Objectives. Acute flaccid paralysis (AFP) has recently emerged as a major central nervous system complication associated with West Nile virus (WNV) infection. The spectrum of clinical presentations of AFP in WNV infection and its sequelae have not been well-studied. Methods. We describe three patients with AFP due to WNV infection and review the clinical presentations of 56 patients with this complication derived from published studies. Results. Patients with AFP and WNV presented with a spectrum of illness ranging from single extremity paralysis to quadriparalysis with cranial nerve involvement. Patients commonly developed respiratory failure (54%) and bladder dysfunction (22%). While fever was nearly universal (92%), signs of meningismus were less common (17%). Cerebrospinal fluid (CSF) analysis generally revealed a modest pleocytosis, and imaging studies were not diagnositic. Persistent neurologic impairment occurred in all survivors; overall mortality rate was high (22%) and was associated with both the extent of paralysis and advanced age. Conclusion. AFP in the setting of WNV is associated with significant mortality and long-term morbidity.

No description available.

Because little is known about juvenile American White Pelicans (Pelecanus erythrorhynchos) this study was conducted to gather more information on disease, general ecology and growth of American White Pelicans from hatching to fledging. In July 2011, American White Pelican regurgitate samples from North and South Dakota sub-colonies were collected/analyzed in preparation for a captive trial. Nutrient content compared between the colonies was found to be significantly different. Concentrations of Immunoglobulin Y and A in regurgitate samples were significantly different between colonies. A captive trial began 29 May 2012 and ended 30 July 2012, in which 16 American White Pelicans were hand raised from hatching to fledging. During the captive trial, various growth parameters, intake and fecal output were examined to determine the effect of the parasite Bolbophorus damnificus in 8 infected and 8 non-infected (parasite free) pelicans. Growth data collected on B. damnificus infected (n = 8) American White Pelicans was compared to previously mentioned parasiteree pelicans (n = 8) to determine effects of the parasite. There were no differences between groups for culmen length (P= 0.214), tarsal length (P = 0.306), body weight (P = 0.884) or intake (P = 0.963). There was also no effect of the parasite on body temperature. Towards the end of the captive trial, several pelicans both on (n = 16) and off (n = 11) trial became naturally infected with West Nile Virus. Clinical symptoms ranged from lethargy and/or wing droop to total paralysis. Progression of disease is detailed in two well-defined case studies with additional information included on clinical signs, physiological parameters, and a review of the pathology of disease for other infected birds.

Scavenging bird of prey have been abundant throughout the Mediterranean region for years, establishing a food acquisition relationship with human activities, their characteristics make them especially suitable for the recognition of dangerous environmental conditions. The West Nile Virus (WNV) considered the most widespread arbovirus has been previously discovered in our 3 species of studio. The analyses from feather follicles and serum samples obtain from different regions in Spain shown a higher seroprevalence against West Nile virus or cross-reacting flaviviruses in the northern part of the country and in the Canary archipelago. Our results showed a general seroprevalence of 19.8% (34 out of 172), a prevalence of 19,8% in Egyptian vultures, a prevalence of 27.1% (13 out of 48) in Griffon vultures and no prevalence in Cinereous vultures. Differences were observed for the body condition off Griffon and Egyptian vultures when anthropized and not anthropized areas were compared, being significantly worse in anthropized areas for Griffon vultures and significantly better for Egyptian vultures. The exposure to the virus of the nestlings increased with the age, showing a higher tend in Egyptian vultures than in Griffon vultures. Our results confirm the circulation and a higher seroprevalence of West Nile virus or cross-reacting flaviviruses than in previous studies.

