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Adenoviruses in Côte D`Ivoire: Investigation of Diversity and Interspecies Transmission

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Adenoviruses in Côte D`Ivoire: Investigation of Diversity and Interspecies Transmission Adenoviruses in Côte d`Ivoire: investigation of diversity and interspecies transmission von Maude Suzanne Pauly Inaugural-Dissertation zur Erlangung der tiermedizinischen Doktorwürde der Tierärztlichen Fakultät der Ludwig-Maximilians-Universität München Adenoviruses in Côte d`Ivoire: investigation of diversity and interspecies transmission von Maude Suzanne Pauly aus Strasburg (Frankreich) München 2015 Aus dem Veterinärwissenschaftlichen Department der Tierärztlichen Fakultät der Ludwig-Maximilians-Universität München Lehrstuhl für Virologie Institut für Infektionsmedizin und Zoonosen Arbeit angefertigt unter der Leitung von Prof. Dr. Sutter Angefertigt am Robert Koch-Institut Mentoren: Dr. Leendertz und Dr. Ehlers Gedruckt mit Genehmigung der Tierärztlichen Fakultät der Ludwig Maximilians Universität München Dekan: Univ.-Prof. Dr. Joachim Braun Berichterstatter: Prof. Dr.Gerd Sutter Korreferent/en: Prof. Dr. Andrea Fischer Tag der Promotion: 31.Januar 2015 This thesis is dedicated to Mamama and Metto, who will always walk beside me and will stay forewer in my heart. Three first author publications based on data collected and analyses performed within the framework of the thesis, were published: “High prevalence and diversity of species D AdV (HAdV D) in human populations of four Sub-Saharan countries.” (Pauly et al. 2014), “Adenovirus in Rural Côte D`Ivoire: High Diversity and Cross-Species Detection.”(Pauly et al. 2015) and “Contact with non- human primates and risk factors for zoonotic disease emergence in the Taï region, Côte d`Ivoire.”(Mossoun et al. 2015) (shared first authorship). Several sections of the papers were slightly adopted or directly copied in this thesis. A student in biotechnology of the University of Applied Sciences (Beuth Hochschule für Technik, Berlin), Nanina Buchwald, did some of the analyses (first AdV screening of the poultry and of the rodents) for her bachelor thesis and was supervised by Maude Pauly and Dr. Bernhard Ehlers. Three PhD students, two from Côte d`Ivoire (Etile Anoh Augustin and Arsène Mossoun), and myself were engaged in the entire project, participated in the field missions and analyzed the collected data. The statistical analysis was done with the scientific support of Siv-Aina Leendertz and the data processing with the help of Arsène Mossoun. 1. Introduction Introduction: English Version In order to achieve the sixth Millennium Development Goal (“fighting infectious diseases and specifically controlling neglected tropical diseases by 2015”) (MDG Africa Steering Group 2008), there is an urgent need for research in tropical Africa, where 53 % of infectious disease outbreaks occur (Chan et al. 2010). Until completion of knowledge on dynamics of infectious diseases (comprising the ecological, evolutionary, social, economic, and epidemiological mechanisms), reduction of morbidity and mortality caused by infectious diseases will unlikely be met. Special focus should be put on viral zoonoses, which ‘‘are diseases or infections naturally transmitted between vertebrates and humans’’ (World Health Organization). More than 25 % of the emerging infectious diseases (EID) are caused by viruses and the majority originated from animal hosts (Jones et al. 2008, Howard and Fletcher 2012). It has been shown that there is a significant disequilibrium concerning global disease surveillance (Jones et al. 2008): too few scientific resources are invested in countries with high biodiversity and low infrastructure, which represent hotspots for disease emergence (e.g. sub-saharan Africa). Thus, it is of paramount importance to develop the capacities of these countries to react quickly and effectively to emerging disease outbreaks as the consequences can have fatal effects on human and animal health, on economy, trade and tourism (Epstein and Price 2009). In sub-Saharan Africa, frequent, long-lasting and intense interspecies contacts increase the risk for interspecies transmission of pathogens. Agriculture and breeding of domestic animals modified pathogen ecology by creating novel livestock-wildlife-human interactions and the perfect environment for the development and spread of pathogen vectors (Pearce-Duvet 2006). In several contexts, host switches could be associated with anthropogenic modifications of the environment or with bushmeat related activities (Wolfe et al. 2005, Engel et al. 2006). Host switches often lead to increased pathogenicity of the pathogen in the new unadapted host population (Parrish et al. 2008). Altered pathogenicity, infectivity, transmissibility and tropism can also be due to recombinant infectious agents emerging after frequent and intense exposure to diverse agents (Walsh et al. 2009, Dehghan et