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Journal articles on the topic 'Trypanosoma brucei. African trypanosomiasis'

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Published: 4 June 2021

Last updated: 18 February 2022

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1

Magez, Stefan, Joar Esteban Pinto Torres, Seoyeon Oh, and Magdalena Radwanska. "Salivarian Trypanosomes Have Adopted Intricate Host-Pathogen Interaction Mechanisms That Ensure Survival in Plain Sight of the Adaptive Immune System." Pathogens 10, no. 6 (2021): 679. http://dx.doi.org/10.3390/pathogens10060679.

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Salivarian trypanosomes are extracellular parasites affecting humans, livestock and game animals. Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense are human infective sub-species of T. brucei causing human African trypanosomiasis (HAT—sleeping sickness). The related T. b. brucei parasite lacks the resistance to survive in human serum, and only inflicts animal infections. Animal trypanosomiasis (AT) is not restricted to Africa, but is present on all continents. T. congolense and T. vivax are the most widespread pathogenic trypanosomes in sub-Saharan Africa. Through mechanical tra

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Kubata, Bruno Kilunga, Michael Duszenko, Zakayi Kabututu та ін. "Identification of a Novel Prostaglandin F2α Synthase in Trypanosoma brucei". Journal of Experimental Medicine 192, № 9 (2000): 1327–38. http://dx.doi.org/10.1084/jem.192.9.1327.

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Members of the genus Trypanosoma cause African trypanosomiasis in humans and animals in Africa. Infection of mammals by African trypanosomes is characterized by an upregulation of prostaglandin (PG) production in the plasma and cerebrospinal fluid. These metabolites of arachidonic acid (AA) may, in part, be responsible for symptoms such as fever, headache, immunosuppression, deep muscle hyperaesthesia, miscarriage, ovarian dysfunction, sleepiness, and other symptoms observed in patients with chronic African trypanosomiasis. Here, we show that the protozoan parasite T. brucei is involved in PG

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3

Katabazi, Aziz, Adamu Almustapha Aliero, Sarah Gift Witto, Martin Odoki, and Simon Peter Musinguzi. "Prevalence of Trypanosoma congolense and Trypanosoma vivax in Lira District, Uganda." BioMed Research International 2021 (June 14, 2021): 1–7. http://dx.doi.org/10.1155/2021/7284042.

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Trypanosomes are the causative agents of animal African trypanosomiasis (AAT) and human African trypanosomiasis (HAT), the former affecting domestic animals prevalent in Sub-Saharan Africa. The main species causing AAT in cattle are T. congolense, T. vivax, and T. b. brucei. Northern Uganda has been politically unstable with no form of vector control in place. The return of displaced inhabitants led to the restocking of cattle from AAT endemic areas. It was thus important to estimate the burden of trypanosomiasis in the region. This study was designed to compare the prevalence of animal Africa

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Pereira, Glaécia AN, Lucianna H. Santos, Steven C. Wang, et al. "Benzimidazole inhibitors of the major cysteine protease of Trypanosoma brucei." Future Medicinal Chemistry 11, no. 13 (2019): 1537–51. http://dx.doi.org/10.4155/fmc-2018-0523.

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Aim: Limitations in available therapies for trypanosomiases indicate the need for improved medicines. Cysteine proteases cruzain and rhodesain are validated targets for treatment of Chagas disease and human African trypanosomiasis. Previous studies reported a benzimidazole series as potent cruzain inhibitors. Results & methodology: Considering the high similarity between these proteases, we evaluated 40 benzimidazoles against rhodesain. We describe their structure-activity relationships (SAR), revealing trends similar to those observed for cruzain and features that lead to enzyme selectivi

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Nayupe, Symon F. "The use of molecular technology to investigate trypanosome infections in tsetse flies at Liwonde Wild Life Reserve." Malawi Medical Journal 31, no. 4 (2020): 233–37. http://dx.doi.org/10.4314/mmj.v31i4.3.

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BackgroundTrypanosomes are protozoan flagellates that cause human African trypanosomiasis (HAT) and African animal trypanosomiasis (AAT). HAT is caused by Trypanosoma brucei rhodesiense in East and Central Africa and T.b. gambiense in West Africa, whereas AAT is caused by a number of trypanosome species, including T. brucei brucei, T. evansi, T. vivax, T. congolense, T. godfreyi and T. simiae. The aim of this study was to establish if tsetse flies at Liwonde Wild Life Reserve (LWLR) are infected with these trypanosomes and thus pose a risk to both humans and animals within and surrounding the

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Morty, Rory E., Patrick Bulau, Roger Pellé, Sherwin Wilk, and Koji Abe. "Pyroglutamyl peptidase type I from Trypanosoma brucei: a new virulence factor from African trypanosomes that de-blocks regulatory peptides in the plasma of infected hosts." Biochemical Journal 394, no. 3 (2006): 635–45. http://dx.doi.org/10.1042/bj20051593.

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Peptidases of parasitic protozoans are emerging as novel virulence factors and therapeutic targets in parasitic infections. A trypanosome-derived aminopeptidase that exclusively hydrolysed substrates with Glp (pyroglutamic acid) in P1 was purified 9248-fold from the plasma of rats infected with Trypanosoma brucei brucei. The enzyme responsible was cloned from a T. brucei brucei genomic DNA library and identified as type I PGP (pyroglutamyl peptidase), belonging to the C15 family of cysteine peptidases. We showed that PGP is expressed in all life cycle stages of T. brucei brucei and is expresse

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Rao, Srinivasa P. S., Suresh B. Lakshminarayana, Jan Jiricek, et al. "Anti-Trypanosomal Proteasome Inhibitors Cure Hemolymphatic and Meningoencephalic Murine Infection Models of African Trypanosomiasis." Tropical Medicine and Infectious Disease 5, no. 1 (2020): 28. http://dx.doi.org/10.3390/tropicalmed5010028.

