Cholera. Infectious diseases of viral etiology with fecal-oral mechanism of transmission. Intestinal infectious diseases with the dominant involvement of colon: shigellosis, amebiasis. Yersiniosis. Protozoal intestinal invasions: lambliosis, balantidiasis.
http://intranet.tdmu.edu.ua/data/books/And-INF.pdf
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 roles”.
http://www.cdc.gov/cholera/general/
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
In 1816 cholera broke out with unusual severity and high mortality in the area of the
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
Cholera was also introduced into
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
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
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
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
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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 (Fig.1). 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 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 produce 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 A1 and peptide A2. Peptide A1 penetrates through the cells membrane. Then it manifests the specific toxication. Peptide A2 connects peptide A1 with peptide B. Peptide B 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).
Fig.1. Vibrio cholera
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 detachments 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.
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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 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 HCO3 and 100 mmole/L Cl (or 5g NaCl, 4g NaHCO3 and 1g KCl in 1 liter of defecation’s. 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.
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Pathological anatomy
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 sigh 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 caot 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 it caot 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 kidney”). 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 %.
In accordance with classification WHO 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 some 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: light, moderate and severe form. In untipical course obliterated, fulminant forms may be present.
The onset of the disease is an acute, as rule. In light 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”(Fig.2).
In 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 times in a day, scanty. In one-third of the patients vomiting may occur 1-2 times. Thirst, light dizziness, weakness trouble 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
Fig.2. “Rice-water” stool in cholera
are no changes 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’s condensation, change it’s pH and electrolytes.
After corresponding therapy a vomiting, dizziness, weakness disappear at the first day. The stool become normal on the 2-3 day of the treatment.
In moderate course (dehydration of the second degree) the loss of fluid is 4-6 %. There is considerable weakness, dizziness, and 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 harsh 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. 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 %. 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 (Fig.3). 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 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 ºC. The pulse is 120-130 in a minute, weak. The arterial pressure is low 80/50 mm. Sometimes the breathlessness occurs. Renal failure is manifested by olyguria, in 25 % – by 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.
Fig.3. Patient with severe course of cholera
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 ºC. The generalized tonic muscles cramp 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 %. 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 10mmol/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).
http://www.cdc.gov/cholera/disease.html
Complications
The next complications may develop in patient with cholera: pneumonia, sometimes abscesses, phlegmon. The row of complications are connected with intensive therapy: pyrogenic reactions, phlebitis, thrombophlebitis, hyperkalemia and other.
Diagnosis
The bacteriological research of material from sick man or corpse is the principal method of laboratory diagnostics. The purpose of bacteriological method is detachment of cholera¢s agent and it¢s identification.
The correct taking 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.
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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
http://www.who.int/mediacentre/factsheets/fs107/en/
Patients needs immediate hospitalization in choleric department. They require emergency treatment which should be started at the pre-admission stage. It’s necessary to put them on special bed (Fig.4) and indicate pathogenetic preparations with the purpose of compensation of liquid and electrolytes loss, and corrections of metabolic changes. Isotonic polyionic solutions – Trisol, Acesolum, Lactasol, Quartasol, Hlosol are indicated. Quartasol 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/minutes. To infuse liquid with such rate, it is necessary to use simultaneously two and more systems for transfusion. Stream introduction of liquid is replaced by dropwise infusion after normalization of pulse, restoration the arterial blood pressure and normalization of body temperature, hemoconcentration and acidosis.
Fig.4. Special bed for treatment cholera patient’s
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 preliminary warm up to 38 – 40 °С, at the first hours of treatment infuse Prednisolon 0,5 gr/kg per day. At infusion there is plenty of solution Trisol the metabolic alkalosis and hyperkalemia can be developed. In these cases infusion therapy is continued with solution Disol.
It cases of not compensated hypokalemia it is necessary to infuse preparations of potassium in addition. At a pernicious vomiting, cramps, anaphylactoid reaction there should be used Dimedrol or Suprastin with Promedol. As at patients with severe current of cholera the clotting develops, Cordiamin, coffein or epinephrin of hydrochlorid is contrindicated.
In case of I-II stages dehydration (liquid loss up to 6 % 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 gr: the content of 1 package dissolve 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 mounth are indicated during early reconvalescence.
Antibiotics are the additional remedies. They accelerate clinical convalescence and prevent the further allocation of choleric vibrions. A preparation 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 vibrio, allocated on
Complication 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 (hypokalemitic ileus).
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 №2. Phillip’s solution № 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 treatment 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
http://www.cdc.gov/cholera/prevention.html
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 year, 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 B 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.
Shigellosis (Dysentery)
Shigellosis is general infectious disease of human, caused by bacterium of genus Shigella.
Shigellosis is characterized by principal damage of mucous membrane of distal section of the large intestine. The disease is accompanied by symptoms of general intoxication, abdominal spastic pain, frequent watery stool with admixture of mucus and blood, and tenesmus.
Historic reference
The term shigellosis was used by Hippocrates to indicate a condition characterized by frequent passage of stool containing blood and mucus accompanied by straining and painful defecation.
In 1898 Shiga conclusively demonstrated that a bacterium was present in the stools of many patients with shigellosis and that agglutinins could be demonstrated in the serum of the infected patient. Two years later, Flexner found a similar but serological different organism in stool of other patients with shigellosis acquired in Philippines.
http://www.cdc.gov/nczved/divisions/dfbmd/diseases/shigellosis/
Etiology
The agents of shigellosis are regarded to genus Shigella, family Enterobacteriacea. There are approximately 50 serotypes of Shigella.
According to modern international classification genus of Shigella is divided into four groups: group A (Sh. Dysentery), group B (Sh. Flexneri), group C (Sh. Bojdii), group D (Sh. Sonnei). Each group is divided into serologic types and subtypes.
All Shigellas are similar morphologically. They are small gram-negative rods, nonmotile and nonencapsulated. Shigellas are facultative anaerobias. They grow well on the simple nutritive mediums. Shigella contain thermostable somatic O-antigen, including group and standard antigens.
Depending on character of toxinoformation Shigella are divided into two groups. Shigella Grigoriev-Shiga’s are treated to the first group. They produce strong exotoxin, having protein’s origin, and also endotoxin. All other types of Shigella (Flexneri, Sonnei) are treated to the second group, they produce only endotoxin. Endotoxin consists of proteins and lipopolysaccharide. Protein part of endotoxin and exotoxin have expressive neurotropic action. Endotoxins has enterotropic action.
Epidemiology
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The sources of infection are ill patients, persons in period of reconvalescence and bacteriocarries. The patients with acute shigellosis are especially dangerous.
The patients with acute shigellosis discharge the agent during all period of the disease, especially during period of expressive colitic syndrome. The persons with obliterated, light forms of the disease are dangerous too. These persons don’t address for medical help and don’t receive treatment. Because, these “atypical” cases of acute shigellosis have predominant epidemiological meaning. The patients with chronic shigellosis are dangerous for other persons, especially in the period of aggravation.
The mechanism of the transmission of the infection is fecal-oral. The transmission of the infection is realized through contaminated food-stuffs and water. Infection of food-stuffs, water, different objects happens due to direct contamination by infected excrements, through dirty hands and also with participation of flies. The factors of transmission have leading meaning in epidemiology of shigellosis. Depending on factors of transmission there are the next ways of contamination – contact, alimentary and water. Now, the alimentary way has more important meaning. Contamination over food-staffs may be through contaminated vegetables and berries with insufficient processing before use. Food-stuffs, prepared for use have the most important meaning in transmission of the infection (milk, milk products, especially, sour cream, meat stuffing and other meat products, bread, soft drinks, fruits, vegetables.
The susceptibility of human is high. It doesn’t depend on sex or age. Shigellosis occurs as in infants as in seniors. However, the morbidity of adult population is lower than children of early age.
Shigellosis is characterized by seasonal spread as the other intestinal infections. It is registered more frequently in summer and autumn.
Pathogenesis
Pathogenesis of shigellosis is complicated. It is studied insufficiently. In some cases the agents perish in the upper section of the gastrointestinal tract under the influence of acidic conditions. In other cases Shigella may pass through intestine, and it is excreted into environment without reply of the macroorganism.
Diverse theories of pathogenesis of shigellosis were pulled out in different years. The next theories are known:
1. Bacteriemic theory. Reproduction of the agent in the blood is the basis of pathogenesis of shigellosis according to this theory.
2. Toxico-infections Shiga’s-Brauer’s theory. Many positions of this theory don’t lose one’s own meaning in modern ideas about pathogenesis of shigellosis.
3. Allergic theory. According to this theory, shigellosis is general allergic infection disease.
4. Nervous-reflexious theory. According to this theory the damage of nervous system has leading meaning in pathogenesis of shigellosis.
