Chemoprophylaxis against malaria in Papua New Guinea: a trial of amodiaquine and a combination of dapsone and pyrimethamine

Abstract

A placebo-controlled chemoprophylaxis trial was carried out in 1980 in 318 semi-immune school children in the Madang area of Papua New Guinea, where there was a high prevalence of strains of Plasmodium falciparum resistant to 4-aminoquinolines. Since prophylaxis with amodiaquine at 5 mg/kg weekly had failed, amodiaquine at a dose of 10mg/kg weekly and Maloprim (half a tablet or one tablet depending on body weight, which gave ranges of dapsone of 1.7-3.3mg/kg and pyrimethamine 0.2-0.4 mg/kg) weekly were tried. Neither regimen was completely successful in preventing parasitaemia, though after 13 weeks of prophylaxis the slide positivity rate was 16% for the amodiaquine group and 2% for the Maloprim group, which was in each case significantly lower than the normal baseline rate in the controls of 42%. Amodiaquine was completely successful in suppressing Plasmodium vivax infections. Breakthrough parasitaemia occurred, with either P. falciparum or P. vivax, in 5% of subjects on Maloprim at some time during the 13-week period of prophylaxis. Significantly more children in both the amodiaquine and Maloprim groups than in the placebo group showed a reduction in spleen size. All groups showed an unexplained fall in haemoglobin level over the study period but the fall was significantly less in both the prophylaxis groups. There was no adverse effect on white cell counts by either drug regimen. Chemoprophylaxis as a component of an integrated malaria control program should not be overlooked, provided that compliance can be maintained. However, in this particular case the principal purpose of the study had been to evaluate the proposed chemoprophylactic regimens in school children before embarking on an intervention study in young children. As a result of this study it was decided not to go ahead with the chemoprophylactic intervention in young children but to adopt an approach based on early presumptive treatment.