MDA and Targeted Control Against Plasmodium Carriage in the Sahel

NCT07281443 | Active Not Recruiting DMC

• 3 other identifiers: 2024_SESSTIM_AMARETI23SANIC216ANR-23-CE35-0002
• Study Type: interventional
• Target: 18,000
• Locations: 1 country
• Sites: 1

Brief Summary

Strategies implemented since 2010 by the Senegalese National Malaria Control Program (NMCP) enabled a reduction of malaria transmission. However, malaria incidence increased again in recent years, especially in the "red zone" of Kedougou, Kolda and Tambacounda regions. Neighbouring Sahelian countries also documented an increase in malaria incidence in the same period. Current interventions include : long-lasting insecticidal nets, free diagnostic and treatment of clinical malaria, home-based case management (PECADOM), intermittent preventive treatment of pregnant women and seasonal malaria chemoprevention for children up to 10 years. These strategies, while efficient to reduce the burden of clinical malaria, do not account for individuals chronically infected with Plasmodium parasites. These carriers often remain asymptomatic and act as a reservoir for persistence during the dry season, and onwards transmission during the wet season. An observational study conducted in Kedougou in 2021 and 2022 by IRD Dakar shed light on the most affected age groups and on risk-factors associated with asymptomatic carriage. Interventions against asymptomatic carriage could complement existing strategies and contribute to reducing malaria transmission. Mass drug administration (MDA) involves proposing a curative treatment of each member of the community, regardless of age, during a coordinated campaign. To this day, it is the only intervention available to deplete the reservoir of Plasmodium carriers, since a large proportion of asymptomatic infections remain undetectable with available field tests. A study conducted by NMCP and Iba Der Thiam University in Thiès (UIDT) in 2021 in Tambacounda showed that regular MDA campaigns during the high transmission season had a significant impact on clinical malaria incidence and on prevalence of carriage. AMARETi project aims to evaluate an intervention to complete current control strategies. The design of this intervention combines the recent results from Kedougou and Tambacounda studies. The intervention consists of an MDA campaign at the start and at the end of the high transmission season, aiming at maximal depletion of the asymptomatic reservoir, and of age-group targeted interventions aiming to reduce chronic reinfection in individuals at highest risk of asymptomatic carriage. The design and implementation of the intervention stem from a co-construction process with members of communities participating in the research, to maximize inclusiveness and adhesion. It aims to ensure the design of interventions that are adapted to age, gender and other factors deemed relevant by researchers and communities. The project will evaluate if this intervention improves significantly the situation compared to current strategy in a stepped-wedge cluster-randomized controlled trial over 2 malaria high transmission seasons. If the results are conclusive, recommendations for scale-up can be made. The primary outcome will be Plasmodium falciparum infection prevalence at the end of the high transmission season. Secondary outcomes include clinical malaria incidence and malaria incidence dynamics, as well as participation, safety and acceptability. Implementation outcomes (not detailed here) will include the assessment of implementation (CFIR's indicators), sustainability (Schell's indicators) and scalability (Coroa's indicators). These indicators use multiple dimensions stemming from qualitative and quantitative data and flexible design to understand each specific outcome (Proctor E, et al, Mental Health and Mental Health Services Research 2011). In addition, a nested study in 10 villages will provide insights on transmission and reservoir restoration mechanisms through follow-up of a cohort and in-depth investigations. AMARETi project will take place from 2024 to 2027 in 7 health posts and 50 villages of Kedougou department, under the leadership of the Kedougou Health District and Region authorities. The local health, administrative and community-based authorities at local and regional level are also key partners in the project, as well as local development committees and health community-based organisations. Healthpost staff and community health workers and volunteers will be essential for the operational field implementation.

Conditions

Malaria, Falciparum; Malaria, Asymptomatic Parasitaemia

Keywords

stepped wedge; cluster randomized controlled trial; CRCT; malaria; Plasmodium falciparum; asymptomatic carriage; mass drug administration; MDA; parasite reservoir; seasonal malaria transmission; Senegal; youth-targeted; seasonal malaria chemoprevention; SMC

Outcome Measures

Primary Outcomes (4)

• Plasmodium falciparum carriage reservoir at the end of the high transmission season (step 0)

  Number of participants with P. falciparum infection (measured by qPCR in cross sectional sample). Survey conducted at step 0 (baseline, year 0, no intervention). Survey takes place 4 months after SMC round 1 i.e. immediately before SMC round 5.

  4 months after SMC round 1, baseline year 0

• Plasmodium falciparum carriage reservoir at the end of the high transmission season (step 1)

  Number of participants with P. falciparum infection (measured by qPCR in cross sectional sample). Surveys conducted at step 1 (year 1, intervention in 50% of clusters). Survey takes place 4 months after SMC round 1 in control villages (i.e. immediately before SMC round 5) and 4 months after MDA1 in intervention villages (i.e. immediately before MDA2).

  4 months after MDA1/SMC round 1, year 1

• Plasmodium falciparum carriage reservoir at the end of the high transmission season (step 2)

  Number of participants with P. falciparum infection (measured by qPCR in cross sectional sample). Surveys conducted at step 2 (year 2). During the final step, intervention MDA3 (at the start of the wet season, replacing SMC round 1) and MDA4 (at the end of the wet season, replacing SMC round 5) take place in all clusters. Survey takes place 4 months after MDA3 in intervention villages (i.e. immediately before MDA4).

  4 months after MDA3, year 2

• Odds ratio of P. falciparum infection associated with intervention/control period status

  The results of the cross sectional surveys at year 0, 1 and 2 (see outcomes 1-3) will be analysed in a multivariable multilevel logistic regression model. Explained variable : P. falciparum infection detected by qPCR. Variable of interest : intervention or control status at village level. Adjustments for individual, household, and cluster-level fixed effects. Including household, village, cluster and temporal random effects.

  4 months after SMC round 1, years 0, 1 and 2

Secondary Outcomes (12)

• Clinical malaria burden

  year 1, year 2

• Spatio-temporal dynamics of clinical malaria incidence

  year 1, year 2

• Mass drug administration safety (active)

  Day 4 after MDA start

• Mass drug administration safety (passive)

  Day 0 to day 7 after MDA start

• Plasmodium falciparum carriage reservoir at the onset of the high transmission season (step 1)

  immediately before MDA1/SMC round 1, year 1

Other Outcomes (4)

• Risk-factors for Plasmodium falciparum infection in a subcohort follow-up

  6 planned cohort visits (from baseline year 0 to 4 months after MDA3, during year 2).

• Subcohort villages parasite reservoir genetic relatedness

  year 1, year 2

• Subcohort villages parasite reservoir multiplicity of infection

  year 1, year 2

Study Arms (2)

MDA and targeted control

EXPERIMENTAL

Interventions: * MDA with DHAp and SLD Primaquine * Targeted control (10-24 years) during the malaria high tranmission season: behaviour * Targeted control (15-24 years) during the malaria high tranmission season: test and treat During intervention period, villages receive 2 rounds of MDA simultaneously to SMC rounds 1 and 5. SMC-eligible children participate in MDA in replacement of round 1 and 5, but receive SMC rounds 2, 3 and 4 routinely. Youth-targeted control activities take place during the high transmission season: behavioural activies throughout and testing of asymptomatic young adults from 1 month after MDA1 to 1 month before MDA2.

Drug: MDA with DHAp and SLD Primaquine; Behavioral: Targeted control (10-24 years) during the malaria high tranmission season: behaviour; Diagnostic Test: Targeted control (15-24 years) during the malaria high tranmission season: test and treat

Routine malaria control

NO INTERVENTION

Control arm will benefit from the routine malaria control strategy implemented by the Senegalese NMCP including: * universal coverage with long-lasting LLINs (renewed every 3 years); * free, community-based access to early diagnostic and treatment of malaria including active case detection activities by CHWs (DSDOM); * IPT for pregnant women using SP; * SMC for children aged 3 months to 10 years using SP+AQ, distributed door-to-door with 3-day DOTS, over 5 rounds (round 1: June; round 5: October)

Interventions

Targeted control (15-24 years) during the malaria high tranmission season: test and treat DIAGNOSTIC_TEST

Voluntary testing for malaria in young adults (15-24 years) using rapid diagnostic tests performed by community health workers during home visits or group testing events organized by the village youth association.

MDA and targeted control

MDA with DHAp and SLD Primaquine DRUG

MDA: 2 rounds of MDA with dihydroartemisinine-piperaquine + single low dose primaquine (PQ) administered instead of SMC round 1 and 5.

MDA and targeted control

Targeted control (10-24 years) during the malaria high tranmission season: behaviour BEHAVIORAL

Communication and community engagement activities by age-groups: * children aged 10-14 and their parents : promote early health seeking behaviour in case of symptoms * young adults (15-24) : promote early health seeking behaviour in case of symptoms, emphasing the importance of mild symptoms.

MDA and targeted control

Eligibility Criteria

• Age: 3 Months - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may not qualify if:

• village inaccessible during rainy season
• village without community health worker and impossible to set up one
• consent (+ assent for youth aged 12-17)
• age \>=3 months
• in the village for \>=4 days at time of MDA initiation
• not pregnant (women 15-49 years with negative pregnancy test or under contraception)
• allergy to artemisinin combination therapy
• pregnant women (referred for administration of IPTp) or women without pregnancy test result
• presenting with acute disease symptoms: in case of fever or history of fever, individuals will be tested with RDT and, if positive, refered to CHW or healthpost for symptomatic malaria treatment according to national guidelines.
• children aged 3-6 months
• lactating women
• age 15-24 (+ assent for youth aged 15-17)
• none. in case of RDT-positivity, participants will be referred for treatment according to national guidelines (recommendation of treatment in case of a positive test, irrespective of symptoms).
• COHORT STUDY 8 villages/clusters selected for an in-depth cohort study
• consent of head of household

Sponsors & Collaborators

• Institut de Recherche pour le Developpement: lead
• Programme National de Lutte contre le Paludisme (PNLP), Senegal: collaborator
• L'université de Thiès: collaborator
• Cheikh Anta Diop University, Senegal: collaborator

Study Sites (1)

District de Santé de Kédougou - Kedougou Health District

Kédougou, Senegal

Location

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: stepped-wedge cluster randomized controlled trial with three steps: step 0, observation of all clusters without intervention; step 1, intervention in 50% of clusters during a year; step 2, interventions in all clusters during a year.

Study Record Dates

• First Submitted: September 29, 2025
• First Posted: December 15, 2025
• Study Start: September 23, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 15, 2025

Record last verified: 2025-12

Locations

SE (1)