Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study. Journal Article

Authors: Musa, Ahmed M.; Younis, Brima; Fadlalla, Ahmed; Royce, Catherine; Balasegaram, Manica; Wasunna, Monique; Hailu, Asrat; Edwards, Tansy; Omollo, Raymond; Mudawi, Mahmoud; Kokwaro, Gilbert; El-Hassan, Ahmed; Khalil, Eltahir
Article Title: Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study.
Journal Title: PLoS Neglected Tropical Diseases
Volume: 4
Issue: 10
ISSN: 19352727
Publisher: Public Library of Science  
Date Published: 2010-10
Start Page: 1
End Page: 7
Notes: --- - Article - ! 'Background: 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. Methods: 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. Findings: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]' - Copyright of PLoS Neglected Tropical Diseases is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) - ! 'Accession Number: 60639005; Musa, Ahmed M. 1; Email Address: Younis, Brima 1 Fadlalla, Ahmed 2 Royce, Catherine 3 Balasegaram, Manica 3 Wasunna, Monique 4 Hailu, Asrat 5 Edwards, Tansy 6 Omollo, Raymond 4 Mudawi, Mahmoud 1 Kokwaro, Gilbert 7,8 El-Hassan, Ahmed 1 Khalil, Eltahir 1; Affiliation: 1: Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan 2: Faculty of Medicine, Gedaref University, Gedaref, Sudan 3: Drugs for Neglected Diseases initiative (DNDi), Geneva, Switzerland 4: Centre for Clinical Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya 5: Addis Ababa University, Addis Ababa, Ethiopia 6: London School of Hygiene and Tropical Medicine, London, United Kingdom 7: Faculty of Pharmacy, University of Nairobi, Nairobi, Kenya 8: Consortium for National Health Research (CNHR), Nairobi, Kenya; Source Info: Oct2010, Vol. 4 Issue 10, p1; Subject Term: KALA-azar; Subject Term: HIV (Viruses); Subject Term: ELECTROCARDIOGRAPHY; Subject Term: SCHISTOSOMIASIS; Subject Term: PHARMACOKINETICS; Subject Term: UNIVERSITY of Khartoum (Khartoum, Sudan); Subject Term: KHARTOUM (Sudan); Subject Term: SUDAN; Subject Term: AFRICA, East; Company/Entity: WORLD Health Organization; Number of Pages: 7p; Illustrations: 1 Diagram, 3 Charts, 1 Graph; Document Type: Article'
SU Authors
  1. Prof. Gilbert Kokwaro
    26 Kokwaro