[show abstract][hide abstract] ABSTRACT: The efficacy of amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP) was assessed in 310 symptomatic children from western Kenya with uncomplicated Plasmodium falciparum malaria. A non-blinded, randomized, 14-day study was performed and parasitologic criteria were used. Of 310 patients included, 238 (77%) completed the study: 120 received AQ and 118 received SP. In those treated with AQ, there were sensitive (S) infections in 107 patients (89.2%, 95% confidence interval [CI] = 82.2, 94.1%), RI resistance in 10 (8.3%, 95% CI = 4.1, 14.8%), RII resistance in 1 (0.8%, 95% CI = 0, 4.6%), and RIII resistance in 2 (1.7%, 95% CI = 0.2, 5.9%). In those treated with SP, there were S infections in 74 patients (62.7%, 95% CI = 53.3, 71.4%), RI resistance in 21 (17.8%, 95% CI = 11.4, 25.9%), RII resistance in 11 (9.3%, 95% CI = 4.7, 16.1%), and RIII resistance in 12 (10.2%, 95% CI = 5.4, 17.1%). Resistance rates were consistently higher in the SP-treated patients (P < 0.001). Resistance to SP in this area has reached such levels that it should no longer be the first-line treatment. Alternative treatment, such as SP plus AQ combination treatment or artemisinin combination treatment, is urgently needed.
The American journal of tropical medicine and hygiene 11/2004; 71(5):537-41. · 2.53 Impact Factor
[show abstract][hide abstract] ABSTRACT: Increasing drug resistance limits the choice of efficacious chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still retains efficacy against P falciparum in many African countries. We assessed the safety, treatment efficacy, and effect on gametocyte carriage of adding artesunate to amodiaquine in three randomised trials in Kenya, Sénégal, and Gabon.
We enrolled 941 children (400 in Kenya, 321 in Sénégal, and 220 in Gabon) who were 10 years or older and who had uncomplicated P falciparum malaria. Patients were randomly assigned amodiaquine (10 mg/kg per day for 3 days) plus artesunate (4 mg/kg per day for 3 days) or amodiaquine (as above) and placebo (for 3 days). The primary endpoints were parasitological cure rates at days 14 and 28. Analysis was by intention to treat and by an evaluability method.
Both regimens were well tolerated. Six patients in the amodiaquine-artesunate group and five in the amodiaquine group developed early, drug-induced vomiting, necessitating alternative treatment. By intention-to-treat analysis, the day-14 cure rates for amodiaquine-artesunate versus amodiaquine were: 175/192 (91%) versus 140/188 (74%) in Kenya (D=16.7% [95% CI 9.3-24.1], p<0.0001), 148/160 (93%) versus 147/157 (94%) in Sénégal (-1.1% [-6.7 to 4.5], p=0.7), and 92/94 (98%) versus 86/96 (90%) in Gabon (8.3% [1.5-15.1], p=0.02). The corresponding rates for day 28 were: 123/180 (68%) versus 75/183 (41%) in Kenya (27.3% [17.5-37.2], p<0.0001), 130/159 (82%) versus 123/156 (79%) in Sénégal (2.9% [-5.9 to 11.7], p=0.5), and 80/94 (85%) versus 70/98 (71%) in Gabon (13.7% [2.2-25.2], p=0.02). Similar rates were obtained by evaluability analysis.
The combination of artesunate and amodiaquine improved treatment efficacy in Gabon and Kenya, and was equivalent in Sénégal. Amodiaquine-artesunate is a potential combination for use in Africa. Further investigations to assess the potential effect on the evolution of drug resistance, disease transmission, and safety of amodiaquine-artesunate are warranted.
The Lancet 04/2002; 359(9315):1365-72. · 39.06 Impact Factor
[show abstract][hide abstract] ABSTRACT: We conducted two randomized clinical trials to determine the in vivo efficacy of amodiaquine and sulfadoxine/pyrimethamine in treating Plasmodium falciparum malaria. Seventy-five patients under the age of 10 years in Kibwezi, Kenya, and 171 patients in Kigoma, Tanzania, were enrolled for treatment. Due to loss of eight patients in Kibwezi and 37 in Kigoma to follow-up, we used best and worst case scenarios for the parasitological response. The in vivo sensitivity of Plasmodium falciparum to amodiaquine was 75% (no loss to follow-up) in Kibwezi and ranged from 85% in the best to 65% in the worst case scenario in Kigoma. The sensitivity to sulfadoxine/pyrimethamine was 70% to 88% in Kibwezi and 65% to 89% in Kigoma. R1 resistance to amodiaquine was 22% in Kibwezi and varied from 6% in the best to 26% for the worst case scenario in Kigoma. The R1 resistance to sulfadoxine/pyrimethamine was 5% to 23% in Kibwezi and 2% to 26% in Kigoma. R2 resistance was 3% for amodiaquine and 7% for sulfadoxine/pyrimethamine in Kibwezi and 9% in Kigoma for each treatment group. There was no statistically significant difference between treatment groups at either study site, except for a slight difference in R1 resistance in the best case scenario, Kibwezi, in favour of S/P. Although both amodiaquine and sulfadoxine/pyrimethamine resistance seems to be increasing, these antimalarials are still effective in parasite clearance.
Tropical Medicine & International Health 07/2000; 5(6):459-63. · 2.94 Impact Factor