Cholera is an acute anthroponosic infectious disease with fecal-oral mechanism of transmission. Cholera is characterized by dehydration due to loss of the fluid with watery diarrhoea and vomiting. Cholera is concerned to the group of the diseases, which are submitted to "International medical-sanitary rules".
Historic reference
Illness and death due to dehydrating diarrhea and vomiting can be recognized in the writings of Hippocrates and Galen. The heartland of cholera is India,the Ganges river's delta. From there it has spred from time to time to many other countries.
There were 7 pandemic of cholera in the world. Fives pandemics of appalling magnitude have occurred during the 19th century, spreading from India through Asia Minor, Egypt and Russia.
In 1816 cholera broke out with unusual severity and high mortality in the area of the Ganges river's delta. Over the next 8 years it spread over much of Asia and the Middle East, but did not invade Europe.
The great pandemic is of importance as being the first to invade Europe. It started in India in 1828 and advancing slowly reached Iran in 1829, extending thence by way of Astrakhan to Russia, Sweden, Northern Europe and England. By 1832 it has spread over the whole Europe. In the same year 1832, it reached Canada and thence extended to Fort Dearborn, where it infected the soldiers who subsequently carried the disease down the Mississippi valley.
Cholera was also introduced into New York and Boston and spread from there to south and west, so that by 1836 cholera was present in most parts of the United States, not disappearing until 1838. It disappeared in Europe in 1839.
The next European outbreak, or third pandemic, lasted from 1844 to 1864 and was traced from India by the way of land and sea, that by land following the caravan route by way of Iran and Russia and that by sea from Indian pilgrims going to Mecca. This pandemic reached the United States in 1848.
The fourth great pandemic invaded Europe by the usual routes and continued from 1865 to 1875. In 1865 it was carried by sea from Bombay to Arabia and Mecca and was then spread by the returning pilgrims throughout Egypt, Syria, and the Southern European ports to the East coast of Africa.
The fifth pandemic (1883-1896) began in India, reaching Egypt and Europe. It was during this epidemic, in 1883 that Koch working in Egypt discovered the cause of cholera, vibrio comma {Spirillum cholera). However, as the epidemic in Alexandria soon subsided, he proceeded to India where, after a study of 42 cases of cholera and 28 autopsies, he gave confirmatory evidence of the etiology of the disease.
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A very serious outbreak of cholera originated in 1891 in pilgrims from the delta of the Ganges attending a religious festival. It was spread of cholera by returning pilgrims and reached Europe in 1892. Almost a million deaths occurred in Russia. It was during this epidemic that cholera appeared with great virulence in Hamburg. In that city within 2 months there were nearly 17,000 cases and over 8,000 deaths. This outbreak gave opportunity for those careful studies as to the transmission of the disease to be later referred to.
It is usual to recognize a sixth pandemic (1900-1926) which began in Aravia and spread over India,China and Philippines. This pandemic continued to cause great mortality in Europe and from 1908 to 1910, there were reported some 71,000 cases and 26,000 deaths in Russia.
The seventh pandemic began in 1961. It is caused by a vibrio cholera El-Tor.
In 1905 Gotschlich isolated six peculiar strains of vibrio cholera from the dead bodies of returned Mecca pilgrims at the quarantine camp of El Tor. These strains, which produced hemolysins, came from typical cases of cholera and agglutinated in the classical typing serum. However, not until 1961 when the "El Tor" biotype produced an epidemic of major proportions in the Philippines was there general agreement that hemolytic vibrio cholera could be responsible for severe epidemic human disease.
Etiology
There are two forms of the vibrio cholera: classical biotype, which was discovered by Koch in 1883 and El Tor biotype.
The vibrion is short. It is gram-negative and curved organism which, from its shape, is often called the comma bacillus. Typically it is small, comma-shaped rod. It frequently occurs in S-shapes, owing to the attachment of a pair of organisms at their ends, and especially in the old and virulent cultures long treads showing a somewhat spiral appearance may be seen. The vibrio cholera is strictly aerobic and grows readily upon ordinary culture media. There are no spores and capsules.
Vibrio cholera has two antigens 4 flagellar H-antigen and somatic O-antigen.
The somatic O- antigens do distinguish V. cholera Ogawa, Inaba and Hikojima, which are responsible for epidemics.
