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Trends Parasitol 2021 May 4. Epub 2021 May 4.

Institute of Biodiversity, Animal Health & Comparative Medicine, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK.

Trypanocides are a key control component of African animal trypanosomiasis (AAT) in tsetse-infested areas of sub-Saharan Africa. While farmers are dependent upon trypanocides, recent research highlights their inappropriate and ineffective use, problems with drug quality, and treatment failure. There are currently gaps in knowledge and investment in inexpensive AAT diagnostics, understanding of drug resistance, and the effective use of trypanocides in the field. Read More

Curr Med Chem 2021 May 3. Epub 2021 May 3.

Medicinal Chemistry Research Laboratory, Department of Chemistry, Jamia Millia Islamia, Jamia Nagar, New Delhi-110025, India.

Human African and American trypanosomiasis are the vector-borne parasitic diseases that have killed millions of people early, and many people are still suffering from these neglected diseases. The causative agents of these infections are parasitic protozoans of the genus Trypanosoma. Current treatment regimens against these endemic diseases have several limitations in terms of safety, efficacy, route of administration, and some of them have lost efficacy due to the emergence of resistance in their respective parasites. Read More

Trop Med Infect Dis 2021 Apr 30;6(2). Epub 2021 Apr 30.

College of Public Health Medical and Veterinary Services, James Cook University, Townsville, QLD 4814, Australia.

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

Front Cell Infect Microbiol 2021 16;11:669079. Epub 2021 Apr 16.

Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.

, spp., and are flagellate protozoans of the family Trypanosomatidae and the causative agents of human African trypanosomiasis, leishmaniasis, and Chagas disease, respectively. These diseases affect humans worldwide and exert a significant impact on public health. Read More

Microorganisms 2021 Apr 13;9(4). Epub 2021 Apr 13.

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, 2610 Wilrijk, Belgium.

Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. Read More

Clin Infect Dis 2021 Apr 27. Epub 2021 Apr 27.

Mathematics Institute, University of Warwick, Coventry, United Kingdom.

Background: The gambiense human African trypanosomiasis (gHAT) elimination programme in the Democratic Republic of Congo (DRC) routinely collects case data through passive surveillance and active screening, with several regions reporting no cases for several years, despite being endemic in the early 2000s.

Methods: We use mathematical models fitted to longitudinal data to estimate the probability that selected administrative regions have already achieved elimination of transmission (EOT) of gHAT. We examine the impact of active screening coverage on the certainty of model estimates for transmission and therefore the role of screening in the measurement of EOT. Read More

Environ Pollut 2021 Apr 15;284:117152. Epub 2021 Apr 15.

Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University Health Science Center, Shenzhen, Guangdong, People's Republic of China. Electronic address:

This systematic review and meta-analysis aimed to investigate the association between air pollution and DNA methylation in adults from published observational studies. PubMed, Web of Science and Embase databases were systematically searched for available studies on the association between air pollution and DNA methylation published up to March 9, 2021. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). Read More

ACS Infect Dis 2021 Apr 19. Epub 2021 Apr 19.

In this Viewpoint, we provide a brief description of two efforts to develop drugs to treat diseases caused by tropical parasites (Malaria, human African trypanosomiasis and Chagas disease). These efforts are largely based in a University setting but draw heavily on Pharma for a complete progression from drug hit discovery to advancement toward clinical trials. The first case is the development of protein farnesyltransferase inhibitors, and the second case is a series of benzthiazoles, the target of which is being investigated. Read More

ACS Infect Dis 2021 Apr 19. Epub 2021 Apr 19.

Department of Parasitology, Instituto de Investigación Biosanitaria (ibs. Granada), Hospitales Universitarios De Granada/University of Granada, Severo Ochoa s/n, 18071 Granada, Spain.

Chagas disease is a tropical infection caused by the protozoan parasite and a global public health concern. It is a paradigmatic example of a chronic disease without an effective treatment. Current treatments targeting are limited to two obsolete nitroheterocyclic drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Read More

PLoS Negl Trop Dis 2021 Apr 15;15(4):e0009276. Epub 2021 Apr 15.

King's College London, Institute of Pharmaceutical Science, Franklin-Wilkins Building, Stamford Street, London, United Kingdom.