5. Theory of intracellular parasitism. According this theory, all features of the shigellosis course are connected with parasitism of Shigella in the epithelium of mucous membrane of distal section of the large intestine.
In was established by investigations of the last years that secondary immune insufficiency plays considerable role in pathogenesis of shigellosis. At present time it is known that development and course of the different forms of shigellosis is connected with some factors. There are functional state of the organism; interaction of the human’s organism, agent and environment; biological properties of the agent (toxigenecity, invasiveness, fermentic activity and other).
Bacteremia of short duration may be observed in decreased resistance, in entering of the large doses of the agent. However, bacteremia hasn’t essential meaning in pathogenesis of shigellosis. Bacteremia is marked only in one third of the patients with Grigoriev’s-Shiga’s shigellosis.
Toxins, which are absorbed from the intestine, play an important role in pathogenesis of shigellosis. At first, toxins influence directly on the mucous membrane of the intestine and substances, disposing under mucous membrane (nervous endings, vessels, receptors). Second, toxins are absorbed and influence to different sections of central nervous system. Involvement of small intestine in pathological process from the first days of the disease is explained by toxinemia (violation of its motile, absorbing and digestive functions). The evidence of toxinemia is delivery of endotoxin into patient’s blood serum from the first days of the disease and its delivery into urine.
Exotoxin of Shigella Grigoriev’s-Shiga’s and protein part of endotoxin possesses significant neurotoxic action. Neurotoxins influence on the central nervous system and peripheral gangiums of vegetative nervous system. It is manifested by severe intoxicative syndrome and violation of all types of the balance of substances.
Lipopolysaccharide part of endotoxin damages principally mucous membrane of distal section of large intestine, and in a less degree, other sections of gastrointestinal tract. It possesses cytotoxic action and causes activation of adenylcyclase.
Activation of adenylatecyclase leads to accumulation of cyclic 3-5 adenosine-monophosphates, increased secretion of electrolytes and water. The violation of water – electrolytes balance is observed in gastrointeritic variants of acute shigellosis course. It is necessary to allow for degree of dehydration of the organism. Dehydration of II-III degree develops in severe course of gastroenterocolitic and gastroenteritic variant of acute shigellosis. In severe (hypertoxic) form it may be development of hypovolemic shock and acute renal insufficiency.
Shigella toxins cause sensibilization of the mucous membrane of the intestine, render damaging action on it with development of inflammatory changes and erosions formation and ulcers in severe course of the disease.
Toxin stimulates discharge of biological active substances (histamine, serotonine, kinines, prostaglandines) into blood, causes violation of microcirculation of the blood in the intestine’s wall, increases intensity of inflammatory process and disorders of functions of the intestine (motorics, absorbtion, secretion).
The violation of innervation of the intestine, microcirculation, electrolytic balance and inflammatory changes of mucous membrane are manifested clinically by sharp spastic pains in the stomach. Spasms of separate sections of the intestine lead to excretion of scanty stool (“fractional stool”). Spastic shortening of the muscles of sigmoid and rectum cause fecal urgency and tenesmus.
Allergic factor plays definite role in pathogenesis of shigellosis. Pathological process develops in large intestine after preliminary sensibility. However, it was shown experimentally, that shigellosis is not typical allergic disease.
However, intracellular parasitism was not confirmed due to biopsy of mucous membrane of the intestine in the patients with shigellosis. It is not expected, that phenomenon of intracellular parasitism plays certain role in shigellosis too.
In shigellosis, the invasion of Shigellas into epithelial cells is observed in large intestine, principally in rectum. It is caused by comparatively prolonged accumulation of intestinal content, toxins and bacteriums in the large intestine. They create favorable conditions for invasion of the agent into epitheliocytes. It is promoted by intestinal dysbacteriosis too. Intestinal dysbacteriosis develops inrarely under influence of antibioticotherapy. This therapy causes destruction of considerable part of symbiotic flora.
The disease may have prolonged or chronic course due to addition of supplementary factors of chronic process. The cases of formation of chronic shigellosis develops due to unfavorable premorbid state, delay of macroorganism functions replacement, decreased activity of immune system.
The recovery of the patients is prolonged in presence of damages at any portions of gastrointestinal tract (defects of masticatory apparatus, anomalies of intestinal tube, gastritis, ulcerous disease, appendicitis, pancreatitis, hepatitis, cholecystitis); presence of supplementary diseases (tuberculosis, brucellosis, malaria, helminthiases); state of endocrine system, dysbalance of vitamins. The factors, promoting to prolonged and chronic course of the disease, are late hospitalization of the patients, incorrect treatment, violation of alimentary regime after discharge of the patients from the hospital.
Pathological anatomy
In shigellosis pathomorphologic changes are revealed, generally, in distal portion of the large intestine (sigmoid, rectum). There are 4 stages of inflammatory changes:
1. acute catarrhal inflammation (Fig.5);
2. fibrinous necrotic (Fig.6);
3. ulcerous and follicle-ulcerous (Fig.7, 8);
4. stage of formation of scars.
Fig.5. Acute catarrhal proctosigmoiditis
Fig.6. Fibrinous-necrotic proctosigmoiditis
Fig.7. Ulcerous colitis
Fig.8. Follicle-ulcerous colitis
At present time fibrinous-necrotic and ulcerous damages occur rarely. Catarrhic inflammatory process is observed more frequently. It is confirmed by data of pathologoanatomic investigations due to biopsy of rectum. Catarrhic inflammation is characterized by edema, hyperemia of mucous membrane and submucous layer of rectum. Small hemorrhages and erosions are observed in the mucous membrane in the part of the patients. In rectoscopy mucous or mucous-hemorrhagic exudation is revealed on the surface of mucous membrane and in the intestine.
In microscopical investigation disorders of vessels are marked: increased permeability, local hemorrhages. Edema of strome and basal membrane leads to dystrophic changes of epithelium, in severe cases – to formation of ulcers and erosions. Hyperproduction of mucus is typical.
Fibrinous-necrotic changes are manifested by dirty, gray and dense coats on mucous of the intestine. The membranes consist of necrotic tissue, leukocytes and fibrin. Necrosis may achieve submucous and muscleous and fated submucous layer. Purulent damages and necrosis lead to formation of ulcers. In shigellosis ulcers are superficial with dense borders.
The regeneration of epithelium begins on the 2-3 day of the disease in acute phase of catarrhic inflammation. However, complete anatomical recovery may be on 4-5 month after discharge the patient from the hospital even in mild course of shigellosis. Regeneration comes slowly in the destructive changes in the intestine, and disorders of vessels are preserved for a long time. Regeneration is combined frequently with focuses of inflammatory changes. In chronic shigellosis the morphological changes are characterized by multiple forms and flabby duration of inflammatory process.
Immunity
In shigellosis postinfectious specific immunity is shaped and typed-specific. The investigations of humoral immunity revealed dependence of the level of blood serum immunoglobulins of the patients with shigellosis from gravity of the disease, kind of the agent, and also, from treatment. Antibodies play essential role in execution of functions of phagocytes. However, presence of antibodies caot be used for rendering of diagnosis and for estimate of complete sanation of the organism from the pathogen. In shigellosis humoral factors of immunity preserve the meaning only during one year.
Immunological examination reveales depression of the tests T-system of immunity with different course of acute shigellosis, which is more expressive in the patients with severe, moderate and lingering course of the disease.
Decrease of the tests T-system of immunity is appearance of short duration. It was mentioned a considerable decrease of functional activity and quantity of T-lymphocytes in the patients with lingering course of shigellosis and in chronic form of the disease.
Investigations of subpopulations of T- and B-lymphocytes were an important stage for deciphering of violation of immune system in shigellosis. These data allow to establish the most important links of pathogenetic process. Corrections of these links may be the most perspective.
Detailed analysis of subpopulations of immune system had proved the presence of secondary immune deficiency in shigellosis. So, decrease of T-supressors is observed in case of moderate and severe course of acute shigellosis. In chronic form of the disease the activity of T-supressors increases, but the level of T-helpers decreases.
However, the factors of cell immunity must be estimated according to humoral and especially, local immunity. It is possible, that absence of the local immune reaction is a risk factor of lingering, chronic forms of the disease development and also for postdysenteric colites.
The local immune response of lymphoid tissue of intestine is promoted by antibodies – forming cells of mucous membrane-produced antibodies of classes IgA, IgG, IgM. The class of IgA has the leading role in the protection of the organism.
Thus, the secondary immune deficiency in patients with different forms of shigellosis is connected in general with violation of regulative and effectoric links of immune system. The causes of secondary immune deficiency development is inhibitory influence of antigenic-toxic complexes of the agent at immune system in infectious diseases.
