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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.
AuthorsE B Doberstyn, A P Hall, K Vetvutanapibul, P Sonkon
JournalThe American journal of tropical medicine and hygiene (Am J Trop Med Hyg) Vol. 25 Issue 1 Pg. 14-9 (Jan 1976) ISSN: 0002-9637 [Print] United States
PMID769572 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article)
Chemical References
  • Drug Combinations
  • Sulfanilamides
  • Sulfadoxine
  • Dapsone
  • Pyrimethamine
Topics
  • Adolescent
  • Adult
  • Clinical Trials as Topic
  • Dapsone (administration & dosage, analogs & derivatives, therapeutic use)
  • Drug Combinations
  • Drug Evaluation
  • Humans
  • Malaria (drug therapy, etiology)
  • Male
  • Plasmodium falciparum (isolation & purification)
  • Pyrimethamine (administration & dosage, adverse effects, therapeutic use)
  • Sulfadoxine (administration & dosage, adverse effects, therapeutic use)
  • Sulfanilamides (therapeutic use)

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