Background: Human African trypanosomiasis (HAT or sleeping sickness) is caused by the parasite Trypanosoma brucei sspp. The disease has two stages, a haemolymphatic stage after the bite of an infected tsetse fly, followed by a central nervous system stage where the parasite penetrates the brain, causing death if untreated. Treatment is stage-specific, due to the blood-brain barrier, with less toxic drugs such as pentamidine used to treat stage 1. Read More

Luminescence 2021 Apr 5. Epub 2021 Apr 5.

General Courses Unit, Faculty of Sciences and Arts, King Khalid University, Dhahran Aljanoub, Saudi Arabia.

α-Difluoromethylornithine is an effective medication for the treatment of African Trypanosomiasis and widely distributed for the treatment of hirsutism. This work provides an adequate analytical protocol for the spectrophotometric and the spectrofluorimetric determination of α-difluoromethylornithine through its interaction with 4-chloro-7-nitrobenzofurazan (NBD-chloride) reagent. After optimization of the reaction conditions (NBD-chloride volume, buffer volume, the best diluting solvent, heating time and temperature and pH of the medium) the reaction product was measured spectrophotometrically at λ = 478 nm and spectrofluorimetrically at λ = 540 nm after λ = 475 nm. Read More

Vaccines (Basel) 2021 Mar 5;9(3). Epub 2021 Mar 5.

Immunoparasitology Laboratory, Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal 59078-970, Brazil.

Research on vaccines against trypanosomatids, a family of protozoa that cause neglected tropical diseases, such as Chagas disease, leishmaniasis, and sleeping sickness, is a current need. Today, according to modern vaccinology, virus-like particle (VLP) technology is involved in many vaccines, including those undergoing studies related to COVID-19. The potential use of VLPs as vaccine adjuvants opens an opportunity for the use of protozoan antigens for the development of vaccines against diseases caused by , spp. Read More

Pathogens 2021 Mar 13;10(3). Epub 2021 Mar 13.

Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, Ozzano Emilia, 40064 Bologna, Italy.

The genus includes flagellated protozoa belonging to the family Trypanosomatidae (Euglenozoa, Kinetoplastida) that can infect humans and several animal species. The most studied species are those causing severe human pathology, such as Chagas disease in South and Central America, and the human African trypanosomiasis (HAT), or infections highly affecting animal health, such as nagana in Africa and surra with a wider geographical distribution. The presence of these species in Europe has been thus far linked only to travel/immigration history of the human patients or introduction of infected animals. Read More

Molecules 2021 Mar 2;26(5). Epub 2021 Mar 2.

Department of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South Africa.

A tailored series of coumarin-based ferrocenyl 1,3-oxazine hybrid compounds was synthesized and investigated for potential antiparasitic activity, drawing inspiration from the established biological efficacy of the constituent chemical motifs. The structural identity of the synthesized compounds was confirmed by common spectroscopic techniques: NMR, HRMS and IR. Biological evaluation studies reveal that the compounds exhibit higher in vitro antiparasitic potency against the chemosensitive malarial strain (3D7 ) over the investigated trypanosomiasis causal agent ( 427) with mostly single digit micromolar IC values. Read More

Pharmaceuticals (Basel) 2021 Mar 7;14(3). Epub 2021 Mar 7.

Centre for Applied Entomology and Parasitology, Keele University, Staffordshire ST5 5BG, UK.

The use of plant-derived natural products for the treatment of tropical parasitic diseases often has ethnopharmacological origins. As such, plants grown in temperate regions remain largely untested for novel anti-parasitic activities. We describe here a screen of the PhytoQuest Phytopure library, a novel source comprising over 600 purified compounds from temperate zone plants, against in vitro culture systems for , , and . Read More

Prog Chem Org Nat Prod 2021 ;115:177-203

School of Pharmacy and Medical Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK.

Cryptolepine, the principal constituent of the West African climbing shrub Cryptolepis sanguinolenta, continues to be of interest as a lead to new therapeutic agents, especially for the treatment of protozoal infections and cancer. This contribution reviews the research published in the last decade, highlighting new synthesis routes to cryptolepine and to analogs of this alkaloid, as well as their pharmacology. Studies relating to the use of C. Read More

Curr Top Med Chem 2021 Mar 31. Epub 2021 Mar 31.

Chemistry and Biotechnology Institute, Federal University of Alagoas, Maceió. Brazil.

