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1
Morais, Mayara Castro de, Jucieudo Virgulino de Souza, Carlos da Silva Maia Bezerra Filho, Silvio Santana Dolabella, and Damião Pergentino de Sousa. "Trypanocidal Essential Oils: A Review." Molecules 25, no. 19 (October 6, 2020): 4568. http://dx.doi.org/10.3390/molecules25194568.
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Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus Trypanosoma. In humans, this includes Chagas disease and African trypanosomiasis. There are few therapeutic options, and there is low efficacy to clinical treatment. Therefore, the search for new drugs for the trypanosomiasis is urgent. This review describes studies of the trypanocidal properties of essential oils, an important group of natural products widely found in several tropical countries. Seventy-seven plants were selected from literature for the trypanocidal activity of their essential oils. The main chemical constituents and mechanisms of action are also discussed. In vitro and in vivo experimental data show the therapeutic potential of these natural products for the treatment of infections caused by species of Trypanosoma.
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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 African trypanosomes in cattle in Lira District using microscopy and polymerase chain reaction amplification (PCR) methods. In this cross-sectional study, a total of 254 cattle from the three villages of Acanakwo A, Barropok, and Acungkena in Lira District, Uganda, were selected by simple random sampling technique and screened for trypanosomiasis using microscopy and PCR methods. The prevalence of trypanosomiasis according to microscopic results was 5/254 (2.0%) as compared to 11/254 (4.3%) trypanosomiasis prevalence according to PCR analysis. The prevalence of trypanosomiasis infection in the animal studied is 11/254 (4.3%). Trypanosoma congolense was the most dominant trypanosome species with a proportion of 9/11 (81.8%), followed by T. vivax 1/11 (9.1%) and mixed infection of T. congolense/T. vivax1/11 (9.1%). Barropok village had the highest prevalence of trypanosomiasis with 6/11 (54.5%). There is a statistically significant relationship ( OR = 6.041 ; 95% CI: 1.634-22.331; p < 0.05 ) between abnormal PCV and trypanosome infection. Polymerase reaction amplification was the most reliable diagnostic method due to its high sensitivity and specificity as compared to the conventional microscopic method. Polymerase reaction amplification appears to have adequate accuracy to substitute the use of a microscope where facilities allow. This study, therefore, underscores the urgent need for local surveillance schemes more especially at the grassroots in Uganda to provide data for reference guideline development needed for the control of trypanosomiasis in Uganda.
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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 (May 31, 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 transmission, T. vivax has also been introduced into South America. T. evansi is a unique animal trypanosome that is found in vast territories around the world and can cause atypical human trypanosomiasis (aHT). All salivarian trypanosomes are well adapted to survival inside the host’s immune system. This is not a hostile environment for these parasites, but the place where they thrive. Here we provide an overview of the latest insights into the host-parasite interaction and the unique survival strategies that allow trypanosomes to outsmart the immune system. In addition, we review new developments in treatment and diagnosis as well as the issues that have hampered the development of field-applicable anti-trypanosome vaccines for the implementation of sustainable disease control.
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ALSFORD, SAM, JOHN M. KELLY, NICOLA BAKER, and DAVID HORN. "Genetic dissection of drug resistance in trypanosomes." Parasitology 140, no. 12 (April 3, 2013): 1478–91. http://dx.doi.org/10.1017/s003118201300022x.
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SUMMARYThe trypanosomes cause two neglected tropical diseases, Chagas disease in the Americas and African trypanosomiasis in sub-Saharan Africa. Over recent years a raft of molecular tools have been developed enabling the genetic dissection of many aspects of trypanosome biology, including the mechanisms underlying resistance to some of the current clinical and veterinary drugs. This has led to the identification and characterization of key resistance determinants, including transporters for the anti-Trypanosoma bruceidrugs, melarsoprol, pentamidine and eflornithine, and the activator of nifurtimox-benznidazole, the anti-Trypanosoma cruzidrugs. More recently, advances in sequencing technology, combined with the development of RNA interference libraries in the clinically relevant bloodstream form ofT. bruceihave led to an exponential increase in the number of proteins known to interact either directly or indirectly with the anti-trypanosomal drugs. In this review, we discuss these findings and the technological developments that are set to further revolutionise our understanding of drug-trypanosome interactions. The new knowledge gained should inform the development of novel interventions against the devastating diseases caused by these parasites.
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Kanté Tagueu, Sartrien, Oumarou Farikou, Flobert Njiokou, and Gustave Simo. "Prevalence of Sodalis glossinidius and different trypanosome species in Glossina palpalis palpalis caught in the Fontem sleeping sickness focus of the southern Cameroon." Parasite 25 (2018): 44. http://dx.doi.org/10.1051/parasite/2018044.
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Tsetse flies are the cyclical vector of human and animal African trypanosomiasis. To improve vector control in order to achieve the elimination of human African trypanosomiasis (HAT) and boost the control of animal diseases, investigations have been undertaken on the tripartite association between tsetse, trypanosome, and symbionts. It is in this light that Sodalis glossinidius and different trypanosomes were identified in Glossina palpalis palpalis caught in Fontem in southern Cameroon. For this study, DNA was extracted from whole flies, and S. glossinidius and different trypanosome species were identified by polymerase chain reaction (PCR). Statistical analyses were performed to compare the trypanosome and S. glossinidius infection rates and to look for an association between these microorganisms. Of the 274 G. p. palpalis caught, 3.3% (9/274) were teneral. About 35% (96/274) of these flies harbored S. glossinidius. Of the 265 non-teneral flies, 37.7% were infected by trypanosomes. The infection rates of Trypanosoma congolense “forest type” and Trypanosoma vivax were 26.04% and 18.11%, respectively. About 6.41% of tsetse harbored mixed infections of T. congolense and T. vivax. Of the 69 tsetse with T. congolense infections, 33.33% (23/69) harbored S. glossinidius while 71.86% (69/96) of flies harboring S. glossinidius were not infected by trypanosomes. No association was observed between S. glossinidius and trypanosome infections. Some wild tsetse harbor S. glossinidius and trypanosomes, while others have no infection or are infected by only one of these microorganisms. We conclude that the presence of S. glossinidius does not favor trypanosome infections in G. p. palpalis of the Fontem focus.
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Makhulu, Edward Edmond, Jandouwe Villinger, Vincent Owino Adunga, Maamun M. Jeneby, Edwin Murungi Kimathi, Enock Mararo, Joseph Wang’ang’a Oundo, Ali Abdulahi Musa, and Lillian Wambua. "Tsetse blood-meal sources, endosymbionts and trypanosome-associations in the Maasai Mara National Reserve, a wildlife-human-livestock interface." PLOS Neglected Tropical Diseases 15, no. 1 (January 6, 2021): e0008267. http://dx.doi.org/10.1371/journal.pntd.0008267.
