A systematic review of Zika virus disease: epidemiological parameters, mathematical models, and outbreaks

BackgroundZika virus (ZIKV) is an Aedes-borne arbovirus that can cause serious risks of neurological complications and birth defects in newborns of mothers infected during pregnancy. ZIKV is classified as a priority pathogen by the World Health Organization. MethodsWe conducted a systematic review of peer-reviewed studies reporting ZIKV epidemiological parameters, transmission models, and outbreaks (PROSPERO #CRD42023393345) to characterise its transmissibility, seroprevalence, risk factors, disease sequelae, and natural history. We performed a meta-analysis of Congenital Zika Syndrome (CZS), pregnancy loss probabilities amongst ZIKV-infected mothers and the proportion of symptomatic cases. FindingsWe extracted information from 574 of 27,491 identified studies. Across 418 included studies assigned a high-quality score, we extracted 969 parameters, 127 outbreak records, and 154 models. We estimated a pooled total random effect of CZS probability (4.65%), pregnancy loss probability (2.48%), and proportion of symptomatic cases (51.20%). Seroprevalence estimates (n=354) were retrieved beyond South America and French Polynesia. The basic reproduction number estimates (n=77) ranged between 1.12 and 7.4. We found 66 human epidemiological delay estimates, ranging 4-12.1 days for the intrinsic incubation period (n=11), 3-50 days for the infectious period (n=15), 5.1-24.2 days for the extrinsic incubation period (n=22), and 7.4-32.9 days for the serial interval (n=27). These data are available in the R package epireview. InterpretationThis study provides the most comprehensive systematic summary of the ZIKV epidemiological information currently available in the literature. Large heterogeneities and inconsistencies in the reporting of parameter estimates, study designs, and parameter definitions were found, underscoring the need for standardised epidemiological definitions in future publications. FundingAcademy of Medical Sciences, British Heart Foundation, Community Jameel, Diabetes UK, Imperial College London, National Institute for Health and Care Research, Royal Society, Schmidt Sciences, UK Department for Business, Energy, and Industrial Strategy, UK Medical Research Council, United Nations Foundation, Wellcome Trust. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Web of Science and PubMed from database inception to October 31, 2024 to collate epidemiological parameters, mathematical models, and outbreaks of Zika virus (ZIKV). We found 66 systematic reviews on ZIKV since 2016: of these, 29 focussed on Congenital Zika Syndrome (CZS) and/or Guillain-Barre Syndrome, 19 on ZIKV transmission, 16 on the distribution and burden of ZIKV infection and disease and the remaining on clinical presentation, severity, forecasting, time-to-event, risk mapping and vaccines and therapeutics. The published systematic reviews included between 4 to 204 publications, and most (75%) had a global scope. Only 5 systematic reviews conducted a meta-analysis assessing the overall probability of CZS upon infection in the mother, and only 1 review investigated the probability of CZS by trimester of pregnancy (using 2 articles). Added value of this studyIn this systematic review, we extracted information from 574 relevant studies, which makes this the most comprehensive synthesis of Zika parameters for outbreak response to date. From 418 studies with a high-quality assessment score, we extracted 969 epidemiological parameters, 127 outbreak records and 154 transmission models, most of which were published after the 2016 outbreak. We extracted and analysed 354 geolocated and time-stamped seroprevalence estimates; 100 basic and 15 effective reproduction number estimates from 21 countries; 66 human epidemiological delays and 22 extrinsic incubation periods. Our meta-analysis provides robust pooled estimates of the proportion of symptomatic cases (51.20%) and CZS probability (4.65%), also stratified by trimester based on maternal ZIKV infection (based on 7 publications), addressing a gap present in most previous reviews. Implications of all the available evidenceThis study provides the most comprehensive overview of ZIKV epidemiology to date, serving as a valuable resource for future modelling studies and stakeholders developing preparedness and response plans to control future outbreaks.