Typhoid fever and paratyphoid
Shigellosis (dysentery)
Typhoid fever, paratyphoid A and B are an acute illnesses from the group of intestinal infections. They are characterized by cyclic course, bacteremia, intoxication, rash on the skin, lesions of the lymphatic apparatus of the small intestine. Besides that, typhoid fever is characterized by high fever of different duration, development of so-called status typhosus, hepatosplenomegaly, lesions of organs of the gastrointestinal tract, relapses and various complications.
History and geographical distribution
Typhoid fever is well known for a long time as an illness of mankind.
The causative agent of typhoid fever was described by Ebert in 1880. Pure culture of the agent was isolated by Gafki in 1884.
Typhoid fever was one of the most widespread and serious infectious disease in 19th century and in the beginning of 20-th century in all countries of the world, especially in the large towns due to groupment of the people and building of waterpipe and canalization allowed to decrease morbidity in the large towns. But almost every calamity (hunger, earthquake) and wars were accompanied by outbreaks of typhoid fever.
Now, the morbidity is sporadic in European countries. However, high level of morbidity occurs in some countries due to features of climate, ecological conditions and social factors (Mexico, India, Afghanistan, countries of Northern Africa and other).
Etiology
The causative agent of typhoid is Salmonella typhi of Enterobacteriacea family, genus Salmonella, serological group D.
Salmonella are not-spore-forming rods and motile by peretrichous flagella (Fig.1). Like other enterobacteria, Salmonella have somatic (O) antigens which are lipopolysaccharide components of the cell wall and flagellar (H) antigens, which are proteins. There are approximately 60 O-antigens, which are designated by numbers at letters. The Kauffmann-White scheme categorizes Salmonella on the basis of somatic antigens, each group having a major determinant which is a strongly reaching somatic antigens and one or more major somatic antigen. Salmonella typhi also has a capsular or virulence (Vi) antigen composed of a homopolymer of N-acetyl galactosaminuronic acid. The presence of Vi-antigen on the cell surface may block agglutination by anti-O serum.
Fig.1. Salmonella typhi
Salmonella can be differentiated from other Enterobacteriaceae on basis of certain biochemical reactions, including fermentation. Most Salmonella ferment glucose and mannose to produce acid and gas but do not ferment lactose or sucrose; S.typhi does not produce gas. Thus, Salmonella typhi has some antigenic and biochemical features. That is why typhoid fever is isolated from the other diseases, caused by Salmonella. Salmonella organisms grow on the media with addition of bile. The resistance of agent of typhoid fever and paratyphoid in the environment is very high. They endure low temperatures very well. The agents of typhoid fever and paratyphoid diseases survive from 1-2 till 25-30 days, in food products.
Epidemiology
Typhoid fever is anthroponosis. The source of infection is sick man or bacteriocarrier. The patients with typhoid fever discharge the agent with stool, urine, rarely – with saliva and milk. The discharge of the agent is observed at the and of incubation period, during all disease, and sometimes in the period of reconvalescence. In some cases the discharge continues till three months (acute carriers) or more than three months (chronic carriers). Chronic carriers may be from six months till some years.
The mechanism of the infection transmission is fecal-oral. The factors of transmission may be water, milk, various food-stuffs and contaminated feces of the patient or bacterial carriers. Flies can play the supplementary role.
Susceptibility to agent of typhoid fever and paratyphoid diseases is rather high, however clinical manifestation can be of different grade. The care rate of typhoid fever and paratyphoid diseases depends on seasonal prevalence. It increases in summer-autumn period, due to consumption of a huge amount of flies, quite often from unknown sources, unwashed fruit and vegetables. The strong immunity develops after disease.
