The article by Harry Most and colleagues in a 1946 issue of The Journal was the first report in the American medical literature on the efficacy of chloroquine (a 4-aminoquinoline) as an antimalarial agent in humans. This study of roughly 300 military personnel who had acquired vivax malaria during World War II demonstrated the superiority of chloroquine over quinacrine (the only synthetic antimalarial compound used clinically at that time) and quinine (an active alkyloid present in cinchona bark extracts, which were used for centuries). The report represented a milestone on the long and winding road toward a highly efficacious and relatively nontoxic synthetic antimalarial agent (reviewed in detail in reference 1) and began a period of about three decades during which the drug served an important role in malaria control programs in endemic areas.
Unfortunately, the days of chloroquine's greatest glory were numbered. In 1961, the first report2 of
Wyler DJ. The Ascent and Decline of Chloroquine. JAMA. 1984;251(18):2420–2422. doi:10.1001/jama.1984.03340420086034
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