V. cholera has 3 fractions of toxin. Cholerogen-exotoxin plays the most important role in the development of dehydration. Cholerogen consists of two types of toxin: cholerogen A and cholerogen B. Cholerogen A consists of peptide Al and peptide A2. Peptide Al penetrates through the cells membrane. Then it manifests the specific toxication. Peptide A2 connects peptide Al with peptide B. Peptide  is untoxic, it connects the whole molecule of toxin with cell receptors. V. cholera survives in low temperature. The boiling kills V. cholera during one minute. It survives in sea water (till 60 days).
Vibrio cholera is present in the intestine and in the rice water-like stool during acute stage of infection.
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Epidemiology
Cholera is anthroponosic intestinal disease with tendency to pandemic spread. Reservoir and source of infection is infected man. Discharge of vibrions is realized with excrement.
The sources of infection may be sick man with typical or obliterated form of cholera, reconvalescent after cholera and clinically healthy vibrio-carriers.
The patients with clinical picture of cholera are the most intensive source of agents. They discharge till 10-20 liters of fluid with watery diarrhea during first 4-5 days of the disease with great content of vibrions (106-109 vibrions in 1 mL).
The source of infection may be reconvalescents-vibriocarriers. They discharge vibrions into environment in average during 2-4 weeks.
Healthy (transitory) carriers can discharge the agent periodically during some month. The mechanism of transmission of the infection is -fecal-oral. It is realized by water, alimentary and contact ways. The leading way of the transmission of the agents of cholera is water. This way may lead to epidemic distribution of cholera. Infection may happen due to use of infected water and also after use this water for wash of vegetables, fruits or bathing.
Food has also been implicated in some epidemics. The cases of cholera were described due to infected milk use, boiled rice and other food-stuffs.
It is established that inhabitants of different water reservoirs (fish, crayfishes, mollusks, frogs and other hydrobionts) are able to accumulate and preserve vibrio El-Tor for a long time. They are temporary reservoir of infection and may be factors of transmission of the agents.
The susceptibility to cholera is general and high. In endemic areas morbidity is observed more frequently in children and elderly persons.
Pathogenesis
Cholera is cyclic infection with essential fermental systems damage of the enterocytes. Vibrions cholera enter the organism through the mouth with water or food. Some part of vibrions perishes under, influence of acid medium of the stomach. Another part of vibrions enters small intestine. Intestine reproduction and destruction of vibrions is accompanied with discharge of large amount of endo- and exotoxic substances. There is no inflammatory reactions.
Cholera is characterized by dehydration due to loss of fluid and salts with watery stool and vomiting. Hypersecretory processes play the leading role in the mechanism of the diarrhea origin. These processes are promoted by activation of ferment adenylcyclase in the epithelial cells of the intestine under action of exotoxin-cholerogen and accumulation of cyclic 3,5-adenosinemonophosphates, leading to increase of secretion of electrolytes and water. In cholera the loss of fluid with stool and vomiting reaches such a great volume in a short period, practically not met during diarrhea of other etiology. The general volume may exceed in some cases up to 2 times the body's mass of the patient. The loss of
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electrolytes plays essential role in pathophysiology of cholera. So, loss of potassium may reach one third its content in the organism. It is manifested by disorder of function of myocardium, damage of kidneys and also paresis of the intestine. In cholera dehydration is isotonic. Fluid contains 135 mmole/L Na, 18 mmole/L K, 48 mmole/L HC03and 100 mmole/L Cl (or 5g NaCl, 4g NaHC03 and lg KCl in 1 liter of defecations. An acute extracellular isotonic dehydration develops in the patients with cholera. It is accompanied with decreasing of the volume of circulated blood and hemoconcentration, leading to hemodynamic disorders and violation of tissue metabolism. Hypovolemia, metabolic acidosis, hypoxia, thrombo-hemorrhagic syndrome and acute renal failure develops.
Anatomic pathology
In cholera basic tragedy happens in a zone of the jejunal capillaries. Liquid get into the intestine from them through the epithelium cells. A venous return is diminished and as a result of that the heart's return diminishes too. Blood pressure decreases. The organism reacts with a tachycardia on that (there is no cholera without tachycardia).
The other compulsory sign is decreased diuresis. It is explained by increase of the water resorbtion by the renal canaliculi. If the loss continues venous flow diminishes acutely. Tachycardia can not compensate it already and blood pressure decreases.
