Fever in the Returned Traveler

CDC Yellow Book 2024

Posttravel Evaluation

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.

Table 11-09 Common causes of fever in the tropics by geographic area

GEOGRAPHIC AREA COMMON FEVER-CAUSING TROPICAL DISEASES OTHER INFECTIONS CAUSING OUTBREAKS OR CLUSTERS OF DISEASE AMONG TRAVELERS

CARIBBEAN

Chikungunya
Dengue
Malaria (on the island of Hispaniola)
Zika

Histoplasmosis, acute
Leptospirosis

CENTRAL AMERICA

Chikungunya
Dengue
Malaria (primarily Plasmodium vivax)
Typhoid or paratyphoid fever
Zika

Coccidioidomycosis
Histoplasmosis
Leishmaniasis
Leptospirosis

SOUTH AMERICA

Chikungunya
Dengue
Malaria (primarily P. vivax)
Zika

Bartonellosis
Histoplasmosis
Leptospirosis
Yellow fever

SOUTH-CENTRAL ASIA

Dengue
Malaria (primarily non–P. falciparum)
Typhoid or paratyphoid fever

Chikungunya
Scrub typhus

SOUTHEAST ASIA

Dengue
Malaria (primarily non–P. falciparum)

Chikungunya
Leptospirosis

SUB-SAHARAN AFRICA

Dengue
Malaria (primarily P. falciparum)
Tickborne rickettsia (main cause of fever in southern Africa)
Schistosomiasis, acute (Katayama fever)

Chikungunya
Meningococcal meningitis
Trypanosomiasis, African
Typhoid or paratyphoid fever

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).

Table 11-10 Clinical findings & fever-associated infectious diseases after tropical travel

  INFECTIOUS DISEASES TO CONSIDER 
CLINICAL FINDING & FEVER BACTERIAL VIRAL PARASITIC FUNGAL OR OTHER

ABDOMINAL PAIN

Typhoid or paratyphoid fever

None

Liver abscess (amebic or pyogenic)

None

ALTERED MENTAL STATUS OR CENTRAL NERVOUS SYSTEM INVOLVEMENT

Meningococcal meningitis
Scrub typhus

Arboviral encephalitides (e.g., JE, WNV)
Rabies
Tick-borne encephalitis

Angiostrongyliasis
Malaria, cerebral
Trypanosomiasis, African

None

ARTHRALGIA OR MYALGIA (SOMETIMES PERSISTENT)

None

Chikungunya
Dengue
Ross River virus
Zika

Sarcocystosis, muscular
Trichinellosis

None

EOSINOPHILIA

None

None

Angiostrongyliasis
Fascioliasis
Sarcocystosis
Schistosomiasis, acute
Trichinellosis
Other parasites (rare)

Drug hypersensitivity reaction

FEVER ONSET >6 WEEKS AFTER TRAVEL

Melioidosis
Tuberculosis

Acute hepatitis B, hepatitis C, hepatitis E

Liver abscess, amebic
Malaria
(Plasmodium ovale, P. vivax)
Trypanosomiasis, African

None

FEVER >2 WEEKS (PERSISTENT)

Brucellosis
Q fever
Tuberculosis
Typhoid or paratyphoid fever

Cytomegalovirus
Epstein-Barr virus
HIV, acute

Leishmaniasis, visceral (rare)
Malaria
Schistosomiasis, acute
Toxoplasmosis

None

HEMORRHAGE

Leptospirosis
Meningococcemia
Rickettsial infections (Spotted fever group)

Viral hemorrhagic fevers (e.g., dengue, Ebola, Lassa, yellow fever)

None

None

JAUNDICE

Leptospirosis

Acute hepatitis A, hepatitis B, hepatitis C, hepatitis E
Viral hemorrhagic fevers (including yellow fever)

Malaria, severe

None

MONONUCLEOSIS SYNDROME

None

Cytomegalovirus
Epstein-Barr virus
HIV, acute

Toxoplasmosis

None

NORMAL OR LOW WHITE BLOOD CELL COUNT

Rickettsial infections
Typhoid or paratyphoid fever

Chikungunya
Dengue
HIV, acute
Zika

Malaria

None

RASH

Meningococcemia
Rickettsial infections
(Spotted fever or Typhus group)
Typhoid or paratyphoid fever (rash may be sparse–absent)