Pathogenesis
The next phases are distinguished in the pathogenesis of typhoid fever:
1. Penetration of the causative agent into the organism.
2. Development of lymphadenitis and lymphangitis.
3. Bacteremia
4. Intoxication.
5. Parenchymatous diffusion.
6. Discharge of the agent from the organism (excretory phase).
7. Allergic reaction, mainly, of lymphoid tissue of the small intestinum.
8. Formation of immunity.
The first phase is penetration of the agent in the macroorganism. However, penetration does not always lead to the development of the pathological process. It depends on the quantity of the agent and the state of barrier functions (stomach in this case). The further path of Salmonella typhi is lymphatic apparatus of intestine.
The second phase is lymphadenitis, lymphangitis. Salmonellae achieve the small intestine and actively penetrate into solitary follicules, Peyer’s patches. There is the reproduction of the agents and formation of the focus of infection. Microorganisms penetrate to regional lymphatic nodes (mesenterial) along the lymphatic patches. There is the other focus of infection. In the lymphatic apparatus, the typical morphological alterations with proliferation of tissue and formation the large typhoid cells develop.
Bacteria achieve the definite quantity and enter into the blood circulation through the thoracic duct. It is the next phase of pathogenesis – bacteremia. In clinic bacteremia means the end of incubation period and beginning of the clinical manifestations. The blood has bactericidal properties. It leads to the death of the part of microbes. Intoxicative syndrome develops. Intoxication is the fourth phase of pathogenesis. The action of endotoxins causes changes of the state of the central nervous system, adynamia, fever, headaches, violations of dream, appetite.
The fifth phase of a pathogenesis is parenchymatous diffusion of microbes. By the flow of the blood Salmonella of typhoid fever and paratyphoid also are delivered over the organism, enter into all organs. Microbes are fixated especially in liver, spleen, bone marrow, skin. Secondary focuses are formed (typhoid granulomas), from which bacteria likewise from the primary focuses (lymphatic apparatus of the intestine) enter into the blood, supporting bacteremia. The settling of microbes in the reticuloendothelial system and their destruction in the structures of reticuloendothelial system causes the cleaning of the organism from infection.
The sixth phase of pathogenesis is discharge of the agent from the organism. The agents enter into the intestine from the liver through the bile ducts. They are excreted into the external environment with feces of the patient. The part of the agents repeatedly penetrates from the small intestine into lymphatic apparatus of the intestine and cause sensibilization to microbes. The expressive changes of lymphoid tissue develop due to repeated implantation of Salmonella typhi with development of morphological changes from cerebral-like swelling to necrosis and formation of ulcers.
This process is considered as the seventh phase of pathogenesis – allergic
response of lymphoid tissue of the small intestine.
Eighth phase of pathogenesis is formation of immunity and restoration of the physiological equilibrium.
Pathological anatomy
Sequential changes in tissue in the ileocecal area of the intestinal tract occur during typhoid fever and have been classified into four phases:
1. hyperplasia;
2. necrosis and sloughing;
3. ulceration;
4. healing.
During the first week of clinical symptoms, hyperplastic changes occur in Peyer’s patches in the ileum and in lymphoid follicles in the cecum, causing there tissue to project into the bowel lumen. The hyperplasia regresses after 7-10 days or undergoes necrosis with sloughing of overlying mucosa leading to the formation of characteristic ulcers that parallel the long axis of the ileum (Fig.2). Small punctuate lesions develop in the cecum. Ulcers usually heal completely with little residual scarring, but they may be the sites of hemorrhage or may penetrate to the serosa and lead to bowel perforation.
Fig.2. Ulcers of ileum
Clinical manifestation
Typhoid fever and paratyphoid are characterized by cyclic course. There are such periods during course of the infectious process: incubation, initial, period of climax, early reconvalescence and outcomes.
The incubation period of typhoid fever is usually 10-14 days but it may be from to 21 days. The incubation period is influenced by the number of organisms ingested. The duration of incubation period also depends on virulence of microorganism and state of macroorganism.
Manifestations of enterocolitis occasionally occur within hours after the ingestion of food or drink contaminated with S. typhi if the dose of organisms is large. In these instances symptoms of nausea, vomiting and diarrhea usually resolve completely before the onset of symptoms of typhoid fever.
