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WHO ultimatum on artemisinin monotherapy is showing results

BMJ 2006; 332 doi: (Published 18 May 2006) Cite this as: BMJ 2006;332:1176

We still need artesunate monotherapy


Seen from Geneva, the WHO "ultimatum" on artemisinin monotherapy may
seem as a landmark in prolonging the useful therapeutic life of the
artemisinin derivatives, 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 P.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 (ACT)strategy. Fifteen years later the same 3 day
regimen remains our first line therapy, but we still need artesunate

A prime example is highlighted in patients with uncomplicated
hyperparasitaemic falciparum malaria (> 4% infected red blood cells),
who are at significant risk of severe malaria and treatment failure. These
infections require a 5-7 day course of treatment with oral artesunate1.
The only alternative is parenteral quinine which is less effective, more
expensive and less well tolerated2. In the second and third trimester of
pregnancy artesunate is also a better drug for uncomplicated falciparum
malaria, but needs to be given for 7 days with a dose adjustment due to
the altered kinetics in pregnant women3 4. We currently treat patients who
experience a recurrence of their parasitaemia following a 3 d course of
mefloquine-artesunate with a 7 d 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 ACTs, WHO 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 may
for Intermitent Preventive Treatment (IPT), amodiaquine, sulphadoxine-
pyrimethamine, atovaquone-proguanil and chlorproguanil-dapsone because
these drugs are the only one we have and must be protected by fixed
combination with an artemisinin derivative.

François Nosten

Elizabeth Ashley

Rose McGready

Ric Price

1. 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. Transactions of
the Royal Society of Tropical Medicine and Hygiene 1998;92(2):207-11.

2. Luxemburger C, Nosten F, Raimond SD, Chongsuphajaisiddhi T, White NJ.
Oral artesunate in the treatment of uncomplicated hyperparasitemic
falciparum malaria. American Journal of Tropical Medicine and Hygiene

3. 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. Clinical
Infectious Diseases 2001;33(12):2009-16.

4. 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(5):367-71.

Competing interests:
None declared

Competing interests: No competing interests

19 June 2006
Francois H Nosten
Elizabeth Ashley, Rose McGready, and Ric Price
SMRU, Mae Sot, 63110 Thailand