Antimalarial Transmission-Blocking Interventions: Past, Present, and Future

Malaria remains a major global health challenge. Appropriate use of current antimalarial tools has reduced the disease burden, but morbidity and mortality remain unacceptably high. It is widely accepted that, to achieve long-term control/eradication, it will be necessary to use interventions that inhibit the transmission of parasites to mosquitoes – these tools are termed transmission-blocking interventions (TBIs). This article aims to outline the rationale for the development of TBIs, with a focus on transmission-blocking drugs and (parasite-derived) transmission-blocking vaccines. We describe and summarise the current status of each of these intervention classes and attempt to identify future requirements in development, with a focus on the challenges of establishing each method within an integrated malarial control programme in the future. Malarial burden can be demonstrably reduced by interventions that inhibit the transmission of Plasmodium through the mosquito. These interventions are termed transmission-blocking interventions (TBIs). Anti-parasitic forms of these interventions can be classified as transmission blocking drugs (TBDs), or transmission blocking vaccines (TBVs). In terms of TBDs, there are currently three clinically approved anti-malarials that show robust transmission-blocking efficacy; primaquine, methylene blue and atovaquone, with additional compounds in clinical development and trials ongoing. Although a wide range of proteins have been examined for TBV activity, there are only five immunogens that unquestionably demonstrate efficacy. Recent trials examining P230 and P25 and the development of a CHMI model to examine efficacy promise to give impetus to further development in the near future.