Differential Diagnosis of Typhoid Fever

Infections to Consider

Malaria should always be ruled out first in patients with a history of fever returning from tropical areas within the last year, as it is a major cause of potentially fatal febrile illness in travelers returning from these areas 1
The American Society of Tropical Medicine and Hygiene recommends that malaria be considered in the differential diagnosis of febrile patients with a history of travel to endemic areas, due to its potential to cause severe disease 1
Dengue fever, which is common in Southeast Asia and South Asia, the same regions where typhoid is endemic, can cause high fever, headache, and malaise similar to typhoid, and may require PCR testing for diagnosis 1, 4
Tuberculosis, particularly miliary tuberculosis, can cause prolonged fever with a subacute or chronic onset, and should be considered especially in immunocompromised patients 5
Brucellosis, which can cause prolonged fever with a subacute or chronic onset, requires serologic testing for diagnosis if suspected 1, 5

The Infectious Diseases Society of America recommends that blood cultures (2-3 specimens) be performed before antibiotic administration, as they are the gold standard for diagnosing typhoid fever 4, 7
A complete blood count, including assessment for lymphopenia and thrombocytopenia, can help differentiate between typhoid, dengue, and malaria 1
Stool cultures for Salmonella, Shigella, Campylobacter, and Yersinia should be performed if diarrhea is present, as these pathogens can cause severe gastrointestinal disease 2, 6, 3

The Centers for Disease Control and Prevention recommend that thick blood smears be performed three times within 72 hours to rule out malaria, due to its potential to cause severe disease 1
Serologic tests, such as those for brucellosis and dengue, may be necessary if these infections are suspected, and should be guided by the patient's clinical presentation and epidemiologic history 1
PCR testing may be necessary for the diagnosis of dengue and other viral hemorrhagic fevers, and should be considered in patients with a compatible clinical presentation 1