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Current anti-trypanosomal therapies suffer from problems of longer treatment duration, toxicity and inadequate efficacy, hence there is a need for safer, more efficacious and ‘easy to use’ oral drugs. Previously, we reported the discovery of the triazolopyrimidine (TP) class as selective kinetoplastid proteasome inhibitors with in vivo efficacy in mouse models of leishmaniasis, Chagas Disease and African trypanosomiasis (HAT). For the treatment of HAT, development compounds need to have excellent penetration to the brain to cure the meningoencephalic stage of the disease. Here we describe deta

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8

Dai, Jennifer. "Resolving Trypanosoma brucei Flagellar Structure by Cryo-Electron Tomography." E3S Web of Conferences 131 (2019): 01012. http://dx.doi.org/10.1051/e3sconf/201913101012.

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Trypanosoma brucei is a unicellular eukaryote that can cause human African trypanosomiasis, which has continued to evolve and spread. The key feature of these parasites is that they have a flagellum consists of a typical 9 + 2 axoneme and a lattice-like paraflagellar rod (PFR). It attached to the cell body and is responsible for cell motility, cytokinesis, and morphogenesis. The present study demonstrates the detailed structure and defines the length of the axoneme and three domains of the paraflagellar rod (PFR) using cryo-electron tomography of Trypanosoma brucei flagella. The performed anal

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Truc, P., and M. Tibayrenc. "Population genetics of Trypanosoma brucei in Central Africa: taxonomic and epidemiological significance." Parasitology 106, no. 2 (1993): 137–49. http://dx.doi.org/10.1017/s003118200007493x.

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SUMMARYIn order to estimate the value of population genetics for both the taxonomy of trypanosomes belonging to the species Trypanosoma brucei and a better understanding of Human African Trypanosomiasis (HAT), we undertook a cellulose acetate electrophoresis isoenzyme study involving 55 stocks isolated from man and animals in Congo, Zaire and Cameroun. Out of the 24 loci surveyed, 15 exhibited variability, which made it possible to delimit 23 zymodemes, divided into 2 groups. The first group equated to the classical subspecies Trypanosoma brucei gambiense, while the second corresponded to the

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Carrington, Mark. "Slippery customers: How African trypanosomes evade mammalian defences." Biochemist 31, no. 4 (2009): 8–11. http://dx.doi.org/10.1042/bio03104008.

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African trypanosomes are excellent parasites and can maintain an infection of a large mammalian host for months or years. In endemic areas, Human African Trypanosomiasis, also called sleeping sickness, has been largely unaffected by the advent of modern medicine, and trypanosomiasis of domestic livestock is a major restraint on productivity in endemic areas and is arguably the major contributor to the institutionalized poverty in much of rural sub-Saharan Africa1,2. A simple way of visualizing the effect of the livestock disease is to compare maps showing the distribution of livestock (www.ilr

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Bakshi, Rahul P., Dongpei Sang, Andrew Morrell, Mark Cushman, and Theresa A. Shapiro. "Activity of Indenoisoquinolines against African Trypanosomes." Antimicrobial Agents and Chemotherapy 53, no. 1 (2008): 123–28. http://dx.doi.org/10.1128/aac.00650-07.

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ABSTRACT African trypanosomiasis (sleeping sickness), caused by protozoan Trypanosoma brucei species, is a debilitating disease that is lethal if untreated. Available drugs are antiquated, toxic, and compromised by emerging resistance. The indenoisoquinolines are a class of noncamptothecin topoisomerase IB poisons that are under development as anticancer agents. We tested a variety of indenoisoquinolines for their ability to kill T. brucei. Indenoisoquinolines proved trypanocidal at submicromolar concentrations in vitro. Structure-activity analysis yielded motifs that enhanced potency, includi

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Morty, Rory E., John D. Lonsdale-Eccles, Reinhardt Mentele, Ennes A. Auerswald, and Theresa H. T. Coetzer. "Trypanosome-Derived Oligopeptidase B Is Released into the Plasma of Infected Rodents, Where It Persists and Retains Full Catalytic Activity." Infection and Immunity 69, no. 4 (2001): 2757–61. http://dx.doi.org/10.1128/iai.69.4.2757-2761.2001.

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ABSTRACT A trypsin-like serine peptidase activity, levels of which correlate with blood parasitemia levels, is present in the plasma of rats acutely infected with Trypanosoma brucei brucei. Antibodies to a trypanosome peptidase with a trypsin-like substrate specificity (oligopeptidase B [OP-Tb]) cross-reacted with a protein in the plasma of trypanosome-infected rats on a Western blot. These antibodies also abolished 80% of the activity in the plasma of trypanosome-infected rats, suggesting that the activity may be attributable to a parasite-derived peptidase. We purified the enzyme responsible

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Bacchi, C. J., K. Sanabria, A. J. Spiess, et al. "In vivo efficacies of 5'-methylthioadenosine analogs as trypanocides." Antimicrobial Agents and Chemotherapy 41, no. 10 (1997): 2108–12. http://dx.doi.org/10.1128/aac.41.10.2108.

