Typhoid fever

Typhoid fever is an acute anthroponous infectious disease with a fecal-oral transmission mechanism, characterized by a cyclical course, intoxication, bacteremia and ulcerative lesions of the lymphatic apparatus of the small intestine.

Typhoid fever is a systemic disease caused by S. typhi. Symptoms include high fever, prostration, abdominal pain, and a pink rash. Diagnosis is based on clinical presentation and confirmed by culture. Treatment is with ceftriaxone and ciprofloxacin.

ICD-10 code

A01.0. Typhoid fever.

Epidemiology of typhoid fever

Typhoid fever is classified as an intestinal infection and a typical anthroponotic disease. The source of infection is only a person - a patient or a bacteria excretor, from whose body the pathogens are excreted into the environment, mainly with feces, less often - with urine. The pathogen is excreted with feces from the first days of the disease, but massive excretion begins after the seventh day, reaches a maximum at the height of the disease and decreases during the recovery period. Bacterial excretion in most cases lasts no more than 3 months (acute bacterial excretion), but 3-5% develop chronic intestinal or, less often, urinary bacterial excretion. Urinary carriers are the most dangerous in epidemiological terms due to the massiveness of bacterial excretion.

Typhoid fever is characterized by the fecal-oral mechanism of pathogen transmission, which can be carried out by water, food, and contact-household routes. Transmission of the pathogen through water, which was prevalent in the past, plays a significant role today. Waterborne epidemics increase rapidly, but quickly end when the use of the contaminated water source is stopped. If epidemics are associated with the use of water from a contaminated well, the diseases are usually focal in nature.

Sporadic diseases are now often caused by drinking water from open reservoirs and industrial water used in various industrial enterprises. Outbreaks are possible associated with the consumption of food products in which typhoid bacteria can survive and multiply for a long time (milk). Infection can also occur through contact-household means, in which the transmission factors are surrounding objects. Susceptibility is significant.

The contagiousness index is 0.4. People aged 15 to 40 years are most often affected.

After the disease, a stable, usually lifelong immunity is developed, however, in recent years, due to antibiotic therapy of patients and its immunosuppressive effect, apparently, the intensity and duration of acquired immunity have become less, as a result of which the frequency of repeated typhoid fever cases has increased.

For typhoid fever, epidemic spread is characterized by a summer-autumn seasonality.

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What causes typhoid fever?

Approximately 400 to 500 cases of typhoid fever occur in the United States each year. Typhoid bacilli are excreted in the stool of asymptomatic carriers and people with active cases of the disease. Inadequate hygiene after defecation can spread S. typhi to public food and water supplies. In endemic areas, where sanitation is usually inadequate, S. typhi is transmitted primarily by water rather than food. In developed countries, the main route of transmission is foodborne, with organisms being introduced into food during preparation from healthy carriers. Flies can carry the organism from feces to food. Typhoid fever is sometimes transmitted directly (fecal-oral). This can occur in children during play and in adults during sex. Rarely, hospital personnel who do not take adequate precautions become infected while changing soiled bed linens.

The pathogen enters the human body through the gastrointestinal tract. Then it enters the blood through the lymphatic system. In acute cases of the disease, ulceration, bleeding and intestinal perforation may occur.

About 3% of untreated patients become chronic carriers. They retain the organism in their gallbladder and excrete it in their stool for more than 1 year. Some carriers have no history of clinical disease. Most of the estimated 2,000 carriers in the United States are elderly women with chronic biliary disease. Obstructive uropathy associated with schistosomiasis may predispose certain patients with typhoid fever to becoming urinary carriers. Epidemiologic data indicate that carriers are more likely to develop hepatobiliary cancer than the general population.

What are the symptoms of typhoid fever?

Typhoid fever has an incubation period (usually 8-14 days) that is inversely related to the number of organisms that enter the body. Typhoid fever usually has a gradual onset, with fever, headache, arthralgia, pharyngitis, constipation, anorexia, and abdominal pain and tenderness when palpating the abdomen. Less common symptoms of typhoid fever include dysuria, nonproductive cough, and epistaxis.

If typhoid fever is left untreated, body temperature rises stepwise over 2–3 days, remains elevated (usually 39.4–40°C) for the next 10–14 days, begins to decline gradually by the end of the 3rd week, and returns to normal values during the 4th week. Prolonged fever is usually accompanied by relative bradycardia and prostration. In acute cases of the disease, central nervous system symptoms such as delirium, stupor, and coma occur. In approximately 10% of patients, a discrete, pink, pale rash (pink spots) appears on the surfaces of the chest and abdomen. These lesions appear during the 2nd week of the disease and disappear within 2–5 days. Splenomegaly, leukopenia, liver dysfunction, proteinuria, and mild consumption coagulopathy are common. Acute cholecystitis and hepatitis may occur.

In later stages of the disease, when gastrointestinal lesions become more prominent, bloody diarrhea may occur and the stool may contain blood (20% occult blood and 10% overt blood). Approximately 2% of patients develop acute bleeding during the 3rd week of illness, with a mortality rate of about 25%. The acute abdomen and leukocytosis during the 3rd week of illness suggest intestinal perforation. The injury usually involves the distal ileum. It occurs in 1-2% of patients. Pneumonia may develop during the 2nd or 3rd week of illness. It is usually due to secondary pneumococcal infection, but S. typhi can also cause pulmonary infiltrates. Bacteremia occasionally leads to focal infections such as osteomyelitis, endocarditis, meningitis, soft tissue abscesses, glomerulitis, or genitourinary tract involvement. Atypical presentations of infection such as pneumonitis, fever without other symptoms, or symptoms consistent with urinary tract infections may result in delayed diagnosis. Recovery may take several months.

