Author(s): Jessica Fairley

As many as 43%–79% of travelers to low- and middle-income countries become ill with a travel-associated health problem. Although most of these illnesses are mild, some travelers become sick enough to seek care from a health care provider. Most posttravel infections become apparent soon after returning from abroad, but incubation periods vary, and some syndromes can present months to years after initial infection or after travel.

When evaluating a patient with a probable travel-associated illness, approach the differential diagnosis by incorporating both the patient presentation and risk factors related to travel (e.g., destination, duration of travel, and exposures; see Table 11-01). Salient points of the history of present illness and the travel and medical history, descriptions of common nonfebrile syndromes, and initial management steps are outlined below. The differential diagnosis and management for a traveler with fever (or febrile syndrome) is discussed in detail in Sec. 11, Ch. 4, Fever in the Returned Traveler.

The Posttravel Evaluation

History of the Present Illness

As with any medical evaluation, the history of the present illness and associated clinical factors are the first considerations when approaching an ill returned traveler. Information about the timing of illness, immunization and prophylaxis history, itinerary, exposures, and comorbidities can help refine the diagnosis.

Timing of Illness in Relation to Travel

Because most common travel-associated infections have short incubation periods, most ill travelers will seek medical attention ≤1 month of returning from their destinations. Dengue and other arboviral infections, influenza, and travelers’ diarrhea are examples of infections with shorter incubation periods (<2 weeks). Diseases with slightly longer incubation periods, ≤4–6 weeks, include viral hepatitis, acute HIV, leishmaniasis, malaria, and typhoid fever, among others. Occasionally, some infections (e.g., leishmaniasis, malaria, schistosomiasis, tuberculosis) might become manifest months or even years after a traveler returns. Consider malaria in the differential diagnosis of any traveler who traveled to a malaria-endemic area ≤1 year of presentation. A detailed travel history that extends beyond a few months before presentation is important. The most common travel-associated infections by incubation period are listed in Table 11-02, Table 11-03, and Table 11-04.

Immunization & Prophylaxis History

When evaluating an ill returned traveler, review the traveler’s vaccination history and malaria prophylaxis used. Fewer than half of US travelers who visit low- and middle-income countries seek pretravel medical advice, increasing the likelihood that they did not receive pretravel vaccines and did not receive or take antimalarial drugs. Although adherence to malaria prophylaxis does not rule out the possibility of malaria, it substantially reduces the risk and increases the possibility of an alternative diagnosis.

Likewise, history of vaccination against hepatitis A and yellow fever would make these diseases unlikely causes of hepatitis or jaundice in a returning traveler. Remember to ask about routine vaccinations like measles-mumps-rubella (MMR) and tetanus-diphtheria-pertussis (Tdap). The most common vaccine-preventable diseases among returned travelers seeking care at GeoSentinel clinics during 1997–2010 included hepatitis A, hepatitis B, influenza, and typhoid fever. More than half of these patients with vaccine-preventable diseases were hospitalized.

Itinerary & Travel Duration

A traveler’s itinerary is crucial to formulating a differential diagnosis because exposures differ depending on the region of travel and the specific areas (e.g., rural vs. urban). A febrile illness with nonspecific symptoms could be dengue, malaria, rickettsial disease, or typhoid fever, among others, depending on the itinerary and endemicity of these infections. Being able to exclude certain infections based on the travel itinerary can help avoid unnecessary testing.

A 2013 study from the GeoSentinel Surveillance Network found that the frequency of certain diseases varied depending on the region of the world visited; among travelers with fevers, for example, dengue was diagnosed most frequently among travelers coming from Asia, while malaria was diagnosed most frequently among travelers returning from Africa.

Travel duration is also a factor because the risk for a travel-associated illness increases with the length of the trip. A tropical medicine specialist can assist with the differential diagnosis and might be aware of outbreaks or the current prevalence of an infectious disease in an area. The 2014–2015 Ebola virus epidemic in West Africa highlighted the importance of epidemiologic factors and travel itineraries in managing patients and protecting staff and the community.

