Special Issue "Human African Trypanosomiasis (HAT, Sleeping Sickness): The Road to Elimination Revisited—Achievements and Remaining Challenges"

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366).

Deadline for manuscript submissions: 30 November 2019.

Special Issue Editor

Guest Editor
Prof. Christian Burri

Department of Medicine, Swiss Tropical & Public Health Institute, Socinstrasse 57, 4051 Basel, Switzerland
Website | E-Mail
Interests: sleeping sickness (human African trypanosomiasis); drug and vaccine development against neglected tropical diseases; clinical trials in low resource settings; implementation research; public health

Special Issue Information

Dear Colleagues,

The positive opinion expressed on 16 November 2018 by the European Medicines Agency on the use of the oral drug fexinidazole against human African trypanosomiasis (HAT) caused by T.b. gambiense may be considered a milestone in the treatment of the disease and contributes an essential component towards its elimination. With tremendous efforts, the treatment could be improved, with respect to the past almost 30 years, from a 35-day treatment with an injectable organoarsenic drug (melarsoprol) presenting a drug-attributable fatality rate of 5%, to a 10-day oral treatment with a 0.1% formulation of fexinidazole. However, this is only one of the many pieces we need to combine in the puzzle of a successful battle against this disease. While the number of T.b. gambiense HAT cases is decreasing, and the dreadful melarsoprol with the much-feared lumbar puncture has been replaced by the new treatment, many other issues still need to be addressed to reach the goal of sustainable disease elimination by 2030. Case identification and diagnosis remain complicated and require substantial screening efforts and specific skills (such as case confirmation by microscopy). Contrary to an old dogma, recent evidence shows that not all patients die from the disease, but some may remain infective over many years; in addition, the relevance and nature of the animal reservoir for T.b. gambiense HAT are still not conclusively resolved. Enough questions for a disease marked for elimination, but, eventually, the human factor will be decisive in the “end game”, where decentralized disease recognition and management in lower level health structures and communities, disease awareness and stigma, unrelenting disease surveillance in known foci, as well as oblivion in areas where HAT has not occurred may play a determining role but have not been studied in depth yet. All these unresolved questions gain a significant importance in the light of the known threat of recurrence at large scale of this disease.

As if HAT caused by T.b. gambiense were not a very neglected disease and all this not enough for a considerable challenge, the other form of the disease caused by T.b. rhodesiense is an even more neglected and much more fulminant illness targeted for elimination, with a clear zoonotic reservoir and still only treatable with the old drugs pentamidine and suramin in the first stage and melarsoprol in the late stage, with stage determination requiring a lumbar puncture.

Given where we stand regarding both diseases, it seems now a close-to-perfect time for an overview, status check, and collection of new ideas and innovative approaches to reach the goal of elimination of these debilitating diseases and prepare against their recurrence.

Prof. Christian Burri
Guest Editor

Manuscript Submission Information

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Keywords

  • sleeping sickness
  • human African trypanosomiasis
  • T. b. gambiense
  • g-HAT
  • T. b. rhodesiense
  • r-HAT
  • elimination
  • neglected tropical diseases

Published Papers (1 paper)

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Research

Open AccessArticle
(+)-Spectaline and Iso-6-Spectaline Induce a Possible Cross-Talk between Autophagy and Apoptosis in Trypanosoma brucei rhodesiense
Trop. Med. Infect. Dis. 2019, 4(3), 98; https://doi.org/10.3390/tropicalmed4030098
Received: 17 May 2019 / Revised: 23 June 2019 / Accepted: 27 June 2019 / Published: 1 July 2019
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Abstract
In our previous study, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of Senna spectabilis and showed no toxic effect on L6 cells. In view of the potential use of piperidine alkaloids in [...] Read more.
In our previous study, two known piperidine alkaloids (+)-spectaline (1) and iso-6-spectaline (2) were isolated from the leaves of Senna spectabilis and showed no toxic effect on L6 cells. In view of the potential use of piperidine alkaloids in S. spectabilis for the treatment of sleeping sickness, further investigation on the cell death actions of the parasite after treatment with compound 1 and 2 suggested that the treated parasites died by a process of autophagy based on the characteristic morphological alterations observed in intracellular T. b. rhodesiense. In search for apoptosis, interestingly, trypanosomes treated with high concentration of compound 1 and 2 after 72 h significantly induced an early apoptosis-like programmed cell death (PCD) such as phosphatidylserine (PS) exposure, loss of mitochondrial membrane potential and caspases activation. No DNA laddering discriminated late apoptosis event. Taken together, these findings demonstrated the potential of compound 1 and 2 as a natural chemotherapeutic capable of inducing a possible cross-talk between autophagy and apoptosis in T. b. rhodesiense. Full article
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