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African trypanosomiasis (AT) is a neglected disease of both humans and animals caused by Trypanosoma parasites, which are transmitted by obligate hematophagous tsetse flies (Glossina spp.). Knowledge on tsetse fly vertebrate hosts and the influence of tsetse endosymbionts on trypanosome presence, especially in wildlife-human-livestock interfaces, is limited. We identified tsetse species, their blood-meal sources, and correlations between endosymbionts and trypanosome presence in tsetse flies from the trypanosome-endemic Maasai Mara National Reserve (MMNR) in Kenya. Among 1167 tsetse flies (1136 Glossina pallidipes, 31 Glossina swynnertoni) collected from 10 sampling sites, 28 (2.4%) were positive by PCR for trypanosome DNA, most (17/28) being of Trypanosoma vivax species. Blood-meal analyses based on high-resolution melting analysis of vertebrate cytochrome c oxidase 1 and cytochrome b gene PCR products (n = 354) identified humans as the most common vertebrate host (37%), followed by hippopotamus (29.1%), African buffalo (26.3%), elephant (3.39%), and giraffe (0.84%). Flies positive for trypanosome DNA had fed on hippopotamus and buffalo. Tsetse flies were more likely to be positive for trypanosomes if they had the Sodalis glossinidius endosymbiont (P = 0.0002). These findings point to complex interactions of tsetse flies with trypanosomes, endosymbionts, and diverse vertebrate hosts in wildlife ecosystems such as in the MMNR, which should be considered in control programs. These interactions may contribute to the maintenance of tsetse populations and/or persistent circulation of African trypanosomes. Although the African buffalo is a key reservoir of AT, the higher proportion of hippopotamus blood-meals in flies with trypanosome DNA indicates that other wildlife species may be important in AT transmission. No trypanosomes associated with human disease were identified, but the high proportion of human blood-meals identified are indicative of human African trypanosomiasis risk. Our results add to existing data suggesting that Sodalis endosymbionts are associated with increased trypanosome presence in tsetse flies.
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Kubata, Bruno Kilunga, Michael Duszenko, Zakayi Kabututu, Marc Rawer, Alexander Szallies, Ko Fujimori, Takashi Inui, et al. "Identification of a Novel Prostaglandin F2α Synthase in Trypanosoma brucei." Journal of Experimental Medicine 192, no. 9 (November 6, 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 production and that it produces PGs enzymatically from AA and its metabolite, PGH2. Among all PGs synthesized, PGF2α was the major prostanoid produced by trypanosome lysates. We have purified a novel T. brucei PGF2α synthase (TbPGFS) and cloned its cDNA. Phylogenetic analysis and molecular properties revealed that TbPGFS is completely distinct from mammalian PGF synthases. We also found that TbPGFS mRNA expression and TbPGFS activity were high in the early logarithmic growth phase and low during the stationary phase. The characterization of TbPGFS and its gene in T. brucei provides a basis for the molecular analysis of the role of parasite-derived PGF2α in the physiology of the parasite and the pathogenesis of African trypanosomiasis.
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Sarataphan, Nachai, Montakan Vongpakorn, Bandit Nuansrichay, Nonglux Autarkool, Tiemjan Keowkarnkah, Pranee Rodtian, Roger W. Stich, and Sathaporn Jittapalapong. "Diagnosis of a Trypanosoma lewisi-like (Herpetosoma) infection in a sick infant from Thailand." Journal of Medical Microbiology 56, no. 8 (August 1, 2007): 1118–21. http://dx.doi.org/10.1099/jmm.0.47222-0.
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Trypanosomes were observed in a peripheral blood smear from a 45-day-old Thai infant displaying fever, anaemia, cough and anorexia. Human trypanosomiasis is not endemic to Thailand, so parasite identification was undertaken to determine likely sources of the infection. Several morphological parameters of the trypanosomes were similar to those of Trypanosoma evansi and statistically different from those of Trypanosoma lewisi-like parasites from a naturally infected indigenous rat. However, duplicate PCR assays with primers flanking trypanosome rRNA internal transcribed spacer 1 (ITS1) resulted in amplicons of ~623 bp that corresponded to the expected size for T. lewisi-like parasites. The ITS1 sequence from the infant's blood was 98 and 49 % identical to T. lewisi and T. evansi sequences, respectively. Based on molecular results, it was concluded that the infant was infected with a T. lewisi-like (Herpetosoma) species.
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Pereira, Glaécia AN, Lucianna H. Santos, Steven C. Wang, Luan C. Martins, Filipe S. Villela, Weiting Liao, Marco A. Dessoy, et al. "Benzimidazole inhibitors of the major cysteine protease of Trypanosoma brucei." Future Medicinal Chemistry 11, no. 13 (July 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 selectivity. This series comprises noncovalent competitive inhibitors (best Ki = 0.21 μM against rhodesain) and micromolar activity against Trypanosoma brucei brucei. A cheminformatics analysis confirms scaffold novelty, and the inhibitors described have favorable predicted physicochemical properties. Conclusion: Our results support this series as a starting point for new human African trypanosomiasis medicines.
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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 (February 7, 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 laboratory and tested by PCR targeting the trypanosomal Internal Transcribed Spacer (ITS-1) as well as suspect Tick-Borne Diseases (TBDs) including Anaplasmamosis, Babesiosis, and Theileriosis. PCR for Anaplasma sp yielded the highest number of positive animals (45.2%), followed by Trypanosoma sp (44%), Theileria sp (42.4%) and Babesia (26.3%); multiple infections were a common occurrence. Interestingly, 373 (29%) of these cattle with low PCVs were negative by PCR, pointing to other possible causes of aneamia, such as helminthiasis. Among the trypanosome infections classified as T. brucei by ITS-PCR, 5.5% were positive by SRA PCR, and were, therefore, confirmed as T. b. rhodesiense. Efforts against HAT should therefore consider packages that address a range of conditions. This may enhance acceptability and participation of livestock keepers in programs to eliminate this important but neglected tropical disease. In addition, we demonstrated that cattle remain an eminent reservoir for T. b. rhodesiense in eastern Uganda, which must be addressed to sustain HAT elimination.
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Adeyemi, O. S., A. F. Sulaiman, and O. M. Iniaghe. "Interaction between Gallotannin and a Recombinant Form of Arginine Kinase of Trypanosoma brucei: Thermodynamic and Spectrofluorimetric Evaluation." Journal of Biophysics 2014 (August 26, 2014): 1–7. http://dx.doi.org/10.1155/2014/675905.
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Current chemotherapies against trypanosomiasis are beset with diverse challenges, a situation which underscores the numerous research efforts aimed at finding newer and effective treatments. Arginine kinase of trypanosome has been validated as target for drug development against trypanosomiasis. The present study investigated the interaction between a recombinant form of the arginine kinase (rTbAK) of trypanosome and gallotannin. The interaction between gallotannin and recombinant arginine kinase of Trypanosoma brucei caused significant decrease of enzyme activity. Kinetic analysis revealed the interaction to be of noncompetitive inhibition. Further thermodynamic analysis showed that the interaction between gallotannin and the recombinant arginine kinase was nonspontaneous and involved hydrophobic forces. The Ksv values and the FRET analysis suggest that static quenching of fluorescence intensity by gallotannin was static. Data revealed inhibitory interactions between gallotannin and rTbAK of trypanosome. Although the mechanism of inhibition is not clear yet, molecular docking studies are ongoing to clearly define the inhibitory interactions between the gallotannin and rTbAK. The knowledge of such binding properties would enrich development of selective inhibitors for the arginine kinase of Trypanosoma brucei.
