Large parts of Latin America experienced explosive zika epidemics during 2015 and 2016. In contrast over the 2016/7 and 2017/8 mosquito seasons very few Zika cases were detected. There is much debate about the underlying reasons for this, but a high level of population immunity acquired during the initial outbreaks is one favoured explanation. ZIKAction has study sites in Kingston, Jamaica and in Rio de Janeiro and in response to the pattern of infection, we have widened to scope of our studies to investigate the seroprevalence of zika , in our study communities.
Since most Zika infections (80%) are thought to be asymptomatic or unrecognised, case reporting tells us little about the scale of the epidemic and measuring the population seroprevalence is the only way to define the burden of infection. Studies in Polynesia have suggested a high population immunity in these small island populations following short lasting zika epidemics. Modelling studies also predict high levels of infection, but is this the case in the larger urban populations and diverse ecological settings in Brazil or in Jamaica?
Understanding this will inform our ongoing and future studies. Accurate serology is essential to perform seroepidemiological studies, but because the flaviviruses Dengue and zika exhibit extensive antigenic cross-reactions this makes the interpretation of serology problematic in populations where both infections are endemic (lanciotti). Currently there are no suitable commercial assays to accurately detect zika IgG antibodies. The one widely available assay for Zika IgG (Euroimmune) is sensitive, but it gives a high and variable rate of non-specific results in populations with a prior exposure to Dengue.
Many groups are working on this challenge, Population based studies screening with the Euroimmune assay and then confirming results with Virus neutralisation (VNT) are underway (Netto). We have established panels of sera to assess the sensitivity of available zika antibody assays using sequential sera from PCR confirmed zika cases and specificity using sera from confirmed dengue cases collected before zika infection was established in Latin America in 2013.We have used these to develop a programme looking at novel antibody assays to deal with the problems posed by cross reactive flavivirus antibodies. Our initial studies have used a promising Mab blocking assay (BOB)(Balmasada), but a range of approaches using different formats( Double Antigen Binding Assays, Immune Complex Binding) , different viral proteins ( NS1 and modified E proteins)and the use of competitor molecules are all under investigation. Our initial seroepidemiological studies combined with modelling approaches have used stored antenatal sera and readily available clinic sera. Studies using more representative population based sera are being planned.
The seroprevalence of Zika and chikungunya virus infections has never been determined in these populations and the data generated from these studies will be important in defining the proportion of adults who are immunologically naïve and thus at risk of future infection. This will guide public health advice and interventions, including vaccination strategies. It will also provide key information to inform the siting, design and conduct of studies of congenital Zika infection.
References:
Lanciotti RS, Kosoy OL, Laven JJ et al 2008. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 14:1232–1239. https://doi.org/10.3201/eid1408.08028
Balmaseda A, Stettler K, Medialdea-Carrera R et al 2017. Antibody-based assay discriminates Zika virus infection from other flaviviruses. Proc Natl Acad Sci U S A 114:8384–8389. https://doi.org/10.1073/pnas.1704984114
Netto EM, Moreira-Soto A, Pedroso C, et al. 2017. High Zika virus seroprevalence in Salvador, northeastern Brazil limits the potential for further outbreaks. mBio 8:e01390-17. http://mbio.asm.org/content/8/6/e01390-17
David Brown is Medical Researcher at Instituto Oswaldo Cruz – FIOCRUZ, Rio de Janeiro, Brazil
