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The prevalence of chloroquine-resistant falciparum malaria was determined for humans living at 28 different sites in the Brazilian Amazon. Blood samples obtained from each patient were defibrinated, placed in vials containing 0.5% glucose and or chloroquine and incubated for 24 hours at 39-40 degrees C without agitation. In vitro sensitivity of the parasite to four different concentrations of chloroquine was determined for each sample. After 24 hours of incubation, trophozoites of Plasmodium falciparum developed to schizonts in all control cultures (no chloroquine) as well as in 80.6, 48.4, 11.8 and 7.5% of the cultures containing 0.5, 1.0, 2.0, and 3.0 nmol chloroquine/ml blood, respectively. Chloroquine-resistant P. falciparum was found in blood samples from all 28 locations, indicating that such resistance is widely spread in the Brazilian Amazon.

In order to determine the effect of Fansidar on plasmodial infection in mice, outbred, adult, Swiss-Webster mice were treated with Fansidar (20 mg sulfadoxine and 1 mg pyrimethamine/kg body weight) at various intervals before and/or after inoculation with blood stages of Plasmodium berghei. Drug therapy resulted in cure if it was given before the parasitemia rose to 53%. Oral administration of Fansidar was more effective in reducing or preventing parasitemia than intramuscular injection. Fatal infections were prevented if mice were treated orally with one dose of Fansidar 2 days before inoculation with P. berghei, whereas only partial protection occurred in animals treated 4 or more days before inoculation. Fansidar administered on two consecutive days provided protection if the drug was given at 3 and 2 days before inoculation. Administration of Fansidar for three consecutive days protected all animals if given on days 8 to 6 before inoculation. After oral administration of Fansidar, the parasitemia dropped dramatically and was undetectable at 60 hr. At 12 hr after oral treatment, schizonts and trophozoites were numerous, but there were few merozoites. Schizonts were the predominant stage at 24 hr, whereas merozoites predominated at 36 hr. Swiss-Webster and C57BL/6 mice became immune to a lethal dose of P. berghei after 4 cycles of inoculation and drug cure. Protective immunity was still present at 472 days after the fifth parasite inoculation.

In April of 1977 an outbreak of falciparum malaria occurred among the Mayongong Indians, located at Uauaris in the Territory of Roraima, Brazil. Blood specimens from 157 Indians were examined for Plasmodium; 62 were found to be infected. In three cases the infection was not cured with chloroquine but responded favorably to the drug combination of sulfadoxine and pyrimethamine (Fansidar).