University of Groningen
Improving antimicrobial therapy for Buruli ulcer
Omansen, Till Frederik
IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.
Document Version
Publisher's PDF, also known as Version of record
Publication date: 2019
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Omansen, T. F. (2019). Improving antimicrobial therapy for Buruli ulcer: Pre-clinical studies towards highly efficient, short-course therapy. University of Groningen.
Copyright
Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).
Take-down policy
If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.
Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.
Improving antimicrobial therapy for Buruli ulcer
Pre-clinical studies towards highly efficient, short-course therapyThis thesis was written within the PhD program at the Graduate School of Medical Sciences (GSMS), University Medical Center Groningen, the Netherlands.
Research described in this thesis was performed at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne Australia, the Center for Tuberculosis Research at the Johns Hopkins School of Medicine, Baltimore, USA and the Department of Neglected Tropical Diseases at the World Health Organization, Geneva, Switzerland. Financial supported was provided by the University of Groningen Junior Scientific Master-class (MD/PhD JSM grant), the Royal Netherlands Academy of Arts and Sciences (KNAW Ter Meulen grant), the Jan Kornelis de Cock Foundation, the Herpes Foundation Groningen and the Buruli ulcer Groningen Foundation. Their support is herewith gratefully acknowledged. Copyright © Till F. Omansen, 2019
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form of by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission from the author or from the copyright-owning journals of previously published chapters.
Improving antimicrobial therapy
for Buruli ulcer
Pre-clinical studies towards highly efficient, short-course therapy
PhD thesis
to obtain the degree of PhD at the University of Groningen
on the authority of the Rector Magnificus prof. E. Sterken
and in accordance with the decision by the College of Deans. This thesis will be defended in public on
Monday 1 April 2019 at 14.30 hours
by
Till Frederik Omansen
born on 6 April 1989 in Bückeburg, Germany
Supervisors
Prof. T.S. van der Werf Prof. Y. Stienstra Prof. E.L. NuermbergerAssessment Committee
Prof. M.P. GrobuschProf. B. de Jong Prof. J.M. van Dijl
Paranymphs
Christian Philipp Rausch Michael Edward Urbanowski
Cover:
Artistic impression of an interview of a health psychologist with a villager in Benin. In this study we assessed the psychosocial stigma and needs of Buruli ulcer affected communi-ties. Consent for taking the original photograph was obtained.
To my mother Gabriele Omansen
COnTenTs
Chapter 1 Introduction and outline of the thesis 11 Chapter 2 Global epidemiology of Buruli ulcer from 2010 – 2017:
an analysis of the 2014 WHO programmatic targets
21 Chapter 3 Treatment for Buruli ulcer: the long and winding road to
antimicrobials-first
39 Chapter 4 Antimicrobial treatment of Mycobacterium ulcerans infection 47 Chapter 5 In-vivo imaging of bioluminescent Mycobacterium ulcerans:
a tool to refine the murine Buruli ulcer tail model
67 Chapter 6 In-vitro activity of avermectins against Mycobacterium ulcerans 87 Chapter 7 Pharmacokinetics of oral, high, repeated-dose avermectins in mice;
no in-vivo efficacy against M. ulcerans
97 Chapter 8 High-dose rifamycins enable shorter oral treatment in a murine
model of Mycobacterium ulcerans disease
109 Chapter 9 Oxazolidinones can replace clarithromycin in combination with
rifampin in a mouse model of Buruli ulcer
123
Chapter 10 Summary 137
Chapter 11 Discussion and Future Perspectives: The future of Buruli ulcer treatment
143
Nederlandse samenvatting 153
Acknowledgements 157
List of publications 161