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5'-Deoxy-5'-(methylthio)adenosine (MTA), a key by-product of polyamine biosynthesis, is cleaved by MTA phosphorylase and is salvaged as adenine and, through conversion of the ribose moiety, methionine. An analog of MTA, 5'-deoxy-5'-(hydroxyethylthio)adenosine (HETA), is a substrate for trypanosome MTA phosphorylase and is active in vitro and in vivo against Trypanosoma brucei brucei, an agent of bovine trypanosomiasis. In this study, HETA and three O-acylated HETA derivatives were examined for their activities against model infections of T. b. brucei and Trypanosoma brucei rhodesiense, the age

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Parwan, Deepika, Ranjan Kumar, and Sumit Aggrawal. "African Trypanosomiasis in Young Female in North India - A Rare Case Report." Annals of Pathology and Laboratory Medicine 8, no. 4 (2021): C71–73. http://dx.doi.org/10.21276/apalm.2997.

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Human African trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease. It is caused by infection with protozoan parasites belonging to the genus Trypanosoma. They are transmitted to humans by tsetse fly (Glossina genus) bites which have acquired their infection from human beings or from animals harboring human pathogenic parasites. Tsetse flies are found just in sub-Saharan Africa though only certain species transmit the disease. We report a case of human African trypanosomiasis in a 28-year-old Indian female who had a travel history to sub–Saharan Africa, Uganda

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15

Masocha, Willias, Martin E. Rottenberg, and Krister Kristensson. "Minocycline Impedes African Trypanosome Invasion of the Brain in a Murine Model." Antimicrobial Agents and Chemotherapy 50, no. 5 (2006): 1798–804. http://dx.doi.org/10.1128/aac.50.5.1798-1804.2006.

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ABSTRACT Passage of Trypanosoma brucei across the blood-brain barrier (BBB) is a hallmark of late-stage human African trypanosomiasis. In the present study we found that daily administration of minocycline, a tetracycline antibiotic, impedes the penetration of leukocytes and trypanosomes into the brain parenchyma of T. brucei brucei-infected C57BL/6 mice. The trypanosome-induced astrocytic and microglial reactions were reduced in the minocycline-treated mice, as were the levels in the brain of transcripts encoding adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and endothelial-le

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Marsela, Megasari, Kyoko Hayashida, Ryo Nakao, et al. "Molecular identification of trypanosomes in cattle in Malawi using PCR methods and nanopore sequencing: epidemiological implications for the control of human and animal trypanosomiases." Parasite 27 (2020): 46. http://dx.doi.org/10.1051/parasite/2020043.

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This study aimed to identify trypanosomes infecting cattle in Malawi in order to understand the importance of cattle in the transmission dynamics of Human African Trypanosomiasis (HAT) and Animal African Trypanosomosis (AAT). A total of 446 DNA samples from cattle blood from three regions of Malawi were screened for African trypanosomes by ITS1 PCR. The obtained amplicons were sequenced using a portable next-generation sequencer, MinION, for validation. Comparison of the results from ITS1 PCR and MinION sequencing showed that combining the two methods provided more accurate species identificat

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Keck, Devin, Callie Stuart, Josie Duncan, Emily Gullette, and Rodrigo Martinez-Duarte. "Highly Localized Enrichment of Trypanosoma brucei Parasites Using Dielectrophoresis." Micromachines 11, no. 6 (2020): 625. http://dx.doi.org/10.3390/mi11060625.

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Human African trypanosomiasis (HAT), also known as sleeping sickness, is a vector-borne neglected tropical disease endemic to rural sub-Saharan Africa. Current methods of early detection in the affected rural communities generally begin with general screening using the card agglutination test for trypanosomiasis (CATT), a serological test. However, the gold standard for confirmation of trypanosomiasis remains the direct observation of the causative parasite, Trypanosoma brucei. Here, we present the use of dielectrophoresis (DEP) to enrich T. brucei parasites in specific locations to facilitate

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Le, Thanh, Claire Beaufay, Duc Nghiem, Tuan Pham, Marie-Paule Mingeot-Leclercq, and Joëlle Quetin-Leclercq. "Evaluation of the Anti-Trypanosomal Activity of Vietnamese Essential Oils, with Emphasis on Curcuma longa L. and Its Components." Molecules 24, no. 6 (2019): 1158. http://dx.doi.org/10.3390/molecules24061158.

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Human African trypanosomiasis (HAT), known as sleeping sickness and caused by Trypanosoma brucei, is threatening low-income populations in sub-Saharan African countries with 61 million people at risk of infection. In order to discover new natural products against HAT, thirty-seven Vietnamese essential oils (EOs) were screened for their activity in vitro on Trypanosoma brucei brucei (Tbb) and cytotoxicity on mammalian cells (WI38, J774). Based on the selectivity indices (SIs), the more active and selective EOs were analyzed by gas chromatography. The anti-trypanosomal activity and cytotoxicity

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Braakman, Hilde M. H., Fred J. J. M. van de Molengraft, Wim W. A. Hubert, and Dolf H. Boerman. "Lethal African trypanosomiasis in a traveler: MRI and neuropathology." Neurology 66, no. 7 (2006): 1094–96. http://dx.doi.org/10.1212/01.wnl.0000209306.41647.13.

