Transmission-Blocking Strategies Against Malaria Parasites During Their Mosquito Stages

Abstract

Malaria is still the most widespread parasitic disease and causes the most infections globally. Owing to improvements in sanitary conditions and various intervention measures, including the use of antimalarial drugs, the malaria epidemic in many regions of the world has improved significantly in the past 10 years. However, people living in certain underdeveloped areas are still under threat. Even in some well-controlled areas, the decline in malaria infection rates has stagnated or the rates have rebounded because of the emergence and spread of drug-resistant malaria parasites. Thus, new malaria control methods must be developed. As the spread of the Plasmodium parasite is dependent on the part of its life cycle that occurs in mosquitoes, to eliminate the possibility of malaria infections, transmission-blocking strategies against the mosquito stage should be the first choice. In fact, after the gametocyte enters the mosquito body, it undergoes a series of transformation processes over a short period, thus providing numerous potential blocking targets. Many research groups have carried out studies based on targeting the blocking of transmission during the mosquito phase and have achieved excellent results. Meanwhile, the direct killing of mosquitoes could also significantly reduce the probability of malaria infections. Microorganisms that display complex interactions with Plasmodium, such as Wolbachia and gut flora, have shown observable transmission-blocking potential. These could be used as a biological control strategy and play an important part in blocking the transmission of malaria.

Malaria vaccine approaches leveraging technologies optimized in the COVID-19 era

“…On the other hand, transmission blocking vaccines (TBVs) present an excellent path to stopping population transmission although with no direct benefits to the vaccinee (26)(27)(28). TBVs are based on the principle that when antibodies against a specific antigen expressed in the sexual stages of the malaria parasite (gametocyte, gamete, zygote and ookinete) are taken up along with gametocytes during a blood meal, they can reduce the number of oocysts in mosquito vectors (26). Potential TBV Bind to basigin and forms a stable merozoite invasion complex with PfCyRPA and PfRipr (12) PfRh5-interacting protein (PfRipr) Forms a stable merozoite invasion complex with PfCyRPA and PfRh5…”

“…target antigens include Pfs230, Pfs48/45, Pf25, and Pfs28, which are expressed on the surface of gametocytes, gametes, zygotes, and ookinete (20,28,29). The advantages of TBVs are summarized elsewhere and their advancement has progressed to clinical trials (26)(27)(28)30). While these efforts have mainly focused on antigens like Pfs25, Pfs230, and Pfs48/45, which were identified in the pre-genome era, new antigen discovery approaches promise to change this (28).…”

Updates on traditional methods for combating malaria and emerging Wolbachia-based interventions

“…Malaria remains one of the world’s most devastating infectious diseases, affecting over 100 countries and resulting in hundreds of thousands of deaths annually ( Ashour and Othman, 2020 ; Yu et al., 2022 ). Between, 2000 and, 2023, there were approximately 2 billion reported cases of malaria worldwide, resulting in 11.7 million deaths ( World Health Organization, 2022a ).…”

“…Traditionally, the development of new antimalarial drugs has been a key component of the fight against malaria. However, the emergence of drug-resistant strains poses significant risks and challenges ( Yu et al., 2022 ). Resistance has also emerged in mosquitoes to insecticides and in Plasmodium parasites to antimalarial drugs ( Skorokhod et al., 2023 ).…”

The circadian clock modulates Anopheles gambiae infection with Plasmodium falciparum

“…This stagnation is caused not only by insufficient coverage with insecticide treated nets (ITNs) and indoor residual spraying (IRS), but also by the selection of mosquito populations that mediate outdoor malaria transmission and/or exhibit multiple insecticide resistance traits. Presently, additional approaches to complement ITNs and IRS are being tested, including some that aim to block the transmission of the Plasmodium parasite to and from the mosquito vectors [ 2 , 3 ]. Such transmission blocking technologies must pass through rigorous testing before they can be implemented [ 4 ].…”