6,547 results match your criteria African Trypanosomiasis Sleeping Sickness


Parasite specific 7SL-derived small RNA is an effective target for diagnosis of active trypanosomiasis infection.

PLoS Negl Trop Dis 2019 Feb 19;13(2):e0007189. Epub 2019 Feb 19.

The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, United Kingdom.

Human and animal African trypanosomiasis (HAT & AAT, respectively) remain a significant health and economic issue across much of sub-Saharan Africa. Effective control of AAT and potential eradication of HAT requires affordable, sensitive and specific diagnostic tests that can be used in the field. Small RNAs in the blood or serum are attractive disease biomarkers due to their stability, accessibility and available technologies for detection. Read More

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http://dx.doi.org/10.1371/journal.pntd.0007189DOI Listing
February 2019

[Epidemiological Situation of the Human African Trypanosomiasis in the Bilolo Municipality of Central African Republic].

Bull Soc Pathol Exot 2018 ;111(1):12-16

Faculté des sciences de la santé, université de Bangui, BP 1450, Bangui, République centrafricaine.

The Human African Trypanosomiasis (HAT) is a disabling and fatal disease caused by a vector-borne parasite still impacting in residual hotbeds. The aim of our study was to update the epidemiological data of HAT in one of Central African Republic foci after the (2012-2014) period of conflict. The survey was carried out in 24 villages in the Bilolo's municipality where 4788 persons were examined by the CATT () technique. Read More

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http://dx.doi.org/10.3166/bspe-2018-0002DOI Listing
January 2018

Novel Minor Groove Binders cure animal African trypanosomiasis in an in vivo mouse model.

J Med Chem 2019 Feb 14. Epub 2019 Feb 14.

Animal African trypanosomiasis (AAT) is a significant socioeconomic burden for sub-Saharan Africa due to its huge impact on livestock health. Existing therapies including those based upon Minor Groove Binders (MGBs), such as the diamidines, which have been used for decades, have now lost efficacy in some places due to the emergence of resistant parasites. Consequently, the need for new chemotherapies is urgent. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.8b01847DOI Listing
February 2019

Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis.

Front Immunol 2019 25;10:39. Epub 2019 Jan 25.

Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Trypanosomiasis has been recognized as a scourge in sub-Saharan Africa for centuries. The disease, caused by protozoan parasites of the genus, is a major cause of mortality and morbidity in animals and man. Human African trypanosomiasis (HAT), or sleeping sickness, results from infections with or with accounting for over 95% of infections. Read More

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https://www.frontiersin.org/article/10.3389/fimmu.2019.00039
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http://dx.doi.org/10.3389/fimmu.2019.00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355679PMC
January 2019
3 Reads

Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents.

PLoS Negl Trop Dis 2019 Feb 8;13(2):e0007129. Epub 2019 Feb 8.

Northeastern University Department of Chemistry & Chemical Biology, Boston, MA, United States of America.

New treatments are needed for neglected tropical diseases (NTDs) such as Human African trypanosomiasis (HAT), Chagas disease, and schistosomiasis. Through a whole organism high-throughput screening campaign, we previously identified 797 human kinase inhibitors that grouped into 59 structural clusters and showed activity against T. brucei, the causative agent of HAT. Read More

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http://dx.doi.org/10.1371/journal.pntd.0007129DOI Listing
February 2019
1 Read

Integration of Human African Trypanosomiasis Control Activities into Primary Health Services in the Democratic Republic of the Congo: A Qualitative Study of Stakeholder Perceptions.

Am J Trop Med Hyg 2019 Feb 4. Epub 2019 Feb 4.

National Program for the Control of Human African Trypanosomiasis, Kinshasa, DRC.

Human African trypanosomiasis is close to elimination in several countries in sub-Saharan Africa. The diagnosis and treatment is currently rapidly being integrated into first-line health services. We aimed to document the perspective of stakeholders on this integration process. Read More

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http://dx.doi.org/10.4269/ajtmh.18-0382DOI Listing
February 2019
1 Read

Human African Trypanosomiasis: Progress and Stagnation.

Infect Dis Clin North Am 2019 Mar;33(1):61-77

Department of Clinical Sciences, Institute of Tropical Medicine, Nationalestraat 155, Antwerpen 2000, Belgium.

Control efforts have considerably reduced the prevalence of human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense in West/Central Africa and to Trypanosoma brucei rhodesiense in East Africa. Management of T brucei gambiense HAT has recently improved, with new antibody-based rapid diagnostic tests suited for mass screening and clinical care, and simpler treatments, including the nifurtimox-eflornithine combination therapy and the new oral drug fexinidazole to treat the second stage of the disease. In contrast, no major advance has been achieved for the treatment of T brucei rhodesiense HAT, a zoonosis that occasionally affects short-term travelers to endemic areas. Read More

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http://dx.doi.org/10.1016/j.idc.2018.10.003DOI Listing

Trypanosoma congolense: In Vitro Culture and Transfection.