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The authors report a case of human African trypanosomiasis with CNS involvement caused by Trypanosoma brucei rhodesiense in a 52-year-old woman, which relapsed after melarsoprol treatment. After a second regimen, she developed a severe toxic polyneuropathy, progressing to coma and eventually death. MRI revealed rapidly progressive multiple white matter lesions as well as damage of the central gray matter and cortex. The autopsy results confirmed the diagnosis of human African trypanosomiasis.

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Patham, Bhargavi, Josh Duffy, Ariel Lane, et al. "Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities." Biochemical Journal 419, no. 2 (2009): 507–17. http://dx.doi.org/10.1042/bj20081787.

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HAT (human African trypanosomiasis), caused by the protozoan parasite Trypanosoma brucei, is an emerging disease for which new drugs are needed. Expression of plasma membrane proteins [e.g. VSG (variant surface glycoprotein)] is crucial for the establishment and maintenance of an infection by T. brucei. Transport of a majority of proteins to the plasma membrane involves their translocation into the ER (endoplasmic reticulum). Thus inhibition of protein import into the ER of T. brucei would be a logical target for discovery of lead compounds against trypanosomes. We have developed a TbRM (T. br

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Dias-Guerreiro, Tatiana, Joana Palma-Marques, Patrícia Mourata-Gonçalves, et al. "African Trypanosomiasis: Extracellular Vesicles Shed by Trypanosoma brucei brucei Manipulate Host Mononuclear Cells." Biomedicines 9, no. 8 (2021): 1056. http://dx.doi.org/10.3390/biomedicines9081056.

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African trypanosomiasis or sleeping sickness is a zoonotic disease caused by Trypanosoma brucei, a protozoan parasite transmitted by Glossina spp. (tsetse fly). Parasite introduction into mammal hosts triggers a succession of events, involving both innate and adaptive immunity. Macrophages (MΦ) have a key role in innate defence since they are antigen-presenting cells and have a microbicidal function essential for trypanosome clearance. Adaptive immune defence is carried out by lymphocytes, especially by T cells that promote an integrated immune response. Like mammal cells, T. b. brucei parasit

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Matovu, Enock, Claire Mack Mugasa, Peter Waiswa, Annah Kitibwa, Alex Boobo, and Joseph Mathu Ndung’u. "Haemoparasitic Infections in Cattle from a Trypanosoma brucei Rhodesiense Sleeping Sickness Endemic District of Eastern Uganda." Tropical Medicine and Infectious Disease 5, no. 1 (2020): 24. http://dx.doi.org/10.3390/tropicalmed5010024.

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We carried out a baseline survey of cattle in Kaberamaido district, in the context of controlling the domestic animal reservoir of Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) towards elimination. Cattle blood was subjected to capillary tube centrifugation followed by measurement of the packed cell volume (PCV) and examination of the buffy coat area for motile trypanosomes. Trypanosomes were detected in 561 (21.4%) out of 2621 cattle screened by microscopy. These 561 in addition to 724 apparently trypanosome negative samples with low PCVs (≤25%) were transported to the l

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Lu, Jun, Suman K. Vodnala, Anna-Lena Gustavsson, et al. "Ebsulfur Is a Benzisothiazolone Cytocidal Inhibitor Targeting the Trypanothione Reductase of Trypanosoma brucei." Journal of Biological Chemistry 288, no. 38 (2013): 27456–68. http://dx.doi.org/10.1074/jbc.m113.495101.

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Trypanosoma brucei is the causing agent of African trypanosomiasis. These parasites possess a unique thiol redox system required for DNA synthesis and defense against oxidative stress. It includes trypanothione and trypanothione reductase (TryR) instead of the thioredoxin and glutaredoxin systems of mammalian hosts. Here, we show that the benzisothiazolone compound ebsulfur (EbS), a sulfur analogue of ebselen, is a potent inhibitor of T. brucei growth with a favorable selectivity index over mammalian cells. EbS inhibited the TryR activity and decreased non-protein thiol levels in cultured para

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Dofuor, Aboagye Kwarteng, Georgina Isabella Djameh, Frederick Ayertey, et al. "Antitrypanosomal Effects of Zanthoxylum zanthoxyloides (Lam.) Zepern. & Timler Extracts on African Trypanosomes." Evidence-Based Complementary and Alternative Medicine 2019 (July 4, 2019): 1–14. http://dx.doi.org/10.1155/2019/1730452.

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African trypanosomiasis is a disease caused by the parasitic protozoa of the Trypanosoma genus. Despite several efforts at chemotherapeutic interventions, the disease poses serious health and economic concerns to humans and livestock of many sub-Saharan African countries. Zanthoxylum zanthoxyloides (Lam.) Zepern. & Timler (Z. zanthoxyloides LZT) is a plant species of important phytochemical and pharmacological relevance in the subtropical zones of the African continent. However, the mechanisms of its antitrypanosomal effects in African trypanosomes remain to be elucidated. The aim of the s

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Boniface, Pone Kamdem, and Ferreira Igne Elizabeth. "Flavonoid-derived Privileged Scaffolds in anti-Trypanosoma brucei Drug Discovery." Current Drug Targets 20, no. 12 (2019): 1295–314. http://dx.doi.org/10.2174/1389450120666190618114857.

