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J Vis Exp 2019 Apr 6(146). Epub 2019 Apr 6.

Univ. Bordeaux UMR INTERTRYP 177 IRD CIRAD; IRD UMR 177 INTERTRYP CIRAD; Centre Hospitalier Université Bordeaux;

This method allows the separation of trypanosomes, parasites responsible for animal and human African trypanosomiasis (HAT), from infected blood. This is the best method for diagnosis of first stage HAT and furthermore this parasite purification method permits serological and research investigations. HAT is caused by Tsetse fly transmitted Trypanosoma brucei gambiense and T. Read More

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):1428-1436

c School of Pharmacy , University of the Western Cape , Bellville , South Africa.

Nanoparticles (NPs) have gained importance in addressing drug delivery challenges across biological barriers. Here, we reformulated pentamidine, a drug used to treat Human African Trypanosomiasis (HAT) in polymer based nanoparticles and liposomes and compared their capability to enhance pentamidine penetration across blood brain barrier (BBB). Size, polydispersity index, zeta potential, morphology, pentamidine loading and drug release profiles were determined by various methods. Read More

Trop Anim Health Prod 2019 Apr 17. Epub 2019 Apr 17.

Department of Veterinary Parasitology and Entomology, Faculty of Veterinary Medicine, University of Ibadan, Nigeria, Ibadan, Nigeria.

African animal trypanosomiasis is a major cause of mortality and economic losses for the livestock industry in Nigeria. Chemotherapy has been the most reliable option for cattle herders, and the most commonly found drug on the market is diminazene aceturate. To ascertain the long-term efficacy of this compound, we sampled a cattle herd in Ogun State, Nigeria, 2 months after they were treated with diminazene aceturate. Read More

Beijing Da Xue Xue Bao Yi Xue Ban 2019 Apr;51(2):197-205

Institute of Systems Biomedicine, State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Science, Beijing 100191, China.

Objective: To investigate functions of proteins and signaling pathways involved in epileptogenesis during the chronic stage of temporal lobe epilepsy in mouse models.

Methods: Kainic acid-induced temporal lobe epilepsy models were conducted, when reaching stage 4 using racine scale, the mice of experimental group were supposed to be successfully established. Pentobarbital sodium was injected to stop epileptic seizure in case of death. Read More

PLoS One 2019 17;14(4):e0215070. Epub 2019 Apr 17.

Malaria Research Unit, UMR 5246 CNRS, Claude-Bernard Lyon-1 University, Villeurbanne, France.

To study the anatomo-biochemical substrates of brain inflammatory processes, Wistar male rats were infected with Trypanosoma brucei brucei. With this reproducible animal model of human African trypanosomiasis, brain cells (astrocytes, microglial cells, neurons) expressing the inducible nitric oxide synthase (iNOS) enzyme were revealed. Immunohistochemistry was achieved for each control and infected animal through eight coronal brain sections taken along the caudorostral axis of the brain (brainstem, cerebellum, diencephalon and telencephalon). Read More

Eur J Med Chem 2019 Apr 3;173:90-98. Epub 2019 Apr 3.

Department of Bioorganic Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89b, 61‒614, Poznań, Poland.

As a group of biologically active compounds, polyether antibiotics (ionophores) show a broad spectrum of interesting pharmacological properties, ranging from anti-bacterial to anti-cancer activities. There is increasing evidence that ionophores, including salinomycin (SAL), and their semi-synthetic analogues are promising candidates for the development of drugs against parasitic diseases. Our previous studies have shown that esterification and amidation of the C1 carboxylate moiety of SAL provides compounds with potent activity against Trypanosoma brucei, protozoan parasites responsible for African trypanosomiasis. Read More

Proc Natl Acad Sci U S A 2019 Apr 5. Epub 2019 Apr 5.

Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.

Ascofuranone (AF) and ascochlorin (AC) are meroterpenoids produced by various filamentous fungi, including (synonym: ), and exhibit diverse physiological activities. In particular, AF is a promising drug candidate against African trypanosomiasis and a potential anticancer lead compound. These compounds are supposedly biosynthesized through farnesylation of orsellinic acid, but the details have not been established. Read More

Parasit Vectors 2019 Apr 2;12(1):151. Epub 2019 Apr 2.

INTERTRYP, Institut de Recherche pour le Développement, University of Montpellier, Montpellier, France.

Background: A number of reports have demonstrated the role of insect bacterial flora on their host's physiology and metabolism. The tsetse host and vector of trypanosomes responsible for human sleeping sickness (human African trypanosomiasis, HAT) and nagana in animals (African animal trypanosomiasis, AAT) carry bacteria that influence its diet and immune processes. However, the mechanisms involved in these processes remain poorly documented. Read More

Int J Mol Sci 2019 Mar 25;20(6). Epub 2019 Mar 25.

Programa de Pós-graduação em Bioquímica, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal 59064-741, Brazil.

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

BJR Case Rep 2018 Dec 18;4(4):20180039. Epub 2018 Jun 18.

Department of Radiology, University College Hospital, London, UK.