In 8-10% of untreated patients, typhoid fever symptoms similar to the initial clinical syndrome disappear after 2 weeks of temperature decline. For unknown reasons, early treatment of typhoid fever with antibiotics increases the incidence of recurrent fever by 15-20%. In contrast to the slow temperature decline during the initial disease, when fever recurs, the temperature drops rapidly if antibiotics are given again. In some cases, fever recurs.

How is typhoid fever diagnosed?

Typhoid fever must be differentiated from the following diseases: other Salmonella infections, major rickettsioses, leptospirosis, disseminated tuberculosis, malaria, brucellosis, tularemia, infectious hepatitis, psittacosis, Yersinia enterocolitica infection, and lymphoma. In the early stages, the disease may resemble influenza, viral upper respiratory tract infections, or urinary tract infections.

Blood, stool, and urine cultures should be obtained. Blood cultures are usually positive only during the first 2 weeks of illness, but stool cultures are usually positive for 3-5 weeks. If these cultures are negative and typhoid fever is suspected, the MO may order cultures of a bone biopsy specimen.

Typhoid bacilli contain antigens (O and H) that stimulate antibody production. A fourfold increase in antibody titers to these antigens in paired specimens collected 2 weeks apart suggests infection with S. typhi. However, this test has only moderate sensitivity (70%) and lacks specificity. Many nontyphoidal salmonellae cross-react, and cirrhosis may produce false-positive results.

How is typhoid fever treated?

Without antibiotics, the mortality rate reaches about 12%. Timely treatment can reduce the mortality rate to 1%. Most deaths occur among weakened patients, infants and the elderly. Stupor, coma and shock indicate a serious illness, with a poor prognosis. Complications mainly occur in those patients who do not receive treatment for typhoid fever, or their treatment is delayed.

Typhoid fever is treated with the following antibiotics: ceftriaxone 1 g/kg intramuscularly or intravenously twice daily (25-37.5 mg/kg for children) for 7-10 days and various fluoroquinolones (eg, ciprofloxacin 500 mg orally twice daily for 10-14 days, gatifloxacin 400 mg orally or intravenously once daily for 14 days, moxifloxacin 400 mg orally or intravenously for 14 days). Chloramphenicol 500 mg orally or intravenously every 6 hours is still widely used, but resistance is increasing. Fluoroquinolones can be used in children. Alternative drugs, the use of which depends on the results of in vitro susceptibility testing, include amoxicillin 25 mg/kg orally 4 times a day, trimethoprim-sulfamethoxazole 320/1600 mg twice a day or 10 mg/kg twice a day (based on the trimethoprim component), and azithromycin 1.00 g on the first day of treatment and 500 mg once a day for 6 days.

In addition to antibiotics, glucocorticoids can be used to treat acute intoxication. Such treatment is usually followed by a decrease in temperature and improvement in the clinical condition. Prednisolone 20-40 mg orally once a day (or equivalent glucocorticoid) given for 3 days is usually sufficient for treatment. Higher doses of glucocorticoids (dexamethasone 3 mg/kg intravenously at the beginning of therapy, and then 1 mg/kg every 6 hours for 48 hours) are used for patients with severe delirium, coma, and shock.

Feedings should be frequent and small. Patients should be kept in bed until fever has subsided below febrile levels. Salicylates, which can cause hypothermia, hypotension, and edema, should be avoided. Diarrhea can be minimized by giving a liquid diet only; parenteral nutrition may be needed for a time. Fluid, electrolyte, and blood replacement therapy may be needed.

Intestinal perforation and associated peritonitis require surgical intervention and expanded antibiotic coverage of gram-negative flora and bacteroids.

Relapses of the disease are treated in the same way, but antibiotic treatment in cases of relapse rarely lasts more than 5 days.

If typhoid fever is suspected in a patient, the local health department should be notified and patients should be kept away from food preparation until evidence has been obtained that they are free of typhoid fever. Typhoid bacilli can be detected for 3-6 months after an acute illness, even in people who do not subsequently become carriers. Therefore, after this period, 3 negative stool cultures should be obtained at weekly intervals to exclude carriage.

Carriers without biliary tract disease should receive antibiotics. The cure rate with amoxicillin 2 g orally 3 times daily for 4 weeks is about 60%. In some carriers with gallbladder disease, eradication can be achieved with trimethoprim-sulfamethoxazole and rifampin. In other cases, cholecystectomy is effective. Before cholecystectomy, the patient should receive antibiotics for 1-2 days. After surgery, antibiotics are also prescribed for 2-3 days.

How to prevent typhoid fever?

Typhoid fever can be prevented if drinking water is purified, milk is pasteurized, chronic carriers are not allowed to handle food, and sick people are adequately isolated. Particular attention should be paid to precautions against the spread of enteric infections. Travelers in endemic areas should avoid eating raw vegetables, food stored and served at room temperature, and untreated water. Water should be boiled or chlorinated before use unless it is known to be safe for consumption.

There is a live attenuated oral typhoid vaccine (strain Ty21a). This typhoid vaccine is approximately 70% effective. It is given every other day. A total of 4 doses are given. Since this vaccine contains live microorganisms, it is contraindicated in immunocompromised patients. In the United States, this vaccine is most often used in children under 6 years of age. An alternative vaccine is the Vi polysaccharide vaccine. It is given as a single dose, intramuscularly, has an effectiveness of 64-72%, and is well tolerated.