Community-led Responses for Elimination (CoRE): a study protocol for a community randomized controlled trial assessing the effectiveness of community-level, reactive focal drug administration for reducing Plasmodium falciparum infection prevalence and incidence in Southern Province, Zambia.

BACKGROUND: Zambia is pushing for, and has made great strides towards, the elimination of malaria transmission in Southern Province. Reactive focal test and treat (RFTAT) using rapid diagnostic tests and artemether-lumefantrine (AL) has been key in making this progress. Reactive focal drug administration (RFDA) using dihydroartemisinin-piperaquine (DHAP), may be superior in accelerating clearance of the parasite reservoir in humans due to the provision of enhanced chemoprophylactic protection of at-risk populations against new infections. The primary aim of this study is to quantify the relative effectiveness of RFDA with DHAP against RFTAT with AL (standard of care) for reducing Plasmodium falciparum prevalence and incidence.

METHODS/DESIGN: The study will be conducted in four districts in Southern Province, Zambia; an area of low malaria transmission and high coverage of vector control. A community randomized controlled trial of 16 health facility catchment areas will be used to evaluate the impact of sustained year-round routine RFDA for 2 years, relative to a control of year-round routine RFTAT. Reactive case detection will be triggered by a confirmed malaria case, e.g., by microscopy or rapid diagnostic test at any government health facility. Reactive responses will be performed by community health workers (CHW) within 7 days of the index case confirmation date. Responses will be performed out to a radius of 140 m from the index case household. A subset of responses will be followed longitudinally for 90 days to examine reinfection rates. Primary outcomes include a post-intervention survey of malaria seropositivity (n = 4800 children aged 1 month to under 5 years old) and a difference-in-differences analysis of malaria parasite incidence, as measured through routine passive case detection at health facilities enrolled in the study. The study is powered to detect approximately a 65% relative reduction in these outcomes between the intervention versus the control.

DISCUSSION: Strengths of this trial include a robust study design and an endline cross-sectional parasite survey as well as a longitudinal sample. Primary limitations include statistical power to detect only a 65% reduction in primary outcomes, and the potential for contamination to dilute the effects of the intervention.

TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02654912 . Registered on 12 November 2015.