hematocrit and viscosity of blood respectively 00,0 — 70,0 and 9,0 — 10,0). The electrolytic composition of blood at dehydration of I and II degrees changes a little. Patients with dehydration have III degrees

e l with to t r about l and t and y e N and r at sh e N and I z N and h and - bodies of Y11.1 — the liyemiya and a gipokhloromiya are expressed Hypaque. At dehydration

of the IV degree, except decrease in content in blood of potassium and chlorine, major deficit of bicarbonate, a decompensated metabolic acidosis (see) and a respiratory alkalosis (see), a hypoxia (see) and acceleration of I and II phases of a blood coagulation with the raised fibrinolysis (see) and a trombotsshpopeniya is noted (see).

The final diagnosis is made on the basis of results bacterial. researches.

Laboratory diagnosis. Apply bacterial. and serol. methods of a research and detection of a specific bacteriophage.

Bakteriol. the method is the basic and serves for diagnosis of a disease and identification of the activator in objects of the environment. It is based on release of pure growth of the activator (see. Bacteriological techniques) and its identification (see Identification of microbes). Allocation of culture is carried out step by step. A research peptone water or 1% peptone water with potassium tellurite for accumulation of cholera vibrioes with the subsequent seedings on dense mediums provides crops of excrements, emetic masses, bile, etc. on liquid low-mediums of alkali reaction (pH 8,0 — 8,2), such as 1% (see). Such accumulation is made twice (I and II Wednesdays of accumulation). In parallel native material is sowed on dense mediums — simple (Hottinger's agar, beef-extract, pH 7,8 — 8,6) and elective (ATsDS — agar color differential medium, etc.). Crops incubate at t ° 37 ° for 1% to peptone water of 6 — 8 hours, on an alkaline agar — 12 — 14 hours, for 1% to peptone water with potassium tellurite — 16 — 18 hours and on dense elective environments — 18 — 24 hours.

On a measure grew from environments of accumulation make seedings on dense mediums, and in case of suspicion on existence of cholera vibrioes — microscopy of smears, studying of mobility and an orientation response of agglutination on glass with cholera serums (see Agglutination). On dense mediums select suspicious colonies, with material from them put reaction to an oxidase (see Oksidazny reactions), and sift the rest of colony on polycarbohydrate environments. At suspicion of cholera with material from colonies put an orientation response of agglutination with cholera serum 01 and Ogava's serums and Inaby. Material from the agglutinated colonies is sifted on polycarbohydrate and usual agar mediums, from neag-glyutiniruyushchikhsya — only on polycarbohydrate. On polycarbohydrate environments select the cultures causing changes, characteristic of vibrioes. (See the section Aetiology) define a sort, a look, a biopitch and a serotype (serovar) of the pure growths received at various investigation phases by the identifying tests.

For receiving affirmative answer of rather reduced identification including the developed agglutination test with cholera serum 01 and Ogava's serums and Inaby and also check of a lysis by a phage With both El-Tor and definition of group on Heyberg. The research takes 18 — 48 hours, in nek-ry cases — to the 72nd hour. At detailed studying of the marked-out culture, except establishment of a look, a biopitch and a serotype, define fa-gotip, virulent and pathogenic properties. For differentiation of virulent and avirulent strains reveal sensitivity to cholera phages and check hemolitic properties of the activator.

Serological methods of a research are additional and give the chance to reveal had, and also to judge tension of immunity at the vaccinated persons by definition of antibodies in serum or a blood plasma and in a filtrate of excrements. For this purpose apply reaction of definition of agglutinins, vibriotsidny antibodies and antitoxins. Except the standard statement of these reactions, define vibriotsidny antibodies in blood serum on the basis of fermentation of carbohydrates, use a method of bystry definition of agglutinins in blood serum using the phase-contrast microscope (see Phase-contrast microscopy)), a method of identification of antibodies in blood serum by means of a neutralization test of antigen (see. Serological researches). Also the method an enzyme-sword-nykh of antibodies is perspective (see Enzim-immunologi-chesky a method).

