Effectiveness of Mass Drug Administration for Reducing Seasonal Malaria Transmission in Zanzibar

Study Overview
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Brief Summary
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The overall aim of this study is to determine the effectiveness of two rounds of mass drug administration (MDA) with dihydroartemisinin-piperaquine (DHAp) + single low dose (SLD) primaquine for reducing seasonal malaria transmission in Shehias considered hotspots on Unguja Island, Zanzibar.

Detailed Description
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Study design: This is a cluster-randomised controlled study with two arms: an intervention arm with two rounds of MDA with dihydroartemisinin-piperaquine (DHAp) + single low dose (SLD) primaquine, and a control arm with no MDA. Study site and study population: The study will be conducted in 16 hotspot Shehias (8 Shehias randomly allocated to each arm), in three districts (West, Central and South districts) in Unguja Island, Zanzibar. Hotspot Shehias [Shehia being the smallest administrative structure in Zanzibar] are defined as Shehias with an annual malaria incidence of >0.8%, calculated as the number of confirmed malaria infections notified at health facilities and during active case detection in 2015 / Shehia projected population for 2015. The study population will include all consenting residents of the selected Shehias, reaching approximately 24000 people. Study implementation: Two rounds of MDA with DHAp (D-ARTEPP, Guilin Pharmaceutical (Shanghai) Co., Ltd., China) and SLD (0.25mg/kg) primaquine (Primaquine, Remedica Ltd.,Cyprus ) will be conducted approximately four weeks apart in the intervention Shehias, at the anticipated lowest point of malaria transmission prior to the onset of malaria transmission associated with the main rains in April-June 2016. The first drug dose including DHAp and SLD primaquine will be given under supervision whenever possible; the other two doses of the standard once daily DHAp regimen will be taken unsupervised at home. Labelled packets containing all three doses will be left with the head of household with clear instructions for individuals not present at the time of the household visit. Study objectives: The primary objective of the study is to determine the effectiveness of two rounds of MDA with DHAp + SLD primaquine for reducing seasonal malaria transmission in Shehias considered hotspots on Unguja Island, Zanzibar. The secondary objectives of the study include determining MDA coverage, compliance, and safety after one and two rounds of DHAp + SLD primaquine.

Official Title
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Effectiveness of Mass Drug Administration (MDA) for Reducing Seasonal Malaria Transmission Towards Its Elimination in Hotspot Areas in Zanzibar - a Cluster-randomised Controlled Trial

Conditions
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Malaria, Plasmodium Infections

Intervention / Treatment
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* Drug: MDA with DHAp and SLD Primaquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Permanent or temporary resident of study Shehias (i.e., persons who stayed in the selected household the night before the interview) Provision of informed consent (refusal must be recorded) Age >6 months Exclusion Criteria: Women pregnant in first trimester (assessed by a specific set of questions designed to exclude pregnancy) Severe disease that requires immediate referral to health facility or hospital Concurrent antimalarial treatment at time of MDA or during the last 14 days Inability to take oral medication Additional exclusion criteria for treatment with SLD Primaquine: Pregnancy (all trimesters, assessed by a specific set of questions designed to exclude pregnancy) Women breast feeding infants aged < 6months

Ages Eligible for Study
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Minimum Age: 6 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MDA with DHAp and SLD Primaquine<br>MDA will be conducted at two time points with an approximate four-week interval. All consenting and eligible community members will be administered age-appropriate treatment dose of dihydroartemisinin-piperaquine (D-ARTEPP, Guilin Pharmaceutical (Shanghai) Co., Ltd., China) and single low dose (0.25mg/kg) primaquine (Primaquine, Remedica Ltd., Cyprus) in house-to-house campaigns. | Drug: MDA with DHAp and SLD Primaquine<br> <br> * Other names: MDA with D-ARTEPP and single low dose Primaquine;|
| No Intervention: Control<br>The control arm (no MDA) will have the standard care offered by the Ministry of Health and Social welfare which applies to both arms. This includes passive case detection of individuals seeking treatment at local health facilities, and universal coverage of long lasting insecticide treated bed nets and indoor residual spraying in the study areas. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative notified malaria incidence in the MDA and control Shehias | Cumulative notified malaria incidence determined as the number of confirmed malaria cases notified at health facilities (monitored through the malaria case notification system during the period of six months) over the Shehia population size determined by population enumeration at the time of the intervention. | 6 months after second round of MDA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PCR determined community prevalence of Plasmodium infections in the MDA and control Shehias | PCR determined community prevalence of Plasmodium infections determined by cross-sectional screening in every other household in the study area at the time of the first round of MDA, and at six months after the second round of MDA. | Baseline and 3 months after second round of MDA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malaria, Plasmodium, Mass drug administration, Malaria elimination, Zanzibar, Dihydroartemisinin-Piperaquine, Single low dose Primaquine