Epidemiology of the highly pathogenic avian. influenza H5N1 in Northern Vietnam: applications for. surveillance and control

Transcription

1 Epidemiology of the highly pathogenic avian influenza H5N1 in Northern Vietnam: applications for surveillance and control DESVAUX Stéphanie, DVM, MSc This thesis is presented for the degree of Doctor of Philosophy of Murdoch University 2012

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3 I declare that this thesis is my own account of my research and contains as its main content work which has not previously been submitted for a degree at any tertiary education institution. DESVAUX Stéphanie iii

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5 Abstract The epidemiology and the sanitary situation of avian influenza changed dramatically with the emergence of the highly pathogenic H5N1 virus (HPAI) in As a consequence, knowledge previously accumulated on the epidemiology and the ecology of the avian influenza viruses was questioned and was required to be updated to understand the current pandemic caused by the virus (Webster, 2007; Sturm-Ramirez, 2005). This PhD combined a number of different epidemiological studies aimed at understanding the epidemiology of the H5N1 virus in the natural and human context of the Red River Delta area in Northern Vietnam. Firstly, retrospectives studies were conducted to identify the determinants of occurrence of HPAI outbreaks at 2 different scales: provincial and regional. Those 2 approaches allowed us to study the influence of the poultry production systems (provincial scale) and the influence of environmental determinants (regional scale). In addition, substantial field work was undertaken to monitor the serological and virological prevalence of HPAI in domestic poultry in our study area. After evaluation of the serological diagnostic tools being used, the data analysis contributed to a better understanding of the epidemiology of the H5N1 virus within a mass vaccination context. Furthermore, an evaluation of the vaccination strategy and implementation was also possible. In addition, to support our findings, a specific protocol to monitor the antibody kinetics of vaccinated poultry under field conditions was also conducted. Finally, a study was undertaken, in collaboration with a sociologist, to better capture the way sanitary information was circulating within our community of poultry farmers and through the formal surveillance system. Together with the results of our epidemiological work, this sociological study enabled us to propose measures to improve the surveillance and control of HPAI at the community level, to assist the people whose livelihoods were most affected. v

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7 vii Peter Brookes, the Times, 12 January 2006

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9 Table of contents CHAPTER 1 - INTRODUCTION The temporal pattern of HPAI H5N1 disease in vietnam The Vietnamese poultry production system The traditional farming system The semi-commercial sector Theorethical framework of the research Research questions and hypothesis Conceptual model Structure of the thesis 10 CHAPTER 2 - LITERATURE REVIEW A brief review of influenza viruses, in particular H5N General introduction to influenza viruses Origin and evolution of the H5N1 HPAI virus History of H5N1 HPAI viruses in vietnam and consequences for the epidemiology of the disease H5N1 pathobiology and consequences for the surveillance Surveillance and control options for H5N1 HPAI in birds General guidelines related to the surveillance of avian influenza Brief history of control and surveillance strategies applied to avian influenza outbreaks: the european experience Surveillance and control options of H5N1 hpai in Vietnam 22 CHAPTER 3 - RISK OF INTRODUCTION OF H5N1 VIRUS FROM CHINA Introduction Materials and methods Questionnaire and study site Identification of key informants and selection of traders and farmers Study population Risk assessment framework Results and discussion Identification of the actors involved in this illegal trade Poultry imported Seasonality of the chinese poultry trading Spatial spreading and risk management by traders and farmers Qualitative risk assessment Conclusions 45 CHAPTER 4 - LOCAL FACTORS INVOLVED IN THE DISSEMINATION OF HPAI H5N1 VIRUS Introduction Materials and methods Study design overview Data source and case and control selection Data collection Data analysis Results Study population Characteristics of the study population Vaccination practices in the village study population 60 ix

10 Analyses at the village-level Analysis at the farm-level Discussion Methodology Intensity of poultry movements and trading activity at the village and farm level Farm-level factors Environmental and infrastructure variables at village and farm level Conclusions 73 CHAPTER 5 - ROLE OF THE ENVIRONMENT IN THE EPIDEMIOLOGY OF THE H5N1 HPAI DISEASE Introduction Materials and methods Study area and study period Outbreak data Environmental variables Poultry population s data Temporal and spatial patterns Statistical analysis Study population for risk factor analysis Results Land cover map Temporal and spatial patterns Risk factor analysis Discussion Conclusions 99 CHAPTER 6 - EVALUATION OF SEROLOGICAL TEST FOR DIAGNOSIS TO H5N1 EXPOSURE Introduction Materials and methods Field data Serological tests Data analysis Results Evaluation of the HI test Evaluation of the H5 ELISA Discussion Conclusions 121 CHAPTER 7 - IMMUNOGENICITY OF THE INACTIVATED H5N1 VACCINE UNDER FIELD CONDITIONS Introduction Materials and methods Farms and bird selection Sampling protocol Data analysis 130 The HI titre kinetics were graphed based on the time elapsed since first vaccination and the mean HI titres of the vaccinated birds Results Discussion Conclusions 135 x

