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Historical 8-Aminoquinoline Combinations: Not All Antimalarial Drugs Work Well Together

G. Dennis ShanksAustralian Defence Force Malaria and Infectious Disease Institute, Enoggera, Australia; University of Queensland, School of Public Health, Brisbane, Australia

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ABSTRACT.

Since their first use in the 1920s, 8-aminoquinolines have been known to have important toxicities such as methemoglobinemia and hemolysis. An empiric pamaquine (plasmochin) combination with quinine was widely used in the British military with relatively little toxicity. Attempts to use pamaquine with a new synthetic antimalarial drug (atabrine, quinacrine) in the 1930–1940s, however, resulted in hemolytic reactions and some deaths from renal failure. An improved 8-aminoquinoline, primaquine, was particularly effective against Plasmodium vivax relapses when combined with either quinine or chloroquine. When used in reduced daily doses (15 mg) over 2 weeks, it was safely given to many thousands of U.S. soldiers returning from Korea. CP tablets (chloroquine 300 mg, primaquine 45 mg weekly) were widely used during the Vietnam War with few hemolytic reactions and no known deaths. Efficacy and toxicity of 8-aminoquinolines is determined in part by the selection of appropriate partner drugs

Author Notes

Address correspondence to G. Dennis Shanks, ADF Malaria and Infectious Diseases Institute, Enoggera, QLD 4051, Australia. E-mail: dennis.shanks@defence.gov.au

Disclaimer: The opinions expressed are those of the author and do not necessarily reflect those of the Australian Defence Force or the US Department of Defence.

Author’s address: G. Dennis Shanks, ADF Malaria and Infectious Diseases Institute, Enoggera, QLD 4051, Australia. E-mail: dennis.shanks@defence.gov.au.

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