Study procedures
infection, parasitemia
BLOOD, PARASITEMIA, INFECTION
Cohort A participants (Flow chart. Eighty-nine candidates were tested for eligibility and fourty-six were included in the study after screening: twenty-three in cohort A (three additional participants started mefloquine prophylaxis in case of dropouts prior to the first immunization), twenty in cohort B, and three in the control groups. Participants in cohort A were randomized to receive immunizations with either three times fifteen NF135-infected mosquitoes (high-dose) or three times five NF135-infected mosquitoes (low-dose). One participant dropped out after the first immunization and two participants after the third immunization, all three because of personal or logistical reasons. Participants in cohort B received one immunization with fifteen NF135-infected mosquitoes (high-dose). The control group was not immunized. Immunized participants from cohort A, and three malaria-naïve control participants were challenged by bites of five NF135-infected mosquitoes. In cohort B, the trial was prematurely ended after the first immunization and participants were not subsequently challengedA safety monitoring committee was appointed to evaluate safety data at prespecified time points throughout the trial: after each immunization, at day 21 and 35 after CHMI, and Follow-up took place from day 6 until day 10 after each immunization in an outpatient setting. Blood samples were collected daily for safety follow-up and retrospective qPCR assessment. Additionally, a thick smear was performed on days 7, 8, and 9 after immunization or if participants were symptomatic. Symptomatic participants with a positive thick smear were treated with a standard curative regimen of 1000 mg atovaquone and 400 mg proguanil once daily for 3 days.Nineteen weeks after the third immunization, participants underwent a CHMI with five NF135-infected mosquitoes using similar procedures as for immunization. After challenge infection, participants were followed up once daily for safety lab measurements and prospective qPCR from day 6 until day 21 post-challenge. All participants were treated with a curative regimen of atovaquone/proguanil at the time of detection of parasitemia or ultimately 28 days after challenge infection.Cohort B participants were included on 31 August 2021, following a COVID-19 pandemic-related delay. Cohort B participants (