Journal ArticleDOI
Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)
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TLDR
Diagnostic staging to distinguish early-stage from late-stage disease when the CNS in invaded is crucial but remains problematic, and new drugs are in the pipeline for treatment of CNS human African trypanosomiasis, giving rise to cautious optimism.Abstract:
Human African trypanosomiasis, or sleeping sickness, is caused by infection with parasites of the genus Trypanosoma, transmitted by the tsetse fly. The disease has two forms, Trypanosoma brucei (T b) rhodesiense and T b gambiense; and is almost always fatal if untreated. Despite a recent reduction in the number of reported cases, patients with African trypanosomiasis continue to present major challenges to clinicians. Because treatment for CNS-stage disease can be very toxic, diagnostic staging to distinguish early-stage from late-stage disease when the CNS in invaded is crucial but remains problematic. Melarsoprol is the only available treatment for late-stage T b rhodesiense infection, but can be lethal to 5% of patients owing to post-treatment reactive encephalopathy. Eflornithine combined with nifurtimox is the first-line treatment for late-stage T b gambiense. New drugs are in the pipeline for treatment of CNS human African trypanosomiasis, giving rise to cautious optimism.read more
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Polyamine metabolism and cancer: treatments, challenges and opportunities
TL;DR: New insights into molecular mechanisms that link the dysregulation of polyamine metabolism with carcinogenesis and strategies for targeting this pathway for cancer therapy are discussed.
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Drug repurposing and human parasitic protozoan diseases
TL;DR: In this paper, drug repurposing or repositioning is discussed with a focus on major human parasitic protozoan diseases such as malaria, trypanosomiasis, toxoplasmosis, cryptosporidiosis and leishmaniasis.
Journal ArticleDOI
Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness
Shilpi Khare,Advait Nagle,Agnes Biggart,Yin H. Lai,Fang Liang,Lauren C. Davis,S. Whitney Barnes,Casey J. N. Mathison,Elmarie Myburgh,Elmarie Myburgh,Mu-Yun Gao,J. Robert Gillespie,Xianzhong Liu,Jocelyn Tan,Monique Stinson,Ianne C. Rivera,Jaime Ballard,Vince Yeh,Todd Groessl,Glenn C. Federe,Hazel X. Y. Koh,John D. Venable,Badry Bursulaya,Michael Shapiro,Pranab Mishra,Glen Spraggon,Ansgar Brock,Jeremy C. Mottram,Jeremy C. Mottram,Frederick S. Buckner,Srinivasa P. S. Rao,Ben G. Wen,John R. Walker,Tove Tuntland,Valentina Molteni,Richard Glynne,Frantisek Supek +36 more
TL;DR: A selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection, underscores the possibility of developing a single class of drugs for these neglected diseases.
Journal ArticleDOI
Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice.
Sandra Trindade,Filipa Rijo-Ferreira,Filipa Rijo-Ferreira,Filipa Rijo-Ferreira,Tânia Carvalho,Daniel Pinto-Neves,Fabien Guegan,Francisco Aresta-Branco,Fabio Bento,Simon A. Young,Andreia Pinto,Jan Van Den Abbeele,Jan Van Den Abbeele,Ruy M. Ribeiro,Ruy M. Ribeiro,Sergio Dias,Terry K. Smith,Luisa M. Figueiredo +17 more
TL;DR: It is discovered that adipose tissue constitutes a third major reservoir for T. brucei during its mammalian life cycle and could potentially explain the weight loss associated with sleeping sickness.
Journal ArticleDOI
Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.
Advait Nagle,Shilpi Khare,Arun Kumar,Frantisek Supek,Andriy Buchynskyy,Casey J. N. Mathison,Naveen Kumar Chennamaneni,Nagendar Pendem,Frederick S. Buckner,Michael H. Gelb,Valentina Molteni +10 more
TL;DR: The disease history and parasite biology is described followed by a summary of the currently available treatments and, finally, review reports of novel small molecules with antileishmanial activity.
References
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Loop Mediated Isothermal Amplification of DNA
TL;DR: The loop-mediated isothermal amplification method (LAMP) as discussed by the authors was developed to solve the problems of the conventional PCR such as repeated thermal cycles and interferences from impurity DNAs.
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Human African trypanosomiasis
TL;DR: If national control programmes, international organisations, research institutes, and philanthropic partners engage in concerted action, elimination of this disease might even be possible, the World Health Organization has stated.
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Nifurtimox-eflornithine combination therapy for second-stage African Trypanosoma brucei gambiense trypanosomiasis: a multicentre, randomised, phase III, non-inferiority trial
Gerardo Priotto,Serena Kasparian,Wilfried Mutombo,Daniel Ngouama,Sara Ghorashian,Ute Arnold,Salah Ghabri,Elisabeth Baudin,Vincent Buard,Serge Kazadi-Kyanza,Medard Ilunga,Willy Mutangala,Gabriele Pohlig,Caecilia Schmid,Unni Karunakara,Els Torreele,Victor Kande +16 more
TL;DR: The efficacy of NECT is non-inferior to that of eflornithine monotherapy, which is suitable for first-line use in HAT control programmes and potentially protective against the emergence of resistant parasites.
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Eliminating human African trypanosomiasis: where do we stand and what comes next?
TL;DR: While the number of new detected cases of HAT is falling, say the authors, sleeping sickness could suffer the "punishment of success," receiving lower priority by public and private health institutions.
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Control and surveillance of African trypanosomiasis: Report of a WHO Expert Committee (WHO Technical Report Series, no. 881). Geneva: World Health Organization, 1998. vi + 113pp. Price SW. fr. 23.-/US$20.70 (ind eveloping countries, Sw. fr. 16.10). ISBN 92-4-120881-3. Available in English; French and Spanish in preparation
TL;DR: This report provides examples of treatment schedules, vector control operations, indicators for monitoring control and surveillance activities and sample calculations for analysing the cost-effectiveness of different strategies, as well as details of methods for cryopreservation of trypanosome-infected blood samples and a description of traps and screens for the control of the insect vector, Glossina.