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Marsela, Megasari, Kyoko Hayashida, Ryo Nakao, Elisha Chatanga, Alex Kiarie Gaithuma, Kawai Naoko, Janelisa Musaya, Chihiro Sugimoto, and Junya Yamagishi. "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 identification than ITS1 PCR alone. Further PCR screening targeting the serum resistance-associated (SRA) gene was conducted to detect Trypanosoma brucei rhodesiense. Trypanosoma congolense was the most prevalent Trypanosoma sp., which was found in Nkhotakota (10.8%; 20 of 185), followed by Kasungu (2.5%; 5 of 199). Of note, the prevalence of T. b. rhodesiense detected by SRA PCR was high in Kasungu and Nkhotakota showing 9.5% (19 of 199) and 2.7% (5 of 185), respectively. We report the presence of animal African trypanosomes and T. b. rhodesiense from cattle at the human–livestock–wildlife interface for the first time in Malawi. Our results confirmed that animal trypanosomes are important causes of anemia in cattle and that cattle are potential reservoirs for human African trypanosomiasis in Malawi.
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Carrington, Mark. "Slippery customers: How African trypanosomes evade mammalian defences." Biochemist 31, no. 4 (August 1, 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.ilri.org/InfoServ/Webpub/Fulldocs/Mappoverty/index.htm) and tsetse flies, the insect vector (www.fao.org/ag/AGAinfo/programmes/en/paat/maps.html): the lack of overlap is remarkable. Tsetse flies are only present in sub-Saharan Africa, and this probably restricted the spread of African trypanosomiasis until historical times. Livestock infections are now present in much of South Asia and South America, a product of long distance trade and adaptation of the trypanosomes to mechanical transmission3. The majority of research is on Trypanosoma brucei as this includes the human infective subspecies. This article provides a description of progress in the understanding the molecular details of how the trypanosome interacts with the mammalian immune system and how these studies have extended beyond this to fundamental aspects of eukaryotic cell biology.
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ROCHANI, ANKIT K., CHANDAN MITHRA, MEETALI SINGH, and UTPAL TATU. "Heat shock protein 90 as a potential drug target against surra." Parasitology 141, no. 9 (June 10, 2014): 1148–55. http://dx.doi.org/10.1017/s0031182014000845.
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SUMMARYTrypanosomiasis is caused by Trypanosoma species which affect both human and animal populations and pose a major threat to developing countries. The incidence of animal trypanosomiasis is on the rise. Surra is a type of animal trypanosomiasis, caused by Trypanosoma evansi, and has been included in priority list B of significant diseases by the World Organization of Animal Health (OIE). Control of surra has been a challenge due to the lack of effective drugs and vaccines and emergence of resistance towards existing drugs. Our laboratory has previously implicated Heat shock protein 90 (Hsp90) from protozoan parasites as a potential drug target and successfully demonstrated efficacy of an Hsp90 inhibitor in cell culture as well as a pre-clinical mouse model of trypanosomiasis. This article explores the role of Hsp90 in the Trypanosoma life cycle and its potential as a drug target. It appears plausible that the repertoire of Hsp90 inhibitors available in academia and industry may have value for treatment of surra and other animal trypanosomiasis.
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Enwezor, F. N. C., R. T. Emmanuel, R. L. Bizi, T. O. Olanrewaju, M. A. Kugama, K. Y. Jarmai, A. A. Tijjani, et al. "Livestock trypanosomiasis, owners’ perception and search for human gambiense parasite in cattle and sheep in remote communities of Iseyin, Nigeria." Nigerian Journal of Parasitology 42, no. 1 (April 14, 2021): 147–57. http://dx.doi.org/10.4314/njpar.v42i1.20.
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The study assessed livestock for human and animal infective trypanosomes in seven remote communities of Iseyin, Oyo State, Nigeria. Blood samples collected at random from 330 cattle and 20 sheep were examined using the buffy coat technique and Leishman stained thin film. Packed cell volume and differential leukocyte counts were determined and interviews conducted. Animals examined showed clinical symptoms; emaciation (2%), rough hair coat (0.57%), body weakness (3.14%), ocular discharge (1.43%), dermatophylosis (0.57%) and ticks (0.57%). Leishman stained thin blood films indicated 34 cattle (9.71%) infected with Trypanosoma congolense, 0% infection in sheep and 100% slides positive for Anaplasma and Babesia parasites with no Trypanosoma brucei species. Anaemia was recorded in male cattle between 1year and 10 years old and was statistically significant (p<0.05). Acute inflammatory responses revealed by neutrophilia, lymphocytopaenia and lymphocytosis; 21.81%, 1.51% and 10% respectively in cattle suggested underlying bacterial orparasitic infections. All (100%) herdsmen confirmed presence of tsetse and other biting flies in bush and canopies around water bodies and stated observable signs and symptoms of trypanosomiasis (samore) which could wipe off the whole herd if untreated. Risk of trypanosome infection remained high as long as the old systems of cattle rearing exist; and urinary schistosomiasis and intestinal ailments due to lack of access to clean and portable water.
Keywords: Livestock;Trypanosoma congolense; Trypanosoma brucei species;Iseyin; Nigeria
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Hassan-Kadle, Ahmed A., Abdalla M. Ibrahim, Hamisi S. Nyingilili, Abdulkarim A. Yusuf, and Rafael F. C. Vieira. "Parasitological and molecular detection of Trypanosoma spp. in cattle, goats and sheep in Somalia." Parasitology 147, no. 14 (September 21, 2020): 1786–91. http://dx.doi.org/10.1017/s003118202000178x.
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AbstractAfrican animal trypanosomiasis (AAT) affects the livestock of 12.3 million Somalis and constrains their development and wellbeing. There is missing data on AAT in the country after the civil war of the 1990s. Therefore, this study has aimed to assess the prevalence of Trypanosoma spp. in 614 blood samples from cattle (n = 202), goats (n = 206) and sheep (n = 206) in Afgoye and Jowhar districts, Somalia using parasitological and molecular methods. Twenty-one out of 614 (3.4%; 95% CI: 2.1–5.2%) and 101/614 (16.4%; 95% CI: 13.6–19.6%) ruminants were positive for Trypanosoma spp. by buffy coat technique (BCT) and internal transcribed spacer 1 (ITS1)-polymerase chain reaction (PCR), respectively. Using ITS1-PCR, the highest prevalence was observed in cattle (23.8%; 95% CI: 18.4–30.1%) followed by goats (17.5%; 95% CI: 12.9–23.3%) and sheep (8.3%; 95% CI: 5.1–12.9%). A total of 74/101 (73.3%; 95% CI: 63.5–81.6%) ruminants were shown coinfection with at least two Trypanosome species. The four T. brucei-positive samples have tested negative for T. b. rhodesiense, by the human-serum-resistance-associated-PCR. Trypanosoma evansi, T. godfreyi, T. vivax, T. brucei, T. simiae and T. congolense were the Trypanosoma species found in this study. This is the first study on the molecular detection of Trypanosoma sp. in ruminants in Somalia. Further investigations and control measures are needed to manage Trypanosomiasis spreading in the country. Studies should also focus on the detection of T. b. rhodesiense in the country.
