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The suppression of malarial parasitaemia by pyrimethamine in combination with dapsone or sulphormethoxine

Departments of Preventive and Social Medicine, Paediatrics and Medical Microbiology and the Institute of Child Health, University of Ibadan, and the Wellcome Laboratories of Tropical Medicine, Beckenham, Kent, UK
Transactions of the Royal Society of Tropical Medicine and Hygiene (Impact Factor: 1.93). 02/1969; 63(2):216-29. DOI: 10.1016/0035-9203(69)90150-3
Source: PubMed

ABSTRACT The antimalarial activity of pyrimethamine in combination either with dapsone or with sulphormethoxine, was compared with that of pyrimethamine alone. In this double-blind controlled study, 280 children, living in an area of stable P. falciparum malaria, were observed during one year. With pyrimethamine alone there was incomplete suppression of parasitaemia with crude parasite rates ranging from 2 to 25%. The first dose of the drug combinations produced a rapid clearance of parasitaemia, and weekly administration of the drug combinations sustained a virtually complete suppression of parasitaemia throughout the year. The drugs were well tolerated and no serious side-effects were encountered among the treated children.

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    • "In hyperendemic areas, infants born to immune mothers are protected against malaria during the first six months of life, reflecting the preceding transfer of protective antibodies from mother to child. Children of five years old or more living in such areas may have high numbers of parasites in their blood, but remain largely asymptomatic (Bruce-Chwatt, 1952; Lucas et al., 1969). Such apparent tolerance is generally believed to be due to " antitoxic " immunity specifically directed against soluble parasite components causing disease (Playfair et al., 1990). "
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    ABSTRACT: Cycloguanil pamoate in an oleaginous suspension was injected into the deep muscle of the buttocks of 10 older children and adults in Ilora, Western State of Nigeria. The suspension and the injection were not resented. Only mild reactions of tenderness and pain lasting about 2 days were noted. The oleaginous suspension as at present constituted is too thick for a quick and comfortable injection.The effectiveness of a single injection of cycloguanil pamoate, combined with a one-dose treatment with chloroquine phosphate was tested in a group of semi-immune African school children aged 6–10 years in a holoendemic malaria region.The curative effect of the drug combination was demonstrated in 93% one week after treatment, and it persisted to about the end of the 6th week. Thereafter, reinfection appeared in 29·0% of the protected group before the 12th week, and in the 18th week asexual malaria parasitaemia had become re-established in over two-thirds of the children. Only 22 of 114 children examined had remained completely free of asexual parasitaemia for up to the 18th week. The dose of cycloguanil used per child ranged from 7·3 mg. to 10·8 mg per kg. of body weight. Chloroquine phosphate in a single oral dose as recommended by the W.H.O. was nearly as effective as the drug combination up to the 6th week.There was evidence of more cases of heavy parasitaemia in the treated children who became reinfected only after 10 weeks of freedom from malaria parasitaemia than in the untreated controls, which suggests that in rural Nigerian school children aged 6–10 years, the immunological ability to suppress malaria parasitaemia very largely depends on the actual and uninterrupted presence of malaria parasites. That the antiparasitic immunity to malaria in this age group studied could be so delicate and capable of being eliminated inside 12 weeks of freedom from parasitaemia is an unexpected finding in the holoendemic malarious region of Nigeria.
    Transactions of the Royal Society of Tropical Medicine and Hygiene 01/1970; 64(6):839-49. DOI:10.1016/0035-9203(70)90103-3 · 1.93 Impact Factor
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    ABSTRACT: As it had been shown in previous trials that very small doses of pyrimethamine and sulfadoxine or dapsone were effective in eliminating Plasmodium falciparum in 2 or 3 days, small-scale field trials were carried out on children to investigate the efficacy of this combination of drugs in suppressing malaria.Doses of pyrimethamine 2 mg with sulfadoxine 40 mg, fortnightly, appeared to be completely successful in suppressing seasonal hyperendemic malaria in a group of 38 Gambian children over a 6-month period. On the other hand, pyrimethamine alone at the recommended dose failed to suppress falciparum malaria in some children of another group. Parasite resistance to the sulfonamide-pyrimethamine combination was not encountered nor was there any suggestion of toxicity. It is concluded that these drugs in combination could have a place in malaria chemoprophylaxis.
    Bulletin of the World Health Organisation 02/1970; 43(4):513-20. · 5.11 Impact Factor
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