Lassa fever outbreaks, mathematical models, and disease parameters: a systematic review and meta-analysis

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Background Understanding the epidemiological parameters and transmission dynamics of Lassa fever, a significant public health threat in west Africa caused by the rodent-borne Lassa virus, is crucial for informing evidence-based interventions and outbreak response strategies. Therefore, our study aimed to collate and enhance understanding of the key epidemiological parameters of Lassa fever. Methods We conducted a systematic review, searching PubMed and Web of Science for peer-reviewed studies published from database inception up to June 13, 2024, to compile and analyse key epidemiological parameters, mathematical models, and outbreaks of Lassa fever. English-language, peer-reviewed, original research articles were included if they reported on Lassa fever outbreak sizes, transmission models, viral evolution, transmission, natural history, severity, seroprevalence, or risk factors. Non-peer-reviewed literature was excluded. Data were extracted by two independent individuals from published literature, focusing on seroprevalence, transmissibility, epidemiological delays, and disease severity. We performed a meta-analysis to calculate pooled estimates of case-fatality ratios (CFRs) and the delay from symptom onset to hospital admission. This study is registered with PROSPERO (identifier number CRD42023393345). Findings The database search returned 5614 potentially relevant studies, and a further 16 studies were identified from backward citation chaining. After de-duplication and exclusion, 193 publications met our inclusion criteria and provided 440 relevant parameter estimates in total. Although Lassa virus is endemic in west Africa, the spatiotemporal coverage of general-population seroprevalence estimates (ranging from 2·6% [6/232] to 58·2% [103/177]) was poor, highlighting the spatial uncertainty in Lassa fever risk. Similarly, only four basic reproduction number estimates (ranging from 1·13 to 1·40) were available. We estimated a pooled total random effect CFR of 33·5% (95% CI 25·8–42·2, I 2 =95%) and found potential variation in severity by geographical regions typically associated with specific Lassa virus lineages. We estimated a pooled total random effect mean symptom-onset-to-hospital-admission delay of 8·19 days (95% CI 7·31–9·06, I 2 =93%), but other epidemiological delays were poorly characterised in the existing literature. Interpretation Our findings highlight the absence of empirical Lassa fever parameter estimates despite its high burden in west Africa. Improved surveillance approaches to capture mild cases in humans and to further cover rodent populations are needed to better understand Lassa fever transmission dynamics. Addressing these gaps is essential for developing accurate mathematical models and informing evidence-based interventions to mitigate the effect of Lassa fever on public health in endemic regions. Funding UK Medical Research Council, National Institute for Health and Care Research, Academy of Medical Sciences, Wellcome, UK Department for Business, Energy, and Industrial Strategy, British Heart Foundation, Diabetes UK, Schmidt Foundation, Community Jameel, Royal Society, and Imperial College London. Translation For the French translation of the abstract see Supplementary Materials section.

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