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Rao, Srinivasa P. S., Suresh B. Lakshminarayana, Jan Jiricek, Marcel Kaiser, Ryan Ritchie, Elmarie Myburgh, Frantisek Supek, et al. "Anti-Trypanosomal Proteasome Inhibitors Cure Hemolymphatic and Meningoencephalic Murine Infection Models of African Trypanosomiasis." Tropical Medicine and Infectious Disease 5, no. 1 (February 17, 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 detailed biological and pharmacological characterization of triazolopyrimidine compounds in HAT specific assays. The TP class of compounds showed single digit nanomolar potency against Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense strains. These compounds are trypanocidal with concentration-time dependent kill and achieved relapse-free cure in vitro. Two compounds, GNF6702 and a new analog NITD689, showed favorable in vivo pharmacokinetics and significant brain penetration, which enabled oral dosing. They also achieved complete cure in both hemolymphatic (blood) and meningoencephalic (brain) infection of human African trypanosomiasis mouse models. Mode of action studies on this series confirmed the 20S proteasome as the target in T. brucei. These proteasome inhibitors have the potential for further development into promising new treatment for human African trypanosomiasis.
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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 (February 24, 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 expressed in four other blood-stream-form African trypanosomes. Trypanosome PGP was optimally active and stable at bloodstream pH, and was insensitive to host plasma cysteine peptidase inhibitors. Native purified and recombinant hyper-expressed trypanosome PGP removed the N-terminal Glp blocking groups from TRH (thyrotrophin-releasing hormone) and GnRH (gonadotropin-releasing hormone) with a kcat/Km value of 0.5 and 0.1 s−1·μM−1 respectively. The half-life of TRH and GnRH was dramatically reduced in the plasma of trypanosome-infected rats, both in vitro and in vivo. Employing an activity-neutralizing anti-trypanosome PGP antibody, and pyroglutamyl diazomethyl ketone, a specific inhibitor of type I PGP, we demonstrated that trypanosome PGP is entirely responsible for the reduced plasma half-life of TRH, and partially responsible for the reduced plasma half-life of GnRH in a rodent model of African trypanosomiasis. The abnormal degradation of TRH and GnRH, and perhaps other neuropeptides N-terminally blocked with a pyroglutamyl moiety, by trypanosome PGP, may contribute to some of the endocrine lesions observed in African trypanosomiasis.
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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 (April 1, 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 for the bulk of this activity from parasite-free T. b. brucei-infected rat plasma and confirmed its identity by protein sequencing. We show that live trypanosomes do not release OP-Tb in vitro and propose that disrupted parasites release it into the host circulation, where it is unregulated and retains full catalytic activity and may thus play a role in the pathogenesis of African trypanosomiasis.
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Srisuton, Phumee, Sunantaraporn, Boonserm, Sor-suwan, Brownell, Pengsakul, and Siriyasatien. "Detection of Leishmania and Trypanosoma DNA in Field-Caught Sand Flies from Endemic and Non-Endemic Areas of Leishmaniasis in Southern Thailand." Insects 10, no. 8 (August 2, 2019): 238. http://dx.doi.org/10.3390/insects10080238.
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Phlebotomine sand flies are tiny, hairy, blood-sucking nematoceran insects that feed on a wide range of hosts. They are known as a principal vector of parasites, responsible for human and animal leishmaniasis worldwide. In Thailand, human autochthonous leishmaniasis and trypanosomiasis have been reported. However, information on the vectors for Leishmania and Trypanosoma in the country is still limited. Therefore, this study aims to detect Leishmania and Trypanosoma DNA in field-caught sand flies from endemic areas (Songkhla and Phatthalung Provinces) and non-endemic area (Chumphon Province) of leishmaniasis. A total of 439 sand flies (220 females and 219 males) were collected. Head and genitalia dissection of female sandflies were done for morphology identification, and the remaining parts of those sand flies were then used for the detection of Leishmania and Trypanosoma parasites. The DNA was extracted from individual female sand flies. Polymerase chain reaction (PCR) anneal, specific to the ITS1 and SSU rRNA gene regions, was used to detect Leishmania and Trypanosoma DNA, respectively. The positive PCR products were cloned and sequenced. The results showed that the female sand fly species in this study consisted of Sergentomyia khawi (35.9%); Se. anodontis (23.6%); Phlebotomus betisi (18.6%); Ph. kiangsuensis (9.5%); Ph. asperulus (6.4%); Se. barraudi (2.3%); 0.9% of each Se. indica, Ph. stantoni, and Ph. major major; and 0.5% of each Se. sylvatica and Ph. mascomai. The PCR and sequence analysis were able to detect Leishmania and Trypanosoma DNA in sand fly samples, which were identified as L. martiniquensis, 1/220 (0.45%) in Se. khawi, 3/220 (1.36%) of T. noyesi in Se. anodontis, and Ph. asperulus. Fourteen (6.36%) of the unidentified trypanosome species in Se. khawi, Se. indica, Se. anodontis, Ph. asperulus, and Ph. betisi were found in all of the areas of this study. Interestingly, we found a 1/220 (0.45%) co-infection sample of L. martiniquensis and Trypanosoma in Se. khawi from Songkhla Province. These data indicate that several species of sand flies might be potential vectors of Leishmania and Trypanosoma parasites in southern Thailand. However, more extensive study for potential vectors using a larger number of sand flies should be conducted to prove whether these sand flies can be natural vectors of leishmaniasis and trypanosomiasis in both humans and animals. In addition, our study could be useful for the future study of infection prevention, including effective vector control for leishmaniasis and trypanosomiasis in Thailand.
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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 (May 10, 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 and she presented with a history of fever, body ache, headache, decreased oral intake, pain lower abdomen, swelling and discharge from forearm chancre since last 4-5 days. Peripheral smear showed heavy parasitemia by flagellated forms of Trypanosoma and the diagnosis of Trypanosoma brucei was given on Peripheral smear report. Serological testing was also done and a diagnosis of West-African trypanosomiasis was confirmed. The patient was successfully treated and made a good recovery. So West-African trypanosomiasis should be considered in the differential diagnosis with presentation of fever with chancre in every person with recent history of travel to African countries as it is universally fatal without treatment.
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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 (February 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 classical subspecies Trypanosoma brucei brucei. These results broadly agree with the current taxonomy, and are corroborated by RFLP analysis of kDNA. Statistical analysis indicates a basically clonal reproduction system of the trypanosomes in the area studied; the zymodemes are equivalent to natural clones (or a family of closely related clones), stable in space and time. Epidemiological hypotheses are proposed according to the geographic distribution of the clones in this area.
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Kunz, E., K. Mätz-Rensing, N. Stolte, P. B. Hamilton, and F. J. Kaup. "Reactivation of a Trypanosoma cruzi Infection in a Rhesus Monkey (Macaca mulatta) Experimentally Infected with SIV." Veterinary Pathology 39, no. 6 (November 2002): 721–25. http://dx.doi.org/10.1354/vp.39-6-721.
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Trypanosoma cruzi-like flagellates were incidentally noted in blood smears of a routinely monitored rhesus monkey experimentally infected with the simian immunodeficiency virus (SIV). Immunodeficiency in the course of the SIV infection reactivated a chronic infection of Chagas' disease that had been unnoticed when the macaque was imported to Europe. The animal developed no specific clinical symptoms of American trypanosomiasis, but histologically a chagasic myocarditis was detected. Analysis of the small subunit rRNA gene of the trypanosome identified the protozoan as T. cruzi.