From the accelerated methods of laboratory diagnosis of cholera most widely apply a luminescent serological method (see the Immunofluorescence) and reaction of indirect hemagglutination — PH of HECTARE (see Hemagglutination). Use also a method of an immobilization of vibrioes cholera O-serum, an agglutination test using the phase-contrast microscope, an agglutination test in peptone water with cholera O-serum, the reaction of adsorption of a phage (RAP). All these methods are additional to the basic bacterial. to a method.

An indirect method of diagnosis of cholera is allocation of a specific bacteriophage (see the Phage diagnosis). For detection of a phage enter the studied material and young bouillon culture of a cholera vibrio into a liquid medium. After an incubation at t ° 37 ° during 6 — 8 hours make filtering via membrane filters No. 1 or No. 2 and in a filtrate determine presence of a phage by a method of Gratsia (see Gratsia a method).

D and f f e r e N of c and and N y y diagnosis. Now to distinguish cholera from other acute intestinal infections quite difficult, especially at the beginning of flash since it proceeds benign more often (cholera with dehydration of the I degree). The greatest difficulties are presented by the differential diagnosis with food toxicoinfections (see Toxicoinfections food) and a salmonellosis (see). These diseases unlike cholera quite often begin with a strong fever, are followed by high temperature of a body, abdominal pains, nausea, vomiting, the diarrhea joins later. The chair is plentiful, but keeps fecal character, has a pungent fetid smell. Differential diagnosis with seldom found gastroenteritichesky form of a salmonellosis proceeding with sharp dehydration is especially difficult. In some cases specification of the diagnosis is impossible without data of a laboratory research. Cholera needs to be differentiated with dysentery (see), for a cut abdominal pains, a chair, tenesmus, false desires, scanty with impurity of slime and blood, on defecation, fervescence, lack of symptoms of dehydration and a pachemia are characteristic. However at patients with the dysentery caused by Grigoriev's shigellas — Shiga, perhaps expressed dehydration, spasms. On a wedge, reminds a current cholera with dehydration of the I—II degree a rotavirusny gastroenteritis (see) it proceeds in the form of epidemic flashes and is more often observed in autumn and winter time. Excrements at a rotavirusny gastroenteritis watery, foamy, rough rumbling in intestines is characteristic, the general weakness, is noted a hyperemia and granularity of a mucous membrane of a throat, sometimes hemorrhages.

Cholera should be differentiated with poisonings with poisonous mushrooms (see Mushrooms, t. 29, additional materials), organic and inorganic chemical drugs or toxic chemicals, at the same time it is necessary to pay special attention to the anamnesis. At poisonings the first a wedge, signs are nausea, vomiting, severe pains in a stomach, a diarrhea joins later, in excrements quite often there is an impurity of blood. Body temperature, as a rule, remains normal (see Poisonings).

Treatment is the most effective during the first hours an onset of the illness. Therefore medical service and, first of all, inf. hospitals, shall be in constant readiness for reception of patients with cholera and have a necessary reserve of medicines.

Treatment is defined by a condition of the patient, first of all degree of dehydration. The III degrees usually enough administration of liquid through a mouth happens the patient to dehydration of I and II, and sometimes and. Best of all for the patient to allow to drink or enter through a stylet into a stomach in the small portions the Oralit liquid containing in 1 l of water 3,5 g of sodium chloride, 2,5 g of hydrosodium carbonate,

1.5 g of potassium chloride and 20 g of glucose (sucrose). The volume of the drunk liquid shall equal to the volume of the liquid lost during a disease by an organism with excrements, emetic masses and urine that is established on degree of dehydration. At the same time bystry disappearance of symptoms of dehydration, recovery of a hemodynamics and function of kidneys is noted. If at administration of liquid in a stomach to lay down. the effect is insufficient, and also in cases of dehydration of the III—IV degree for compensation of already available fluid losses enter during

2 hours solution of a kvartasola or trisola in the volume corresponding to a lose of weight of a body. Kvartasol contains 4.75 g of sodium chloride in 1 l of depyrogenized water. 1,5 g of potassium chloride,

2.6 g of sodium acetate and 1 g of a gidrokar-bonat of sodium. Trisol, or the solution 5:4:1 which gained wide international recognition contains 5 g of sodium chloride in 1 l of depyrogenized water. 4 g of hydrosodium carbonate and 1 g of potassium chloride. Solutions enter intravenously or vnutriarterial->. Before introduction they should be warmed up to t ° 38 — 40 °. The first

2 — 3 l pour with a speed of 100 — 120 ml of 1 min., then gradually reduce the speed of perfusion to 30 — 60 ml in 1 min.

