Nathan Ford: Improving treatment for severe malaria

Nathan Ford Major advances in drug therapy are rare, particularly in the neglected field of tropical diseases. So it was quite appropriate that when the results of the largest trial ever done on severe malaria were presented in Atlanta last November, they were met with cheers from the crowd. The trial, which found a clear mortality reduction among children in Africa if artesunate is given instead of quinine, must now be followed up with a rapid plan for supporting implementation, if patients at risk in the poorest parts of the world are to benefit.

Severe malaria claims around 800 000 lives a year, mostly children in Africa. For hundreds of years quinine has acted as the mainstay of malaria treatment. Over the past decade, evidence from large randomised trials in Asia and Africa found that artesunate resulted in fewer deaths, fewer side effects, and more rapid parasite clearance than quinine.  According to a Cochrane meta-analysis published in March, treating malaria with artesunate instead of quinine reduced the risk of death by 39% in adults and 24% in children. As a vote of confidence in the validity, precision, and generalisability of the accumulated evidence, the Cochrane collaboration, which as a rule concludes that more research is needed far more often than not, this time surmised that further research is unnecessary.

The World Health Organization responded to the evidence, revising its guidelines for severe malaria earlier this week. However, while the process of translating evidence into guidelines is streamlined to the point that it is now subject to its own strict methodology, the process of translating guidelines issued in Geneva into benefits for patients in Africa, is fraught with operational challenges, political trade-offs, lack of funds, and limited resources.

Changing practice across a continent cannot be expected to occur without organised support.  This week, a report released by Médecins Sans Frontières outlines some of the anticipated barriers to making the switch. These include donor support to finance the initially higher unit cost of artesunate ($US3.30) compared with quinine ($US1.30), and providing confidence to manufacturers to scale up production, technical support to translate evidence into national protocols, and training to shift the habits of health workers, many of whom have been used to administering quinine for decades.

Without a clear implementation plan, there is a risk of a vicious cycle of passivity whereby national governments are reluctant to fully change practice because of insufficient funds, donors impartially fund whatever countries request, and manufacturers fail to meet the potential demand because production is not stimulated by a clear forecast of need.

Patients and providers in malaria-endemic regions have been here before. In 2001, WHO recommended a switch to artemisinin-based therapy for the treatment of uncomplicated malaria, but higher costs, erratic supplies, and unclear donor commitments meant that patients continued to be given drugs that, due to high levels of resistance, no longer worked.

If new evidence of similar magnitude of mortality reduction was found for a major childhood killer in Europe or the USA, and the new treatment cost just an extra $US2, there would be a clear plan to ensure a rapid change in policy and practice. With over 2000 deaths from severe malaria every day, the need for a coordinated international response to support African countries to make the switch is clear.

This blog also appears on the PLoS Speaking of Medicine site.

Nathan Ford has worked with Médecins Sans Frontières (MSF) since 1998, and is currently the medical coordinator for MSF’s International Campaign for Access to Essential Medicines.