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Annual Review of Pathology Jan 2023African trypanosomes are bloodstream protozoan parasites that infect mammals including humans, where they cause sleeping sickness. Long-lasting infection is required to... (Review)
Review
African trypanosomes are bloodstream protozoan parasites that infect mammals including humans, where they cause sleeping sickness. Long-lasting infection is required to favor parasite transmission between hosts. Therefore, trypanosomes have developed strategies to continuously escape innate and adaptive responses of the immune system, while also preventing premature death of the host. The pathology linked to infection mainly results from inflammation and includes anemia and brain dysfunction in addition to loss of specificity and memory of the antibody response. The serum of humans contains an efficient trypanolytic factor, the membrane pore-forming protein apolipoprotein L1 (APOL1). In the two human-infective trypanosomes, specific parasite resistance factors inhibit APOL1 activity. In turn, many African individuals express APOL1 variants that counteract these resistance factors, enabling them to avoid sleeping sickness. However, these variants are associated with chronic kidney disease, particularly in the context of virus-induced inflammation such as coronavirus disease 2019. Vaccination perspectives are discussed.
Topics: Humans; Apolipoprotein L1; COVID-19; Inflammation; Trypanosoma brucei rhodesiense; Trypanosomiasis, African
PubMed: 36055769
DOI: 10.1146/annurev-pathmechdis-031621-025153 -
Parasites & Vectors Apr 2019African trypanosomes cause human African trypanosomiasis and animal African trypanosomiasis. They are transmitted by tsetse flies in sub-Saharan Africa. Although most...
African trypanosomes cause human African trypanosomiasis and animal African trypanosomiasis. They are transmitted by tsetse flies in sub-Saharan Africa. Although most famous for their mechanisms of immune evasion by antigenic variation, there have been recent important studies that illuminate important aspects of the biology of these parasites both in their mammalian host and during passage through their tsetse fly vector. This Primer overviews current research themes focused on these parasites and discusses how these biological insights and the development of new technologies to interrogate gene function are being used in the search for new approaches to control the parasite. The new insights into the biology of trypanosomes in their host and vector highlight that we are in a 'golden age' of discovery for these fascinating parasites.
Topics: Africa South of the Sahara; Animals; Host-Parasite Interactions; Humans; Insect Vectors; Trypanosoma; Trypanosoma brucei brucei; Trypanosomiasis, African; Tsetse Flies
PubMed: 31036044
DOI: 10.1186/s13071-019-3355-5 -
ELife Oct 2016Trypanosome parasites are hiding in human skin, a discovery that may undermine efforts to eliminate sleeping sickness by 2020.
Trypanosome parasites are hiding in human skin, a discovery that may undermine efforts to eliminate sleeping sickness by 2020.
Topics: Animals; Humans; Skin; Trypanosoma brucei gambiense; Trypanosomiasis, African; Tsetse Flies
PubMed: 27740910
DOI: 10.7554/eLife.21506 -
Antimicrobial Agents and Chemotherapy Feb 2020Suramin is 100 years old and is still being used to treat the first stage of acute human sleeping sickness, caused by Suramin is a multifunctional molecule with a wide... (Review)
Review
Suramin is 100 years old and is still being used to treat the first stage of acute human sleeping sickness, caused by Suramin is a multifunctional molecule with a wide array of potential applications, from parasitic and viral diseases to cancer, snakebite, and autism. Suramin is also an enigmatic molecule: What are its targets? How does it get into cells in the first place? Here, we provide an overview of the many different candidate targets of suramin and discuss its modes of action and routes of cellular uptake. We reason that, once the polypharmacology of suramin is understood at the molecular level, new, more specific, and less toxic molecules can be identified for the numerous potential applications of suramin.
Topics: Animals; Humans; Suramin; Trypanocidal Agents; Trypanosoma brucei rhodesiense; Trypanosomiasis, African
PubMed: 31844000
DOI: 10.1128/AAC.01168-19 -
The New England Journal of Medicine Dec 2016
Topics: Female; Humans; Middle Aged; Skin; Trypanosoma brucei rhodesiense; Trypanosomiasis, African
PubMed: 27974038
DOI: 10.1056/NEJMicm1604333 -
Molecules (Basel, Switzerland) Oct 2020Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus . In humans, this includes Chagas disease and African trypanosomiasis. There are few... (Review)
Review
Trypanosomiases are diseases caused by parasitic protozoan trypanosomes of the genus . In humans, this includes Chagas disease and African trypanosomiasis. There are few therapeutic options, and there is low efficacy to clinical treatment. Therefore, the search for new drugs for the trypanosomiasis is urgent. This review describes studies of the trypanocidal properties of essential oils, an important group of natural products widely found in several tropical countries. Seventy-seven plants were selected from literature for the trypanocidal activity of their essential oils. The main chemical constituents and mechanisms of action are also discussed. In vitro and in vivo experimental data show the therapeutic potential of these natural products for the treatment of infections caused by species of .
