Antivenom cross-neutralization and neutralization: a systematic review of non-clinical studies in Asia region

Abstract

Background: Cross-neutralizing strategy has been applied to improve access to antivenoms which is a key to reduce mortality and disability of snakebite envenoming. However, preclinical studies have been conducted to discover antivenom’s cross-neutralizing ability when clinical studies may not be ethically applicable. This study aimed to identify and summarize scattered evidence regarding Asia antivenom’s preclinical efficacy.

Methods: We performed a systematic review to search for articles published up to May 30, 2022, in PubMed, Scopus, Web of Science, and Embase. Reference searching of eligible articles was done. Preclinical studies reported the available Asia antivenom’s neutralizing ability against Asia snake lethality were included. Quality assessment was performed using the SYRCLE’s risk of bias tool and the adapted ARRIVE guideline. Cross-neutralizing and neutralizing ability were summarized. Availability of Asia antivenoms was analyzed by comparing data from included studies with Snakebite Information and Data Platform developed by the World Health Organization.

Results: Forty-eight studies were included. Most studies assessed antivenom efficacy against snakes from Southeast Asia (56%), followed by South Asia (36%) and East Asia (19%). Twenty-two (49%) medically important snakes had antivenom(s) with confirmed neutralizing ability against their lethality. Situation analysis of availability of effective antivenom in Asia demonstrated that locally produced antivenoms did not cover all medically important snakes in each country. Among countries without local antivenom production, preclinical studies were conducted only in Bangladesh, Sri Lanka, and Malaysia. Husbandry, total number of animals used, group outcome reporting, and adverse events were not reported in any studies which limited risk of bias assessment.

Conclusions: Cross-neutralizing of antivenoms against some medically important snakes in Asia was confirmed. This strategy may improve access to geographically effective antivenoms and bypass investment in new antivenom development, especially in countries without local antivenom production. Database should be developed to fulfill a lacking snakebite-information system.