Chemotherapeutic activity of combination doses of chloroquine, pyrimethamine, and sulfamethoxy-diazine, a long-acting sulfanilamide, against Plasmodium berghei infections in mice.

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.