Abstract
Flaviviruses circulate worldwide and cause a number of medically relevant human diseases, such as dengue, Zika, yellow fever, and tick-borne encephalitis (TBE). Serology plays an important role in the diagnosis of flavivirus infections, but can be impeded by antigenic cross-reactivities among flaviviruses. Therefore, serological diagnosis of a recent infection can be insufficiently specific, especially in areas where flaviviruses co-circulate and/or vaccination coverage against certain flaviviruses is high. In this study, we developed a new IgM assay format, which is well suited for the specific diagnosis of TBE, Zika and dengue virus infections. In the case of TBE and Zika, the IgM response proved to be highly specific for the infecting virus. In contrast, primary dengue virus infections induced substantial amounts of cross-reactive IgM antibodies, which is most likely explained by structural peculiarities of dengue virus particles. Despite the presence of cross-reactive IgM, the standardized nature and the quantitative read-out of the assay even allowed the serotype-specific diagnosis of recent dengue virus infections in most instances.
Highlights
Flavivirus infections are of global importance for human health and pose increasing threats, as illustrated by the spread of dengue (DEN), Zika, West Nile, and tick-borne encephalitis virus (TBE) viruses
The latter situation is prominent in Central Europe, because of its high TBE vaccination coverage and many travelers returning from holiday destinations where they might have been at risk for dengue and Zika virus infections
Zika virus infection was confirmed by PCR in 3 of the 20 patients using samples obtained 2–4 days after symptom onset (Z4, Z7 and Z20 in Table 4), when the sera were still negative in routine Zika and dengue IgM ELISAs
Summary
Flavivirus infections are of global importance for human health and pose increasing threats, as illustrated by the spread of dengue (DEN), Zika, West Nile, and tick-borne encephalitis virus (TBE) viruses (reviewed in [1,2]). These pathogens are transmitted to humans by specific arthropod vectors, either mosquitoes (dengue, Zika, West Nile, yellow fever, and Japanese encephalitis viruses) or ticks (TBE virus). The problem is not unusual in travelers with pre-existing vaccine-induced immunity returning with ill-defined diseases from endemic areas The latter situation is prominent in Central Europe, because of its high TBE vaccination coverage and many travelers returning from holiday destinations where they might have been at risk for dengue and Zika virus infections
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