Curr Protoc Microbiol 2019 Feb 1:e77. Epub 2019 Feb 1.

School of Biological Sciences, University of Bristol, Bristol, United Kingdom.

Trypanosoma congolense, together with T. vivax and T. brucei, causes African animal trypanosomiasis (AAT), or nagana, a livestock disease carried by bloodsucking tsetse flies in sub-Saharan Africa. Read More

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http://dx.doi.org/10.1002/cpmc.77DOI Listing
February 2019

A participatory epidemiological study of major cattle diseases amongst Maasai pastoralists living in wildlife-livestock interfaces in Maasai Mara, Kenya.

Trop Anim Health Prod 2019 Jan 25. Epub 2019 Jan 25.

International Livestock Research Institute, (ILRI), P. O BOX 30709, Nairobi, 00100, Kenya.

Livestock-wildlife interactions promote the transmission of a wide range of infectious diseases that constraint livestock production. We used a participatory appraisal approach to find out and rank infectious diseases of concern to pastoralists in a zone of intense wildlife-livestock interaction and another zone with limited interactions. Four villages were selected purposively in areas with intensive cattle-wildlife interactions (zone 1), and another two in areas with low to moderate cattle-wildlife interactions (zone 2). Read More

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http://dx.doi.org/10.1007/s11250-018-01790-1DOI Listing
January 2019
1 Read

A pharmacokinetic-pharmacodynamic assessment of the hepatic and bone-marrow toxicities of the new trypanoside fexinidazole.

Antimicrob Agents Chemother 2019 Jan 22. Epub 2019 Jan 22.

Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Thailand

Fexinidazole is a novel oral treatment for , human African trypanosomiasis: -HAT. Fexinidazole also has activity against the causative agent of Chagas disease. During the course of a dose ranging assessment in chronic indeterminate Chagas disease, delayed neutropenia and significant increases in hepatic transaminases were observed and clinical investigations were suspended. Read More

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http://dx.doi.org/10.1128/AAC.02515-18DOI Listing
January 2019
2 Reads

Discovery of Sustainable Drugs for Neglected Tropical Diseases: Cashew Nut Shell Liquid (CNSL)-Based Hybrids Target Mitochondrial Function and ATP Production in Trypanosoma brucei.

ChemMedChem 2019 Jan 21. Epub 2019 Jan 21.

Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126, Bologna, Italy.

In the search for effective and sustainable drugs for human African trypanosomiasis (HAT), we developed hybrid compounds by merging the structural features of quinone 4 (2-phenoxynaphthalene-1,4-dione) with those of phenolic constituents from cashew nut shell liquid (CNSL). CNSL is a waste product from cashew nut processing factories, with great potential as a source of drug precursors. The synthesized compounds were tested against Trypanosoma brucei brucei, including three multidrug-resistant strains, T. Read More

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http://dx.doi.org/10.1002/cmdc.201800790DOI Listing
January 2019
1 Read

Potent Antitrypanosomal Activities of 3-Aminosteroids against African Trypanosomes: Investigation of Cellular Effects and of Cross-Resistance with Existing Drugs.

Molecules 2019 Jan 12;24(2). Epub 2019 Jan 12.

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.

Treatment of animal African trypanosomiasis (AAT) requires urgent need for safe, potent and affordable drugs and this has necessitated this study. We investigated the trypanocidal activities and mode of action of selected 3-aminosteroids against . The in vitro activity of selected compounds of this series against (Savannah-type, IL3000), (bloodstream trypomastigote, Lister strain 427 wild-type (427WT)) and various multi-drug resistant cell lines was assessed using a resazurin-based cell viability assay. Read More

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http://www.mdpi.com/1420-3049/24/2/268
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http://dx.doi.org/10.3390/molecules24020268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359104PMC
January 2019
3 Reads

Genetic diversity of trypanosomes pathogenic to livestock in tsetse flies from the Nech Sar National Park in Ethiopia: A concern for tsetse suppressed area in Southern Rift Valley?

Infect Genet Evol 2019 Jan 11;69:38-47. Epub 2019 Jan 11.

Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Brazil; INCT-EpiAmO - Instituto Nacional de Epidemiologia na Amazônia Ocidental, Brazil. Electronic address:

In Ethiopia, home to the largest African herd of cattle, animal trypanosomiasis is a major constraint to the efforts made for food self-sufficiency. We searched for trypanosomes in tsetse flies caught in the Nech Sar National Park (NSNP), Southern Rifty Valley, Ethiopia, at the district of Arba Minch where intensive tsetse control is successfully improving cattle productivity. Despite narrow geographical and temporal scales of our survey, we found a remarkable diversity of trypanosomes using the sensitive and discriminative method of fluorescent fragment length barcoding. Read More

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http://dx.doi.org/10.1016/j.meegid.2019.01.010DOI Listing
January 2019
2 Reads

A Microfluidic-Based Microscopy Platform for Continuous Interrogation of Trypanosoma brucei during Environmental Perturbation.

