Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study.
A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for...
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ftdoajarticles:oai:doaj.org/article:391462a9ef5a4d678b54f969996a7060 2023-05-15T15:17:09+02:00 Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. Ahmed M Musa Brima Younis Ahmed Fadlalla Catherine Royce Manica Balasegaram Monique Wasunna Asrat Hailu Tansy Edwards Raymond Omollo Mahmoud Mudawi Gilbert Kokwaro Ahmed El-Hassan Eltahir Khalil 2010-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000855 https://doaj.org/article/391462a9ef5a4d678b54f969996a7060 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2964291?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000855 https://doaj.org/article/391462a9ef5a4d678b54f969996a7060 PLoS Neglected Tropical Diseases, Vol 4, Iss 10, p e855 (2010) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2010 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000855 2022-12-31T00:59:15Z A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days.This randomized, open-label, dose-finding, phase II study assessed the two above high-dose PM treatment regimens. Patients with clinical features and positive bone-marrow aspirates for VL were enrolled. All patients received their assigned courses of PM intramuscularly and adverse events were monitored. Parasite clearance in bone-marrow aspirates was tested by microscopy at end of treatment (EOT, primary efficacy endpoint), 3 months (in patients who were not clinically well) and 6 months after EOT (secondary efficacy endpoint). Pharmacokinetic data were obtained from a subset of patients weighing over 30 kg.42 patients (21 per group) aged between 4 and 60 years were enrolled. At EOT, 85% of patients (95% confidence interval [CI]: 63.7% to 97.0%) in the 20 mg/kg/day group and 90% of patients (95% CI: 69.6% to 98.8%) in the 15 mg/kg/day group had parasite clearance. Six months after treatment, efficacy was 80.0% (95% CI: 56.3% to 94.3%) and 81.0% (95% CI: 58.1% to 94.6%) in the 20 mg/kg/day and 15 mg/kg/day groups, respectively. There were no serious adverse events. Pharmacokinetic profiles suggested a difference between the two doses, although numbers of patients recruited were too few to make it significant (n = 3 and n = 6 in the 20 mg/kg/day and 15 mg/kg/day groups, respectively).Data suggest that both high dose regimens were more efficacious than the standard 15 mg/kg/day PM for 21 days and could be further evaluated in phase III studies in East Africa. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 4 10 e855 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Ahmed M Musa Brima Younis Ahmed Fadlalla Catherine Royce Manica Balasegaram Monique Wasunna Asrat Hailu Tansy Edwards Raymond Omollo Mahmoud Mudawi Gilbert Kokwaro Ahmed El-Hassan Eltahir Khalil Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
A recent study has shown that treatment of visceral leishmaniasis (VL) with the standard dose of 15 mg/kg/day of paromomycin sulphate (PM) for 21 days was not efficacious in patients in Sudan. We therefore decided to test the efficacy of paramomycin for a longer treatment duration (15 mg/kg/day for 28 days) and at the higher dose of 20 mg/kg/day for 21 days.This randomized, open-label, dose-finding, phase II study assessed the two above high-dose PM treatment regimens. Patients with clinical features and positive bone-marrow aspirates for VL were enrolled. All patients received their assigned courses of PM intramuscularly and adverse events were monitored. Parasite clearance in bone-marrow aspirates was tested by microscopy at end of treatment (EOT, primary efficacy endpoint), 3 months (in patients who were not clinically well) and 6 months after EOT (secondary efficacy endpoint). Pharmacokinetic data were obtained from a subset of patients weighing over 30 kg.42 patients (21 per group) aged between 4 and 60 years were enrolled. At EOT, 85% of patients (95% confidence interval [CI]: 63.7% to 97.0%) in the 20 mg/kg/day group and 90% of patients (95% CI: 69.6% to 98.8%) in the 15 mg/kg/day group had parasite clearance. Six months after treatment, efficacy was 80.0% (95% CI: 56.3% to 94.3%) and 81.0% (95% CI: 58.1% to 94.6%) in the 20 mg/kg/day and 15 mg/kg/day groups, respectively. There were no serious adverse events. Pharmacokinetic profiles suggested a difference between the two doses, although numbers of patients recruited were too few to make it significant (n = 3 and n = 6 in the 20 mg/kg/day and 15 mg/kg/day groups, respectively).Data suggest that both high dose regimens were more efficacious than the standard 15 mg/kg/day PM for 21 days and could be further evaluated in phase III studies in East Africa. |
format |
Article in Journal/Newspaper |
author |
Ahmed M Musa Brima Younis Ahmed Fadlalla Catherine Royce Manica Balasegaram Monique Wasunna Asrat Hailu Tansy Edwards Raymond Omollo Mahmoud Mudawi Gilbert Kokwaro Ahmed El-Hassan Eltahir Khalil |
author_facet |
Ahmed M Musa Brima Younis Ahmed Fadlalla Catherine Royce Manica Balasegaram Monique Wasunna Asrat Hailu Tansy Edwards Raymond Omollo Mahmoud Mudawi Gilbert Kokwaro Ahmed El-Hassan Eltahir Khalil |
author_sort |
Ahmed M Musa |
title |
Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
title_short |
Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
title_full |
Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
title_fullStr |
Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
title_full_unstemmed |
Paromomycin for the treatment of visceral leishmaniasis in Sudan: a randomized, open-label, dose-finding study. |
title_sort |
paromomycin for the treatment of visceral leishmaniasis in sudan: a randomized, open-label, dose-finding study. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doi.org/10.1371/journal.pntd.0000855 https://doaj.org/article/391462a9ef5a4d678b54f969996a7060 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 4, Iss 10, p e855 (2010) |
op_relation |
http://europepmc.org/articles/PMC2964291?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000855 https://doaj.org/article/391462a9ef5a4d678b54f969996a7060 |
op_doi |
https://doi.org/10.1371/journal.pntd.0000855 |
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PLoS Neglected Tropical Diseases |
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10 |
container_start_page |
e855 |
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