It is known, that endotoxinemia is one of the mechanisms of pathogenesis of shigellosis. Toxins of the agent render depressive influence on hemopoesis, phagocytosis and cause the disorder of microcirculation. Correlation is marked between degree of intoxication, level of depression of cell immunity and natural resistance of the organism.
The study of different cells populations, their metabolic activity allow to determine their role in different forms of shigellosis. These investigations give a possibility of application of basic regulation of cell’s functions with use immunocorrecting therapy for preventation of the formation of lingering, chronic forms of the disease and postdysenteric colites.
There are the next clinical variants of acute shigellosis:
1. colitic variant;
2. gastroenterocolitic variant;
3. gastroenteric variant.
Depending on gravity of the course of the disease there are mild, moderate and severe course of shigellosis, and also carriers.
Clinical manifestations
http://www.nlm.nih.gov/medlineplus/ency/article/000295.htm
Colitic symptomocomplex is typical for shigellosis. Incubation period lasts from 2 till 5 days, rarely – 7 days.
Mild course. Onset of the disease is acute. The temperate pains appears in the lower part of the stomach, principally, in the left iliac area. These pains precede act of the defecation. Tenesmus are observed in some patients. Stool is from 3-5 till 10 times a day. It contains mucus, sometimes – blood. Temperature is normal or subfebrile. Catarrhic inflammation of mucous membrane is observed at rectorhomanoscopy, sometimes erosions and hemorrhages.
Moderate course. Onset of the disease is acute or with short prodromal period. It is characterized by weakness, malaise, discomfort in the stomach. Then, spasmatic pain appears in the lower part of the stomach, tenesmus. At first, stool has fecal character. Then, mucus and blood appear in stool. Stool loses fecal character and has appearance of “rectal spit” (excretion of scanty stool – “fractional stool”), with mucus and blood. Stool is accompanied by fecal urgency and tenesmus. Stool is from 10-15 times a day.
In patients with medium serious course of acute shigellosis temperature increases up to 38-39 °C for 2-3 days. Subfebrile temperature is possible. The patients complain of weakness, headache. It may be collapse, dizziness. The skin is pale. Hypotonia, relative tachycardia are observed. Tenderness and condensation of sigmoid are revealed. In the peripheral blood leukocytosis and temperate neutrophylosis are observed. In coprocystoscopy erythrocytes (more then 30-40 in the field of vision) are revealed. In rectorhomanoscopy diffusive catarrhic inflammation, local changes (hemorrhages, erosions ulcers) are revealed. In patients with moderate course of acute shigellosis functional and morphological restoration may be prolonged – till 2-3 months.
Severe course. Onset of the disease is acute. Temperature is increased up to 39 ˚C and higher. The patients complain of headache, harsh weakness, nausea, something vomiting. Strong abdominal spasmodic pains, frequent stool with smaller volume “without account”, with mucus and blood are marked.
There are hypotonia, harsh tachycardia, breathlessness, skin cyanosis. Harsh tenderness at the left iliac area, especially in the area of sigmoid are marked during palpation of the stomach. It is possible pasesis of intestine. There are expressive leukocytosis neutrophylosis with shift to the left. ESR is accelerated.
During microscopical examination of stool erythrocytes are marked through the field of the vision. In rectorhomanoscopy infusive catarrhic or fibrinous inflammation, presence of the local changes (erosions, ulcers) are marked. The functional and morphological restoration of intestine is longer than 3-4 months in patients after colitic variant of acute shigellosis.
Gastroenterocolitic variant of shigellosis. The principal feature of this variant of the acute shigellosis course is acute impetuous onset of the disease after short incubation period (6-8 hours). More frequent way of the transmission of the infection is alimentary. The factors of transmission are milk, milk products and other.
Intoxicative syndrome and symptoms of gastroenteritis are observed in the initial period. The manifestations of enterocolitis predominate in the period of climax.
There are mild, moderate and severe course of gastroenterocolitic variant of acute shigellosis. During estimate of the disease course gravity it is necessary to allow for not only degree of intoxication and damage of gastrointestinal tract, but also degree of dehydration, because repeated vomiting and plentiful diarrhea are observed. It may lead to dehydration of I-II-III degree.
Gastroenteritic variant of shigellosis. The principal feature of this variant of the acute shigellosis course is predominance of clinical symptoms of gastroenteritis and presence of certain degree dehydration symptoms. Nowedays, besides clinically distinct sings of the disease, lingering and obliterated course of shigellosis is observed. Obliterated course is characterized by insignificant clinical manifestations. The great ratio of the patients do not apply to physician. Careful bacteriological examination of the patient with different gastrointestinal disorders of unknown etiology has large meaning for correct diagnostics. In these patients catarrhic inflammatory changes of mucous membrane of distal portion of rectum is revealed in the majority of cases during rectorhomanoscopy.
Clinical recovery comes through 2-3 weeks in the majority of the patients with uncomplicated course of all variants of acute shigellosis. Complete functional and morphological restoration of gastrointestinal tract happens in 1-2 months and later. Relapses may arise in some part of the patients. The factors, promoting to relapses of the disease are the violation of diet, alcohol use, incorrect therapeutic tactics. The disease may have lingering course. Insufficient reactivity of the organism, sharp decrease of cell immunity in acute period of the disease promote to lingering course of shigellosis.
Lingering course of shigellosis. Shigellosis is estimated as lingering, if clinical manifestations of the disease are observed over 3-4 weeks. Declination to lingering course of the disease depends on gravity of the course of shigellosis in acute period. Colitic variant of severe course of acute shigellosis has prolonged course more frequently than moderate variant. The period of functional and morphological restoration of the intestine is over 3 months. In some patients lingering course is manifested only by persistent bacterioexcretion. Bacterioexcretion is combined with prolonged inflammatory process in rectum.
Bacterioexcretion. dysfunction of intestine is absent at the period of examination and preceded 3 months in presence of bacterioexcretion (subclinical bacterioexcretion) or excretion of Shigella after clinical recovery (reconvalescent excretion) in this form of infectious process.
Diagnosis
The principal methods of diagnostics of shigellosis are bacteriological and serological methods of investigation.
Excretion of coproculture of Shigella is more reliable method of confirmation of diagnosis of shigellosis. It is necessary to take the material for bacteriological investigation before beginning of the treatment.
Diagnosis may be confirmed by serological methods. Reaction of indirect agglutination with standard erythrocytic diagnosticum is used more widely. Diagnostic titer is 1:200 with increase of titer in 7-10 days.
Treatment
http://emedicine.medscape.com/article/182767-medication
The Complex of treatment is indicated, which depends on features of disease. In the first days the diet №4, and diet №2 (till clinical convalescence) are indicated.
At mild current of shigellosis etiotropic agents are not applied, at disease of average degree of gravity use basically preparations of Nitrofuranes: Furazolidon, Nifuroxasid 0.1 gr. 4 times per day. Use derivatives of 8-oxyquinoline – Enteroseptol, Intestopan, among other groups of preparations – Intetrix, Nalidix acid, Ftalazol. At ambulatory treatment of shigellosis with moderate stage of gravity Sulfanilamid preparations of prolonged action are indicated – Phthazin, Sulfadimethoxin.
In case of severe shigellosis current use antibiotics – Ampicillin or a Polymyxin; when there is no effect – Ciprofloxacin or Ofloxacin in combination with Gentamicin or Cefazolin are prescribed. Duration of course of etiotropic treatment at moderate current of shigellosis is 2 – 3 days, at severe case it lasts not longer than 4 – 5 days.
Solution of Regidron, in severe cases Quartasol, Lactosol are applying per os with the purpose of desintoxication and rehydratation. For the adsorption of bacterial toxins and metabolites from the intestine lumen and for their subsequent removing from the organism Enterodes, coal microspherical sorbents, Sillard P, Smecta are used. Rectal pollination with Sillard P in a dose 6 gm (1 – 3 procedures) is effective. There are proved Methyluracil, Pentoxyl, Thymalin as natural factors of nonspecific protection of the organism lysozyme and stimulators of regeneration. Calcy gluconate, Dimedrol, Suprastin, Tavegil is indicated as pathogenetic treatment.
According to parameters of coprocytogram use mono or polycomponental fermental preparations. At presence of plenty of fat drops in feces Pancreatin, Pancitrat, Pancurmen, and at detection of cellulose, Amyl, muscular fibers – Pansinorm, Festal, Mezym-forte, Abomin, Vobensim are applied.
There are indicated widely vitamins preparations, these are ascorbic acid, nicotinic acid, Thiamin chlorid, Riboflavin, Pyridoxine hydrochloride, Calcy Pangamat, folic acid, Rutin. It is better to use per os the balanced vitamin complexes – Dekamevit, Glutamevit.
Collibacterin, Bifidumbacterin, Bificol, Lactobacterin, Bactisubtil, Linex, Hilac forte, α – bacterin, Enterole-250 are indicated for elimination of intestinal dysbacteriosis and restoration of the normal biocenosis. Course of treatment is 2 weeks and longer.
