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Home , African trypanosomiasis

Human African Sleeping Sickness The battle is not over until it is won

Sleeping sickness, or human African trypa- . The latter, however, is still the nosomiasis, threatens millions of people in first-line treatment for the less commonT.b. 36 countries across sub-Saharan . The rhodesiense HAT. Democratic Republic of the Congo bears the To contribute to the WHO elimination goal, a brunt, accounting for 83% of all cases. In the ‘test and treat’ strategy that would be imple- 1960s there were less than 5,000 patients mented at the primary healthcare level is on suffering from the disease in the whole of the the horizon, with potential simple oral pills continent. However, the end of the 20th cen- for both the early and late stage as well as tury – with internal conflict, competing health both types of HAT, that are currently in devel- priorities, and decolonization – witnessed a opment, along with new rapid diagnostics, halt in the successful control methods, and which together would remove the need for the number of cases reported rose painful and dangerous lumbar punc- steeply, peaking in 1998 with tures. This would mean that rural over 37,000 cases reported in health centres, rather than hos- that year. Nowadays, thanks pitals, will play an increasingly to the combined efforts of important role, especially as the WHO, National Sleeping number of reported cases con- Sickness Control Pro- tinues to dwindle. grammes, NGOs and other partners, the disease has once more been brought under control, and since 2010 the number of reported cases has fallen below 8,000. The WHO has laid out a roadmap to elimi- nate the disease as a public health problem by 2020, when less than one case per 10,000 inhabitants in at least 90% of endemic foci is expected.(1) Maximizing efficiency through a ‘WHO network’ of partners and stakehold- Ideal Target Product Profile ers(2) in order to achieve elimination is cur- for HAT rently underway. A new treatment for adults and The most advanced stage of the disease is children: determined after multiple and complex diag- > Effective against both stages of nostic procedures, including a painful lumbar the disease puncture, and is treated with a combina- > Active against both causative parasite tion of oral and intravenously administered sub-species: brucei drugs. - combination gambiense and T.b. rhodesiense treatment (NECT), introduced by DNDi and > Less than 0.1% drug-related partners in 2009, was the first improved mortality treatment option for patients with advanced > At least 95% efficacy at 18 months sleeping sickness to be developed in 25 follow-up years, and has reduced the time required > Safe for pregnant and breastfeeding to spend in hospital during administra- women tion, from 14 to 10 days. By the end of 2012, > Easy to use: short-course NECT, which features on the WHO Essen- (7, maximum 10 days), oral, once a tial Medicines Lists for adults and children, day, requiring no monitoring was being used to treat 96% of late-stage > Affordable T.b. gambiense HAT patients in endemic > Adapted to tropical climates countries, thus virtually replacing the pre- (three-year shelf-life) vious and toxic -based treatment,

(1) Control and surveillance of human African trypanosomiasis: report of a WHO technical committee (2013). World Health Organization. (2) http://www.who.int/neglected_diseases/HAT_roll_out_strategy_2013/en/# human African trypanosomiasis (HAT)

