This community-based cluster randomized controlled trial aims to evaluate the effectiveness of time-limited, community-wide mass drug administration (MDA) with dihydroartemisinin-piperaquine (DHA-PPQ) and single low-dose primaquine (SLD-PQ) on Plasmodium falciparum transmission compared to standard-of-care seasonal malaria chemoprevention (SMC). The study will be conducted in a moderate-to-low malaria transmission setting of Senegal with optimized malaria control measures (e.g., proactive community case management and piperonyl butoxide pyrethroid long-lasting insecticidal nets (PBO LLINS)).
Over the past two decades in Senegal, the scale-up of malaria control measures \[e.g., access to prompt testing and case management, LLINs, and SMC\] has led to a 78% reduction in malaria incidence. However, gains have not been uniform, with lower transmission areas in the north implementing pre-elimination activities and higher transmission areas in the south implementing control interventions (including SMC). The purpose of this study is determine whether MDA will be able to rapidly reduce malaria incidence in areas of moderate-to-low malaria transmission of southern Senegal (where control activities are ongoing) so that the program can reorient their malaria strategy to implement elimination interventions in these settings. The study aims to deliver three rounds of community-wide MDA with DHA-PPQ + SLD-PQ. MDA drugs will be administered over the course of three days. All three doses of DHA-PPQ will be given via supervised DOT (as per administration of SMC by national malaria guidelines) through a door-to-door approach. The research objectives are: 1. To evaluate the impact of three rounds of MDA with DHA-PPQ and SLD-PQ on village-level confirmed malaria case incidence, malaria prevalence, and on reaching a target malaria incidence of \<5 cases per 1000 person-years compared to standard-of-care SMC when provided in the context of optimized control (proactive community case management + PBO LLINs). 2. To determine the cost, coverage, operational feasibility, and acceptability of three rounds of MDA with DHA-PPQ and SLD-PQ compared to standard-of-care SMC. 3. To determine the impact of three rounds of MDA with DHA-PPQ and SLD-PQ compared to standard-of-care SMC on parasite population dynamics and drug resistance.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
10,715
DHA-PPQ will be given over the course of three consecutive days using 160mg/20mg or 320mg/40mg of dihydroartemisinin/piperaquine tablets. DHA-PPQ will be administered via age-based dosing. All three doses will be directly observed and given orally with water and without food.
Primaquine will be given once with the first dose of DHA-PPQ. Primaquine will be administered in an aqueous solution according to age-based dosing guidelines.
Tambacounda Health District
Tambacounda, Senegal
Difference in village-level confirmed incidence of malaria
Village-level malaria incidence will be defined as the number of individuals diagnosed with malaria through proactive case detection and passive malaria surveillance at the health facility-level over the total village population measured during census.
Time frame: one year post-MDA
Difference in parasite prevalence by microscopy during high malaria transmission season
Parasite prevalence will be assessed via microscopy from samples obtained during cross-sectional survey conducted at the end of the transmission season.
Time frame: 3 months after last round of MDA
Difference in parasite prevalence by polymerase chain reaction (PCR) during high malaria transmission season
Parasite prevalence will be assessed via polymerase chain reaction from samples obtained during cross-sectional survey conducted at the end of the transmission season.
Time frame: 3 months after last round of MDA
Difference in serological markers of recent infection
Difference in seroprevalence from samples obtained during cross-sectional survey conducted at the end of the transmission season.
Time frame: 3 months after last round of MDA
Difference in the change in prevalence of drug resistance markers
Prevalence of drug resistance markers (K13 and plasmepsin copy number) will be assessed from samples taken during the baseline and endline cross-sectional surveys.
Time frame: Change from baseline to endline; 1 year period
Difference in the change in prevalence of parasite population dynamics
Prevalence of parasite population dynamics (multiplicity of infection) will be assessed from samples taken during the baseline and endline cross-sectional surveys.
Time frame: Change from baseline to endline; 1 year period
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