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The Parasite's Way of Life
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Another example is provided by sand flies that when infected with Leishmania parasites feed more frequently. Likewise, trypanosome-infected tsetse flies seem to become more active and increase their feeding frequency, increasing the likelihood of transmission. Additionally, it may be no accident that vector-borne parasites such as trypanosomes are often among the most virulent. It has been suggested by some, for instance, that the extreme lethargy of humans infected with trypanosomes is actually a strategy on the part of the parasite; a comatose victim of sleeping sickness is in no condition to shoo away a tsetse fly in search of a meal. If this proposed scenario is in fact the case, enhanced virulence may be viewed as an adaptation to increase the likelihood of transmission. In Chapter 7 the relationship between virulence and transmission will be more fully explored.
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.
Flies (Biting)
Published in Gail Miriam Moraru, Jerome Goddard, The Goddard Guide to Arthropods of Medical Importance, Seventh Edition, 2019
Gail Miriam Moraru, Jerome Goddard
There have been intensive efforts to control tsetse flies with insecticides and traps (Figure 19.29), which have yielded measurable successes (see discussion in Section A about declining case numbers). Tsetse fly bites are generally self-limiting. Antiseptic and soothing lotions may relieve pain and itching. Persons sensitive to tsetse fly bites may require antihistamine and other treatment to control the immune response. People who have been bitten in endemic areas for sleeping sickness should be followed up for development of the disease. Treatment for HAT differs according to the form and phase of the disease. Generally, it is treated with pentamidine, although suramin, eflornithine, nifurtimox, and melarsoprol may also be used. However, melarsoprol may be fatal in 3–10% of patients treated,40,41 and there are other complicating factors with all these drugs. Physicians attempting to treat a patient with HAT should seek the most up-to-date treatment recommendations from the WHO or the Parasitic Drug Service, Centers for Disease Control, Atlanta, GA.
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
Neglected tropical diseases (NTDs) are a group of 20 diverse conditions that are mainly prevalent in tropical areas, where they mostly affect impoverished communities characterized by very precarious hygienic conditions. In fact, studies suggest that the epidemiology of NTDs is often related to environmental conditions. Many NTDs are vector-borne diseases, have animal reservoirs, and are associated with multi-stage life cycles. All these factors make their public health control very challenging. Human African Trypanosomiasis (HAT), also known as the sleeping sickness, is caused by microscopic parasites of the species Trypanosoma brucei. It is transmitted by the tsetse fly (Glossina species), found only in sub-Saharan Africa. Two different subspecies of the parasite cause distinct disease patterns in humans: T. brucei gambiense (Tbg) establishes the slowly progressing African trypanosomiasis in western and central Africa, while T. brucei rhodesiense (Tbr) induces the more acute African trypanosomiasis in eastern and southern Africa [1].
Synthesis, antiproliferative and antitrypanosomal activities, and DNA binding of novel 6-amidino-2-arylbenzothiazoles
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Livio Racané, Valentina Rep, Sandra Kraljević Pavelić, Petra Grbčić, Iva Zonjić, Marijana Radić Stojković, Martin C. Taylor, John M. Kelly, Silvana Raić-Malić
Human African trypanosomiasis (HAT,) or sleeping sickness, is a neglected tropical disease (NTD) caused by Trypanosoma brucei, a protozoan parasite transmitted to humans through the bite of a blood-sucking tsetse fly33,34. The drugs currently used to treat HAT are not effective against all stages and subspecies of the parasite, so further clinical investigation is needed to develop new antitrypanosomal drugs. Some 2-benzylsulfanyl- and 2-arylbenzothiazole derivatives have been found to exhibit good trypanocidal activity at low concentrations35,36. Optimisation of anti-parasite activity, physicochemical parameters and ADME properties afforded the fluoro-substituted benzothiazole, with a 2-cyclopropanecarboxamide at position 2, which displayed promising in vivo efficacy37.