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Objective: Human African Trypanosomiasis (HAT), also known as sleeping sickness is one of the 20 neglected tropical diseases listed by the World Health Organization, which lead to death if left untreated. This disease is caused by Trypanosoma brucei gambiense, which is the chronic form of the disease present in western and central Africa, and by T. brucei rhodesiense, which is the acute form of the disease located in eastern and southern Africa. Many reports have highlighted the effectiveness of flavonoid-based compounds against T. brucei. Methods: A literature search was conducted for natural

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Coley, April F., Heidi C. Dodson, Meredith T. Morris, and James C. Morris. "Glycolysis in the African Trypanosome: Targeting Enzymes and Their Subcellular Compartments for Therapeutic Development." Molecular Biology International 2011 (April 11, 2011): 1–10. http://dx.doi.org/10.4061/2011/123702.

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Subspecies of the African trypanosome, Trypanosoma brucei, which cause human African trypanosomiasis, are transmitted by the tsetse fly, with transmission-essential lifecycle stages occurring in both the insect vector and human host. During infection of the human host, the parasite is limited to using glycolysis of host sugar for ATP production. This dependence on glucose breakdown presents a series of targets for potential therapeutic development, many of which have been explored and validated as therapeutic targets experimentally. These include enzymes directly involved in glucose metabolism

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Dofuor, Kwain, Osei, et al. "N-(Isobutyl)-3,4-methylenedioxy Cinnamoyl Amide." Molbank 2019, no. 3 (2019): M1070. http://dx.doi.org/10.3390/m1070.

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The plant Zanthoxylum zanthoxyloides (Lam.) Zepern. & Timler is one of the most important medicinal species of the genus Zanthoxylum on the African continent. It is used in the treatment and management of parasitic diseases in sub-Saharan Africa. These properties have inspired scientists to investigate species within the genus for bioactive compounds. However, a study, which details a spectroscopic, spectrometric and bioactivity guided extraction and isolation of antiparasitic compounds from the genus Zanthoxylum is currently non-existent. Tortozanthoxylamide (1), which is a derivative of

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Michel-Todó, Lucas, Pascal Bigey, Pedro A. Reche, María-Jesus Pinazo, Joaquim Gascón, and Julio Alonso-Padilla. "Design of an Epitope-Based Vaccine Ensemble for Animal Trypanosomiasis by Computational Methods." Vaccines 8, no. 1 (2020): 130. http://dx.doi.org/10.3390/vaccines8010130.

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African animal trypanosomiasis is caused by vector-transmitted parasites of the genus Trypanosoma. T. congolense and T. brucei brucei are predominant in Africa; T. evansi and T. vivax in America and Asia. They have in common an extracellular lifestyle and livestock tropism, which provokes huge economic losses in regions where vectors are endemic. There are licensed drugs to treat the infections, but adherence to treatment is poor and appearance of resistances common. Therefore, the availability of a prophylactic vaccine would represent a major breakthrough towards the management and control of

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Faria, Joana, Carolina B. Moraes, Rita Song, et al. "Drug Discovery for Human African Trypanosomiasis." Journal of Biomolecular Screening 20, no. 1 (2014): 70–81. http://dx.doi.org/10.1177/1087057114556236.

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Human African trypanosomiasis (HAT) is a vector-transmitted tropical disease caused by the protozoan parasite Trypanosoma brucei. High-throughput screening (HTS) of small-molecule libraries in whole-cell assays is one of the most frequently used approaches in drug discovery for infectious diseases. To aid in drug discovery efforts for HAT, the SYBR Green assay was developed for T. brucei in a 384-well format. This semi-automated assay is cost- and time-effective, robust, and reproducible. The SYBR Green assay was compared to the resazurin assay by screening a library of 4000 putative kinase in

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Graça, Nuno A. G., Luis Gaspar, David M. Costa, et al. "Activity of Bisnaphthalimidopropyl Derivatives against Trypanosoma brucei." Antimicrobial Agents and Chemotherapy 60, no. 4 (2016): 2532–36. http://dx.doi.org/10.1128/aac.02490-15.

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ABSTRACTCurrent treatments for African trypanosomiasis are either toxic, costly, difficult to administer, or prone to elicit resistance. This study evaluated the activity of bisnaphthalimidopropyl (BNIP) derivatives againstTrypanosoma brucei. BNIPDiaminobutane (BNIPDabut), the most active of these compounds, showedin vitroinhibition in the single-unit nanomolar range, similar to the activity in the reference drug pentamidine, and presented low toxicity and adequate metabolic stability. Additionally, using a murine model of acute infection and live imaging, a significant decrease in parasite lo

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Dubois, Melissa E., Karen P. Demick, and John M. Mansfield. "Trypanosomes Expressing a Mosaic Variant Surface Glycoprotein Coat Escape Early Detection by the Immune System." Infection and Immunity 73, no. 5 (2005): 2690–97. http://dx.doi.org/10.1128/iai.73.5.2690-2697.2005.

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ABSTRACT Host resistance to African trypanosomiasis is partially dependent on an early and strong T-independent B-cell response against the variant surface glycoprotein (VSG) coat expressed by trypanosomes. The repetitive array of surface epitopes displayed by a monotypic surface coat, in which identical VSG molecules are closely packed together in a uniform architectural display, cross-links cognate B-cell receptors and initiates T-independent B-cell activation events. However, this repetitive array of identical VSG epitopes is altered during the process of antigenic variation, when former an

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Werbovetz, Karl A., Edward S. Riccio, Anna Furimsky, et al. "Evaluation of Antitrypanosomal Dihydroquinolines for Hepatotoxicity, Mutagenicity, and Methemoglobin Formation In Vitro." International Journal of Toxicology 33, no. 4 (2014): 282–87. http://dx.doi.org/10.1177/1091581814533971.

