Update on human African trypanosomiasis (sleeping sickness)

Kennedy, Peter G. E.

doi:10.1007/s00415-019-09425-7

Cited by 86 publications

(74 citation statements)

References 26 publications

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“…Human African trypanosomiasis (HAT), also known as sleeping sickness, is a neglected tropical disease. Despite a decreasing number of new infections in recent years, still 70 million people in 36 African countries are at risk of becoming infected ( 1 ). In response to the declining incidence, the World Health Organization (WHO) has targeted HAT for elimination as a public health problem by 2020 ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Analyzing editosome function in high-throughput

Campo

Leeder

Reißig

et al. 2020

Nucleic Acids Research

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Mitochondrial gene expression in African trypanosomes and other trypanosomatid pathogens requires a U-nucleotide specific insertion/deletion-type RNA-editing reaction. The process is catalyzed by a macromolecular protein complex known as the editosome. Editosomes are restricted to the trypanosomatid clade and since editing is essential for the parasites, the protein complex represents a near perfect target for drug intervention strategies. Here, we report the development of an improved in vitro assay to monitor editosome function. The test system utilizes fluorophore-labeled substrate RNAs to analyze the processing reaction by automated, high-throughput capillary electrophoresis (CE) in combination with a laser-induced fluorescence (LIF) readout. We optimized the assay for high-throughput screening (HTS)-experiments and devised a multiplex fluorophore-labeling regime to scrutinize the U-insertion/U-deletion reaction simultaneously. The assay is robust, it requires only nanogram amounts of materials and it meets all performance criteria for HTS-methods. As such the test system should be helpful in the search for trypanosome-specific pharmaceuticals.

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Section: Introductionmentioning

confidence: 99%

Analyzing editosome function in high-throughput

Campo

Leeder

Reißig

et al. 2020

Nucleic Acids Research

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“…Trials to test fexinidazole's efficacy against rhodesiense HAT, however, are also currently underway in Malawi and about to begin in Uganda [12]. Fexinidazole, a nitroimidazole treatment that can be taken orally once a day for 10 days [11][12][13], in many ways simplifies HAT treatment regimens, enabling new forms of patient management.…”

Section: Introductionmentioning

confidence: 99%

“…Until recently, HAT programmes have had to balance the risks of administering drugs that were either ineffective or too toxic. Melarsoprol, for example, the only drug effective against the second meningo-encephalitic stage of rhodesiense HAT, is notoriously painful to administer and can cause post-treatment reactive encephalopathy, contributing to a treatment-associated fatality rate of about 6% [13,14]. Suramin, a safer drug, can only be used for the first haemo-lymphatic stage because it cannot penetrate the blood-brain barrier.…”

Section: Introductionmentioning

confidence: 99%

Centering Patient Expectations of a Novel Home-Based Oral Drug Treatment among T. b. rhodesiense Human African Trypanosomiasis Patients in Uganda

Lee

Apio²,

Palmer

2020

TropicalMed

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The recent approval of fexinidazole for human African trypanosomiasis (HAT) caused by T. b. gambiense enables improved patient management that is pivotal to elimination. Effective in both the early and late stages of the disease, it obviates the need for invasive lumbar punctures which guide therapy, in some patients. Unlike existing injectable treatments requiring systematic hospitalisation, fexinidazole’s oral administration will allow many patients to be treated in an outpatient or home-based setting. Drawing on interviews with 25 T. b. rhodesiense HAT patients managed under existing protocols in Uganda where trials of fexinidazole will begin shortly, this article explores patient expectations of the new protocol to help HAT programmes anticipate patient concerns. Alongside frightening symptoms of this life-threatening illness, the pain and anxiety associated with lumbar punctures and intravenous injections of melarsoprol contributed to a perception of HAT as a serious illness requiring expert medical care. While preferring a new protocol that would avoid these uncomfortable procedures, patients’ trust in the care they received meant that nearly half were hesitant towards shifting care out of the hospital setting. Clinical observation is an important aspect of existing HAT care for patients. Programmes may need to offer extensive counselling and monitoring support before patients are comfortable accepting care outside of hospitals.

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“…Human African trypanosomiasis (HAT), also known as sleeping sickness, is a neglected tropical disease. Despite a decreasing number of new infections in recent years, still 70 million people in 36 African countries are at risk of becoming infected (Kennedy, 2019). In response to the declining incidence, the World Health Organization (WHO) has targeted HAT for elimination as a public health problem by 2020 (Barrett, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Five drugs are currently used in the treatment of HAT (Büscher et al, 2017). All of them are toxic to different degrees (Kennedy, 2019). In addition, they suffer from a multitude of complications including parenteral administration (Gilbert, 2014), poor efficacy, clinical side effects and increasing levels of resistance (Baker et al, 2013;Barrett et al, 2011;Fairlamb and Horn, 2018).…”

Section: Introductionmentioning

confidence: 99%

Analyzing editosome function in high-throughput

Campo

Leeder

Reissig³

et al. 2020

Preprint

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Mitochondrial gene expression in African trypanosomes and other trypanosomatid pathogens requires a U-nucleotide specific insertion/deletion-type RNA-editing reaction. The process is catalyzed by a macromolecular protein complex known as the editosome. Editosomes are restricted to the trypanosomatid clade and since editing is essential for the parasites, the protein complex represents a near perfect target for drug intervention strategies. Here we report the development of an improved in vitro assay to monitor editosome function. The test system utilizes fluorophore-labeled substrate RNAs to analyze the processing reaction by automated, high-throughput capillary electrophoresis (CE) in combination with a laser-induced fluorescence (LIF) readout. We optimized the assay for high-throughput screening (HTS)-experiments and devised a multiplex fluorophore-labeling regime to scrutinize the U-insertion/U-deletion reaction simultaneously. The assay is robust, it requires only nanogram amounts of materials and it meets all performance criteria for HTS-methods. As such the test system should be helpful in the search for trypanosome-specific pharmaceuticals.

show abstract

Update on human African trypanosomiasis (sleeping sickness)

Cited by 86 publications

References 26 publications

Analyzing editosome function in high-throughput

Analyzing editosome function in high-throughput

Centering Patient Expectations of a Novel Home-Based Oral Drug Treatment among T. b. rhodesiense Human African Trypanosomiasis Patients in Uganda

Analyzing editosome function in high-throughput

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