Evaluation of ELISA-based sero-diagnosis of dengue fever in travelers

Abstract Diagnosis of dengue virus infection in travelers is often based on commercially available ELISA-based serological assays and not on the more difficult and costly procedures of Hemagglutination inhibition (HI), virus isolation or RT-PCR. These standard assays are not quantitative and are designed to diagnose primary and secondary dengue virus infections by testing for IgG and IgM antibodies. However, cross reactivity between various flaviviruses and the fact that most travelers today are prevaccinated against Japanese encelphalitis (JE) and yellow fever (YF) create a potential problem in such diagnosis. Our study was aimed at measuring the extent of false positive diagnosis in prevaccinated travelers which we have assessed by testing for dengue IgG and IgM antibodies in a group of prevaccinated healthy travelers using the PanBio indirect IgG ELISA and IgM capture ELISA kits. The IgM test was negative in all healthy vaccinees, thus, being highly specific. However, the kit had a disadvantage, which was recognized in other travelers clinically ill with dengue fever (DF), in which the IgM response was detected only 4–8 days after onset of the clinical symptoms. The IgG test yielded 11–17 and 15–44% positives in healthy travelers vaccinated against JE and YF, respectively. We conclude that the specificity of the IgG-ELISA assay in prevaccinated travelers is much lower than in unvaccinated populations. Thus, an IgG-positive results in a vaccinated traveler and IgM negative result during the 1st week of the illness period, are both inconclusive.