Neglected tropical diseases (NTDs) are a group of approximately 20 diseases that affect part of the population in Sub- and Tropical countries. In the past, pharmaceutical industries and governmental agencies have invested in the control, elimination and eradication of such diseases. Among these diseases, Chagas disease (CD) and Human African trypanosomiasis (HAT) are a public health problem, mainly in the countries from the American continent and sub-Saharan African. Read More

BMC Med 2021 Apr 1;19(1):86. Epub 2021 Apr 1.

Mathematics Institute, University of Warwick, Coventry, CV4 7AL, UK.

Background: Gambiense human African trypanosomiasis (gHAT) has been brought under control recently with village-based active screening playing a major role in case reduction. In the approach to elimination, we investigate how to optimise active screening in villages in the Democratic Republic of Congo, such that the expenses of screening programmes can be efficiently allocated whilst continuing to avert morbidity and mortality.

Methods: We implement a cost-effectiveness analysis using a stochastic gHAT infection model for a range of active screening strategies and, in conjunction with a cost model, we calculate the net monetary benefit (NMB) of each strategy. Read More

Kidney Int 2021 Mar 29. Epub 2021 Mar 29.

Renal Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA; Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA; Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA. Electronic address:

APOL1 kidney risk variants (RVs) were identified in 2010 as major drivers of glomerular, tubulointerstitial, and renal microvascular disease in individuals with sub-Saharan African ancestry. In December 2020, the "APOL1 at Ten" conference summarized the first decade of progress and discussed controversies and uncertainties that remain to be addressed. Topics included trypanosome infection and its role in the evolution of APOL1 kidney RVs, clinical phenotypes in APOL1-associated nephropathy, relationships between APOL1 RVs and background haplotypes on cell injury and molecular mechanisms initiating disease, the role of clinical APOL1 genotyping, and development of novel therapies for kidney disease. Read More

ACS Infect Dis 2021 04 26;7(4):917-926. Epub 2021 Mar 26.

Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic.

Human African Trypanosomiasis caused by species is one of the most damaging neglected tropical diseases. While the number of newly diagnosed cases per year is record low, there is still high interest in the development of new antitrypanosomal agents in case of resistance to currently used drugs and their combinations, and to replace drugs with serious side effects. We report a series of 7-methyl-7-deazapurine (5-methyl-pyrrolo[2,3-]pyrimidine) ribonucleosides bearing alkyl, methylsulfanyl, methylamino, or diverse alkoxy groups at position 6 that was prepared through glycosylation of 6-chloro-7-methyl-7-deazapurine followed by nucleophilic substitutions or cross-coupling reactions at position 6 and deprotection. Read More

J Ethnopharmacol 2021 Mar 19;276:114055. Epub 2021 Mar 19.

Department of Biochemistry, University of Ilorin, Ilorin, Nigeria. Electronic address:

Ethnomedicinal Relevance: Natural products derived from plants have served the primary healthcare needs of millions of indigenous people for centuries, many of which have been documented and scientifically validated. Morinda lucida Benth (Rubiaceae), also referred to as brimstone tree, is an ethnomedicinal plant which has been widely used in traditional medicine for several decades, particularly in the African continent. Various parts of the plant, including stem bark, leaves and root, have been applied in traditional medicine for the management of various pathological conditions such as malaria, diabetes, hypertension, inflammation, typhoid fever, cancer, cognitive disorders, sickle cell disease, trypanosomiasis, onchocerciasis and various fevers. Read More

J Biol Chem 2021 Mar 18:100566. Epub 2021 Mar 18.

Institute of Plant Sciences, University of Bern, Bern, Switzerland. Electronic address:

Trypanosoma brucei is a species of unicellular parasite that can cause severe diseases in livestock and humans, including African trypanosomiasis and Chagas disease. Adaptation to diverse environments and changes in nutritional conditions are essential for T. brucei to establish an infection when changing hosts, or during invasion of different host tissues. Read More

J Biol Chem 2021 Mar 18:100565. Epub 2021 Mar 18.

