As efforts to control malaria are stalling, and the disease is particularly severe in children under the age of two, it is imperative for countries in sub-Saharan Africa, with areas of moderate-to-high transmissions, to implement Perennial Malaria Chemoprevention (PMC) delivered through the Expanded Program on Immunization (EPI), which is the only feasible, sustainable and cost-effective strategy to reach this high-risk group. PMC is a full therapeutic course of antimalarial medicine (with sulfadoxine-pyrimethamine, SP) delivered to infants in the context of routine immunisation services during the first two year of life.

PMC has been shown to be safe, efficacious in reducing clinical malaria, anaemia and hospital admissions, and to be highly cost-effective; for all these reasons, the World Health Organization (WHO) recommended in 2010 Intermittent Preventive Treatment for Infants (IPTi) for malaria prevention. Only one African country – Sierra Leone –put  IPTi into policy and practice. Concerned with this slow adoption, WHO in 2019 recommended adaptations be urgently tested through pilots assessing impact, operational feasibility and cost effectiveness. In 2022, WHO expanded that recommendation to cover children through the age of two because of studies documenting the value in children aged 12 to 24 months. The name for this preventive treatment has consequently changed to Perennial Malaria Chemoprevention (PMC) as the updated recommendation is no longer just for infants.

MULTIPLY is the pilot implementation of PMC in selected districts in Mozambique, Sierra Leone and Togo to maximise the delivery and uptake of PMC, to achieve the full potential of this intervention. Working with the ministries of health in Mozambique, Sierra Leone and Togo, MULTIPLY will give up to 6 doses of PMC in the first two years of life. PMC will be given at health facilities and EPI mobile outreach clinics using a paediatric dispersible formulation of SP, alongside routine vaccinations and vitamin A supplementation.

Through this implementation, capacity will be built and fundamental programmatic issues to achieving effectiveness will be assessed, including:

  1. PMC operational feasibility and acceptability;
  2. Impact on health services integration, i.e. on EPI immunisations and vitamin A administration coverage;
  3. Cost and cost-effectiveness of PMC delivery including through the outreach EPI platform;
  4. Impact on malaria incidence, anaemia, overall mortality, SP resistance development and the safety of the intervention.

The integration of PMC with EPI contacts, together with social and behaviour change communication campaigns to inform communities of the importance of EPI, and the malaria protection afforded by PMC delivered at the EPI, could lead to an increased demand for EPI.

MULTIPLY is a 40-month project funded by The European & Developing Countries Clinical Trials Partnership (EDCTP) aiming to:

  1. Build capacity and establish an environment to support transition to Ministries of Health for scale-up and sustainable PMC in project countries
  2. Generate and disseminate knowledge to the WHO and Ministries of Health of project countries to inform recommendations and guidance for PMC delivery, integrated within national Maternal, New-born and Child Health (MNCH), National Malaria Control Program (NMCP), Nutrition and EPI policy and/or guidelines.
  3. Strengthen South-South and South-North networks to fight poverty-related diseases such as malaria.
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Work packages description

The workplan is made up of five work packages (WP) that are implemented by highly experienced researchers from institutions in Africa (Sierra Leone, Mozambique and Togo) and Europe (France, Spain and Switzerland), in close collaboration with the Ministries of Health of Sierra Leone, Mozambique and Togo, coordinated by ISGlobal.

WP1: Project Management

WP1, led by ISGlobal, manages the project’s strategic direction, optimising the role of the project committees and supervising WP leaders as they execute their tasks. This WP supports the consortium by monitoring the project progress and providing guidance and supervision to the project partners to maximise the scientific quality of the project’s outputs, including quality assurance mechanisms, to ensure the project reaches the objectives and fulfilment of ethical issues.
The objectives of WP1 are:

  • To drive the progress of the project, steering the partners’ efforts to achieve the project’s objectives and milestones, ensuring that the work is undertaken to the highest quality standards.
  • To ensure efficient operational management including administrative, financial and legal issues, and appropriate liaison with the EDCTP.
  • To ensure that the project is appropriately managed according to the workplan in organising and supervising all the project activities.
  • To provide resources, procedures and tools to ensure the timely delivery of study results at the highest quality level and within budget, including quality control procedures on deliverables and interim and final review of the project achievements from a management perspective.
  • To enable appropriate communication and work dynamics to help drive the Consortium as a team towards successful completion.
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WP2: Implementation

