Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial
Abstract Background Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. Methods In a randomized controlled...
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doaj-eb9d798676cb4594a4fc094ffc6a20f12020-11-25T03:39:13ZengBMCBMC Infectious Diseases1471-23342017-12-011711910.1186/s12879-017-2924-5Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trialPauline Byakika-Kibwika0Jane Achan1Mohammed Lamorde2Carine Karera-Gonahasa3Agnes N. Kiragga4Harriet Mayanja-Kizza5Noah Kiwanuka6Sam Nsobya7Ambrose O. Talisuna8Concepta Merry9Department of Medicine, College of Health Sciences, Makerere UniversityMedical Research Council UnitInfectious Diseases InstituteInfectious Diseases InstituteInfectious Diseases InstituteDepartment of Medicine, College of Health Sciences, Makerere UniversitySchool of Public Health, Makerere UniversityDepartment of Pathology, Makerere UniversityUniversity of Oxford-KEMRI-Wellcome Trust ProgrammeInfectious Diseases InstituteAbstract Background Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. Methods In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda. Results We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1–2) vs 3 (2–3), P < 0.001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms. Conclusion In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed. Trial registration The study was registered with the Pan African Clinical Trial Registry ( PACTR201110000321348 ).http://link.springer.com/article/10.1186/s12879-017-2924-5ArtesunateQuinineArtemisinin combination therapySevere malariaRe-infection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pauline Byakika-Kibwika Jane Achan Mohammed Lamorde Carine Karera-Gonahasa Agnes N. Kiragga Harriet Mayanja-Kizza Noah Kiwanuka Sam Nsobya Ambrose O. Talisuna Concepta Merry |
spellingShingle |
Pauline Byakika-Kibwika Jane Achan Mohammed Lamorde Carine Karera-Gonahasa Agnes N. Kiragga Harriet Mayanja-Kizza Noah Kiwanuka Sam Nsobya Ambrose O. Talisuna Concepta Merry Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial BMC Infectious Diseases Artesunate Quinine Artemisinin combination therapy Severe malaria Re-infection |
author_facet |
Pauline Byakika-Kibwika Jane Achan Mohammed Lamorde Carine Karera-Gonahasa Agnes N. Kiragga Harriet Mayanja-Kizza Noah Kiwanuka Sam Nsobya Ambrose O. Talisuna Concepta Merry |
author_sort |
Pauline Byakika-Kibwika |
title |
Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial |
title_short |
Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial |
title_full |
Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial |
title_fullStr |
Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial |
title_full_unstemmed |
Intravenous artesunate plus Artemisnin based Combination Therapy (ACT) or intravenous quinine plus ACT for treatment of severe malaria in Ugandan children: a randomized controlled clinical trial |
title_sort |
intravenous artesunate plus artemisnin based combination therapy (act) or intravenous quinine plus act for treatment of severe malaria in ugandan children: a randomized controlled clinical trial |
publisher |
BMC |
series |
BMC Infectious Diseases |
issn |
1471-2334 |
publishDate |
2017-12-01 |
description |
Abstract Background Severe malaria is a medical emergency associated with high mortality. Adequate treatment requires initial parenteral therapy for fast parasite clearance followed by longer acting oral antimalarial drugs for cure and prevention of recrudescence. Methods In a randomized controlled clinical trial, we evaluated the 42-day parasitological outcomes of severe malaria treatment with intravenous artesunate (AS) or intravenous quinine (QNN) followed by oral artemisinin based combination therapy (ACT) in children living in a high malaria transmission setting in Eastern Uganda. Results We enrolled 300 participants and all were included in the intention to treat analysis. Baseline characteristics were similar across treatment arms. The median and interquartile range for number of days from baseline to parasite clearance was significantly lower among participants who received intravenous AS (2 (1–2) vs 3 (2–3), P < 0.001). Overall, 63.3% (178/281) of the participants had unadjusted parasitological treatment failure over the 42-day follow-up period. Molecular genotyping to distinguish re-infection from recrudescence was performed in a sample of 127 of the 178 participants, of whom majority 93 (73.2%) had re-infection and 34 (26.8%) had recrudescence. The 42 day risk of recrudescence did not differ with ACT administered. Adverse events were of mild to moderate severity and consistent with malaria symptoms. Conclusion In this high transmission setting, we observed adequate initial treatment outcomes followed by very high rates of malaria re-infection post severe malaria treatment. The impact of recurrent antimalarial treatment on the long term efficacy of antimalarial regimens needs to be investigated and surveillance mechanisms for resistance markers established since recurrent malaria infections are likely to be exposed to sub-therapeutic drug concentrations. More strategies for prevention of recurrent malaria infections in the most at risk populations are needed. Trial registration The study was registered with the Pan African Clinical Trial Registry ( PACTR201110000321348 ). |
topic |
Artesunate Quinine Artemisinin combination therapy Severe malaria Re-infection |
url |
http://link.springer.com/article/10.1186/s12879-017-2924-5 |
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