Academic journal article Bulletin of the World Health Organization

Averting a Malaria Disaster in Africa-Where Does the Buck Stop?

Academic journal article Bulletin of the World Health Organization

Averting a Malaria Disaster in Africa-Where Does the Buck Stop?

Article excerpt

Drug-resistant malaria--the gathering storm

The serious threat posed by drug-resistant malaria in Africa is widely acknowledged (1). Chloroquine resistance is now universal, and the days of treating malaria with a single cheap drug are generally believed to be numbered. Resistance to sulfadoxine-pyrimethamine (SP) the natural successor to chloroquine was increasing by the end of the 1990s. It was argued then that the only way to protect this or any other single drug is to give it in combination with another unrelated antimalarial as combination drug therapy (CDT) as in the case of tuberculosis (TB) treatment (1). Since the 1990s, the accelerating emergence and spread of resistance to SP has been documented in many areas, with parasitological failure rates of around 20% being widely reported, and up to 40-80% in certain areas (2, 3). Two relatively cheap drugs could potentially replace SP as monotherapy; amodiaquine (an older drug with similarities to chloroquine) and chlorproguanil-dapsone (Lapdap, an anti-folate). Both are currently effective in many areas where SP resistance already occurs, but this situation may well not last for much longer (2, 4). Resistance to amodiaquine already exists at an appreciable level in some areas (up to 26% in Kenya) (5). Because of its similarity to SP, there is a concern that resistance to chlorproguanil-dapsone may follow rapidly if it is deployed widely in areas of widespread SP resistance. We therefore face a crisis in treating malaria which is one of the most important causes of morbidity and mortality in Africa. The proposed CDT has received widespread scientific support and has the potential for returning Africa to sustainable, highly effective antimalarial treatment. The solution has, however, one serious drawback.

It has been suggested for some years that combinations of drugs, and especially combinations that include artemisinin drugs, will be highly effective in treating malaria. There is indirect evi-dence from south-east Asia (but not from Africa) that these combinations could also delay or halt the emergence of drug resistance. An informal expert consultation held by WHO in 2001 supported the conclusion that combinations of drugs are the best, and possibly the only, long-term solution (6). Setting aside the question of cost, the consultation proposed a list of three artemisinin-containing combinations (lumefantrine--artemether, amodiaquine--artesunate and SP--artesunate) that they considered to have the greatest potential, and one non-artemisinin combination (SP--amodiaquine) was suggested as a fall-back option. Subsequent studies have confirmed that these combinations are highly effective and sale (4, 5). A number of technical questions (for example on local effectiveness and safety in pregnancy) have yet to be answered and operational studies are required. One potential advantage of artemisinins, namely that they reduce transmission by reducing gametocyte carriage (7), has not been confirmed in Africa and may not be relevant in areas with high transmission of malaria.

The principle that combination therapy could provide a rapid solution to a serious crisis and do so in a sustainable manner has, however, gained widespread support.

Cost--the major flaw

There remains a serious problem with combination therapy, and that is its cost (1, 8, 9). Chloroquine and SP cost approximately US$ 0.15 for a course of treatment. Negotiation between the WHO and some drug companies has already successfully reduced the cost of combination treatment to between US$ 0.90 and US$ 1.4 for a course of treatment for children up to seven years old and to approximately US$ 2 per adult dose. There are theoretical reasons for assuming that the cost might fall over time (10), but it seems unlikely to fall substantially below that negotiated by WHO in the immediate future, and making policy based on the assumption that cost may fall significantly is rash. It is well established that combination therapies are more expensive than current monotherapy and that the true opportunity cost of switching to combination therapy will significantly exceed current drug price estimates. …

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