Collectings of herbs and fruits of a bilberry, mint peppery, knot-herb ordinary, camomiles medicinal, herbs of a yarrow, centaury are helpful ordinary. Collecting with the shepherd’s bag ordinary, grasses of St.-Johns wort are effective at hemocolitis. Fermentative and putrefactive processes reduces at lingering colitis, that is why collecting of grass of a sage-brush, a horsetail field, grasses of a yarrow ordinary, roots of snakeweed are applied.
Broths and juices of herbs, oil of dog rose for microclysters after a cleansing enema, 0,5 % solution of a colloid silver as medical clysters, insufflations of Oxygen are used locally for stimulation of reparative processes in the mucosa of colon.
Prophylaxis
Prophylaxis of shigellosis includes complex of measures, directed to revealing of the source of infection, interrupting the ways of transmission, increasing of the organism resistance. Keeping the rules of personal hygiene and rules of food’s cooking plays the principal role in prophylaxis of the disease. Sanitary education of population has an important meaning in shigellosis prophylaxis too.
AMEBIASIS
Acute intestinal infectious disease caused by Entamoeba histolytica. It is most commonly asymptomatic but symptoms ranging from mild diarrhea to dysentery may occur.
Etiology
There are 2 forms of E. histolytica: motile trophozoite and a cyst. The trophozoite, parasitic form, dwells in the bowel lumen, where it feeds on bacteria or tissue. With diarrhea, the fragile trophozoites pass unchanged in the liquid stool and rapidly die. If diarrhea is not present, the organisms usually encyst before leaving the gut.
http://www.cdc.gov/parasites/amebiasis/biology.html
Epidemiology
The cyst, the infective form of the organism resists environmental changes and may be spread either directly from person to person or indirectly via food or water.
Direct spread appears to be more where it occurs in situations of compromised personal hygiene (among sexual partners, particularly male homosexuals and institutionalized).
Indirect spread is more frequent in areas of the world where sanitation is poor, including migrant labor camps and other.
Fruits and vegetables may be contaminated when they are fertilized human faces, washed in polluted water, or prepared began asymptomatic cysts-passer.
Pathogenesis
Excystation of ingested cysts occurs in the small intestine. The released trophozoites are carried to the colon, where they grow and multiply in the bowel lumen as commensals. The trophozoites penetrate the mucous membrane mainly in regions of fecal stasis – the cecum, appendix, ascending colon, sigmoid colon and rectum.
The earliest lesion is a small abscess, usually in the sub mucosa; later, ulcers become ragged and undermined.
The lesions are focal and discrete in mild cases but may spread and become confluent, with hemorrhage, edema, and sloughing of large areas of mucosa (Fig.9, 10).
Fig.9. Hemorrhages and edema of mucosa of sigmoid colon
Fig.10. Ulcers of sigmoid colon
Although penetration by the ameba is limited by the muscular coat, it is occasionally destroyed and perforation results, amebas enter the radials of the portal vein and are carried to the liver. Most of the amebas are probably destroyed, but one or more large hepatic abscesses develop if the survivors are numerous and multiply. Further spread of the disease is usually by direct extension from the liver into the pleura, right lung, and pericardium.
Clinical manifestation
Because of the infrequency of virulent strains, most patients, particularly those living in temperate elimates are a symptomatic symptom occur with tissue invasion and may be so vague as to be recalled only after successful at therapy, but more often intermittent diarrhea and constipation, flatulence and cramping abdominal pain occur. There may be tenderness over the liver and ascending colon and the stool may contain mucus and blood (Fig.11).
Fig.11. “Raspberry jelly” stool in amebiasis
Complications
Hepatic amebiasis, liver abscess, subacute appendicitis, lungs, brain and other organs are occasionally infected by hematogenous spread from the intestines. Skin lesions, especially around the perineum and buttocks and particularly traumatic and operative wounds are occasionally infected with amebas.
Diagnosis
Stool examination is usually negative and recovery of the trophozoite from pus in uncommon. In patients with amebic liver abscess, therapeutic trial of amebicides may be the single most helpful diagnostic tool.
Serologic tests are positive in almost all patients with amebic liven abscess and in 80 % of those with acute amebic dysentery.
Differential diagnose
Performed with irritable bowel syndrome, regional enteritis, and diver ticulitis. Amebic dysentery may be confused with salmonellosis, schistosomiasis or ulcerative colitis.
Hepatic amebiasis and amebic abscess must be differentiated from other hepatic infections, including abscesses due to bacterial infection and infected echinococcus cysts.
Treatment
Course A (symptomatic intestinal amebiasis). Metromidazole, iodoquinol or diloxanide furoate may be given orally. For adults, metronidaze 750 mg orally tid for 10 days is recommended. The comparable dose of lodoquinoe is 650 mg tid or 30 to 40 mg/kg/day.
Course B (symptomatic intestinal amebiasis). Metronidazole should be given in combination with iodoquinol. In severe dysentery, emetine 1 mg/kg/day (maximum 65 mg).
Course C (extraintestinal amebiasis). Metromidazole given in the dosage mentioned above, in the drug of choice. Alternatively, emetine or dehydroemetine can be given for 5 days in the manner described for severe amebic dysentery.
Criteria of curation: Since amebiasis tends to relapse, stools should be reexamined with reasonable frequency – if feasible 1, 3 and 6 mo after treatment.
PSEUDOTUBERCULOSIS
http://www.cdc.gov/nczved/divisions/dfbmd/diseases/yersinia/
Definition.
Pseudotuberculosis is an acute infectious disease characterized by the polymorphism of the clinical manifestations, affection of the alimentary tract, locomotor system, liver and other organs, general intoxication, exanthema and frequently prolonged course with relapses.
History and Geographic Spreading.
The French scientists L. Malasser and W. Vignal first reported on the pseudotuberculosis microbe. In 1883 they isolated it from the organs of a guinea pig infected with the suspension of the caseous regenerated lymph node of the child who had died from ‘tuberculosis’ meningitis.
In 1885 C. Eberth introduced the term ‘pseudotuberculosis’ when he observed spontaneous epizootic in the rabbits, it was accompanied by an abrupt emaciation of the animals. At the post-mortem examination of the dead animals the anatomic pathological changes of the timer organs looked like the tuberculosis ones, but it was impossible to discover the tuberculosis pathogen, and the morphological characteristics of the isolated pathogen were identical to the microbe.
In 1889 A Pfeiffer studied the characteristics of this microbe in detail and gave it the name ‘Bacterium pseudotuberculosis rodentium’, he connected the isolation of this pathogen with a certain clinical picture in animals.
Etiology.
The pseudotuberculosis microbe is a polymorph bacillus, which does not form spores and often has an ovoid form. It is Gram-negative, well painted by all aniline dyes. The question of a capsule in the pseudotuberculosis bacteria is still under discussion. The pseudotuberculosis bacteria grown at a temperature of 4-30°C are actively mobile, have flagellum, whose length is 3-5 times bigger than the length of the body of the bacterial cell. At a temperature higher than 30°C the flagellum atrophy and the mobility of the bacteria ceases. The pseudotuberculosis microbe is a facultative anaerobe, it is quite undemanding to the nutrition, and that is why it grows well on the common dense nutrient media, it can grow on the media without peptone. This characteristic of the pathogen was used to distinguish the pseudotuberculosis bacteria from the plague pathogen.
The bacteria contain H-antigen and 0-antigen, which determine their variability. The H-antigen is thermolabile and is destroyed at boiling, it is synthesized at a temperature of 2-30°C best of all. The flagellum antigen does not have a diagnostic value as it has a component “a”, which is common to all serologic variants. The somatic 0-antigen of the pseudotuberculosis microbe serologic variants. The somatic 0-antigen of the pseudotuberculosis microbe determines its antigenic peculiarity. It is thermostable, it is not destroyed at a temperature of 100-120°C during two hours. With the help of such thermal processing of the pseudotuberculosis microbe culture it is possible to prepare an antigen to receive hyperimmune serums, which are used for the serologic identification of the isolated strains of the pseudotuberculosis microbe.
The recent investigations ascertained that the virulence of yersinia is primarily determined by plasmids which are present in the cells of these microorganisms, plasmids are carriers of the extrachromosome genetic information. In bacteria they determine the resistance to antibiotics, synthesize antigens and toxins. One of the factors of the yersinia pathogenicity is their ability for the adhesion to a host’s cells. The adhesion is necessary to attach a microorganism to a macroorganism’s cell. The molecules of the toxins and other biologically active substances are brought to a cell’s receptors at adhesion.The adhesion is completed by an invasion of a microorganism in a host’s cell. The replication of yersinia with the following lysis of a host’s cell takes place in a cell cytoplasm. The speed of lysis directly depends on the number of the bacteria penetrating a cell. Thus, yersinia can penetrate a host’s cells, replicate in their cytoplasm destroying the cells of the infected person.