The organism includes a pressory mechanisms to preserve functions of the vital important organs (heart, brain, kidneys). A capillary spasm begins. It improves for some time blood supply of the heart and brain. Blood pressure is equated but venous return decreases more. As a result of it oxygen transport to the organs and tissues and metabolic products transport are violated. pH balance of the organism changes to acidosis. The organism reacts on acidosis. It includes a new compensatory mechanism. It is dyspnea. Respiratory alkalosis develops, but
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it can not cause neutral pH balance due to violation of microcirculations.
A pressory mechanism is proper for kidneys too. The kidneys capillaries are spasmated. Tissue acidosis develops. Resorbtion of water and products of metabolism is alterated. That excludes the kidney as organ regulating homeostasis. Renal filtration stops entirely under the decrease of blood pressure less than 80 mm. The kidney is sensitive for hypoxia. Hypoxia causes dystrophic changes in the epithelium of the sinous canals.
These changes are reversible in case of moderate hypoxia (a renovation period is not shorter than a week). But if the patient did not get from the hypovolemic shock a necrosis of the sinous canals comes (death from anuria -"shock kidney1')- In case of prolonged loss of water all compensatory mechanisms become unable to keep blood pressure. An original decompensation comes. It coincides with the loss of the liquid equal to 8-12 % of the body's weight. Then the unreversable changes become and therapy is uneffective. The volume of loss shouldn't be more than 10 %.
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In accordance with WHO classification the patients with cholera may be divided on three groups:
1. The first degree of dehydration. There are the patients which have loss of fluid volume equaled to 5 % of body weight.
2. The second degree of dehydration. There are the patients which have loss of fluid volume equal to 6-9 % of body weight.
3. The third degree of dehydration. The patients which have loss of fluid volume over 10 % of body weight. That dehydration is dangerous for life if the reanimation measures are not entertained.
According to classification of V. I. Pocrovsky patients can be divided in four groups:
1. The first degree of dehydration with loss of fluid 1-3 % of body weight.
2. The second degree of dehydration with loss of fluid 4-6 % of body weight.
3. The third degree of dehydration with loss of fluid 7-9 % of body weight.
4. The fourth degree of dehydration with loss of fluid more then 10 % of body weight.
It's worth to underline that the clinical manifestation of the third degree of dehydration (by the WHO classification) or the fourth degree (by classification of V. I. Pocrovsky) is hypovolemic shock.
Clinical manifestations
Clinical manifestations of cholera, caused by classic vibrion and vibrion El-Tor are similar.
Incubation period is from several hours till 5 days (in average 48 hours). Cholera may be present in typical and untypical forms. In typical course the next forms of the disease are differented in accordance with the degree of dehydration: mild, moderate and severe form. In untypical course obliterated, fulminant forms may be present.
The onset of the disease is an acute, as a rule. In case of mild course of cholera the gradual development occurs in the part of the patients. The prodromal period may be 1-1.5 days. The patients mark weariness, ailing, headache, sometimes subfebrile temperature, heartbeating, sweet.
A diarrhoea is the first clinical manifestation of cholera. It appears suddenly, without the pain, often at night or in the morning. Diarrhoea is accompanied by gurgation in the stomach. After 1-2 defecation stool has typical shape. It is cloudy, white, fluid, without smell and "rice water-like".
The mild course (dehydration of the first degree). The loss of fluid is till 3 % of body weight. In majority patients stool may be till 10 time per day, scanty. In one-third of the patients vomiting may occur 1-2 times. Thirst, light dizziness, weakness trpuble the patients. Their state is satisfactory. Skin is humid, usual color. The mucous of the mouth is dry. There is no hypothermia. Subfebrile temperature may be in the part of the patients. There are no changes
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of the pulse and arterial pressure. An insignificant painfulment occurs due to palpation of the stomach. The changes of the blood are not typical. There is no blood condensation, changes of it's pH and electrolytes balance.
After proper therapy a vomiting, dizziness, weakness disappear on the first day. The stool become normal on the 2-3 day of the treatment.
Middle-severe course (dehydration of the second degree). The loss of fluid is 4-6 %. There is considerable weakness, dizziness, thirst in patients. A quantity of the defecation is from 10 till 20 times in a day. The stool is liquid, plentiful. Dehydration appears already after 3-5 defecation at the half of the patients. A vomiting is annexed early, and it is rice-water-like. The skin is pale. The moderate cyanosis of lips and extremities may be in the part of the patients. There is horse whishpering voice. Turgor of the skin decreases. The feature of this degree of dehydration is appearance of the cramps without tonic tension. The pulse is frequent up to 100 per minute. The arterial pressure is decreases till 100 mm. There may be olyguria.