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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 (December 31, 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 LWLR. MethodsA total of 150 tsetse flies were caught. Of these, 82 remained alive after capture and were dissected such that the mid-gut could be examined microscopically for trypanosomes. DNA extractions were performed from both mid-guts and the 68 dead flies using a Qiagen Kit. Amplification techniques involved the Internal Transcriber Spacer 1 (ITS 1) conventional polymerase chain reaction (PCR) with primers designed to identify trypanosome species, and Repetitive Insertion Mobile Element – Loop Mediated Isothermal Amplification (RIME LAMP), a sequence specific to T. brucei.ResultsAnalysis showed that 79/82 (96.3%) of the mid-guts examined microscopically were positive for trypanosomes and that 75/150 (50%) of the DNA extracts (from the mid-gut, and tsetse fly carcasses) were positive for T. brucei, as determined by the RIME LAMP method. ITS1 PCR further showed that 87/150 (58.0%) flies were positive for trypanosomes, of which 56/87 (64.4%) were T. brucei, 9/87 (10.3%) were T. vivax; 7/87 (8.1%) were T. simiae; 6/87 (6.9%) were T. congolense, and 6/87 (6.9%) were T. godfreyi. Ten samples had a mixture of infections. ConclusionOur analysis demonstrated a mixture of infections from trypanosome species in tsetse flies at LWLR, and that T. brucei, the species that causes HAT, was the most common. Our study successfully used molecular techniques to demonstrate the presence of T. b. rhodesiense at LWLR, a species that causes HAT in both East and Central Africa.
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Abah, Samuel, Silas Lendzele Sevidzem, Alexandre Michel Njan Nloga, Archile Paguem, Abdoulmoumini Mamoudou, Jacques François Mavoungou, and Andre Zoli. "“Silent” circulation of Trypanosoma spp. in Tabanids (Diptera: Tabanidae) and Cattle in a Tsetse free Range land of Ngaoundere (Adamawa-Cameroon)." International Journal of Biological and Chemical Sciences 14, no. 7 (December 7, 2020): 2611–18. http://dx.doi.org/10.4314/ijbcs.v14i7.19.
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The Adamawa region falls within the tsetse belt of Cameroon but harbours isolated pockets of tsetse free range lands like Ngaoundere. There is no report on the occurrence of tsetse and bovine trypanosomosis in Ngaoundere. To provide information on this subject, two Vavoua traps were used to trap vectors of bovine trypanosomiasis and at the same time, blood was collected from cattle. Genomic DNA was extracted from buffy coat of cattle blood (n=42) and biting flies (n=53). The nested PCR was used to screen the samples for Trypanosoma spp. During the 14 days of trapping in November and December 2017 in Ngaoundere, 127 flies were documented and classified under two taxa: Tabanidae and Stomoxyini. Three Trypanosoma spp. DNA was isolated from tabanid (18.9%) samples and identified as T. theileri, T. vivax and T. evansi and two of them that is T. theileri (4%) and T. vivax (3%) were also detected in cattle (7%). There was no case of trypanosome DNA isolated from all the screened Stomoxyini. This result indicates the “silent” transmission of T. theileri and T. vivax by tabanids in the absence of glossines in Ngaoundere.Keywords: Trypanosomes, tabanids, stomoxyini, PCR, Ngaoundere, Adamawa-Cameroon.
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Werbovetz, Karl A., Edward S. Riccio, Anna Furimsky, Julian V. Richard, Shanshan He, Lalitha Iyer, and Jon Mirsalis. "Evaluation of Antitrypanosomal Dihydroquinolines for Hepatotoxicity, Mutagenicity, and Methemoglobin Formation In Vitro." International Journal of Toxicology 33, no. 4 (May 12, 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-2,2,4-trimethylquinolin-6-yl acetate showed outstanding in vitro selectivity for Trypanosoma brucei compared to the HepG2, Hep3B, Huh7, and PLC5 hepatocyte cell lines. 1-Benzyl-1,2-dihydro-2,2,4-trimethylquinolin-6-ol hydrochloride and 1-(2-methoxybenzyl)-1,2-dihydro-2,2,4-trimethylquinolin-6-yl acetate were not mutagenic when screened in the Ames assay, with or without metabolic activation. The latter 2 compounds promoted time- and dose-dependent formation of methemoglobin when incubated in whole human blood, but such levels were below those typically required to produce symptoms of methemoglobinemia in humans. Although compounds capable of quinone imine formation require careful evaluation, these in vitro studies indicate that antitrypanosomal dihydroquinolines merit further study as drug candidates against the neglected tropical disease human African trypanosomiasis.
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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 analysis revealed the double-headed structure of the outer-arm dynein, the internal structure of PFR and identified repeating structure in the flagella. Since these structures are critical to the pathogenicity of Trypanosoma brucei, and understanding their organization would help in finding treatments against African trypanosomiasis.
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Bacchi, C. J., K. Sanabria, A. J. Spiess, M. Vargas, C. J. Marasco, L. M. Jimenez, B. Goldberg, and J. R. Sufrin. "In vivo efficacies of 5'-methylthioadenosine analogs as trypanocides." Antimicrobial Agents and Chemotherapy 41, no. 10 (October 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 agent of East African sleeping sickness. HETA was curative (>60%) for infections caused by 5 of 11 clinical isolates of T. b. rhodesiense when it was given to mice at 200 mg/kg of body weight for 7 days as a continuous infusion in osmotic pumps. HETA at 150 to 200 mg/kg also extended the life spans of the mice infected with four additional isolates two- to fivefold. Di- and tri-O-acetylated derivatives of HETA also proved curative for the infections, while a tri-O-propionyl derivative, although also curative, was not as effective. This study indicates that substrate analogs of MTA should be given important consideration for development as novel chemotherapies against African trypanosomiasis.
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Isoun, T. T., M. J. Isoun, and V. O. Anosa. "PLASMA FREE AMINO ACID PROFILES OF CATTLE INFECTED WITH TRYPANOSOMA VIVAX: A PRELIMINARY REPORT." Nigerian Journal of Animal Production 6 (January 19, 2021): 94–96. http://dx.doi.org/10.51791/njap.v6i.2675.
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EMACIATION and poor productivity have been recognised as some of the major features of the chronic form of bovine trypanosomiasis. However, the biochemical and nutritional bases of the Wasting and reduced growth rates of cattle with trypanosomiasis are yet to be adequately elucidated, such data may be needed, not only for the clinical management of the disease but also in the proper husbandry practice of cattle in endemic areas of trypanosomiasis for animal protein production.
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Ibrahim, Mahamat Alhadj Moussa, Judith Sophie Weber, Sen Claudine Henriette Ngomtcho, Djoukzoumka Signaboubo, Petra Berger, Hassane Mahamat Hassane, and Sørge Kelm. "Diversity of trypanosomes in humans and cattle in the HAT foci Mandoul and Maro, Southern Chad—A matter of concern for zoonotic potential?" PLOS Neglected Tropical Diseases 15, no. 6 (June 9, 2021): e0009323. http://dx.doi.org/10.1371/journal.pntd.0009323.