In the subsequent carry out correction of the proceeding fluid losses and electrolytes. For the purpose of more exact accounting of losses use scales beds or a so-called cholera bed. During this period the volume and speed of the entered liquid depend on the frequency of a chair, volume of excrements and the number of emetic masses: the more the organism loses liquids, the more intensively it should be entered. Therefore each 2 hours count the volume of the lost liquid and respectively change rate of administering of solution. E.g., if the patient in the last 2 hours lost 2,5.g, then enter 2,5 l of solution.

Administration of salt solution continues before the termination of a diarrhea and a complete recovery of function of kidneys that on average for patients with II and III degree of dehydration makes 25 — 30 hour. The patient with the IV degree of dehydration (algid) salt solution is entered most often during 2 — 4 days. On average during this time they receive apprx. 36 l of liquid. Dominance of amount of urine over quantity of excrements allows to predict time of normalization of a chair for 6 — 12 hours and to stop intravenous administration of liquid in the absence of vomiting. It is necessary to remember that through lungs and skin the adult patient in days loses 1 — 1,5 l of liquid, it needs also to be considered at compensation of its daily losses.

The forced administration of liquid can cause an overhydratation (excess content of liquid) with possible edematization of a brain in children and elderly people and lungs (see the Fluid lungs, Hypostasis and swelling of a brain) therefore intravenous infusions at them at primary regidratation carry out more slowly (during 3 — 4 hours and more).

In the period of reconvalescence appoint salts of potassium, is more often in the form of the solution consisting of 100 g of potassium acetate. 100 g of hydropotassium carbonate and 100 g of potassium citrate in 1 l of water. Patients drink this solution on 100 ml

3 times a day.

Careful leaving shall be provided to the patient. During vomiting it is necessary to support the head of the patient. The disease of cholera is followed by considerable fall of temperature of a body therefore it is necessary to take all measures to warming of the patient, in chambers shall be warm. After the termination of vomiting the diet shall consist of mucous soups, liquid porridges, curdled milk. mashed potatoes, kissels; appoint vitamins.

All patient and one vibriononosite-million each 6 hours within 5 days appoint tetracycline on 0,3 — 0,5 g. Smaller single and daily doses delay recovery and extend terms of allocation of cholera vibrioes. At intolerance levomycetinum or furasolidone can be applied by the patient of tetracycline.

Had cholera write out from a hospital after disappearance of all a wedge, symptoms and receiving negative takes three bacterial. researches of excrements. Bakteriol. researches are conducted in 24 — 36 hours after the end of treatment by antibiotics within 3 days in a row. The first fence of excrements is carried out after appointment to a convalescent of salt laxative (20 — 30 g of magnesium sulfate). Once produce bacterial. research of duodenal contents.

Forecast. Thanks to the diagnostic methods applied in a crust, time and timely treatment lethal outcomes at cholera are observed less than in 1% of cases though before introduction of modern methods of rehydration therapy lethal outcomes made up to 50% and more.

Prevention. Epidemic wellbeing on cholera can be reached by implementation of actions of administrative, utility and medical character. For this purpose is formed and the comprehensive anti-epidemic plan by the Ministries of Health of federal and autonomous republics, regional, regional, regional and city public health departments together with departmental bodies of health care on the republic, the region, the area, the city and the area is annually adjusted. Plathe N is approved by councils of ministers of federal and autonomous republics, regional, regional, city and regional executive committees of Councils of People's Deputies. In particular, it is provided in the plan: preparation of the respective rooms and drawing up schemes of expansion of hospitals in them for patients with cholera, provisional hospitals, insulators (see), observators (see. Observation point) and bacteriological laboratories (see); creation of material and technical resources for the listed institutions; training of medics on epidemiology, laboratory diagnosis, clinic and treatment of cholera (differentially for various categories of trainees); arrangement available in the area (the republic, the region) of forces for providing in need of treatment-and-prophylactic and anti-epidemic actions. Treatment-and-prophylactic and anti-epidemic actions differ depending on an epidemic situation a little: at threat of spread of cholera, in the center of cholera and after elimination of the center of cholera.