There are no changes of the red blood. Erythrocyte sedimentation rate (ESR) is lightly accelerated. Leukocytosis, neutrophylosis with the shift of the formula to the left, lymphopenia, monocytopenia and uneosinophilia occur in the part of the patients. Hematocrit is 51-54 L/L. The relative density of the plasma is 1026-1029. The change of electrolytes is insignificant. Hypokalemia and hypochlorinemia are more expressed. Hypotension disappears usually through 20-30 minutes from the onset of rehydration. Turgor is restored through 3-4 hours. The skin becomes pink. A vomiting continues till a day. Rarely a vomiting is observed on the second day. The stool becomes facesic through 1-3 days, and it becomes normal to 4-5 day. The general loss of the fluid is 5-7 liters in this patients.
Severe course (dehydration of the third degree) occurs more rarely, approximately in 10 % of the patients. The loss of fluid is 7-9 % of body weight. The detachment this degree of dehydration is connected with necessity of prevention of development extremly severe course. There are no secondary changes of the important system of the organism due to this degree of dehydration. Because, it may be possible rapid compensation of dehydration and restoration of electrolytes. The third degree is characterized by more intensive clinical manifestations of dehydration and unfirm compensation.
The disease develops impetuously. The stool, is watery, abundant from the first hours of the disease. Sometimes the patient cannot count a quantity of defecations. In patients sharp weakness, adynamia, severe thirst, cramps of the muscles are observed. The state of the patients is serious and very serious.
A cyanosis of lips and extremities is observed. The skin is cold and shriveled. The turgor decreases. The face is pinched, eyes are deeply sunken in the orbits. In a third of the patients a symptom of "black eyeglasses" is observed. The mucous of the mouth cavity is dry. The lips are dry too. Tongue is dry and covered. A voice becomes hoarse. The cramps are often of long duration, with
Choler
tonic character. Cramps are accompanied with pain. The cramps of the trunk muscles and diaphragm are not observed. The temperature is 35.7-35.5 °Ñ. The pulse is 120-130 per minute, weak. The arterial pressure is low 80/50 mm Hg. Sometimes the breathlessness occurs. Renal failure is manifested with olyguria, in 25 % of patient - with anuria. There are erythrocytosis, leucocytosis, neutrophylosis with the shift of the formula to the left, lymphopenia, uneosinophilia. The concentration of hemoglobin increases. Protein and leukocytes are observed in urine. Hematocrit is 55-65 L/L in these patients. The relative density of plasma is 1030-1035. There is considerable change of electrolytes. Hypokalemia, hypochlorinemia are expressive.
Extremly severe course (dehydration of the forth degree) or decompensated dehydration. It occurs more rarely than the other clinical variants. The loss of fluid is 10 % of body weight and more. In this case the organism cannot compensate the indigence of water-electrolytes balance and function of the significant organs. It leads to hypovolemic shock. The relapsing vomiting is observed. Decompensated dehydration may develop through 6-8 hours and even at the first 2-3 hours. The state of the patients is serious and very serious. In the last hours diarrhoea and vomiting may be absent. It is connected with paresis of the stomach and intestine muscles, with hypokalemia and metabolic acidosis. At the same time there are expressive symptoms of dehydration: cold clammy skin, intensive total cyanosis.
The color of the hand's clusters,nouse,aural areas,lips and eyelids is violet or black. The face is pinched, eyes deeply sunken in orbits. There is impression of the suffering and entreaty about help on the face (facies cholerica).
The skin is shriveled. The turgor of the skin is decreased ("washwoman's hands")- A voice becomes hoarse. The temperature is 34.5 °Ñ. The generalized tonic muscles cramps are observed, including muscles of the abdomen and back. The agonizing hiccup may be due to clonic spasm of diaphragm. There is no pulse. The arterial pressure is not determined. The breathing is frequent and superficial. There is anuria. The condensation of the blood is observed. In peripheral blood the concentration of hemoglobin increases. Expressive leucocytosis, neutrophylosis, lymphopenia, uneosinophilia occur. Hematocrit is higher than 66 L/L. The relative density of the plasma is 1036 and more. The alterations of electrolytes are very expressive: hypokalemia, hypochlorinemia. Hyponatremia is expressed in a smaller degree. Dehydration has isotonic character. The deficit bicarbonium (more than lOmmol/L) leads to decompensated metabolic acidosis and respiratory alkalosis.
