ABSTRACT
In a malaria endemic area of Brazil where P. falciparum is highly resistant to chloroquine and Fansidar, we conducted an in vivo study to evaluate the therapeutic response of proguanil plus sulfametoxazole against Plasmodium falciparum malaria. Twenty-five adult subjects with uncomplicated P. falciparum malaria received supervised drug administration and were followed for 28 days in an inpatient hospital or in a malaria free-transmission area. The therapeutic regimen was proguanil 100 mg BID plus sulfamethoxazole 1,000 mg BID for 7 days. Of those who took all medications (n=21), 17 (81%) were cured. Recrudescent parasitemia during follow-up occurred in four (19%) patients on days 14, 19, 20 and 21 after beginning of treatment. The remaining four (16%) subjects did not complete their therapeutic regimen because the incidence of side effects. Considering the shortage of falciparum malaria therapeutic options and the urgent need for new regimens to deal with the spread of drug resistant P. falciparum, one might consider the study results as a lead to study analogous compounds, hopefully with fewer adverse reactions.
Subject(s)
Adolescent , Adult , Aged , Antimalarials/therapeutic use , Brazil/epidemiology , Proguanil/therapeutic use , Drug Administration Schedule , Drug Resistance , Drug Therapy, Combination , Endemic Diseases/prevention & control , Female , Follow-Up Studies , Humans , Malaria, Falciparum/drug therapy , Male , Microbial Sensitivity Tests , Middle Aged , Sulfamethoxazole/therapeutic use , Treatment OutcomeABSTRACT
From March 1996 to August 1997, a study was carried out in a malaria endemic area of the Brazilian Amazon region. In vivo sensitivity evaluation to antimalarial drugs was performed in 129 patients. Blood samples (0.5 ml) were drawn from each patient and cryopreserved to proceed to in vitro studies. In vitro sensitivity evaluation performed using a radioisotope method was carried out with the cryopreserved samples from September to December 1997. Thirty-one samples were tested for chloroquine, mefloquine, halofantrine, quinine, arteether and atovaquone. Resistance was evidenced in 96.6 percent (29/30) of the samples tested for chloroquine, 3.3 percent (1/30) for quinine, none (0/30) for mefloquine and none for halofantrine (0/30). Overall low sensitivity was evidenced in 10 percent of the samples tested for quinine, 22.5 percent tested for halofantrine and in 20 percent tested for mefloquine. Means of IC 50 values were 132.2 (SD: 46.5) ng/ml for chloroquine, 130.6 (SD: 49.6) ng/ml for quinine, 3.4 (SD: 1.3) ng/ml for mefloquine, 0.7 (SD: 0.3) ng/ml for halofantrine, 1 (SD: 0.6) ng/ml for arteether and 0.4 (SD: 0.2) ng/ml for atovaquone. Means of chloroquine IC 50 of the tested samples were comparable to that of the chloroquine-resistant strain W2 (137.57 ng/ml) and nearly nine times higher than that of the chloroquine-sensitive strain D6 (15.09 ng/ml). Means of quinine IC 50 of the tested samples were 1.7 times higher than that of the low sensitivity strain W2 (74.84 ng/ml) and nearly five times higher than that of the quinine-sensitive strain D6 (27.53 ng/ml). These results disclose in vitro high resistance levels to chloroquine, low sensitivity to quinine and evidence of decreasing sensitivity to mefloquine and halofantrine in the area under evaluation