title: Safety and effectiveness of first line eflornithine for Trypanosoma brucei gambiense sleeping sickness in Sudan: cohort study.
abstract: OBJECTIVE
  To assess the safety and effectiveness of eflornithine as first line treatment for human African trypanosomiasis.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  Control programme in Ibba, southern Sudan.
  
  
  METHODS
  1055 adults and children newly diagnosed with second stage disease in a 16 month period.
  
  
  METHODS
  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 > or =100x10(9)/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: 20-99x10(9)/l (2.35, 1.36 to 4.06); > or =100x10(9)/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.
authors.affiliation: Epicentre, 75011 Paris, France.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Priotto
authors.forename: Loretxu
authors.initials: L
authors.lastname: Pinoges
authors.forename: Isaac Badi
authors.initials: IB
authors.lastname: Fursa
authors.forename: Barbara
authors.initials: B
authors.lastname: Burke
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicolay
authors.forename: Guillaume
authors.initials: G
authors.lastname: Grillet
authors.forename: Cathy
authors.initials: C
authors.lastname: Hewison
authors.forename: Manica
authors.initials: M
authors.lastname: Balasegaram
mesh_terms: D000328:Adult; D002648:Child; D015331:Cohort Studies; D000518:Eflornithine / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D012307:Risk Factors; D013397:Sudan; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014353:Trypanosomiasis, African / Q000188:drug therapy*
chemical_list: D014344:Trypanocidal Agents; D000518:Eflornithine