Biochemistry 2019 Feb 29;58(7):875-882. Epub 2019 Jan 29.

Department of Chemistry , Clemson University , Clemson , South Carolina 29634 , United States.

The African trypanosome, Trypanosoma brucei, is the causative agent of human African trypanosomiasis (HAT). African trypanosomes are extracellular parasites that possess a single flagellum that imparts a high degree of motility to the microorganisms. In addition, African trypanosomes show significant metabolic and structural adaptation to environmental conditions. Read More

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http://dx.doi.org/10.1021/acs.biochem.8b01269DOI Listing
February 2019
1 Read

Fexinidazole: First Global Approval.

Authors:
Emma D Deeks

Drugs 2019 Feb;79(2):215-220

Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand.

Fexinidazole Winthrop (hereafter referred to as fexinidazole) is a DNA synthesis inhibitor developed by the Drugs for Neglected Diseases initiative (DNDi), in collaboration with Sanofi, for the oral treatment of human African trypanosomiasis (HAT) [commonly known as 'sleeping sickness'] and Chagas' disease. The drug is a 5-nitroimidazole derivative first discovered by Hoechst AG (now part of Sanofi) and was identified by the DNDi in 2005 as having activity against Trypanosoma brucei gambiense and T. b. Read More

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http://link.springer.com/10.1007/s40265-019-1051-6
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http://dx.doi.org/10.1007/s40265-019-1051-6DOI Listing
February 2019
3 Reads

Resolving the apparent transmission paradox of African sleeping sickness.

PLoS Biol 2019 Jan 11;17(1):e3000105. Epub 2019 Jan 11.

Wellcome Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, United Kingdom.

Human African trypanosomiasis (HAT), or African sleeping sickness, is a fatal disease found throughout sub-Saharan Africa. The disease is close to elimination in many areas, although it was similarly close to elimination once before and subsequently reemerged, despite seemingly low rates of transmission. Determining how these foci persisted and overcame an apparent transmission paradox is key to finally eliminating HAT. Read More

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http://dx.doi.org/10.1371/journal.pbio.3000105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345479PMC
January 2019
3 Reads

Circumventricular Organs and Parasite Neurotropism: Neglected Gates to the Brain?

Front Immunol 2018 11;9:2877. Epub 2018 Dec 11.

Department Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Circumventricular organs (CVOs), neural structures located around the third and fourth ventricles, harbor, similarly to the choroid plexus, vessels devoid of a blood-brain barrier (BBB). This enables them to sense immune-stimulatory molecules in the blood circulation, but may also increase chances of exposure to microbes. In spite of this, attacks to CVOs by microbes are rarely described. Read More

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https://www.frontiersin.org/article/10.3389/fimmu.2018.02877
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http://dx.doi.org/10.3389/fimmu.2018.02877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302769PMC
December 2018
7 Reads

Identification of Novel Potential Inhibitors of Pteridine Reductase 1 in via Computational Structure-Based Approaches and in Vitro Inhibition Assays.

Molecules 2019 Jan 1;24(1). Epub 2019 Jan 1.

Research Unit in Bioinformatics (RUBi), Department of Biochemistry and Microbiology, Rhodes University, P.O. Box 94, Grahamstown 6140, South Africa.

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. Read More

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http://dx.doi.org/10.3390/molecules24010142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337619PMC
January 2019
1 Read
2.416 Impact Factor

Trans-sialidase Protein as a Potential Serological Marker for African Trypanosomiasis.

Protein J 2019 Jan 2. Epub 2019 Jan 2.

Global Health and Tropical Medicine, Institute of Hygiene and Tropical Medicine, Universidade Nova de Lisboa, Lisbon, Portugal.

Trypanosoma brucei is the etiological agent of African trypanosomiasis responsible for human and animal infections. T. brucei is transmitted by infected tsetse flies. Read More

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http://link.springer.com/10.1007/s10930-018-09808-1
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http://dx.doi.org/10.1007/s10930-018-09808-1DOI Listing
January 2019
10 Reads

A Tale of Three Species: Adaptation of Sodalis glossinidius to Tsetse Biology, Metabolism, and Host Diet.

MBio 2019 Jan 2;10(1). Epub 2019 Jan 2.

Department of Biology, University of York, York, United Kingdom

The tsetse fly is the insect vector for the parasite, the causative agent of human African trypanosomiasis. The colonization and spread of the trypanosome correlate positively with the presence of a secondary symbiotic bacterium, The metabolic requirements and interactions of the bacterium with its host are poorly understood, and herein we describe a metabolic model of metabolism. The model enabled the design and experimental verification of a defined medium that supports growth This has been used subsequently to analyze aspects of metabolism, revealing multiple unique adaptations of the symbiont to its environment. Read More

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http://dx.doi.org/10.1128/mBio.02106-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315101PMC
January 2019
2 Reads

Mathematical Modelling of Human African Trypanosomiasis Using Control Measures.

