Fever in the Returning Traveler



Key Clinical Questions







  1. What infections should be considered?



  2. What questions should be asked in the travel history?



  3. What diagnostic tests should be conducted?



  4. Which patients should be hospitalized?



  5. What clinical factors put patients at risk for serious complications?



  6. When should an infectious disease physician be consulted?







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Case 190-1




THE GREAT PRETENDER


A middle-aged male was brought in by police to the emergency room of an inner-city hospital with confusion and fever to 104°F, after being found in an incoherent state without identification. Shortly after arrival, his condition deteriorated. He became agitated, hypoxic, and hypotensive and was intubated and transferred to the intensive care unit. A chest radiograph showed diffuse infiltrates. Blood tests were most notable for a hematocrit of 18%, creatinine 2.8 mg/dL, and moderate elevations of liver enzymes. A lumbar puncture was normal. The hematology laboratory technician happened to review the patient’s blood smear before going home that evening and made a diagnosis of falciparum malaria with 30% parasitemia. The patient was started urgently on intravenous quinidine and exchange transfusions. He was eventually found to be a Nigerian immigrant who had recently traveled to his native country without taking malaria prophylaxis. After a stormy hospital course complicated by acute respiratory distress syndrome and acute renal failure, he made a full recovery.


Fever in travelers is malaria until proven otherwise. Malaria has been called “the mime” for its ability to simulate a wide variety of other infectious syndromes. Hence, the diagnosis of malaria is often missed or delayed, sometimes with fatal consequences, especially when patients present for care outside of endemic areas. For example, during the Vietnam War, returning soldiers who presented with malaria to civilian hospitals had a 10-fold higher mortality than those who presented to hospitals in the Veterans Administration system, which had much greater familiarity with diagnosing and treating malaria.







Introduction





International travelers are commonly plagued by medical problems, particularly after travel to a resource-poor setting. About 8% of travelers to developing countries seek medical care while they are away or after they return. Although fever in the traveler may be caused by mild illnesses, it may also be a harbinger of potentially lethal infection. The evaluation of the febrile traveler is complicated by the wide array of possible etiologies. It is critical to consider which infections are endemic to the area visited, potential exposures, the time between exposure and the onset of symptoms, and associated clinical findings. This chapter reviews the common causes of fever in returning travelers and the appropriate initial diagnostic evaluation.






Epidemiology





GeoSentinel, a worldwide network of travel and tropical medicine clinics, provides the largest database for travel-related infections. From 1996 to 2004, the five most common diagnoses for patients with systemic febrile illnesses presenting to GeoSentinel clinics from the developing world were malaria, dengue, mononucleosis due to Epstein-Barr virus or cytomegalovirus, rickettsial infection, and typhoid fever.






In the GeoSentinel database, malaria was the predominant cause of systemic febrile illnesses overall, and it was one of the three top causes from each of the six regions of the developing world. Malaria was the leading cause of systemic febrile illness in travelers returning from Sub-Saharan Africa and Central America. In the United States, more than 50% of cases of imported malaria occurred among immigrant families who had made recent visits to their country of origin. Dengue was the second most likely cause of systemic febrile illnesses overall and the leading cause for fever in travelers to Southeast and South Central Asia, the Caribbean, and South America. Rickettsial infections were an important cause of fever in travelers to Sub-Saharan Africa, and they were often infected with Rickettsia africae (African tick-bite fever). Typhoid fever was especially common in travelers to South Central Asia, but it also occurred in travelers to other regions.






In a later GeoSentinel study of returning travelers with fever, 35% presented with a systemic febrile illness, 15% with acute diarrheal disease, and 14% with respiratory symptoms. Among those with systemic febrile illnesses, 59% were diagnosed with malaria, 18% with dengue, 6% with typhoid or paratyphoid fever, and 5% with rickettsial illness. Additional causes of febrile syndromes included mononucleosis syndromes (Epstein-Barr virus, cytomegalovirus, acute HIV infection, or toxoplasmosis), leptospirosis, amebic liver abscess, viral meningitis, and relapsing fever.






Among patients with fever and diarrhea, the most common diagnoses were traveler’s diarrhea, Campylobacter, nontyphoidal Salmonella species, and shigellosis. In those with fever and respiratory symptoms, nearly half were diagnosed with bronchitis or an acute unspecified respiratory infection. Other common diagnoses were bacterial pneumonia, tonsillitis, influenza or an influenza-like illness, and sinusitis.






What Information Should Be Elicited from the Medical History?





It is critical to identify all regions that the traveler has visited in the past year, including layovers or short stops. The Centers for Disease Control and Prevention (CDC) Web site (www.cdc.gov) has a travel site that lists common infections by each country and region, as well as reports on disease outbreaks. The World Health Organization Web site (www.who.int) also has information about disease outbreaks. It is particularly important to identify regions of travel where malaria and dengue are endemic.






It is also necessary to define the dates of travel and the timing of symptom onset, which may permit the estimation of the approximate incubation period. Table 190-1 lists the incubation periods for several bacteria, viruses, fungi, and parasites that cause fever in returning travelers. Some infections can be excluded based on an incubation period that is inconsistent with the timing of fever. For example, a traveler presenting with a systemic febrile infection three weeks after returning would be very unlikely to have dengue, which nearly always presents within 14 days. The duration of the trip can also be helpful. Malaria is more often reported in long-term (> 6 months) than short-term travelers, though 5% of patients with malaria in the GeoSentinel database had traveled for less than one week. Some infections are seasonal, but some seasonal infections (such as influenza) may present at unusual times given that peak seasons may differ in tropical climes.







Table 190-1 Infectious Causes of Fever and Associated Incubation Periods in Returning Travelers