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

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

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Other: Enhanced Community Case Management (CCM); Other: Monthly Screening and Treatment (MSAT)

• Study Type: Interventional
• Enrollment (Actual): 907
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Burkina Faso
  • Ouagadougou, Burkina Faso
    • Centre national de recherche et de formation sur le paludisme

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participants should be permanent residents of the compound
2. 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:

1. Any (chronic) illness that would affect with study participation
2. Pre-existing severe chronic health conditions
3. Current participation in malaria vaccine trials or participation in such trials in the last 2 years
4. History of intolerance to artemether-lumefantrine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care; 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; 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); 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
Experimental: CCM+MSAT; 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); 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; Other: Monthly Screening and Treatment (MSAT); 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The detectability of infections by highly sensitive rapid diagnostic tests.	For a selection of samples, the detectability of infections is assessed by conventional rapid diagnostic test and by highly sensitive rapid diagnostic tests and related to i. histidine rich protein-2 (HRP2) concentrations; ii. duration of infection; iii. parasite density by molecular diagnostics.	Throughout study, an average of 18 months
The relationship between the proportion of infected mosquitoes and gametocyte density.	Gametocyte density and sex ratio will be assessed by molecular methods and associated with the proportion of infected mosquitoes and the burden of infection in mosquitoes	Throughout study, an average of 18 months.
The impact of infection characteristics on the transmissibility of infections to mosquitoes	Under this outcome, we aim to determine the impact of gametocyte sex-ratio, other gametocyte characteristics, duration of infection and clonal complexity of malaria infections on the transmissibility of infections to mosquitoes	Throughout study, an average of 18 months.
The impact of human host characteristics on the transmissibility of infections to mosquitoes	Under this outcome, we aim to determine the impact of red blood cell haemoglobinopathies, haemoglobin concentration, inflammatory markers, naturally acquired antibody responses to gametocyte antigens and other host characteristics on the transmissibility of infections to mosquitoes	Throughout study, an average of 18 months
Association between total parasite density and gametocyte density	Under this outcome, we aim to evaluate the relationship between asexual parasite density and gametocyte density in P. falciparum infections	Throughout study, an average of 18 months
Malaria transmission potential based on measured gametocyte densities	Under this outcome, we aim to determine malaria transmission potential of infections based on the gametocyte density	Throughout study, an average of 18 months
Number of acquired clones based on genotyping	Under this outcome, we aim to examine the complexity of P. falciparum infection by measuring the number of clones present in infections	Throughout study, an average of 18 months
The duration of infections in the dry season	Under this outcome, we aim to evaluate the duration of P. falciparum carriage during the dry season	Month 6-12, between end of season survey January/February 2019 and end of dry season survey June 2019
To quantify mosquito exposure in relation to incident infections	Under this outcome, we aim to quantify mosquito exposure and relate this to number of incident infections	Throughout study, an average of 18 months

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: Radboud University Medical Center; Centre national de recherche et de formation sur le paludisme; Institute for Disease Modeling, Bellevue, US
• Investigators: Principal Investigator: Alfred Tiono, PhD, MD, Centre national de recherche et de formation sur le paludisme; Principal Investigator: Chris Drakeley, PhD, London School of Hygiene and Tropical Medicine, Faculty of Infectious and Tropical Diseases, London, United Kingdom; Principal Investigator: Teun Bousema, PhD, Radboud University Medical Centre, Nijmegen, the Netherlands

Publications and helpful links

General Publications

• Collins KA, Ouedraogo A, Guelbeogo WM, Awandu SS, Stone W, Soulama I, Ouattara MS, Nombre A, Diarra A, Bradley J, Selvaraj P, Gerardin J, Drakeley C, Bousema T, Tiono A. Investigating the impact of enhanced community case management and monthly screening and treatment on the transmissibility of malaria infections in Burkina Faso: study protocol for a cluster-randomised trial. BMJ Open. 2019 Sep 13;9(9):e030598. doi: 10.1136/bmjopen-2019-030598.

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2018
• Primary Completion (Actual): February 14, 2020
• Study Completion (Actual): February 14, 2020

Study Registration Dates

• First Submitted: July 19, 2018
• First Submitted That Met QC Criteria: October 10, 2018
• First Posted (Actual): October 15, 2018

Study Record Updates

• Last Update Posted (Actual): February 28, 2020
• Last Update Submitted That Met QC Criteria: February 27, 2020
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: diagnostic; falciparum; transmission; elimination; gametocyte; anopheles
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: INDIE-1a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Anonymised individual participant data may be shared on a digital repository or upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No