FACT SHEET

WHAT IS THE IMPACT OF HAT? WHAT ARE THE CURRENT Melarsoprol, still the only The number of reported cases in TREATMENTS AND THEIR drug available for stage 2 2012 was fewer than 8,000, but LIMITATIONS? T.b. rhodesiense, is a toxic the actual number of cases is Available treatments have arsenic derivative that causes estimated to be 20,000.(1) Fatal pain and fatal limitations, are difficult to T. b. gambiense if untreated, the disease affects administer, often toxic, and are in up to 5% of patients who (3) mainly those living in remote stage-specific. receive it, and is increasingly areas with limited access to ineffective, with reports of drug T. b. rhodesiense > Stage 1: and Epidemic adequate health services. The resistance and treatment failure. , require injections and Endemic disease is found in 36 countries are ineffective for stage 2. Eflornithine, today rarely used in sub-Saharan Africa, but alone, is difficult to administer 8 countries report 97% of all > Stage 2: NECT (nifurtimox- as treatment requires trained cases (see map), and over eflornithine combination health staff and an extended two-thirds of those are reported therapy), available since 2009, is hospital stay (56 intravenous in the Democratic Republic of a simplified therapy option for infusions taking two hours each the Congo.(2) Almost eliminated stage 2 T.b. gambiense sleeping to administer, over 14 days, four in the 1960s, sickness, with only 14 injections times per day). increased again as a result of of eflornithine over 7 days and war, population displacement, 10 days of oral treatment with , and the collapse of nifurtimox. While not the most adequate support to the control appropriate treatment to support activities conducted within elimination efforts as it requires health systems. a hospital setting, NECT does Recent successes and an provide a major improvement in impressive drop in the number case management. of reported cases call for renewed hope, but there is still work to be done, as some areas are not covered by surveillance and control efforts. WHAT IS DNDi DOING TO ADDRESS UNMET TREATMENT NEEDS? At its inception, DNDi’s short-term strategy was to make better use of existing HOW IS HAT TRANSMITTED? treatments by combining drugs already in use. In September 2009, DNDi and partners HAT is transmitted to humans by launched the first new treatment for sleeping sickness in 25 years: nifurtimox and two sub-species of the parasite eflornithine combination therapy (NECT). NECT was included on the WHO Essential (T. b.) Medicines List (EML) in 2009, and extended to the EML for children in 2013. Since June through the bite of the : T. b. gambiense (West and 2013, all countries endemic to T.b. gambiense are using NECT as first-line treatment Central Africa, responsible for for second stage HAT, with the exception of Nigeria. the vast majority of cases) and As a medium-term strategy, DNDi initiated a compound mining effort to identify existing T.b. rhodesiense (East Africa). chemical compounds with potential against kinetoplastid diseases. This resulted in the Man is the essential reservoir rediscovery of , which completed Phase I clinical development in 2011. for T.b. gambiense. Fexinidazole entered a pivotal Phase II/III study in 2012 and is currently recruiting WHAT ARE THE SYMPTOMS? patients in the DRC. Two complementary studies will examine efficacy and safety in adults HAT occurs in two stages: with stage 1 and early stage 2 HAT, and children aged 6-14 years. is the industrial partner for this project. > Stage 1: the haemolymphatic stage – includes non-specific In order to build a strong pipeline for long-term drug discovery, DNDi initially established symptoms like headaches and a HAT Lead Optimization Consortium resulting in the identification of theOxaborole bouts of fever (and generally SCYX-7158. SCYX-7158 successfully progressed through pre-clinical development, goes undiagnosed without entering Phase I clinical development in early 2012, which is nearing completion. Other active HAT surveillance). backup compounds were evaluated by the consortium and remain available for further i > Stage 2: the later, neurologic development if necessary. stage – occurs when the parasite crosses the blood-brain barrier In addition, DNDi supports the HAT Platform that was launched in Kinshasa, Democratic and is characterized by serious Republic of the Congo (DRC) in 2005. The HAT Platform is a clinical research and cycle disruptions, access-supporting network that brings together key players in the fight against sleeping , progressive mental sickness from Angola, the , Chad, DRC, Republic of the Congo, deterioration, and ultimately, Sudan, South Sudan, and those involved in HAT from the international research without effective treatment, arena. death. A is needed to differentiate between the two By 2018, DNDi aims to deliver from its HAT-specific portfolio: DRC-DND Tshiamala, Simon credits: Photo - stages to choose an appropriate > An oral, safe, effective treatment to be used for both stage 2 and stage 1 HAT treatment.

(1) Control and surveillance of human African trypanosomiasis: report of a WHO expert committee (2013); WHO, Geneva, Switzerland (2) Eliminating human African trypanosomiasis: where do we stand and what comes next? Simarro PP, Jannin J, Cattand P (2008) PLoS Med 5: e55. doi:10.1371/journal.pmed.0050055. (3) Clinical description of encephalopathic syndromes and risk factors for their occurrence and outcome during melarsoprol treatment of human African trypanosomiasis. Blum J, Nkunku S, Burri C. (2001) Trop Med Int Health;6:390-400.

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