Anti-Zika Virus ELISA (IgG or IgM)
IIFT Arbovirus Fever Mosaic 2 (IgG or IgM)
EUROIMMUN and Roche announced that they have entered into an option agreement under which Roche gains access to intellectual property in the field of Zika virus immunodiagnostics assigned to EUROIMMUN.
Anti-Zika virus IgA may indicate an acute infection in anti-Zika virus IgM-negative patients.
Especially in secondary flavivirus infections specific IgM - the classical marker of acute infection – is often found at low titer, sometimes being even undetectable, while synthesis of specific IgG is rapidly stimulated. Shortly after infection, the IgG titer then levels off at moderate concentration, indistinguishable from IgG titers in convalescent infections. Similar situations have also been observed in patients with Zika virus (ZIKV) infections, recently, making it difficult to discriminate between an acute secondary and a past infection. Since ZIKV is suspected to be associated with major neurological consequences (Guillan-Barré syndrome, microcephaly in newborns), diagnosis of acute infections though is highly crucial. We analysed the course of anti-ZIKV IgA, IgM and IgG titers in two confirmed patients for whom sequential serum samples were available asking whether IgA as alternative to IgM could indicate an acute phase of infection.
First data from the EUROIMMUN Anti-Zika virus ELISA (IgA) were presented at the IMED - International Meeting on Emerging Diseases and Surveillance (Vienna, Austria on November 4-7, 2016) and the 1st International Conference on Zika Virus in February 2017 in Washington DC, USA.
ELISA and indirect immunofluorescence tests (IIFT) have been developed for sensitive and specific detection of antibodies against Zika virus in patient serum samples. The assays are suitable for diagnosing acute infections as well as for disease surveillance. In particular, serological analysis can aid the differentiation of infections with Zika virus, dengue virus and chikungunya virus, which manifest with similar symptoms and are endemic in much the same geographic regions.
Serological tests provide a much longer window for diagnosis than direct detection methods. Detection of the virus by RT-PCR is only effective during the viraemic phase within the first week after onset of symptoms, and may already be negative by the time a patient consults their doctor. Anti-Zika virus antibodies appear around day 4 to 7 after symptom onset. IgM antibodies reach their peak after two to three weeks and remain detectable for several months, while IgG are assumed to persist life-long. The detection of specific IgM antibodies or a significant rise in the specific IgG titer in a pair of samples taken at least two weeks apart is evidence of an acute infection.
Anti-Zika Virus ELISA (IgM or IgG) provide fully automated antibody detection using microplates coated with a recombinant protein from Zika virus. This highly specific antigen avoids cross-reactivity with other flaviviruses. Preliminary data from panels of serologically well characterised sera indicate that there is no cross-reactivity with flaviruses like dengue, West Nile and Japanese encephalitis viruses. Larger studies are underway to confirm this.
Anti-Zika Virus IIFT (IgM or IgG) utilise Zika virus-infected cells as the antigenic substrate. Positive and negative results are evaluated by fluorescence microscopy. With the Arbovirus Fever Mosaic 2 the Zika virus substrate is incubated in parallel with substrates for chikungunya virus and dengue virus serotypes 1 to 4. This BIOCHIP combination can help in differential diagnostic delimitation of Zika, dengue and chikungunya virus infections. Due to the use of whole virus particles, cross reactivities between flavivirus antibodies such as dengue and Zika virus can occur.
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The German Society of Gynaecology and Obstetrics (DGGG) recommends test systems based on Zika virus NS1 antigen for the diagnosis of Zika virus infections.
231. DGGG Statement, p. 4, 2nd para. (only available in German): "Due to the antigenic similarity with other Flaviviruses (e.g. dengue virus), significant cross reactions can occur in the IIFT (based on whole virus antigen). This effect is considerably less pronounced in the NS1 EIA* (a recombinant protein is used as antigen) owing to the high specificity (Huzly et al., 2016).
*EUROIMMUN Anti-Zika-Virus ELISA
The Growing Global Threat of Zika, Dengue and Chikungunya Viruses
Medlab Magazine. 2016