Cox’s Conference: Enteric Fever

In last week’s Ambulatory Cox’s Conference, Dr. Roger Fan presented a case of a young female who presented with fevers, rash, and headache. Our expert discussant, Dr. James Luby guided us through the differential diagnosis for the constellation of symptoms – fever, rash, and headache.

In a patient with an acute presentation of fever, rash, and headache the differential diagnosis is broad and includes infectious, autoimmune, and drug-related reactions etiologies. It is important to elicit a thorough history from the patient including travel history, exposures (insects, animals, sick contacts), medications, immunization history, and immune status of the host. The patient had history of recent travel to Nepal to visit family. Our differential diagnosis in this patient included common viral illnesses (EBV, CMV, and HIV), tick-born illnesses (Rocky Mountain spotted fever, Ehrlichiosis/anaplasmosis, and Lyme disease), meningococcal infection, disseminated gonococcal infection, and travel related illnesses (Malaria, Dengue fever, Typhoid/paratyphoid (enteric fever), Zika and Chikungunya). The patient was diagnosed with Salmonella typhi (enteric fever).


Enteric Fever Pearls:

  • Classically caused by Salmonella enterica serotype Typhi, however other serotypes including S. enterica Paratyphi A, B, or C can cause a similar syndrome.1
  • Typhoid and enteric fever can be used interchangeably
  • More common in children and young adults
  • Most prevalent in poor areas with overcrowding and poor access to sanitation (south-central Asia, Southeast Asia, and southern Africa have the highest incidence of S. Typhi infection).
  • US has ~ 200-300 cases of S. Typhi per year (80% of these cases are in travels to countries where enteric fever is endemic). 2

Clinical Presentation:

  • Classic presentation includes fever, abdominal pain, constipation/diarrhea, “rose spots” (salmon-colored macules on trunk and abdomen), and headaches. Less common manifestations include cough, arthralgias/myalgias, intestinal perforation, and neurologic manifestations (encephalopathy, acute psychosis, myelitis, and disorded sleep patterns).1
  • Symptoms begin ~ 5-21 days after ingestion of the causative organism (typically through contaminated water or food).
  • Common laboratory derangements include cytopenias – anemia, leukopenia (leukocytosis more common in children), and elevated liver enzymes.


  • Must have high clinical suspicion in patients who have traveled to endemic areas.
  • Blood and stool cultures should be obtained. Blood cultures are 40-80% sensitive. Stool studies have a 30-40% sensitivity.1
  • Positive cultures can take several days to incubate, empiric therapy should be started in patients with a high clinical suspicion.
  • Serology testing can be performed, however positive results may represent prior exposure.


  • In patients with severe or complicated disease (organ dysfunction, systemic toxicity, or requires hospitalization), initial therapy with ceftriaxone is appropriate.3
  • In patients with uncomplicated disease who can be treated as an outpatient, fluroquinolone or azithromycin is first line.3
  • Multi-drug resistant strains of S.Typhi are prevalent worldwide. These strains can be commonly resistant to ampicillin, trimethoprim-sulfamethaxazole, and chloramphenicol. Increasing resistance to fluroquinolones is also a growing issue, particularly in South Asia.3



  1. Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med 2002; 347:1770.
  2. Lynch MF, Blanton EM, Bulens S, et al. Typhoid fever in the United States, 1999-2006. JAMA 2009; 302:859.
  3. Kariuki S, Gordon MA, Feasey N, Parry CM. Antimicrobial resistance and management of invasive Salmonella disease. Vaccine 2015; 33 Suppl 3:C21.

One thought on “Cox’s Conference: Enteric Fever”

  1. A few other clinical pearls about typhoid fever include that it is one of the classic infections with pulse-temperature dissociation (I.e. relative bradycardia along with fevers). Also the diagnostic test with best yield is bone marrow culture which is positive in over 90% of cases.

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