Eleni Nastouli is WP4 ZIKA-VD Co-Lead and works for the Department of Clinical Virology, University College London Hospitals NHS Trust, Great Ormond Street Hospital for Children NHS Trust, London, UK
The main focus of our group has been the optimisation of the current algorithm for testing pregnant women and their infants recruited in the ZIKAction studies. We started recruitment in Jamaica which is exciting and in order to answer the questions around vertical transmission in symptomatic and asymptomatic women at a given site and at a given time we were faced with challenging dilemmas around the optimal sampling protocol and importantly the optimal testing strategy for arbovirus infections (Zika, dengue and chikungunya).
Available serological assays for Zika IgM and IgG detection have limitations in their performance (sensitivity and specificity) especially in populations heavily pre-exposed to dengue. This was demonstrated in evaluations of multiple assays in Rio de Janeiro at the Oswaldo Cruz Foundation (FIOCRUZ) using panels of carefully selected sera. We have been following very closely the rapid developments in the field and reviewed available evaluation data from the CDC, WHO and the NIH. Ana Bispo’s group in Rio evaluated novel assays like the BOB assay developed by HUMABS BioMed hopefully giving us access to assays with improved performance. Our group led by UCL and Fiocruz in collaboration with Jamaican colleagues has finalised the testing algorithm based on data from currently available assays; that includes a screening and confirmatory strategy and incorporation of enhanced molecular testing as well as a clinical interpretation algorithm for testing and providing results in real time. It is also becoming clear that in order to aid the interpretation and statistical analysis of the vertical transmission study results we need a sero-epidemiology study at the recruitment sites to inform on background sero-prevalence and an active surveillance data monitoring scheme of circulating viruses at the time of recruitment. Specific study protocols have been prepared and are ready for Ethics submission. The UCL group have been working on optimising/modifying existing protocols for detection of Zika, dengue and chikungunya RNA with particular focus on sensitivity and selecting the optimal sampling strategy given that recent data suggest prolonged detection of Zika in whole blood as opposed to plasma. We are developing a quality control scheme for molecular diagnostics to allow testing at different sites as well as whole genome sequencing methods using an established pipeline for other RNA viruses.
Our priorities in the next few months are 1) to ensure proper collection and storage of study samples at recruiting sites, 2) establish serological and molecular testing according to our algorithms at these sites, 3) adapt those algorithms accordingly as new data become available, including our own data, 4) perform the sero-prevalence studies we need and 5) prioritise development of assays critical for our pregnancy studies, like Zika IgG avidity.
