Background In 2012 human African trypanosomiasis (HAT), also known as sleeping sickness, was targeted for elimination as a public health problem, set to be achieved by 2020. The World Health Organization (WHO) provides here the 2018 update on the progress made toward that objective. Global indicators are reviewed, in particular the number of reported cases and the areas at risk. Recently developed indicators for the validation of HAT elimination at the national level are also presented. Methodology/Principal Findings With 977 cases reported in 2018, down from 2,164 in 2016, the main global indicator of elimination is already well within the 2020 target (i.e. 2,000 cases). Areas at moderate or higher risk (i.e. ≥ 1 case/10,000 people/year) are also steadily shrinking (less than 200,000 km2 in the period 2014–2018), thus nearing the 2020 target [i.e. 90% reduction (638,000 km2) from the 2000–2004 baseline (709,000 km2)]. Health facilities providing diagnosis and treatment of gambiense HAT continued to increase (+7% since the previous survey), with a better coverage of at-risk populations. By contrast, rhodesiense HAT health facilities decreased in number (-10.5%) and coverage. At the national level, eight countries meet the requirements to request validation of gambiense HAT elimination as a public health problem (i.e. Benin, Burkina Faso, Cameroon, Cote d’Ivoire, Ghana, Mali, Rwanda, and Togo), while for other endemic countries more efforts are needed in surveillance, control, or both. Conclusions/Significance The 2020 goal of HAT elimination as a public health problem is within grasp, and eligible countries are encouraged to request validation of their elimination status. Beyond 2020, the HAT community must gear up for the elimination of gambiense HAT transmission (2030 goal), by preparing for both the expected challenges (e.g. funding, coordination, integration of HAT control into regular health systems, development of more adapted tools, cryptic trypanosome reservoirs, etc.) and the unexpected ones.

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Monitoring the elimination of human African trypanosomiasis at continental and country level: Update to 2018.

Background 
Human African trypanosomiasis (HAT) is a neglected tropical disease targeted for elimination ‘as a public health problem’ by 2020 The indicators to monitor progress towards the target are based on the number of reported cases, the related areas and populations exposed at various levels of risk, and the coverage of surveillance activities Based on data provided by the National Sleeping Sickness Control Programmes (NSSCP), Non-Governmental Organizations (NGOs) and research institutions—and assembled in the Atlas of HAT—the World Health Organization (WHO) provides here an update to 2016 for these indicators, as well as an analysis of the epidemiological situation


Results 
Trends for the two primary indicators of elimination are on track for the 2020 goal: 2,164 cases of HAT were reported in 2016 (as compared to the milestone of 4,000 cases), and for the period 2012–2016 280,000 km2 are estimated to be at moderate risk or higher (ie ≥ 1 case/10,000 people/year), as compared to the milestone of 230,000 km2 These figures correspond to reductions of 92% and 61% as compared to the respective baselines (ie 26,550 HAT cases in the year 2000, and 709,000 km2 exposed at various levels of risk for the period 2000–2004) Among the secondary indicators, an overall improvement in the coverage of at risk populations by surveillance activities was observed Regarding passive surveillance, the number of fixed health facilities providing gambiense HAT diagnosis or treatment expanded, with 1,338 enumerated in endemic countries in 2017 (+52% as compared to the survey completed only sixteen months earlier) Concerning rhodesiense HAT, 124 health facilities currently provide diagnosis or treatment The broadening of passive surveillance is occurring in a context of fairly stable intensity of active case finding, with between 18 million and 24 million people screened per year over the period 2012–2016


Discussion 
Elimination of HAT as a public health problem by 2020 seems within reach, as the epidemiological trends observed in previous years are confirmed in this latest 2016 monitoring update However, looking beyond 2020, and in particular to the 2030 goal of elimination of transmission as zero cases for the gambiense form of the disease only, there is no room for complacency Challenges still abound, including ensuring the effective integration of HAT control activities in the health system, sustaining the commitment of donors and HAT endemic countries, and clarifying the extent of the threat posed by cryptic reservoirs (eg human asymptomatic carriers and the possible animal reservoirs in gambiense HAT epidemiology) WHO provides through the network for HAT elimination the essential coordination of the wide range of stakeholders to ensure synergy of efforts

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Monitoring the elimination of human African trypanosomiasis: Update to 2016

African trypanosomes cause lethal and neglected tropical diseases, known as sleeping sickness in humans and nagana in animals Current therapies are limited, but fortunately, promising therapies are in advanced clinical and veterinary development, including acoziborole (AN5568 or SCYX-7158) and AN11736, respectively These benzoxaboroles will likely be key to the World Health Organization’s target of disease control by 2030 Their mode of action was previously unknown We have developed a high-coverage overexpression library and use it here to explore drug mode of action in Trypanosoma brucei Initially, an inhibitor with a known target was used to select for drug resistance and to test massive parallel library screening and genome-wide mapping; this effectively identified the known target and validated the approach Subsequently, the overexpression screening approach was used to identify the target of the benzoxaboroles, Cleavage and Polyadenylation Specificity Factor 3 (CPSF3, Tb92741340) We validated the CPSF3 endonuclease as the target, using independent overexpression strains Knockdown provided genetic validation of CPSF3 as essential, and GFP tagging confirmed the expected nuclear localization Molecular docking and CRISPR-Cas9-based editing demonstrated how acoziborole can specifically block the active site and mRNA processing by parasite, but not host CPSF3 Thus, our findings provide both genetic and chemical validation for CPSF3 as an important drug target in trypanosomes and reveal inhibition of mRNA maturation as the mode of action of the trypanocidal benzoxaboroles Understanding the mechanism of action of benzoxaborole-based therapies can assist development of improved therapies, as well as the prediction and monitoring of resistance, if or when it arises

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Clinical and veterinary trypanocidal benzoxaboroles target CPSF3.

https://discovery.dundee.ac.uk/ws/files/28906117/1_s2.0_S1471492218300679_main.pdf

Melarsoprol Resistance in African Trypanosomiasis.

Salivarian trypanosomes are single cell extracellular parasites that cause infections in a wide range of hosts. Most pathogenic infections worldwide are caused by one of four major species of trypanosomes including (i) Trypanosoma brucei and the human infective subspecies T. b. gambiense and T. b. rhodesiense, (ii) Trypanosoma evansi and T. equiperdum, (iii) Trypanosoma congolense and (iv) Trypanosoma vivax. Infections with these parasites are marked by excessive immune dysfunction and immunopathology, both related to prolonged inflammatory host immune responses. Here we review the classification and global distribution of these parasites, highlight the adaptation of human infective trypanosomes that allow them to survive innate defense molecules unique to man, gorilla, and baboon serum and refer to the discovery of sexual reproduction of trypanosomes in the tsetse vector. With respect to the immunology of mammalian host-parasite interactions, the review highlights recent findings with respect to the B cell destruction capacity of trypanosomes and the role of T cells in the governance of infection control. Understanding infection-associated dysfunction and regulation of both these immune compartments is crucial to explain the continued failures of anti-trypanosome vaccine developments as well as the lack of any field-applicable vaccine based anti-trypanosomosis intervention strategy. Finally, the link between infection-associated inflammation and trypanosomosis induced anemia is covered in the context of both livestock and human infections.

https://biblio.ugent.be/publication/8614888/file/8614889.pdf

Salivarian Trypanosomosis: A Review of Parasites Involved, Their Global Distribution and Their Interaction With the Innate and Adaptive Mammalian Host Immune System.

https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers18-09/010072405.pdf

José-Ramon Franco

Papers

Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination?