IMPRIMA

The challenge

As countries progress towards malaria elimination, additional strategies will be needed to identify and treat malaria infections and prevent transmission of the malaria parasite. One tool that is not yet fully used is single low-dose primaquine. Unlike most other antimalarials, primaquine acts on gametocyte stages of the parasite’s life cycle, the form taken up by mosquitoes and transmitted to a new host. 

Although the antimalarial activity of primaquine is well-established, its use has been held back because of its effects on people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, which is common in sub-Saharan Africa. G6PD is important to red blood cell function, and people with G6PD deficiency are at increased risk of anaemia when given standard primaquine doses. 

However, a single low dose of primaquine is still effective against gametocytes and can safely be given to children with G6PD deficiency. The WHO recommends using single low-dose primaquine alongside conventional malaria treatments like artemisinin combination therapies (ACT). Nevertheless, residual fears about impacts on children with G6PD deficiency have led to limited use of single low-dose primaquine. 

A further obstacle has been the formulation of primaquine. Standard tablets are large and bitter-tasting, making them difficult to administer to young children.

The project

Through a previous EDCTP2-funded project, the Developing Paediatric Primaquine, the team has been working on a child-friendly version of primaquine suitable for single low-dose use in children. It has developed smaller tablets, shown that they have the same biological properties as existing products, and worked with children and caregivers on preferred flavourings to mask the bitter taste of primaquine.

The Global Health EDCTP3-funded IMPRIMA project will work with national malaria control programmes in Burkina Faso, Burundi and Madagascar to understand and address barriers to the introduction of this new child-friendly version of primaquine, providing a model for introduction in other countries. Burkina Faso and Burundi have signalled an interest in introducing single low-dose primaquine for children, while Madagascar has introduced it for adults but not yet for children.

In particular, the project will address residual concerns about the effects of primaquine on children with G6PD. It will carry out a trial comparing standard ACT treatment of malaria in children with enhanced treatment including single low-dose primaquine, paying particular attention to the risk of anaemia. The trial will be undertaken in Burkina Faso, Burundi and Madagascar, countries with different geographies and intensities of malaria transmission. 

The project team will also carry out extensive community engagement to understand and address community concerns and to pave the way for successful implementation.

Impact

The IMPRIMA project will generate key evidence on the efficacy and safety of single low-dose primaquine. It will:

• Provide national decision-makers in Burkina Faso, Burundi and Madagascar with key evidence on the safety of single low-dose primaquine, the likely main barrier to introduction.
• Demonstrate to other countries the feasibility of introducing primaquine into their malaria control programmes.

Although not directly benefiting individuals with malaria infections, routine use of single low-dose primaquine would help to disrupt malaria transmission, delivering population-level benefits and accelerating malaria elimination.