Fever in Returned Travelers
Fever commonly accompanies serious illness in returned travelers. Because it can signal a rapidly progressive infection such as malaria, the clinician must initiate early evaluation, especially in people who have visited areas with malaria in recent months (see Chapter 3, Malaria). The initial focus in evaluating a febrile returned traveler should be on identifying infections that are rapidly progressive, treatable, or transmissible. In some instances, public health officials must be alerted if the traveler may have been contagious while traveling or infected with a pathogen of public health importance (such as yellow fever or Ebola) at the origin or destination.
Use of History, Location of Exposure, and Incubation to Limit Differential Diagnosis
Often the list of potential diagnoses is long, but multiple recent studies help to identify more common diagnoses. A large proportion of illnesses in returned travelers is caused by common, cosmopolitan infections (such as bacterial pneumonia or pyelonephritis), so these must be considered along with unusual infections. Because the geographic area of travel determines the relative likelihood of major causes of fever, it is essential to identify where the febrile patient has traveled and lived (Table 5-2). Details about activities (such as freshwater exposure in schistosomiasis-endemic areas, animal bites, sexual activities, tattoos, or local medical care with injections) and accommodations in areas with malaria (bed nets, window screens, air conditioning) during travel may provide useful clues. Preparation before travel (such as hepatitis A vaccine or yellow fever vaccine) will markedly reduce the likelihood of some infections, so this is a relevant part of the history. A history of travel and residence should be an integral part of every medical history.
|Geographic Area||Common Tropical Disease Causing Fever||Other Infections Causing Outbreaks or Clusters in Travelers|
|Caribbean||Chikungunya, dengue, malaria (Haiti), Zika||Acute histoplasmosis, leptospirosis|
|Central America||Chikungunya, dengue, malaria (primarily Plasmodium vivax ), Zika||Leptospirosis, histoplasmosis, coccidioidomycosis|
|South America||Chikungunya, dengue, malaria (primarily P. vivax ), Zika||Bartonellosis, leptospirosis, enteric fever, histoplasmosis|
|South-central Asia||Dengue, enteric fever, malaria (primarily non-falciparum)||Chikungunya|
|Southeast Asia||Dengue, malaria (primarily non-falciparum)||Chikungunya, leptospirosis|
|Sub-Saharan Africa||Malaria (primarily P. falciparum ), tickborne rickettsiae (main cause of fever in southern Africa), acute schistosomiasis, dengue||African trypanosomiasis, chikungunya, enteric fever, filariasis|
Because each infection has a characteristic incubation period (although the range is extremely wide with some infections), the time of exposures needs to be defined in different geographic areas (Table 5-3). This knowledge will allow the clinician to 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 can occasionally occur months or even >1 year after return. In the United States, >90% of reported cases of Plasmodium falciparum malaria manifest within 30 days of return, but almost half of cases of P. vivax malaria manifest >30 days after return.
