Mary Elizabeth Wilson

Initial Focus

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 persons who have visited areas with malaria in recent months (see the Malaria section in Chapter 2). 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 en route or infected with a pathogen of public health importance (e.g., yellow fever) 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 significant proportion of illnesses in returned travelers is caused by common, cosmopolitan infections (e.g., bacterial pneumonia, 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 4-4). Details about activities (e.g., freshwater exposure in schistosomiasis-endemic areas, animal bites, sexual activities, local medical care with injections) and accommodations in malaria-endemic areas (e.g., use of bed nets, presence of window screens, air conditioning) during travel may provide useful clues. Preparation before travel (e.g., hepatitis A vaccine, yellow fever vaccine) will markedly reduce the likelihood of some infections, so this is a relevant part of the history. 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 4-5). This knowledge may allow the clinician to exclude some infections from the differential diagnosis. The majority of 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 more than a year after return. In the United States, >90% of reported cases of falciparum malaria manifest within 30 days of return, but almost half of cases of vivax manifest >30 days after return. A history of prior travel and residence should be an integral part of every medical history.

Findings Requiring Urgent Attention

Presence of associated signs, symptoms, or laboratory findings can help to focus attention on specific infections (Table 4-6). 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 (e.g., skin lesions, 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. See Box 4-1 for a list of initial studies for diagnosing patients with unexplained fever.

CDC’s Division of Global Migration and Quarantine is responsible for preventing the transmission of illnesses across international borders, and in particular, for preventing transmission of such illnesses into the United States. The following syndromes deserve further scrutiny because of their potential for signaling a disease of public health importance. Fever accompanied by—

• skin rash
• difficulty breathing
• shortness of breath
• persistent cough
• decreased consciousness
• bruising or unusual bleeding (without previous injury)
• persistent diarrhea
• persistent vomiting (other than air sickness)
• jaundice
• paralysis of recent onset

Persons who travel to visit friends and relatives (VFRs) often do not seek pre-travel medical advice. Review of GeoSentinel surveillance data showed that a greater proportion of immigrant VFRs presented with serious, potentially preventable travel-related illnesses (and required hospitalization) than did tourist travelers.

Change over Time

Clinicians now have access to many resources on the Internet that can help to provide information about geographic-specific risks, current disease activity, and other useful information, such as drug-susceptibility patterns for pathogens. Infectious diseases are dynamic, as is demonstrated by a recent review of adult returned travelers with fever and rash seen during 2006–2007 at a Paris hospital. The most common diagnosis was chikungunya fever, followed by dengue and African tick bite fever. In contrast, because of the wide use of vaccine, hepatitis A infection is becoming less common 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 flu season.

The tables in this section help to identify some of the more common infections by presenting findings or other characteristics by geographic 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 the 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.
• Malaria is the most common cause of acute undifferentiated fever after travel to sub-Saharan Africa and to some other tropical areas.
• 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 more exotic diagnoses.
• Patients with malaria may be afebrile at the time of evaluation but typically give a history of chills.
• Malaria, especially falciparum, can progress rapidly. Diagnostic studies should be done promptly and treatment instituted immediately if malaria is diagnosed (see the Malaria section in Chapter 2).
• A history of taking malaria chemoprophylaxis does not exclude the possibility of malaria.
• Patients with malaria can have prominent respiratory (including adult respiratory distress syndrome), gastrointestinal, or central nervous system findings.
• 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 infections, including acute HIV, can cause acute febrile infections.
• Consider infection control, public health implications and requirements for reportable diseases.

References

• Ryan ET, Wilson MW, Kain K. Illness after international travel. N Engl J Med. 2002;347(7):505–16.
• Wilson ME, Weld LH, Boggild B, et al.; GeoSentinel Surveillance Network. Fever in returned travelers: results from the GeoSentinel Surveillance Network. Clin Infect Dis. 2007;44(12):1560–8.
• Bottieau E, Clerinx J, Schrooten W, et al. Etiology and outcome of fever after a stay in the tropics. Arch Intern Med. 2006;166(15):1642–8.
• O’Brien D, Tobin S, Brown GV, Torresi J. Fever in returned travelers: review of hospital admissions for a 3-year period. Clin Infect Dis. 2001;33(5):603–9.
• Jensenius M, Fournier PE, Raoult D. Rickettsioses and the international traveler. Clin Infect Dis. 2004;39(10):1493–9.
• Bottieau E, Clerinx J, Van den Enden E, et al. Infectious mononucleosis-like syndromes in febrile travelers returning from the tropics. J Travel Med. 2006;13(4):191–7.
• Freedman DO, Weld LH, Kozarsky PE, et al. Spectrum of disease and relation to place of exposure in ill returned travelers. N Engl J Med. 2006;354(2):119–30.
• Leder K, Tong S, Weld L, et al.; GeoSentinel Surveillance Network. Illness in travelers visiting friends and relatives: a review of the GeoSentinel Surveillance Network. Clin Infect Dis. 2006;43(9):1185–93.
• Hochedez P, Canestri A, Guihot A, et al. Management of travelers with fever and exanthema, notably dengue and chikungunya infections. Am J Trop Med Hyg. 2008;78(5):710–3.
• Wilson ME, Freedman DO. The etiology of travel-related fever. Curr Opin Infect Dis. 2007;20(5):449–53.