Summary of data from the ten selected studies.

Malaria is a significant health problem in the world and has been increased by the emerging resistance to insecticides and antimalarial drugs. New measures must therefore be implemented as an emergency to break the cycle of Plasmodium parasite transmission by the Anopheles mosquitoes. This systematic review assessed the effectiveness of paratransgenesis, an engineering approach that utilizes symbiotic microbes to deliver antiplasmodial molecules into the midgut of the mosquito as a transmission-blocking agent. PubMed, ScienceDirect, and Web of Science were searched in accordance with the PRISMA guidelines, yielding 1,289 records. Ten eligible studies were then included after screening. The chosen articles studied bacterial and fungal symbionts, such as Asaia, Serratia, Pantoea, Enterobacter, and Aspergillus oryzae, that have been engineered to produce effector proteins, such as Scorpine, EPIP, Defensin, and SM1–2 peptides. The delivery of oral sugar meals was always associated with colonization of the mosquito midguts, and results reported high levels of inhibition of oocysts or sporozoites in the mosquitoes. Scorpine was the strongest and most commonly used effector with a high level of up to 97.8% inhibition of P. falciparum oocysts in various microbial systems. The combination of two or multiple-effector approaches increased the efficacy in some cases, surpassing 89% parasite inhibition. The risk of bias measurement showed moderate variation in the methods, yet it was in favor of the sound findings. All evidence suggests that paratransgenesis is a potentially important malaria control tool, complementing existing approaches to malaria control. Nevertheless, ecological safety, microbial stability, and field validation are the key obstacles before the translation to large-scale use.