Zika virus surveillance in human and mosquito populations in Cabo Verde – exploring molecular and serological tools for the surveillance of emerging infectious diseases
The first confirmed cases of Zika virus disease in the Americas were described in Northeast Brazil in May 2015, following the introduction from French Polynesia. Five months later, the first confirmed cases of autochthonous transmission and Zika congenital syndrome were reported in Cabo Verde, Africa. Following the outbreak, human and entomological samples across endemic regions in Cabo Verde were collected to provide insights into outbreak dynamics. In this thesis, I profile the Aedes aegypti mosquito population on Cabo Verde, the primary vector of Zika virus transmission. This work investigates their susceptibility to insecticides, through the targeted sequencing of a cross-section of entomological samples collected in Praia, the capital city. The analysis revealed two Aedes aegypti mosquitoes with detectable levels of Zika virus. Building on these findings, I applied molecular techniques to profile the vectors’ virome and proceeded to enrich and sequence whole-genome data for Zika virus. The resulting sequence data, combined with a global Zika sequence dataset, were placed phylogenetically into the broader epidemiological context of the 2015-2016 Zika epidemic, revealing two discrete introductions of Zika that occurred from the Americas to Cabo Verde in this period. In parallel, I describe the findings of a sero-epidemiological study based on a cross-sectional cohort of human participants, sampled shortly after the cessation of Zika transmission. By comparing a panel of arbovirus serological assays and using a multivariate logistic modelling approach, key risk-factors for Zika seropositivity were determined. This work was followed up by an investigation on how virus serological diagnostics may be improved. I initially formulate a novel in-silico meta-analysis pipeline, which may guide the selection of specific antigenic targets for immunoassay development. This approach is applied in the context of another emerging infectious disease, SARS-CoV-2. Expanding on this, I report a refined, novel molecular methodology for the translation of in-silico reverse antigen design techniques into scalable immunoassays. Overall, this thesis describes the application of molecular and serological techniques to understand the dynamics of the Zika outbreak in Cabo Verde. I develop novel methodologies to improve on current serological tools, translating them to address current challenges in the surveillance of emerging infectious diseases.
https://researchonline.lshtm.ac.uk/id/eprint/4670855/10.17037/PUBS.04670855
https://researchonline.lshtm.ac.uk/id/eprint/4670855/1/2022_ITD_PhD_WARD_DSR.pdf