At the forefront of DNDi’s efforts to develop new treatments is the need to understand the realities and treatment needs of patients and health care staff in the field. The ultimate goal for human African trypanosomiasis (HAT) is a truly simplified
treatment which can be orally administered, impl...emented at the primary health care level, and effective against both stages of the disease.
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Human African trypanosomiasis (HAT), or sleeping sickness, is a painful and protracted disease transmitted through the bite of infected tsetse flies and it is found in rural parts of sub-Saharan Africa. Sleeping sickness has two clinical phases but this review focuses only on treatment of the second...-stage, which is characterized by neurological changes and almost invariably fatal without treatment. There are only a few drugs currently available for second-stage sleeping sickness, all with considerable adverse events and variable efficacy.
The review includes nine trials with 2577 participants. Each trial reported different comparisons of the drugs currently available to treat second stage HAT (melarsoprol, eflornithine, nifurtimox) so no meta-analysis was possible.
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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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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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This document focuses on the management of patients affected by gambiense HAT and
constitutes an update to the WHO therapeutic guidance issued in 2013. The main changes in recommendations concern the criteria and methods for deciding the treatment among the new set of therapeutic options and the pa...rticular conditions that apply to treatment with fexinidazole, as outlined below. Because HAT is a serious, life-threatening disease and because the efficacy of fexinidazole depends on swallowing the medicine after an appropriate intake of food as well as on completing the full 10-day
treatment schedule, the recommendations regarding fexinidazole administration are considered key elements that must be carefully followed. When the conditions listed in these guidelines are not met for any individual patient, the alternative available treatments should be prescribed.
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Arsenical monotherapies were previously very successful for treating human African trypanosomiasis (HAT).
Melarsoprol resistance emerged as early as the 1970s and was widespread by the late 1990s.
Melarsoprol resistance represents the only example of widespread drug resistance in HAT patients wher...e the genetic mechanism has been established.
The current goal of elimination of HAT as a public health problem by 2020 may be undermined by the emergence and spread of resistance to current or new drugs.
Insights into potential resistance mechanisms for current and new drugs will facilitate predictions of the likelihood of resistance and will also facilitate rational approaches to minimizing, monitoring, and tackling the future emergence of resistance.
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Sleeping sickness is a neglected tropical disease affecting rural communities in sub-Saharan Africa. The reduction in the number of reported cases in recent years indicates that disease transmission is under control. However, many aspects of patient management still need to be improved. Undiagnosed ...patients or inappropriate treatment due to an incorrect determination of the disease stage could in fact lead to its re-emergence. There is thus a strong need for new diagnostic and staging tools to keep the disease under control and to improve the clinical care of patients. This review describes the most promising biomarkers proposed so far for the diagnosis and stage determination of patients suffering from sleeping sickness, with a particular emphasis on their translation into diagnostic tools for field applications.
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Human African Trypanosomiasis, also known as sleeping sickness is a devastating parasitic disease. It is a neglected tropical disease affecting communities in Africa. In this video we take a look at the disease, how it presents and and ways to control it.
Since 2000, concerted efforts by national programmes, supported by public–private partnerships, nongovernmental organizations, donors and academia under the auspices and coordination of the World Health Organization (WHO), have produced important achievements in the control of human African trypan...osomiasis (HAT). As a consequence, the disease was targeted for elimination as a public health problem by 2020. The Sixty-sixth World Health Assembly endorsed this goal in resolution WHA66.12 on neglected tropical diseases, adopted in 2013.
National sleeping sickness control programmes (NSSCPs) are core to progressing control of the disease and in adapting to the different epidemiological situations. The involvement of different partners, as well as the support and trust of long-term donors, has been crucial for the achievements.
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Over the past twenty years, huge efforts made by a broad coalition of stakeholders curbed the last epidemic and brought the disease to the brink of elimination. In this paper, the latest figures on disease occurrence, geographical distribution and control activities are presented. Strong evidence in...dicates that the elimination of sleeping sickness ‘as a public health problem’ by 2020 is well within reach. In particular, fewer than one thousand new cases were reported in 2018, and the area where the risk of infection is estimated as moderate, high or very high has shrunk to less than 200,000 km2. More than half of this area is in the Democratic Republic of the Congo. The interruption of transmission of the gambiense form, targeted by the World Health Organization (WHO) for 2030, will require renewed efforts to tackle a range of expected and unexpected challenges. The rhodesiense form of the disease represents a small part of the overall HAT burden. For this form, the problem of under detection is on the rise and, because of an important animal reservoir, the elimination of disease transmission is not envisioned at this stage.
