Transmission-blocking activity of antimalarials for Plasmodium vivax malaria in Anopheles darlingi

Author summaryVivax malaria is the most prevalent and widespread human malaria outside the African continent. The control of vivax malaria is based on vector control and effective radical cure of infected people. However, the elimination of the sexual stages of Plasmodium vivax present in infected people is important to block malaria transmission from human to mosquito vector. Here, we assessed the potential of currently used antimalarial drugs for vivax malaria therapy for blocking malaria transmission in the mosquito vector Anopheles darlingi. We observed that the antimalarials tested were able to block the infection of mosquitoes; however, treatment based on the artemisinin combination proved to be the fastest for blocking transmission in mosquitoes, using blood taken 4 h after treatment. As such, patients in endemic areas who receive the first line vivax malaria treatment, chloroquine and primaquine, could need protection from bites of the malaria vector for at least 24 h after the initial dose in order to interrupt malaria transmission. Our observations provide an overview of the transmission-blocking profile of antimalarials currently used in Brazil for the treatment of vivax malaria and they also provide a platform for the evaluation of new antimalarials, such as tafenoquine or other compounds for combating the sexual stages of P. vivax, which may impact the epidemiology of malaria. Malaria is caused by parasite of the genus Plasmodium and is still one of the most important infectious diseases in the world. Several biological characteristics of P. vivax contribute to the resilience of this species, including early gametocyte production, both of which lead to efficient malaria transmission to mosquitoes. This study evaluated the impact of currently used drugs on the transmission of P. vivax. Participants received one of the following treatments for malaria: i) chloroquine [10 mg/kg on day 1 and 7.5 mg/kg on day 2 and 3] co-administered with Primaquine [0.5 mg/kg/day for 7 days]; ii) Chloroquine [10 mg/kg on day 1 and 7.5 mg/kg on day 2 and 3] co-administered with one-dose of Tafenoquine [300 mg on day 1]; and iii) Artesunate and Mefloquine [100 mg and 200 mg on day 1, 2 and 3] co-administered with Primaquine [0.5 mg/kg/day for 14 days]. Patient blood was collected before treatment and 4 h, 24 h, 48 h and 72 h after treatment. The blood was used to perform a direct membrane feeding assay (DMFA) using Anopheles darlingi mosquitoes. The results showed 100% inhibition of the mosquito infection after 4 h using ASMQ+PQ, after 24 h for the combination of CQ+PQ and 48 h using CQ+TQ. The density of gametocytes declined over time in all treatment groups, although the decline was more rapid in the ASMQ+PQ group. In conclusion, it was possible to demonstrate the transmission-blocking efficacy of the malaria vivax treatment and that ASMQ+PQ acts faster than the two other treatments.