Key populations brief.
Краткое руководство
Background: Traumatic stress may arise from various incidents often leading to posttraumatic stress disorder (PTSD). The lifetime prevalence of PTSD is estimated at 1% – 2% in Western Europe, 6% – 9% in North America and at just over 10% in countries exposed to long-term
violence. In South Afri...ca, the lifetime prevalence for PTSD in the general population is estimated at 2.3%.
Aim: To examine the prevalence of posttraumatic stress symptomatology and related psychological functioning in a community sample of adolescents.
Setting: Low-socioeconomic communities in KwaZulu-Natal.
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What are the local beliefs and practices around illnesses and death, the transmission of disease and spirituality, which affect decision-making (around health-seeking behaviour, caring for relatives and nature of burials) and can inform effective behaviour change interventions for preventing Ebola i...n Sierra Leone?
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Direct acting antivirals (DAAs) have revolutionized treatment for hepatitis C. Combi-
nations of DAAs can cure infection with HCV in 12 weeks, are highly effective and
have limited side-effects. Affordability of DAAs has improved significantly, but access remains lim-
i...ted. Initially, due to their high prices, affordability of DAAs was limited in high-, middle- and low-
income countries alike. Now there is a divide between those countries where, because of intellectual
property barriers, prices have remained (very) high and other countries where generics are, or can be,
available at much lower prices. The result is a dual market
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Overcoming barriers in low- and middle-income countries
For the first time, this year’s report includes information on hepatitis C diagnostics. With a focus on selected countries with diverse HCV epidemics, the report provides updates on the various dimensions of access to HCV diagnostics and pha...rmaceutical products, including product pricing, the regulatory environment and patent status, which together shape the national hepatitis response in different settings. It highlights key areas for action by ministries of health and other government decision-makers, pharmaceutical manufacturers and technical partners.
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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 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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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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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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The twentieth century ended with human African trypanosomiasis (HAT) epidemics raging across many parts of Africa. Resistance to existing drugs was emerging, and many programs aiming to contain the disease had ground to a halt, given previous success against HAT and the competing priorities associat...ed with other medical crises ravaging the continent. A series of dedicated interventions and the introduction of innovative routes to develop drugs, involving Product Development Partnerships, has led to a dramatic turnaround in the fight against HAT caused by Trypanosoma brucei gambiense. The World Health Organization have been able to optimize the use of existing tools to monitor and intervene in the disease. A promising new oral medication for stage 1 HAT, pafuramidine maleate, ultimately failed due to unforeseen toxicity issues. However, the clinical trials for this compound demonstrated the possibility of conducting such trials in the resource-poor settings of rural Africa.
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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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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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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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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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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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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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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 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 an endemic disease in 36 sub-Saharan African countries, typically occurring in underdeveloped areas, where
health systems face significant difficulties of diverse natures.