Methemoglobinemia Provoked by Malarial Chemoprophylaxis in Vietnam

Abstract

Six American soldiers were evacuated from Vietnam because they became cyanotic while taking antimalarial drugs. Investigations of these and two additional subjects revealed a markedly decreased concentration of NADH methemoglobin reductase in red blood cells and a decreased capacity of erythrocytes to reduce methemoglobin to hemoglobin in vitro. Two of the subjects were identical twins; a study of 19 members of their family revealed three additional enzyme-deficient members and 10 additional relatives with low enzyme values. Chloroquine, primaquine and diaminodiphenylsulfone were each shown to provoke methemoglobinemia in enzyme-deficient subjects in doses that have no effect on normal persons. The cyanosis produced by antimalarial drugs permitted clinical recognition of a usually undetected enzymatic defect of the erythrocyte. Heterozygotes with a deficiency of NADH methemoglobin reductase may be more numerous than has been realized, and the continued use of antimalarial drugs in Vietnam may provide new information about the true prevalence of this defect.