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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 -
Parasite Immunology Aug 2011
Topics: Animals; Genetic Variation; Humans; Livestock; Trypanocidal Agents; Trypanosoma; Trypanosomiasis, African; Virulence
PubMed: 21609334
DOI: 10.1111/j.1365-3024.2011.01302.x -
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 -
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 -
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 -
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 -
Current Opinion in Infectious Diseases Oct 2022Gambiense human African trypanosomiasis (gHAT), a disease that has killed hundreds of thousands as recently as the 1990s, could be on the verge of elimination or even... (Review)
Review
PURPOSE OF REVIEW
Gambiense human African trypanosomiasis (gHAT), a disease that has killed hundreds of thousands as recently as the 1990s, could be on the verge of elimination or even eradication. This review describes recent developments that give us reasons for optimism as well as some caveats.
RECENT FINDINGS
New developments in diagnostic and vector control tools, and especially in treatment, make it possible to strive for elimination of transmission of gHAT by 2030, perhaps even eradication.
SUMMARY
Gambiense human African trypanosomiasis is a deadly infectious disease affecting West and Central Africa, South Sudan and Uganda, and transmitted between humans by tsetse flies. The disease has caused several major epidemics, the latest one in the 1990s. Thanks to recent innovations such as rapid diagnostic tests for population screening, a single-dose oral treatment and a highly efficient vector control strategy, interruption of transmission of the causative parasite is now within reach. If indeed gHAT has an exclusively human reservoir, this could even result in eradication of the disease. Even if there were an animal reservoir, on the basis of epidemiological data, it plays a limited role. Maintaining adequate postelimination surveillance in known historic foci, using the newly developed tools, should be sufficient to prevent any future resurgence.
Topics: Animals; Humans; Trypanosomiasis, African; Tsetse Flies; Uganda
PubMed: 35942856
DOI: 10.1097/QCO.0000000000000860 -
Frontiers in Immunology 2019Trypanosomiasis 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... (Review)
Review
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. Historically there have been major epidemics of the infection, followed by periods of relative disease control. As a result of concerted disease surveillance and treatment programmes, implemented over the last two decades, there has been a significant reduction in the number of cases of human disease reported. However, the recent identification of asymptomatic disease carriers gives cause for some concern. The parasites evade the host immune system by switching their surface coat, comprised of variable surface glycoprotein (VSG). In addition, they have evolved a variety of strategies, including the production of serum resistance associated protein (SRA) and -specific glycoprotein (TgsGP) to counter host defense molecules. Infection with either disease variant results in an early haemolymphatic-stage followed by a late encephalitic-stage when the parasites migrate into the CNS. The clinical features of HAT are diverse and non-specific with early-stage symptoms common to several infections endemic within sub-Saharan Africa which may result in a delayed or mistaken diagnosis. Migration of the parasites into the CNS marks the onset of late-stage disease. Diverse neurological manifestations can develop accompanied by a neuroinflammatory response, comprised of astrocyte activation, and inflammatory cell infiltration. However, the transition between the early and late-stage is insidious and accurate disease staging, although crucial to optimize chemotherapy, remains problematic with neurological symptoms and neuroinflammatory changes recorded in early-stage infections. Further research is required to develop better diagnostic and staging techniques as well as safer more efficacious drug regimens. Clearer information is also required concerning disease pathogenesis, specifically regarding asymptomatic carriers and the mechanisms employed by the trypanosomes to facilitate progression to the CNS and precipitate late-stage disease. Without progress in these areas it may prove difficult to maintain current control over this historically episodic disease.
Topics: Animals; Antiprotozoal Agents; Blood-Brain Barrier; Brain; Delayed Diagnosis; Humans; Incidence; Neglected Diseases; Pentamidine; Severity of Illness Index; Suramin; Treatment Outcome; Trypanosoma brucei gambiense; Trypanosoma brucei rhodesiense; Trypanosomiasis, African
PubMed: 30740102
DOI: 10.3389/fimmu.2019.00039 -
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 -
Parasites & Vectors Jan 2021In the 1980s and 1990s, great strides were taken towards the elimination of tsetse and animal African trypanosomiasis (AAT) in Zimbabwe. However, advances in recent...
BACKGROUND
In the 1980s and 1990s, great strides were taken towards the elimination of tsetse and animal African trypanosomiasis (AAT) in Zimbabwe. However, advances in recent years have been limited. Previously freed areas have been at risk of reinvasion, and the disease in tsetse-infested areas remains a constraint to food security. As part of ongoing control activities, monitoring of tsetse and AAT is performed regularly in the main areas at risk. However, a centralized digital archive is missing. To fill this gap, a spatially explicit, national-level database of tsetse and AAT (i.e. atlas) was established through systematic data collation, harmonization and geo-referencing for the period 2000-2019.
METHODS
The atlas covers an area of approximately 70,000 km, located mostly in the at-risk areas in the north of the country. In the tsetse component, a total of 33,872 entomological records were assembled for 4894 distinct trap locations. For the AAT component, 82,051 samples (mainly dry blood smears from clinically suspicious animals) were collected at 280 diptanks and examined for trypanosomal infection by microscopy.
RESULTS
Glossina pallidipes (82.7% of the total catches) and Glossina morsitans morsitans (17.3%) were the two tsetse species recorded in the north and northwest parts of the country. No fly was captured in the northeast. The distribution of AAT follows broadly that of tsetse, although sporadic AAT cases were also reported from the northeast, apparently because of transboundary animal movement. Three trypanosome species were reported, namely Trypanosoma brucei (61.7% of recorded infections), Trypanosoma congolense (28.1%) and Trypanosoma vivax (10.2%). The respective prevalences, as estimated in sentinel herds by random sampling, were 2.22, 0.43 and 0.30%, respectively.
DISCUSSION
The patterns of tsetse and AAT distributions in Zimbabwe are shaped by a combination of bioclimatic factors, historical events such as the rinderpest epizootic at the turn of the twentieth century and extensive and sustained tsetse control that is aimed at progressively eliminating tsetse and trypanosomiasis from the entire country. The comprehensive dataset assembled in the atlas will improve the spatial targeting of surveillance and control activities. It will also represent a valuable tool for research, by enabling large-scale geo-spatial analyses.
Topics: Animal Distribution; Animals; Atlases as Topic; Databases, Factual; Insect Vectors; Livestock; Trypanosoma; Trypanosomiasis, African; Tsetse Flies; Zimbabwe
PubMed: 33446276
DOI: 10.1186/s13071-020-04555-8