WHO convened the fifth stakeholders meeting on the elimination of HAT due to infection with Trypanosoma brucei gambiense (g-HAT) and Trypanosoma brucei rhodesiense (r-HAT) in Geneva, Switzerland, on 7–9 June 2023. The meeting was held again in person after the coronavirus disease (COVID-19) pandem...ic and jointly for both forms of the disease. The previous meetings on g-HAT held in 2014, 2016 and 2018, as well as on r-HAT in 2015, 2017 and 2019, and jointly for g-HAT and r-HAT in 2021 (8) reinforced the partnership and commitment for HAT elimination and structured the mechanisms of collaboration within the WHO network for HAT elimination. The network includes NSSCPs, groups developing new tools, international and nongovernmental organizations involved in disease control, and donors.
Fewer than 1000 cases of HAT annually have been reported over the past 5 years, which is a historic achievement. The area at risk has been substantially reduced. The elimination of HAT as a public health problem at the global level has been achieved.
The new road map for neglected tropical diseases (NTDs) 2021−2030 (“the road map”) with the target to interrupt the transmission of g-HAT requires the strengthened and sustained efforts of all stakeholders, national authorities and partners, under WHO coordination. It will take disproportionally high efforts and innovative strategies to find the last cases of g-HAT and neutralize its transmission. Given the limited resources and other competing public health priorities, this is a challenge that requires our joint commitment.
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Having established the goal of eliminating transmission of gambiense human African trypanosomiasis (g-HAT) to humans, the HAT-e-TAG considered which elements should be developed to assess this goal.
Database with maps and country-specific numbers
Front. Trop. Dis. , 09 May 2023 Sec. Neglected Tropical Diseases Volume 4 - 2023 | https://doi.org/10.3389/fitd.2023.1087003
The number of reported cases of chronic African trypanosomiasis (sleeping sickness). The disease is caused by parasites that are spread by tsetse flies and otherinsects. The disease is typically fatal if not treated.
Human African trypanosomiasis is caused by Trypanosoma brucei gambiense in West and Central Africa and by T. brucei rhodesiense in East Africa; both species are endemic in Uganda. Trypanosoma brucei gambiense accounts for 98% of all cases of African trypanosomiasis, and T. brucei rhodesiense account...s for 2%. African trypanosomiasis has been targeted for eradication by the World Health Organization (WHO) and, as a result of control efforts, there has been a dramatic decrease (> 95%) in the number of reported cases worldwide.
Professional version as well as patient education
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Human African Trypanosomiasis (HAT, sleeping sickness) and Animal African Trypanosomiasis (AAT) are neglected tropical diseases generally caused by the same etiological agent, Trypanosoma brucei. Despite important advances in the reduction or disappearance of HAT cases, AAT represents a risky reserv...oir of the infections. There is a strong need to control AAT, as is claimed by the European Commission in a recent document on the reservation of antimicrobials for human use. Control of AAT is considered part of the One Health approach established by the FAO program against African Trypanosomiasis. Under the umbrella of the One Health concepts, in this work, by analyzing the pharmacological properties of the therapeutic options against Trypanosoma brucei spp., we underline the need for clearer and more defined guidelines in the employment of drugs designed for HAT and AAT. Essential requirements are addressed to meet the challenge of drug use and drug resistance development. This approach shall avoid inter-species cross-resistance phenomena and retain drugs therapeutic activity.
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The development of this target product profile (TPP) was led by the WHO Department of Control of Neglected Tropical Diseases (NTD) following standard WHO guidance for TPP development. In order to identify and prioritize diagnostic needs, a WHO NTD Diagnostics Technical Advisory Group (DTAG) was form...ed, and different subgroups were created to advise on specific NTDs, including a subgroup working on the human African trypanosomiasis (HAT) diagnostic innovation needs. This group of independent experts included leading scientists, public health officials and endemic-country end-user representatives. Standard WHO Declaration of Interest procedures were followed. A landscape analysis of the available products and of the development pipeline was conducted, and the salient areas with unmet needs were identified.
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Gambiense human African trypanosomiasis is a deadly infectious disease affecting West and Central Africa, South Sudan and Uganda, and transmitted between humans by tsetse flies. The disease has caused several major epidemics, the latest one in the 1990s. Thanks to recent innovations such as rapid di...agnostic tests for population screening, a single-dose oral treatment and a highly efficient vector control strategy, interruption of transmission of the causative parasite is now within reach. If indeed gHAT has an exclusively human reservoir, this could even result in eradication of the disease. Even if there were an animal reservoir, on the basis of epidemiological data, it plays a limited role. Maintaining adequate postelimination surveillance in known historic foci, using the newly developed tools, should be sufficient to prevent any future resurgence.
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More countries eliminate human African trypanosomiasis as a public health problem: Benin and Uganda (gambiense form) and Rwanda (rhodesiense form)
Human African trypanosomiasis (HAT), or sleeping sickness, transmitted by tsetse flies in sub-Saharan Africa, is a life-threatening disease that afflict...s poor rural populations. It is caused by trypanosome parasites of 2 subspecies: Trypanosoma brucei gambiense in West and Central Africa, and T. b. rhodesiense in East Africa.
HAT transmission can be reduced and interrupted by deploying and maintaining capacities for testing people at risk in order to detect and treat cases, and by controlling tsetse populations that are in contact with humans.