Actions at threat of distribution x about l e r y. The area (area, edge) appears threatened if in the neighboring administrative territory, including the adjacent countries, or in the territory of not adjacent foreign state. about the Crimea there are intensive direct transport bonds, cases of cholera accepted wide epidemic spread occurance. A complex of actions for the prevention of cholera in districts where there is a threat of a drift of this disease, hold I on previously developed plans, to-rye are adjusted according to specifically developed epidemic situation.

The general management of actions for prevention of cholera is performed by the extraordinary anti-epidemic commissions (EAEC) of the republic, area (edge), the city, area. At ChPK the permanent operational body — the anti-epidemic headquarters headed by the manager of regional (regional), city public health department or the chief physician of the area is created.

In the territory where the possibility of a drift of cholera is supposed, patients with acute actively come to light went. - kish. also are hospitalized by diseases in provisional departments with obligatory single bacterial. inspection on cholera; if necessary vaccination of the population is carried out (see below); the persons arriving from places, unsuccessful on cholera without certificates of passing of an observation (see) in the center or with incorrectly issued certificate are exposed to a 5-day observation with single bacterial. inspection on cholera. Sale of antibiotics and sulfanamide drugs without recipe of the doctor is forbidden. Water of open reservoirs and sources of the centralized water supply, and also economic and household drain waters are investigated on existence of cholera vibrioes. Bodies and healthcare institutions carry out the each decade analysis of incidence of acute intestinal infections from them etiol. interpretation. Control for a dignity amplifies. protection of water sources (see. Sanitary protection of reservoirs) and the mode of chlorination of water (see Chlorination of drinking water)', amount of residual chlorine in network of water supply systems is carried to 0,3 — 0,4 mg on 1 l. In the settlements which do not have the centralized water supply use of drinking water and the economic and household purposes from open reservoirs (the rivers, canals, lakes) without preliminary disinfecting is forbidden (see Disinfecting of water). For providing the population with water delivery of high-quality mains water will be organized. Field camps, educational institutions, the enterprises and institutions are provided with the chlorinated or svezhekipyacheny water. Control for a dignity amplifies. condition of settlements, catering establishments and food industry. Special attention is paid to maintenance due a dignity. states in places of mass accumulation of people (the markets, transport, stations, campings, hotels, etc.) and in public bathrooms. Fight against flies, especially in places of their possible breeding is carried out. On all highways, districts, conducting from unsuccessful on cholera, forces of medics will organize the temporary sanitary checkpoints (SC), and by forces of militia — the check-points (CP). SKP will be organized also on railway, river, marinas and bus stations, and also at the airports (see the Quarantine, a karantinization).

Obligations for identification of patients are assigned to SKP with went. - ksh. frustration; identification of persons, areas, following from unsuccessful on cholera, and verification of presence at them observation certificates. Also providing transport -

z infek tsio nna of m and means mi is assigned to SKP.

The patients revealed on SKP with went. - kish. frustration send to the next provisional hospital, and on the persons who were in contact with such patients following from districts, unsuccessful on cholera, lists are formed, to-rye SES for implementation of overseeing by these persons and their inspection are transferred to a vibri-ononositelstvo in territorial (at the place of residence).

The passenger trains and vessels making flights from areas, unsuccessful on cholera, are followed by the crews consisting of the medic and the representative of militia. Enter duties of the crews accompanying trains and vessels: identification of patients with went. - kish. frustration and the persons which were in contact with them, control of observance a dignity. states on vehicles, carrying out a dignity. - a gleam. works among passengers. The patient revealed along the line with went. - kish. frustration immediately temporarily isolate in one of the released compartments (cabin), take away material for bacterial from it. researches (excrements, emetic masses), carry out the current disinfection in public places.

Administrative and medical events for the prevention of a drift of cholera from foreign countries are held according to the existing International medical and sanitary rules (see) and Rules on sanitary patrolling of the USSR from delivery and spread of quarantine and other infectious diseases (see. Sanitary patrolling).

