A blog authored by MMV's André-Marie Tchouatieu, shared on the World Malaria Day blog series
By André-Marie Tchouatieu
Associate Director, Access & Product Management, Medicines for Malaria Venture
In some parts of Africa, more than 60% of malaria cases occur in just 4 months of the year, during the rainy season. Around 39 million African children under 5 years of age live in these regions of defined malaria seasonality, where an estimated 152 000 die each year from malaria1.
Most of these young children live in the Sahel and sub-Sahel region, where the World Health Organization (WHO) recommends Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP+AQ) for those aged between 3 and 59 months in areas of high seasonal malaria transmission, in which SP and AQ remain effective.2
SMC relies on the intermittent dosing of an antimalarial during the malaria season to protect children from malaria, by maintaining therapeutic drug concentrations in the blood throughout the period of greatest risk.
While this regimen is highly effective, the threat of drug resistance could undermine the life-saving impact of SMC over time; as a result of this risk, long-term planning to develop alternative SMC treatments is necessary.
MMV, a leading product development partnership (PDP) in the field of antimalarial drug research and development, is a partner in ACCESS-SMC; a UNITAID-funded project co-led by Malaria Consortium and Catholic Relief Services (CRS), which is supporting National Malaria Control Programmes in seven countries in the Sahel region to roll out SMC. MMV is driving the discussion regarding future SMC treatment options, focusing on 2 key issues: research focused on new medicines for chemoprevention and the repurposing of existing medicines.
New medicines for chemoprevention
In addition to being efficacious and well tolerated, new medicines for SMC should have a long shelf-life, provide long-duration protection, offer simple administration, and be formulated as child-friendly fixed-dose combinations suitable for community distribution channels.
The bitter taste of AQ makes it difficult to ensure correct dosing in children, as it may cause them to gag or spit out the medicine. Also, the current tablets are very hard to crush before mixing them with water and administering them to children. As such, there is a need for a child-friendly and taste-masked formulation both for the current regimen and for future medicines for SMC.
In general, oral medicines are preferable for ease of administration and acceptability; however, an injectable formulation might be desirable if only one injection per season were required.
The process to discover and develop a new antimalarial normally takes between 13-15 years. As a result, with the threat of drug resistance undermining SP+AQ today, this current option may be rendered ineffective long before new medicines are developed.
Medium-term alternatives to SP+AQ – before de novo compounds are developed into new medicines may consist of re-purposing existing treatments for SMC. For example, dihydroartemisinin-piperaquine (DHA-PQP) has good preventive efficacy when studied as a potential SMC therapy. However, its widespread use for SMC would likely increase the risk of artemisinin and piperaquine resistance. Additionally, given its comparatively short half-life, DHA is not an ideal partner drug for SMC. Furthermore, the WHO is not recommending the use of ACTs for chemoprevention. A possible way forward would be to evaluate other partner drugs coupled with PQP, such as azithromycin.
Whether new medicines are developed or existing medicines are re-purposed for SMC, regulatory approval for this specific use of medicines is imperative. As the regulatory route for registering a drug developed expressly for SMC is unprecedented, MMV is consulting with various regulatory experts and agencies to determine a suitable regulatory strategy for future SMC drugs.
It is a great achievement that last year more than 3 million children received SMC through the ACCESS-SMC project. Looking to the future, while continuing to improve the current drug, we need to be prepared with the next-generation of chemoprevention medicines, in order to reach millions of children still at risk of dying from malaria. In 2016, ACCESS-SMC aims to provide an estimated 30 million treatments to vulnerable children. Follow our progress, sign-up for the ACCESS-SMC newsletter / sign-up for the MMV newsletter.
1. Cairns M, et al. Estimating the potential public health impact of seasonal malaria chemoprevention in African children. Nat Commun. 2012. 3:881.
2. World Health Organization. ‘Seasonal Malaria Chemoprevention’ (Last update: 7 August 2013)