The second factor of the yersinia pathogenicity is their invasiveness. The virulence of the yersinia is stipulated by their invasiveness directed at the phagocytosis suppression and the ability of the microorganism to form toxins. Such ferments as neurominidase, hyaluronidase are found nowadays, they are produced by the pathogenic strains of yersinia. The most important factor of the yersinia pathogenicity is their ability to produce thermostable enterotoxin.
Thus, different biologically active substances, which are necessary to initiate and develop an infectious process, are produced in the process of the yersinia pathogen vital activity. Besides this it is established that the yersiniosis pathogen strains of different pathogenicity circulate in the human population.
Epidemiology.
Before the 60-s of the XIX century the epidemiology of the human yersiniosis was almost unstudied. It is explained by the fact that the disease appeared in the form of sporadic cases. In such situations it was often impossible to discover the pathogen, find the disease source, discover the mechanism of its spreading. The situation changed when the Far East scarlatiniform fever mainly manifested by massive epidemic outbreaks was brought to light in the Far East.
Yersiniosis mainly embraces the urban population as in the cities there are more opportunities for the development of big outbreaks among the contingents of people united by public feeding. On the other hand, a more active revealing and better diagnostics of the disease as compared with the rural area is of a certain importance. Children fall ill the most often as compared with the other age groups of the population. The epidemic outbreaks are quite often observed in the organized collectives, especially, the preschool ones. First of all such outbreaks depend on the conditions of the fruit and vegetables storage as well as the condition of feeding the population.
Animals are a reservoir of the infection under the natural conditions. The pseudotuberculosis microbe was isolated from the organs and excrement of many kinds of the mammals, birds, reptiles, fish and arthropoda. Such a diverse and spontaneous infection of many kinds of animals by the pseudotuberculosis microbe gives a ground to think that none of them are a specific biological host of this pathogen and it testifies that in case its ubicvator spreading in nature all kinds of animals get involved in the general process of the microbe circulation and serve as a more or less long reservoir of the pathogen depending on the species susceptibility to it.
Rodents are the most. frequent reservoir of the pseudotuberculosis microbe. It is explained by the fact that on the one hand, rodents are distinguished by a high susceptibility and sensitivity to the pseudotuberculosis microbe and on the other hand, they are considerably widespread on the Earth and the speed of their replication is high.
The infection of humans can occur at a direct contact with domestic and wild animals, birds while skinning them and processing the carcasses. A possible mechanism of the infection of humans is using the food and water contaminated by the discharge of rodents and birds – carriers of the pseudotuberculosis microbe. Besides this there are a number of convincing investigations confirming that soil is a reservoir of the pseudotuberculosis pathogens. The authors think that the pseudotuberculosis microbe cannot exist in the soil for a long time without reproduction as it cannot form spores. It has saprophytic and parasitic characteristics and correspondingly has two natural biospheres of existing – the warm-blooded animals and environment. The pseudotuberculosis pathogen was isolated during the bacteriologic investigation of the soil from the fields where vegetables and edible roots, as well as wash-outs from them (beet-roots, carrots, cabbages, onions, potatoes).
The epidemiological examination of many outbreaks of the disease made it possible to ascertain that among all the food staffs vegetables, edible roots, dry food, some dry products, which are eaten without any thermal processing, are of the most importance in the pathogen transmission. The importance of vegetables and edible roots as a factor of the pathogen transmission was proved by the isolation of the pseudotuberculosis microbe from them during the outbreaks, the microbes were identical by their serologic variant to the cultures isolated from the sick people who had eaten that food. Such outbreaks most often occur when dishes from fresh cabbage are used as food at the public feeding places.
Raw vegetables and eatable roots get infected by the pseudotuberculosis microbe considerably more often and in more foci than different pickings. The dissemination of the vegetables and eatable roots by the pseudotuberculosis microbe can occur in the autumn while loading them into the vegetable storage places if the latter ones have not been disinfected after sorting the contaminated vegetables of the previous year harvest. The findings of the pseudotuberculosis microbe in the washouts from the floor and shelves of the vegetable storage places confirm this.
Besides vegetables and edible roots, the second important factor in the pseudotuberculosis pathogen transmission is dairy products. Such diary products as cottage cheese, cheese, and, perhaps, sour cream are the most important. It is necessary to note that the pasteurization of milk (at a temperature of 65°C for 30 minutes) does not destroy the pathogen.
Water can also be a factor of the pseudotuberculosis microbe transmission under the favorable conditions.
Pathogenesis.
The pseudotuberculosis pathogenesis cannot be considered to be thoroughly studied so far. The pathogens mainly penetrate the human organism through the mouth with the infected food and water. A further movement of the microbes to the esophagus and then stomach characterizes this phase. The acid medium of the stomach contents ruins most pathogenic microbes of the intestinal group perhaps including the pseudotuberculosis pathogen. Having overcome the stomach barrier, the pathogen gets into the intestines and an enteral phase develops, it is characterized by the penetration of the microbe into the mucous membrane of the intestines, then it goes to the regional mesenteric lymph nodes along the lymph paths. Here they reproduce and accumulate, later overcoming the lymphatic barrier the bacteria penetrate the blood and cause the reciprocal reaction of the organism to the toxic substances, which get into the blood vessels during the destruction and life of bacteria.
Besides the mentioned above facts, it was ascertained by a series of profound experimental investigations that it is not only the intestines epithelium, but also the epithelium of all the alimentary tract is the entrance gate of the infection, the alimentary tract begins with the throat where develops the first affect in the form of stomatitis, glossitis, tonsillitis, pharyngitis, which go with regional cervical, submaxillary lymphadenitis.
In more rare cases some authors mention an airborne way of infection, even marking out a pulmonary form of this infection. They think that the pseudotuberculosis microbe possesses pneumotropism with the development of pneumonia and even lung abscess. As the clinical picture of pneumonia develops in later terms of the disease in experimental pseudotuberculosis, the lungs may be only an entrance gate for the development of the generalized process. Taking into account all the mentioned above facts, there is a ground to suppose that irrespective of the entrance gate pseudotuberculosis immediately takes a course of a generalized infection.
The mechanism and sequence of the development of separate periods of the infectious process in each person are different. Depending on the condition of a microorganism, the activity of nonspecific defense as well as the dose and degree of the pathogen virulence, the pathological process can stop at any of its phases. The pathogen of the disease can be blocked by the secretory immunoglobulins even on the mucous membranes of the intestines and respiratory tracts. While overcoming this barrier and yersinia pseudotuberculosis penetration the regional lymph nodes with the lymph How, different macrophagal elements, immunoglobulins and immunocompetement cells take defensive measures. The infectious process can cease at this stage if the organism resistance is good. In such cases the patients note only unpleasant feelings or a slight pain in the area of the affected lymph nodes. Such erased forms of the disease are observed only at the thorough investigation of the contact persons in the infection focus. The bacteriemia, pseudotuberculosis process generalize and all its clinical symptoms are observed if the defensive factors of the organism are weakened as a result of another disease, supercooling, starving, immune deficiency conditions.
The clinical process has periods of remissions and acute conditions. The recovery occurs after any phase. Thus, in human pseudotuberculosis there are two expressed pathogenic stages: 1) the pathogen penetration, primary and regional focal manifestations of the disease; 2) bacteriemia, hematogenic drift and septicemia, which develops, as a rule, after the first period, though sometimes it is not expressed distinctly.
The hematogenic dissemination of the pseudotuberculosis pathogen results in the development of the phase of the secondary focal changes in the organs and tissues. As a rule, this stage is accompanied by an expressed organism allergization.
It is clinically manifested by a certaiumber of symptoms: different kinds of rash on the skin, the affection of the joints, most often in the form of arthralgia, less often – arthritis, the involvement of the ileocecal part of the intestines, liver, spleen, less often – other organs (the lungs, kidneys, pancreatic, brain). There is hyperplasia of the lymphoid elements in the regional lymph nodes, it often results in a considerable change of the organ’s picture. The cortical substance abruptly widens, and the secondary polyps are located in several rows up to the organ’s gate. During the development of the pathological process the pseudotuberculosis microbes replicate and accumulate in the lymph nodes. Clinically the secondary focal phase of the pseudotuberculosis pathogenesis is closely connected with the relapses of this disease.
The following phase of the pseudotuberculosis pathogenesis development is the phase of the specific immunity increase, which is followed by the release of the organism from the pathogen and recovery. Cultivating a strong antimicrobic immunity completes the disease. The possibility of the development of the disease chronic form is very rare.
Anatomic pathology.
