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The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
The threat of drug resistance is not the only reason to welcome the arrival of new anti-parasitic drugs. As previously discussed, the difficulty of achieving selective toxicity against eukaryotic parasites is an important reason that we have so few safe and effective anti-parasitic drugs to begin with. In certain cases, available drugs carry substantial baggage in the form of side effects or complex treatment regimens. All the drugs currently used to treat the later stages of African trypanosomiasis, for instance, require either injection or intravenous administration, sometimes for as long as 2 weeks. They also cause serious side effects. The problem is almost as grim when considering treatment options for American trypanosomiasis (Chagas disease). Currently, there are only two available drugs, both of which can cause adverse reactions. Nifurtimox can cause symptoms ranging from anorexia to nerve damage. Benznidazole may sometimes cause severe skin inflammation. New treatment options against these and other parasitic diseases have been slow in coming, but at least some new and safer drugs are at least in trials, offering hope that new treatment options may be on the horizon.
Tsetse Flies
Published in Jerome Goddard, Public Health Entomology, 2022
Flies in the genus Glossina are called tsetse flies, which are vectors of several trypanosomes (protozoans) of people and animals. The main disease associated with tsetse flies is human African trypanosomiasis (HAT), caused by subspecies of the protozoan Trypanosoma brucei. A related disease of cattle is called Nagana. Other than the possibility for sleeping sickness transmission, bites by tsetse flies are generally only of minor consequence. However, some individuals may become sensitized to the saliva, leading to welts.
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Published in Anton Sebastian, A Dictionary of the History of Medicine, 2018
Sleeping Sickness Terminal presentation of African trypanosomiasis. The presence of trypanosomes in cerebrospinal fluid of patients affected with it was demonstrated in Uganda by Aldo Castellani (1879–1971) in 1902. See African trypanosomiasis.
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].
Immunotoxins and nanobody-based immunotoxins: review and update
Published in Journal of Drug Targeting, 2021
Mohammad Reza Khirehgesh, Jafar Sharifi, Fatemeh Safari, Bahman Akbari
African protozoan parasite Trypanosoma brucei causes African trypanosomiasis or sleeping sickness. Apolipoprotein L-I (apoL-I) lysis the African trypanosomes except for resistant forms such as Trypanosoma brucei rhodesiense because of expression of a protein known as apoL-I neutralising serum resistance-associated (SRA). Tr-apoL-I, a modified format of apoL-I without the SRA-interacting domain, can overcome this resistance. The cell surface of Trypanosoma brucei rhodesiense is covered by a variant surface glycoprotein (VSG). As a result, many anti-VSG nanobodies are developed. For example, NbAn33, a non-trypanolytic Nb, can access the preserved cryptic epitopes of the VSG. Conjugation of NbAn33 to the Tr-apoL-I led to the generation of recombinant IT (NbAn33–Tr-apoL-I). The IT recognised and lysed the resistant Trypanosoma strains in the in vitro study in a dose-dependent manner. Also, in vivo studies in mouse models showed that the IT leads to complete parasite clearance and did not show any adverse symptoms [155].
Design, synthesis, and antiprotozoal evaluation of new 2,4-bis[(substituted-aminomethyl)phenyl]quinoline, 1,3-bis[(substituted-aminomethyl)phenyl]isoquinoline and 2,4-bis[(substituted-aminomethyl)phenyl]quinazoline derivatives
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Jean Guillon, Anita Cohen, Clotilde Boudot, Alessandra Valle, Vittoria Milano, Rabindra Nath Das, Aurore Guédin, Stéphane Moreau, Luisa Ronga, Solène Savrimoutou, Maxime Demourgues, Elodie Reviriego, Sandra Rubio, Sandie Ferriez, Patrice Agnamey, Cécile Pauc, Serge Moukha, Pascale Dozolme, Sophie Da Nascimento, Pierre Laumaillé, Anne Bouchut, Nadine Azas, Jean-Louis Mergny, Catherine Mullié, Pascal Sonnet, Bertrand Courtioux
Furthermore, another neglected disease caused by Trypanosomatidae parasites of the Trypanosoma genus is the human African trypanosomiasis (HAT), or sleeping sickness, almost invariably fatal unless treated. This infection is transmitted to humans through the bite of an infected tsetse fly. Brain involvement causes various neurological disturbances, including sleep disorders, progression to coma and, ultimately, death. There are two clinical forms: the slowly progressing form (gambiense HAT), caused by infection with Trypanosoma brucei gambiense (currently 98% of cases), and the faster progressing form (rhodesiense HAT), caused by infection with Trypanosoma brucei rhodesiense. As a neglected tropical disease targeted by the WHO for elimination, a historically low number of cases (<1000) was reported in 2018. The recent approval of a new medicine (fexinidazole) for the treatment of gambiense HAT has opened new possibilities for the management of cases and thus led to recent WHO interim guidelines for this treatment27. A veterinary form of this parasitic disease exists. Named Nagana, it is caused by Trypanosoma brucei brucei which contaminates African livestock, thus having a significant economic impact.