Untreated patients die.,The cause of the death is an acute heart's failure (at the first three days of the disease) or renal failure (up to 14-16 day).
Complications
The next complications may develop in patient with cholera: pneumonia, sometimes abscesses, phlegmon. The number of complications are connected
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with intensive therapy: pyrogenic reactions, phlebitis, thrombophlebitis, hyperkalemia and other.
Diagnosis
The bacteriological research of material from the patient or corpse is the principal method of laboratory diagnostics. The purpose of bacteriological method is detachment of cholerays agent and itys identification.
The correct collection of the material has a great meaning for bacteriological research as the delivery of material to the laboratory. A quantity of the material is 0.1-0.2 gm, because the enormous quantity of the agent is contained at stool. It is necessary to take a bigger quantity of the agent from the patient with light form or carriers. The sowing is done to the dense or liquid nutritive mediums near patient's bed. If there is no possibility delivering of the material to the laboratory, quickly, it is necessary adding of conservant, because vibrio cholera begins to perish already at the first 1-2 hours in usual conditions. An alkaline peptonic water is used for the sowing. The material for the sowing is necessary to take till beginning of the treatment. The preliminary answer may be through 12 hours, the final - through 24 hours.
The serological methods may be also used for diagnostics of cholera. There are methods of discovering antibodies to vibrio cholera in blood, the methods of detaching antigens of vibrio cholera at stool and other materials. At the last years luminescent-serological method is used. The result may be received through 1.5-2 hours.
Differential diagnosis
Differential diagnostics of cholera is performed with toxical food-borne infections, esherichiosis, rotaviral gastroenteritis. In some untypical cases of cholera, especially in obliterated course of the disease it is necessary to perform differentiation of gastrointestinal form of salmonellosis, gastroenterocolitic variant of acute shigellosis, poisoning with mashrooms, organic and inorganic chemical remedies.
Treatment
Patients needs immediate hospitalization in choleric department. They require emergency treatment which should be started at the pre-admission stage. It's necessary to prescribe pathogenetic preparations with the purpose of compensation of liquid and electrolytes loss,and corrections of metabolic changes. Isotonic polyionic solutions - threesault,acgsault,iactasault,quartasault,hlosault are indicated. Quartasault is more effective.
Quantity of liquid,which should be infused for initial rehydratation (during 1-2 hours), should correspond to stage of the organism dehydratation. At III and IV stages of dehydratation it makes accordingly 7-9-10 % of body weight and more. Polyionic solutions infuse in vein initially-stream introduction, then volumetric rate 70-120 mL/minute. To infuse liquid with such rate,it is necessary to use simultaneously two and more systems for transfusion. Stream introduction
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of liquid is replaced by dropwise infusion after normalization of pulse,restoration the arterial blood pressure and normalization of body temperature, hemoconcentration and acidosis.
The next infusions of polyionic solutions is determined by rate of proceeding loss of water and salts. The compensatory rehydratation is provided during several days in severe cases. For definition of its volume it is necessary every 2 hours to determine quantity of excrements and vomitive masses to investigate clinical (a pulse rate, the arterial pressure, body temperature) and every 4-6 hours laboratory (relative density of blood plasma, haematocrite number, concentration of electrolytes in blood plasma and erythrocytes, pH, concentration of standard Sodii hydrogenii) parameters.
For prevention of side reactions of polyionic solutions should be preliminary warmed up to 38 - 40 °Ñ, at the first hours of treatment infuse prednisolon 0.5 gm/kg per day. At infusion there is plenty of solution threesault the metabolic alkalosis and hyperkalemia can be developed. In these cases infusion therapy is continued with solution desault.
*
It cases of not compensated hypokalemia it is necessary to infuse preparations of potassium in addition. At a pernicious vomiting, cramps, anaphylactoid reaction dimedrol or suprastin with promedol should be used. As at patients with severe course of cholera the clotting develops, cordiamin, coffein or epinephrin of hydrochlorid is contrindicated.
In case of HI stages dehydration (liquid loss up to á % of body weight) and more severe dehydration is managed by intravenous injection of saline solutions, at absence of vomiting recommend to apply peroral indication of glucosani in tablets or rehydroni in packages 18.9 gm: dissolve the content of 1 package in 1 L of boiled water and drink small portions.
Water-salt therapy should be over after appearance of excrements of normal character and at prevalence of quantity of urine over quantity of excrements in the last 6-12 hours.
Panangin or asparcam during 1 month are indicated during early reconvalescence.
Antibiotics are the additional remedies. They accelerate clinical convalescence and prevent the further allocation of choleric vibrioes. A remedy of a choice is ciprofloxacin: 0.25-0.5 gm 2 times per day, in serious cases enlarge up to 0.75-2 times per day during 5-7 days or erythromicin, or laevomycetin. Tetracyclin and doxycyclin are effective. However, for the last years the majority of choleric vibrio culture, allocated on territory of Ukraine, appeared not to be sensitive to this antibiotic. For sanitation of vibrio carriers use the same antibiotics during 3-5 days.
Complications of rehydration. It may be pyrogenic reaction to solutions, hypokalemia, hyperkalemia.
Hypokalemia is observed more than 25 % of the patients with III degree of dehydration. The clinical manifestations are: distention of the stomach, pain in the stomach (hypokalemic.ileus).
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The next formula may be used for correction of potassium: \A4xPx(5-X)= mLof 1 % KC1,
where 1.44 - coefficient,
P - weight of the patient, X - contant of potassium in patient's serum. 5 - normal content of potassium in blood serum. Hyperkalemia develops in 15 % of the patients. The clinical manifestations are: red face and upper part of the body, cardialgia, typical changes of ECG, bradycardia. In this case it is necessary to inject Phillips solution ¹2. Phillip's solution ¹ 1 is injected again after signs of hyperkalemia elimination.
Etiotropic therapy is performed with antibiotics. Antibiotics cause shortening of diarrhoea duration and give possibility to decrease a quantity of fluid for injection. Doxicycline is prescribed in dose 0.1 mg through 12 hours at the first day, than 0.3-0.5 mg through 6 hours during 3 days. Tetracycline is used for teratment of the patients with cholera in dose 0.3-0.5 mg through 6 hours during 5 days. It is possible to use chloramphenicol in 0.5 mg dose through 6 hours during 5 days.
Prophylaxis
The measures of prophylaxis depend on epidemic situation in the country. The information of world health organisation about cases of cholera in different countries has an important meaning.
The incidence of disease can be diminished by sanitary-hygienic measures, sanitary disposal of human feces, purification and protection of water supplies, pasteurization of milk and milk products, strict sanitary supervision of preparation and serring of flood exclusion of persons with diarrhea from handling food, organization of the work about diseases of gastrointestinal tract and their examination on cholera.
Specific prophylaxis of cholera is performed by corpuscular vaccine and cholerogen-anatoxin.
Parenterally inoculated killed complete cell vaccine has been available for years, this vaccine stimulates high titers of serum vibriocidal antibodies, but it does not induce antibodies to toxin. Protection by vaccine has been induced for approximately 1 years, with vaccine efficacy approximately 70 %. Local gastrointestinal tract immunity against the organism and against the toxin should provide a better, less reactogenic immunogen using recombinant DNA technology an "attenuated" V. cholerae organism that lacks the genes for production of the A and  subunits of toxin was created. A plasmid containing the subunit gene was then constructed and inserted. Thus a candidate live V. cholera vaccine containing all the cell-was antigens necessary for adherence and the capacity to produce only the subunit of toxin has been engineered.
Cholera
Control questions:
1. Definition of cholera.
2. Etiology of cholera.
3. Classification of clinical forms of disease.
4. Clinical symptoms and signs of cholera.
5. Differential diagnosis with toxic food-borne diseases, esherihiosis, salmonellosis, shigelosis, poisoning by salts of heavy metals.
6. Classic bacteriologic cholera diagnosis, methods of express-diagnosis.
7. Dehydration during cholera (dehydration primary, compensatory).
8. Etiotropic therapy and medical supervision after contacts with cholera patient.
9. Preventive measures in spot of cholera outbreak: quarantine measures,observation, disinfection measures, immediate prophylaxis of cholera, specific prophylaxis and terms of discharge from the hospital.