Clinical diagnosis is often difficult, as infectious exanthematous diseases such as measles, rubella, click here human parvovirus B19, dengue, human herpes virus (HHV)-6, roseola infantum, and scarlet fever have overlapping clinical symptoms. In Brazil, from 1994 to 1998, 327 patients presenting with pathologies characterized by variable combinations of exanthema, cough, conjunctivitis, coryza, and fever were studied. A laboratory-confirmed diagnosis was achieved in 71.3% of cases: 33% were diagnosed with dengue fever, 20% with rubella, 9.2% with human parvovirus B19, 6.7% with measles,
and 2.1% with HHV-6. These results underline the important proportion of cosmopolitan febrile exanthemas. In France, Hochedez and colleagues screened 62 returning travelers presenting with fever and exanthema for exotic (if returning from endemic areas) and cosmopolitan infections. They found a specific etiology in over 90% of the patients. The three main diagnoses were chikungunya, dengue, and African tick bite fever, followed by infectious mononucleosis, human immunodeficiency virus-1 primary infection, cytomegalovirus primary infection, CDK inhibition measles, rubella, chicken pox, streptococcal infections, primary toxoplasmosis, acute schistosomiasis, and adverse drug reactions.
Travelers presenting with febrile exanthema should therefore be screened not only for arboviral infections according to the area visited but also for more common infections. The diagnosis of dengue fever is based on the detection of NS1 Ag, antibodies (IgM and IgG) or reverse transcription (RT)-PCR (virus isolation is used less often). For early diagnosis (onset < 5 days), detection of NS1 Ag may
be used, but its moderate sensitivity requires the presence of both NS1 Ag and IgM for a definite diagnosis. IgM are positive 4 to 5 days after disease onset and remain so for up to 3 to 6 months. IgG appear approximately 7–10 days after onset and are detectable thereafter for life. RT-PCR detection of viral RNA is a very reliable technique for patients presenting within 5 to 7 days of the onset of symptoms, but this method is more expensive, nonstandardized, and only a few centers in France use it unless routinely. Consequently, serological tests are commonly used to establish or confirm a diagnosis of dengue. Currently available commercial rapid tests offer good sensitivity, but they lack specificity, which may lead to false-positive results as in our index case. Overall, possible explanations for false-positive results include cross-reactive flavivirus-specific antibodies, nonspecific binding of antibodies secreted in the course of various infections such as mononucleosis or hepatitis, and rheumatoid factor. Cross-reactivity with measles antibodies is not commonly assumed by biologists and, to our knowledge, has only been reported once in Belgium.