Comput Math Methods Med 2018 22;2018:5293568. Epub 2018 Nov 22.

African Institute for Mathematical Sciences, Biriwa, Cape Coast, Ghana.

Human African trypanosomiasis (HAT), commonly known as sleeping sickness, is a neglected tropical vector-borne disease caused by trypanosome protozoa. It is transmitted by bites of infected tsetse fly. In this paper, we first present the vector-host model which describes the general transmission dynamics of HAT. Read More

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https://www.hindawi.com/journals/cmmm/2018/5293568/
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http://dx.doi.org/10.1155/2018/5293568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282183PMC
November 2018
4 Reads

Modelling appropriate use of trypanocides to restrict wide-spread multi-drug resistance during chemotherapy of animal African trypanosomiasis.

Parasitology 2018 Dec 20:1-7. Epub 2018 Dec 20.

Centre for Biotechnology and Bioinformatics, University of Nairobi,P.O. Box 30197, Nairobi,Kenya.

Trypanocide resistance remains a huge challenge in the management of animal African trypanosomiasis. Paucity of data on the prevalence of multi-drug resistant trypanosomes has greatly hindered optimal veterinary management practices. We use mathematical model predictions to highlight appropriate drug regimens that impede trypanocide resistance development in cattle. Read More

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http://dx.doi.org/10.1017/S0031182018002093DOI Listing
December 2018

Improvement of Aqueous Solubility of Lapatinib-derived Analogs: Identification of a Quinolinimine as a Lead for Human African Trypanosomiasis Drug Development.

J Med Chem 2018 Dec 19. Epub 2018 Dec 19.

Lapatinib, an approved EGFR inhibitor, was explored as a starting point for the synthesis of new hits against Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). Previous work culminated in 1 (NEU-1953), which was part of a series typically associated with poor aqueous solubility. In this report, we present various medicinal chemistry strategies that were used to increase the aqueous solubility and improve the physicochemical profile without sacrificing anti-trypanosome potency. Read More

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http://dx.doi.org/10.1021/acs.jmedchem.8b01365DOI Listing
December 2018
3 Reads

Trypanosoma brucei PRMT1 Is a Nucleic Acid Binding Protein with a Role in Energy Metabolism and the Starvation Stress Response.

MBio 2018 12 18;9(6). Epub 2018 Dec 18.

Department of Microbiology and Immunology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA

In and related kinetoplastid parasites, transcription of protein coding genes is largely unregulated. Rather, mRNA binding proteins, which impact processes such as transcript stability and translation efficiency, are the predominant regulators of gene expression. Arginine methylation is a posttranslational modification that preferentially targets RNA binding proteins and is, therefore, likely to have a substantial impact on biology. Read More

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http://mbio.asm.org/lookup/doi/10.1128/mBio.02430-18
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http://dx.doi.org/10.1128/mBio.02430-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299225PMC
December 2018
7 Reads

Gluconeogenesis is essential for trypanosome development in the tsetse fly vector.

PLoS Pathog 2018 12 17;14(12):e1007502. Epub 2018 Dec 17.

Laboratoire de Microbiologie Fondamentale et Pathogénicité (MFP), Université de Bordeaux, CNRS UMR-5234, Bordeaux, France.

In the glucose-free environment that is the midgut of the tsetse fly vector, the procyclic form of Trypanosoma brucei primarily uses proline to feed its central carbon and energy metabolism. In these conditions, the parasite needs to produce glucose 6-phosphate (G6P) through gluconeogenesis from metabolism of non-glycolytic carbon source(s). We showed here that two phosphoenolpyruvate-producing enzymes, PEP carboxykinase (PEPCK) and pyruvate phosphate dikinase (PPDK) have a redundant function for the essential gluconeogenesis from proline. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312356PMC
December 2018

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites.

Front Microbiol 2018 30;9:2655. Epub 2018 Nov 30.

Department of Pathology, Wexner Medical Center, The Ohio State University, Columbus, OH, United States.

The neglected tropical diseases (NTDs) caused by protozoan parasites are responsible for significant morbidity and mortality worldwide. Current treatments using anti-parasitic drugs are toxic and prolonged with poor patient compliance. In addition, emergence of drug-resistant parasites is increasing worldwide. Read More

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http://dx.doi.org/10.3389/fmicb.2018.02655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284052PMC
November 2018

Drug Discovery for Kinetoplastid Diseases: Future Directions.

ACS Infect Dis 2019 Feb 13;5(2):152-157. Epub 2018 Dec 13.

Novartis Institute for Tropical Diseases (NITD) , 5300 Chiron Way , Emeryville , California 94608 , United States.