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N1-Benzylated dihydroquinolin-6-ols and their corresponding esters display exceptional activity against African trypanosomes in vitro, and administration of members of this class of compounds to trypanosome-infected mice results in cures in a first-stage African trypanosomiasis model. Since a quinone imine intermediate has been implicated in the antiparasitic mechanism of action of these compounds, evaluation of the hepatotoxic, mutagenic, and methemoglobin-promoting effects of these agents was performed. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-benzyl-1,2-dihydro-

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Kwofie, Kofi D., Nguyen Huu Tung, Mitsuko Suzuki-Ohashi, et al. "Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth." Antimicrobial Agents and Chemotherapy 60, no. 6 (2016): 3283–90. http://dx.doi.org/10.1128/aac.01916-15.

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Trypanosoma bruceiparasites are kinetoplastid protozoa that devastate the health and economic well-being of millions of people in Africa through the disease human African trypanosomiasis (HAT). New chemotherapy has been eagerly awaited due to severe side effects and the drug resistance issues plaguing current drugs. Recently, there has been an emphasis on the use of medicinal plants worldwide.Morinda lucidaBenth. is a popular medicinal plant widely distributed in Africa, and several research groups have reported on the antiprotozoal activities of this plant. In this study, we identified three

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Dickie, Emily A., Simon A. Young, and Terry K. Smith. "Substrate specificity of the neutral sphingomyelinase from Trypanosoma brucei." Parasitology 146, no. 5 (2018): 604–16. http://dx.doi.org/10.1017/s0031182018001853.

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AbstractThe kinetoplastid parasite Trypanosoma brucei causes African trypanosomiasis in both humans and animals. Infections place a significant health and economic burden on developing nations in sub-Saharan Africa, but few effective anti-parasitic treatments are currently available. Hence, there is an urgent need to identify new leads for drug development. The T. brucei neutral sphingomyelinase (TbnSMase) was previously established as essential to parasite survival, consequently being identified as a potential drug target. This enzyme may catalyse the single route to sphingolipid catabolism o

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Lundkvist, Gabriella B., Krister Kristensson, and Marina Bentivoglio. "Why Trypanosomes Cause Sleeping Sickness." Physiology 19, no. 4 (2004): 198–206. http://dx.doi.org/10.1152/physiol.00006.2004.

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African trypanosomiasis or sleeping sickness is hallmarked by sleep and wakefulness disturbances. In contrast to other infections, there is no hypersomnia, but the sleep pattern is fragmented. This overview discusses that the causative agents, the parasites Trypanosoma brucei, target circumventricular organs in the brain, causing inflammatory responses in hypothalamic structures that may lead to dysfunctions in the circadian-timing and sleep-regulatory systems.

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Ojo, Kayode K., J. Robert Gillespie, Aaron J. Riechers, et al. "Glycogen Synthase Kinase 3 Is a Potential Drug Target for African Trypanosomiasis Therapy." Antimicrobial Agents and Chemotherapy 52, no. 10 (2008): 3710–17. http://dx.doi.org/10.1128/aac.00364-08.

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ABSTRACT Development of a safe, effective, and inexpensive therapy for African trypanosomiasis is an urgent priority. In this study, we evaluated the validity of Trypanosoma brucei glycogen synthase kinase 3 (GSK-3) as a potential drug target. Interference with the RNA of either of two GSK-3 homologues in bloodstream-form T. brucei parasites led to growth arrest and altered parasite morphology, demonstrating their requirement for cell survival. Since the growth arrest after RNA interference appeared to be more profound for T. brucei GSK-3 “short” (Tb10.161.3140) than for T. brucei GSK-3 “long”

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Ngay, Lukusa, Veerle Lejon, and Mumba Ngoyi. "PO 8421 LITERATURE REVIEW OF BIOMARKERS FOR HUMAN AFRICAN TRYPANOSOMIASIS POST-TREATMENT FOLLOW-UP." BMJ Global Health 4, Suppl 3 (2019): A35.3—A36. http://dx.doi.org/10.1136/bmjgh-2019-edc.92.

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IntroductionHuman African trypanosomiasis (HAT) is caused by Trypanosoma brucei gambiense and rhodesiense and is transmitted to humans by tsetse flies in sub-Saharan Africa. To detect cure or treatment failure, patients are followed up after treatment integrating the use of biomarkers in blood or cerebrospinal fluid (CSF).MethodsA systematic review of the literature according to the PRISMA Statement for Reporting Systematic Reviews was done, focusing on biological markers for HAT post-treatment follow-up. Articles were retrieved from PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) by using keywo

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Untucht, Christopher, Janine Rasch, Elena Fuchs, Manfred Rohde, Simone Bergmann, and Michael Steinert. "An optimized in vitro blood–brain barrier model reveals bidirectional transmigration of African trypanosome strains." Microbiology 157, no. 10 (2011): 2933–41. http://dx.doi.org/10.1099/mic.0.049106-0.

