Clinical Pearls & Morning Reports
In a traveler with dietary and environmental exposures returning from Southeast Asia with undifferentiated fever, initial considerations include malaria, enteric (typhoid or paratyphoid) fever, scrub or murine typhus, leptospirosis, melioidosis, and diseases associated with arboviruses, such as dengue or Japanese encephalitis. Read the latest NEJM Clinical Problem-Solving Article here.
Q: What are some of the clinical manifestations of typhoid fever?
A: Typhoid fever is an infection caused by the gram-negative bacillus Salmonella typhi, which is transmitted through the fecal–oral route in areas with poor sanitation. Fever is the prominent symptom; it may be accompanied by other, nonspecific symptoms of insidious onset, including malaise, headache, nonproductive cough, and generalized abdominal discomfort. Diarrhea or constipation may occur during this period. Early findings on physical examination, such as a maculopapular “rose spot” rash on the torso and the arms and legs, hepatosplenomegaly, and coated tongue are inconsistently present. Pulse–temperature disassociation (relative bradycardia) is sometimes seen. Gastrointestinal bleeding, one of the most commonly reported complications, may develop after several weeks of illness and is caused by inflammation and necrosis of Peyer’s patches, the small intestinal sites of the organism’s entry. Intestinal perforation resulting from necrotizing lymphadenitis is a rare complication that is associated with a high fatality rate and merits urgent surgical intervention.
Q: Is the definitive diagnosis of typhoid fever easily made?
A: Definitive diagnosis of typhoid fever can be challenging, since the sensitivity of blood culture has been reported to be as low as 40% and that of urine or stool culture to be lower. Serologic tests for antibodies against S. typhi, such as the Widal test, are problematic, since a positive reaction in areas where the organism is endemic may represent previous infection. Given the challenges associated with laboratory diagnosis, prompt initiation of empirical antibiotic treatment is generally warranted for patients in whom typhoid fever is suspected, since this approach has been associated with improved outcomes.
A: The most commonly used oral agents for uncomplicated cases include fluoroquinolones (except in instances when the likelihood of resistance is thought to be high, which is particularly the case in patients who have traveled from southern Asia) and azithromycin. In one report, more than 90% of U.S. travelers returning from India and Bangladesh had either resistance or intermediate sensitivity to ciprofloxacin. For patients with severe illness, intravenous cephalosporins, such as ceftriaxone, are indicated. Although drug resistance is common in Southeast Asia, resistance to third-generation cephalosporins is rare. Most patients with uncomplicated disease have a good response to antibiotic therapy, although a small number have clinical relapse 2 or 3 weeks after symptom resolution and should be treated with an additional course of antibiotics.
A: Because antibiotic resistance is becoming particularly common, the prevention of typhoid fever remains critical. Patient counseling before travel should include discussion of frequent handwashing and strict hygiene practices with regard to the intake of food and water. The Centers for Disease Control and Prevention recommends vaccination (parenteral capsular polysaccharide or oral live-attenuated) against typhoid fever for travelers to areas in which S. typhi is endemic. Both forms of the vaccine have an estimated efficacy of approximately 50% in numerous international regions and 80% for U.S. travelers returning from Southeast Asia. Injectable and oral vaccines offer 2 and 5 years of protection, respectively; if longer-lasting immunity is required, booster immunization is recommended. The parenteral vaccine is not effective against the related, nearly indistinguishable illness of paratyphoid fever (which is caused by infection with S. enterica serotype paratyphi). Immunocompromised patients should not receive the live oral vaccine.