If left untreated, uncomplicated malaria can quickly progress to severe malaria − a life-threatening condition that can kill within a few hours. The first point-of-care for many patients with severe malaria is a community-level health-care worker or a primary care facility. Those presenting with severe malaria should be treated as quickly as possible with injectable artesunate (Inj AS), followed by oral treatment with an ACT when the patient is sufficiently well; however, most local health posts do not have the Inj AS or personnel trained in its administration. As a result, patients need to be referred to higher-level facilities, creating delays in access to critically-needed treatment. In such cases, WHO recommends the use of rectal artesunate (RAS) as a pre-referral intervention.1 RAS buys time until Inj AS can be administered – and can mean the difference between life and death.2,3
With funding from UNITAID, MMV has been working with two Indian pharmaceutical companies, Cipla and Strides Shasun, to obtain WHO prequalification for their RAS products. Both companies submitted their dossiers to the WHO Prequalification of Medicines Programme in 2015.
In 2016, the Expert Review Panel (ERP) of the Global Fund issued a 12-month authorization for procurement of Cipla’s product. The authorization allows RAS to be procured while awaiting WHO prequalification, and offers a landmark opportunity for donor financing to support broad uptake of this critically-needed medicine.
Through renewed UNITAID funding, MMV will support the registration of RAS in several high-burden African countries. In parallel, MMV will be working with implementing partners and host countries to design pilot introduction programmes for RAS. These will develop and test tool kits to help reinforce correct use of RAS and referral of patients to health-care facilities for treatment with Inj AS followed by an oral ACT. This will form part of an integrated severe malaria management approach.
Prof. Christian Lengeler explains the importance of RAS and MMV’s role in introducing the first quality-assured version of the product.
1. How is RAS being used today?
Unfortunately, today, the use is minimal. There are very few countries that have policies in place and even fewer countries implementing its use.
2. Why is RAS an important tool in the management of severe malaria?
The reality is that more than 400,000 people, mostly children, die each year from malaria. Most of these children live in remote areas far from health-care services. RAS has the potential to help address a substantial part of this mortality burden. It's a drug that is easy to administer and so can be used in very remote settings. It’s the most important new intervention for severe malaria management
since the WHO prequalification of Inj AS.
3. What is the implication of the Global Fund's authorization of a RAS product?
It's an absolutely essential first step in a relatively long chain of events that will help RAS achieve maximum impact. The Global Fund is the main funder supporting procurement of malaria medicines in endemic countries but it can only purchase ERP-authorized or WHO-prequalified medicines.
ERP authorization will allow immediate and time-limited procurement by the Global Fund. The next step will be WHO prequalification of the drug, which will allow its continued purchase with donor funds beyond the ERP-time limit and therefore further expand its access. Meanwhile, we must refine the strategy of how RAS will be used in the field. We must not forget it will be used to address severe disease far away from health systems – one of the most difficult tasks in malaria control.
4. How do you see MMV’s role in this process?
The granting of the ERP authorization for an RAS product is the latest important step in a process to ensure widespread availability of a quality RAS product initiated over 20 years ago. In 2013−2014, building on the earlier work of WHOTDR, MMV engaged two companies to develop quality RAS products and worked to define requirements for WHO prequalification, thus helping put this tool back on the agenda.
Moving forward, MMV's role is to continue to support the WHO prequalification of the product, to help better forecasting of RAS needs at country level and ensure a robust pipeline to secure its availability.
- World Health Organization. Guidelines for the treatment of malaria. Second edition (2010).
- Gomes MF et al. “Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial.” The Lancet. 373(9663):557-66 (2009).
- WHO-TDR website. Rectal artesunate testing and delivery (2016).