Department of Chemistry, Biochemistry Division, Johannes Gutenberg-University, Mainz, Germany; Centre for Biomolecular Magnetic Resonance (BMRZ), Goethe University, Frankfurt, Germany; current address: Faculty of Chemistry and Earth Sciences, Institute of Organic and Macromolecular Chemistry, Friedrich-Schiller-University, Jena, Germany; Cluster of Excellence 'Balance of the Microverse', Friedrich-Schiller-University, Jena, Germany. Electronic address:

Rhodesain is the lysosomal cathepsin L-like cysteine protease of T. brucei rhodesiense, the causative agent of Human African Trypanosomiasis. The enzyme is essential for the proliferation and pathogenicity of the parasite as well as its ability to overcome the blood-brain barrier of the host. Read More

Bioorg Med Chem Lett 2021 May 17;40:127957. Epub 2021 Mar 17.

Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nam. 2, CZ-16000 Prague 6, Czech Republic; Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, CZ-12843 Prague 2, Czech Republic. Electronic address:

Trypanosoma brucei parasites cause Human African Trypanosomiasis and the current drugs for its treatment are often inefficient and toxic. This urges the need to development of new antitrypanosomal agents. We report the synthesis and biological profiling of 3'-deoxy-3'-fluororibonucleosides derived from 7-deazaadenine nucleosides bearing diverse substituents at position 7. Read More

Front Chem 2020 28;8:630888. Epub 2021 Jan 28.

Other, Cambridge, United Kingdom.

The eukaryotic pathogens , and are responsible for debilitating diseases that affect millions of people worldwide. The numbers of drugs available to treat these diseases, Human African Trypanosomiasis, Chagas' disease and Leishmaniasis are very limited and existing treatments have substantial shortcomings in delivery method, efficacy and safety. The identification and validation of novel drug targets opens up new opportunities for the discovery of therapeutic drugs with better efficacy and safety profiles. Read More

Eur J Med Chem 2021 May 8;217:113319. Epub 2021 Mar 8.

State Key Laboratory of Microbial Metabolism, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China. Electronic address:

The protozoan parasite Trypanosoma brucei (T. brucei) causes human African trypanosomiasis (HAT), which is a fatal and neglected disease in the tropic areas, and new treatments are urgently needed. Leucyl-tRNA synthetase (LeuRS) is an attractive target for the development of antimicrobial agents. Read More

Curr Opin Immunol 2021 Mar 11;72:13-20. Epub 2021 Mar 11.

School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.

Human African trypanosomiasis, or sleeping sickness, results from infection by two subspecies of the protozoan flagellate parasite Trypanosoma brucei, termed Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, prevalent in western and eastern Africa respectively. These subspecies escape the trypanolytic potential of human serum, which efficiently acts against the prototype species Trypanosoma brucei brucei, responsible for the Nagana disease in cattle. We review the various strategies and components used by trypanosomes to counteract the immune defences of their host, highlighting the adaptive genomic evolution that occurred in both parasite and host to take the lead in this battle. Read More

Curr Opin Neurol 2021 Jun;34(3):439-446

NIHR University College London Hospitals Biomedical Research Centre, UCL Queen Square Institute of Neurology, London, UK.

Purpose Of Review: Malaria, Chagas Disease and Human African Trypanosomiasis are vector-borne protozoan illnesses, frequently associated with neurological manifestations. Intriguing but ignored, limited mainly to resource-limited, tropical settings, these disorders are now coming to light because of globalisation and improved diagnosis and treatment. Enhanced understanding of these illnesses has prompted this review. Read More

J Clin Sleep Med 2021 Mar 9. Epub 2021 Mar 9.

Department of Mental Health, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Osun State, Nigeria.

Abstract: Interest in sleep and sleep disorders in Africa dates back thousands of years, influenced by various cultural and religious beliefs. However, the practice of sleep medicine as a specialty has been inadequate when compared to other regions of the world. The objective of this study was to explore the current status of sleep medicine in Africa vis-a-vis the education, professional societies and facilities, and to identify challenges of the specialty in the region. Read More

Biomolecules 2021 02 12;11(2). Epub 2021 Feb 12.

Department of Chemistry and Biochemistry, Wake Forest University, Winston-Salem, NC 27101, USA.

Nitroaromatic antibiotics show activity against anaerobic bacteria and parasites, finding use in the treatment of infections, tuberculosis, trichomoniasis, human African trypanosomiasis, Chagas disease and leishmaniasis. Despite this activity and a clear need for the development of new treatments for these conditions, the associated toxicity and lack of clear mechanisms of action have limited their therapeutic development. Nitroaromatic antibiotics require reductive bioactivation for activity and this reductive metabolism can convert the nitro group to nitric oxide (NO) or a related reactive nitrogen species (RNS). Read More