The onset of typhoid fever is insidious in contrast to sepsis produced by most other gram-negative organisms. The initial manifestations are nonspecific and consist of fever, malaise, anorexia, headache and myalgias. Remittent fever is prominent with gradually increasing evening temperature elevations from less than 38 °C to values in the range of 40 °C by the end of the first week of illness.
The disease turns into the next stage (climax of the disease) at the end of the first week. The appearance of the patients is very typical in this period. The skin is pale. Patient is apathethic. Intoxication is increased. Temperature is constant and most typical syndrome of typhoid fever and paratyphoid. At first the temperature was described by Vunderlish in 19 century. Temperature curve riminds trapezium. The phase of increase of the temperature is near one week. The phase of climax is near two weeks. The phase of decrease of the temperature is near one week. Temperature curve of Vunderlish occurs rarely. Temperature curve has wave-like character more frequently (temperature curve of Botkin).
Chills and diaphoreses are seen in about one-third of the patient even in the absence of antimicrobial therapy. Either constipation or diarrhea may occur. Respiratory symptoms, including cough and sore throat may be prominent. Neuropsychiatries manifestations, including confusion, dizziness, seizures, or acute psychotic behavior, may be predominant in an occasional case. Status typhosus is observed in serious course of the disease.
In present time patient with typhoid fever usually appears acutely ill. Fever is usually prominent, and in many instances the pulse is slow relative to the temperature.
In typhoid fever symptoms of violation of cardiovascular system are constant and expressive. The basis of hemodynamic disorder is violation of the tonus of the vessels, damage of heart muscle due to intoxication. Myocardiodystrophy develops as a result. In typhoid fever relative bradycardia is the clinical feature of cardiovascular disorders. The muffed heart sounds, systolic murmur at the heart apex, hypotension are marked inrarely. Relative bradycardia develops due to endotoxin action of the agent on X pair of cerebrospinal nerves.
Rose spots, 2-4 mm erythematous, maculopapular lesions that blanch on pressure, appear on the upper abdomen or on the lateral surface of the body. Roseolas are few (5-15) in number (Fig. 1). The lesions are transient and resolve in hours to days. Rose spots are observed on the 7-10 day of the disease near in half of patients. Sometimes they dissapears, sometimes exist longer than fever.
Cervical lymphoadenopathy may be present. Examination of the chest may reveal moist rales. The abdomen is tender, especially in the lower quadrants. Abdominal distention is common, and peristalsis is often hypoactive. The sensation of displacing air – and fluid-filled loops of bowel on palpating of the abdomen is considered to be characteristic. In percussion short sound is marked in ileocaecal area due to enlarged mesenteric lymphatic nodes (Padalka symptom).
Fig.3. Rose spots
Hepatomegaly is noted in about 40-50 % of the patient, and a soft, tender spleen can be palpated in about 40-60 %. In about 10 % of the patients, changes in consciousness are present and manifest as lethargy, delirium, or coma.
Without antimicrobial therapy, the disease pursues a prolonged course with slow resolution of signs and symptoms 3-4 weeks after onset if there are no complications. Sustained fever is common during the second and third weeks of disease. Fever decreases slowly by lysis, unlike the resolution by crisis seen in the preantibiotic era in many cases of pneumococcal pneumonia. Headache, confusion, respiratory symptoms, and abdominal pain and distention gradually resolve, and the pulse more characteristically reflects degree of fever acute manifestations subsiding. Profound weight loss invariably occurs in untreated patient. Many of the complications of typhoid fever occur during the period of resolution in the third or fourth week after onset.
