We still need artesunate monotherapy

Editor—Seen from Geneva, the World Health Organization's “ultimatum” on artemisinin monotherapy may seem a landmark in prolonging the useful therapeutic life of the artemisinin derivatives,¹ but for the clinicians in the field, the matter is different.

In 1991 on the Thai-Myanmar border we were facing the prospect of untreatable Plasmodium falciparum malaria as drug resistance emerged to standard antimalarial agents. The problem was circumvented by combining artesunate or artemether with mefloquine and the development of the artemisinin combination therapy strategy. Fifteen years later the same three day regimen remains our first line therapy, but we still need artesunate monotherapy.

A prime example is highlighted in patients with uncomplicated hyperparasitaemic falciparum malaria (> 4% infected red blood cells), who are at risk of severe malaria and treatment failure. These infections require a five to seven day course of treatment with oral artesunate.² The only alternative is parenteral quinine, which is less effective, more expensive, and less well tolerated.³ In the second and third trimester of pregnancy, artesunate is also a better drug for uncomplicated falciparum malaria, but it needs to be given for seven days with a dose adjustment because of the altered kinetics in pregnant women.⁴,⁵ We currently treat patients who experience a recurrence of their parasitaemia after a three day course of mefloquine-artesunate with a seven day course of artesunate combined with tetracycline or clindamycin. Obviously we would like to prescribe appropriate antimalarial therapy without the need for artesunate tablets but this is unlikely to be possible in the near future. Hence we hope that some manufacturers will continue to supply artesunate alone to be used in specific circumstances.

After resisting the change to artemisinin combination therapies, the World Health Organization is now going to the opposite extreme. Instead, it should encourage antimalarial drug manufacturers to phase out the production of single drug tablets of mefloquine (except perhaps for intermittent preventive treatment), amodiaquine, sulphadoxine-pyrimethamine, atovaquone-proguanil, and chlorproguanil-dapsone because these drugs are all we have and must be protected by fixed combination with an artemisinin derivative.