al. 2013). To mitigate disease threats to public health, livestock economies and wildlife conservation, extensive pathogen-specific risk analyses with a multidisciplinary approach have to be conducted in tropical Africa. Against this background, a project on “Capacity Building for the Detection and Prevention of Neglected Zoonotic Infectious Diseases in Tropical Africa” was designed by an international and multidisciplinary team. The two main study regions, the Taï region in Côte d`Ivoire (CI) and the Salonga National Park in Democratic Republic of the Congo (DRC) are remote, rural regions, for which information on incidence and prevalence of infectious diseases is limited. As the local population consists of breeders, cultivators and hunters, contact to livestock and wildlife is frequent and intense. It is thus the perfect environment to investigate whether overlapping human and animal habitat can influence rates and patterns of pathogen transmission between humans, livestock and wildlife. Investigated pathogens in the project were retroviruses, cytomegaloviruses and adenoviruses (AdV). All of them are endemic in tropical Africa and can cause disease in (immunosuppressed) human and animal host. The present study represents the part of the project devoted to the study of AdV. AdV have been detected in mammals, birds, fishes, amphibians and reptiles, worldwide. Most AdV infections are asymptomatic in human and animal hosts. However, AdV-induced symptoms include gastroenteritis, kerato-konjunctivitis and pneumonitis. Bacterial co-infection, young age and immunosuppression enhance the risk to develop severe symptoms. More recently, zoonotic transmissions have been repeatedly reported for different AdV, and AdV recombinants have been detected (Horwitz and Wold Introduction 8 2007, Harrach et al. 2008, Hoppe et al. 2015, Hoppe et al. 2015). Little is known about epidemiology, phylogeny and pathogenicity of AdV in humans and animals living in the Taï region in Côte d`Ivoire. As AdV prevalence and diversity have already been described in non-human primates of the region (Wevers et al. 2011, Hoppe et al. 2015), the present thesis focused mainly on humans and domestic animals (livestock and companion animals). It has been shown that livestock can play key roles as intermediate host or as “bridge” for the transmission of wildlife pathogens to humans, as they are more likely to come into contact with wildlife (Daszak et al. 2000, Pearce-Duvet 2006, Wood et al. 2012). The general goal of this PhD thesis was to identify and estimate the risk for cross-species transmission of AdV between humans and domestic animals. The gathered knowledge may be beneficial in formulating prevention recommendations to reduce pathogen transmission in areas where humans, livestock and wildlife cohabit. Based on the general goal of the thesis, the particular aims of the present study were: 1)To determine the type and prevalence of AdV in feces of humans and domestic animals in rural Côte d`Ivoire 2) To perform phylogenetic and recombination analysis of the identified sequences to characterize the circulating AdV strains. 3) To statistically analyze behavioral and demographic data to identify risk factors for zoonotic disease transmission 4) To assess the occurrence of zoonotic transmission of AdV 5)To unravel factors that might facilitate AdV spread, and symptoms associated with adenoviral infection. Introduction 9 Table of Contents 1. Introduction ................................................................................................................................ 4 2. Literature Review ..................................................................................................................... 12 2.1 Adenoviruses: General features ............................................................................................. 12 2.2 Mastadenovirus ...................................................................................................................... 19 2.2.1 Genus specific features ................................................................................................... 19 2.2.2 Epidemiology in humans ................................................................................................. 19 2.2.3 Epidemiology in mammals .............................................................................................. 20 2.3 Atadenovirus ........................................................................................................................... 24 2.3.1 Genus specific features ................................................................................................... 24 2.3.2 Epidemiology ................................................................................................................... 25 2.4 Siadenovirus .....................................................................................................................
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