Human African Trypanosomiasis (HAT) is a neglected tropical disease that affected 3797 people worldwide in 2014. Without treatment mortality approaches 100%. Due to its low incidence and non-specific clinical features, diagnosis can be challenging and the role of MRI in diagnosis of HAT has not been evaluated outside of case reports. Read More

Antimicrob Agents Chemother 2019 Mar 25. Epub 2019 Mar 25.

Department of Microbiology, Hellenic Pasteur Institute, Athens, Greece

The protozoan parasite () is the causative agent of Human African trypanosomiasis (HAT). The disease is fatal if untreated whereas most drug treatments are inadequate due to high toxicity, difficulties in administration and low CNS penetration. Glycogen Synthase Kinase-3 short (GSK3s) is essential for parasite survival and thus represents a potential drug target that could be exploited for HAT treatment. Read More

Molecules 2019 Mar 23;24(6). Epub 2019 Mar 23.

GNOS Research Group, Louvain Drug Research Institute, Université catholique de Louvain, UCLouvain, 1200 Bruxelles, Belgium.

Human African trypanosomiasis (HAT), known as sleeping sickness and caused by , 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 () and cytotoxicity on mammalian cells (WI38, J774). Based on the selectivity indices (SIs), the more active and selective EOs were analyzed by gas chromatography. Read More

PLoS Negl Trop Dis 2019 03 25;13(3):e0007283. Epub 2019 Mar 25.

Molecular Parasitology and Entomology Unit, Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon.

Background: Human African Trypanosomiasis (HAT) is a neglected tropical disease caused by infections due to Trypanosoma brucei subspecies. In addition to the well-established environmental and behavioural risks of becoming infected, there is evidence for a genetic component to the response to trypanosome infection. We undertook a candidate gene case-control study to investigate genetic associations further. Read More

Heliyon 2019 Mar 7;5(3):e01304. Epub 2019 Mar 7.

MCNSL, Department of Chemistry, Faculty of Sciences, University Moulay Ismail, Meknes, Morocco.

The quantitative structure-activity relationship (QSAR) of sixty 2-phenylimidazopyridines derivatives with anti-Human African Trypanosomiasis (anti-HAT) activity has been studied by using the density functional theory (DFT) and statistical methods. Becke's three-parameter hybrid method and the Lee-Yang-Parr B3LYP functional employing 6-31G(d) basis set are used to calculate quantum chemical descriptors using Gaussian 03W software, and the five Lipinski's parameters were calculated using ChemOffice software. In order to obtain robust and reliable QSAR model, the original dataset was randomly divided into training and prediction sets comprising 48 and 12 compounds, respectively. Read More

Exp Parasitol 2019 Mar 18;200:24-29. Epub 2019 Mar 18.

Laboratory of Biochemistry, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, 790-8578, Japan.

Cases of human African trypanosomiasis caused by infection with a protozoan parasite, Trypanosoma brucei, are decreasing due to enhanced surveillance and control. However, effective and safe treatments for this disease are still needed. In this study, we investigated the antitrypanosomal activity of citrus fruit peel. Read More

BMC Res Notes 2019 Mar 18;12(1):151. Epub 2019 Mar 18.

Centre for Biotechnology and Bioinformatics, University of Nairobi, Nairobi, Kenya.

Objective: In Sub-Saharan Africa, there is an increase in trypanosome non-susceptibility to multiple trypanocides, but limited information on judicious trypanocide use is accessible to smallholder farmers and agricultural stakeholders in disease endemic regions, resulting in widespread multi-drug resistance. Huge economic expenses and the laborious nature of extensive field studies have hindered collection of the requisite large-scale prospective datasets required to inform disease management. We examined the efficacy of community-led data collection strategies using smartphones by smallholder farmers to acquire robust datasets from the trypanosomiasis endemic Shimba hills region in Kenya. Read More

Oxid Med Cell Longev 2019 7;2019:6587150. Epub 2019 Feb 7.

Laboratório de Síntese e Vetorização de Moléculas, Departamento de Ciências Biológicas, Universidade Estadual da Paraíba, 58071-160 João Pessoa-PB, Brazil.

The term refers to a group of infections caused by various classes of pathogens, including protozoa, viruses, bacteria, and helminths, most often affecting impoverished populations without adequate sanitation living in close contact with infectious vectors and domestic animals. The fact that these diseases were historically not considered priorities for pharmaceutical companies made the available treatments options obsolete, precarious, outdated, and in some cases nonexistent. The use of plants for medicinal, religious, and cosmetic purposes has a history dating back to the emergence of humanity. Read More

PLoS Genet 2019 03 15;15(3):e1008005. Epub 2019 Mar 15.

Dept. of Molecular Cellular and Developmental Biology, Yale University, New Haven, Connecticut, United States of America.

