Resistance to dihydroartemisinin.

In Response: The original title of our article was "Lack of Plasmodium falciparum in Vitro and Genomic Resistance to Dihydroartemisinin in Travelers Returning to France from Africa." EID's shortening of the title (1) led to the perception that the letter title was misleading, but it was not on purpose. We have recently tested the 50% inhibitory concentration for artemether of the s769N PfATPase6 isolate that we had kept in liquid nitrogen, and it showed susceptibility.

We underline that the previously reported clinical or parasitologic failures to some artemisinin-based combination therapies (2,3) were not synonymous with the emergence of resistance to artemisinin compounds. In the study by Grandesso et al., a combination of artesunate plus amodiaquine was given to children <5 years of age who lived in an area in which amodiaquine alone was ineffective to adequately treat uncomplicated falciparum malaria in 1 of 3 cases at day 28 (2). Such a combination (artesunate plus amodiaquine) was nearly equivalent in 1 of 3 cases to a 3-day artesunate monotherapy, which may fail to completely cure children because of the short half-life of artesunate. In the study by Bukirwa et al., no recrudescence occurred in patients treated with artesunate plus amodiaquine and only 2 of 199 patients treated with artemether plus lumefantrine experienced recrudescence at day 28 (3). As Birkiwa et al. themselves acknowledged, artemether plus lumefantrine was not administered with food, and it is known that lumefantrine is absorbed better when it is taken with a small amount of fat. Thus, the clinical failures observed did not necessarily reflect P. falciparum resistance to artemisinin compounds.

References

(1.) Cojean S, Hubert V, Le Bras J, Durand R. Resistance to dihydroartemisinin. Emerg Infect Dis. 2006; 12:1798-9.

(2.) Grandesso F, Hagerman A, Kamara S, Lam E, Checchi F, Balkan S, et al. Low efficacy of the combination artesunate plus amodiaquine for uncomplicated falciparum malaria among children under 5 in Kailahun, Sierra Leone. Trop Med Int Health. 2006;11:1017-21.

(3.) Bukirwa H, Yeka A, Kamya MR, Talisuna A, Banek K, Bakyaita N, et al. Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda. PLoS Clin Trials. 2006;1:e7.

Address for correspondence: Remy Durand, Hopital Avicenne, Laboratoire de Parasitologie Mycologie, 125 rue de Stalingrad, 93009 Bobigny CEDEX, France; email: remy.durand@ avc.aphp.fr

Sandrine Cojean, * ([dagger]) Veronique Hubert, * Jacques Le Bras, * ([dagger]) ([double dagger]) and Remy Durand * ([double dagger]) ([section])

* Hopital Bichat Claude Bernard, Paris, France; ([dagger]) Universite Paris 5; Paris, France; ([double dagger]) Hopital Avicenne, Bobigny, France; and ([section]) Universite Paris 13, Bobigny, France