Kinetoplastid parasites have caused human disease for millennia. Significant achievements have been made toward developing new treatments for leishmaniasis (particularly on the Indian subcontinent) and for human African trypanosomiasis (HAT). Moreover, the sustained decrease in the incidence of HAT has made the prospect of elimination a tantalizing reality. Read More

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http://dx.doi.org/10.1021/acsinfecdis.8b00298DOI Listing
February 2019
1 Read

Detection of Wolbachia and different trypanosome species in Glossina palpalis palpalis populations from three sleeping sickness foci of southern Cameroon.

Parasit Vectors 2018 Dec 12;11(1):630. Epub 2018 Dec 12.

Molecular Parasitology and Entomology Unit (MPEU), Department of Biochemistry, Faculty of Science, University of Dschang, PO Box 67, Dschang, Cameroon.

Background: African trypanosomiases are caused by trypanosomes that are cyclically transmitted by tsetse. Investigations aiming to generate knowledge on the bacterial fauna of tsetse have revealed distinct symbiotic microorganisms. Furthermore, studies addressing the tripartite association between trypanosomes-tsetse-symbionts relationship have so far been contradictory. Read More

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http://dx.doi.org/10.1186/s13071-018-3229-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292098PMC
December 2018

Data and tools to integrate climate and environmental information into public health.

Infect Dis Poverty 2018 Nov 29;7(1):126. Epub 2018 Nov 29.

The International Research Institute for Climate and Society, The Earth Institute, Columbia University, 61 Route 9W, Lamont-Doherty, Palisades, NY, 10964, USA.

Background: During the last 30 years, the development of geographical information systems and satellites for Earth observation has made important progress in the monitoring of the weather, climate, environmental and anthropogenic factors that influence the reduction or the reemergence of vector-borne diseases. Analyses resulting from the combination of geographical information systems (GIS) and remote sensing have improved knowledge of climatic, environmental, and biodiversity factors influencing vector-borne diseases (VBDs) such as malaria, visceral leishmaniasis, dengue, Rift Valley fever, schistosomiasis, Chagas disease and leptospirosis. These knowledge and products developed using remotely sensed data helped and continue to help decision makers to better allocate limited resources in the fight against VBDs. Read More

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http://dx.doi.org/10.1186/s40249-018-0501-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292116PMC
November 2018

Understanding Structure-Activity Relationships for Trypanosomal Cysteine Protease Inhibitors by Simulations and Free Energy Calculations.

J Chem Inf Model 2019 Jan 21;59(1):137-148. Epub 2018 Dec 21.

Laboratório de Modelagem Molecular e Planejamento de Fármacos, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas , Universidade Federal de Minas Gerais , Avenida Antônio Carlos 6627 , Belo Horizonte , MG 31270-901 , Brazil.

The protozoan cysteine proteases cruzain in Trypanosoma cruzi and rhodesain in Trypanosoma brucei are therapeutic targets for Chagas disease and Human African Trypanosomiasis (HAT), respectively. A benzimidazole series was previously characterized as potent noncovalent competitive cruzain and rhodesain inhibitors with activity against trypanosomes. Common structure-activity relationships (SAR) trends and structural modifications leading to selectivity against each enzyme were described. Read More

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http://pubs.acs.org/doi/10.1021/acs.jcim.8b00557
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http://dx.doi.org/10.1021/acs.jcim.8b00557DOI Listing
January 2019
5 Reads

Monitoring the elimination of human African trypanosomiasis: Update to 2016.

PLoS Negl Trop Dis 2018 12 6;12(12):e0006890. Epub 2018 Dec 6.

World Health Organization, Control of Neglected Tropical Diseases, Innovative and Intensified Disease Management, Geneva, Switzerland.

Background: Human African trypanosomiasis (HAT) is a neglected tropical disease targeted for elimination 'as a public health problem' by 2020. The indicators to monitor progress towards the target are based on the number of reported cases, the related areas and populations exposed at various levels of risk, and the coverage of surveillance activities. Based on data provided by the National Sleeping Sickness Control Programmes (NSSCP), Non-Governmental Organizations (NGOs) and research institutions-and assembled in the Atlas of HAT-the World Health Organization (WHO) provides here an update to 2016 for these indicators, as well as an analysis of the epidemiological situation. Read More

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http://dx.plos.org/10.1371/journal.pntd.0006890
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http://dx.doi.org/10.1371/journal.pntd.0006890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283345PMC
December 2018
17 Reads

The elimination of human African trypanosomiasis is in sight: Report from the third WHO stakeholders meeting on elimination of gambiense human African trypanosomiasis.

PLoS Negl Trop Dis 2018 12 6;12(12):e0006925. Epub 2018 Dec 6.

Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.

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http://dx.doi.org/10.1371/journal.pntd.0006925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283460PMC
December 2018

The Hsp70/J-protein machinery of the African trypanosome, Trypanosoma brucei.

Cell Stress Chaperones 2019 Jan 1;24(1):125-148. Epub 2018 Dec 1.

