We still need artesunate monotherapy

doi:10.1136/bmj.333.7557.45

BMJ 2006;333:45 (1 July), doi:10.1136/bmj.333.7557.45

Letter

We still need artesunate monotherapy

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

In 1991 on the Thai-Myanmar border we were facing the prospectof untreatable Plasmodium falciparum malaria as drug resistanceemerged to standard antimalarial agents. The problem was circumventedby combining artesunate or artemether with mefloquine and thedevelopment of the artemisinin combination therapy strategy.Fifteen years later the same three day regimen remains our firstline therapy, but we still need artesunate monotherapy.

A prime example is highlighted in patients with uncomplicatedhyperparasitaemic falciparum malaria (> 4% infected red bloodcells), who are at risk of severe malaria and treatment failure.These infections require a five to seven day course of treatmentwith oral artesunate.² The only alternative is parenteral quinine,which is less effective, more expensive, and less well tolerated.³In the second and third trimester of pregnancy, artesunate isalso a better drug for uncomplicated falciparum malaria, butit needs to be given for seven days with a dose adjustment becauseof the altered kinetics in pregnant women.^{4 5} We currently treatpatients who experience a recurrence of their parasitaemia aftera three day course of mefloquine-artesunate with a seven daycourse of artesunate combined with tetracycline or clindamycin.Obviously we would like to prescribe appropriate antimalarialtherapy without the need for artesunate tablets but this isunlikely to be possible in the near future. Hence we hope thatsome manufacturers will continue to supply artesunate aloneto 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 manufacturersto phase out the production of single drug tablets of mefloquine(except perhaps for intermittent preventive treatment), amodiaquine,sulphadoxine-pyrimethamine, atovaquone-proguanil, and chlorproguanil-dapsonebecause these drugs are all we have and must be protected byfixed combination with an artemisinin derivative.

François Nosten, director

SMRU{at}tropmedres.ac, Shoklo Malaria Research Unit (SMRU), Mae Sot, 63110 Thailand

Elizabeth Ashley, Rose McGready, Ric Price

Shoklo Malaria Research Unit (SMRU), Mae Sot, 63110 Thailand

Competing interests: None declared.

References

Rehwagen C. WHO ultimatum on artemisinin monotherapy is showing results [news extra]. BMJ 2006; 332: 1176. (20 May.)[Free Full Text]
Price R, Luxemburger C, van Vugt M, Nosten F, Kham A, Simpson J, et al. Artesunate and mefloquine in the treatment of uncomplicated multidrug-resistant hyperparasitaemic falciparum malaria. Transact R Soc Trop Med Hygiene 1998;92: 207-11.
Luxemburger C, Nosten F, Raimond SD, Chongsuphajaisiddhi T, White NJ. Oral artesunate in the treatment of uncomplicated hyperparasitemic falciparum malaria. Am J Trop Med Hygiene 1995;53: 522-5.[Abstract/Free Full Text]
McGready R, Cho T, Keo NK, Thwai KL, Villegas L, Looareesuwan S, et al. Artemisinin antimalarials in pregnancy: a prospective treatment study of 539 episodes of multidrug-resistant Plasmodium falciparum. Clin Infect Dis 2001;33: 2009-16.[CrossRef][ISI][Medline]
McGready R, Stepniewska K, Ward SA, Cho T, Gilveray G, Looareesuwan S, et al. Pharmacokinetics of dihydroartemisinin following oral artesunate treatment of pregnant women with acute uncomplicated falciparum malaria. Eur J Clin Pharmacol 2006;62: 367-71.[Medline]