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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
The mammalian bloodstream form of Trypanosoma brucei undergoes a change from long and slender to a shorter form known as “stumpy” in preparation for transmission back to the tsetse fly vector. Development into this transmissible form is controlled by the parasites themselves, which monitor their density in the blood. In a process very similar to the quorum sensing observed in many bacteria, the slender forms release a signal called stumpy induction factor (SIF). This soluble protein has only recently been characterized. When slender forms are exposed to enough SIF, indicating that the population of parasites in the blood is sufficiently high, the signal to develop into the stumpy form passes a threshold and development proceeds (Figure 3.26). Metazoans too seem to adjust their life cycle in response to such environmental cues. Filarial worms, for instance, increase their production of microfilariae in response to more aggressive host responses.
The Role Of The World Health Organization
Published in F. Y. Liew, Vaccination Strategies of Tropical Diseases, 2017
Sleeping sickness, which is due to infection with the protozoal parasites Trypanosoma brucei gambiense and T. b. rhodiense, occurs in a wide belt of central and west Africa. Control is based on diagnosis and treatment of infection, and on measures to control the tsetse fly vector. Chemotherapy, especially at the stage of advanced cerebral disease, leaves much to be desired. However, there is some prospect of new drugs to replace the inherently toxic organic arsenicals which are currently the only effective therapy at that stage. Vaccination would be a valuable additional method of disease control, especially for the control of epidemics.
Pentamidine
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Pentamidine was originally developed because of its antitrypanosomal activity (King et al., 1937; Lourie and Warrington, 1939). Pentamidine is active against Pneumocystis jirovecii as third-line treatment, and as second-line prophylaxis for P. jirovecii pneumonia (PJP). Pentamidine is also active against Trypanosoma brucei gambiense stage I (hemolymphatic) human African trypanosomiasis (HAT). Pentamidine is a third-line treatment for Leishmania donovani infection (Old World leishmaniasis; kala-azar) and may have a role in secondary prophylaxis in AIDS patients. Pentamidine is active against American tegumentary (cutaneous and mucocutaneous) leishmaniasis (Tuon et al., 2008). Drug repositioning studies that investigate possible new uses for licensed drugs have found that pentamidine has in vitro anticancer effects against renal cell cancer, melanoma, and glioma (Smith et al., 2010; Jung et al., 2011; Qiu et al., 2012; Zerbini et al., 2014; Capoccia et al., 2015). In a Drosophila model, pentamidine reverses splicing defects of myotonic dystrophy and rescues contractility and rhythmicity of myotonic dystrophy heart dysfunction (Warf et al., 2009; Chakraborty et al., 2015).
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.
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].
Comparative in vitro transportation of pentamidine across the blood-brain barrier using polycaprolactone nanoparticles and phosphatidylcholine liposomes
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Geofrey Omarch, Yunus Kippie, Shireen Mentor, Naushaad Ebrahim, David Fisher, Grace Murilla, Hulda Swai, Admire Dube
Human African Trypanosomiasis (HAT) is a fatal vector borne trypanosomal infection characterized by wasting condition in which there is a slow progressive loss of condition accompanied by increasing anaemia and weakness to the point of extreme emaciation, collapse and death often due to heart failure [1,2]. The disease is endemic in 36 countries of Sub-Saharan Africa and impacts about 70 million people [3–5]. Two distinct subspecies of the Trypanosoma brucei are the causative parasites of the disease [6]. Trypanosoma brucei gambiense which is confined to the Central and West Africa causes a chronic infection and Trypanosoma brucei rhodesience which is found in the East and South of Africa causes an acute form of the disease [3].