Human African Trypanosomiasis African Human • Ch ristian Burri Human African Trypanosomiasis (Sleeping Sickness) The Road to Elimination Revisited—Achievements and Remaining Challenges Edited by Christian Burri Printed Edition of the Special Issue Published in Tropical Medicine and Infectious Disease www.mdpi.com/journal/tropicalmed Human African Trypanosomiasis (Sleeping Sickness) Human African Trypanosomiasis (Sleeping Sickness) The Road to Elimination Revisited—Achievements and Remaining Challenges Special Issue Editor Christian Burri MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Special Issue Editor Christian Burri Swiss Tropical & Public Health Institute Switzerland Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Tropical Medicine and Infectious Disease (ISSN 2414-6366) (available at: https://www.mdpi.com/ journal/tropicalmed/special issues/HAT). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year, Article Number, Page Range. ISBN 978-3-03928-963-9 (Pbk) ISBN 978-3-03928-964-6 (PDF) Cover image courtesy of Swiss Tropical & Public Health Institute. Trypanosoma brucei; F. Brand, Swiss TPH; Picture taken with the transmission electron microscope at the Center for Cellular Imaging and NanoAnalytics, University of Basel, Switzerland c 2020 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Special Issue Editor ...................................... vii Preface to ”Human African Trypanosomiasis (HAT, Sleeping Sickness)” ............. ix Christian Burri Sleeping Sickness at the Crossroads Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 57, doi:10.3390/tropicalmed5020057 ........ 1 Emma Michelle Taylor and James Smith Product Development Partnerships: Delivering Innovation for the Elimination of African Trypanosomiasis? Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 11, doi:10.3390/tropicalmed5010011 ........ 13 Philippe Neau, Heinz H¨anel, Val´erie Lameyre, Nathalie Strub-Wourgaft and Luc Kuykens Innovative Partnerships for the Elimination of Human African Trypanosomiasis and the Development of Fexinidazole Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 17, doi:10.3390/tropicalmed5010017 ........ 31 Florent Mbo, Wilfried Mutombo, Digas Ngolo, Patrice Kabangu, Olaf Valverde Mordt, Nathalie Strub Wourgaft and Erick Mwamba How Clinical Research Can Contribute to Strengthening Health Systems in Low Resource Countries Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 48, doi:10.3390/tropicalmed5020048 ........ 45 Shona J Lee, Renah J Apio and Jennifer J Palmer Centering Patient Expectations of a Novel Home-Based Oral Drug Treatment among T. b. rhodesiense Human African Trypanosomiasis Patients in Uganda Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 16, doi:10.3390/tropicalmed5010016 ........ 55 Jean-Benoˆıt Falisse, Erick Mwamba-Miaka and Alain Mpanya Whose Elimination? Frontline Workers’ Perspectives on the Elimination of the Human African Trypanosomiasis and Its Anticipated Consequences Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 6, doi:10.3390/tropicalmed5010005 ......... 69 Jennifer J. Palmer, Caroline Jones, Elizeous I Surur and Ann H Kelly Understanding the Role of the Diagnostic ‘Reflex’ in the Elimination of Human African Trypanosomiasis Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 52, doi:10.3390/tropicalmed5020052 ........ 85 Matthieu Nkieri, Florent Mbo, Papy Kavunga, Pathou Nganzobo, Titus Mafolo, Chalet Selego and Eric Mwamba Miaka An Active Follow-up Strategy for Serological Suspects of Human African Trypanosomiasis with Negative Parasitology Set up by a Health Zone Team in the Democratic Republic of Congo Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 53, doi:10.3390/tropicalmed5020053 ........103 Enock Matovu, Claire Mack Mugasa, Peter Waiswa, Annah Kitibwa, Alex Boobo and Joseph Mathu Ndung’u Haemoparasitic Infections in Cattle from a Trypanosoma brucei Rhodesiense Sleeping Sickness Endemic District of Eastern Uganda Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 24, doi:10.3390/tropicalmed5010024 ........113 v Junior Mudji, Jonathan Benhamou, Erick Mwamba-Miaka, Christian Burri and Johannes Blum The Flipside of Eradicating a Disease; Human African Trypanosomiasis in a Woman in Rural Democratic Republic of Congo: A Case Report Reprinted from: Trop. Med. Infect. Dis. 2019, 4, 142, doi:10.3390/tropicalmed4040142 .......123 Junior Mudji, Anna Blum, Leticia Grize, Rahel