TYPHOID FEVER AND PARATYPHOID

Typhoid fever, paratyphoid A and  are 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.

Historic reference

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 20th century in all countries of the world, especially in the large towns due to groupment of the people. 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. 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-0 serum.

Salmonella can be differentiated from other Enterobacteriaceae on basis of certain biochemical reactions, including fermentation. Most Salmonella ferment

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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 end 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 into 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 (It is stomach in this case). The further path of Salmonella typhi is lymphatic apparatus of intestine.

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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.

Anatomic pathology

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 the lymphoid follicles in the cecum, causing

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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. 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.

Clinical manifestations

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 7 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 °Ñ to values in the range of 40 °Ñ 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 Wunderlich in 19th 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 Wunderlich 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.

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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. 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

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appropriate antimicrobial and pathogenetic therapy. However, in certain specific geographic areas of Indonesia, India, and Nigeria, fatality rations of 9-32 % have been reported last 10-15 years. It is likely that these results are consequent to suboptimal health and medical care rather that an increase in the clinical severity of typhoid fever.

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 percent, due to chloramphenicol use. There is an important sign of the massive intestinal hemorrhage symptom of "scissors". 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.

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 paratyphoid

Epidemiology, pathogens, morphology and clinics of paratyphoid A and B, have, in principal, mutual signs with typhoid fever. However, paratyphoids have some clinical features.

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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 measleslike 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  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  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 (Widal's test) against typhoid fever O-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-O-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, e.g., detection 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.

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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

Antibacterial1 therapy is indicated to all patients. The basic preparation is levomycetin (chloramfenicole) in tablets 0.5. It is administered per os (PO) in dose of 0.5 gm (4 times per day) for half an hour before meal till the 10th 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 should be prescribed -0.5 intramuscularly (IM) daily dose 3-4 gm or in suppositoriums, 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 10th day of normal body temperature. Alternative remedies are bactrim, azitromicin (sumamed) and fluoroquinolones derivates ciprofloxacin and ofloxacin, which are effective in case of tolerance to levomycetin. Also cefalosporines of III generation: cefoxim or ceftriaxone may be used.

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

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mg threefold under a skin with 7 days interval or twice the same dose, or 800 mg with 10 days interval.

Plentiful drinking, sorbents (SKN, VesTa), sillard P, enterodes are prescribed as desintoxication agents at mild disease course. Solution of glucose intravenously (IV) with solution of ascorbic acid, qurtasault, acesault, lactasault, 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 ¹ 2. For stimulation of nonspecific organism resistance and reparative process methyluracil, pentoxil, thimalin are indicated

During antibiotic therapy the intestinal dysbacteriosis may develop. Nistatin or levorin, one of bacterial remedies bificol, bifidumbacterin, lactobacterin are indicated in such cases. If allergical reactions have appeared, calcii gluconate, dimedrol, di prazin, tavegil, gismanal, zestra, loratidin, alegra, telfast are indicated.

A strict confinement to bed (position of the patient on back), cold on stomach region, forbiding of feeding for 10-12 hours are necessary in case of intestinal bleeding. Ascorbic acid in tablets, Vicasole, calcy chlorid, hypertonic solution of sodii chloride 5-10 mL (IV), an aminocapronicy acid, etamsylat, adroxone, gelatinole, infusions of the donor blood, saline solutions are indicated in such case.

The immediate surgical operation is indicated in case of intestinal wall perforation. In case of infectional-toxic shock, dofamin, high doses of prednisolone, reopolyglycin, quartasault or lactasault in a vein (a single dose 0.05-0.15 gm, in serious cases up to 0.4 gm) in isotonic solution of sodii chloridum, contrical are indicated.

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 a 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 %.

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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.

Control questions:

1. Epidemiology of typhoid fever and paratyphoid.

2. Phases of typhoid fever pathogenesis.

3. Clinic of initial period of typhoid fever.

4. Clinical manifestations of acute phase.

5. Clinical manifestations of paratyphoid fever.

6. Clinical classification of typhoid fever.

7. Specific and nonspecific complications.

8. Clinic of the intestinal bleeding and its medical treatment.

9. Clinic of bowel perforation, tactician of doctor.

10. Changes in the clinical blood test due to typhoid fever.

11. Differential diagnosis of typhoid fever.

12. Laboratory diagnosis of typhoid fever.

13. Blood collection for hemoculture.

14. Collection of material for ñîðãî- and urine culture.

15. Antibacterial therapy of typhoid fever.

16. Pathogenetic therapy of typhoid fever and paratyphoid.

18. Antiepidemic measures in the place of typhoid fever outbreak.

19. Prophylaxis of typhoid fever.

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Date: 2014-12-21; view: 1175