During the course of
antimalarial screening, it was discovered that
sulfamethoxydiazine, a long-acting
sulfanilamide extensively used in genitourinary tract
infections, not only was effective against Plasmodium berghei
infections in mice when administered alone but also was active when used in combination with
chloroquine, in effect making it possible to use half as much of the latter
drug as normally required to achieve the same results. The triple combination of
chloroquine,
sulfamethoxydiazine, and
pyrimethamine, when administered in a ratio of 30:10:1, was found to be potentiating against both blood-induced and sporozoite-induced P. berghei NK(65)
infections. Mean effective dose values were calculated for
chloroquine,
sulfamethoxydiazine, and
pyrimethamine against blood-induced P. berghei
infection, and when a combination of the three drugs was administered therapeutically in the ratio given above, only one-tenth as much
chloroquine, one-thirtieth as much
sulfamethoxydiazine, and one-sixtieth as much
pyrimethamine were needed to cure 50% of murine
infections as was needed for each
drug alone. The triple combination also showed enhanced activity against lethal sporozoite-induced P. berghei NK(65)
infection in A/J strain mice.