M e r about and r and I am t and I in the center of cholera y. The center of cholera are separate households, the inhabited site (group of the houses), the district of the city, the settlement, the city or group inhabited point in, combined production, a ladder by gortny bonds, proximity of an arrangement to the place where patients with cholera or vibriononositel are found. At detection of diseases (or vib-riononositelstvo) in a number of settlements all administrative territory of the area, area, edge can be the center of cholera.

The anti-epidemic and sanitary and preventive actions directed to localization and elimination of the center of cholera are: restrictive measures and a quarantine (see the Quarantine, a karanpsh-nization); identification and hospitalization of patients with cholera; identification and hospitalization of patients with acute went. - kish. diseases; identification and hospitalization of vibriononositel; identification and isolation of the persons adjoining to patients, vib-riononositel, and also being in contact with objects of the environment infectiousness to-rykh is established; epidemiological inspection (see) in each separate case of cholera; bacterial. inspection of patients, vibriononositel, the persons adjoining to the patient and also objects of the environment; treatment of patients with cholera and vibriononositel; the current and final disinfection (see); cleaning of the inhabited places (see), supply with high-quality water, a dignity. - a gigabyte. the mode at the enterprises of the food industry, objects of public catering and trade; sanitarnoprosvetitelny work among the population.

Actions after elimination of the center x au l e r y. For the persons who had cholera, and vibriononositel after their sanitation dispensary observation for the term determined by the orders M3 of the USSR is established. Or a vibriononositel (upon termination of his sanitation) the chief physician would report about an extract of the person who had cholera to the manager of regional (city) public health department io to the residence of written out. Dispensary observation is made by an office, infectious diseases (see). Workers of head constructions of a water supply system, the milk industry, the milk and cheese-making plants, farms, drain points, etc., workers and about production, processing, storage, preparation, transportation and sale of food stuffs, drinks, workers but cleaning and a wash of the production equipment, stock and a container at the food enterprises, all employees of catering establishments, persons servicing sanatoria to lay down. - the prof. and child care facilities, are written out for work after fivefold daily bacterial. inspections on vibriononos an itelstvo. Bakteriol. inspection of persons of the specified categories before their extract for work begins in 36 hours after the termination of treatment antibiotics.

In the course of dispensary observation special attention is paid bacterial. to inspection of had. In the first month bacterial is carried out. the research of excrements

of 1 times in 10 days and once — bile, during the subsequent period of excrements is investigated once a month. The persons who had cholera, and debrided vibriononositel are removed from dispensary observation after the negative bacteriological research of excrements on cholera. Removal from the dispensary account is carried out by the commission as a part of hl. doctor of policlinic, infectiologist, district doctor and regional epidemiologist.

Within a year after elimination of outbreak of cholera active identification of patients with acute is carried out went. - kish. frustration at all stages of rendering medical aid to the population, and also by carrying out household bypasses of 1 times in 5 — 7 days. The revealed patients immediately are hospitalized irrespective of weight and a wedge, displays of a disease. All hospitalized patients are exposed triple (3 days in a row) to inspection on a vib-riononositelstvo, definition of credits of vibriotsidny antibodies in pair blood sera is carried out. Treatment by antibiotics and sulfanamide drugs of these patients can be begun after establishment of the diagnosis of a disease.

At least once in 10 days taking into account an epidemic situation and a dignity. - a gigabyte. conditions of the settlement are carried out bacterial. researches of water from sources of drinking water supply, open reservoirs, economic and household drain waters on existence of cholera vibrioes. The amount of residual chlorine in the parting water supply system systematically is supported at the level of 0,3 — 0,4 mg/l.

The constant close check behind observance a dignity is conducted. - a gigabyte. the mode at catering establishments, the food industry and trade in food products. Close constant control behind timely and high-quality cleaning of settlements, behind the correct maintenance of dumps is exercised. Regular fight against flies is carried out. cart is systematically conducted, - a gleam. work (lectures, conversations, performances in a local press, on radio, television, the edition of instructions, leaflets, etc.) but prevention of cholera and others went. - kish. infectious diseases. Vaccination (revaccination) against cholera of all population of this territory is carried out.

All listed actions are carried out during 1 year after elimination of outbreak of cholera before the end of the next epidemic season under a condition if for this year new cases of diseases or vibriononositel do not come to light.

