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Environments of Health and Disease in Tropical Africa before the Colonial Era
Published in Lori Jones, Disease and the Environment in the Medieval and Early Modern Worlds, 2022
The archive of long-standing colonial efforts to control the tsetse fly in Africa is one of the most obvious ones where such fragments of past African systems of knowledge can be located. Tsetse flies are vectors of parasites responsible for trypanosomiasis (also known as sleeping sickness), a deadly disease that affects both humans and cattle. The disease has a long history in Africa, and its complex epidemiological framework and ecological entanglements make it one of the most interesting case studies of diseased landscapes on the continent. Colonial archives provide a clear case of transfers of long-standing indigenous knowledge about the fly and the disease it causes from vernacular science to colonial institutions.
Unexplained Fever In Patients Returning From The Tropics Including U.F. Associated With Hypereosinophilia
Published in Benedict Isaac, Serge Kernbaum, Michael Burke, Unexplained Fever, 2019
Sleeping sickness is a disease contracted in rural areas or in forest galleries after the bite of a glossina. T. gambiense infection is a purely human disease present in West and Central Africa. T. rhodesiense infection is an anthropozoonosis, present in East Africa.
The Application of Fragment-based Approaches to the Discovery of Drugs for Neglected Tropical Diseases
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Christina Spry, Anthony G. Coyne
Sleeping Sickness, which is also known as Human African trypanosomiasis or HAT, is caused by two subspecies of T. brucei (T. b. gambiense and T. b. rhodesiense) that are transmitted predominantly through the bite of an infected tsetse fly. In the first stage of the disease, parasites multiply in subcutaneous tissues, blood and lymph, before crossing the blood-brain barrier and infecting the central nervous system in the second stage of the disease. Without treatment, sleeping sickness is invariably fatal (WHO 2017). Currently, five drugs, each with undesirable side effects, are available for the treatment of sleeping sickness, and the stage of the disease dictates which should be administered. As for Chagas disease, early treatment provides better prospects for a cure. Unfortunately, the drugs required to treat the second stage of the disease are challenging to administer and/or toxic (and, in some cases, lethal) (WHO 2018c). Hence, although the incidence of sleeping sickness has been declining due to sustained control efforts, and in 2017 there were just 1447 new cases (WHO 2018d), there is a need for safe and effective new drugs.
Metabolomic profile, anti-trypanosomal potential and molecular docking studies of Thunbergia grandifolia
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Heba A. S. El-Nashar, Ahmed M. Sayed, Hany A. M. El-Sherief, Mostafa E. Rateb, Lina Akil, Ibrahim Khadra, Taghreed A. Majrashi, Sara T. Al-Rashood, Faizah A. Binjubair, Mahmoud A. El Hassab, Wagdy M. Eldehna, Usama Ramadan Abdelmohsen, Nada M. Mostafa
Trypanosomiasis or sleeping sickness is a protozoan disease that infects animals and humans transmitted by the bite of Glossina (tsetse) fly carrying Trypanosoma brucei1. Currently, trypanosomiasis affects more than 50 million cattle and 70 million people in sub-Saharan Africa2. The available current medicines record lack of efficiency, resistance, and toxicity, so there is an urgent need for the development of novel, safe, efficacious, cost-effective drugs with new mechanism of action3,4. In African countries where trypanosomiasis is prevalent, natural products (herbal extracts) have traditionally been utilised for centuries and are still extensively used to cure infections and other parasitic diseases5,6. Interestingly, about 30% of the world population has confidence in traditional therapies due to their wide availability and affordability7. Moreover, various drugs like quinine and artemisinin were established as plant-derived potential antiprotozoal agents8.
Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents
Published in Expert Opinion on Therapeutic Patents, 2023
Francesco Melfi, Simone Carradori, Cristina Campestre, Entela Haloci, Alessandra Ammazzalorso, Rossella Grande, Ilaria D’Agostino
Infection is usually divided into two stages: firstly, the haemolymphatic stage and, secondly, the meningoencephalitic phase, which is characterized by the central nervous system (CNS) entry. Chancre at the site of inoculation may proceed with the symptoms of the first stage after being bitten by an infected fly (more commonly with Tbr and sparingly with Tbg despite, in this case, it is observed in travelers from non-endemic countries). Common symptoms/signs for both types of diseases during the first stage can include fatigue, malaise, headache, weakness, pruritis, weight loss, arthralgia, hepatosplenomegaly, and intermittent fevers. In the second stage of the disease, it is clinically relevant to the invasion of the CNS, which causes a variety of neuropsychiatric manifestations (i.e. reversed sleep/wake cycle characterized by nocturnal insomnia and daytime somnolence) but with a less frequent fever, thus conferring the epithet of African sleeping sickness to the disease. Other important and fatal symptoms comprehend mental, motor, sensory, and neurologic alterations. Signs and symptoms of this disease remain nonspecific and variable, hampering clinical diagnosis of the disease.
Anti-trypanosomatid structure-based drug design – lessons learned from targeting the folate pathway
Published in Expert Opinion on Drug Discovery, 2022
Joanna Panecka-Hofman, Ina Poehner, Rebecca C. Wade
Therefore, even in the best-controlled case of sleeping sickness, better treatments, that overcome resistance and have reduced side effects, are needed. Unfortunately, drug design efforts against trypanosomiases are not generally profitable for pharmaceutical companies, since these so-called ‘neglected diseases’ occur mostly in poor regions of the world [21]. However, in recent years, there have been several initiatives to advance drug design against neglected tropical diseases. These include (i) the Drugs for Neglected Diseases initiative (DNDi, https://dndi.org [22]), (ii) the Trypanogen and Trypanogen+ projects funded by AAS/Wellcome under the H3Africa initiative (http://trypanogen.net/ [23]), (iii) two EU-funded projects that focused on targeting specific biochemical pathways of parasites causing the diseases: New Medicines for Trypanosomatidic Infections (NMTrypI [24], https://fp7-nmtrypi.eu/ [25], https://cordis.europa.eu/project/id/603240 [26]) and Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target Neglected Parasitic Diseases (PDE4NPD, https://cordis.europa.eu/project/id/602666 [27]). One of the focuses of the NMTrypI project, in which the authors of the present article participated, was targeting the parasite folate pathways. We here review recent efforts in anti-trypanosomatid structure-based drug design (SBDD) from this perspective.