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

Malaria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03705624
• Other study ID #: INDIE-1a
• Status: Completed
• Phase: N/A
• Start date: August 6, 2018
• Est. completion date: February 14, 2020

Study information

• Verified date: August 2018
• Source: London School of Hygiene and Tropical Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 907
• Est. completion date: February 14, 2020
• Est. primary completion date: February 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Malaria

Intervention

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
• 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.

Locations

Country	Name	City	State
Burkina Faso	Centre National de Recherche et de Formation sur le Paludisme	Ouagadougou

Sponsors (4)

Lead Sponsor	Collaborator
London School of Hygiene and Tropical Medicine	Centre National de Recherche et de Formation sur le Paludisme, Burkina Faso, Institute for Disease Modeling, Bellevue, US, Radboud University

Country where clinical trial is conducted

Burkina Faso, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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.
Other	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.
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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