Differential diagnosis of arbovirus infections
Serological tests for Zika virus (ZIKV), dengue virus (DENV) and chikungunya virus (CHIKV) allow differential diagnosis of infections, especially beyond the short viremic phase when direct detection is no longer effective. These infections are difficult to tell apart clinically, as they manifest with similar symptoms and are endemic in much the same regions. Antibodies against DENV, ZIKV and CHIKV are detectable from around day four to seven after symptom onset. Primary infections are characterized by the occurrence of IgM antibodies, with IgG appearing shortly afterwards. In a secondary flavivirus infection, IgM may be delayed, of reduced intensity or not detectable at all. In these cases a significant increase in the IgG concentration is indicative of an active infection.
ZIKV antibodies can be detected specifically using ELISA based on recombinant ZIKV NS1 protein. This highly specific antigen avoids cross-reactivity with other flavivirus antibodies which may be present from previous infections or vaccinations, e.g. DENV, West Nile, yellow fever, tick-borne encephalitis and Japanese encephalitis viruses. A combination of Anti-ZIKV IgM and IgG ELISA provides an overall sensitivity of 97% at a specificity of 100%. In DENV infections, detection of the highly specific early antigen NS1 by ELISA serves as a first-line screening test in both acute primary infections and re-infections with another DENV serotype. Antibodies against DENV serotypes 1 to 4 are detected using ELISA based on highly purified virus particles, while CHIKV antibodies are determined using ELISA based on a virus-specific structural protein.
Indirect immunofluorescence tests (IIFT) with virus-infected cells are also suitable for detection of DENV, ZIKV and CHIKV antibodies. However, cross reactions between flavivirus antibodies should be taken into account. Arbovirus BIOCHIP mosaics combine different substrates in one test field and aid clarification of cross reactivities, supporting differential diagnosis.
