Radical Cure of Infections with Plasmodium cynomolgi: a Function of Total 8-Aminoquinoline Dose *

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Abstract
A series of studies on rhesus monkeys infected with sporozoites of the M and B strains of Plasmodium cynomolgi have shown: 1) at the same total course doses (with quinine as a companion blood schizonticidal drug) 7-day and 14-day dosage regimens of pamaquine, pentaquine, or isopentaquine are essentially equally effective in producing radical cure of infections with the M strain; 2) at the same total course dose (with chloroquine as a companion drug) a 7-day dosage regimen of primaquine is at least as effective as a 14-day dosage regimen in inducing radical cure of infections with the B strain, and may be slightly more effective; 3) at the same total course doses (with chloroquine as a companion drug), single dose, 3-day, and 7-day dosage regimens of primaquine or 4-methyl primaquine are essentially equally effective in producing radical cure of infections with the B strain. These observations have led to the conclusion that the total dose of 8-aminoquinoline administered is the primary determinant of radical curative activity, rather than the duration of drug treatment. This total dose concept derives support from currently available observations on the capacity of primaquine to cure naturally acquired and induced infections with P. vivax and underpins the current search for 8-aminoquinoline derivatives which will cure such infections when administered in single dose or three daily dose treatment regimens.