Only the sporadic cases of human pseudotuberculosis in the form of the septic-typhoid form, which was diagnosed during the autopsy and confirmed by the pathogen isolation, had been described before the early 50-s of the XX century. The pathoanatomists found small necrotic or abscess-like grayish-white nodes in the enlarged liver and spleen, as well as in the lungs. Many researchers call these abscesses necrotic granulomas. Such granulomas with the central necrosis are considered to be a characteristic symptom of pseudotuberculosis. Besides this, there is swelling and necrosis of the lymph nodes follicles of the intestines and mesentery, hyperemia of the peritoneum covering them, edema and infiltration of the distal part of the iliac and proximal part of the large intestine, catarrhal-desquamative and ulceric enteritis (ileitis), congestional plethora, brain edema, dystrophy of the parenchymatous organs and hemorrhage in them. In some cases there is a picture of catarrhal, phlegmonous and gangrenous appendicitis. In combination with the mechanism of the disease development it is possible to suppose that the lymph nodes of the mesentery as well as the iliac intestine and vermicular process serve as a depot for the microorganisms for a long time, it is clinically manifested by a pain in the area of the right iliac enteritis.
There are ofteo visible changes in the area of the vermicular process in the patients with the appendicular form of pseudotuberculosis during the surgery. Nevertheless, it was possible to discover cellular-tissue reactions characteristic of the initial stage of the pathologic pseudotuberculosis process development and having differential-diagnostic value.
In pseudotuberculosis acute terminal ileitis the inflammatory infiltration in the intestine wall has a diffusive or focal character, sometimes similar to the granular tissue. The inflammatory changes, which are not of a destructive character, also take the serous membrane. The polymorph cells, among which there are a lot of eosinophils, considerably infiltrate the mucous membrane of the intestine, there are cryptabscesses, clinoid necrosis and ulceration. The micro abscesses were found in the plate mucous membrane itself. At the study of the pathology of the distant mesenteric lymph nodes in the patients with pseudotuberculosis it was ascertained that the cellular-tissue changes in them are of a double character: on the one hand, they reflect the immune morphologic reaction, on the other hand, – testify of an inflammatory reaction developing in response to the bacterial infection.
The granulomas develop in the lymphatic follicles, the vessel reaction increases and the inflammatory infiltrates develop in case of the progressive pathologic process. The morphogenesis of granulomas both in the appendix and in the lymph nodes is principally the same. The destruction in the follicles increases in the form of ‘avalanche’, which is manifested by a peripheric growth of the necrotic focus. The inflammatory process ceasing is accompanied by the decrease of the exudate phenomena and limiting the destruction foci by a connective tissue capsule from the surrounding lymphoid tissue.
In those cases when there were no changes on the part of the vermicular process, the clinical picture was stipulated by an inflammatory reaction in the lymph nodes of the mesenteric, the terminal part of the iliac intestine and the nodes located in the area of the blind gut and the initial part of the ascending part of the large intestine. The nodes increased up to 1-3 cm in a diameter, they were pink-red, red or brown. They were dense in consistence, elastic or mollified with the necrosis foci. Sometimes there were microabscesses in the form of yellowish-whitish dots under the serous membrane. In some patients the lymph nodes merged in the conglomerates with a diameter of 5-6 cm, they looked like tumor-like neoplasm. The inflammation often transferred from the lymph nodes to the surrounding tissues, especially, to the distal part of the small intestine including the vermicular process.
Diffusive ileitis is also a severe complication in pseudotuberculosis, it results in the contraction of the ileum lumen, invagination, comissural ileus and paralytic obstruction, necrosis and perforation of the intestines. The phenomena of peritonitis stipulated by the mesenteric node disintegration have been described.
There are a lot of reports on the involvement of the cardiovascular and nervous system, liver, spleen, kidneys and adrenal glands in the pathological process in pseudotuberculosis.
The pathomorphologic basis of the infection is acute generalized reactive reticulocytosis with the primary affection of the lymphatic apparatus of the intestines, mesenteric lymph nodes, liver, spleen. There are specific of pseudotuberculosis foci – granulomas and micro abscesses in the organs, which are rich in the macrophage elements. The nonspecific changes of a dystrophic type often develop in other organs.
Clinical manifestations.
The diversity of the pseudotuberculosis clinical manifestations, the involvement of different organs and systems in the pathologic process are the basis for the suggestions of numerous classifications of this disease. The least cumbersome classification, though it does not lack drawbacks, is the classification by N. U. Zalmower, which is based on the syndrome principle with the following clinical forms:
1. A scarlatiniform characterized by the general intoxication symptoms, fine-dot rash, fever;
2. A arthralgic form resulting in the joints affection, it takes a course of arthralgia, less often – arthritis;
3. An abdominal form with the primary affection of different parts of the alimentary tract, sometimes in the initial period;
4. A generalized form with the affection of different organs and systems when it is impossible to pick out any main syndrome;
5. An icteric form, in which the affection of the liver with a jaundice syndrome is the primary symptom.
The clinical manifestations of pseudotuberculosis are characterized by a great polymorphism with the prevalence of the general intoxication, which makes an early diagnostics extremely difficult. As well as other acute diseases pseudotuberculosis has a certain cyclic recurrence. The development of the cycle’s periods with a certain time limitation, which is accompanied by different morphologic, immunologic and clinical changes, results in a characteristic picture of the disease. There are following periods in pseudotuberculosis: an initial period, a high point, a period of acute courses and relapses, convalescence.
Evaluating the descriptions of the clinic given in the literature and observing the patients, it is necessary to note that in each separate case these periods can be manifested in different ways depending on the reactivity of the macroorganism, virulence of the pathogen, the time when the treatment began, the quantity of the daily and course doses of the medications and other factors. All the periods of the disease can be observed in the typical cases in half the patients (especially, in case of the pathogenic therapy and short courses of some antibiotics). In other cases some of them cannot be observed or they can be slightly manifested. There can be only separate symptoms of the initial period without a temperature rise in the deleted forms of the disease.
Judging by the epidemiological history, the incubation period in this infection most often lasts 7-10 days with the fluctuations from 3 to 18 days. In this period the disease does not usually have any clinical manifestations, the people consider themselves to be practically healthy and continue working.
The initial period is the time when the first symptoms of the disease develop till the highest possible development of the clinical picture with the symptoms of the local affection.
In most patients the disease has an acute course with a rapid temperature rise, which is accompanied by chills. The prodromal phenomena in the form of malaise, slight chills, the development of uncertain pains in the abdomen, which developed 1-2 days before the onset of the disease, were described only in separate cases.
This period is clinically characterized by expressed polymorphism and absence of specific symptoms typical of only this disease. The temperature rise is accompanied by a headache of different intensity with its primary location in the forehead and temple areas, pains in the muscles, joints, waist, general asthenia, weakness and lack of appetite. In a number of cases the sick people complain of the pain in the throat at swallowing. In some cases patients complain of pains in the stomach, diarrhea 2-3 times a day, nausea and single or recurrent vomiting. There is brief fainting in some patients in the first hours of the disease together with general asthenia. An early toxicosis resulting in a lethal outcome can develop in rare cases, especially, in children during 2-4 days.
While examining the patients it is possible to observe hyperemia of the face and neck, some puffiness of the face, hyperemia of the conjunctiva and an injection of the sclera vessels, there is a pale nose-lip triangle in some patients. There is often herpetic rash on the lips and the nose wings, expressed hyperemia of the throat, which is of different intensity, less often – an enanthema on the soft palate, angina. During the first days of the disease the tongue has a grayish-white patch, which begins to clear and becomes raspberry with expressed papilla on the third day.
There are symptoms of acute catarrh of the upper respiratory tract such as a running nose, cough, pains in the throat at swallowing in most patients in the initial period of the disease. Similar symptoms of the disease sometimes result in diagnosing catarrh of the upper respiratory tract and difficulties in deciphering the outbreak. When the massive diseases appeared during the first outbreak of the FESF in the Far East, all the cases were diagnosed as grippe and only the development of rash in the patients caused alarm in the doctors and made them turn to the infectious doctors. The symptoms of the local affection of the alimentary tract and locomotor system, which were manifested by the increasing pains in the abdomen and joints, develop in a quarter of the patients at the end of the initial period.
Such diversity of symptoms testifies about the involvement of different organs and systems in the pathological process even in the first days of pseudotuberculosis infection, which is often a reason for a false diagnostics in this period. The most part of such patients are treated at home, the smaller part is sent to a hospital with the diagnoses: acute respiratory disease, polyarthritis, gastroenteritis, catarrhal angina, scarlatina and others. These diagnoses often remain the final ones as a doctor examines a patient for a second time only in the period of convalescence and does not pay attention to some important symptoms of the disease (rash, ‘raspberry’ tongue, pain in the ileocecal area, etc.)