|Disease||Usual Incubation Period (Range)||Distribution|
|Incubation <14 Days|
|Chikungunya||2–4 days (1–14 days)||Tropics, subtropics|
|Dengue||4–8 days (3–14 days)||Tropics, subtropics|
|Encephalitis, arboviral (Japanese encephalitis, tickborne encephalitis, West Nile virus, other)||3–14 days (1–20 days)||Specific agents vary by region|
|Enteric fever||7–18 days (3–60 days)||Especially in Indian subcontinent|
|Acute HIV infection||10–28 days (10 days to 6 weeks)||Worldwide|
|Influenza||1–3 days||Worldwide, can also be acquired while traveling|
|Legionellosis||5–6 days (2–10 days)||Widespread|
|Leptospirosis||7–12 days (2–26 days)||Widespread, most common in tropical areas|
|Malaria, Plasmodium falciparum||6–30 days (98% onset within 3 months of travel)||Tropics, subtropics|
|Malaria, P. vivax||8 days to 12 months (almost half have onset >30 days after completion of travel)||Widespread in tropics and subtropics|
|Spotted fever rickettsiosis||Few days to 2–3 weeks||Causative species vary by region|
|Zika virus infection||3–14 days||Widespread in Latin America, endemic through much of Africa, Southeast Asia, and Pacific Islands|
|Incubation 14 Days to 6 Weeks|
|Encephalitis, arboviral; enteric fever; acute HIV; leptospirosis; malaria||See above incubation periods for relevant diseases||See above distribution for relevant diseases|
|Amebic liver abscess||Weeks to months||Most common in resource-poor countries|
|Hepatitis A||28–30 days (15–50 days)||Most common in resource-poor countries|
|Hepatitis E||26–42 days (2–9 weeks)||Widespread|
|Acute schistosomiasis (Katayama syndrome)||4–8 weeks||Most common in sub-Saharan Africa|
|Incubation >6 Weeks|
|Amebic liver abscess, hepatitis E, malaria, acute schistosomiasis||See above incubation periods for relevant diseases||See above distribution for relevant diseases|
|Hepatitis B||90 days (60–150 days)||Widespread|
|Leishmaniasis, visceral||2–10 months (10 days to years)||Asia, Africa, Latin America, southern Europe, and the Middle East|
|Tuberculosis||Primary, weeks; reactivation, years||Global distribution, rates and levels of resistance vary widely|
Findings Requiring Urgent Attention
Presence of associated signs, symptoms, or laboratory findings can focus attention on specific infections (Table 5-4). Findings that should prompt urgent attention include hemorrhage, neurologic impairment, and acute respiratory distress. Even if an initial physical examination is unremarkable, it is worth repeating the examination, as new findings may appear that will help in the diagnostic process (such as skin lesions or tender liver). Although most febrile illnesses in returned travelers are related to infections, the clinician should bear in mind that other problems, including pulmonary emboli and drug hypersensitivity reactions, can be associated with fever.
|Common Clinical Findings||Infections to Consider after Tropical Travel|
|Fever and rash||Dengue, chikungunya, Zika, rickettsial infections, enteric fever (skin lesions may be sparse or absent), acute HIV infection, measles|
|Fever and abdominal pain||Enteric fever, amebic liver abscess|
|Undifferentiated fever and normal or low white blood cell count||Dengue, malaria, rickettsial infection, enteric fever, chikungunya, Zika|
|Fever and hemorrhage||Viral hemorrhagic fevers (dengue and others), meningococcemia, leptospirosis, rickettsial infections|
|Fever and arthralgia or myalgia, sometimes persistent||Chikungunya, dengue, Zika|
|Fever and eosinophilia||Acute schistosomiasis, drug hypersensitivity reaction, fascioliasis and other parasitic infections (rare)|
|Fever and pulmonary infiltrates||Common bacterial and viral pathogens, legionellosis, acute schistosomiasis, Q fever, leptospirosis|
|Fever and altered mental status||Cerebral malaria, viral or bacterial meningoencephalitis, African trypanosomiasis, scrub typhus|
|Mononucleosis syndrome||Epstein-Barr virus infection, cytomegalovirus infection, toxoplasmosis, acute HIV infection|
|Fever persisting >2 weeks||Malaria, enteric fever, Epstein-Barr virus infection, cytomegalovirus infection, toxoplasmosis, acute HIV infection, acute schistosomiasis, brucellosis, tuberculosis, Q fever, visceral leishmaniasis (rare)|
|Fever with onset >6 weeks after travel||Plasmodium vivax or ovale malaria, acute hepatitis (B, C, or E), tuberculosis, amebic liver abscess|
Fever accompanied by any of the following syndromes deserves further scrutiny, because it may indicate a disease of public health importance:
- Skin rash with or without conjunctivitis
- Difficulty breathing
- Shortness of breath
- Persistent cough
- Decreased consciousness
- Bruising or unusual bleeding (without previous injury)
- Persistent diarrhea
- Persistent vomiting (other than air or motion sickness)
- Paralysis of recent onset
People who travel to visit friends and relatives (VFRs) often do not seek pretravel medical advice and are at higher risk for some diseases than other travelers. A review of GeoSentinel Surveillance Network data showed that a larger proportion of immigrant VFRs than tourist travelers presented with serious (requiring hospitalization), potentially preventable travel-related illnesses.
