Effectiveness of Nifurtimox Eflornithine Combination Therapy (NECT) in T. b. gambiense second stage sleeping sickness patients in the Democratic Republic of Congo: Report from a field study

PLoS Negl Trop Dis. 2021 Nov 8;15(11):e0009903. doi: 10.1371/journal.pntd.0009903. eCollection 2021 Nov.

Abstract

Background: Nifurtimox-eflornithine combination therapy (NECT) for the treatment of second stage gambiense human African trypanosomiasis (HAT) was added to the World Health Organization's Essential Medicines List in 2009 after demonstration of its non-inferior efficacy compared to eflornithine therapy. A study of NECT use in the field showed acceptable safety and high efficacy until hospital discharge in a wide population, including children, pregnant and breastfeeding women, and patients with a HAT treatment history. We present here the effectiveness results after the 24-month follow-up visit.

Methodology/principal findings: In a multicenter, open label, single arm phase IIIb study, second stage gambiense HAT patients were treated with NECT in the Democratic Republic of Congo. Clinical cure was defined 24 months after treatment as survival without clinical and/or parasitological signs of HAT. Of the 629 included patients, 619 (98.4%) were discharged alive after treatment and were examined for the presence of trypanosomes, white blood cell count in cerebro-spinal fluid, and disease symptoms. The clinical cure rate of 94.1% was comparable for all subpopulations analyzed at the 24-month follow-up visit. Self-reported adverse events during follow-up were few and concerned mainly nervous system disorders, infections, and gastro-intestinal disorders. Overall, 28 patients (4.3%) died during the course of the trial. The death of 16 of the 18 patients who died during the follow-up period was assessed as unlikely or not related to NECT. Within 24 months, eight patients (1.3%) relapsed and received rescue treatment. Sixteen patients were completely lost to follow-up.

Conclusions/significance: NECT treatment administered under field conditions was effective and sufficiently well tolerated, no major concern arose for children or pregnant or breastfeeding women. Patients with a previous HAT treatment history had the same response as those who were naïve. In conclusion, NECT was confirmed as effective and appropriate for use in a broad population, including vulnerable subpopulations.

Trial registration: The trial is registered at ClinicalTrials.gov, number NCT00906880.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antiprotozoal Agents / administration & dosage*
  • Antiprotozoal Agents / adverse effects
  • Child
  • Child, Preschool
  • Democratic Republic of the Congo
  • Drug Therapy, Combination
  • Eflornithine / administration & dosage*
  • Eflornithine / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Nifurtimox / administration & dosage*
  • Nifurtimox / adverse effects
  • Pregnancy
  • Treatment Outcome
  • Trypanocidal Agents / administration & dosage*
  • Trypanosoma brucei gambiense / drug effects
  • Trypanosoma brucei gambiense / genetics
  • Trypanosoma brucei gambiense / physiology
  • Trypanosomiasis, African / drug therapy*
  • Trypanosomiasis, African / parasitology
  • Trypanosomiasis, African / pathology
  • Young Adult

Substances

  • Antiprotozoal Agents
  • Trypanocidal Agents
  • Nifurtimox
  • Eflornithine

Associated data

  • ClinicalTrials.gov/NCT00906880

Grants and funding

The study was funded through the Drugs for Neglected Diseases initiative (DNDi, Geneva, Switzerland), which was involved in the conception of the study, the interpretation of results and in the preparation of this manuscript. DNDi would like to acknowledge the following donors for their support of DNDi’s NECT related activities: UK aid, UK (Grants 2006-2008 and 2008-2013) https://www.ukaiddirect.org/; French Ministry for Europe and Foreign Affairs (MEAE), France (FSP 2006-83) https://www.diplomatie.gouv.fr/en/french-foreign-policy/development-assistance/; French Development Agency, (AFD) France (CZZ 1732) https://www.afd.fr/en; Republic and Canton of Geneva, International Solidarity Service, Switzerland Convention 2010-2012) https://www.ge.ch/dossier/soutenir-solidarite-internationale; Spanish Agency for International Development Cooperation (AECID), Spain (MoU 2007-2008) https://www.aecid.es/EN/aecid Swiss Agency for Development and Cooperation (SDC), Switzerland (642.33/2010/0779/02 PZO/NID) https://www.eda.admin.ch/deza/en/home/sdc/activities.html; Médecins Sans Frontières International (MSF) (MoU 2006-2008) https://www.msf.org/; Medicor Foundation, Liechtenstein (2007 grant) https://www.medicor.li/en/about-us/foundation-board.html; and other anonymous individuals and organizations. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.