Topics: Animals; Chagas Disease; Humans; Oils, Volatile; Plant Extracts; Trypanocidal Agents; Trypanosoma brucei brucei; Trypanosoma cruzi; Trypanosomiasis, African
PubMed: 33036315
DOI: 10.3390/molecules25194568 -
Trends in Parasitology Jun 2018Arsenicals were introduced as monotherapies for the treatment of human African trypanosomiasis, or sleeping sickness, over 100 years ago. Toxicity has always been an... (Review)
Review
Arsenicals were introduced as monotherapies for the treatment of human African trypanosomiasis, or sleeping sickness, over 100 years ago. Toxicity has always been an issue but these drugs have proven to be both effective and quite durable. Unfortunately, melarsoprol-resistant parasites emerged as early as the 1970s and were widespread by the late 1990s. Resistance was due to mutations affecting an aquaglyceroporin (AQP2), a parasite solute and drug transporter. This is the only example of widespread drug resistance in trypanosomiasis patients for which the genetic basis is known. This link between melarsoprol and AQP2 illustrates how a drug transporter can improve drug selectivity but, at the same time, highlights the risk of resistance when the drug uptake mechanism is dispensable for parasite viability and virulence.
Topics: Aquaglyceroporins; Drug Resistance; Humans; Melarsoprol; Mutation; Trypanosoma brucei gambiense; Trypanosomiasis, African
PubMed: 29705579
DOI: 10.1016/j.pt.2018.04.002 -
International Journal of Molecular... Aug 2023Human African trypanosomiasis is a neglected tropical disease caused by the extracellular protozoan parasite , and targeted for eradication by 2030. The COVID-19... (Review)
Review
Human African trypanosomiasis is a neglected tropical disease caused by the extracellular protozoan parasite , and targeted for eradication by 2030. The COVID-19 pandemic contributed to the lengthening of the proposed time frame for eliminating human African trypanosomiasis as control programs were interrupted. Armed with extensive antigenic variation and the depletion of the B cell population during an infectious cycle, attempts to develop a vaccine have remained unachievable. With the absence of a vaccine, control of the disease has relied heavily on intensive screening measures and the use of drugs. The chemotherapeutics previously available for disease management were plagued by issues such as toxicity, resistance, and difficulty in administration. The approval of the latest and first oral drug, fexinidazole, is a major chemotherapeutic achievement for the treatment of human African trypanosomiasis in the past few decades. Timely and accurate diagnosis is essential for effective treatment, while poor compliance and resistance remain outstanding challenges. Drug discovery is on-going, and herein we review the recent advances in anti-trypanosomal drug discovery, including novel potential drug targets. The numerous challenges associated with disease eradication will also be addressed.
Topics: Animals; Humans; Trypanosomiasis, African; Pandemics; COVID-19; Trypanosoma brucei brucei; Trypanosoma
PubMed: 37569903
DOI: 10.3390/ijms241512529 -
PLoS Neglected Tropical Diseases Apr 2017Sleeping sickness, also known as human African trypanosomiasis (HAT), is a neglected disease that impacts 70 million people living in 1.55 million km2 in sub-Saharan... (Review)
Review
Sleeping sickness, also known as human African trypanosomiasis (HAT), is a neglected disease that impacts 70 million people living in 1.55 million km2 in sub-Saharan Africa. Since the beginning of the 20th century, there have been multiple HAT epidemics in sub-Saharan Africa, with the most recent epidemic in the 1990s resulting in about half a million HAT cases reported between 1990 and 2015. Here we review the status of HAT disease at the current time and the toolbox available for its control. We also highlight future opportunities under development towards novel or improved interventions.
Topics: Africa South of the Sahara; Animals; Humans; Neglected Diseases; Trypanosomiasis, African; Tsetse Flies
PubMed: 28426685
DOI: 10.1371/journal.pntd.0005454 -
The FEBS Journal Mar 2018Trypanosoma brucei comprise the causative agents of sleeping sickness, T. b. gambiense and T. b. rhodesiense, as well as the livestock-pathogenic T. b. brucei. The... (Review)
Review
Trypanosoma brucei comprise the causative agents of sleeping sickness, T. b. gambiense and T. b. rhodesiense, as well as the livestock-pathogenic T. b. brucei. The parasites are transmitted by the tsetse fly and occur exclusively in sub-Saharan Africa. T. brucei are not only lethal pathogens but have also become model organisms for molecular parasitology. We focus here on membrane transport proteins of T. brucei, their contribution to homeostasis and metabolism in the context of a parasitic lifestyle, and their pharmacological role as potential drug targets or routes of drug entry. Transporters and channels in the plasma membrane are attractive drug targets as they are accessible from the outside. Alternatively, they can be exploited to selectively deliver harmful substances into the trypanosome's interior. Both approaches require the targeted transporter to be essential: in the first case to kill the trypanosome, in the second case to prevent drug resistance due to loss of the transporter. By combining functional and phylogenetic analyses, we were mining the T. brucei predicted proteome for transporters of pharmacological significance. Here, we review recent progress in the identification of transporters of lipid precursors, amino acid permeases and ion channels in T. brucei.
Topics: Animals; Antiprotozoal Agents; Humans; Insect Vectors; Membrane Transport Proteins; Phylogeny; Protozoan Proteins; Trypanosoma brucei brucei; Trypanosomiasis, African; Tsetse Flies
PubMed: 29063677
DOI: 10.1111/febs.14302