RESUMEN
Ebola virus disease poses a recurring risk to human health. We conducted a systematic review (PROSPERO CRD42023393345) of Ebola virus disease transmission models and parameters published from database inception to July 7, 2023, from PubMed and Web of Science. Two people screened each abstract and full text. Papers were extracted with a bespoke Access database, 10% were double extracted. We extracted 1280 parameters and 295 models from 522 papers. Basic reproduction number estimates were highly variable, as were effective reproduction numbers, likely reflecting spatiotemporal variability in interventions. Random-effect estimates were 15·4 days (95% CI 13·2-17·5) for the serial interval, 8·5 days (7·7-9·2) for the incubation period, 9·3 days (8·5-10·1) for the symptom-onset-to-death delay, and 13·0 days (10·4-15·7) for symptom-onset-to-recovery. Common effect estimates were similar, albeit with narrower CIs. Case-fatality ratio estimates were generally high but highly variable, which could reflect heterogeneity in underlying risk factors. Although a substantial body of literature exists on Ebola virus disease models and epidemiological parameter estimates, many of these studies focus on the west African Ebola epidemic and are primarily associated with Zaire Ebola virus, which leaves a key gap in our knowledge regarding other Ebola virus species and outbreak contexts.
RESUMEN
BACKGROUND: The R21/Matrix-M vaccine has demonstrated high efficacy against Plasmodium falciparum clinical malaria in children in sub-Saharan Africa. Using trial data, we aimed to estimate the public health impact and cost-effectiveness of vaccine introduction across sub-Saharan Africa. METHODS: We fitted a semi-mechanistic model of the relationship between anti-circumsporozoite protein antibody titres and vaccine efficacy to data from 3 years of follow-up in the phase 2b trial of R21/Matrix-M in Nanoro, Burkina Faso. We validated the model by comparing predicted vaccine efficacy to that observed over 12-18 months in the phase 3 trial. Integrating this framework within a mathematical transmission model, we estimated the cases, malaria deaths, and disability-adjusted life-years (DALYs) averted and cost-effectiveness over a 15-year time horizon across a range of transmission settings in sub-Saharan Africa. Cost-effectiveness was estimated incorporating the cost of vaccine introduction (dose, consumables, and delivery) relative to existing interventions at baseline. We report estimates at a median of 20% parasite prevalence in children aged 2-10 years (PfPR2-10) and ranges from 3% to 65% PfPR2-10. FINDINGS: Anti-circumsporozoite protein antibody titres were found to satisfy the criteria for a surrogate of protection for vaccine efficacy against clinical malaria. Age-based implementation of a four-dose regimen of R21/Matrix-M vaccine was estimated to avert 181â825 (range 38â815-333â491) clinical cases per 100â000 fully vaccinated children in perennial settings and 202â017 (29â868-405â702) clinical cases per 100â000 fully vaccinated children in seasonal settings. Similar estimates were obtained for seasonal or hybrid implementation. Under an assumed vaccine dose price of US$3, the incremental cost per clinical case averted was $7 (range 4-48) in perennial settings and $6 (3-63) in seasonal settings and the incremental cost per DALY averted was $34 (29-139) in perennial settings and $30 (22-172) in seasonal settings, with lower cost-effectiveness ratios in settings with higher PfPR2-10. INTERPRETATION: Introduction of the R21/Matrix-M malaria vaccine could have a substantial public health benefit across sub-Saharan Africa. FUNDING: The Wellcome Trust, the Bill & Melinda Gates Foundation, the UK Medical Research Council, the European and Developing Countries Clinical Trials Partnership 2 and 3, the NIHR Oxford Biomedical Research Centre, and the Serum Institute of India, Open Philanthropy.