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.
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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A clear understanding of the knowledge, attitudes and practices (KAP) of a particular community is necessary in order to improve control of human African trypanosomiasis (HAT).New screening and diagnostic tools and strategies were introduced into South Sudan, as part of integrated delivery of primar...y healthcare. Knowledge and awareness on HAT, its new/improved screening and diagnostic tools, the places and processes of getting a confirmatory diagnosis and treatment are crucial to the success of this strategy.
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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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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), 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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This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospita...ls in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included.
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In support of the London Declaration goals, PATH aims to catalyze engagement of the diagnostics industry and product development efforts. As part of this work, PATH conducted a diagnostic landscape analysis to identify gaps and evaluated current and nascent HAT diagnostics that may provide solutions....
We conducted literature reviews and interviews with key stakeholders to identify use cases for HAT diagnostics, understand current practices, and analyze progress toward more robust diagnostics across
different biomarkers.
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This analysis focused on the chronic form of HAT caused by T. b. gambiense, as it contributes to the majority of disease burden. Information from the literature review,
product development landscape, and stakeholder interviews was compiled to:
- Identify use cases and understand current diagnosti...c practices and tools associated with each use case.
- Analyze progress toward robust diagnostics for HAT across different biomarkers.
- Develop recommendations for steps to improve the availability, access, and adoption of HAT diagnostic tools.
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Sleeping sickness is controlled by case detection and treatment but this often only reaches less than 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because of expense. We conducted a full scale field trial of a refined vector control tec...hnology. From preliminary trials we determined the number of insecticidal tiny targets required to control tsetse populations by more than 90%. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda (overall target density 5.7/km2). In 12 months tsetse populations declined by more than 90%. A mathematical model suggested that a 72% reduction in tsetse population is required to stop transmission in those settings. The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this new method of vector control to case detection and treatment is strong. We outline how such a component could be organised.
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Treatment of second-stage gambiense human African trypanosomiasis relied on toxicarsenic-based derivatives for over 50 years. The availability and subsequent use of eflornithine,initially in monotherapy and more recently in combination with nifurtimox (NECT), has drasticallyimproved the pro...gnosis of treated patients. However, NECT logistic and nursing requirementsremain obstacles to its deployment and use in peripheral health structures in rural sub-SaharanAfrica. Two oral compounds, fexinidazole and SCYX-7158, are currently in clinical development.The main scope of this article is to discuss the potential impact of new oral therapies to improvediagnosis-treatment algorithms and patients’access to treatment, and to contribute to reach theobjectives of the recently launched gambiense humanAfrican trypanosomiasis elimination program
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Un comité OMS d’experts sur la trypanosomiase humaine africaine (THA) : lutte et surveillance, s’est réuni à Genève (Suisse), du 22 au 26 avril 2013. Le Dr H. Nakatani, sous-directeur général pour le VIH/SIDA, la tuberculose, le paludisme et les maladies tropicales négligées, a ouvert la... réunion au nom du Dr M. Chan, directeur-général de l’OMS.
La THA est une maladie qui afflige les populations rurales de l’Afrique, là où prolifère la mouche tsé-tsé (ou glossine), vecteur des trypanosomes qui en sont la cause. On distingue deux formes de THA : la forme à T. b. gambiense ou forme gambienne, endémique en Afrique de l’Ouest et en Afrique centrale et qui
représente actuellement 95 % des cas, et la forme à T. b. rhodesiense ou forme rhodésienne, endémique en Afrique de l’Est et en Afrique australe, à laquelle sont dus les 5 % restants.
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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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The objectives of the meeting were:
1. To update the current status of the disease transmission, country capacities and plans for tackling the disease.
2. To understand the epidemiology including disease distribution and risk, the models
for estimating under-detection, the geographical variati...ons of in clinical presentation,
the roles of domestic and wild animal reservoirs and the subsequent different
transmission patterns and control approaches, including vector control.
3. To update current research and development efforts for improving diagnostic and
treatment tools.
4. To define the goals for achieving the control of r-HAT, the need for a multisectoral
approach and to discuss the strategy for controlling r-HAT and the coordination
mechanisms.
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The epidemiology of the disease is mediated by the interaction of the parasite (trypanosome) with the vectors (tsetse flies), as well as with the human and animal hosts within a particular environment. Related to these interactions, the disease is confined in spatially limited areas called “foci..., which are located
in Sub-Saharan Africa, mainly in remote rural areas. The risk of contracting HAT is, therefore, determined by the possibility of contact of a human being with an infected tsetse fly. Epidemics of HAT were described at the beginning of the 20th century; intensive activities have been set up to confront the disease, and it was under control in the 1960s, with fewer than 5,000 cases reported in the whole continent.
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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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FIND and Standard Diagnostics (SD) have developed a lateral flow rapid diagnostic test (RDT) to screen for
T.b. gambiense HAT that is cheap and easy to use. The tests are packed individually and are stable at 40°C for
up to 25 months; they are performed on fresh blood obtained from a finger prick..., and no instrument or electricity is required. The RDT detects host antibodies to infection in populations that are at risk, or in suspect individuals. Positive cases are subjected to further confirmatory methods to identify HAT patients.
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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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The previous report of the WHO Expert Committee on this disease
followed a meeting in 1995. Intensive, coordinated efforts against HAT during
the intervening 18 years have resulted in a decrease in incidence to a point at
which elimination is considered feasible. This report provides informati...on about
new diagnostic approaches, new therapeutic regimens and better understanding
of the distribution of the disease with high-quality mapping. The roles of human
and animal reservoirs and the tsetse fly vectors that transmit the parasites are
emphasized. The new information has formed the basis for an integrated strategy
with which it is hoped that elimination of HAT will be achieved. The report also
contains recommendations on the approaches that will lead to elimination of the
disease.
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A wide spectrum of disease severity has been described for Human African Trypanosomiasis (HAT) due to
Trypanosoma brucei rhodesiense (T.b. rhodesiense), ranging from chronic disease patterns in southern countries of East Africa to an increase in virulence towards the north. However, only limited d...ata on the clinical presentation of T.b. rhodesiense HAT is available. From 2006-2009 we conducted the first clinical trial program (I MPAMEL III) in T.b. rhodesiense endemic areas of
Tanzania and Uganda in accordance with international standards (ICH-GCP). The primary and secondary outcome measures were safety and efficacy of an abridged melarsoprol schedule for treatment of second stage disease. Based on diagnostic findings and clinical examinations at baseline we describe the clinical presentation of T.b. rhodesiense HAT in second stage patients from two distinct geographical settings in East Africa.
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