Interventions for the management of snakebite envenoming: An overview of systematic reviews

Introduction: Snakebite is a neglected tropical disease that leads to more than 120,000 deaths every year. In 2019, World Health Organization (WHO) launched a strategy to decrease its global burden by 2020. There is a range of issues around different interventions for the management of snakebite. Decisions around these interventions should be informed by evidence from systematic reviews (SR). Methods: An overview of SRs was conducted by searching 12 electronic databases, PROSPERO, contacting experts and screening the bibliography of included reviews. Screening, data extraction, and quality assessment (through AMSTAR-2) was done by at least two overview authors independently with discrepancies sorted by consensus. A narrative synthesis was conducted. Principle findings: The overview found 13 completed SRs that has looked at various aspects of management of snakebite envenomation. There was one SR on first aid, nine on effectiveness and safety of snake anti-venom (SAV), two on drugs to prevent adverse reactions due to SAV therapy, and one on surgical interventions for management of snakebite envenomation. All, except one, SR was appraised to have critically low confidence as per AMSTAR-2 Criteria. Evidence base was restricted to few studies for most interventions. Discussion: High quality evidence from SRs is required to inform guidelines and health system decisions which can bring down the burden of snakebite. The review indicates the need to fund high-quality SRs, evidence gaps and core outcome sets which can inform guideline recommendations, funding priorities for conduct of future trials. Variation in species distribution as well as intra-species variation in venom composition implies the need for conduct of region or, nation or state (sub-national) specific randomised controlled trials and SRs on different SAVs and their dosing regimens. Author summary: Snakebite is a neglected tropical disease which has received priority attention in the global health space with WHO setting a target to decrease death and disability due to snakebite to 50% by 2030. High quality systematic reviews can inform policy and practice. We searched 13 electronic databases and PROSPERO, screened reference lists, and contacted experts. We identified 13 completed systematic reviews which has reviewed effectiveness and safety for first-aid, snake anti-venoms, drugs to prevent adverse reactions and fasciotomy. Evidence for interventions often came from few studies. We judged confidence on the results of the systematic reviews using AMSTAR-2 and all except one review was judged to have critically low confidence. Evidence with respect to specific geographic settings and for many specific anti-venoms is unavailable at the synthesis level and at the primary study level. Evidence related to late adverse reactions, wound-related outcomes, quality of life, duration of hospitalisation, cost, and disability is scarcely reported. Funding evidence gap maps, systematic reviews and development of core-outcome sets based on the results of this overview and subsequent conduct of randomised controlled trials for snakebite envenomation is essential.