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The transmigration of African trypanosomes across the human blood–brain barrier (BBB) is the critical step during the course of human African trypanosomiasis. The parasites Trypanosoma brucei gambiense and T. b. rhodesiense are transmitted to humans during the bite of tsetse flies. Trypanosomes multiply within the bloodstream and finally invade the central nervous system (CNS), which leads to the death of untreated patients. This project focused on the mechanisms of trypanosomal traversal across the BBB. In order to establish a suitable in vitro BBB model for parasite transmigration, different

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Steketee, Pieter C., Emily A. Dickie, James Iremonger, et al. "Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition." PLOS Pathogens 17, no. 7 (2021): e1009734. http://dx.doi.org/10.1371/journal.ppat.1009734.

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Animal African Trypanosomiasis (AAT) is a debilitating livestock disease prevalent across sub-Saharan Africa, a main cause of which is the protozoan parasite Trypanosoma congolense. In comparison to the well-studied T. brucei, there is a major paucity of knowledge regarding the biology of T. congolense. Here, we use a combination of omics technologies and novel genetic tools to characterise core metabolism in T. congolense mammalian-infective bloodstream-form parasites, and test whether metabolic differences compared to T. brucei impact upon sensitivity to metabolic inhibition. Like the bloods

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Mulenga, Gloria M., Boniface Namangala, Kalinga Chilongo, et al. "Challenges in the Diagnostic Performance of Parasitological and Molecular Tests in the Surveillance of African Trypanosomiasis in Eastern Zambia." Tropical Medicine and Infectious Disease 6, no. 2 (2021): 68. http://dx.doi.org/10.3390/tropicalmed6020068.

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African animal trypanosomiasis (AAT) control programs rely on active case detection through the screening of animals reared in disease endemic areas. This study compared the application of the polymerase chain reaction (PCR) and microscopy in the detection of trypanosomes in cattle blood in Mambwe, a rural district in eastern Zambia. Blood samples were collected from 227 cattle and tested for infection with trypanosomes using microscopy and Ribosomal RNA Internal Transcribed Spacers (ITS)-PCR. Microscopy on the buffy coat detected 17 cases, whilst thin and thick smears detected 26 cases and 28

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Kimuda, Magambo Phillip, Dustin Laming, Heinrich C. Hoppe, and Özlem Tastan Bishop. "Identification of Novel Potential Inhibitors of Pteridine Reductase 1 in Trypanosoma brucei via Computational Structure-Based Approaches and in Vitro Inhibition Assays." Molecules 24, no. 1 (2019): 142. http://dx.doi.org/10.3390/molecules24010142.

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Pteridine reductase 1 (PTR1) is a trypanosomatid multifunctional enzyme that provides a mechanism for escape of dihydrofolate reductase (DHFR) inhibition. This is because PTR1 can reduce pterins and folates. Trypanosomes require folates and pterins for survival and are unable to synthesize them de novo. Currently there are no anti-folate based Human African Trypanosomiasis (HAT) chemotherapeutics in use. Thus, successful dual inhibition of Trypanosoma brucei dihydrofolate reductase (TbDHFR) and Trypanosoma brucei pteridine reductase 1 (TbPTR1) has implications in the exploitation of anti-folat

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Subramanya, Sandesh, C. Frank Hardin, Dietmar Steverding, and Kojo Mensa-Wilmot. "Glycosylphosphatidylinositol-specific phospholipase C regulates transferrin endocytosis in the African trypanosome." Biochemical Journal 417, no. 3 (2009): 685–94. http://dx.doi.org/10.1042/bj20080167.

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GPI-PLC (glycosylphosphatidylinositol-specific phospholipase C) is expressed in bloodstream-form Trypanosoma brucei, a protozoan that causes human African trypanosomiasis. Loss of genes encoding GPI-PLC reduces the virulence of a pleomorphic strain of the parasite, for reasons that are not clear. In the present paper, we report that GPI-PLC stimulates endocytosis of transferrin by 300–500%. Surprisingly, GPI-PLC is not detected at endosomes, suggesting that the enzyme does not interact directly with the endosomal machinery. We therefore hypothesized that a diffusible product of the GPI-PLC enz

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Andreassend, Sarah K., Stephen J. Bentley, Gregory L. Blatch, Aileen Boshoff, and Robert A. Keyzers. "Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products." Marine Drugs 18, no. 2 (2020): 81. http://dx.doi.org/10.3390/md18020081.

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The Trypanosoma brucei Hsp70/J-protein machinery plays an essential role in survival, differentiation, and pathogenesis of the protozoan parasite, and is an emerging target against African Trypanosomiasis. This study evaluated a set of small molecules, inspired by the malonganenones and nuttingins, as modulators of the chaperone activity of the cytosolic heat inducible T. brucei Hsp70 and constitutive TbHsp70.4 proteins. The compounds were assessed for cytotoxicity on both the bloodstream form of T. b. brucei parasites and a mammalian cell line. The compounds were then investigated for their m

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Namyanja, Monica, Zhi-Shen Xu, Claire Mack Mugasa, et al. "Preliminary evaluation of a Trypanosoma brucei FG-GAP repeat containing protein of mitochondrial localization." AAS Open Research 2 (November 19, 2019): 165. http://dx.doi.org/10.12688/aasopenres.12986.1.

