COMMENTARY

Returning Travelers With Fever: Dengue or Dengue Lookalike?

Tyler Sharp, PhD

Disclosures

February 13, 2017

Editorial Collaboration

Medscape &

The Returning Traveler With Febrile Illness

The recent emergence of Zika and chikungunya viruses in the Americas has made more difficult a previously challenging task: diagnosing acute febrile illness in patients returning from the tropics solely on the basis of their history and physical examination (Figure).

Figure. Maculopapular rash, a common finding in returning travelers with febrile illness. (a). Dengue. (b). Chikungunya. (c). Zika.

The rash of leptospirosis (not shown) is a maculopapular or petechial, nonpruritic rash that can be present on the extremities, face, or trunk, or diffusely throughout the body.

Tens of thousands of travelers return to the United States each year with fever. Therefore, the purpose of this article is to provide clinicians with a clinical and epidemiologic summary of some of the most common causes of acute febrile illness in returning travelers (Table).

Table. Signs and Symptoms of Common Causes of Acute Febrile Illness in Travelers

Sign/Symptom Zika Dengue Chikungunya Leptospirosis
Fever ++ +++ +++ +++
Rash ++ ++ ++ ++
Conjunctivitis + - - +
Arthralgia ++ + +++ +
Myalgia ++ +++ ++ +++
Headache + ++ ++ ++
Minor bleeding - ++ - ++
Shock - + - +
Leukopenia + +++ + -
Thrombocytopenia -/+ ++ + ++

+++: nearly always present; ++: frequently present; +: may be present; -: infrequently or never present

However, in all cases, the take-home message is that accurate diagnosis based on history and physical examination alone is exceedingly difficult; hence, a high index of suspicion should be coupled with a broad differential diagnosis. Laboratory-based testing should be ordered to conclusively diagnose the disease.

Dengue

Dengue is one of the most common causes of acute febrile illness in travelers returning from the tropics (see the Centers for Disease Control and Prevention [CDC] Dengue Map), where its mosquito vector is endemic. Most clinical manifestations of dengue are nonspecific, although minor bleeding (eg, petechiae, gingival bleeding) occurs in roughly one third of patients. Leukopenia and thrombocytopenia are common laboratory findings, but are not always present.[1]

Like influenza, dengue is both seasonal and cyclical; the annual incidence is highest in the summer rainy season, and epidemics tend to occur every 3-5 years. US Food and Drug Administration (FDA)-approved molecular diagnostic testing by reverse-transcriptase polymerase chain reaction (RT-PCR) is the most specific diagnostic option, but viral nucleic acid is most often detectable only within the first 5 days after illness onset. Thereafter, anti-DENV immunoglobulin M enzyme-linked immunosorbent assay (ELISA) is likely to be positive, but antibodies may cross react with other flaviviruses (eg, West Nile and Zika viruses).

Both RT-PCR and immunoglobulin M ELISA are available in many state public health laboratories, some city health department laboratories, and selected hospitals. Test results typically take 1-10 days to become available. Rapid diagnostic tests for dengue have not yet been approved by the FDA.

Chikungunya

Although chikungunya has probably been endemic in parts of sub-Saharan Africa and southern Asia for decades, it first emerged in the Americas in 2013, where it caused explosive outbreaks.[2] Although its incidence is currently low, cases are still being reported throughout the Americas. To track cases in the United States, click on "CHIK" on this CDC map.

Fever and arthralgia are the most common clinical manifestations of chikungunya, although these features may also be present in other acute febrile illnesses. Diagnostic testing algorithms and turnaround time mirror those of dengue, and both molecular and serologic diagnostic tests are available.

Diagnostic testing is available through a few commercial laboratories, many state health departments, and the CDC.

Zika

Zika emerged in the Americas in 2014 and has since been shown to cause microcephaly and other severe birth defects in developing fetuses of some pregnant women infected during pregnancy. Zika virus infection also has been associated with Guillain-Barré syndrome and severe thrombocytopenia, although both are rare complications.

Most infected individuals will not develop clinical manifestations of infection, and most of those who do will experience rash, fever, arthralgia, or conjunctivitis. The reported incidence of conjunctivitis is variable.

Most infections occur after mosquito bites, although sexual transmission is also possible. Diagnostic testing algorithms are similar to those for dengue and chikungunya, although the virus may also be detectable in urine. Refer to the CDC Testing for Zika website for up-to-date guidance on recommended approaches to Zika diagnostic testing.

Leptospirosis

A common but often overlooked tropical infectious disease, leptospirosis is a bacterial zoonosis transmitted by direct or indirect contact with animal urine.[3] Rats and dogs are the most frequently recognized vectors, although nearly all mammals can be vectors. Leptospirosis is endemic throughout the tropics and subtropics, and cases may be misdiagnosed as dengue or other common causes of acute febrile illness. Exposure to animal urine by walking barefoot, swimming in lakes or rivers, or caring for sick animals is often associated with infection.

Complications, including severe renal and liver injury and hemorrhage, occur in approximately 10% of patients. Case-fatality rates among hospitalized patients can be as high as 10%, especially in those who do not receive early antibiotic therapy (ie, penicillin-derivative antibiotics). The incidence is highest in the summer rainy season, and outbreaks can be associated with heavy rains and flooding, when bacteria that have been shed in the soil are liberated and may then come into contact with mucosal surfaces. Only serologic diagnostic testing is available from commercial laboratories in the United States, although additional testing can be requested from CDC through state and local health departments.

Influenza

Influenza is a common cause of respiratory illness throughout the world, yet clinicians may not consider it as a cause of acute febrile illness in returning travelers. Although fever and myalgia are common, respiratory symptoms, such as cough and clear rhinorrhea, occur more frequently in patients with influenza than other acute tropical febrile illnesses.

Seasonal and annual trends in areas where the traveler was present should be considered during diagnosis. CDC offers an up-to-date interactive map of infectious disease outbreaks worldwide. Both rapid and laboratory-based diagnostic tests are widely available, as are antiviral medications.

Other Causes of Acute Febrile Illness in Travelers

Many causes of acute febrile illness that were not covered specifically in this article should be considered when evaluating febrile returning travelers. These include malaria, bacterial infections, viral gastroenteritis, and viral respiratory illnesses other than influenza. Clinicians should always collect a complete travel history, including exposures, to guide diagnosis and management.

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