The chemotherapy of rodent malaria, XXVIII

Abstract

Using a relapse technique resistance of the Plasmodium berghei N strain to mefloquine can be developed slowly, but the progress is more rapid in the chloroquine-resistant NS line. Mefloquine resistance in all these lines is very unstable in the absence of drug selection pressure. Resistance develops also when the N strain is submitted to slowly increasing mefloquine dosage in consecutive passages, the resulting parasites having a similar morphology at light microscopic level to chloroquine-resistant P. berghei RC line parasites. Like the latter they occupy polychromatophilic red blood cells almost exclusively. When the parasites are exposed to mixtures of mefloquine with pyrimethamine, sulfaphenazole or primaquine, resistance to each component of the mixtures develops more slowly than to the individual components used alone. It is strongly recommended that mefloquine should be deployed only for the prevention or treatment of malaria in man caused by chloroquine-resistant P. falciparum. While it is appreciated that data based on rodent malaria models may not necessarily predict the situation in human malaria, the authors suggest that, for large scale use, mefloquine should not be employed until a 2nd antimalarial has been identified that will minimize the risk of parasites becoming resistant to this potentially valuable new compound.