Change over Time
Clinicians have access to resources on the Internet that provide information about geographic-specific risks, disease activity, and other useful information, such as drug-susceptibility patterns for pathogens. Infectious diseases are dynamic, as demonstrated by the introduction and spread of chikungunya virus in the Americas beginning in late 2013 and the rapid spread of Zika virus in the Americas in 2015 and 2016. In contrast, because of the wide use of vaccine, hepatitis A infection is now infrequently seen in travelers.
Common infections in returned travelers may be seen at unexpected times of the year. Because influenza transmission can occur throughout the year in tropical areas, and the peak season in the Southern Hemisphere is May to August, clinicians in the Northern Hemisphere must be alert to the possibility of influenza outside the usual US influenza season.
Travelers may acquire infections caused by common bacteria that are unusually resistant. Bacteria that produce extended-spectrum β-lactamases and carbapenem-resistant Enterobacteriaceae, including bacteria expressing the metalloprotease NDM-1, which confers resistance to many available antibiotics, have been found in infections acquired during travel, most often related to medical care (both elective and emergency). Enteric fever, the term used to describe either typhoid or paratyphoid fever, has also become increasingly resistant to fluoroquinolones (see Chapter 3, Typhoid & Paratyphoid Fever).
The tables in this section identify some common infections by presenting findings or other characteristics, by area of travel and by incubation periods. These highlight only the most common infections. The listed references and websites should be consulted for more detailed information. In most studies, a specific cause for fever is not identified in about 25% of returned travelers.
Keep in Mind
- Initial symptoms of life-threatening and self-limited infections can be identical.
- Fever in returned travelers is often caused by common, cosmopolitan infections, such as pneumonia and pyelonephritis, which should not be overlooked in the search for exotic diagnoses.
- Travelers may be infected with highly drug-resistant pathogens.
- Patients with malaria may be afebrile at the time of evaluation but typically give a history of fever or chills.
- Malaria is the most common cause of acute undifferentiated fever after travel to sub-Saharan Africa and to some other tropical areas.
- Malaria, especially P. falciparum , can progress rapidly. Diagnostic studies should be done promptly and treatment instituted immediately if malaria is diagnosed (see Chapter 3, Malaria).
- A history of taking malaria chemoprophylaxis does not exclude the possibility of malaria.
- Patients with malaria can have prominent respiratory (including acute respiratory distress syndrome), gastrointestinal, or central nervous system findings.
- Dengue is the most common cause of febrile illness among people who seek medical care after travel to Latin America or Asia.
- Other arboviral infections are emerging as causes of fever in travelers, including chikungunya and Zika.
- Viral hemorrhagic fevers are important to identify but are rare in travelers; bacterial infections, such as leptospirosis, meningococcemia, and rickettsial infections, can also cause fever and hemorrhage and should be always be considered because of the need to institute prompt, specific treatment.
- Sexually transmitted diseases, including acute HIV, can cause acute febrile infections.
- Consider infection control, public health implications, and requirements for reportable diseases.
- Bottieau E, Clerinx J, Schrooten W, Van den Enden E, Wouters R, Van Esbroeck M, et al. Etiology and outcome of fever after a stay in the tropics. Arch Intern Med. 2006 Aug 14-28;166(15):1642–8. [PMID:16908798]
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- Jensenius M, Davis X, von Sonnenburg F, Schwartz E, Keystone JS, Leder K, et al. Multicenter GeoSentinel analysis of rickettsial diseases in international travelers, 1996–2008. Emerg Infect Dis. 2009 Nov;15(11):1791–8. [PMID:19891867]
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Mary Elizabeth Wilson