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 3rd week, and reaches normal levels during the 4th 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 about 10 to 20% of patients, discrete, pink, blanching lesions (rose spots) appear in crops on the chest and abdomen during the 2nd 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.

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 3rd week, with a case fatality rate of about 25%. An acute abdomen and leukocytosis during the 3rd week may suggest intestinal perforation, which usually involves the distal ileum and occurs in 1 to 2% of patients.

Pneumonia may develop during the 2nd or 3rd 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 8 to 10% of untreated patients with typhoid fever, symptoms and signs similar to the initial clinical syndrome recur about 2 weeks after defervescence. For unclear reasons, antibiotic therapy during the initial illness increases the incidence of febrile relapse to 15 to 20%. 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 2nd relapse occurs.

Other infections causing a similar presentation to that of typhoid fever include other Salmonella infections Nontyphoidal Salmonella Infections Nontyphoidal salmonellae are gram-negative bacteria that primarily cause gastroenteritis, bacteremia, and focal infection. Symptoms may be diarrhea, high fever with prostration, or symptoms... read more , the major rickettsioses Overview of Rickettsial and Related Infections Rickettsial diseases (rickettsioses) and related diseases (anaplasmosis, ehrlichiosis, Q fever, scrub typhus) are caused by a group of gram-negative, obligately intracellular coccobacilli. All... read more , leptospirosis Leptospirosis Leptospirosis is an infection caused by one of several pathogenic serotypes of the spirochete Leptospira. Symptoms are biphasic. Both phases involve acute febrile episodes; the second... read more , disseminated tuberculosis Extrapulmonary Tuberculosis (TB) Tuberculosis outside the lung usually results from hematogenous dissemination. Sometimes infection directly extends from an adjacent organ. Symptoms vary by site but generally include fever... read more , malaria Malaria Malaria is infection with Plasmodium species. Symptoms and signs include fever (which may be periodic), chills, rigors, sweating, diarrhea, abdominal pain, respiratory distress, confusion... read more , brucellosis Brucellosis Brucellosis is caused by Brucella species, which are gram-negative bacteria. Symptoms begin as an acute febrile illness with few or no localized signs and may progress to a chronic stage... read more , tularemia Tularemia Tularemia is a febrile disease caused by the gram-negative bacterium Francisella tularensis; it may resemble typhoid fever. Symptoms are a primary local ulcerative lesion, regional lymphadenopathy... read more , infectious hepatitis Overview of Acute Viral Hepatitis Acute viral hepatitis is diffuse liver inflammation caused by specific hepatotropic viruses that have diverse modes of transmission and epidemiologies. A nonspecific viral prodrome is followed... read more , psittacosis Community-Acquired Pneumonia Community-acquired pneumonia is defined as pneumonia that is acquired outside the hospital. The most commonly identified pathogens are Streptococcus pneumoniae, Haemophilus influenzae... read more , Yersinia enterocolitica infection Other Yersinia Infections Plague is caused by the gram-negative bacterium Yersinia pestis. Symptoms are either severe pneumonia or large, tender lymphadenopathy with high fever, often progressing to septicemia... read more , and lymphoma Overview of Lymphomas Lymphomas are a heterogeneous group of tumors arising in the reticuloendothelial and lymphatic systems. The major types are Hodgkin lymphoma Non-Hodgkin lymphoma See table . Lymphomas were once... read more .

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 no longer recommended because it no longer reliably predicts susceptibility to ciprofloxacin. Blood cultures are usually positive only during the first 2 weeks of illness, but stool cultures are usually positive during the 3rd to 5th weeks. If these cultures are negative and typhoid fever is strongly suspected, culture from a bone marrow biopsy specimen 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; many nontyphoidal Salmonella strains cross-react, and liver cirrhosis causes false-positives.

Without antibiotics, the case fatality rate is about 12%. With prompt therapy, the case fatality rate is 1%. Most deaths occur in malnourished people, infants, and older people.

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.

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

In general, preferred antibiotics include

Chloramphenicol 500 mg orally or IV every 6 hours is still widely used, but resistance is increasing.

Fluoroquinolones may be used in children, but caution is required. For fluoroquinolone-resistant strains, azithromycin 1 g orally on day 1, then 500 mg once a day for 6 days can be tried. Resistance rates to alternative therapies (eg, amoxicillin, trimethoprim/sulfamethoxazole [TMP/SMX]) are high, so use of these drugs depends on in vitro sensitivity.

Corticosteroids may be added to antibiotics to treat severe toxicity. Defervescence and clinical improvement usually follow. Prednisone 20 to 40 mg orally once a day (or equivalent) for the first 3 days of treatment usually suffices. Higher doses of corticosteroids (dexamethasone 3 mg/kg IV initially, followed by 1 mg/kg IV every 6 hours for 48 hours total) are used in patients with marked delirium, coma, or shock.

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 broader 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.

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.