Exposures

Knowing a patient’s exposures during travel (e.g., consumption of contaminated food or water, insect bites, freshwater swimming) also can assist with the differential diagnosis. In addition to malarial parasites, mosquitoes transmit viruses (e.g., chikungunya, dengue, yellow fever, Zika) and filarial parasites (e.g., Wuchereria bancrofti). Depending on the clinical syndrome, a history of a tick bite could suggest a diagnosis of tick-borne encephalitis, African tick-bite fever, or other rickettsial infections. Tsetse flies are the vector for transmission of Trypanosoma brucei, a protozoan that causes African sleeping sickness. Tsetse flies are large, and their bites are painful; patients often recall being bitten. Freshwater bathing, swimming, wading, or other contact can put travelers at risk for leptospirosis, schistosomiasis, and other diseases.

Accommodations and activities also can influence the risk of acquiring certain diseases while abroad. Travelers who visit friends and relatives are at greater risk for malaria, typhoid fever, and other diseases, often because they stay longer, travel to more remote destinations, have more contact with local water sources, and typically do not seek pretravel advice (see Sec. 9, Ch. 9, Visiting Friends & Relatives: VFR Travel). Travelers backpacking and camping in rural areas have a greater risk for certain diseases than those staying in luxury, air-conditioned hotels.

Comorbidities

Underlying illnesses can affect a traveler’s susceptibility to infection as well as the clinical manifestations and severity of disease. An increasing number of international travelers are immunosuppressed, whether due to HIV infection, treatment with immune-modulating medications, being an organ transplant recipient, or other primary or acquired immunodeficiencies (see Sec. 3, Ch. 1, Immunocompromised Travelers). In addition, several factors associated with travel can exacerbate underlying conditions (e.g., chronic lung disease, inflammatory bowel disease, ischemic heart disease).

Symptoms & Illness Severity

Although the symptoms of many infectious and travel-associated syndromes overlap, the initial symptoms and presentation should ultimately guide the differential diagnosis: gastrointestinal symptoms and febrile illnesses are the most common syndromes in returning travelers. Remember that conditions such as appendicitis, urinary tract infections, and domestically acquired viral infections also can present in returning travelers.

Severity of illness is not only important for patient triage but also can help clinicians distinguish certain infections. Is the traveler hemodynamically stable? Is the infection potentially life-threatening (e.g., malaria)? Does the traveler have a severe respiratory syndrome or signs of hemorrhagic fever? Some suspected illnesses might necessitate prompt involvement of public health authorities. For more details, see General Management, later in this chapter.

Common Syndromes

The 3 most common clinical syndromes after travel to low- and middle-income countries are dermatologic conditions, diarrheal diseases, and systemic febrile illnesses, each of which is described in more detail elsewhere in this section (see Dermatologic Conditions, Persistent Diarrhea in Returned Travelers, and Fever in the Returned Traveler). Evaluate febrile travelers returning from malaria-endemic destinations immediately. Other common clinical presentations and findings include animal bites and scratches, asymptomatic eosinophilia, and respiratory illnesses.

Animal Bites & Scratches

Promptly evaluate any traveler who reports animal exposures during travel (see Sec. 4, Ch. 7, Zoonotic Exposures: Bites, Stings, Scratches & Other Hazards). Consider travelers with animal bites and scratches as high-risk for rabies exposure, and provide rabies postexposure prophylaxis, as indicated (see Sec. 5, Part 2, Ch. 18, Rabies). If the traveler was exposed to a macaque, herpes B postexposure prophylaxis might be indicated (see Sec. 5, Part 2, Ch. 1, B Virus).

Asymptomatic Eosinophilia

Eosinophilia in a returning traveler suggests possible helminth infection. Allergic diseases, hematologic disorders, and a few other viral, fungal, and protozoan infections also can cause eosinophilia. Eosinophilia can be present during pulmonary migration of parasites (e.g., Ascaris, hookworm, schistosomiasis, Strongyloides).

Other parasitic infections associated with eosinophilia include lymphatic filariasis, chronic strongyloidiasis, acute trichinellosis, and visceral larva migrans. These infections might be asymptomatic, but also could have associated symptoms (e.g., rash, swelling). In an outbreak of sarcocystosis among travelers returning from Tioman Island, Malaysia, those affected presented with eosinophilia and myalgias and had eosinophilic myositis on muscle biopsy (see Sec. 5, Part 3, Ch. 18, Sarcocystosis).

