Project Paper to provide an additional grant for: Human Development Systems Strengthening Project (HDSSP)(P145965, H9360)
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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The Transformation Agenda (TA) ushered in an ambitious reform process intended to transform the World Health Organization (WHO) into an organization that is proactive, results-driven, accountable and which meets stakeholder expectations, towards transforming and improving public health services in t...he African Region. It aimed to achieve a WHO that is pro-results, which optimally and creatively targets technical work as well as make operations more responsive, with greater effectiveness in both communications and partnerships. The Africa Region has been the epicentre of the human immunodeficiency virus (HIV) epidemic and it’s one of the leading causes of disease and death on the continent. The WHO, with partners, has worked tirelessly for many years to control the threat and reduce the negative impact of the disease. Since the early 2000s, significant progress has been made in the global fight against the scourge of HIV. However, the WCA subregion was falling concerningly behind ESA on several key indicators of progress. In 2016, the WHO joined UNAIDS, UNICEF and other partners in a call for a strong and urgent response to support WCA countries to develop catch-up plans to triple and fast-track ART coverage, to enable the region to catch up with ESA by the end of 2020. Implementation of a widespread test-and-treat strategy, coupled with the scale-up of differentiated service delivery (DSD) and mobilization of requisite funding, accelerated WCA’s progress towards this goal. The HIV treatment catch-up and fast-track plan has achieved its target of seeing the West and Central African region (WCA) catch up with the Eastern and Southern African region’s (ESA) antiretroviral coverage rate of 78% in 2021, albeit later than the 2020 target time frame. A 33% improvement was achieved in WCA, against 21% in ESA, between 2015–2020. WCA achieved a significant 42% increase, compared to ESA’s 23%, between 2015 and 2021, to see WCA draw level with ESA at 78%. In the Democratic Republic of the Congo (DRC) alone, progress of up to 47% was observed between 2015 and 2020, for example. In addition, 1.6 million more People Living with HIV (PLHIV) were enrolled on antiretroviral treatment (ART) between 2015 and 2020.
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