MDA and Targeted Control Against Plasmodium Carriage in the Sahel (AMARETI)

French Public Scientific and Technological Institution (EPST)

Status: Active, not recruiting

Conditions: Malaria, Falciparum; Malaria, Asymptomatic Parasitaemia

Treatments: 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

Study type: Interventional

Funder types: Other

Identifiers

NCT07281443

2024_SESSTIM_AMARETI

23SANIC216 (Other Grant/Funding Number)

ANR-23-CE35-0002 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 18,000 estimated patients

Sex: All

Ages: 3 months to 100 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Randomisation unit : cluster, defined as village or group of eligible villages <3km from each other

VILLAGE-LEVEL CRITERIA Inclusion

• in Kedougou health district
• population <1500 inhabitants
• >5km from international border
• >3km from a town with 1500 inhabitants or higher
• >3km from another village/cluster

Exclusion

• village inaccessible during rainy season
• village without community health worker and impossible to set up one

INDIVIDUAL-LEVEL: MDA with DHA-piperaquine and single low dose primaquine Inclusion

• 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)

Exclusion (excluded from DHA-piperaquine and primaquine)

• 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.

Exclusion (excluded from primaquine only, eligible for DHA-p)

• children aged 3-6 months
• lactating women

INDIVIDUAL-LEVEL: youth-targeted testing and treatment activity Inclusion

• age 15-24 (+ assent for youth aged 15-17)
• consent Exclusion
• 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

Household inclusion

• consent of head of household
• not planning to move out of study village
• 50% of more members aged >=15 years agree to participate

Individual participant inclusion

• household member or visitor staying longer than 1 night
• consent (+ assent for youth aged 12-17)
• age >=6 months

Individual participant exclusion

• in another study on malaria or health

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18,000 participants in 2 patient groups

MDA and targeted control

Experimental group

Description:

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.

Treatment:

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

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

Drug: MDA with DHAp and SLD Primaquine

Routine malaria control

No Intervention group

Description:

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)