11 CHAPTER 8 - EVALUATION OF H5N1 VACCINATION EFFECTIVENESS AND IMPACT ON THE EPIDEMIOLOGY OF THE H5N1 HPAI DISEASE Introduction Materials and methods Study design overview Study sites Sampling strategy Sample size calculation Data collection Laboratory tests Data analysis Results Study population Viral circulation over a one-year period Variation in vaccination practices Change in seroprevalence of the study population over the study period Limited vaccination implementation effectiveness Duration of (protective) immunity against H5N1 under field conditions Modeling of the determinants of the vaccine immunogenicity Serological evidence of exposure to the H5N1 virus in non-vaccinated poultry Determinants of the seropositivity in the non-vaccinated birds Discussion Conclusions 171 CHAPTER 9 - FORMAL AND INFORMAL SURVEILLANCE SYSTEMS IN VIETNAM: HOW TO BUILD BRIDGES? Introduction to the study The human component of the surveillance systems Application of socio-antropology to the surveillance of HPAI in Vietnam Analytical grid used for interpretation of the results Formal and informal surveillance systems: how to build bridges? Introduction Materials and methods Results Discussion Perspective arising from the study: how to build bridges? Reduce the gap between experience-based versus pandemic-based policy by working at achieving an epidemiological consensus Enhance trust into institutions Strengthen credibility and responsibility of the actors at the interface Assist farmers to re-frame the disease Common construction of the object under surveillance: harmonization and acceptation of the H5N1 case definition 199 CHAPTER 10 - GENERAL DISCUSSION Main determinants of the occurrence of H5N1 HPAI in Vietnam China, a recurrent source of introduction of viruses Water bodies, reservoirs of viruses during epidemics Traders, main spreaders of viruses Broilers flocks, sentinels of the villages or danger for the village? Duck production, a significant determinant for the occurrence of outbreaks and for virus circulation Vaccination as a control tool in an endemic country: the drawbacks 204 xi

12 Minimum herd immunity threshold difficult to reach despite huge human and financial investments Inactivated vaccines need to be improved to induce longer immunity in domestic poultry Need for harmonized protocols to evaluate the immunogenicity under field conditions Perspectives: Control and surveillance options for a H5N1 HPAI endemic country with limited resources Vietnamese endemic areas, an example of living with disease? Zoning approach Improve biosecurity and surveillance at the local level, a commonplace but necessary step 210 GENERAL CONCLUSION 213 ANNEXES 225 Annex 1 - Poultry production system review Annex 2 - Poultry production chain Annex 3 - Modeling the chicken broiler flux Annex 4 - Modeling the social network of the poultry trader Annex 5 - Questionnaires of the study on illegal poultry trade from China Annex 6 - Individual-based modelling applied to the epidemiology of HPAI epidemiology Annex 7 - Processing of MODIS images Annex 8 - Poster presented at the SVEPM conference, March, Annex 9 - Initial results of the market protocol Annex 10 - Summary Protocol and results of the wild birds study Annex 11 - Pictures from field work Annex 12 - Supplementary information related to the study on information system xii

13 Acknowledgments I sincerely thank my supervisors team for their support and guidance during this thesis: To Stan Fenwick for being a very efficient and dedicated guide during all this process. To Trevor Ellis, for his meticulousness and efficiency in reviewing the papers. To John Edward, a role-model and a friend for several years now, who warmly welcomed me at Murdoch University. To François Roger from Cirad, a decisive encounter in my professional life, who introduced me to epidemiology and who is at the origin of this story. My sincere gratitude for the trust he puts on me since I am in his team. I acknowledge the support from the French Ministry of Agriculture allowing me, as a civil servant, to conduct this PhD and the French Ministry of Foreign and European Affairs for project funding (Gripavi). I thank the external examiners for their review and very useful comments. I thank all the persons who contributed directly to this thesis and in particular: Pham Thi Thanh Hoa who was very precious for the data collection during all the time spent in Vietnam. Marisa Peyre, for her support on the evaluation of the vaccination. Annelise Tran from Cirad and Sebastian Tollis, master student in 2009 who processed the satellite images. Nguyen Cong Oanh who collected the field data related to the study on the risk of introduction from China (not an easy task!) and to Cecilia Henriquez, a master student who performed the initial descriptive analysis of the data. Vladimir Grobois for his skill in explaining statistics and his incredible patience to answer all the (stupid) questions I had during the last 2 years and Lucas Léger, for his perseverance in R and his help on spatial statistics. Muriel Figuié for the very rewarding collaboration we had that helped me to look at my work differently. A special dedication to : the AGIRs team : c est une chance de pouvoir mêler le travail à l amitié. Je vais quitter les collègues, mais je compte bien garder les amis. Carlène : pour le soutien mutuel et les échanges fructueux sur les subtilités des méthodes statistiques! xiii

14 A ma petite famille qui équilibre ma vie, A ma grand-mère qui va être rassurée que je termine ENFIN mes études xiv