Author(s): Mary Elizabeth Wilson

Fever often accompanies serious illness in returned travelers. The most common life-threatening tropical disease associated with fever in returned travelers is malaria. Because an increased temperature can signal a rapidly progressive infection, initiate early evaluation, especially in people who have visited areas with malaria in recent months (see Sec. 5, Part 3, Ch. 16, Malaria).

The initial focus in evaluating a febrile returned traveler should be on identifying infections that are potentially life-threatening, treatable, or transmissible. In some instances, public health officials must be alerted if the traveler was possibly contagious while traveling or infected with a pathogen of public health concern (e.g., Ebola virus, yellow fever virus) at the origin or destination. During an outbreak (e.g., the Ebola epidemic in West Africa), special screening protocols could be needed. A specific cause for fever might not be identified in ≥25% of returned travelers.

Narrowing the Differential Diagnosis

Most illnesses in returned travelers (e.g., diarrhea, pneumonia, or pyelonephritis) are caused by common and cosmopolitan infections that must be considered along with the more unusual ones. Because the geographic area of travel determines the relative likelihood of major causes of fever, identifying where the febrile patient traveled and/or lived is essential (see Table 11-09). Ask about travel-related activities (e.g., cave exploration, dental or medical care, sexual activity, newly acquired tattoos); exposures (e.g., animal bites, freshwater exposure in schistosomiasis-endemic areas); and living arrangements (e.g., dwelling type, use of mosquito nets, air conditioning, window screens), any of which might elicit useful clues. Pretravel preparation (e.g., vaccinations, malaria prophylaxis) will markedly reduce (although not eliminate) the likelihood of some infections, so this is also a relevant part of the history.

Because each infection has a characteristic incubation period (the range is extremely wide for some), define timing of exposure for different geographic areas; this can help exclude some infections from the differential diagnosis. Most serious febrile infections manifest within the first month after return from tropical travel, yet infections related to travel exposures occasionally occur months or even >1 year after return. In the United States, >90% of reported cases of Plasmodium falciparum malaria manifest ≤30 days of return, but almost half of cases of P. vivax malaria manifest >30 days after return.

Findings Requiring Urgent Attention

Presence of fever plus certain associated signs, symptoms, or laboratory findings can suggest specific infections (see Table 11-10). Findings that should prompt urgent attention include hemorrhage, low blood pressure, altered consciousness, and high respiratory rate. Even if an initial physical examination is unremarkable, repeat the exam if the diagnosis is not clear, because new findings might appear that will help in the diagnostic process (e.g., skin lesions, a tender liver). Although most febrile illnesses in returned travelers are related to infections, bear in mind that other conditions, including pulmonary emboli and drug hypersensitivity reactions, also can be associated with fever.

Fever accompanied by a syndrome (see Table 11-11) deserves further scrutiny, because it could indicate a disease of public health concern, for which immediate infection containment and control measures are indicated.

Travelers visiting friends and relatives (VFR) often do not seek pretravel medical advice and are at greater risk for some diseases than other travelers. GeoSentinel Surveillance Network data showed that a larger proportion of VFR travelers than tourist travelers presented with serious (requiring hospitalization), potentially preventable travel-related illnesses (see Sec. 9, Ch. 9, Visiting Friends & Relatives: VFR Travel).

Changes Over Time

Clinicians have access to online resources that provide information about geographic-specific risks, disease activity, and other useful information (e.g., drug-susceptibility patterns for pathogens). Infectious disease outbreaks are dynamic, as demonstrated by the Ebola epidemics in West Africa, spread of chikungunya virus in the Americas beginning in late 2013, nosocomial spread of travel-associated Middle East respiratory syndrome in Korea in 2015, the rapid spread of Zika virus in the Americas in 2015 and 2016, and the global spread of coronavirus disease 2019 (COVID-19). In contrast, because of the wide use of vaccine, hepatitis A infection is now infrequently seen in US travelers.

Infections with typical seasonal transmission in the United States might occur at different times of the year, or throughout the year in the tropics and subtropics. For example, influenza transmission can occur throughout the year in tropical areas, and the peak season in the Southern Hemisphere is late spring/early summer into the fall; clinicians in the Northern Hemisphere should be alert to the possibility of influenza outside the usual wintertime influenza season.

Travelers can become colonized or infected by bacteria resistant to commonly used antibiotics (see Sec. 11, Ch. 5, Antimicrobial Resistance). Bacteria that produce extended-spectrum β-lactamases and carbapenem-resistant Enterobacterales, including bacteria expressing the metalloprotease NDM-1, have been found in infections acquired during travel, sometimes related to elective or emergency medical care. Travelers to South and Southeast Asia are at high risk of acquiring multidrug-resistant Enterobacterales. Enteric fever (typhoid or paratyphoid fever) has become increasingly resistant to fluoroquinolones, third-generation cephalosporins, and azithromycin, especially in Asia (see Sec. 5, Part 1, Ch. 24, Typhoid & Paratyphoid Fever).

Clinical Tips

For more clinical tips about fever in returning travelers, see Box 11-01.