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Chapter 11 Posttravel Evaluation

Fever

Mary Elizabeth Wilson

INITIAL FOCUS

Fever commonly accompanies serious illness in returned travelers, and 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, clinicians must initiate early evaluation, especially in people who have visited areas with malaria in recent months (see Chapter 4, 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 importance (such as yellow fever or Ebola viruses) at the origin or destination. During an outbreak such as the Ebola epidemic in West Africa, special screening protocols may be needed. It is important to know that a specific cause for fever may not be identified in approximately 25% or more of returned travelers.

USE OF HISTORY, LOCATION OF EXPOSURE, AND INCUBATION TO LIMIT DIFFERENTIAL DIAGNOSIS

A large proportion of illnesses in returned travelers are caused by common, cosmopolitan infections (such as diarrhea, 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 11-03). Details about activities (such as freshwater exposure in schistosomiasis-endemic areas, animal bites, sexual activities, tattoos, or local medical care with injections) and accommodations (bed nets, window screens, air conditioning, type of dwelling) during travel may provide useful clues. Preparation before travel (for example, vaccinations and malaria prophylaxis) will markedly reduce the likelihood of some infections, so this is also 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 exposure needs to be defined in different geographic areas. 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.

Table 11-03. Common causes of fever in the tropics, by geographic area

GEOGRAPHIC AREA COMMON TROPICAL DISEASE CAUSING FEVER OTHER INFECTIONS CAUSING OUTBREAKS OR CLUSTERS IN TRAVELERS
Caribbean Chikungunya, dengue, malaria (Hispaniola), Zika Acute histoplasmosis, leptospirosis
Central America Chikungunya, dengue, malaria (primarily Plasmodium vivax), Zika, enteric fever Leptospirosis, histoplasmosis, coccidioidomycosis, leishmaniasis
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, scrub typhus
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 (Katayama fever), dengue African trypanosomiasis, chikungunya enteric fever, meningococcal meningitis

FINDINGS REQUIRING URGENT ATTENTION

Presence of fever plus certain associated signs, symptoms, or laboratory findings can suggest specific infections (Table 11-04). 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, it should be repeated if diagnosis is not clear, as new findings may appear that will help in the diagnostic process (such as skin lesions or a 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 also be associated with fever.

Fever accompanied by any of the following syndromes deserves further scrutiny, because it may indicate a disease of public health importance, where immediate infection control and containment measures are indicated:

  • Skin rash with or without conjunctivitis (for example, measles, meningococcemia, hemorrhagic fevers such as Ebola)
  • Rapid respiratory rate (for example, influenza, Middle East respiratory syndrome [MERS], pneumonic plague)
  • Persistent cough (for example, tuberculosis, pertussis)
  • Decreased consciousness (for example, meningococcal meningitis, rabies)
  • Bruising or unusual bleeding without previous injury (for example, hemorrhagic fevers)
  • Persistent voluminous diarrhea (for example, cholera)
  • Persistent vomiting other than air or motion sickness (for example, norovirus infection)
  • Jaundice (for example, hepatitis A)
  • Flaccid paralysis of recent onset (for example, polio)

Travelers visiting 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 VFRs than tourist travelers presented with serious (requiring hospitalization), potentially preventable travel-related illnesses (see Chapter 9, Visiting Friends & Relatives: VFR Travel).

Table 11-04. Clinical findings and select associated infectious diseases

COMMON CLINICAL FINDINGS INFECTIONS TO CONSIDER AFTER TROPICAL TRAVEL
Fever and rash Dengue, chikungunya, Zika, measles, spotted fever or typhus group rickettsioses, enteric fever (skin lesions may be sparse or absent), meningococcemia, acute HIV infection, varicella
Fever and abdominal pain Enteric fever, amebic or pyogenic liver abscess
Fever and normal or low white blood cell count Dengue, malaria, rickettsial infection, enteric fever, chikungunya, Zika, acute HIV
Fever and hemorrhage Viral hemorrhagic fevers (for example, dengue, yellow fever, Ebola, Lassa fever), meningococcemia, leptospirosis, spotted fever group rickettsial infections
Fever and arthralgia or myalgia (sometimes persistent) Chikungunya, dengue, Zika, Ross River virus, muscular sarcocystosis, trichinellosis
Fever and eosinophilia Acute schistosomiasis, drug hypersensitivity reaction; fascioliasis, sarcocystosis, trichinellosis, angiostrongyliasis, and other parasitic infections (rare)
Fever and respiratory symptoms/pulmonary infiltrates Influenza and other common bacterial and viral pathogens, legionellosis, tuberculosis, acute schistosomiasis, Q fever, leptospirosis, Middle East respiratory syndrome, acute histoplasmosis or coccidioidomycosis, psittacosis, melioidosis, pneumonic plague
Fever and altered mental status/central nervous system involvement Cerebral malaria, arboviral encephalitides (for example, Japanese encephalitis, West Nile virus), meningococcal meningitis, rabies, African trypanosomiasis, scrub typhus, angiostrongyliasis, tickborne encephalitis, rabies
Fever and jaundice Acute viral hepatitis (A, B, C, E), yellow fever and other viral hemorrhagic fevers, severe malaria, leptospirosis
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, melioidosis, African trypanosomiasis

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 disease outbreaks are dynamic, as demonstrated by the Ebola epidemic in West Africa in 2014–2015, introduction and spread of chikungunya virus in the Americas beginning in late 2013, nosocomial spread from travel-associated MERS in Korea in 2015, 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 US travelers.

Infections with typical seasonal transmission in the United States may 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 April to September; clinicians in the Northern Hemisphere must be alert to the possibility of influenza outside the usual “winter” influenza season.

Travelers may acquire infections caused by bacteria resistant to commonly used antibiotics (see Antimicrobial Resistance in this chapter). Bacteria that produce extended-spectrum β-lactamases and carbapenem-resistant Entero­bacteriaceae, including bacteria expressing the metalloprotease NDM-1, have been found in infections acquired during travel, most often related to medical care (both elective and emergency). Travelers to South and Southeast Asia are at high risk of acquiring multidrug-resistant Enterobacteriaceae. Enteric fever (typhoid or paratyphoid fever), has become increasingly resistant to fluoroquinolones and third-generation cephalosporins and azithromycin in some regions (see Chapter 4, Typhoid & Paratyphoid Fever).

KEEP IN MIND

  • Malaria is the most common cause of acute undifferentiated fever after travel to sub-Saharan Africa and some other tropical areas.
  • Malaria, especially P. falciparum, can progress rapidly. Diagnostics should be done promptly and treatment instituted immediately if malaria is diagnosed (see Chapter 4, Malaria).
  • A history of taking malaria prophylaxis does not exclude the possibility of malaria.
  • Patients with malaria may be afebrile at the time of evaluation but typically give a history of fever or chills. They 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 viruses.
  • Fever in returned travelers is often caused by common infections, such as diarrhea, pneumonia, and pyelonephritis, which should not be overlooked in the search for exotic diagnoses.
  • The possibility that travelers may be infected or colonized with drug-resistant pathogens should be considered, especially among those who have been hospitalized abroad.
  • Viral hemorrhagic fevers other than dengue (for example, Ebola, Lassa fever, Marburg hemorrhagic fever) 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 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.

BIBLIOGRAPHY

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  6. Mendelson M, Han PV, Vincent P, von Sonnenburg F, Cramer JP, Loutan L, et al. Regional variation in travel-related illness acquired in Africa, March 1997–May 2011. Emerg Infect Dis. 2014 Apr;20(4):532–41.
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