Assessment of parasite clearance following treatment of severe malaria with intravenous artesunate in Ugandan children enrolled in a randomized controlled clinical trial

Abstract Background Malaria 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-mala...

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Bibliographic Details
Published in:Malaria Journal
Main Authors: Pauline Byakika-Kibwika, Patience Nyakato, Mohammed Lamorde, Agnes N. Kiragga
Format: Article in Journal/Newspaper
Language:English
Published: BMC 2018
Subjects:
ACT
Online Access:https://doi.org/10.1186/s12936-018-2552-6
https://doaj.org/article/48d3ef27ae164a29b441f2a1eb95d061
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Summary:Abstract Background Malaria 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. Methods Parasite 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). Results One 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) ...