Parasitic infections are rare in most travelers, so consider other etiologies for eosinophilia; for instance, eosinophilia can be a sign of a hematologic malignancy. See Section 5 for more information on specific diseases.

Respiratory Illnesses

Respiratory illnesses are frequent among returned travelers and are typically associated with common respiratory viruses, including influenza and now, severe acute respiratory syndrome coronavirus 2, the cause of coronavirus disease 2019 (COVID-19). Since the pandemic began in early 2020, coronavirus disease (COVID-19) has overtaken influenza in overall global incidence. And although historically influenza has been the most common vaccine-preventable disease associated with international travel, COVID-19 could surpass it in that regard. To make that determination, however, a better understanding of the epidemiology of travel-associated COVID-19 transmission is needed (see Sec. 5, Part 2, Ch. 3, COVID-19).

If the travel history is appropriate and respiratory symptoms do not have a clear alternative diagnosis, include other emerging respiratory infections (e.g., avian influenza, Middle East respiratory syndrome [MERS]) in the differential diagnosis. In suspected cases of an emerging respiratory infection, alert local public health authorities and the Centers for Disease Control and Prevention (CDC) immediately. See relevant chapters in Section 5 for more information on these emerging infections; for a list of febrile respiratory illnesses that can occur after exposures in tropical destinations, see Table 11-10 in the chapter, Fever in the Returned Traveler.

Delayed illness onset and chronic cough after travel could be tuberculosis, especially in a long-term traveler or health care worker. Helminths and helminth infections associated with pulmonary symptoms include Ascaris, hookworms (Ancylostoma or Necator), paragonimiasis, schistosomiasis, and strongyloidiasis.

General Management

Triage

Most posttravel illnesses can be managed on an outpatient basis, but some patients, especially those with systemic febrile illnesses, might need to be hospitalized. Furthermore, potentially severe, transmissible infections (e.g., COVID-19, Ebola, MERS) require enhanced infection control measures and often, higher levels of care. Severe clinical presentations (e.g., acute respiratory distress, hemodynamic instability, mental status changes) require inpatient care. Have a low threshold for admitting a febrile patient if malaria is suspected; complications can occur rapidly. Management in an inpatient setting is especially vital for patients unlikely to follow up reliably or who have no one at home to assist if symptoms quickly worsen.

Initial Evaluation

After conducting a thorough physical exam, paying particular attention to skin manifestations or evidence of prior insect bites, order tests based on chief complaint and exposure history. Frequently useful tests include complete blood count with differential (to look for anemia, eosinophilia, leukocytosis, leukopenia, thrombocytopenia); blood cultures and malaria rapid diagnostic tests (depending on the presence of fever and travel itinerary); a complete metabolic profile (to identify electrolyte, renal, or liver dysfunction); serologic or PCR tests for arboviral infections (as needed); and stool cultures and ova and parasite exams. These tests often can help narrow the differential diagnosis and determine disease severity.

Antimicrobial Resistance

Be aware of the risk to international travelers for acquiring antimicrobial resistant organisms. Carefully consider travel history when caring for patients, both to identify effective treatments for infections and to ensure infection control interventions are in place to prevent spread of antimicrobial resistance (see Sec. 11, Ch. 5, Antimicrobial Resistance).

Consultation

Consult an infectious disease specialist when managing complicated or severe travel-associated infections, or when the diagnosis remains unclear. A tropical medicine or infectious disease specialist should be involved in cases that require specialized treatment (e.g., leishmaniasis, severe malaria, and neurocysticercosis).

Involve local, state, and federal public health authorities whenever managing transmissible, high-consequence infections. CDC provides on-call assistance with the diagnosis and management of parasitic infections at 404-718-4745 (for parasitic infections other than malaria) or 770-488-7788 (toll-free at 855-856-4713) for malaria, during business hours. After business hours or for other conditions, call the CDC Emergency Operations Center at 770-488-7100.