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EPIDEMIOLOGY AS a TOOL to IMPROVE PREVENTION of HUMAN RABIES LOCAL and GLOBAL HEALTH IMPLICATIONS of POSTEXPOSURE PROPHYLAXIS DATA Par Arnaud P

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EPIDEMIOLOGY AS a TOOL to IMPROVE PREVENTION of HUMAN RABIES LOCAL and GLOBAL HEALTH IMPLICATIONS of POSTEXPOSURE PROPHYLAXIS DATA Par Arnaud P EPIDEMIOLOGY AS A TOOL TO IMPROVE PREVENTION OF HUMAN RABIES LOCAL AND GLOBAL HEALTH IMPLICATIONS OF POSTEXPOSURE PROPHYLAXIS DATA Par Arnaud P. TARANTOLA Thèse de Doctorat d’Epidémiologie Clinique Arnaud Tarantola To cite this version: Arnaud Tarantola. EPIDEMIOLOGY AS A TOOL TO IMPROVE PREVENTION OF HUMAN RA- BIES LOCAL AND GLOBAL HEALTH IMPLICATIONS OF POSTEXPOSURE PROPHYLAXIS DATA Par Arnaud P. TARANTOLA Thèse de Doctorat d’Epidémiologie Clinique. Infectious diseases. Université Sorbonne - Paris Cité, 2018. English. tel-01893018 HAL Id: tel-01893018 https://hal-riip.archives-ouvertes.fr/tel-01893018 Submitted on 11 Oct 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Thèse de Doctorat de l’Université Sorbonne Paris Cité Préparée à l’Université Paris Diderot ECOLE DOCTORALE PIERRE LOUIS DE SANTE PUBLIQUE A PARIS (ED393) Inserm UMR 1153, Service de biostatistiques et information médicale (SBIM), Equipe ECSTRA, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France Centre National de Référence de la Rage; Unité Dynamique des Lyssavirus et adaptation à l'Hôte, Institut Pasteur, 25-28 Rue du Docteur Roux, 75015, Paris, France EPIDEMIOLOGY AS A TOOL TO IMPROVE PREVENTION OF HUMAN RABIES LOCAL AND GLOBAL HEALTH IMPLICATIONS OF POSTEXPOSURE PROPHYLAXIS DATA, INSTITUT PASTEUR DU CAMBODGE, 2003-2014 Par Arnaud P. TARANTOLA Thèse de Doctorat d’Epidémiologie Clinique Dirigée par Jean-Yves MARY et Hervé BOURHY Soutenue publiquement à Paris le 10 Septembre 2018 JURY Président du Jury: Yazdan YAZDANPANAH, PUPH, Université Paris 7 Rapporteur: Rachid SALMI, PUPH, Université de Bordeaux Rapporteur: Philippe GAUTRET, PU, Université Aix-Marseille Examinatrice: Hélène PEIGUE-LAFEUILLE, PUPH, Université Auvergne Examinatrice: Elisabeth DELAROCQUE-ASTAGNEAU, PUPH, Université Versailles Saint-Quentin Directeur de Thèse: Jean-Yves MARY, DR Inserm, Université Paris 7 Co-Directeur de Thèse Hervé BOURHY, Chef de Laboratoire Institut Pasteur, Université Paris 7 DOI: 10.13140/RG.2.2.27381.01761 EPIDEMIOLOGY AS A TOOL TO IMPROVE PREVENTION OF HUMAN RABIES: LOCAL AND GLOBAL HEALTH IMPLICATIONS OF PEP DATA, INSTITUT PASTEUR DU CAMBODGE, 2003-2014. Dedication To TVB, a Cambodian child whose untimely death by rabies at age 9 despite post- exposure prophylaxis was the triggering event for this research and the ultimate modification of WHO recommendations on rabies PEP worldwide. To Emile Roux, medical doctor and researcher with a medical thesis on rabies prevention, whose dedication, work and ethics lay the groundwork for rabies prevention in humans. To Yolande and Daniel Tarantola, for showing the way. To our friends in France for their faithful friendship during our travels, despite the distance. To Elsa and Margaux, for the joy. And – last but not least - to Anne Rachline, for her very, very great patience and for making everything possible. Arnaud Tarantola 2 PhD Epidemiology / 2018 Ecole Doctorale Pierre Louis, Université Sorbonne Paris Cité EPIDEMIOLOGY AS A TOOL TO IMPROVE PREVENTION OF HUMAN RABIES: LOCAL AND GLOBAL HEALTH IMPLICATIONS OF PEP DATA, INSTITUT PASTEUR DU CAMBODGE, 2003-2014. Acknowledgements Dr. Jean-Yves Mary, for his kindness, forbearance and curiosity, and for guiding me through this thesis in many ways. Pr. Hervé Bourhy for his friendship, his generous guidance and unrelenting support for the work done on rabies in Cambodia. Dr. Sok Touch and Dr. Ly Sovann, Ministry of Health of Cambodia, for their invaluable support of our rabies work in Cambodia. To the very wonderful team at Institut Pasteur du Cambodge (IPC), especially that of the epidemiology and public health Unit and the rabies prevention center, and to all those who successively acted there to prevent rabies in Cambodia. Drs. Sophie Blanchi and Julien Cappelle for their major contribution on geographical analysis and boosted regression tree modeling. Lydie Martorana for her irreplaceable and effective long-distance help to meet the administrative constraints linked with a PhD. Pr. Alice Dautry and Division Internationale, Institut Pasteur de Paris for financing initial work and the Action Concertée Interpasteurienne which lay the groundwork for the ongoing Rabies Elimination Support through Integrative Science and salvage Therapy (RESIST) program. Acknowledgements for their editorial help and/or answers to nagging questions on rabies (by alphabetical order): Jacques Barrat; Debbie