P. Falciparum Infection Dynamics and Transmission to Inform Elimination (INDIE-1a)

Study Overview
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Brief Summary
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In the current randomized trial, the investigators will test the ability of two experimental approaches to malaria infection management to reduce malaria transmission potential. Compounds in Saponé, Burkina Faso, will be randomized to 1 of 3 study arms: arm 1 - current standard of care with passively monitored malaria infections; arm 2 - standard of care plus enhanced community case management (CCM), comprising active weekly screening for fever, and detection and treatment of infections in fever positive individuals using conventional rapid diagnostic tests (RDTs); or arm 3 - standard of care and enhanced CCM, plus monthly screening and treatment (MSAT) using RDTs. The study will be conducted over approximately 18 months covering two high transmission seasons and the intervening dry season

Official Title
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P. Falciparum Infection Dynamics and Transmission to Inform Elimination (INDIE-1a)

Conditions
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Malaria

Intervention / Treatment
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* Other: Enhanced Community Case Management (CCM)
* Other: Monthly Screening and Treatment (MSAT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants should be permanent residents of the compound Participants should be willing to participate in repeated assessments of health and infection status and willing to donate a maximum of 37mL of blood (children <10 years of age) or 52mL of blood (older individuals) during an 18-month period Exclusion Criteria: Any (chronic) illness that would affect with study participation Pre-existing severe chronic health conditions Current participation in malaria vaccine trials or participation in such trials in the last 2 years History of intolerance to artemether-lumefantrine
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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Cluster randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care<br>Standard of care with passively monitored malaria incidence at health centers that receive appropriate diagnostic and clinical supplies and Seasonal Malaria Chemoprevention (SMC) for children less than 5 years of age | |
| Experimental: CCM<br>Standard of care supplemented with enhanced Community Case Management for malaria (CCM) involving weekly active screening for fever using a research-grade thermometer by a trained health worker. A measured temperature ≥37.5°C or reported fever in the last 24 hours will prompt screening with a conventional rapid diagnostic test (RDT). RDT positive individuals will be treated with artemether-lumefantrine (AL) according to national guidelines | Other: Enhanced Community Case Management (CCM)<br>* Enhanced Community Case Management for malaria (CCM) involving weekly active screening for fever using a research-grade thermometer by a trained health worker. A measured temperature ≥37.5°C or reported fever in the last 24 hours will prompt screening with a conventional rapid diagnostic test (RDT). RDT positive individuals will be treated with AL according to national guidelines<br>|
| Experimental: CCM+MSAT<br>Standard of Care supplemented with CCM and Monthly Screening and Treatment (MSAT) regardless of symptoms with a conventional RDT. Screening will be performed by research staff with 25-35 days between screening rounds; RDT positive individuals will be treated with AL according to national guidelines. | Other: Enhanced Community Case Management (CCM)<br>* Enhanced Community Case Management for malaria (CCM) involving weekly active screening for fever using a research-grade thermometer by a trained health worker. A measured temperature ≥37.5°C or reported fever in the last 24 hours will prompt screening with a conventional rapid diagnostic test (RDT). RDT positive individuals will be treated with AL according to national guidelines<br>Other: Monthly Screening and Treatment (MSAT)<br>* Monthly Screening and Treatment (MSAT) regardless of symptoms with a conventional RDT. Screening will be performed by research staff with 25-35 days between screening rounds; RDT positive individuals will be treated with AL according to national guidelines.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasite prevalence and density by molecular detection at the end of study cross-sectional survey. | The primary outcome measure is parasite prevalence in the cross-sectional survey conducted at the end of the transmission season of year 2. If CCM and MSAT result in the early detection of infections, parasite prevalence at the end of the study will be lower in these arms compared to the control arm. | Month 18 (end of second transmission season; January-February 2020) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parasite prevalence and density by molecular detection at the end of year 1 cross-sectional survey. | Parasite prevalence and density in the cross-sectional survey conducted at the end of the transmission season of year 1. If CCM and MSAT result in the early detection of infections, parasite prevalence will be lower in these arms compared to the control arm. | Month 6 (end of first transmission season; January-February 2019) | 
| Parasite prevalence and density by molecular detection at the end of dry season cross-sectional survey. | Parasite prevalence and density in the cross-sectional survey conducted at the end of the dry season. If CCM and MSAT result in the early detection of infections, parasite prevalence will be lower in these arms compared to the control arm. | Month 12 (prior to second transmission season; June 2019) | 
| Gametocyte prevalence and or density in P. falciparum infections at the end of study cross-sectional survey | Gametocyte prevalence in qPCR detected infections is assessed by molecular methods and compared between study arms. | Month 18 (end of second transmission season; January-February 2020) | 
| Gametocyte prevalence and or density in P. falciparum infections at the end of year 1 cross-sectional survey | Gametocyte density of male and female gametocytes will be assessed by molecular methods and compared between study arms. | Month 6 (end of first transmission season; January-February 2019) | 
| Gametocyte prevalence and or density in P. falciparum infections at the end of dry season cross-sectional survey | Gametocyte density of male and female gametocytes will be assessed by molecular methods and compared between study arms. | Month 12 (prior to second transmission season; June 2019) | 
| Gametocyte prevalence and or density in P. falciparum during all study visits | Gametocyte density of male and female gametocytes will be assessed by molecular methods and compared between study arms. | Throughout study, an average of 18 months | 
| The number of incident infections. | Regular visits by CCM and MSAT will result in the identification of malaria infections that are not detected during passive case detection. The numbers of infections that are detected in each arm are quantified and compared between arms. | Throughout study, an average of 18 months | 
| Infectivity to mosquitoes of P. falciparum infections | For a selection of infections, infectiousness to mosquitoes is assessed by membrane feeding assays. | Throughout study, an average of 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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falciparum, gametocyte, elimination, anopheles, transmission, diagnostic