Safety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort study

Hdl Handle:
http://hdl.handle.net/10144/25192
Title:
Safety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort study
Authors:
Priotto, G; Pinoges, L; Badi Fursa, I; Burke, B; Nicolay, N; Grillet, G; Hewison, C; Balasegaram, M
Journal:
BMJ/British Medical Journal
Abstract:
Objective: To assess the safety and effectiveness of eflornithine as first line treatment for human African trypanosomiasis. Design: Cohort study. Setting: Control programme in Ibba, southern Sudan. Participants: 1055 adults and children newly diagnosed with second stage disease in a 16 month period. Main outcome measures: Deaths, severe drug reactions, and cure at 24 months. Results: 1055 patients received eflornithine for 14 days (400 mg/kg/day in adults and 600 mg/kg/day in a subgroup of 96 children). Overall, 2824 drug reactions (2.7 per patient) occurred during hospital stay, 1219 (43.2%) after the first week. Severe reactions affected 138 (13.1%) patients (mainly seizures, fever, diarrhoea, and bacterial infections), leading to 15 deaths. Risk factors for severe reactions included cerebrospinal fluid leucocyte counts ≥100x109/l (adults: odds ratio 2.6, 95% confidence interval 1.5 to 4.6), seizures (adults: 5.9, 2.0 to 13.3), and stupor (children: 9.3, 2.5 to 34.2). Children receiving higher doses did not experience increased toxicity. Follow-up data were obtained for 924 (87.6%) patients at any follow-up but for only 533 (50.5%) at 24 months. Of 924 cases followed, 16 (1.7%) died during treatment, 70 (7.6%) relapsed, 15 (1.6%) died of disease, 403 (43.6%) were confirmed cured, and 420 (45.5%) were probably cured. The probability of event free survival at 24 months was 0.88 (0.86 to 0.91). Most (65.8%, 52/79) relapses and disease related deaths occurred after 12 months. Risk factors for relapse included being male (incidence rate ratio 2.42, 1.47 to 3.97) and cerebrospinal fluid leucocytosis: 20-99x109/l (2.35, 1.36 to 4.06); ≥100x109/l (1.87, 1.07 to 3.27). Higher doses did not yield better effectiveness among children (0.87 v 0.85, P=0.981). Conclusions: Eflornithine shows acceptable safety and effectiveness as first line treatment for human African trypanosomiasis. Relapses did occur more than 12 months after treatment. Higher doses in children were well tolerated but showed no advantage in effectiveness.
Affiliation:
Epicentre, Paris, France; Médecins Sans Frontières, Paris, France
Issue Date:
5-Mar-2008
URI:
http://hdl.handle.net/10144/25192
DOI:
10.1136/bmj.39485.592674.BE
PubMed ID:
18321960
PubMed Central ID:
PMC2276259; PMC2276259; PMC2276259
Additional Links:
http://www.bmj.com/cgi/content/full/bmj.39485.592674.BEv1; http://dx.doi.org/10.1136/bmj.39485.592674.BE
Submitted date:
2008-05-08
Type:
Article
Language:
en
ISSN:
09598138; 14685833
Sponsors:
Funding: French section of Médecins Sans Frontières.
Appears in Collections:
Trypanosomiasis/Sleeping Sickness

Full metadata record

DC FieldValue Language
dc.contributor.authorPriotto, G-
dc.contributor.authorPinoges, L-
dc.contributor.authorBadi Fursa, I-
dc.contributor.authorBurke, B-
dc.contributor.authorNicolay, N-
dc.contributor.authorGrillet, G-
dc.contributor.authorHewison, C-
dc.contributor.authorBalasegaram, M-
dc.date.accessioned2008-05-08T15:19:13Z-
dc.date.available2008-05-08T15:19:13Z-
dc.date.issued2008-03-05-
dc.date.submitted2008-05-08-
dc.identifier.citationBMJ 2008;336:705-708en
dc.identifier.issn09598138-
dc.identifier.issn14685833-
dc.identifier.pmid18321960-
dc.identifier.doi10.1136/bmj.39485.592674.BE-
dc.identifier.urihttp://hdl.handle.net/10144/25192-
dc.description.abstractObjective: To assess the safety and effectiveness of eflornithine as first line treatment for human African trypanosomiasis. Design: Cohort study. Setting: Control programme in Ibba, southern Sudan. Participants: 1055 adults and children newly diagnosed with second stage disease in a 16 month period. Main outcome measures: Deaths, severe drug reactions, and cure at 24 months. Results: 1055 patients received eflornithine for 14 days (400 mg/kg/day in adults and 600 mg/kg/day in a subgroup of 96 children). Overall, 2824 drug reactions (2.7 per patient) occurred during hospital stay, 1219 (43.2%) after the first week. Severe reactions affected 138 (13.1%) patients (mainly seizures, fever, diarrhoea, and bacterial infections), leading to 15 deaths. Risk factors for severe reactions included cerebrospinal fluid leucocyte counts ≥100x109/l (adults: odds ratio 2.6, 95% confidence interval 1.5 to 4.6), seizures (adults: 5.9, 2.0 to 13.3), and stupor (children: 9.3, 2.5 to 34.2). Children receiving higher doses did not experience increased toxicity. Follow-up data were obtained for 924 (87.6%) patients at any follow-up but for only 533 (50.5%) at 24 months. Of 924 cases followed, 16 (1.7%) died during treatment, 70 (7.6%) relapsed, 15 (1.6%) died of disease, 403 (43.6%) were confirmed cured, and 420 (45.5%) were probably cured. The probability of event free survival at 24 months was 0.88 (0.86 to 0.91). Most (65.8%, 52/79) relapses and disease related deaths occurred after 12 months. Risk factors for relapse included being male (incidence rate ratio 2.42, 1.47 to 3.97) and cerebrospinal fluid leucocytosis: 20-99x109/l (2.35, 1.36 to 4.06); ≥100x109/l (1.87, 1.07 to 3.27). Higher doses did not yield better effectiveness among children (0.87 v 0.85, P=0.981). Conclusions: Eflornithine shows acceptable safety and effectiveness as first line treatment for human African trypanosomiasis. Relapses did occur more than 12 months after treatment. Higher doses in children were well tolerated but showed no advantage in effectiveness.en
dc.description.sponsorshipFunding: French section of Médecins Sans Frontières.en
dc.language.isoenen
dc.relation.urlhttp://www.bmj.com/cgi/content/full/bmj.39485.592674.BEv1en
dc.relation.urlhttp://dx.doi.org/10.1136/bmj.39485.592674.BEen
dc.rightsPublished by: BMJ Publishing Group Ltd Archived on this site with kind permission from BMJ, [url]http://www.bmj.com/[/url]en
dc.subjectSleeping Sicknessen
dc.subjectSudanen
dc.titleSafety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort studyen
dc.typeArticleen
dc.contributor.departmentEpicentre, Paris, France; Médecins Sans Frontières, Paris, Franceen
dc.identifier.journalBMJ/British Medical Journalen
dc.identifier.pmcidPMC2276259en
dc.identifier.pmcidPMC2276259en
dc.identifier.pmcidPMC2276259-

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