Typhoid Fever

For typhoid fever, the incubation period (usually 8 to 14 days) is inversely related to the number of organisms ingested. Onset is usually gradual, with fever, headache, arthralgia, pharyngitis, constipation, anorexia, and abdominal pain and tenderness. Less common symptoms include dysuria, nonproductive cough, and epistaxis.

Without treatment, the temperature rises in steps over 2 to 3 days, remains elevated (usually 39.4 to 40° C) for another 10 to 14 days, begins to fall gradually at the end of the third week, and reaches normal levels during the fourth week. Prolonged fever is often accompanied by relative bradycardia and prostration. Central nervous system symptoms such as delirium, stupor, or coma occur in severe cases. In uncomplicated cases, 5 to 30% of patients may have discrete, pink, blanching lesions (rose spots) in crops on the chest and abdomen during the second week and resolve in 2 to 5 days.

Splenomegaly, leukopenia, anemia, liver function abnormalities, proteinuria, and a mild consumption coagulopathy are common. Acute cholecystitis and hepatitis may occur.

Typhoid Fever (Rose Spots)

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This photo shows discrete, pink, blanching lesions called rose spots (arrows). Rose spots appear in crops on the chest and abdomen in some people who have typhoid fever.

Photo courtesy of Charles N. Farmer, Armed Forces Institute of Pathology, via the Public Health Image Library of the Centers for Disease Control and Prevention.

Late in the disease, when intestinal lesions are most prominent, florid diarrhea may occur, and the stool may contain blood (occult in 20% of patients, gross in 10%). In about 2% of patients, severe bleeding occurs during the third week, with a high case fatality rate (1). An acute abdomen and leukocytosis during the third week may suggest intestinal perforation, which usually involves the distal ileum and occurs in 1 to 2% of patients.

Pneumonia may develop during the second or third week and may be due to secondary pneumococcal infection, although S. Typhi itself can also cause pneumonia. Bacteremia occasionally leads to focal infections such as osteomyelitis, endocarditis, meningitis, soft-tissue abscesses, glomerulitis, or genitourinary tract involvement.

Atypical presentations of typhoid fever, such as pneumonitis, fever only, or, very rarely, symptoms consistent with urinary tract infection, may delay diagnosis.

Convalescence may last several months.

In up to 10% of untreated patients with typhoid fever, symptoms and signs similar to the initial clinical syndrome recur about 2 weeks after defervescence (1). For unclear reasons, antibiotic therapy during the initial illness often increases the incidence of febrile relapse. If antibiotics are restarted at the time of relapse, the fever abates rapidly, unlike the slow defervescence that occurs during the primary illness. Occasionally, a second relapse occurs.

• Cultures

Typhoid fever should be considered in patients with fever in or those returning from endemic areas, particularly if fever has lasted more than 3 days or there is diarrhea, abdominal pain, or constipation.

Cultures of blood, stool, and urine should be obtained. Because drug resistance is common, standard susceptibility testing is essential. The nalidixic acid susceptibility screening test is not recommended because it does not reliably predict susceptibility to ciprofloxacin. Blood cultures are usually positive only during the first 2 weeks of illness and are not highly sensitive, but stool cultures are usually positive during the third to fifth weeks. If these cultures are negative and typhoid fever is strongly suspected, culture from a bone marrow biopsy specimen (which is highly sensitive) may reveal the organism.

Typhoid bacilli contain antigens O and H that stimulate the host to form corresponding antibodies. A 4-fold rise in O and H antibody titers in paired specimens obtained 2 weeks apart suggests S. Typhi infection (Widal test). However, this test is only moderately (70%) sensitive and lacks specificity (1); many nontyphoidal Salmonella strains cross-react, and liver cirrhosis causes false-positives.

Other infections causing a similar presentation to that of typhoid fever include other Salmonella infections, the major rickettsioses, leptospirosis, disseminated tuberculosis, malaria, brucellosis, tularemia, infectious hepatitis, psittacosis, Yersinia enterocolitica infection, and lymphoma.

Antibiotic resistance is common and increasing, particularly in endemic areas, so susceptibility testing should guide antibiotic selection.

In general, preferred antibiotics include

• Fluoroquinolones for 7 to 10 days

Nutrition should be maintained with frequent feedings. While febrile, patients are usually kept on bed rest. Salicylates (which may cause hypothermia and hypotension), as well as laxatives and enemas, should be avoided. Diarrhea may be minimized with a clear liquid diet; parenteral nutrition may be needed temporarily. Fluid and electrolyte therapy and blood replacement may be needed.

Intestinal perforation and associated peritonitis call for surgical intervention and broad gram-negative and anti–Bacteroides fragilis coverage.

Relapses are treated the same as the initial illness, although duration of antibiotic therapy seldom needs to be > 5 days.

Patients must be reported to the local health department and prohibited from handling food until proven free of the organism. Typhoid bacilli may be isolated for as long as 3 to 12 months after the acute illness in people who do not become carriers. Thereafter, 3 stool cultures at monthly intervals must be negative to exclude a carrier state.

Without antibiotics, the case fatality rate is about 10 to 15%. With prompt therapy, the case fatality rate is 1% (1). Most deaths occur in people who are undernourished, infants, and older adults.

Stupor, coma, or shock reflects severe disease and a poor prognosis.

Complications occur mainly in patients who are untreated or in whom treatment is delayed.

Drinking water should be purified, and sewage should be disposed of effectively.

Chronic carriers should avoid handling food and should not provide care for patients or young children until they are proved free of the organism; adequate patient isolation precautions should be implemented. Special attention to enteric precautions is important.

Travelers in endemic areas should avoid ingesting raw leafy vegetables, other foods stored or served at room temperature, and untreated water (including ice cubes). Unless water is known to be safe, it should be boiled or chlorinated before drinking.