Jose R Franco, Pere P Simarro, Abdoulaye Diarra, Jose A Ruiz-Postigo, Mireille Samo, Jean G Jannin

After inclusion of the nifurtimox-eflornithine combination therapy (NECT) in the Model List of Essential Medicines for the treatment of second-stage gambiense human African trypanosomiasis (HAT), the World Health Organization, in collaboration with National Sleeping Sickness Control Programs and nongovernmental organizations set up a pharmacovigilance system to assess the safety and efficacy of NECT during its routine use. Data were collected for 1735 patients treated with NECT in nine disease endemic countries during 2010-2011. At least one adverse event (AE) was described in 1043 patients (60.1%) and a total of 3060 AE were reported. Serious adverse events (SAE) were reported for 19 patients (1.1% of treated), leading to nine deaths (case fatality rate of 0.5%). The most frequent AE were gastrointestinal disorders (vomiting/nausea and abdominal pain), followed by headache, musculoskeletal pains, and vertigo. The most frequent SAE and cause of death were convulsions, fever, and coma that were considered as reactive encephalopathy. Two hundred and sixty-two children below 15 years old were treated. The characteristics of AE were similar to adults, but the major AE were less frequent in children with only one SAE and no deaths registered in this group. Gastrointestinal problems (vomiting and abdominal pain) were more frequent than in adults, but musculoskeletal pains, vertigo, asthenia, neuropsychiatric troubles (headaches, seizures, tremors, hallucinations, insomnia) were less frequent in children. Patient follow-up after treatment is continuing, but initial data could suggest that NECT is effective as only a low number of relapses have so far been reported (19 cases). However, additional monitoring is required to assess the efficacy of the treatment, particularly in children. NECT has given satisfactory results of safety in the usual conditions where HAT patients are managed and it is currently the best option for treatment of second stage of gambiense HAT.