Rash is one of the most striking symptoms of this period. It develops on the 1-4th day of the disease, sometimes on the 5-6th day. According to its character it is often fine-spotted on the hyperemic background or normal skin. During the first outbreak of the disease in some patients it is fine-spotted, and in combination with angina, the enlargement of the submandibular lymph nodes, ‘raspberry’ tongue, the development of peeling typical of scarlatina in the later period gave a ground to first diagnose ‘scarlatina’ in all patients. Later during the development of other pseudotuberculosis outbreaks and the exposure of the sporadic cases of this disease it was found out that the rash can be spotty (looking like German measles and measles) and confluent erythematous. The spreading of the rash can be different, if it is spread all over the body, it is mainly located on the symmetrical parts. The rash is not often found on the face and neck. There is often hyperemia and swelling of the skin on the hands and feet – the symptoms of ‘gloves’ and ‘socks’. The petechial-hemorrhagic elements are mainly localized in the natural folds of the skin and on the side surfaces of the chest. The development of hemorrhages in the form of stripes and changes on the side surfaces of the shoulders and in the area of the armpit line. There are endothelial symptoms of plait, pinch with hemorrhages in the patients with a severe form. The development of rash can be accompanied by the deterioration of the patients’ condition, pulse acceleration, hypotonia and even a collapse condition.
There is scaly laminar peeling on the skin of the chest, abdomen, lobes of the ear and then on the back surface of the hands, feet, palms during the 2-3rd week of the disease. The duration of the initial period is 1-5 days.
The highest point of the pseudotuberculosis infection is manifested by the maximum development of fever and other symptoms of intoxication and expressed signs of the local affection. The highest point of the disease, especially, the first days are characterized by considerable intoxication, which is manifested by the affection of the central nervous system – general asthenia, hypotonia, dizziness, intense headache, tactile hyperesthesia, photophobia, vomiting, insomnia, increased excitability or suppression. In a severe course there are manifestations of meningoencephalitis with the symptoms characteristic of it: a headache, nausea, vomiting, drowsiness, suppression, consciousness disorders, signs of irritation of the meninges and the substance of the brain. There are such meningeal symptoms as rigidity of the neck muscles, Kernig and Brudzinsky symptoms, in the cerebrospinal liquid the cytosis is more than 400 cells, increase of the protein contents. Besides the mentioned symptoms there are characteristic disorders of the vegetative nervous system function. In some patients the affection of the nervous system is similar to the intercostal and nape neuralgia or lumbosacral radiculitis.
The changes on the part of the locomotor system are observed almost in all patients. There is often arthralgia, sometimes with very intense pains in the sacrum, waist, joints and less often – acute polyarthritis, which is characterized by swelling of the tissues around the joints with hyperemia of the skin. The radiocarpal, interphalangeal, knee and ankle joints are most often affected in pseudotuberculosis, less often – shoulder and hip joints. Acute polyarthritis is often confused with the attacks of acute rheumatism in case of the poor knowledge of the pseudotuberculosis clinic. The pain syndrome depends on the severity of the disease and can be weak or strong, hindering independent movement. The joints are swollen, painful, hot.
Most patients complain of myalgia in the acute period of the disease. It prevails in the muscles of the neck, abdomen, and extremities. In some cases myalgia of the abdomen muscles is sharply expressed, which stimulates “acute abdomen”. In such cases it is necessary to pay attention even to slight manifestations of other symptoms of the disease.
The submaxillary, neck and axillary lymph nodes can be enlarged in the acute period of the disease. They are slightly painful, elastic, not united with one another and the surrounding tissue.
The changes on the part of the cardiovascular system at the highest point of the disease are manifested by hypotonia, dullness of the heart sounds, and in some patients there is a systolic murmur over the top and extrasystole. In spite of the fact that in a considerable number of patients the subjective symptoms of the heart affection (pain, heartbeat, arrhythmia, and others) are extremely rare, the electrocardiograms show changes, some of them are considerable. The decrease of the P and T waves voltage is the most frequent of them, less often – the deformation as a result of the toxic-infectious influences on the cardiac muscle. There were sometimes symptoms of its diffusive affection.
The respiratory organs also get involved in the pathological process in pseudotuberculosis. The pains in the throat, hyperemia of the fauces mucous membrane, spotted enanthema on the mucous membrane of the soft palate, rhinitis, cough, dry rale in the lungs testify of their affection. There is dulling of the percussion sound over the pulmonary fields and moist rale in the limited areas in some patients who suffer a severe course of the disease. The x-ray investigations usually demonstrate the intensification of the bronchial-vascular picture, the opacity of the roots, less often – infiltration of the lung tissue.
In a mild case of the disease the affection of the alimentary tract is manifested by complaints of a bad appetite, nausea, less often – vomiting diarrhea. The stool is fluidity or watery 3-5 times a day with admixture of mucous. The pain in the abdomen is observed in half of the patients and is often revealed only at palpation. The tongue furred, it becomes raspberry when it gets cleared.
The changes of the alimentary tract are expressed more strongly and prevail over the rest ones in a more severe course. In this case a pseudotuberculosis abdominal form is diagnosed. It is characterized by a pain in the epigastria area of the abdomen, umbilical or right iliac area, less often -in the right hypochondrium and left iliac area. The abdominal syndrome is clinically revealed primarily in the form of the symptoms of mesenteric lymphadenitis, terminal ileitis, acute appendicitis. Mesenteric adenitis of the pseudotuberculosis etiology without any other manifestations is quite often observed in the countries of Western Europe. The affection of the mesentery lymph nodes can occur in different periods of the infectious process, more often in the initial period and at the high point of the disease. In this case there are pains in the right iliac and para umbilical, the palpation demonstrates an enlarged, painful and “grumbling” cecum and mesenteric lymph nodes. Such patients come to hospital with various diagnoses: “acute appendicitis”, “acute cholecystitis”, etc. These patients can come to both infectious and surgical hospitals, and only the carefully collected history of the disease and the clinical investigation data allow to diagnose pseudotuberculosis.
The intensity of the pains in the ileocecal area can be different. In some patients they are revealed only at palpation, in others they are constant aches, in some patients they are so intense that the patients groan and take a forced position with their knees pulled to the abdomen. The patients cannot remain in the same position for a long time. The pains subside and cease troubling the patients on the 2-3th day from the time of their appearance. However, in 3-4 days they recommence and become more intense,
The local manifestations of mesadenitis are usually accompanied by general symptoms as well. They are a temperature increase, sometimes up to 39°C, chills, which intensify with the development of pains in the abdomen, diarrhea – 2-3 stools a day without admixture of mucous and blood, nausea, and vomiting in almost half of the patients. Besides the patients complain of headaches, pains in the joints of the upper and lower extremities, body muscles, general asthenia, sore throat.
The skin of the face, neck, chest is often hyperemic in the patients with mesenteric lymphadenitis. In separate cases there is fine-spotted rash, which rise above the skin in the area of the chest, abdomen, groin folds, inner surfaces of the shoulders, forearms and thighs, the rash gets pale at pressing.
There is muscles tension and other symptoms of the peritoneum irritation, which are very similar to the picture of the ‘acute abdomen’ in case of a severe course of the disease. However, in contrast to acute appendicitis in the mesadenitis patients the pains in the abdomen do not increase when the abdominal press is strained. This new symptom was observed in all the cases of pseudotuberculosis mesadenitis.
The clinic of acute appendicitis in pseudotuberculosis has its peculiarities connected with the fact that besides the affection of the vermicular process the patients have the manifestations of the main disease. As a rule, the patients, in whom the appendicular syndrome develops during treatment in the infectious hospitals or who arrived with the diagnosis ‘pseudotuberculosis’ and have an expressed appendicular syndrome are not operated on, and the disease has a favorable outcome after the conservatory treatment. It is natural that such patients should be carefully observed by both an infectious doctor and a surgeon in order not to miss authentic appendicitis, whose pathogen can be pseudotuberculosis along with other microbes. It is known that the pseudotuberculosis microbe is isolated in about 7% cases during the bacteriological investigation of the processes ablated during the appendectomy. The surgical aspects of pseudotuberculosis are of great practical interest and need to be thoroughly studied.
Regional ileitis in the abdominal form of pseudotuberculosis is more often observed in the relapse and remission period of the disease. In this case the pains in the abdomen develop on the background of the seeming convalescence, they are accompanied by a recurring rise of the body temperature up to 38-39°C and chills. The pains are usually moderate, they are of an attack-like character. In 2-3 days from their appearance they become less intense, in some cases they cease troubling a patient. However, on the 3-4th day they increase and become very intense.
