Abstract
BackgroundMalaria control largely depends on availability of highly efficacious drugs, however, over the years, has been threatened by emergence of drug resistance. It is, therefore, important to monitor the impact of recurrent anti-malarial treatment on the long-term efficacy of anti-malarial regimens, especially in sub-Saharan African countries with high malaria transmission. Evaluation of parasite clearance following treatment of severe malaria with intravenous artesunate among patients in Eastern Uganda, was performed, as a contribution to monitoring anti-malarial effectiveness.MethodsParasite clearance data obtained from a clinical trial whose objective was to evaluate the 42-day parasitological treatment outcomes and safety following treatment of severe malaria with intravenous artesunate plus artemisinin-based combination therapy among patients attending Tororo District Hospital in Eastern Uganda, were analysed. Serial blood smears were performed at 0, 1, 2, 4, 6, 8, 10, 12, 16, 20, 24 h, followed by 6-hourly blood smears post start of treatment until 6 h post the first negative blood smear when parasite clearance was achieved. Study endpoints were; parasite clearance half-life (the time required for parasitaemia to decrease by 50% based on the linear portion of the parasite clearance slope) and parasite clearance time (time required for complete clearance of initial parasitaemia).ResultsOne hundred and fifty participants with severe malaria were enrolled. All participants were treated with intravenous artesunate. All study participants tolerated artesunate well with rapid recovery from symptoms and ability to take oral mediation within 24 h. No immediate adverse events were recorded. The median (IQR) number of days to complete parasite clearance was of 2 (1–2). The median (IQR) time to clear 50% and 99% parasites was 4.8 (3.61–7.10) and 17.55 (14.66–20.66) h, respectively. The median estimated clearance rate constant per hour was 0.32. The median (IQR) slope half-life was 2.15 (1.64, 2.61) h.ConclusionParasite clearance following treatment with intravenous artesunate was rapid and adequate. This finding provides supportive evidence that resistance to artemisinins is unlikely to have emerged in this study area. Continuous monitoring of artemisinin effectiveness for malaria treatment should be established in high malaria transmission areas in sub-Saharan Africa where spread of resistance would be disastrous.Trial registration The study was registered with the Pan African Clinical Trial Registry (PACTR201110000321348). Registered 7th October 2011, http://www.pactr.org/)
Highlights
Malaria control largely depends on availability of highly efficacious drugs, over the years, has been threatened by emergence of drug resistance
This study aimed to evaluate malaria parasite clearance following treatment of patients with severe malaria using intravenous artesunate in Tororo District Hospital in Eastern Uganda
It is possible that parasite clearance times were shorter than what has been documented from other studies because we evaluated parasite clearance following intravenous administration of artesunate, while most previous studies from Asia evaluated parasite clearance following oral administration of artemisinin treatment, the current findings are comparable to those from studies performed in the African countries in which oral artesunate was administered [7, 16]
Summary
Malaria control largely depends on availability of highly efficacious drugs, over the years, has been threatened by emergence of drug resistance It is, important to monitor the impact of recurrent antimalarial treatment on the long-term efficacy of anti-malarial regimens, especially in sub-Saharan African countries with high malaria transmission. Resistance to artemisinins which manifests as loss of the intracellular ring stage parasite susceptibility and slower parasite clearance [5], was reported initially on the Thai-Cambodia border [6, 7] and is likely to spread to other malaria endemic areas It is imperative for malaria control programmes to establish mechanisms for monitoring artemisinin efficacy and risk for spread of artemisinin resistance especially in areas with high malaria transmission where recurrent malaria infections and treatment occur
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