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Background African trypanosomes are parasites mainly transmitted by tsetse flies. They cause trypanosomiasis in humans (HAT) and animals (AAT). In Chad, HAT/AAT are endemic. This study investigates the diversity and distribution of trypanosomes in Mandoul, an isolated area where a tsetse control campaign is ongoing, and Maro, an area bordering the Central African Republic (CAR) where the control had not started. Methods 717 human and 540 cattle blood samples were collected, and 177 tsetse flies were caught. Trypanosomal DNA was detected using PCR targeting internal transcribed spacer 1 (ITS1) and glycosomal glyceraldehyde-3 phosphate dehydrogenase (gGAPDH), followed by amplicon sequencing. Results Trypanosomal DNA was identified in 14 human samples, 227 cattle samples, and in tsetse. Besides T. b. gambiense, T. congolense was detected in human in Maro. In Mandoul, DNA from an unknown Trypanosoma sp.-129-H was detected in a human with a history of a cured HAT infection and persisting symptoms. In cattle and tsetse samples from Maro, T. godfreyi and T. grayi were detected besides the known animal pathogens, in addition to T. theileri (in cattle) and T. simiae (in tsetse). Furthermore, in Maro, evidence for additional unknown trypanosomes was obtained in tsetse. In contrast, in the Mandoul area, only T. theileri, T. simiae, and T. vivax DNA was identified in cattle. Genetic diversity was most prominent in T. vivax and T. theileri. Conclusion Tsetse control activities in Mandoul reduced the tsetse population and thus the pathogenic parasites. Nevertheless, T. theileri, T. vivax, and T. simiae are frequent in cattle suggesting transmission by other insect vectors. In contrast, in Maro, transhumance to/from Central African Republic and no tsetse control may have led to the high diversity and frequency of trypanosomes observed including HAT/AAT pathogenic species. Active HAT infections stress the need to enforce monitoring and control campaigns. Additionally, the diverse trypanosome species in humans and cattle indicate the necessity to investigate the infectivity of the unknown trypanosomes regarding their zoonotic potential. Finally, this study should be widened to other trypanosome hosts to capture the whole diversity of circulating trypanosomes.
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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 (October 1, 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 human cell lines were used, including ECV304, HBMEC and HUVEC, as well as C6 rat astrocytes. Validation of the BBB models with Escherichia coli HB101 and E. coli K1 revealed that a combination of ECV304 cells seeded on Matrigel as a semi-synthetic basement membrane and C6 astrocytes resulted in an optimal BBB model system. The BBB model showed selective permeability for the pathogenic E. coli K1 strain, and African trypanosomes were able to traverse the optimized ECV304–C6 BBB efficiently. Furthermore, coincubation indicated that paracellular macrophage transmigration does not facilitate trypanosomal BBB traversal. An inverse assembly of the BBB model demonstrated that trypanosomes were also able to transmigrate the optimized ECV304–C6 BBB backwards, indicating the relevance of the CNS as a possible reservoir of a relapsing parasitaemia.
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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 (September 29, 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, including alkylamino substitutions on N-6, methoxy groups on C-2 and C-3, and a methylenedioxy bridge between C-8 and C-9. Detailed analysis of eight water-soluble indenoisoquinolines demonstrated that in trypanosomes the compounds inhibited DNA synthesis and acted as topoisomerase poisons. Testing these compounds on L1210 mouse leukemia cells revealed that all eight were more effective against trypanosomes than against mammalian cells. In preliminary in vivo experiments one compound delayed parasitemia and extended survival in mice subjected to a lethal trypanosome challenge. The indenoisoquinolines provide a promising lead for the development of drugs against sleeping sickness.
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Afililla, Zhaza, Lucia Tri Suwanti, Sri Agus Sudjarwo, Setiawan Koesdarto, Muchammad Yunus, and Hani Plumeriastuti. "Prevalence of Trypanosomiasis of Wild Rats (Rattus sp.) in Banyuwangi." Journal of Parasite Science 1, no. 2 (November 26, 2019): 39. http://dx.doi.org/10.20473/jops.v1i2.16283.
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The aim of this research was to investigate the number of prevalence of Trypanosomiasis of wild rats in Banyuwangi. Sixty wild rats were trapped from human residence, markets and rice fields in Banyuwangi. Rat`s blood smear was stained by Giemsa. The result show that one (1.67%.) of 60 blood sample was appear Trypanosoma sp.. The prevalence of Trypanosomiasis of wild rats in Banyuwangi was 1.67%.
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Magri, Alice, Roberta Galuppi, and Marialetizia Fioravanti. "Autochthonous Trypanosoma spp. in European Mammals: A Brief Journey amongst the Neglected Trypanosomes." Pathogens 10, no. 3 (March 13, 2021): 334. http://dx.doi.org/10.3390/pathogens10030334.
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The genus Trypanosoma includes flagellated protozoa belonging to the family Trypanosomatidae (Euglenozoa, Kinetoplastida) that can infect humans and several animal species. The most studied species are those causing severe human pathology, such as Chagas disease in South and Central America, and the human African trypanosomiasis (HAT), or infections highly affecting animal health, such as nagana in Africa and surra with a wider geographical distribution. The presence of these Trypanosoma species in Europe has been thus far linked only to travel/immigration history of the human patients or introduction of infected animals. On the contrary, little is known about the epidemiological status of trypanosomes endemically infecting mammals in Europe, such as Trypanosomatheileri in ruminants and Trypanosomalewisi in rodents and other sporadically reported species. This brief review provides an updated collection of scientific data on the presence of autochthonous Trypanosoma spp. in mammals on the European territory, in order to support epidemiological and diagnostic studies on Trypanosomatid parasites.
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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 (e.g., the trypanosome hexokinases), as well as cellular components required for development and maintenance of the essential subcellular compartments that house the major part of the pathway, the glycosomes.
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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 (May 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 and nascent VSG proteins are transiently expressed together in a mosaic surface coat. Thus, T-independent B-cell recognition of the trypanosome surface coat may be disrupted by the introduction of heterologous VSG molecules into the coat structure. To address this hypothesis, we transformed Trypanosoma brucei rhodesiense LouTat 1 with the 117 VSG gene from Trypanosoma brucei brucei MiTat 1.4 in order to produce VSG double expressers; coexpression of the exogenous 117 gene along with the endogenous LouTat 1 VSG gene resulted in the display of a mosaic VSG coat. Results presented here demonstrate that the host's ability to produce VSG-specific antibodies and activate B cells during early infection with VSG double expressers is compromised relative to that during infection with the parental strain, which displays a monotypic coat. These findings suggest a previously unrecognized mechanism of immune response evasion in which coat-switching trypanosomes fail to directly activate B cells until coat VSG homogeneity is achieved. This process affords an immunological advantage to trypanosomes during the process of antigenic variation.
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Marsden, Philip D. "The control of Latin American trypanosomiasis." Revista da Sociedade Brasileira de Medicina Tropical 30, no. 6 (December 1997): 521–27. http://dx.doi.org/10.1590/s0037-86821997000600014.
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The author presents his personal point of view on the present situation of Chagas' disease control in Latin America countries. He compares the situation with African trypanosomiasis. He comments on the existence of cases in other Continents. He emphazises the success of the fighting against domiciliated triatomine bugs by using residual inseticides. He discusses other forms of Trypanosoma cruzi transmission.
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Bailey, J. W., and D. H. Smith. "The Quantitative Buffy Coat for the Diagnosis of Trypanosomes." Tropical Doctor 24, no. 2 (April 1994): 54–56. http://dx.doi.org/10.1177/004947559402400204.
