The Use of Artemisinin and its Derivatives as Anti-Malarial Drugs: Report of a Joint CTD/DMT/TDT Informal Consultation, Geneva, 10-12 June 1998

Artemisinin and its derivatives, first discovered, tested and marketed in China, produce more rapid resolution of fever and parasitaemia than aIl known antimalarial agents. Due to these remarkable properties, there are concerns that their uncontrolled and widespread use, particularly as oral formulations, will result in the rapid development of drug resistance. These concerns were reflected in the recommendations made by WHO Informal Consultations in 1993 and 1995 (WHO, 1994; 1996). Since these recommendations were made, further experience with the use of artemisinin and its derivatives bas been obtained. The prevalence of drug-resistant falciparum malaria bas increased and national antimalarial drug policies have consequently changed, particularly in Africa south of the Sahara. Sulfadoxine/pyrimethamine replaced chloroquine as the first-line treatment of uncomplicated malaria in Malawi in 1993 and in Botswana, Kenya and South Africa in 1997. This raised difficulties in the choice of the second line drug to be used for failures of sulfadoxine/pyrimethamine therapy since only a limited number of antimalarial drugs are available. For example, amodiaquine was chosen in Malawi because mefloquine was considered to be too expensive and to have an unacceptable potential for adverse reactions; oral quinine was also unacceptable because of patient compliance with the required 7 -clay regimen. These difficulties are compounded by reports of increasing resistance to sulfadoxine/pyrimethamine in some areas of East Africa where the use of this combination has increased. The availability of oral formulations of artemisinin drugs would increase the choice of drugs for use in malaria programmes in Africa if (i) they could be made available at an affordable price and (ii) their use would not lead to the early development of resistance. Papua New Guinea also faced with an unacceptable level of chIoroquine failures decided in 1997 to change its antimalarial drug policy, pending efficacy trials, to a combination of chloroquine plus sulfadoxine/pyrimethamine as the first-line drug with oral artesunate alone as the second-line, and parenteral or rectal artesunate for the treatment of severe disease (Drs K. Palmer and Allan Schapira, WPRO Mission Report October 1997). ln light of these considerations, an informal consultation on the use of artemisinin and its derivatives as antimalarial drugs was held in Geneva from 10-12 June 1998 to update WHO policies on the use of these drugs. It brought together persons with experience in preclinical and clinical evaluation of drugs, regulatory affairs, and the use of these drugs in malaria control programmes, together with representatives of the International Federation of Pharmaceutical Manufacturers Associations.