Enteric Fever: Typhoid and Paratyphoid Fever

Infection with the gram-negative bacteria Salmonella enterica serotype Typhi ( S . Typhi) or S. enterica serotype Paratyphi A, B, or C ( S. Paratyphi A, B, or C) may result in a serious febrile illness known as enteric fever. The illness is called typhoid fever or paratyphoid fever once the causative agent has been identified. Pathogenic Salmonella bacteria causing invasive disease are a particular problem in parts of the world with poor sanitation and hygiene, as the disease is transmitted by food and water contaminated with human waste. In endemic areas, the estimated number of individuals with enteric fever at any one time may exceed 10 per 100,000 population. Cases reported in the United States, Canada, Western Europe, Australia, Japan, and other industrialized countries are relatively rare—usually acquired by travelers abroad and diagnosed when symptoms become manifest after return home. Enteric fever can be a mild uncomplicated illness with fever, headache, and malaise, or it can develop into a more severe life-threatening illness manifested by prolonged high fever as high as 39°C to 40°C (102°F to 104°F), prostration, hepatosplenomegaly, intestinal hemorrhage or perforation, and altered mental status. Children and older adults tend to experience more serious illness with infection, although persons in all age groups are susceptible. Infections caused by S . Typhi and S . Paratyphi cannot be distinguished from each other based on clinical presentation alone (which may be similar to that of other infectious diseases—such as malaria, dengue, leptospirosis, brucellosis, and typhus—causing fever in endemic regions), although paratyphoid fever tends to be a milder typhoid-like illness. The diagnosis is confirmed by isolation of the organism from blood, stool, urine, or other clinical specimens including bone marrow. The Widal-Felix agglutination reaction is still used as a test for typhoid fever in certain endemic countries but has relatively low sensitivity and specificity and should not be performed before the second week of illness. Rapid diagnostic tests (RDTs) for detecting typhoid with relatively high sensitivity and specificity have become commercially available in several countries where enteric fever is endemic and yield results that are more timely and less labor intensive than culture. Multidrug-resistant (MDR) typhoid strains resistant to chloramphenicol, ampicillin, and cotrimoxazole first appeared in the 1980s. In the 1990s and 2000s S . Typhi and S . Paratyphi strains with decreased susceptibility to fluoroquinolone antibiotics and to some cephalosporins emerged on the Indian subcontinent and in Southeast Asia and Central Asia, making treatment of serious infections more challenging. Among untreated typhoid patients the fatality rate can be as high as 20%. Approximately 5% of those with acute disease become chronic carriers. Efficacious vaccines against typhoid fever are available for the protection of travelers and for mass immunization programs of children residing in highly endemic areas, but a safe and effective vaccine against paratyphoid fever is not currently available.

A 29-year-old graduate student came to the university health center with complaints of fever, headache, stomachache, loss of appetite, and feeling weak over the previous 2 days. He and his wife had just returned a week earlier from a 2-week trip to Mumbai to visit his ailing father, who was in the hospital. The patient stated that he was generally healthy before the onset of his current illness and that the trip to India was unexpected, so neither he nor his wife received any pretravel health advice. His review of systems was remarkable for his report of general malaise, anorexia, diffuse abdominal discomfort, and no bowel movements in the previous 2 days. He denied shaking chills and sweats, stiff neck, photophobia, nausea and vomiting, or change in the color of his urine. Vital signs were blood pressure (BP) 116/78, temperature 103°F, pulse 96, and respiration 20. The patient was an ambulatory but ill-appearing Indian male accompanied by his wife. Physical exam was remarkable for a macular erythematous rash on the trunk that was barely visible against the patient’s natural skin tone; bowel sounds were present and abdominal exam showed mild tenderness to deep palpation in all four quadrants but no enlargement of liver and spleen; rectal exam was unremarkable and the stool guaiac test was negative. Blood samples were drawn for a complete blood count, blood chemistries, malaria smear, and blood cultures. Additional blood was drawn to perform a RDT for malaria, and an extra tube was drawn as an acute serum sample. A urine sample was sent for a urinalysis (UA) and a stool sample was sent for culture of enteric pathogens. The patient and his wife waited in clinic for the initial stat lab results. The blood count and white blood cell differential were within normal limits (WNL), the malaria smear and RDT test were reported negative; glucose, blood urea nitrogen (BUN), bilirubin, and electrolytes were WNL; the UA was normal; and cultures of blood and stool were pending. A presumed diagnosis of typhoid fever was made on the basis of the history of travel to a highly endemic area for enteric fever, the clinical presentation, and the preliminary laboratory results. Another blood sample was sent for culture, and the patient was started on an oral antibiotic regimen of azithromycin 1 g by mouth once daily for 7 days at the advice of an infectious diseases consultant. The patient was discharged to home with arrangements for daily telephone follow-up and a clinic follow-up appointment in 1 week. Three days after his discharge from the clinic, the lab reported that two out of three blood cultures were positive for S . Typhi but the stool culture was negative. The patient reported having no fever and feeling much better by day 4 on treatment. He was instructed to complete his antibiotic course and to return for his follow-up appointment.