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The use of quantitative buffy coat (QBC®) tubes developed for malaria diagnosis is described in the diagnosis of African trypanosomiasis. One hundred and thirty-four patients with Trypanosoma gambiense were examined using QBC® plus either haematocrit (HCT) or mini anion exchange centrifugation (MAEC) or both. QBC® was the only method that detected all 134 patients. QBC® proved to be the most sensitive diagnostic test for the detection of trypanosomes in blood. It is simple to use, gives fast results and would be a useful test at the district hospital level.
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Rae, P. F., M. V. Thrusfield, A. Higgins, C. G. G. Aitken, T. W. Jones, and A. G. Luckins. "Evaluation of enzyme immunoassays in the diagnosis of camel (Camelus dromedarius) trypanosomiasis: a preliminary investigation." Epidemiology and Infection 102, no. 2 (April 1989): 297–307. http://dx.doi.org/10.1017/s0950268800029976.
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SUMMARYThree enzyme immunoassays were used for the serodiagnosis of Trypanosoma evansi in camels in the Sudan in order to evaluate their ability to discriminate between infected and non-infected animals. Two assays were used for the detection of trypanosomal antibodies, one using specific anti-camel IgG conjugate and another using a non-specific Protein A conjugate. The third assay detected the presence of trypanosomal antigens using anti-T. evansi antibodies in a double antibody sandwich assay. Inspection of the frequency distribution of assay results suggested that the ELISA for circulating trypanosomal antibodies using specific antisera and the ELISA for circulating antigens can distinguish between non-infected camels and infected camels exhibiting patent infections or not. The ELISA using Protein A conjugate to bind non-specifically to camel immunoglobulin did not appear to discriminate between infected and non-infected animals.
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Mulenga, Gloria M., Boniface Namangala, Kalinga Chilongo, Chrisborn Mubamba, Kyoko Hayashida, Lars Henning, and Bruce Gummow. "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 (April 30, 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 cases, respectively. In total, microscopy detected 40 cases. ITS-PCR-filter paper (FP) on blood spots stored on FP detected 47 cases, and ITS-PCR-FTA on blood spots stored on Whatman FTA Classic cards detected 83 cases. Using microscopy as the gold standard, ITS-PCR-FTA had a better specificity (SP) and sensitivity (SE) (SP = 72.2%; SE = 77.5%; kappa = 0.35) than ITS-PCR-FP (SP = 88%; SE = 60%; kappa = 0.45). The prevalence of Trypanosoma brucei s.l. was higher on ITS-PCR-FTA (19/227) than on ITS-PCR-FP (0/227). Our results illustrate the complexities around trypanosomiasis surveillance in rural Africa and provide evidence of the impact that field conditions and staff training can have on diagnostic results, which in turn impact the success of tsetse and trypanosomiasis control programs in the region.
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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 (April 10, 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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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 (March 23, 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 of some major compounds (isolated or commercial) were also determined. Our results showed for the first time the selective anti-trypanosomal effect of four EOs, extracted from three Zingiberaceae species (Curcuma longa, Curcuma zedoaria, and Zingiber officinale) and one Lauraceae species (Litsea cubeba) with IC50 values of 3.17 ± 0.72, 2.51 ± 1.08, 3.10 ± 0.08, and 2.67 ± 1.12 nL/mL respectively and SI > 10. Identified compounds accounted for more than 85% for each of them. Among the five major components of Curcuma longa EO, curlone is the most promising anti-trypanosomal candidate with an IC50 of 1.38 ± 0.45 µg/mL and SIs of 31.7 and 18.2 compared to WI38 and J774 respectively.
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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 (June 26, 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 their identification in a future diagnostic assay. DEP refers to physical movement that can be selectively induced on the parasites when exposing them to electric field gradients of specific magnitude, phase and frequency. The long-term goal of our work is to use DEP to selectively trap and enrich T. brucei in specific locations while eluting all other cells in a sample. This would allow for a diagnostic test that enables the user to characterize the presence of parasites in specific locations determined a priori instead of relying on scanning a sample. In the work presented here, we report the characterization of the conditions that lead to high enrichment, 780% in 50 s, of the parasite in specific locations using an array of titanium microelectrodes.
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Zilberstein, D., J. Wilkes, H. Hirumi, and A. S. Peregrine. "Fluorescence analysis of the interaction of isometamidium with Trypanosoma congolense." Biochemical Journal 292, no. 1 (May 15, 1993): 31–35. http://dx.doi.org/10.1042/bj2920031.
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Isometamidium chloride (Samorin) is the only compound recommended for prophylaxis against bovine trypanosomiasis in sub-Saharan Africa. The fluorescence property of this compound was used to investigate the interaction of the molecule with in vitro-derived bloodstream forms of Trypanosoma congolense IL 1180. Incubation of isometamidium with trypanosomes at 37 degrees C for 180 min resulted in a gradual alteration of the lambda max. with time (from 600 to 584 nm) and an increase in the intensity of trypanosome-associated fluorescence of approx. 2-fold. The alteration in fluorescence was temperature-dependent and inhibited by the addition of N-ethylmaleimide. In contrast, with intact cells addition of digitonin caused a rapid increase in fluorescence intensity to approximately four times that observed with intact cells. Uptake of isometamidium was also determined using radiolabelled drug; the results indicated that the time course of the uptake process resembled the fluorescence profile and was temperature-dependent. The results therefore indicate that the alteration of fluorescence is due to interaction of isometamidium with an intracellular component(s) and that isometamidium is transported across the plasma membrane via a protein carrier. The data also indicate that the described fluorescence technique can be used to investigate the role of membrane transport in resistance to isometamidium.
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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 (January 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-folates. We carried out molecular docking of a ligand library of 5742 compounds against TbPTR1 and identified 18 compounds showing promising binding modes. The protein-ligand complexes were subjected to molecular dynamics to characterize their molecular interactions and energetics, followed by in vitro testing. In this study, we identified five compounds which showed low micromolar Trypanosome growth inhibition in in vitro experiments that might be acting by inhibition of TbPTR1. Compounds RUBi004, RUBi007, RUBi014, and RUBi018 displayed moderate to strong antagonism (mutual reduction in potency) when used in combination with the known TbDHFR inhibitor, WR99210. This gave an indication that the compounds might inhibit both TbPTR1 and TbDHFR. RUBi016 showed an additive effect in the isobologram assay. Overall, our results provide a basis for scaffold optimization for further studies in the development of HAT anti-folates.
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Lopes, Sabrina Thabla Pereira, Bruno Da Silva Prado, Gustavo Henrique Chaves Martins, Hiran Esmeraldo Albuquerque Beserra, Marcos Antônio Celestino de Souza Filho, Luanna Soares de Melo Evangelista, Janaina De Fátima Saraiva Cardoso, Ana Lys Bezerra Barradas Mineiro, and José Adalmir Torres De Souza. "Trypanosoma vivax in Dairy Cattle." Acta Scientiae Veterinariae 46 (April 30, 2018): 5. http://dx.doi.org/10.22456/1679-9216.86772.
