Big marijuana--lessons from big tobacco.

highly efficient vector, a nonimmune population, and mining conditions that encouraged both vector breeding and malaria transmission fueled recurrent epidemics of malaria, which apparently started in the 1940s or early 1950s; 80% of the cases were P. falciparum. In 1955, public health authorities in Pailin began distributing chloroquine to workers daily; later, the frequency was reduced to twice a week. In 1960, they began administering chloroquine indirectly through medicated salt. This method increased coverage but made it difficult to ensure that each worker consumed an adequate dose of the drug. The repeated application of subcurative concentrations of chloroquine to a highly infected population set the stage for the emergence of chloroquine-resistant strains of P. falciparum. The subsequent transmission of resistant strains of falciparum to new waves of nonimmune workers, month after month, and their treatment with high but often noncurative doses of chloroquine amplified resistance. By 1973, 90% of falciparum malaria cases were resistant to chloroquine, and 70% exhibited high levels of resistance. From the Thai–Cambodian border, resistant falciparum malaria spread to surrounding areas along with the returning migrant workers. Secondary patterns of dispersal from these surrounding areas contributed to the wider dissemination of chloroquine resistance throughout South and Southeast Asia. Mass drug-administration (MDA) programs elsewhere in the world during the 1950s and 1960s may also have contributed to the rise of chloroquine resistance. There is a strong correlation between the geographic areas where MDA programs were initiated and the places where chloroquine resistance first emerged. Also contributing to the development of resistance was the widespread availability of chloroquine in shops and private pharmacies, lax regulation of use of the drug, and the absence of effective primary care systems. It is not surprising that Pailin was an early site for the emergence of artemisinin resistance. Some observers have suggested that malaria parasites in that region may be particularly prone to mutation. Yet it is clear that although the drugs have changed, the social and economic conditions under which they are used have not. Pailin remains the center of an extensive migrant labor system, with limited health resources. In addition, the widespread availability in the region of cheap counterfeit drugs containing subclinical quantities of artemisinin and the marketing and use of noncombination forms of the drug have created an ideal mix of conditions for both the development and spread of artemisinin resistance.4 An intensive campaign is currently under way to eliminate artemisinin resistance in the greater Mekong Delta region and prevent its further spread. These efforts focus on identifying and treating to cure all cases of malaria in the region. Whether these efforts will be successful is unclear. But efforts to address the social and economic conditions that contribute to the spread of malaria and foster antimalarial resistance, including the marketing of monotherapies and counterfeit drugs, are essential steps for preventing artemisinin-based drugs from following the path of chloroquine. Given the cyclical history of drug development followed by the emergence of resistance, it is also critical that investments continue to be made in the development and production of new generations of antimalarial therapies.