Artesunate versus artemether for the treatment of recrudescent multidrug-resistant falciparum malaria.

Abstract

Abstract. The therapeutic efficacy and toxicity of artesunate (2mg/kg/day for five days, then 1 mg/kg/day for two days: total ϭ 12 mg/kg) was compared with that of artemether (4 mg/kg followed by 2 mg/kg/day for two days, then 1 mg/kg/day for four days: total ϭ 12 mg/kg) for the treatment of recrudescent multidrug-resistant falciparum malaria in an open randomized trial in 443 patients living on the western border of Thailand. Parasite and fever clearance times were similar in both groups; within 48 hr 94% (95% confidence interval [CI] ϭ 91-96%]) of the treated patients were aparasitemic and 93% (95% CI ϭ 89-96%) were afebrile. Symptom resolution and resolution of hepatomegaly were slightly slower in the artesunate group; adjusted hazards ratio ϭ 1.5 (95% CI ϭ 1-2.0, P Ͻ 0.01) and 2.2 (95% CI ϭ 1.4-8, P ϭ 0.04), respectively. There was no significant difference in times to resolution or development of anemia or splenomegaly between treatment groups. By day 28, 3% (95% CI ϭ 0.3-5%) of the patients treated with artesunate and 6% of those treated with artemether (95% CI ϭ 2-9%) had recurrent infections (P ‫؍‬ 0.3). Both regimens were very well tolerated, with no significant adverse effects attributable to either derivative. Overall, these data suggest that the two oral artemisinin derivatives are safe, highly effective, and result in equivalent therapeutic responses in the treatment of drug-resistant falciparum malaria.On the western border of Thailand, Plasmodium falciparum has developed resistance to nearly all the available antimalarial drugs. Mefloquine has been the treatment of choice for uncomplicated falciparum malaria in this region since 1985, but nearly 50% of the patients now fail with high dose (25mg/kg) mefloquine when given alone. 1 These recrudescent infections have a higher failure rate when retreated with mefloquine again, and constitute the reservoir and driving force for drug resistance. 2The artemisinin derivatives are the most potent antimalarial compounds available for human use. 3 They have excellent efficacy against multidrug-resistant strains of P. falciparum and they are very well tolerated. Although more than a million people have now been treated with artemisinin, or one of its derivatives, there is still no consensus concerning the most appropriate dose, treatment regimen, or choice of derivative. The antimalarial efficacy of oral artesunate in uncomplicated malaria appears to be a function of the duration of therapy. 4,5 Recrudescence rates are unacceptably high in patients given less than five days of treatment. Combined treatment with mefloquine improves efficacy and allows shorter courses of artesunate to be given. 6,7 Since 1994, a combination regimen (MAS3) of mefloquine (25 mg/kg) plus a three-day course of artesunate (12 mg/kg) has become the treatment of choice for uncomplicated falciparum malaria in this area.1 The recrudescence rate by day 63 with this treatment is less than 10%, 8 but patients whose infections do recur are symptomatic and their management poses a difficult p...

Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives.

“…Studies involving 2,593 of the patients described here have been reported previously. [6][7][8][9][10][11][12][13] The epidemiology of malaria at this site has also been described in detail recently. 14 Transmission of malaria is low (approximately one vivax, and one falciparum malaria infection per person every two years) and seasonal.…”

“…Treatment with one of the drug regimens (Table 1) was assigned to patients in comparative randomized studies as described previously. [6][7][8][10][11][12][13] Drug administration was observed in all cases. If vomiting occurred Ͻ 30 min after drug administration, the full dose was repeated, and if vomiting occurred between 30 and 60 min, half the dose was repeated.…”

Antimalarial drug resistance and combination chemotherapy

“…This was intended speci¢cally to delay the onset of resistance to me£oquine (Peters & Robinson 1984), but it did not work because P. falciparum in Thailand was already highly resistant to pyrimethamine^sulphadoxine. More recently, artemisinin and its derivatives have been combined with other antimalarials, notably me£oquine, and have accelerated recoveries, increased cure rates, reduced transmissibility, and appear also to have delayed the development of further resistance and reduced the incidence of disease (Price et al 1997). The rationale behind antimalarial combinations, and suggestions for future use of this strategy to treat all malaria are presented below.…”

Therapeutic Efficacy and Effects of Artesunate-Mefloquine and Mefloquine Alone on Malaria-Associated Anemia in Children with Uncomplicated Plasmodium falciparum Malaria in Southwest Nigeria

“…[1][2][3][4] As part of the strategy to combat the spread of antimalarial drug resistance globally, the World Health Organization recommended the use of artemisininbased combination therapies (ACTs) because they quickly reduce the burden of parasitemia and gametocytemia and the chance of drug resistance. 1,[5][6][7][8][9] Artesunate-mefloquine (AMQ) combination is not considered a viable option for use as first-line therapy in Africa because of intense transmission. 2 However AMQ, co-packaged as well as fixed dose formulations, is readily available and used in Africa.…”