Single-Dose Therapy of Falciparum Malaria Using Pyrimethamine in Combination with Diformyldapsone or Sulfadoxine *

Abstract

Patients with naturally acquired chloroquine-resistant falciparum malaria were studied in Thailand. The fixed combination of pyrimethamine 75 mg and sulfadoxine 1,500 mg (adult dose) cured 85% of patients with an average pretreatment parasite count of 60,000 per mm(3). The fixed combination of pyrimethamine 50 mg and 800 mg diformyldapsone (DFD) cured 43% of patients with an average pretreatment parasite count of only 17,000 per mm(3). The difference in cure rates was statistically significant (p less than 0.01). Pyrimethamine alone was ineffective. Pyrimethamine-DFD, in the dose tested, was not sufficiently active for the treatment of established infections. Pyrimethamine-sulfadoxine did produce an acceptable cure rate but clinical improvement was often slow. We do not recommend that pyrimethamine-sulfadoxine be administered alone. Optimal results are obtained when a short course of quinine (2 to 6 days) is given until parasitemia has been eliminated, then a dose of pyrimethamine-sulfadoxine to assist in the radical cure of the falciparum infection. A modification to the W.H.O. classification is suggested. An RIII response (early treatment failure) is diagnosed if the patient's clinical condition and/or parsite density worsens within a few hours after administration of the test regimen; distinct improvement occurring within a few hours of the subsequent initiation of an intravenous infusion of quinine confirms the diagnosis of an RIII response. The RII response has been defined as marked reduction, but not clearance of asexual parasitemia. It is suggested that an RII response may be diagnosed before 7 days have elapsed.

Potentiating effect of pyrimethamine and sulfadoxine against dihydrofolate reductase from pyrimethamine-sensitive and pyrimethamine-resistant Plasmodium chabaudi

“…3). the results obtained are similar to those reported when various combinations of antifols and sulfonamides were used (14,22,28). The estimated and calculated fractional inhibitions of approximately 0.25 (Table 2) imply that in vivo effect of drug combination is much more potent than the effect on dihydrofolate reductase activity.…”

Estudo sobre malária e parasitoses intestinais em indígenas da tribo Nadëb-Maku, Estado do Amazonas, Brasil

“…Por ter se esgotado o Fansidar® e ter-se únicamente Mefloquina, utilizou-se essa droga em doses baixas, uma vez que se conhece a eficácia deste fármaco no tratamento da malária falciparum 3,10 . Esta parece ter sido a primeira vez que se utiliza a Mefloquina em ameríndios.…”

Tracking Origins and Spread of Sulfadoxine-Resistant Plasmodium falciparum dhps Alleles in Thailand

“…CQ resistance was first reported in this region in the early 1960s (16,20,53). In 1973, the malaria control program of Thailand introduced SP as the first-line drug for the treatment of uncomplicated falciparum malaria (7,11,12,30,41). The efficacy of SP decreased sharply, and by 1980, the cure rate dropped to Ͻ25% in some Thai provinces (8,10,21,37).…”