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

doi:10.1136/bmj.39485.592674.BE

BMJ 2008;336:705-708 (29 March), doi:10.1136/bmj.39485.592674.BE (published 5 March 2008)

Research

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

Gerardo Priotto, medical epidemiologist¹, Loretxu Pinoges, statistician¹, Isaac Badi Fursa, registered medical assistant², Barbara Burke, medical doctor², Nathalie Nicolay, medical doctor¹, Guillaume Grillet, medical doctor², Cathy Hewison, medical doctor², Manica Balasegaram, medical doctor²

¹ Epicentre, 75011 Paris, France, ² Médecins Sans Frontières, Paris, France

Correspondence to: G Priotto gpriotto{at}epicentre.msf.org

Objective To assess the safety and effectiveness of eflornithineas 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 secondstage disease in a 16 month period.

Main outcome measures Deaths, severe drug reactions, and cureat 24 months.

Results 1055 patients received eflornithine for 14 days (400mg/kg/day in adults and 600 mg/kg/day in a subgroup of 96 children).Overall, 2824 drug reactions (2.7 per patient) occurred duringhospital stay, 1219 (43.2%) after the first week. Severe reactionsaffected 138 (13.1%) patients (mainly seizures, fever, diarrhoea,and bacterial infections), leading to 15 deaths. Risk factorsfor severe reactions included cerebrospinal fluid leucocytecounts $≥$ 100x10⁹/l (adults: odds ratio 2.6, 95% confidence interval1.5 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 dosesdid not experience increased toxicity. Follow-up data were obtainedfor 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%) wereconfirmed cured, and 420 (45.5%) were probably cured. The probabilityof event free survival at 24 months was 0.88 (0.86 to 0.91).Most (65.8%, 52/79) relapses and disease related deaths occurredafter 12 months. Risk factors for relapse included being male(incidence rate ratio 2.42, 1.47 to 3.97) and cerebrospinalfluid 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 effectivenessamong children (0.87 v 0.85, P=0.981).

Conclusions Eflornithine shows acceptable safety and effectivenessas first line treatment for human African trypanosomiasis. Relapsesdid occur more than 12 months after treatment. Higher dosesin children were well tolerated but showed no advantage in effectiveness.

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