title: Epidemiology of the emergence and spread of drug-resistant falciparum malaria in South-East Asia and Australasia.
abstract: A review is presented of the development of drug-resistant malaria in Païlin on the Thai-Kampuchean border and its spread to other parts of the region and beyond. Resistance of P. falciparum to chloroquine appears to have emerged in this area in the early 1960s and evidence of resistance to the combination of sulfadoxine and pyrimethamine and to the combination of diaphenylsulfone and pyrimethamine came from the same area towards the end of the same decade. The factors leading to the emergence and increase of drug resistance appear to have been: the continuous introduction of non-immune migrants to a hyperendemic malaria area, an increase in already intense transmission resulting from the living and working conditions of the migrants and prolonged drug pressure resulting from individual drug consumption and mass drug administration, particularly from the medicated salt project which covered the area in which resistance emerged. These conditions lead to the selection of resistant mutants. Moreover, resistant parasites were exposed to multiple and increasing doses of chloroquine, pyrimethamine and sulfathiazole during repeated passages through non-immune hosts who were being treated for primary attacks, early recrudescences and reinfections. This probably resulted in increasing the degree of resistance and in the selection of parasites resistant to sulfathiazole with cross-resistance to other sulfonamides. In Irian Jaya, Indonesian New Guinea, where there had been a chloroquinized salt project, the level of chloroquine resistance was much lower than in Païlin; this is associated with the absence of a non-immune population and the lower dose of chloroquine base used in the salt. The spread of chloroquine resistance is then discussed. At first resistance was found only in three foci in South-East Asia where A. balabacensis is the vector of malaria. It then spread to all A. balabacensis areas, and finally to areas outside the area of distribution of A. balabacensis. The spread of resistance is found to be favoured by the presence of the vector A. balabacensis and by the introduction of a non-immune population.
mesh_terms: D000962:Antimalarials / Q000627:therapeutic use*; D001210:Asia, Southeastern; D002160:Cambodia; D002738:Chloroquine / Q000627:therapeutic use; D003622:Dapsone / Q000627:therapeutic use; D004338:Drug Combinations; D004352:Drug Resistance, Microbial; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000469:parasitology; D010139:Pacific Islands; D010963:Plasmodium falciparum / Q000187:drug effects*; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D013785:Thailand
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; D013413:Sulfadoxine; D002738:Chloroquine; D003622:Dapsone; D011739:Pyrimethamine