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Background: Trypanosoma vivax is a protozoan that causes reproductive disorders and decreased production in domestic and wild ungulate animals. The bovine are the main hosts of the disease and the transmission occurs by the bite of hematophagous insects, mainly tabanids. Several diagnostic techniques can be used to detect the parasite, both in parasitologicalform and by serological kits. In Brazil, the disease has been reported in bovines, goats and sheep of some states, with high morbidity and mortality and due to the scarcity of results on the epidemiology of the disease, this work had the objective to report the presence of T. vivax in a female bovine of a dairy herd in Parnaíba county, Piauí.Case: The animal naturally infected by Trypanosoma vivax, was a three-year-old cow from a dairy farm in the Parnaíba county, located in the north of Piauí state. The farm had a herd whith 62.20% of young Girolando breed cows and the breeding system used was semi-confinement, with two mechanical milking per day. At the time of a Veterinarian’s technicalvisit to the property, it was observed the occurrence of abortions, mastitis, estrus repetitions and cows with hematuria, leading to the suspicion of the bovine leptospirosis occurrence. Blood samples were collected from 78 cows from the herd for hematological, biochemical and serological tests, and 72 (92.30%) were reactive to some Leptospira serovars. All the exams were carried out at the Federal University of Piauí (UFPI). In the group of animals negative for leptospirosis, a female was diagnosed positive for bovine trypanosomiasis, confirming the result in the blood smear. This animal had no clinical signs characteristic of the disease at the time of the evaluation.Discussion: Blood trypomastigote forms of Trypanosoma vivax were visualized on several slides of the animal smear and all the morphological structures of the parasite found were clearly seen under microscopyas described in the literature. The hematological alterations observed were normochromic normocytic anemia, thrombocytopenia, leukocytosis due tolymphocytosis, monocytosis and eosinophilia. The anemia and leukocytosis clinical condition found in the specific animal is commonly found in bovines naturally infected by trypanosomiasis in the chronic phase of the disease. The results of the serum biochemistry revealed decreased blood glucose and increased renal and hepatic parameters, as well as the inversion of the albumin-globulin ratio. Similar laboratory results were also described previously. The animal had a good body score, a good diet and showed no clinical signs of the disease. A good nutrition may have controlled the T. vivax parasitaemia, avoiding the characterization of the clinical condition. This fact can be attributed to the differences in pathogenicity of the parasite and/or susceptibility of a particular host. In the area of the farm where the cattle were housed the presence ofseveral tabanids was noticed and the increase of these insects in the environment is considered a risk factor, predisposing, even, the occurrence of new outbreaks. The epidemiological situation of the disease in Brazil is described, for the most part, by reports of outbreaks or specific events, revealing the lack of more consistent studies. With this result it is knownthat trypanosomiasis exists in the dairy herd of the state of Piauí, being important to carry out new work to diagnose the epidemiological situation of the disease within the productive context of our region.Keywords: bovine, dairy herd, trypanosomiasis.
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Patham, Bhargavi, Josh Duffy, Ariel Lane, Richard C. Davis, Peter Wipf, Sheara W. Fewell, Jeffrey L. Brodsky, and Kojo Mensa-Wilmot. "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 (March 27, 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. brucei microsome) system that imports VSG_117 post-translationally. Using this system, MAL3-101, equisetin and CJ-21,058 were discovered to be small molecule inhibitors of VSG_117 translocation into the ER. These agents also killed bloodstream T. brucei in vitro; the concentrations at which 50% of parasites were killed (IC50) were 1.5 μM (MAL3-101), 3.3 μM (equisetin) and 7 μM (CJ-21,058). Thus VSG_117 import into TbRMs is a rapid and novel assay to identify ‘new chemical entities’ (e.g. MAL3-101, equisetin and CJ-21,058) for anti-trypanosome drug development.
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Alanazi, Abdullah D., Robert Puschendorf, Bashir Salim, Mohamed S. Alyousif, Ibrahim O. Alanazi, and Hajri R. Al-shehri. "Molecular detection of equine trypanosomiasis in the Riyadh Province of Saudi Arabia." Journal of Veterinary Diagnostic Investigation 30, no. 6 (September 11, 2018): 942–45. http://dx.doi.org/10.1177/1040638718798688.
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We conducted a cross-sectional study to detect trypanosome infections of horses and donkeys in the Riyadh Province of Saudi Arabia. DNA was extracted from blood samples collected from 368 horses and 142 donkeys, and subjected to universal first ribosomal internal transcribed spacer region (ITS1)-PCR followed by Trypanosoma evansi species–specific RoTat1.2-PCR. The universal ITS1-PCR revealed T. evansi infection in horses ( n = 12; 3.3%) and donkeys ( n = 4; 2.8%). There was no significant effect of sex or age on the prevalence of trypanosomiasis in horses or donkeys. Application of the RoTat1.2-PCR revealed that the RoTat1.2 VSG gene was absent from the positive ITS1-PCR samples of 3 horses and 1 donkey. This discrepancy could be explained by the circulation of T. evansi type B in Saudi Arabia; however, this suspicion requires confirmation.
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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 required for energy management are phosphotransferases. These enzymes present a nitrogenous group or a phosphate as acceptors, and the most clear examples are arginine kinase, nucleoside diphosphate kinase, and adenylate kinase. Trypanosoma and Leishmania have the largest number of phosphotransferase isoforms ever found in a single cell; some of them are absent in mammals, suggesting that these enzymes are required in many cellular compartments associated to different biological processes. The presence of such number of phosphotransferases support the hypothesis of the existence of an intracellular enzymatic phosphotransfer network that communicates the spatially separated intracellular ATP consumption and production processes. All these unique features make phosphotransferases a promising start point for rational drug design for the treatment of human trypanosomiasis.
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Mbang Nguema, Ornella, Marielle Bouyou Akotet, Jacques Mavoungou, and Denise Patricia Mawili Mboumba. "Variations of Glossina sp. and trypanosome species frequency within different habitats in a sleeping sickness focus, Gabon." Journal of Infection in Developing Countries 13, no. 01 (January 31, 2019): 67–72. http://dx.doi.org/10.3855/jidc.9654.
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Introduction: Knowledge of the infectious status of the Glossina is an indicator of risk of resurgence of Human African Trypanosomiasis (HAT). Environmental conditions have an impact on the density and diversity of both vector and Trypanosoma. The aim of the study was to determine the diversity and the infection rate of Glossina as well as the diversity of trypanosome species within habitats of an old HAT focus, in Gabon.
Methodology: Glossina were captured in September 2012 in three ecological sites. Vavoua traps were installed for twelve days. All captured flies were identified. Glossina were selected for trypanosome identification by Polymerase Chain Reaction.
Results: 1178 Glossina were captured: 55.8% in degraded forest, 28.9% in flood area and 15.4% in secondary forest. Glossina fusca congolensis (37%) and G.palpalis palpalis (36.4%) were the most abundant vector species. G. fusca congolensis was predominant in secondary forest and in flood area, while in degraded forest, it was G.palpalis palpalis. Trypanosoma infection rate was 30.7%, 42% in secondary forest, 32% in degraded forest and 18% in flood area. Trypanosoma congolense savannah was the main species detected (18.7%) followed by T.brucei brucei (10.7%) and T. brucei gambiense (4%). T. congolense savannah type was predominant in the secondary forest and in degraded forest (66.7% versus 55.5%).
Conclusion: Glossina density and trypanosome infection rate varied according to the habitat within HAT focus. The density of tsetse was the highest in degraded forest while the infection rate was highest in secondary forest. Continuous disease surveillance and control measures are needed.