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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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