Malaria treatment failures after artemisinin-based therapy in three expatriates: could improved manufacturer information help to decrease the risk of treatment failure ?

Manufacturers information and drug content included in twenty-five artemisinin-containing specialities were reviewed.A substantial number of manufacturers do not follow current WHO recommendations regarding treatment duration and doses.This study shows that drug packaging and their inserts should be improved.Artemisinin derivatives, such as artesunate, artemether and dihydroartemisinin, are the most parasiticidal of all the antimalarial drugs against Plasmodium falciparum [1]. Their pharmacokinetic (rapid absorption, short half life ~1 hour) and pharmacodynamic (high parasite reduction ratio) properties mitigate against the development of resistance. In vivo resistance to this drug class has not yet been described [2]. However, several challenges remain, including the limited availability of GMP quality drugs, the emergence of fake drugs, and their optimal deployment in malaria-endemic countries. Artemisinin-based drugs are easily available in several malaria-endemic countries and are sold as mono- or combination therapies. They are manufactured in several countries, packaged differently and contain package inserts of varying quality and accuracy. WHO currently recommends malaria-endemic countries to use three days of an artemisinin-based combination treatment (ACT) e.g. artemether/lumefantrine (A/L), artesunate (4 mg/kg/day) plus an effective, longer acting partner drug, such as amodiaquine or mefloquine [3]. If used alone, seven days of treatment of an artemisinin derivative is necessary because shorter courses result in unacceptably high rates of recrudescence. Most recently, WHO has called drug manufacturers to switch the production of artemisinin monotherapies towards combined therapies because of the risk of developing drug resistance. Artesunate monotherapy of ≤ 5 days duration in South-East Asian and African patients is associated with a failure rate of up to 50% and the four doses regimen of artemether/lumefantrine has resulted in failure rates of between 1