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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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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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Human African trypanosomiasis (HAT) has been an alarming global public health issue. The disease affects mainly poor and marginalized people in low-resource settings and is caused by two subspecies of haemoflagellate parasite, Trypanosoma brucei and transmitted by tsetse flies. Progress made in HAT ...control during the past decade has prompted increasing global dialogue on its elimination and eradication. The disease is targeted by the World Health Organization (WHO) for elimination as a public health problem by 2020 and to terminate its transmission globally by 2030, along-side other Neglected Tropical Diseases (NTD). Several methods have been used to control tsetse flies and the disease transmitted by them. Old and new tools to control the disease are available with constraints.
Currently, there are no vaccines available. Efforts towards intervention to control the disease over the past decade have seen considerable progress and remarkable success with incidence dropping progressively, reversing the upward trend of reported cases. This gives credence in a real progress in its elimination. This study reviews various control measures, progress and a highlight of control issues, vector and parasite barriers that may have been hindering progress towards its elimination.
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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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The objectives of the meeting were:
1. To step up the commitment of national authorities and technical and financial partners toWHO’s elimination objective for g-HAT.
2. To share achievements, challenges and views on the elimination goal among countries and implementing partners.
3. To assess t...he status of critical technical aspects to be solved in research and development of drugs and diagnostic tools, epidemiology, vector control and animal reservoirs.
4. To define the mechanisms for strengthening and organizing collaboration and coordination among stakeholders.
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In 2012, the World Health Organisation (WHO) set out a roadmap for the control, elimination, or eradication of 17 neglected tropical diseases by 2020. Many were skeptical about the achievability of such goals. Now, still two years away from that end point, good news is emerging for gambiense human A...frican trypanosomiasis (HAT), or sleeping sickness, caused by the tsetse-fly−transmitted protozoan parasite Trypanosoma brucei gambiense in West and Central Africa. The Rhodesiense form of the disease is being pursued under a separate programme.
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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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Background: East African trypanosomiasis is an uncommon, potentially lethal disease if not diagnosed and treated in a timely manner. South Africa, as a centre for emergency medical evacuations from much of sub-Saharan Africa, receives a high proportion of these patients, mostly tourists and expatria...te residents.
Methods: The cases of East African trypanosomiasis patients evacuated to South Africa, for whom diagnostic and clinical management advice was provided over the years 2004–2018, were reviewed, using the authors’ own records and those of collaborating clinicians.
Results: Twenty-one cases were identified. These originated in Zambia, Malawi, Zimbabwe, Tanzania, and Uganda. Nineteen cases (90%) had stage 1 (haemolymphatic) disease; one of these patients had fatal myocarditis. Of the two patients with stage 2 (meningoencephalitic) disease, one died of melarsoprol encephalopathy. Common problems were delayed diagnosis, erroneous assessment of severity, and limited access to treatment.
Conclusions: The key to early diagnosis is recognition of the triad of geographic exposure, tsetse fly bites, and trypanosomal chancre, plus good microscopy. Elements for successful management are rapid access to specific drug treatment, skilled intensive care, and good laboratory facilities. Clinical experience and the local stock of antitrypanosomal drugs from the World Health Organization have improved the chance of a successful outcome in the management of East African trypanosomiasis in South Africa; the survival rate over the period was 90.5%.
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Human African trypanosomiasis (HAT), or sleeping sickness, is an endemic disease in 36 sub-Saharan African countries, typically occurring in underdeveloped areas, where
health systems face significant difficulties of diverse natures.
Human African trypanosomiasis (HAT), also called sleeping sickness, is a parasitic infection that almost invariably progresses to death, unless treatment is provided. HAT caused devastating epidemics during the 20th century. Thanks to sustained and coordinated efforts during the past 15 years the nu...mber of reported cases has fallen to a historic low. Fewer than 3,000 cases were reported in 2015, and the disease is targeted for elimination by the World Health Organization. Despite recent success, HAT still poses a heavy burden on the rural communities where this highly focal disease occurs, most notably in Central Africa. Since patients are also reported from non-endemic countries outside Africa, HAT should be considered in differential diagnosis for all travellers, tourists, migrants and expatriates who have visited or lived in endemic areas. In the absence of a vaccine, disease control relies on case detection and treatment, and vector control. Available drugs are sub-optimal, but ongoing clinical trials give hope for safer and simpler treatments.
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