Complications
Complications of typhoid fever can be classified as secondary to toxemia (myocarditis, hyperpyrexia, hepatic and bone marrow damage), secondary to local gastrointestinal lesions (haemorrhage and perforation), secondary to prolonged severe illness (suppurative parotitis decubiti, and pneumonia), secondary to growth and persistence of typhoid fever bacilli (relapse, localized infection – meningitis, endocarditis, osteomyelitis or arthritis – and secondary to therapy (bone marrow suppression, hypersensitive reactions and toxic shock).
In the preantimicrobial era, 12-16 % of the patients with typhoid fever died, frequently from complications in the third or fourth week of the disease. Fatalities still occur occasionally, probably in less than one percent of the patients receiving appropriate antimicrobial and pathogenetic therapy. However, in certain specific geographic areas of
The complications attributed to “toxemia” might be considered as manifestations of severe disease. Toxic myocarditis occur in severely ill patients, frequently children, and is manifested by tachycardia, weak pulse, muffled heart sounds, and hypotension. The electrocardiogram shows low voltage and T-wave flattening or inversion. Atrial or ventricular arrhythmia may occur.
Major intestinal hemorrhage is usually a late complication that occur during the second or third week of illness. In the preantimicrobial era, gross intestinal hemorrhage occurred in about 5-7 % of the patient with typhoid fever. The incidence of hemorrhage requiring transfusions has been reduced to 1 or 2 %, due to chloramphenicol use. There is an important sign of the massive intestinal hemorrhage symptom of “scissors” (Fig.4). Suddenly the temperature is decreased up to normal or subnormal. But tachycardia is observed. The arterial pressure is reduced. Intestinal perforation usually occurs during third week of illness. Perforation occurs in the terminal ileum where the number of lymphoid aggregates is the largest and ulcerations most frequent. In general, perforation has reported in recent years in one percent or less of cases as compared with 2-5 % in several series collected in the preantibiotic era.
Fig.4. Decreasing of temperature and tachycardia (“scissors” symptom)
Relapse, a recurrence of the manifestation of typhoid fever after initial clinical response, occur in about 8-12 % of the patient who have not received antimicrobial therapy. The relapse rate was found to be doubled in patients receiving chloramphenicol therapy for 2 weeks. Ampicillin probably does not affect the rate of relapse.
Localization of infection, which may lead to abscess formation, can occur in almost any organ or tissue. Although bacteremia can be assumed to develop in all patient with typhoid fever, localized infections such as meningitis, endocarditis, osteomyelitis, or thyroiditis occur in less then one percent.
The chronic carrier state is detained as documented excretion of S. typhi in stool or urine for a year or more. The chronic carrier state usually follows typhoid fever but as many as one – third of the chronic carriers give no history consistent with this illness. Underlying biliary or urinary tract diseases, especially with stone formation, increase the probability of the chronic enteric or urinary carrier state in patients with typhoid fever. One to 3 % of the patients with typhoid fever become chronic enteric carriers; however, the incidence is higher in older patients (at the sixth decade) and in women.
Clinical features of paratyphoids
Epidemiology, pathogens, morphology and clinics of paratyphoid A and B, have, in principal, mutual signs with typhoid fever. However, paratyphoids have some clinical features.
In paratyphoid A incubation period is shorter than in typhoid fever. It’s duration is 8-10 days. The onset of the disease is an acute. Sometimes, the onset of the disease is accompanied by cough, catarrh. Facial hyperemia, blood injection of the sclera’s vessels, herpes on the lips are observed during examination. The temperature is wave-like or remittent. The fever is accompanied by chills and than by diaphoreses. In paratyphoid A the rash appeares in more early periods than in typhoid fever. The rash is polymorphic. Roseolas, petechias and measles-like rash may be observed. The intoxication is temperate. There is no status typhosus. There is normal quantity of leukocytes in peripheral blood. But leukocytosis and lymphocytosis may occur too.
In majority of the patients the disease has a moderate course. But the severe forms may be observed too, with complications (intestinal hemorrhage, intestinal perforation and other). The relapses are frequently observed in case of paratyphoid A.