Dipteran or "true" flies occupy nearly every terrestrial habitat, and have evolved to feed upon a wide variety of sources including fruit, pollen, decomposing animal matter, and even vertebrate blood. Here we analyze the molecular, genetic and cellular basis of odor response in the tsetse fly Glossina morsitans, which feeds on the blood of humans and their livestock, and is a vector of deadly trypanosomes. The G. Read More

Met Ions Life Sci 2019 Jan;19

Metal compounds seem to be a promising approach in the search of new therapeutic solutions for neglected tropical diseases. In this chapter, efforts in the design of prospective metal-based drugs for the treatment of Chagas disease, human African trypanosomiasis, and leishmaniasis are discussed. Careful selection of the metal center (including organometallic cores) and the types and number of coordinated ligands is essential for controlling the reactivity of the complexes and hence, tuning their biological properties. Read More

Exp Parasitol 2019 Apr 3;199:40-46. Epub 2019 Mar 3.

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11 Inada, Obihiro, Hokkaido, 080-8555, Japan; Research Center for Global Agromedicine, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11 Inada, Obihiro, Hokkaido, 080-8555, Japan. Electronic address:

Human African trypanosomosis (HAT) and animal African trypanosomosis (AAT) are diseases of economic importance in humans and animals that affect more than 36 African countries. The currently available trypanocidal drugs are associated with side effects, and the parasites are continually developing resistance. Thus, effective and safe drugs are needed for the treatment of HAT and AAT. Read More

Bioorg Med Chem 2019 Apr 25;27(8):1517-1528. Epub 2019 Feb 25.

Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address:

Previously synthesized tubulin inhibitors showed promising in vitro selectivity and activity against Human African Trypanosomiasis. Current aim is to improve the ligand efficiency and reduce overall hydrophobicity of the compounds, by lead optimization. Via combinatorial chemistry, 60 new analogs were synthesized. Read More

Trends Parasitol 2019 04 28;35(4):302-315. Epub 2019 Feb 28.

Division of Structural Biology of Infection and Immunity, German Cancer Research Center, Heidelberg, Germany. Electronic address:

Trypanosoma brucei, which causes African trypanosomiasis, avoids immunity by periodically switching its surface composition. The parasite is coated by 10 million identical, monoallelically expressed variant surface glycoprotein (VSG) molecules. Multiple distinct parasites (with respect to their VSG coat) coexist simultaneously during each wave of parasitemia. Read More

PLoS Pathog 2019 02 28;15(2):e1007470. Epub 2019 Feb 28.

Yale School of Public Health, Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, United States of America.

Tsetse flies (Glossina spp.) vector pathogenic trypanosomes (Trypanosoma spp.) in sub-Saharan Africa. Read More

PLoS Negl Trop Dis 2019 02 28;13(2):e0007051. Epub 2019 Feb 28.

Institut de Recherche pour le Développement, UMR INTERTRYP, Université de Montpellier-IRD-CIRAD, Montpellier, France.

Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease that is fatal if untreated, caused by Trypanosoma brucei gambiense and T. brucei rhodesiense. In its 2012 roadmap, WHO targeted HAT for elimination as a public health problem in 2020 and for zero transmission in 2030. Read More

PLoS Negl Trop Dis 2019 02 25;13(2):e0006842. Epub 2019 Feb 25.

Division of Collaboration and Education, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.

To improve our knowledge on the epidemiological status of African trypanosomiasis, better tools are required to monitor Trypanosome genotypes circulating in both mammalian hosts and tsetse fly vectors. This is important in determining the diversity of Trypanosomes and understanding how environmental factors and control efforts affect Trypanosome evolution. We present a single test approach for molecular detection of different Trypanosome species and subspecies using newly designed primers to amplify the Internal Transcribed Spacer 1 region of ribosomal RNA genes, coupled to Illumina sequencing of the amplicons. Read More

PLoS Negl Trop Dis 2019 02 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

Nat Commun 2019 02 18;10(1):803. Epub 2019 Feb 18.

Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.

The unicellular parasite Trypanosoma brucei is transmitted between mammals by tsetse flies. Following the discovery that flagellar phosphodiesterase PDEB1 is required for trypanosomes to move in response to signals in vitro (social motility), we investigated its role in tsetse flies. Here we show that PDEB1 knockout parasites exhibit subtle changes in movement, reminiscent of bacterial chemotaxis mutants. 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 Mar 13;62(6):3021-3035. Epub 2019 Mar 13.

Department of Biological and Geographical Sciences, School of Applied Sciences , University of Huddersfield , Huddersfield HD1 3DH , U.K.

Animal African trypanosomiasis (AAT) is a significant socioeconomic burden for sub-Saharan Africa because of its huge impact on livestock health. Existing therapies including those based on minor groove binders (MGBs), such as the diamidines, which have been used for decades, have now lost efficacy in some places because of 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 02 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 Apr;100(4):899-906

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 Apr 27;63(4). Epub 2019 Mar 27.

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

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

ChemMedChem 2019 Mar 5;14(6):621-635. Epub 2019 Feb 5.

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 Apr 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 02;38(1):50-57

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 01 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 2019 Jan 10;62(2):665-687. Epub 2019 Jan 10.

Department of Chemistry and Chemical Biology , Northeastern University , Boston , Massachusetts 02115 , United States.

Lapatinib, an approved epidermal growth factor receptor 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 antitrypanosomal potency. Read More