Biotechnology Innovation Centre, Rhodes University, Grahamstown, South Africa.

The etiological agent of the neglected tropical disease African trypanosomiasis, Trypanosoma brucei, possesses an expanded and diverse repertoire of heat shock proteins, which have been implicated in cytoprotection, differentiation, as well as progression and transmission of the disease. Hsp70 plays a crucial role in proteostasis, and inhibition of its interactions with co-chaperones is emerging as a potential therapeutic target for numerous diseases. In light of genome annotations and the release of the genome sequence of the human infective subspecies, an updated and current in silico overview of the Hsp70/J-protein machinery in both T. Read More

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http://dx.doi.org/10.1007/s12192-018-0950-xDOI Listing
January 2019
1 Read

Carbohydrate-naphthalene diimide conjugates as potential antiparasitic drugs: Synthesis, evaluation and structure-activity studies.

Eur J Med Chem 2019 Feb 19;163:54-66. Epub 2018 Nov 19.

Department of Chemistry, University of Pavia, V. le Taramelli 10, 27100, Pavia, Italy. Electronic address:

The neglected tropical diseases Human African Trypanosomiasis and leishmaniasis are caused by infection with trypanosomatid parasites Trypanosoma brucei and Leishmania spp, respectively. The genomes of these organisms contain multiple putative G-quadruplex (G4) forming sequences which have recently been proposed to mediate processes relevant for parasite survival. Therefore, G4 could be considered as potential targets for a novel approach towards the development of antiparasitic drugs. Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.11.043DOI Listing
February 2019

Discovery of 2-(1H-imidazo-2-yl)piperazines as a new class of potent and non-cytotoxic inhibitors of Trypanosoma brucei growth in vitro.

Bioorg Med Chem Lett 2018 Dec 22;28(23-24):3689-3692. Epub 2018 Oct 22.

Departments of Chemistry and Biology, IRBM Science Park, Via Pontina km 30,600, 00071 Pomezia, Rome, Italy.

The identification of a new series of growth inhibitors of Trypanosoma brucei rhodesiense, causative agent of Human African Trypanosomiasis (HAT), is described. A selection of compounds from our in-house compound collection was screened in vitro against the parasite leading to the identification of compounds with nanomolar inhibition of T. brucei growth. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S0960894X183083
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http://dx.doi.org/10.1016/j.bmcl.2018.10.028DOI Listing
December 2018
4 Reads

Insights into antitrypanosomal drug mode-of-action from cytology-based profiling.

PLoS Negl Trop Dis 2018 11 26;12(11):e0006980. Epub 2018 Nov 26.

Wellcome Trust Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, United Kingdom.

Chemotherapy continues to have a major impact on reducing the burden of disease caused by trypanosomatids. Unfortunately though, the mode-of-action (MoA) of antitrypanosomal drugs typically remains unclear or only partially characterised. This is the case for four of five current drugs used to treat Human African Trypanosomiasis (HAT); eflornithine is a specific inhibitor of ornithine decarboxylase. Read More

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http://dx.plos.org/10.1371/journal.pntd.0006980
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http://dx.doi.org/10.1371/journal.pntd.0006980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283605PMC
November 2018
8 Reads

Anilinoquinoline based inhibitors of trypanosomatid proliferation.

PLoS Negl Trop Dis 2018 11 26;12(11):e0006834. Epub 2018 Nov 26.

Northeastern University, Department of Chemistry & Chemical Biology, Boston, United States of America.

We recently reported the medicinal chemistry re-optimization of a series of compounds derived from the human tyrosine kinase inhibitor, lapatinib, for activity against Plasmodium falciparum. From this same library of compounds, we now report potent compounds against Trypanosoma brucei brucei (which causes human African trypanosomiasis), T. cruzi (the pathogen that causes Chagas disease), and Leishmania spp. Read More

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http://dx.doi.org/10.1371/journal.pntd.0006834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283615PMC
November 2018
1 Read

The population genomics of multiple tsetse fly (Glossina fuscipes fuscipes) admixture zones in Uganda.

Mol Ecol 2019 Jan;28(1):66-85

Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut.

Understanding the mechanisms that enforce, maintain or reverse the process of speciation is an important challenge in evolutionary biology. This study investigates the patterns of divergence and discusses the processes that form and maintain divergent lineages of the tsetse fly Glossina fuscipes fuscipes in Uganda. We sampled 251 flies from 18 sites spanning known genetic lineages and the four admixture zones between them. Read More

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http://doi.wiley.com/10.1111/mec.14957
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http://dx.doi.org/10.1111/mec.14957DOI Listing
January 2019
17 Reads

Bacterial diversity obtained by culturable approaches in the gut of Glossina pallidipes population from a non sleeping sickness focus in Tanzania: preliminary results.

BMC Microbiol 2018 Nov 23;18(Suppl 1):164. Epub 2018 Nov 23.

