Repeat Ivermectin Mass Drug Administrations for Control of Malaria: a Pilot Safety and Efficacy Study

Cumulative incidence of malaria episodes in a cohort of village children ≤ 5 years of age (as assessed by active case surveillance in study villages - malaria episode defined as ≥38.0°C fever or history of fever in the last 24 hours + positive rapid diagnostic test for Plasmodium falciparum). Incidence is reported as malaria episodes per child over the course of the trial, a higher incidence is a worse outcome.

Time frame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm

Population: Note that the primary outcome measure comes only from malaria incidence measurements within this child cohort (590 children). It is not a measure of malaria incidence from all enrolled participants from the study villages (2712 participants).

The number of adverse events. Adverse events data were collected via passive case detection from total population.

Time frame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm

Population: Per protocol, the secondary outcome was a measure of all adverse events, excluding uncomplicated malaria episodes that were reported in the primary outcome, that occurred among the total enrolled population from the study villages (2712 participants).

Change in human IgG reactivity (optical density; ∆OD) to an Anopheles salivary gland antigen (peptide gSG6-P1) over the trial period. A score of 0 indicates no change in seroreactivity from from immediately before to immediately after the trial, suggesting consistent mosquito biting throughout the trial. A positive score indicates increasing seroreactivity and thus increasing mosquito biting on participants from immediately before to immediately after the trial. A negative score indicates decreasing seroreactivity and thus decreasing mosquito biting on participants from immediately before to immediately after the trial.

Time frame: Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm

Population: We sampled finger capillary blood pre-intervention from a subset of enrolled participants located in 8 households at the center of each study village, and then re-sampled their blood immediately after the intervention period. Data were reported only from participants that gave both sets of samples (221 of 2712 participants).

The entomological inoculation rate (EIR per week per person) is the measure of the human biting rate per person per week, multiplied by the sporozoite rate (in biting mosquitoes) per week, an estimated from sampling mosquitoes from 8 households located in the center of each study village. The EIR was calculated for each of the 6 sampling weeks of the treatment phase.

Time frame: 6 sampling periods over 18 weeks, starting in week 2 following the first MDA, and sampling every 3 weeks thereafter until week 17 of the treatment phase.

Population: The mean EIR was calculated across the 6 sampling periods in the 8 study villages (4 villages in each arm). EIR was calculated from the number of mosquitoes captured in select houses and the number of enrolled participants who lived in each sampled house (324/1265 in single MDA arm, and 271/1447 in repeated MDA arm).

Examination of new P. falciparum clones acquired from the beginning to the end of the intervention (molecular force of infection; mFOI) per child. Molecular genotyping used capillary blood taken at the time of diagnosis of each positive malaria episode and consisted of nPCR of the msp2 gene. We calculated the multiplicity of infection (MOI) per malaria episode, and then calculated the molecular force of infection (mFOI) associated with malaria episodes per child (over course of the trial)

Time frame: Approximately 18 weeks, from the start of the first MDA to 3 weeks following the last MDA in the Experimental arm

Population: Molecular genotyping was performed on blood samples from 132 enrolled cohort children who were selected using a random sequence generator. Genotyping was successful on blood spots corresponding to 153 malaria episodes, which allowed us to calculate the mFOI over the trial from 76 enrolled children from the cohort.

Prevalence of soil transmitted helminth infections in children between 6-10 years old from the beginning to the end of the intervention

Time frame: Approximately 20 weeks, from before the start of the first MDA to 4 weeks following the last MDA in the Experimental arm

Population: This outcome was only measured in older enrolled children between 6-10 years of age, who were not in our primary outcome cohort, and who were eligible to be treated with ivermectin due to their height \>90 cm (232 of 2712 participants).