In some patients pseudotuberculosis begins with the symptoms of regional ileitis. In such cases the pseudotuberculosis symptoms are poorly expressed. This results in the diagnostic mistakes. In case of regional ileitis the pains in the stomach are often accompanied by nausea. In half of the patients there is vomiting, sometimes repeated. The affection of the terminal part of the ileum can be accompanied by watery stool up to 3 times a day without an admixture of mucous and blood. The abdomen is sometimes bloated. The right iliac area is the most painful, there is also muscle tension of the front wall of the abdomen. The similarity of the clinical picture of regional ileitis to that of acute appendicitis is a characteristic feature. In many cases it is extremely difficult to diagnose the case before a surgery.
The patients with the pseudotuberculosis abdominal form often have gastroenteritis. Its development can be observed in all periods of the disease. Gastroenteritis usually has a rapid development. The disease starts with pains in the abdomen, nausea, vomiting, it is usually accompanied by the abdomen inflation, watery or pasty stool up to 2-3 times a day, general asthenia, chills, headache and other pseudotuberculosis manifestations. Sometimes gastroenteritis takes a chronic course. In these cases patients complain of the periodic pains in the abdomen, which disturb them, general asthenia, headache, general malaise. The stool in such patients is unstable. There is an expressed asthenia right after the meals. The pains in the abdomen can resemble attacks and do not have a distinct localization. The symptoms of the general intoxication are often expressed.
The affection of the alimentary system is not only limited by the pathologic changes of the gastrointestinal tract. The liver affection is often observed in this or that degree in almost half the patients, actually it is acute parenchymatous hepatitis, its expressiveness depends on the severity of the disease. The affection of the liver is manifested by the enlargement of its size, icteric color of the skin and scleras, the bilirubin increase in the blood, it sometimes resembles the clinic of viral hepatitis.
The thorough comparison of the clinical symptoms with the biochemical investigations shows the involvement of the pancreatic gland in the pathologic process. The patients develop pains in the abdomen, which resemble attacks and are localized in the epigastric area, in the right and left hypochondrium. In some cases they irradiate in the waist or back. The patients complain of nausea, vomiting and general asthenia. There can be watery stool. The amylase level of blood and urine as well as the lipase activity in blood can confirm the diagnosis. Some authors pay much attention to elastase. In 1986 V. A. Ivanis noted that the elastase level depended on the severity of the disease and its indexes normalized in the period of convalescence.
The generalized form of the disease is characterized by the combination of a high temperature, exanthema, and severe intoxication with all the main syndromes of the disease: terminal ileitis, parenchymatous hepatitis, acute polyarthritis, meningeal symptoms and a long relapsing character.
Diagnosis.
The polymorphism of the clinical manifestations of the initial period and absence of the specific symptoms, which are characteristic of only pseudotuberculosis, hinder its early diagnostics. This obliges a doctor to diagnose pseudotuberculosis on the basis of the epidemiological, clinical and laboratory investigations all together. It is not difficult to recognize the infection during the massive diseases as it is possible to clearly establish different stages of the disease during the simultaneous examination of a number of patients. In case of the sporadic cases the diagnostics is more difficult and demands additional epidemiological data confirmed by the bacteriological investigations.
In the clinical aspect an acute onset, chills, general asthenia, malaise, frequent pains in the throat at swallowing are typical. The hyperemia of the skin of the face, neck, fauces mucous membrane, moderately expressed signs of scleritis and conjunctivitis, in some patients – the yellowness of the scleras are considered to be early symptoms during the external examination of the patients. Sometimes during the first day of the disease there is redness and edema of the palms and soles skin, which is accompanied by itching. Such a rapid development of the disease with intoxication and the above mentioned objective data together with the epidemiological situation allow to suspect pseudotuberculosis.
It is necessary to take into account the major symptoms of the disease during the following days at the highest point of the disease. They are a fever with the alternation of the temperature rise up to 40°C and the temperature decrease down to the subfebrile indexes, the development of the spotted (scarlatiniform) or fine-spotted, less often – petechial rash, the involvement of the joints in the pathological process, dysfunction of the intestines, enlargement of the liver with the development of the jaundice syndrome, “raspberry tongue”. In the later terms of the disease it is necessary to take into account the development of acute forms and relapses with predomination of the abdominal or arthralgic syndromes in the clinical diagnostics. As a rule, the two mentioned above primary syndromes of pseudotuberculosis develop together with cerebrostenic syndrome.
There are no reliable diagnostic tests on pseudotuberculosis among the nonspecific laboratory signs. In particular the blood clinical analysis is not informative. The changes of the morphological blood contents do not take place in all the patients and they are of a moderate character.
The specific laboratory diagnostics of pseudotuberculosis is very important in its diagnosing. It is of primary importance in the mild and unexpressed forms of the disease, especially, occurring in the form of separate sporadic cases.
The specific laboratory diagnostics of pseudotuberculosis is represented by the bacteriologic and serologic methods of investigation in the medical practice nowadays.
The main material for the bacteriologic investigation is excrement and in a lesser degree – washouts from the fauces, urine and the appendicular processes, which are ablated during the surgery. The pseudotuberculosis patients excrete bacteria with mucous from the fauces, excrement, urine. The duration of their excreting with mucous and urine is not long. The pseudotuberculosis pathogen is found in excrement during all the disease and in the period of relapses. In separate cases it can be excreted with excrement for about 75 days. The excrement inoculations are done on the differential-diagnostic medium №67 where it is easy to distinguish the pseudotuberculosis colonies from other microbes.
The serologic investigations began to be done after the discovery of the Far East scarlatiniform fever. In the beginning the agglutination reaction with alive cultures as an antigen was used, later a reaction of indirect hemagglutination as well as the reaction of the bacterial lysis, method of fluorescent antibodies and others. In spite of the fact that the pseudotuberculosis diagnostics is improving every year, it does not satisfy the practical doctors so far. The percentage of the bacteriologic confirmation of the diagnosis remains low, and the reaction of indirect agglutination, which is used everywhere, is not enough sensitive and specific. The reaction of coagglutination and immune ferment analysis, which make it possible to discover both the antigen and antibodies to it during the first 3-5 days from the disease onset, is considered to be promising.
Treatment.
It is impossible to agree with the recommendations of some author about the possibility of treating the pseudotuberculosis patients at home. In spite of some positive results the possibility of sudden acute forms development and relapses obliges to treat the patients only in hospital and to thoroughly follow the regimen and an according nursing.
The patients do not need a special diet. The nutrition is typical of the patients with an acute fever. The food should be easily assimilating and high-calorie, containing a sufficient amount of vitamins. A daily food allowance should contain 3200-3500 big calories. The patients with the predominant liver affection, are prescribed diet №5 containing a sufficient amount of carbohydrates and a limitation of fat, especially, refractory.
The treatment depends on the clinical form, the period and gravity of disease. Among etiotropic agents use Levomycetin, Metacyclin, Tetracyclin, Streptomycin, Gentamicin, Ampicillin in moderate therapeutic doses during not less than 7 days and more. At serious current of disease, the septic form the best results can be gained if simultaneously use 2 – 3 antibiotics and one of them infuse into vein: course of treatment prolong up to 10 – 14 days, and through 6 – 7 days it is replaced by preparations with the account of antibioticosensitivity of allocated yersinias. Cefazolin (Kefzol), Cefotaxim (Claforan) are effective. As alternative preparation may be Bactrim (Biseptol). Less effective are Nitrofuranes and Sulfanilamid preparations.
With the purpose of desintoxication and Rehydratation of organism indicate 5 % solution of a glucose, a seralbum, Reopolyglycin, Trisol, Quartasol. Widely use vitamin, antihistamine preparations and agents stimulating regenerative processes – Diprazin, Suprastin, Tavegil, Methyluracil (Methacil), Pentoxyl, Apylac, Natrii nucleinic, Thymalin etc. At gastroenterocolitic form indicate Enterosorbents (activated microspherical coals, Sillard P, Enterosgel, Smecta), replaceable fermental therapy (Festal, Pancreatin, Pancurmen, Pancitrat), diet № 4 is indicated. Colibacterin, Bificol and other biological preparations are indicated in case of development of dysbacteriosis . At acute tonsillitis indicate gargles. Development of arthritis, myocarditis, Reiter syndrome is the indication to use Indomethacin, Ibufrofen, Diclofenac-Natrii (Ortophen) and other not steroid preparations.
All the patients are prescribed vitamin therapy in the form of complex B, vitamins A, C, PP and others.
The therapeutic tactics should be strictly individual in case of every patient who is to be constantly looked after. Only an individual approach and a complex of the treatment measures can bring invariable success and allow to achieve good results.
Prophylaxis.
In spite of the achieved success in the pseudotuberculosis study, the problems of the specific prophylaxis have not been worked out so far.
A complex of nonspecific measures directed at the source and transmission factors is widely used in the medicine to prevent the pseudotuberculosis spreading.