UMR 177, IRD-CIRAD, CIRAD TA A-17/G, Campus International de Baillarguet, 34398, Montpellier Cedex 5, France.

Background: Glossina pallidipes is a haematophagous insect that serves as a cyclic transmitter of trypanosomes causing African Trypanosomiasis (AT). To fully assess the role of G. pallidipes in the epidemiology of AT, especially the human form of the disease (HAT), it is essential to know the microbial diversity inhabiting the gut of natural fly populations. Read More

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http://dx.doi.org/10.1186/s12866-018-1288-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251091PMC
November 2018
1 Read

Enhancing vector refractoriness to trypanosome infection: achievements, challenges and perspectives.

BMC Microbiol 2018 Nov 23;18(Suppl 1):179. Epub 2018 Nov 23.

Molecular Department, Vector and Vector Borne Diseases Institute, Tanzania Veterinary Laboratory Agency, Majani Mapana, Off Korogwe Road, Box, 1026, Tanga, Tanzania.

With the absence of effective prophylactic vaccines and drugs against African trypanosomosis, control of this group of zoonotic neglected tropical diseases depends the control of the tsetse fly vector. When applied in an area-wide insect pest management approach, the sterile insect technique (SIT) is effective in eliminating single tsetse species from isolated populations. The need to enhance the effectiveness of SIT led to the concept of investigating tsetse-trypanosome interactions by a consortium of researchers in a five-year (2013-2018) Coordinated Research Project (CRP) organized by the Joint Division of FAO/IAEA. Read More

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http://dx.doi.org/10.1186/s12866-018-1280-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251094PMC
November 2018
12 Reads
2.729 Impact Factor

Towards improving tsetse fly paratransgenesis: stable colonization of Glossina morsitans morsitans with genetically modified Sodalis.

BMC Microbiol 2018 Nov 23;18(Suppl 1):165. Epub 2018 Nov 23.

Department of Biomedical Sciences, Unit of Veterinary Protozoology, Institute of Tropical Medicine Antwerp, Antwerp, Belgium.

Background: Tsetse flies (Glossina sp.) refractory to trypanosome infection are currently being explored as potential tools to contribute in the control of human and animal African trypanosomiasis. One approach to disrupt trypanosome transmission by the tsetse fly vector involves the use of paratransgenesis, a technique that aims to reduce vector competence of disease vectors via genetic modification of their microbiota. Read More

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http://dx.doi.org/10.1186/s12866-018-1282-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251102PMC
November 2018

Combining paratransgenesis with SIT: impact of ionizing radiation on the DNA copy number of Sodalis glossinidius in tsetse flies.

BMC Microbiol 2018 Nov 23;18(Suppl 1):160. Epub 2018 Nov 23.

Insect Pest Control Laboratory, Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture, Vienna International Centre, P.O. Box 100, 1400, Vienna, Austria.

Background: Tsetse flies (Diptera: Glossinidae) are the cyclical vectors of the causative agents of African Trypanosomosis, which has been identified as a neglected tropical disease in both humans and animals in many regions of sub-Saharan Africa. The sterile insect technique (SIT) has shown to be a powerful method to manage tsetse fly populations when used in the frame of an area-wide integrated pest management (AW-IPM) program. To date, the release of sterile males to manage tsetse fly populations has only been implemented in areas to reduce transmission of animal African Trypanosomosis (AAT). Read More

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http://dx.doi.org/10.1186/s12866-018-1283-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251162PMC
November 2018
7 Reads

Prevalence of symbionts and trypanosome infections in tsetse flies of two villages of the "Faro and Déo" division of the Adamawa region of Cameroon.

BMC Microbiol 2018 Nov 23;18(Suppl 1):159. Epub 2018 Nov 23.

Institut de Recherche pour le Développement (IRD)-CIRAD, UMR 177, Montpellier, France.

Background: Tsetse flies are vectors of human and animal African trypanosomiasis. In spite of many decades of chemotherapy and vector control, the disease has not been eradicated. Other methods like the transformation of tsetse fly symbionts to render the fly refractory to trypanosome infection are being evaluated. Read More

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http://dx.doi.org/10.1186/s12866-018-1286-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251084PMC
November 2018
5 Reads

Complementary Quantitative Structure⁻Activity Relationship Models for the Antitrypanosomal Activity of Sesquiterpene Lactones.

Int J Mol Sci 2018 Nov 22;19(12). Epub 2018 Nov 22.

Institute of Pharmaceutical Biology and Phytochemistry (IPBP), University of Muenster, PharmaCampus Corrensstrasse 48, D-48149 Muenster, Germany.