WP2 is led by Dr. Francisco Saúte (FM, Mozambique) in close collaboration with Dr. Didier Ekouevi (UL, Togo) and Prof. Mohammed Samai (COMAHS, Sierra Leone) and the Ministries of Health of Sierra Leone, Mozambique and Togo.
The main objectives WP2 are:

  • To implement PMC delivered alongside the EPI in the first two years of life, at health facilities and EPI mobile-outreach clinics in selected districts of Togo and Mozambique.
  • To increase the uptake of PMC delivered alongside the EPI in the first two years of life, at health facilities and EPI mobile-outreach clinics in the selected districts of Sierra Leone.
  • To build capacity and establish an environment to support transition to the Ministries of Health for scale-up and sustainable PMC in Sierra Leone, Mozambique and Togo.
WP3: Evaluation and Impact

WP3 is led by Dr. Valérie Briand (IRD) with the support of ISGlobal in close collaboration with MULTIPLY partners.

WP3 includes research activities to evaluate the impact of MULTIPLY. These studies evaluate the coverage, operational feasibility, acceptability, cost and impact of PMC. Specific research protocols and informed consent procedures, ethical clearance and the preparation of all essential documents relevant for these activities are managed under WP3. The objective is to ensure that the evaluation is carried out within the outlined timeframe to the highest quality and ethical standards.

The objectives of WP3 are:

  • To assess PMC coverage alongside the EPI platform.
  • To determine the impact of PMC on health services integration, i.e. on EPI immunisation and vitamin A administration coverage.
  • To assess PMC operational feasibility.
  • To assess PMC acceptability among care providers, families and policy makers.
  • To assess the cost and cost-effectiveness of PMC delivery including through the outreach EPI platform.
  • To determine the impact of PMC on malaria incidence, anaemia and overall mortality in the target group.
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WP4: SP Resistance Monitoring

WP4 is led by Prof. Mohammed Samai (COMAHS, Sierra Leone) with the support of ISGlobal in close collaboration with MULTIPLY partners.

Two health facility-based cross-sectional surveys will be conducted before MULTIPLY PMC implementation and after two years of implementation to monitor trends in the development of parasite resistance to SP that might be associated with the intervention.

The prevalence of parasite isolates carrying mutations associated with SP resistance will be assessed before and after implementation through health facility-based surveys, whereby trends over time in the prevalence of parasites with dhfr/dhps resistant mutations will be assessed in children 24 to 59 months of age with a positive malaria rapid diagnostic test (RDT) and/or thick blood smear residing in the MULTIPLY districts.

Monitoring the prevalence of alleles associated with resistance to drugs is, by standard protocol, done by collecting samples from children with evidence of infection. The rationale for this is that any over or misuse of the drug in any sub-population may select parasites strains resistant to SP and that those strains are then transferred by mosquitos to the general population and will be most easily detected in children.

The objectives of WP4 are:

  • To determine whether PMC in the context of the MULTIPLY project is associated with development of parasite resistance to SP assessed through molecular markers in the population
  • To detect trends over time in the proportion of symptomatic children with a positive RDT residing in the areas where MULTIPLY PMC is implemented who carry parasites with dhfr/dhps mutations.
WP5: Networking, Dissemination & Exploitation

WP5 is led by Prof. Didier Ekouevi (UL, Togo) with the support of ISGlobal. This transversal WP is decisive for the overall significance of the project. Activities within this WP are carefully designed to harmonise messages delivered to specific target audience to maximise the impact of the project outcomes.

The objectives of WP5 are:

  • To design and implement a Communication and Dissemination Plan.
  • To create and disseminate electronic and hardcopy materials to ensure clear and aligned messages regarding the progression and project outputs.
  • To develop a Scientific Publication plan for the scientific dissemination of the findings of the project.
  • To design and implement communication tools and processes to adequately implement the plans included in this WP.
  • To facilitate translation of project results into policy.
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