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The main purpose of the meeting was to review tsetse control tools, activities and their contribution to the elimination of gHAT and the monitoring thereof. Seven endemic countries provided reports on recent and ongoing vector control interventions at the national level (Angola, Cameroon, Côte d’...Ivoire, Chad, Democratic Republic of the Congo, Guinea and Uganda). Country reports focused on the in situations implementing and supporting vector control activities, the tools and the approaches in use, the coverage of the activities in space and time and their impacts on tsetse populations. Future perspectives for vector control in the respective countries were also discussed, including opportunities and challenges to sustainability.
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After 100 years of chemotherapy with impractical and toxic drugs, an oral cure for human African trypanosomiasis (HAT) is available: Fexinidazole. In this case, we review the history of drug discovery for HAT with special emphasis on the discovery, pre-clinical development, and operational challenge...s of the clinical trials of fexinidazole. The screening of the Drugs for Neglected Diseases initiative (DNDi) HAT-library by the Swiss TPH had singled out fexinidazole, originally developed by Hoechst (now Sanofi), as the most promising of a series of over 800 nitroimidazoles and related molecules. In cell culture, fexinidazole has an IC50 of around 1 µM against Trypanosoma brucei and is more than 100-fold less toxic to mammalian cells. In the mouse model, fexinidazole cures both the first, haemolymphatic, and the second, meningoencephalitic stage of the infection, the latter at 100 mg/kg twice daily for 5 days. In patients, the clinical trials managed by DNDi and supported by Swiss TPH mainly conducted in the Democratic Republic of the Congo demonstrated that oral fexinidazole is safe and effective for use against first- and early second-stage sleeping sickness. Based on the positive opinion issued by the European Medicines Agency in 2018, the WHO has released new interim guidelines for the treatment of HAT including fexinidazole as the new therapy for first-stage and non-severe second-stage sleeping sickness caused by Trypanosoma brucei gambiense (gHAT). This greatly facilitates the diagnosis and treatment algorithm for gHAT, increasing the attainable coverage and paving the way towards the envisaged goal of zero transmission by 2030.
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DNDi is now striving to make fexinidazole available to the majority of people who have T.b. gambiense sleeping sickness. We are supporting a three-year access and pharmacovigilance study that began in 2020 and have so far carried out in-country training of relevant staff in 250 hospitals and... health centres in T.b. gambiense-endemic countries; and updated national treatment and pharmacovigilance guidelines in Angola, Central African Republic, the Democratic Republic of Congo, Equatorial Guinea, Guinea, and Chad.
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Human African trypanosomiasis (HAT) is a lethal neglected tropical disease (NTD) transmitted by the bite of infected tsetse flies. The disease is also known as “sleeping sickness”. During the 20th century it caused enormous suffering in the endemic areas in sub-Saharan Africa. HAT transmission l...ast soared in the late 1990s, triggering a renewed, coordinated and very successful control effort. In this paper, we present achievements towards HAT elimination, with a focus on the WHO road map targets for 2020. In particular, reported cases continue to decline, from over 30,000 cases per year at the turn of the century to 663 cases in 2020. Despite the impact of the COVID-19 pandemic, HAT surveillance was largely sustained, and the network of health facilities able to diagnose and treat the disease further expanded. Looking to the future, the World Health Organization (WHO) set bold new targets for HAT in its 2021–2030 road map for NTDs, namely: the elimination of transmission of gambiense HAT, which occurs in western and central Africa, and the elimination as a public health problem of rhodesiense HAT, which is found in eastern and southern Africa. The strong commitment of national health authorities and the international community will be essential if these goals are to be achieved.
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HAT diagnosis relies on laboratory techniques because clinical signs and symptoms are unspecific. Serodiagnostic tests exist only for Tbg and are based on the detection of specific antibodies, thus they are not confirmatory of infection. With the current low disease prevalence, the positive predicti...ve value of serological tests is particularly low. Field-applicable tools include the card agglutination test for trypanosomiasis (CATT) used mainly in active screening by specialized mobile teams, and the rapid diagnostic tests that are more suitable for individual testing at point-of-care. Confirmation of Tbg infection requires microscopic examination of body fluids necessitating specific training. The best performing methods are laborious and reach 85–95% diagnostic sensitivity when performed by skilled personnel.
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HAT diagnosis relies on laboratory techniques because clinical signs and symptoms are unspecific. Serodiagnostic tests exist only for Tbg and are based on the detection of specific antibodies, thus they are not confirmatory of infection. With the current low disease prevalence, the positive predicti...ve value of serological tests is particularly low. Field-applicable tools include the card agglutination test for trypanosomiasis (CATT) used mainly in active screening by specialized mobile teams, and the rapid diagnostic tests that are more suitable for individual testing at point-of-care.
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PLoS Negl Trop Dis 16(11): e0010885. https://doi.org/10.1371/journal.pntd.0010885
HAT diagnosis in non-endemic countries is rare and can be challenging, but alertness and
surveillance must be maintained to contribute to WHO’s elimination goals. Early detection is
particularly important as it co...nsiderably improves the prognosis.
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DNDi’s long-term goal for sleeping sickness, also known as human African trypanosomiasis (HAT), is to develop and register two new drugs that are effective against both Stage 1 and Stage 2 of the disease and both subspecies of the parasite, T.b. gambiense and T.b. rhodesiense. T.b. rhodesiense is ...an acute form of the disease, occurring primarily in Eastern and Southern Africa. Better treatments for T.b. rhodesiense sleeping sickness are urgently needed.
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