Paratyphoid B incubation period is 5-10 days. The onset of the disease is acute, with expressive chill, myalgia and diaphoreses. At the initial period of the disease the intoxication may be combined with symptoms of acute gastroenteritis. The temperature is not prolonged. Status typhosus is absent in majority of the patients. The symptoms of intoxication disappeares very quickly. The rash is polymorphic, plenty. It appears at the earlier period. In some cases the course of paratyphoid B may be severe with septic manifestations (purulent meningitis, meningoencephalitis, septicopyemia). In peripheral blood leukocytosis and neutrophylosis are observed.
Diagnosis
Definitive diagnosis of typhoid fever and paratyphoid is made on the basis of pathogen isolation from the patient’s blood. Isolation of the organism from stool, especially in endemic areas, does constitute strong presumptive evidence of typhoid fever in the patient with a typical clinical course. Serologic studies may be helpful, but in many cases of typhoid fever there is no increase in titer of agglutinins during the course of infection, and other illnesses, especially infections with other gram – negative bacilli, may cause nonspecific elevations of agglutinins because of cross – reaching antigens. In untreated disease only about 50 % of the patient have a fourfold or greater increase in titer of agglutinins (Vidal’s test) against typhoid fever 0 antigen at any time during the course of disease.
Antimicrobial therapy may also impede immunologic response. Immunization with typhoid fever vaccine may produce an impressive increase in titer of anti-0 agglutinins and nonspecific changes in titer may occur during the course of many febrile illnesses. Agglutinins against H antigen, irrespective of change of titer, are not of value in diagnosis. A number of other serodiagnostic methods, defection of IgM antibody to S. typhi lipopolysaccharide antigen by an enzymelinked immunosorbent assay (ELISA), are being studied and seen promising, but none is ready for routine diagnostic use.
The majority of isolates of S. typhi from blood are obtained as a result of the first blood culture, but a second or third culture should be collected in suspected cases, as these culture significantly improve the percentage of positives. Stool cultures become positive in about one – third to two – thirds of the patients during the second through fourth week of illness.
Differential diagnosis
The differential diagnosis of typhoid fever requires consideration of many disease processes characterized by fever and abdominal complaints.
Early in the disease the predominance of fever and upper respiratory tract symptoms may suggest influenza or other viral infections. Cough and fever suggest acute bronchitis and, when coupled with rales, raise the question of bacterial pneumonia. Headache, confusion, and fever may prompt consideration of bacterial or aseptic meningitis or meningoencephalitis. Delirium, catatonia, or coma may suggest a diagnosis of psychosis or other neuropsychiatries illness. The abdominal findings may lead to a consideration of acute appendicitis, acute cholecystitis, or intestinal infarction. Bacillary, amebic or ischemic colitis may enter the differential diagnosis if blood diarrhea occurs. As fever continues over a period of weeks, other possibilities might include brucellosis, yersinosis, lymphoma, inflammatory bowel disease, bacterial endocarditis, miliary tuberculosis, malaria, sepsis, epidemic typhus and many other diseases.
Treatment
Antibacterial therapy is indicated to all patients. The basic preparation is Levomycetin (Chloramfenicole) in tablets 0.5. It is indicated inside on 0.5 (4 times per day for half an hour before meal till the 10-th day of body temperature stabilization, a daily dose is reduced usually till 1.5 on the last 4 – 5 days of treatment. At severe course of illness it is possible to increase a daily dose gradually, on first days Levomycetin should be taken up to 3 gm, but not more. If using of the Levomycetin (PO) is impossible (a nausea, vomiting, a pain in epigastric area) Levomycetin succinate in bottles 0.5 (IM) daily dose 3 – 4 gm or in suppositoriums should be prescribed, and in serious cases intravenous or endolymphatic 0.5 – 1 ( 2 times in days) application.
