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.