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WHO Interim Guidelines for the Treatment of Gambiense Human African Trypanosomiasis

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WHO Interim Guidelines for the Treatment of Gambiense Human African Trypanosomiasis WHO interim guidelines for the treatment of gambiense human African trypanosomiasis August 2019 V4--WHO interim guidelines for the treatment HAT.indd 1 8/15/2019 5:13:01 PM V4--WHO interim guidelines for the treatment HAT.indd 2 8/15/2019 5:13:01 PM WHO interim guidelines for the treatment of gambiense human African trypanosomiasis WHO interim guidelines for the treatment of gambiense human African trypanosomiasis ISBN 978-92-4-155056-7 © World Health Organization 2019 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. WHO interim guidelines for the treatment of gambiense human African trypanosomiasis. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris. Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see http://www.who.int/about/licensing. Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resul- ting from infringement of any third-party-owned component in the work rests solely with the user. General disclaimers. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in pre- ference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. Printed in France. Contents Acknowledgements v Abbreviations and acronyms vii Executive summary viii 1 Introduction 1 1.1 Goal 1 1.2 Target audience 1 1.3 Guiding principles 2 2 Methodology and process of developing the guidelines 3 3 Background 3 3.1 Epidemiology and burden 3 3.2 Case management until now 6 3.3 Changes in case management established in these guidelines 6 3.4 Relevance of older guidelines 7 4 Case definitions, assessment of patients and treatment choice 8 4.1 Case definitions for treatment 8 4.2 Disease categorization for treatment 8 4.3 Categorization of patients: clinical examination and situations where CSF examination is needed 9 4.4 First-choice treatment 9 4.5 Second-choice and rescue treatments 11 5 Fexinidazole 12 5.1 Presentation 12 5.2 Posology 12 5.3 Food concomitant with fexinidazole 14 5.4 Directly observed treatment 14 5.5 Special populations 15 5.6 Contraindications and warnings 15 5.7 Adverse reactions 15 6 Pentamidine 16 6.1 Presentation 16 6.2 Posology and administration 16 6.3 Adverse reactions 17 7 NECT 18 7.1 Presentation 18 7.2 Posology and administration 19 7.3 Stopping and resuming treatment with NECT 23 7.4 Adverse reactions 23 8 Eflornithine monotherapy 24 8.1 Presentation 24 8.2 Posology and administration 24 8.3 Adverse reactions 25 9 Melarsoprol 26 9.1 Posology and administration 26 9.2 Adverse reactions 27 10 Treatment in pregnancy 28 11 Follow-up after treatment 29 12 Treatment of relapses 30 Annex 1: Symptoms and signs consistent with severe HAT 31 Annex 2: Guideline development methods 32 WEB ANNEXES All web annexes are available through weblink: https://www.who.int/trypanosomiasis_african/resources/9789241550567/en/ Web annex 1: Systematic evidence review report and evidence summaries Web annex 2: PICO questions, Evidence-to-Decision tables, Guideline Development Group recommendations Web annex 3: Summary of declared interests iv Acknowledgements The World Health Organization (WHO) is sincerely grateful to the many professionals from a range of backgrounds and specialties who contributed their time and expertise to the development of this guidance. Guideline Development Group Members: Andreas Lindner (Institute of Tropical Medicine and International Health, Berlin), Erick Mwamba (Ministry of Health, Democratic Republic of the Congo), François Chappuis (Hôpitaux Universitaires de Genève), Jorge Seixas (Instituto de Higiene e Medicina Tropical, Lisbon), Leon Kazumba (University of Kinshasa), Michael Barrett (University of Glasgow), Olema Erphas (Ministry of Health, Uganda), Veerle Lejon (Institut de Recherche pour le Développement, Montpellier) Guidelines methodologist: Elie Akl (American University of Beirut, Lebanon) Experts providing specialized input on clinical assessment aspects: Johannes Blum (Swiss Tropical and Public Health Institute, Basel), Peter Kennedy (University of Glasgow, UK) WHO Secretariat: Abdoulaye Diarra (AF/RGO/CDS/CDU, Brazzaville, Augustin Kadima Ebeja (AF/ACO/SRC/COD/CD3, Kinshasa), Gerardo Priotto, Jose Ramon Franco Minguell, Pere Perez Simarro, Raquel Mercado (HQ/CDS/NTD/IDM), Geneva. External peer review The following experts reviewed the pre-final guidelines document and provided valuable input: Serena Kasparian (Médecins Sans Frontières, Montreal), Philippe Büscher (Institute of Tropical Medicine, Antwerp), Enock Matovu (Makerere University, Kampala, Uganda), Vincent Jamonneau (Institut de Recherche pour le Développement, Montpellier). Systematic evidence review The following researchers conducted the systematic reviews and developed the evidence profiles and GRADE tables: Gemma Villanueva (senior systematic reviewer and lead reviewer, Cochrane Response), Hanna Bergman (systematic reviewer, Cochrane Response), Katrin Probyn (systematic reviewer, Cochrane Response), Nicholas Henschke (senior systematic reviewer, Cochrane Response), Chantelle Garritty (senior scientist, Cochrane Response), Vittoria Lutje (information specialist, Cochrane Infectious Diseases Group, UK), Paul Garner (principal investigator, Cochrane Infectious Diseases Group, UK). Conceptual validation with users The changes to recommendations were discussed and validated conceptually with the directors or focal points of national sleeping sickness control programmes of the following disease-endemic countries: Benin, Burkina Faso, Cameroon, Congo, Côte d’Ivoire, Gabon, Ghana, Guinea, Equatorial Guinea, Mali, Nigeria, South Sudan, Central African Republic, Democratic Republic of the Congo, Chad and Togo. v Overall coordination Gerardo Priotto and Jose Ramon Franco Minguell (HAT Programme, WHO) coordinated the development of the guidelines. Steering Committee The Guidelines Steering Committee comprised the following WHO staff: Abdoulaye Diarra (Communicable Diseases Unit (AF/RGO/CDS/CDU), Brazzaville), Gerardo Priotto, Jose Ramon Franco Minguell, Daniel Dagne, Sophie Lambert and Lise Grout (Innovative and Intensified Disease Management (HQ/CDS/NTD/IDM), Geneva), Nicola Magrini, (Innovation, Access and Use (HQ/HIS/EMP/IAU), Geneva) and Pere Perez Simarro (Consultant). vi Abbreviations and acronyms CSF cerebrospinal fluid DOT directly observed treatment EMA European Medicines Agency EPAR European Public Assessment Report EtD Evidence to Decision tables GDG Guideline Development Group GRADE Grading of Recommendations, Assessment, Development and Evaluation HAT human African trypanosomiasis LP lumbar puncture NECT nifurtimox–eflornithine combination therapy PICO population, intervention, comparator and outcomes STAG Strategic and Technical Advisory Group WBC white blood cell WHO World Health Organization vii Executive summary Human African trypanosomiasis (HAT), or sleeping sickness, is a parasitic infection that is almost invariably fatal unless treated. It is a neglected tropical disease that occurs in sub-Saharan Africa. The infection is transmitted to humans through the bite of an infected tsetse fly. The parasite multiplies
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