Chikungunya
Dengue
HIV, acute
Measles
Varicella
Zika

None

None

RESPIRATORY SYMPTOMS & PULMONARY INFILTRATES

Legionellosis
Leptospirosis
Melioidosis
Plague, pneumonic
Pneumococcus and other common bacterial respiratory pathogens
Psittacosis
Q fever
Tuberculosis

Coronavirus infections (including COVID-19, MERS)
Influenza and other common viral respiratory pathogens

Schistosomiasis, acute

Coccidioidomycosis, acute
Histoplasmosis, acute

Abbreviations: COVID-19, coronavirus disease 2019; JE, Japanese encephalitis; MERS, Middle East respiratory syndrome; WNV, West Nile virus.

Table 11-11 Febrile syndromes in travelers: potential diseases of public health concern requiring immediate infection containment & control

FEBRILE SYNDROMES (i.e., SYMPTOMS & FEVER) POTENTIAL DISEASES OF PUBLIC HEALTH SIGNIFICANCE

BRUISING OR UNUSUAL BLEEDING (EASILY, WITHOUT PREVIOUS INJURY)

Viral hemorrhagic fever

COUGH (PERSISTENT)

Pertussis

DECREASED CONSCIOUSNESS

Meningococcal meningitis

DIARRHEA (PERSISTENT, VOLUMINOUS)

Cholera

FLACCID PARALYSIS (RECENT ONSET)

Polio
Other enteroviruses

JAUNDICE

Hepatitis A

RAPID RESPIRATORY RATE

Coronavirus disease 2019 (COVID-19)
Influenza
Middle East respiratory syndrome (MERS)
Pneumonic plague

RASH (WITH OR WITHOUT CONJUNCTIVITIS)

Measles
Meningococcemia
Viral hemorrhagic fevers

VOMITING (PERSISTENT, OTHER THAN AIR OR MOTION SICKNESS)

Norovirus

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.

Box 11-01 Fever in returning travelers: clinical tips

ANTIMICROBIAL RESISTANT ORGANISMS (see Sec. 11, Ch. 5, Antimicrobial Resistance)
Travelers could be infected or colonized with drug-resistant pathogens, especially travelers who were hospitalized abroad or who took antimicrobial agents to treat travelers’ diarrhea.

ARBOVIRAL INFECTIONS (see the chapters in Section 5: Chikungunya, Dengue, Zika)
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 viruses.

COMMON INFECTIONS

Do not overlook common infections (e.g., diarrhea, pneumonia, pyelonephritis) in the search for exotic diagnoses.

FEVER & BLEEDING (see Sec. 5, Part 1, Ch. 10, Leptospirosis; Sec. 5, Part 1, Ch. 13, Meningococcal Disease; Sec. 5, Part 1, Ch. 18, Rickettsial Diseases; and Sec. 5, Part 2, Ch. 25, Viral Hemorrhagic Fevers)

Viral hemorrhagic fevers other than dengue (e.g., Ebola, Lassa fever, Marburg hemorrhagic fever) are important to identify but rare in travelers.

Because of the need to institute prompt, specific treatment, always consider the possibility of bacterial infections (e.g., leptospirosis, meningococcemia, rickettsial infections) that can also cause fever and hemorrhage.

INFECTION CONTROL & PUBLIC HEALTH

Keep in mind infection control, public health implications, and requirements for reportable diseases.

MALARIA (see Sec. 5, Part 3, Ch.16, Malaria)

Malaria is the most common cause of acute undifferentiated fever after travel to sub-Saharan Africa and some other tropical areas.

Malaria can progress rapidly (especially Plasmodium falciparum); evaluate promptly and initiate treatment immediately, if diagnosed.

A history of taking malaria chemoprophylaxis does not exclude the possibility of malaria.

Patients with malaria can be afebrile at the time of evaluation, but typically give a history of fever or chills; have prominent respiratory (including acute respiratory distress syndrome), gastrointestinal, or central nervous system findings.

SEXUALLY TRANSMITTED INFECTIONS (see Sec. 11, Ch. 10, Sexually Transmitted Infections)

Sexually transmitted infections, including acute HIV, can cause acute febrile infections.

The following authors contributed to the previous version of this chapter: Mary Elizabeth Wilson

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