The lack of adequate drugs to treat human African trypanosomiasis (HAT), commonly known as sleeping sickness, has been at the heart of DNDi ’s existence to mobilise R&D to address the treatment needs of the most neglected populations. Throughout the twentieth century, HAT epidemics have devastated remote and rural populations throughout sub-Saharan Africa and reinforced the poverty in which it thrives. A recent study in the Democratic Republic of the Congo (DRC) has shown that the cost of a HAT outbreak to each affected household was equivalent to 5 months’ income for that household. The common name of sleeping sickness is often used for HAT because it can disrupt the patient’s sleep cycle in its advanced stage (when the parasites cross the blood-brain barrier and enter into a patient’s central nervous system). However, the name suggests a benign disease, which HAT certainly is not. Fatal if let untreated, the advanced stage (stage 2) of HAT riddles the patient with a host of neurological disturbances, ranging from tremors to hallucinations to coma and death. As shown in the table on page 2, there are serious limitations for all existing treatments for stage 2 HAT. For many years, the only drug available was the arsenical drug, melarsoprol, which kills one in every 20 patients who are treated with it and which is increasingly ineffective. Eflornithine, an improved treatment option over melarsoprol, has had limited adoption because it is complicated to administer, with 56 slow intravenous infusions required over 14 days. Even though the drug itself is available through a WHOadministered donation programme since 2001, the combined cost of purchase, storage, and transportation of the drug and the associated materials has been a major hurdle to its use in the remote areas where HAT abounds. Moreover, there exists a real risk of parasites developing resistance against this trypanostatic drug.

Thus, it is clear that eflornithine monotherapy is not the ideal solution. New, and much better treatment options are urgently needed for HAT; DNDi has made significant progress in building a pipeline of drug discovery and development for this fatal disease over the past years, with projects such as nitroimidazoles, fexinidazole, and the HAT-specific lead optimisation programme. However, due to the long, high-risk process of drug development, these innovations still have a long way to go before reaching patients. In the meantime, it is critical to improve treatment options for patients in the short term by making better use of existing medicines. For that reason, DNDi decided in 2004 to partner with Epicentre and Médecins Sans Frontières (MSF) to reinforce their pioneering efforts in exploring alternative treatments, in particular Nifurtimox-Eflornithine Combination Therapy (NECT). This trial is one of the few randomised controlled trials to be successfully completed in the field of HAT, and has been compliant with international Good Clinical Practice (GCP) standards as verified through an independent audit. Limited health infrastructure, poor clinical research capacity, political instability, and the remoteness of the study population are all barriers that must be overcome in successfully conducting such a study on HAT. Moreover, patients must have follow-up for 18 months after treatment in order to establish treatment efficacy assessment. Such an accomplishment could not have been made without the effort and dedication of many people and groups. Epicentre and MSF initiated the study and implemented two out of four study sites; the national control programmes in the Republic of the Congo (RoC) and in the DRC hosted one and three study sites, respectively; the Swiss Tropical Institute (STI) implemented two study sites and critically contributed in ensuring that the trial was conducted according to international standards; and last but not least, the local investigators and healthcare workers who diagnosed, treated, and followed up with the patients throughout the five years of the study. Many others have also contributed to the study as it entailed rehabilitation of treatments centres and associated labs, training, audit, and continuous logistics support. Together with all our partners, we have established a solid evidence base on safety and efficacy of NECT. This data will be presented to the World Health Organization (WHO) in its evaluation of adding nifurtimox, to be used in combination with eflornithine, to its Model List of Essential Medicines. It's important that we synergise our research efforts to prevent overlaps and gaps in knowledge. An important facet of this is the HAT Platform, which serves to strengthen clinical trial capacity in the region and provide a forum for learning and exchange between the national programmes of the endemic countries. Also, in complement to the NECT study, the UNICEF/UNDP/ The World Bank, and WHO Special Programme for Research and Training in Tropical Diseases (TDR) has sponsored clinical research currently ongoing on NECT in Uganda – this research helps to strengthen the evidence base on NECT. To ensure that this treatment is made available in a timely manner to all patients, it is critical that each and every partner, playing their unique and critical role, work together: sanofi-aventis and Bayer to donate drugs; WHO to coordinate these donations, work with MSF Logistics to make adapted treatment kits, and advise endemic countries on appropriate use; and national control programmes and NGOs adopting and using the new treatments. The adoption of NECT will provide a meaningful, down-to-earth improvement in patient care. However, this is only the first step in the greater journey of improving treatment options for HAT that we and our partners have embarked upon.


Pour éviter les chevauchements et combler les lacunes, il est important que les efforts de recherche s’opèrent en synergie. C’est là un des rôles de la Plateforme THA qui vise à renforcer les capacités régionales de recherche clinique et constitue un forum pour apprendre et échanger entre les programmes nationaux des pays endémiques. Par ailleurs, d’autres essais cliniques de l’association thérapeutique NECT sont actuellement en cours en Ouganda, bénéficiant du soutien du Programme spécial UNICEF/ PNUD/Banque mondiale/OMS de recherche et de formation concernant les maladies tropicales (TDR). Ces nouvelles données devraient venir renforcer les résultats de la première étude NECT en RDC et en République du Congo.

Pour que les patients puissent bénéficier le plus rapidement possible du nouveau traitement combiné, les partenaires doivent maintenant agir de concert, chacun dans son rôle respectif : les firmes pharmaceutiques sanofi-aventis et Bayer pour les donations de médicaments ; l’OMS pour la coordination de ces dons, la préparation de kits de traitements en collaboration avec les services logistiques de MSF et le conseil aux pays endémiques ; les programmes nationaux de lutte contre la THA et les organisations non gouvernementales pour adopter et utiliser le nouveau traitement.
L’adoption de la combinaison thérapeutique de nifurtimox et d’éflornithine sera une amélioration concrète et significative pour les patients. Néanmoins il ne s’agit là que d’un premier pas sur la longue route menant à un traitement mieux adapté pour soigner la maladie du sommeil. Un périple dans lequel nous sommes tous embarqués.