Community-led Responses for Elimination: Controlled Trial of Reactive Case Detection Versus Reactive Drug Administration

Study Overview
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Brief Summary
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This study is designed to compare the effectiveness of reactive focal drug administration (RFDA) using dihydroartemisinin+piperaquine (DHAP) versus reactive focal test and treat (RFTAT) using artemether+lumefantrine (AL) as a routine process for identifying and eliminating malaria transmission as measured through achieving zero seropositivity in children under five in Southern Province, Zambia. These two strategies are potential candidates for expanded malaria operational surveillance and elimination for low malaria transmission areas.

Detailed Description
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The study is a cluster randomized controlled trial designed to evaluate the impact of RFDA intervention against current standard of care for the impact on seropositivity in children under five years, passive surveillance for confirmed malaria case incidence, and elimination of transmission from hotspots. It will be conducted among a background population of  130,000 people in  30,000 households in 16 health center catchment areas across several districts in Southern Province. The government of Zambia is pursuing malaria elimination as a national goal on an accelerated timeline and this trial will help evaluate two treatment-based strategies for supporting malaria elimination. The secondary objectives of the study include: 1). Compare the effectiveness of RFDA using DHAP with RFTAT using AL in reducing rapid diagnostic test (RDT) confirmed malaria incidence through passive case detection at health facilities; 2). Compare the effectiveness of RFDA using DHAP with RFTAT using AL in reducing the prevalence of malaria and preventing re-infection in individuals receiving reactive responses; 3). Compare the cost-effectiveness of RFDA using DHAP with RFTAT using AL in reducing the burden of malaria in the community; 4). Measure the proportion of P. falciparum infections likely attributable to importation and local transmission using parasite genotyping as well as defining genotype spatial distribution; 5). Assess the utility of using serology to measure short term changes in malaria transmission and evaluate malaria elimination programs; and 6). Assess the feasibility of using remotely sensed malaria risk maps to identify areas with higher potential for local malaria transmission.

Official Title
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Community-led Responses for Elimination (CoRE): A Cluster Randomized Controlled Trial of Reactive Case Detection Versus Reactive Drug Administration in Malaria Elimination Areas in Southern Province Zambia

Conditions
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Malaria

Intervention / Treatment
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* Drug: Reactive Focal Drug Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: anyone not excluded and consenting Exclusion Criteria: contraindications from manufacturer for medications including currently taking haloperidol, artane, Phenergan (Promethazine), chlorpromazine, erythromycin, Azithromycin, clarithromycin, Ketoconazole, fluconazole, mefloquine (as prophylaxis), lumefantrine (in Coartem), quinine, Septrin anyone seriously ill currently taking antimalarial medicines allergy to artemisinin drugs pregnant women in first trimester children under 3 months of age reported heart condition

Ages Eligible for Study
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Minimum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reactive Focal Drug Administration<br>This is the experimental arm and is described by a reactive response to passively detected index case of malaria. The reactive response consists of treating all individuals within a defined radius of each RDT-confirmed incident malaria case with dihydroartemisinin-piperaquine (DHAP). | Drug: Reactive Focal Drug Administration<br>* This is the experimental arm and is described by a reactive response to passively detected index case of malaria. The reactive response consists of treating all individuals within a defined radius of each RDT-confirmed incident malaria case with dihydroartemisinin-piperaquine (DHAP).<br>|
| No Intervention: Reactive Focal Test and Treat<br>This is the current standard of care in Southern Province and is described by a reactive response to passively detected index case of malaria. The reactive response consists of testing all individuals within a defined radius of each RDT-confirmed incident malaria case with an RDT and treating all positive individuals with artemether-lumefantrine (AL). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Malaria seropositivity in children under five | Malaria seropositivity in children under five after two-year intervention within health center catchment areas | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of malaria confirmed by RDT or microscopy as measured through passive case detection at health posts and health centers | Quality-improved incidence of malaria data confirmed by malaria rapid diagnostic test (RDT) or microscopy as measured through passive case detection at health posts and health centers in the study area. | 24 months | 
| PCR parasite prevalence among individuals participating at 0, 30 and 90 days following a reactive research response for a period of 24 months | Polymerase Chain Reaction (PCR)-based testing for malaria parasite prevalence of individuals participating in each community at 0, 30 and 90 days following a reactive research response for a period of 24 months | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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malaria, elimination, surveillance and response, dihydroartemisinin+piperaquine