Briggs; Philippe Buchy; Mina Bui-Jones; Philippe Dussart; Mirjam Duijvestijn; Marie-France Estadieu; Emma Finn; Yves Froehlich; Lea Knopf; Jean-François Meister; Artem Metlin; Anne-Marie Moulin; Emma Quilliam; Mark Weeden. The historical review benefited from the invaluable help of the Musée Pasteur and of many libraries which digitize rare and old texts before making them freely accessible on the internet: Gallica at Bibliothèque Nationale de France, Medic@ at Bibliothèque Interuniversitaire de Santé, the Internet Archive, the Wellcome Library, and others. Other contributors of information are cited or acknowledged in the text. Many references documents and webpages accessible through a shifting internet were archived using WebCite® (http://www.webcitation.org/), which we gratefully acknowledge. Arnaud Tarantola 3 PhD Epidemiology / 2018 Ecole Doctorale Pierre Louis, Université Sorbonne Paris Cité EPIDEMIOLOGY AS A TOOL TO IMPROVE PREVENTION OF HUMAN RABIES: LOCAL AND GLOBAL HEALTH IMPLICATIONS OF PEP DATA, INSTITUT PASTEUR DU CAMBODGE, 2003-2014. Table of contents SCIENTIFIC PRODUCTION ..........................................................................................................9 ARTICLES PUBLISHED IN PEER-REVIEWED JOURNALS ................................................................................. 9 ARTICLES ACCEPTED OR UNDER REVIEW ................................................................................................ 9 LIST OF ABBREVIATIONS ......................................................................................................... 10 RESUME ................................................................................................................................. 11 SYNTHESE EN FRANÇAIS .......................................................................................................... 12 1. PARTIE 1: CONTEXTE ET RATIONNEL ................................................................................ 12 1.1 PASTEUR ET SON EPOQUE .................................................................................................. 12 1.2 ASPECTS VIROLOGIQUES .................................................................................................... 13 1.3 PHYSIOPATHOLOGIE ET ANATOMOPATHOLOGIE ........................................................................ 13 1.4 ASPECTS CLINIQUES DE LA RAGE .......................................................................................... 14 1.5 DIAGNOSTIC DE LA RAGE ................................................................................................... 15 1.6 ASPECTS EPIDEMIOLOGIQUES DES MORSURES ET DE LA RAGE TRANSMISE PAR LE CHIEN AU CAMBODGE ... 16 1.7 LA PREVENTION DE LA RAGE CHEZ L’HUMAIN ........................................................................... 16 1.8 AMELIORER L’ACCES A UNE PROPHYLAXIE POST-EXPOSITION DANS LES PAYS EN DEVELOPPEMENT .......... 17 2. PARTIE 2: OBSTACLES A L’UTILISATION DU VACCIN ET DES IMMUNOGLOBULINES ANTIRABIQUES AU CAMBODGE ............................................................................................... 18 2.1 INTRODUCTION ............................................................................................................... 18 2.2 METHODE ..................................................................................................................... 19 2.3 RESULTATS .................................................................................................................... 19 2.4 DISCUSSION ET CONCLUSION .............................................................................................. 20 3. PARTIE 3: AMELIORER L’ACCES GEOGRAPHIQUE A LA PREVENTION ANTIRABIQUE .............. 21 3.1 INTRODUCTION ............................................................................................................... 21 3.2 METHODE ..................................................................................................................... 21 3.3 RESULTATS .................................................................................................................... 23 3.4 DISCUSSION ET CONCLUSION .............................................................................................. 24 4. PARTIE 4: AMELIORER L’ACCES FINANCIER A LA PREVENTION ANTIRABIQUE ....................... 24 4.1 INTRODUCTION ............................................................................................................... 24 4.2 METHODE ..................................................................................................................... 25 4.3 RESULTATS ...................................................................................................................
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