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Background: Trypanosoma brucei, a causative agent of African Trypanosomiasis, is known to cross the blood brain barrier during the second stage of the disease. It was previously suggested that this parasite crosses the blood brain barrier in a manner similar to that of lymphocytes. This would imply that trypanosomes possess integrins that are required to interact with adhesion molecules located on the blood brain barrier microvascular endothelial cells, as a first step in traversal. To date, no T. brucei integrin has been described. However, one T. brucei putative FG-GAP repeat containing prot

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Harris, Tajie H., Nicole M. Cooney, John M. Mansfield, and Donna M. Paulnock. "Signal Transduction, Gene Transcription, and Cytokine Production Triggered in Macrophages by Exposure to Trypanosome DNA." Infection and Immunity 74, no. 8 (2006): 4530–37. http://dx.doi.org/10.1128/iai.01938-05.

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ABSTRACT Activation of a type I cytokine response is important for early resistance to infection with Trypanosoma brucei rhodesiense, the extracellular protozoan parasite that causes African sleeping sickness. The work presented here demonstrates that trypanosome DNA activates macrophages to produce factors that may contribute to this response. Initial results demonstrated that T. brucei rhodesiense DNA was present in the plasma of C57BL/6 and C57BL/6-scid mice following infection. Subsequently, the effect of trypanosome DNA on macrophages was investigated; parasite DNA was found to be less st

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NYAKUNDI, J. N., B. CRAWLEY, R. A. SMITH, and V. W. PENTREATH. "The relationships between intestinal damage and circulating endotoxins in experimental Trypanosoma brucei brucei infections." Parasitology 124, no. 6 (2002): 589–95. http://dx.doi.org/10.1017/s0031182002001701.

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The involvement of intestinal damage in experimental African trypanosomiasis was investigated in rats infected with Trypanosoma brucei brucei by measuring the urinary excretion of the previously administered non-metabolizable sugar probes, D-mannitol and lactulose, and the flux of FITC-dextran across isolated, everted gut segments. There was increased urinary recovery and flux of the sugar probes across the intestine which were significant (P<0·05) and maximum at day 21 of the infection, but subsequently reduced, in the terminal stages of infection (day 33 p.i.). In the case of the everted

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Moreno, Cláudia, Adriana Temporão, Taffarel Torres, and Marcelo Sousa Silva. "Trypanosoma brucei Interaction with Host: Mechanism of VSG Release as Target for Drug Discovery for African Trypanosomiasis." International Journal of Molecular Sciences 20, no. 6 (2019): 1484. http://dx.doi.org/10.3390/ijms20061484.

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The protozoan Trypanosoma brucei, responsible for animal and human trypanosomiasis, has a family of major surface proteases (MSPs) and phospholipase-C (PLC), both involved in some mechanisms of virulence during mammalian infections. During parasitism in the mammalian host, this protozoan is exclusively extracellular and presents a robust mechanism of antigenic variation that allows the persistence of infection. There has been incredible progress in our understanding of how variable surface glycoproteins (VSGs) are organised and expressed, and how expression is switched, particularly through re

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Pereira, Claudio A., León A. Bouvier, María de los Milagros Cámara, and Mariana R. Miranda. "Singular Features of Trypanosomatids' Phosphotransferases Involved in Cell Energy Management." Enzyme Research 2011 (April 4, 2011): 1–12. http://dx.doi.org/10.4061/2011/576483.

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Trypanosomatids are responsible for economically important veterinary affections and severe human diseases. In Africa, Trypanosoma brucei causes sleeping sickness or African trypanosomiasis, while in America, Trypanosoma cruzi is the etiological agent of Chagas disease. These parasites have complex life cycles which involve a wide variety of environments with very different compositions, physicochemical properties, and availability of metabolites. As the environment changes there is a need to maintain the nucleoside homeostasis, requiring a quick and regulated response. Most of the enzymes req

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Lejon, Veerle, Jo Robays, François Xavier N'Siesi, et al. "Treatment Failure Related to Intrathecal Immunoglobulin M (IgM) Synthesis, Cerebrospinal Fluid IgM, and Interleukin-10 in Patients with Hemolymphatic-Stage Sleeping Sickness." Clinical and Vaccine Immunology 14, no. 6 (2007): 732–37. http://dx.doi.org/10.1128/cvi.00103-07.

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ABSTRACT Human African trypanosomiasis treatment is stage dependent, but the tests used for staging are controversial. Central nervous system involvement and its relationship with suramin treatment failure were assessed in 60 patients with parasitologically confirmed hemolymphatic-stage Trypanosoma brucei gambiense infection (white blood cell count of ≤5/μl and no trypanosomes in the cerebrospinal fluid [CSF]). The prognostic value of CSF interleukin-10, immunoglobulin M (IgM; as determined by nephelometry and the point-of-care LATEX/IgM test), total protein, and trypanosome-specific antibody

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Chechet, G. D., J. Yahaya, and A. J. Nok. "In vitro and in vivo anti-trypanosomal potentials of Afrormosia laxiflora and Khaya senegalensis against Trypanosoma brucei brucei." Nigerian Veterinary Journal 39, no. 3 (2018): 269–84. http://dx.doi.org/10.4314/nvj.v39i3.10.

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Animal African trypanosomiasis (AAT) also known as Nagana is a resurgent disease in Africa. Medicinal plants are being used in less developed countries for the treatment of various diseases including trypanosomiasis, due to the high cost of currently available drugs. Most of these plants have been useful sources of treatment of various diseases based on information obtained from folk medicine but have not been scientifically certified. Here, we investigated the in vitro and in vivo anti-trypanosomal potentials of the methanol extract of Aformorsia laxiflora and Khaya senegalensis against T. b.

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