falciparum–infected erythrocytes were inoculated intravenously into malaria-naive adults, bypassing the liver and directly establishing a blood-stage infection. ( B) In this issue, Collins and colleagues describe a new model of malaria transmission from humans to mosquitoes using CHMI. In the mosquito, gametes fuse and ultimately form sporozoites that migrate to the mosquito salivary gland to complete the life cycle. ![]() A small percentage of blood-stage parasites differentiate into male and female gametocytes - the nonpathogenic sexual forms taken up by mosquitos during blood meals. Asexual blood-stage parasites cause disease by triggering inflammation and sequestering in blood vessels of vital organs. After seven to ten days, merozoites exit the liver into the bloodstream and begin a 48-hour cycle of asexual replication within erythrocytes. Sporozoites migrate to the liver and invade hepatocytes, where they differentiate into merozoites and replicate asexually without causing symptoms. falciparum infection begins in humans when Anopheles mosquitos inject sporozoites into the skin and blood. falciparum malaria: the life cycle of natural infection and a new model of human-to-mosquito transmission. falciparum gametocytes in healthy malaria-naive volunteers at densities infectious to mosquitoes, thereby demonstrating the potential for evaluating transmission-blocking interventions in this model. We report the safe and reproducible induction of P. Transaminase elevations were transient, asymptomatic, and resolved without intervention. Three AEs were assessed as severe - fatigue, elevated alanine aminotransferase, and elevated aspartate aminotransferase - and were attributed to malaria infection. Adverse events (AEs) were mostly mild or moderate. Compared with results in untreated controls (n = 7), primaquine (15 mg, n = 5) significantly reduced gametocyte burden (P = 0.01), while artefenomel (500 mg, n = 4) had no effect. Male and female gametocytes were detected in all participants, and transmission to mosquitoes was achieved from 8 of 11 (73%) participants evaluated. To investigate in vivo gametocytocidal drug activity in this model, participants were either given an experimental antimalarial, artefenomel (500 mg), or a known gametocytocidal drug, primaquine (15 mg), or remained untreated during the period of gametocyte carriage. Primary end points were development of gametocytemia, the transmissibility of gametocytes from humans to mosquitoes, and the safety and tolerability of the CHMI transmission model. Seven to eight days after inoculation, participants received piperaquine (480 mg) to attenuate asexual parasite replication while allowing gametocytes to develop and mature. falciparum–infected erythrocytes to initiate blood-stage infection. Seventeen healthy malaria-naive volunteers underwent CHMI by intravenous inoculation of P. ![]() Here, we describe a new model for evaluating malaria transmission from humans to Anopheles mosquitoes using controlled human malaria infection (CHMI). However, models for early clinical evaluation of candidate transmission-blocking interventions are currently unavailable. Drugs and vaccines that can interrupt the transmission of Plasmodium falciparum will be important for malaria control and elimination.
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