Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1–5 years

Abstract

SummaryA randomized, open trial involving 260 Tanzanian children, aged 1᎐5 years, with acute Plasmodium falciparum malaria was conducted to evaluate the efficacy of the combination antimalarial CGP 56697 (artemether and benflumetol), and to compare it with chloroquine, the standard drug used for malaria treatment in the Kilombero area. Children who had received rescue medication within the first 48 h or had a negative slide at the same time were excluded. Seven-day parasitological cure rates were 94% (95% CI 88᎐97.5) for CGP 56697 and 35.4% (95% CI 25.9᎐45.8) for chloroquine. Using the same definition, the 14-day parasitological cure rates were 86.4% (95% CI 78.5᎐92.2) for CGP 56697 and 10.3% (95% CI 5.1᎐18.1) for chloroquine. Gametocytes were more effectively suppressed by CGP 56697 than by chloroquine. There were no major adverse events with either drug. CGP 56697 is highly efficacious against P. falciparum in this area of Tanzania. The study contributes to the discussion on treatment strategies, particularly whether chloroquine may still fulfil its role as first-line drug in an area of high malaria transmission and very high levels of chloroquine resistance.

Distinction of recrudescences from new infections by pcr‐rflp analysis in a comparative trial of cgp 56 697 and chloroquine in Tanzanian children.

“…Our analyses consider a rather more inclusive group of patients (Table 1) than those of Hatz et al (1998) did: we also included patients whose parasitaemia never cleared. The numbers of patients who were thus included in the analyses, and the numbers for whom samples were analysed by PCR-RFLP for each time point are shown in Table 1.…”

“…The study was conducted in Ifakara, Tanzania, a holoendemic area with perennial transmission (Hatz et al 1998). Patients were children aged 1-5 years living within 5 km of the out-patient clinic of St. Francis Hospital, Ifakara.…”

“…The use of both drugs in conjunction both provides effective treatment and reduces the chance of recrudescence. The data presented here derive from an efficacy trial of such a combination drug made of artemether and benflumetol (CGP 56 697) (Hatz et al 1998).…”

The safety and efficacy of sulfadoxine-pyrimethamine, amodiaquine, and their combination in the treatment of uncomplicated Plasmodium falciparum malaria.

“…A Day-7 parasitological chloroquine failure rate of 65% has been described in children aged 1-5 years. 20 SP has been available at health facilities for many years as a secondline malaria treatment. AQ has not been readily available, and there are no previous local efficacy estimates.…”

African children with malaria in an area of intense Plasmodium falciparum transmission: features on admission to the hospital and risk factors for death.

“…Sixty percent of the pediatric outpatients with malaria have positive urine test results for chloroquine and estimates of 7-day parasitologic resistance of up to 65% are reported. 13 Fifteen percent of malaria admissions less than 2 years old were involved in either an anemia prevention study 14 or an ongoing malaria vaccine trial. Although non-placebo recipients may have a modified risk of developing malaria, it seems unlikely that once admitted, risk factors for death would be different from non-study children.…”