Wampfler, Marie-Th´er`ese Ruf, Lieselotte Cnops, Beatrice Nickel, Christian Burri and Johannes Blum Gambiense Human African Trypanosomiasis Sequelae after Treatment: A Follow-Up Study 12 Years after Treatment Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 10, doi:10.3390/tropicalmed5010010 ........129 Jorge Seixas, Jorge Atouguia, Teofilo ´ Josenando, Gede˜ao Vatunga, Constantin Miaka Mia Bilenge, Pascal Lutumba and Christian Burri Clinical Study on the Melarsoprol-Related Encephalopathic Syndrome: Risk Factors and HLA Association Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 5, doi:10.3390/tropicalmed5010005 .........145 Ulrich-Dietmar Madeja and Ulrike Schroeder From Colonial Research Spirit to Global Commitment: Bayer and African Sleeping Sickness in the Mirror of History Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 42, doi:10.3390/tropicalmed5010042 ........161 Harry P. De Koning The Drugs of Sleeping Sickness: Their Mechanisms of Action and Resistance, and a Brief History Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 14, doi:10.3390/tropicalmed5010014 ........169 Emily A. Dickie, Federica Giordani, Matthew K. Gould, Pascal M¨aser, Christian Burri, Jeremy C. Mottram, Srinivasa P. S. Rao and Michael P. Barrett New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 29, doi:10.3390/tropicalmed5010029 ........193 Srinivasa P S Rao, Suresh B Lakshminarayana, Jan Jiricek, Marcel Kaiser, Ryan Ritchie, Elmarie Myburgh, Frantisek Supek, Tove Tuntland, Advait Nagle, Valentina Molteni, Pascal M¨aser, Jeremy C Mottram, Michael P Barrett and Thierry T Diagana Anti-Trypanosomal Proteasome Inhibitors Cure Hemolymphatic and Meningoencephalic Murine Infection Models of African Trypanosomiasis Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 28, doi:10.3390/tropicalmed5010028 ........209 Frederick S. Buckner, Andriy Buchynskyy, Pendem Nagendar, Donald A. Patrick, J. Robert Gillespie, Zackary Herbst, Richard R. Tidwell and Michael H. Gelb Phenotypic Drug Discovery for Human African Trypanosomiasis: A Powerful Approach Reprinted from: Trop. Med. Infect. Dis. 2020, 5, 23, doi:10.3390/tropicalmed5010023 ........223 Christopher K. Kariuki, Benoit Stijlemans and Stefan Magez The Trypanosomal Transferrin Receptor of Trypanosoma Brucei—A Review Reprinted from: Trop. Med. Infect. Dis. 2019, 4, 126, doi:10.3390/tropicalmed4040126 .......241 Kah Tee Lim, Chiann Ying Yeoh, Zafarina Zainuddin and Mohd. Ilham Adenan (+)-Spectaline and Iso-6-Spectaline Induce a Possible Cross-Talk between Autophagy and Apoptosis in Trypanosoma brucei rhodesiense Reprinted from: Trop. Med. Infect. Dis. 2019, 4, 98, doi:10.3390/tropicalmed4030098 ........259 vi About the Special Issue Editor Christian Burri PhD, is the Deputy Head of the Department of Medicine and the Head of the Medicines Implementation Research Unit at the Swiss TPH, and Professor of Pharmacy & Clinical Pharmacology at the Department of Pharmaceutical Sciences, University of Basel. For almost 25 years, he has been involved in the management and conduct of clinical trials on drugs and vaccines against neglected tropical and poverty-related diseases, mainly in low income countries. In 2018, he handed over this service-oriented responsibility and founded a research group studying the implementation of medicines in resource-low settings in the two main fields of interests of access and pharmacoepidemiology. Throughout his training and professional career, he has had the privilege of becoming involved in most aspects of drug research and development, including gene cloning and parasite cultivation, drug screening, pharmacology and toxicology, lead selection, the conducting of clinical trials of Phases I–III, quality management, ethical and regulatory tasks, but also in various aspects of public health and the implementation of new interventions. Despite his involvement on a broad range of topics and contribution to various diseases, the original and continued passion of Prof. Burri is sleeping sickness (human African trypanosomiasis), where he has significantly contributed to improvement of the treatment. Prof. Burri has been trained as a pharmacist at the University of Bern, Switzerland, holds a PhD in medical parasitology from the University of Basel, and conducted postdoctoral training in molecular pharmacology at the Johns Hopkins University, Baltimore. He has held a Diploma in Pharmaceutical Medicine of the