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Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis.
Front Immunol. 2019; 10:39.FI

Abstract

Trypanosomiasis has been recognized as a scourge in sub-Saharan Africa for centuries. The disease, caused by protozoan parasites of the Trypanosoma genus, is a major cause of mortality and morbidity in animals and man. Human African trypanosomiasis (HAT), or sleeping sickness, results from infections with T. brucei (b.) gambiense or T. b. rhodesiense with T. b. gambiense 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 T. b. gambiense-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.

Authors+Show Affiliations

Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

30740102

Citation

Kennedy, Peter G E., and Jean Rodgers. "Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis." Frontiers in Immunology, vol. 10, 2019, p. 39.
Kennedy PGE, Rodgers J. Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis. Front Immunol. 2019;10:39.
Kennedy, P. G. E., & Rodgers, J. (2019). Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis. Frontiers in Immunology, 10, 39. https://doi.org/10.3389/fimmu.2019.00039
Kennedy PGE, Rodgers J. Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis. Front Immunol. 2019;10:39. PubMed PMID: 30740102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical and Neuropathogenetic Aspects of Human African Trypanosomiasis. AU - Kennedy,Peter G E, AU - Rodgers,Jean, Y1 - 2019/01/25/ PY - 2018/10/03/received PY - 2019/01/08/accepted PY - 2019/2/12/entrez PY - 2019/2/12/pubmed PY - 2019/12/18/medline KW - CNS KW - diagnostic staging KW - human African trypanosomiasis KW - neurology KW - sleeping sickness KW - tsetse fly SP - 39 EP - 39 JF - Frontiers in immunology JO - Front Immunol VL - 10 N2 - Trypanosomiasis has been recognized as a scourge in sub-Saharan Africa for centuries. The disease, caused by protozoan parasites of the Trypanosoma genus, is a major cause of mortality and morbidity in animals and man. Human African trypanosomiasis (HAT), or sleeping sickness, results from infections with T. brucei (b.) gambiense or T. b. rhodesiense with T. b. gambiense 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 T. b. gambiense-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. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/30740102/Clinical_and_Neuropathogenetic_Aspects_of_Human_African_Trypanosomiasis_ L2 - https://doi.org/10.3389/fimmu.2019.00039 DB - PRIME DP - Unbound Medicine ER -