Specific prevention. A question of preventive immunization (see) various contingents and groups of the population decides in each case depending on an epidemic situation.

Preventive immunization by corpuscular vaccines (see Vaccines) prevents clinically expressed diseases of cholera approximately at 40 — 50% of vaccinated people on average for

5 — 6 months. At the same time the specified degree and duration of effect of preventive immunization are observed only after double hypodermic introduction of a vaccine with 7 — a 10-day interval; after single hypodermic introduction of a vaccine tension and duration of the forming immunity are considerably less expressed.

The committee of WHO on the international epidemiological surveillance behind infectious diseases in December, 1970 noted that in a crust, time vaccination is not an effective method of prevention of spread of cholera, it is confirmed by the fact that in group of the vaccinated patients degree of incidence decreased approximately by 50% in comparison with nevaktsiniro-bathrooms, however action of a vaccine continued the most bigger 6 months. Moreover, it was established that in usual conditions (i.e. not within special experiences) vaccination does not give also this extent of decrease in incidence of cholera for the population of the country in general.

At the solution of a question of expediency of carrying out mass anticholeraic inoculations at the arisen epidemic of cholera it is necessary to consider existence of forces and means for hospitalization of all patients, the isolation which were with them in contact, active identification and hospitalization of all persons, suffering from disorder of function of intestines, and also isolation of the persons which were with them in contact, laboratory inspection of all centers i.e. for holding actions, to-rye in the shortest possible time shall provide localization and elimination of the arisen center.

Carrying out in a short time of inoculations to a large number of people (taking into account hypodermic introduction of a cholera vaccine) will demand a huge number of medical staff. At the same time it must be kept in mind that poslepri-vivochny immunity at a part of vaccinated comes not earlier than the 20th day from the beginning of immunization; during this time the epidemic center can be liquidated by means of other anticholeraic measures.

On the basis of the stated data in our country use of vaccinal prevention of cholera as the measures capable to localize and liquidate the arising outbreaks of cholera in a short time was recognized inexpedient. Experiment of the Soviet Union on elimination of outbreak of cholera without mass vaccination on the basis of epidemiologically reasonable measures was approved by Committee of WHO experts (1970), to-ry noted that this experience shall serve as an example for other countries facing identical problems.

Mass anticholeraic immunization of the population is quite justified only in cases of anticipation of possible epidemic of cholera or in the territories adjoining on areas and the countries, unsuccessful on cholera, where anti-epidemic events are held insufficiently actively. It is more necessary in settlements with unsatisfactory sanitary and utility conditions where the increased incidence of intestinal infections is noted that indicates a possibility of development of epidemic of cholera in them. In the settlements with good sanitary and utility conditions provided with high-quality drinking water and effective treatment facilities of sewer system it is hardly reasonable to enter system of immunoprevention of cholera.

At emergence of indications to performing immunoprevention first of all do inoculations to the employees of network of public catering, persons occupied in production, storage, transportation and implementation of food stuffs, to personnel of head constructions of a water supply system, etc.

Along with a usual corpuscular vaccine in recent years in the USSR the new vaccine is developed — caring rogen-anatoksinony Comprehensive study of this vaccine showed that it has immunogene advantage before a corpuscular vaccine and slight reactogenicity, however epidemiol. immunological efficacy is still unknown, t. to it it can be established only at controlled testing.) carried out in the conditions of spread of cholera in a certain territory. Choleragen-anatoxin is entered subcutaneously annually once, at a revaccination (according to epidemic indications) — not earlier than in 3 months after primary application. For adults (18 years are also more senior) the dose of drug for primary immunization and a revaccination makes 0,5 ml, for children at the age of 15 — 17 years — 0,3 and 0,5 ml, at the age of 11 — 14 years — 0,2 and 0,4 ml, at the age of 7 — 10 years — 0,1 and 0,2 ml.

Considering data epidemiol. inspections, information on an epidemic situation in our country and abroad, the M3 of the USSR resolves an issue of need of carrying out preventive inoculations against cholera, defines the contingents of the population which are subject to immunization.

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of Item H. Bypi of experts, V. I. Pokrovsky;

And. II, Avtsyn, V. A. Shakhlamov (stalemate. An.), E. A. Vedmina (ztiol. laboratory diagnosis).