When there is no effect after using of Levomycetin during next 5 days and there are contraindications, that is effective to prescribe Ampicillin till the 10-th day of normal body temperature. Alternative preparations may be Bactrim, Azitromicin (Sumamed) and fluoroquinolones preparations Ciprofloxacin and Ofloxacin to which steady to Levomycetin stames are sensitive. Also may be used cefalosporines of III generation: Cefoxim or Ceftriaxone.
To prevent relapses and formation of chronic bacteriocarrier the antibiotic therapy is desirable for carrying out in a complex with Vi-antigen, stimulating creation of specific immunity. Preparation of typhoid bacteria is injected on 400 mgm under a skin on 7 days interval or twice the same dose, or 800 mgm on 10 days interval.
Plentiful drinking, sorbents (SКN, VЕSТА), Sillard P, Enterodes are prescribed as desintoxication agents at mild disease course. Solution of glucose (IV) with solution of ascorbic acid, Qurtasault, Acesole, Lactasole, a solution of donor Albumin are injected at moderate disease course. If process has severe course, Reopolyglycin is injected both with polyionic colloid solutions at increasing of intoxication for 7 days, Prednisolonum 30-60 mg and more per day parenterally during 5–7 days. Oxybarotherapy, Plasmaferesis are indicated. Inhibitors of proteolytic enzymes – Contrical, Gordoxe, Trasylole should be prescribed.
Obligatory components of complex therapy are bed regime and diet № 2. For stimulation of nonspecific organism resistance and reparative process there are indicated Methyluracil, Pentoxil, Thimalin.
During antibiotic therapy the intestinal dysbacteriosis may be developed. Nistatin or Levorin one of bacterial preparations Bificol, Bifidumbacterin, Lactobacterin are indicated in such cases. If allergical reactions have appeared, Calcy gluconate, Dimedrol, Diprazin, Tavegil, Gismanal, Zestra, Loratidin, Alegra, Telfast are indicated.
A strict confinement to bed (position of the patient on back), cold on stomach region, forbiding reception of nutrition on 10 – 12 hours are necessary at intestinal bleeding. There are indicated ascorbic acid in tablets, Vicasole, Calcy chlorid, hypertonic solution of Sody chloride 5-10 mL (I.V.), Aminocapronicy acid, Etamsylat, Adroxone, Gelatinole, infusions of the donor blood, saline solutions.
The immediate surgical operation is indicated in case of intestinal wall perforation. Dofamin, high doses of Prednisolone, Reopolyglycin, Qurtasole or Lactasole in a vein trickle and then trickling (a single dose 0.05-0.15 gm, in serious cases up to 0.4 gm) in isotonic solution of Sodium chloridum, Contricali are indicated too in case of infectional-toxic shock.
Treatment of chronic bacteriocarrier is not developed. It is possible to achieve the time termination of allocation salmonelas by realization of 10-day’s course of treatment by Ampicillin in a daily dose of 2 gm in combination with immunostimalatores and di- or monovalent vaccine in a combination with cleared Vi-antigen.
Prophylaxis
Control of Salmonella typhi infection transmitted from person to person depends on high standards of personal hygiene, maintenance of a supply of uncontaminated water, proper sewage dispose and identification, treatment, and follow-up of chronic carriers. Hand washing is of paramount importance in controlling person – to person spread although hands of convalescent carriers are often contaminated after defecation detectable Salmonella are easily removed by washing the hands with soap and water.
Typhoid fever vaccine, a saline suspension of aceton or heat/phenol killed S. typhi enhances the resistance of human beings to infection with S. typhi under experimental and natural conditions. Vaccine efficacy ranges from 51 to 67 %.
There is also renewed interest in testing the capsular polysaccharide of S. typhi (Vi antigen) as a parenteral typhoid fever vaccine.
Typhoid fever vaccine should be considered for persons with intimate continuing exposure to a documented typhoid fever carrier and for persons traveling to areas where there is a recognized appreciable risk to exposure to typhoid fever.
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
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
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
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
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.