Three complementary quantitative structure⁻activity relationship (QSAR) methodologies, namely, regression modeling based on (i) "classical" molecular descriptors, (ii) 3D pharmacophore features, and (iii) 2D molecular holograms (HQSAR) were employed on the antitrypanosomal activity of sesquiterpene lactones (STLs) toward , the causative agent of the East African form of human African trypanosomiasis. In this study, an extension of a previous QSAR study on 69 STLs, models for a much larger and more diverse set of such natural products, now comprising 130 STLs of various structural subclasses, were established. The extended data set comprises a variety of STLs isolated and tested for antitrypanosomal activity within our group and is furthermore enhanced by 12 compounds obtained from literature, which have been tested in the same laboratory under identical conditions. Read More

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http://dx.doi.org/10.3390/ijms19123721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321053PMC
November 2018

Targeting the Pentose Phosphate Pathway: Characterization of a New 6PGL Inhibitor.

Biophys J 2018 Dec 6;115(11):2114-2126. Epub 2018 Nov 6.

Laboratoire des Biomolécules, LBM, Département de Chimie, École Normale Supérieure, PSL University, Sorbonne Université, CNRS, 75005 Paris, France.

Human African trypanosomiasis, or sleeping sickness, is a lethal disease caused by the protozoan parasite Trypanosoma brucei. However, although many efforts have been made to understand the biochemistry of this parasite, drug development has led to treatments that are of limited efficiency and of great toxicity. To develop new drugs, new targets must be identified, and among the several metabolic processes of trypanosomes that have been proposed as drug targets, carbohydrate metabolism (glycolysis and the pentose phosphate pathway (PPP)) appears as a promising one. Read More

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http://dx.doi.org/10.1016/j.bpj.2018.10.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289167PMC
December 2018
13 Reads

Drug quality analysis of isometamidium chloride hydrochloride and diminazene diaceturate used for the treatment of African animal trypanosomosis in West Africa.

BMC Vet Res 2018 Nov 20;14(1):361. Epub 2018 Nov 20.

Bioengineering Department, Vrije Universiteit Brussel, Pleinlaan 2, B-1050, Brussels, Belgium.

Background: Diminazene diaceturate (DA) and isometamidium chloride hydrochloride (ISM) are with homidium bromide, the main molecules used to treat African Animal Trypanosomosis (AAT). These drugs can be purchased from official suppliers but also from unofficial sources like local food markets or street vendors. The sub-standard quality of some of these trypanocides is jeopardizing the efficacy of treatment of sick livestock, leading thus to economic losses for the low-resource farmers and is contributing to the emergence and spread of drug resistance. Read More

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http://dx.doi.org/10.1186/s12917-018-1633-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247674PMC
November 2018
8 Reads

Thiazole, thio and semicarbazone derivatives against tropical infective diseases: Chagas disease, human African trypanosomiasis (HAT), leishmaniasis, and malaria.

Eur J Med Chem 2019 Jan 12;162:378-395. Epub 2018 Nov 12.

São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, SP, Brazil. Electronic address:

Thiazole, thiosemicarbazone and semicarbazone moieties are privileged scaffolds (acting as primary pharmacophores) in many compounds that are useful to treat several diseases, mainly tropical infectious diseases. In this review article, we critically analyzed the contribution of these scaffolds to medicinal chemistry in the last five years, focusing on tropical infectious diseases, such as Chagas disease, human African trypanosomiasis (HAT), leishmaniasis, and malaria. We also present perspectives for their use in drug design in order to contribute to the development of new drugs. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S02235234183096
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http://dx.doi.org/10.1016/j.ejmech.2018.11.013DOI Listing
January 2019
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In vitro Anti-Trypanosomal Activities of Indanone-Based Chalcones.

Drug Res (Stuttg) 2018 Nov 16. Epub 2018 Nov 16.

Centre for Chemico- and Biomedicinal Research, Rhodes University, Grahamstown, South Africa.

Human African trypanosomiasis is a neglected infectious disease that affects mostly people living in the rural areas of Africa. Current treatment options are limited to just four drugs that have been in use of four to nine decades. The life-threatening toxic side-effects associated with the use of these drugs are disconcerting. Read More

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http://dx.doi.org/10.1055/a-0775-0737DOI Listing
November 2018
1 Read

Trypanosoma brucei: β2-selective proteasome inhibitors do not block the proteasomal trypsin-like activity but are trypanocidal.

Mol Biochem Parasitol 2019 Jan 13;227:1-4. Epub 2018 Nov 13.

Leiden Institute of Chemistry, Leiden University, 2333 CC, Leiden, the Netherlands.

Previous studies indicated that the proteasome of the protozoan parasite Trypanosoma brucei is particularly sensitive to inhibition of the trypsin-like activity. In this study, three newly developed β2 subunit-specific inhibitor (LU-102, LU-002c and LU-002i) were tested for their ability to block the trypsin-like activity of the trypanosomal proteasome. At 10 μM, none of the compounds affected the proteasomal trypsin-like activity in cell lysates of bloodstream forms of T. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S01666851183019
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http://dx.doi.org/10.1016/j.molbiopara.2018.11.002DOI Listing
January 2019
9 Reads