A trial of suppression of malaria by administration of combined sulphadoxine-pyrimethamine tablets every 28 days was undertaken in West Malaysia during 1972. One thousand subjects were followed over a 10-month period, including control groups on placebo and on weekly chloroquine. Subjects were examined monthly for parasitaemia, drug reactions, leucopenia, teratogenicity and haemolysis among the subjects deficient in glucose-6-phosphate dehydrogenase. Rates of new infections in the placebo group were 8.0% with Plasmodium falciparum and 6.2% with P. vivax; in the group receiving weekly chloroquine, 5.1% P. falciparum and 0.3% P. vivax; and in the group receiving monthly sulphadoxine-pyrimethamine, 0.3% P. Falciparum and 1.0% P. vivax. The effective rate of cure of new infections with P. falciparum by a single suppressive dose of combined sulphadoxine-pyrimethamine given the following month was 88.7%. No serious side effects were observed.
Serum was collected from six adults participating in a field trial of sulfadoxine and pyrimethamine in combination which was being administered once monthly for malaria suppression. Samples were drawn during each of two consecutive months three hours, and 7, 14 and 28 days following a dose of 1 500 mg sulfadoxine. Serum sulfadoxine concentration was measured using the method of Bratton and Marshall (1939). Initial serum concentrations averaged 19-9 plus or minus 2-4 (SD) mg/100 ml and decayed to 6-2 plus or minus 2-8 mg/100 ml at 14 days. Serum sulfadoxine concentrations were still detectable at 28 days following a dose (2-1 plus or minus 1-5 mg/100 ml). Elimination half-time averaged 195 plus or minus 44 hours. The presistent serum concentrations of sulfadoxine following monthly doses documented here during field-use of this drug are in agreement with the successful clinical results reported for such a regimen (Lewis and Ponnampalam, 1974; O'Holohan and Hugoe-Mathews, 1971; Wolfensberger, 1971).
The jungle habitat of the Temuan aborigines harbors a variety of infectious diseases, the most notable being malaria. Our study of 15 genetic systems in the Temuan revealed substantial polymorphism and within-population genetic diversity. The polymorphisms for Hb beta, G6PD, and El are of interest in regard to genetic adaptation to malaria. Among the polymorphisms investigated we conclude that G6PD deficiency and elliptocytosis are likely to have malaria-resistant effects as evidenced by their low association with malarial parasitemia or their higher frequency in adults than in children. These findings suggest that the malarial habitat of the Temuans is livable in the long range sense for them because of the cluster of malaria-resistant alleles in their gene pool (G6PD)-, El, and possibly, but not tested here because of its low frequency, Hb beta E). The same condition probably holds for the Semai, the nearest aborigine neighbors of the Temuan (although the Semai have not been tested for malarial parasitemia and for these polymorphisms simultaneously), since the Semai have substantial Hb betaE, G6PD-, and El. The Temuan have a cultural identity system of rituals, beliefs, and certain aspects of language which effectively isolates them genetically from Malays and other nonaborigines. This system hinders the dilution of the malaria-resistant alleles of the Temuan gene pool with the malaria-susceptible alleles of the nonaborigine gene pools.