Monitoring the use of nifurtimox-eflornithine combination therapy (NECT) in the treatment of second stage gambiense human African trypanosomiasis

Abstract

Abstract: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 gastroin testinal 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 musculosk eletal 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.

6-Arylpyrazine-2-carboxamides: A New Core for Trypanosoma brucei Inhibitors

“…With respect to HIV/AIDS, for example, while the majority of the population might be at low risk, certain behaviour can result in high risk for certain subsectors (145). In the case of malaria in Africa, the population at risk is essentially the total population of countries with malaria transmission (146,147), because the risk is general in endemic areas, although this is not the case for forecasting specific malaria epidemic situations (148). For schistosomiasis, the population at risk is estimated as the total population living in areas where "transmission is known to occur", and estimates of the population at risk for filariasis have been based on the population living in areas where the climate is suitable for transmission (149).…”

“…nausea and vomiting) were the most frequent (61%), followed by neurological (all, 34%; convulsions, 9%) and psychiatric (all, 16%; agitation, 6%) adverse events. A pharmacovigilance programme set up by WHO in 2010 showed an overall case fatality rate of 0.5% among 1735 patients treated with NECT in 22 centres in nine endemic countries (148). Data from both the field study and the pharmacovigilance programme showed that NECT was better tolerated by children than by adults, with notably fewer neuropsychiatric adverse events.…”

Genetic dissection of drug resistance in trypanosomes

“…fEflornithine monotherapy treatment failures reported in some foci (Barrett et al 2011), as well as a limited number of NECT relapses (Franco et al 2012). …”

“…More recently, there have been a number of anecdotal reports of eflornithine monotherapy treatment failures, though it is not known if these were due to the presence of eflornithine-resistant parasites (Barrett et al 2011). NECT has only been in use since 2009, however its use against T. b. gambiense HAT is now widespread, with 59% of all second stage cases treated with this combination therapy in 2010 (Simarro et al 2012 b ), and there are already reports of small numbers of relapses (Franco et al 2012). It is not known whether these were due to the presence of drug-resistant trypanosomes, although this is a possibility, given the ease with which parasites resistant to either drug can be selected in the laboratory (see below).…”

Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection

“…), and resistance might soon be an issue, as up to 2% of cases relapse after NECT treatment (Franco et al. ).…”