The urgent need for more research on Wolbachia-based mosquito interventions in public health

The release of Wolbachia pipientis-infected Aedes aegypti mosquitoes has emerged as a novel strategy to reduce the transmission of arboviruses such as dengue, chikungunya, and Zika. Wolbachia-based approaches to dengue control include population replacement, which reduces vector competence by establishing Wolbachia in wild populations of Aedes aegypti, and population suppression, which lowers mosquito densities through cytoplasmic incompatibility. Field trials of the population replacement strategy, based on wMel Wolbachia-infected mosquitoes, have shown variable success and concerns persist about long-term efficacy, safety and ecological impact. Uncertainties arise from an incomplete understanding of the mechanisms underlying pathogen blocking, possible bacteria and vector strain-specific effects, and the influence of environmental, host, and viral factors on the success of such a strategy. Moreover, some Wolbachia strains may enhance mosquito susceptibility to certain pathogens. Additionally, large-scale deployment raises the possibility of biodiversity disruption and the emergence of viral resistance. Given these unresolved concerns, it is premature and potentially irresponsible to expand the program to new areas without first rigorously assessing its safety, efficacy and sustainability.