Mosquito-borne viruses, including dengue virus (DENV), Usutu virus (USUV), West Nile virus (WNV), and Japanese encephalitis virus (JEV), are rapidly emerging, global pathogens. Though the number of people impacted by each virus varies, there have been thousands to millions of people infected. The focus of this thesis work centers around USUV and WNV; both have RNA genomes and belong to the Flaviviridae virus family. Both WNV and USUV were initially isolated in Africa and have since spread to Europe; interestingly, WNV has also spread globally and is considered endemic in the Americas. Similar to other flaviviruses, USUV and WNV are maintained in a mosquito vector-avian host transmission cycle, with spillover infection into humans. Human infections of WNV and USUV are usually asymptomatic, but in severe cases can cause neuroinvasive disease. WNV and USUV belong to the JEV serocomplex group, which indicates that antibodies produced against these viruses share a common antigen; the common antigen is hypothesized to be the envelope (E) protein on the outside of the virion. Neutralizing antibodies against both WNV and USUV have been found in birds and humans across Europe. In vitro cross-neutralization of WNV and USUV has been modeled experimentally and been observed in clinical settings. The neutralizing antibody response generated against WNV has been studied extensively in mouse models; however, there are few studies which examine the neutralizing antibody response generated against USUV. Whether prior WNV exposure protects against USUV disease is also unknown. The main goal of this thesis was to characterize how a primary flavivirus exposure would influence a secondary flavivirus exposure; specifically, we wanted to observe if WNV exposure would protect against USUV disease in vivo and generate a cross-neutralizing antibody response in vitro. For the WNV exposure, we used an attenuated vaccine strain of WNV that contains the WNV E gene (D2/WN-V3) developed by our collaborators. We hypothesized that treatment with D2/WN-V3 would protect against USUV infection. Two in vivo models were used: CD-1 mice and interferon alpha-beta receptor 1 deficient (Ifnar1-/-) mice. We discovered that sera from mice vaccinated with D2/WN-V3 neutralized both WNV and USUV in vitro. In the Ifnar1-/- model, we observed that vaccinated mice had higher survival rates and lower USUV viremia levels after USUV challenge. This work helps characterize the consequences of flavivirus antibody cross-neutralization in vitro and cross-protection in vivo. As the flavivirus field moves toward the goal of creating a pan-flavivirus vaccine, both cross-reactive antibodies and cross-protection need to be considered. / Master of Science / West Nile virus (WNV) and Usutu virus (USUV) are mosquito-borne viruses that were originally isolated in Africa during the 20th century. Both viruses are maintained through a transmission cycle between mosquito vectors and avian hosts. Mosquitos transfer the infectious agent (WNV or USUV) through feeding on a bird (usually a passerine species); once in the bird, the virus can replicate to high levels. Human infections of WNV and USUV from mosquitos can also occur, with symptoms ranging from mild febrile illness to severe encephalitis or meningitis. Over the past few decades, WNV and USUV have spread to Europe, most likely through infected migratory birds. Interestingly, mosquito surveillance studies in mainland Europe have found mosquitos that tested positive for both USUV and WNV. In Europe, antibodies for both viruses have been found in humans and birds, indicating a previous exposure to WNV, USUV, or both. The neutralizing antibody response is a critical immune defense against viral infections. Neutralizing antibodies bind strongly to the outside of the virion (virus particle), preventing the virion from interacting with and infecting the host cell. For WNV and USUV, one of the targets that neutralizing antibodies bind to is the outer envelope (E) protein of the virion. In clinical settings and experimental studies, cross-neutralization of WNV and USUV has been documented. During cross-neutralization, a serum sample containing neutralizing antibodies against WNV can also neutralize USUV, and vice versa. Although the neutralizing response against WNV has been characterized in humans and lab animal models such as mice, there is little research regarding the neutralizing response against USUV. Importantly, whether prior WNV exposure provides protection against USUV infection is currently unknown. The main goal of this thesis was to characterize the disease outcome and neutralizing response against USUV after a WNV exposure. For the WNV exposure, we used a vaccine strain of WNV that contains the E gene (D2/WN-V3) developed by our collaborators. We predicted that vaccinated mice would avoid USUV clinical signs of disease and generate neutralizing responses to WNV and USUV. To do this work, we used two laboratory mouse models: mice with an intact immune response system (CD-1) and mice with a stunted immune response (Ifnar1-/-). We discovered that serum from vaccinated mice did cross-neutralize WNV and USUV. In the Ifnar1-/- model, vaccinated mice had higher survival rates and lower levels of virus in blood after USUV infection compared to unvaccinated mice. Ultimately, this work highlights the importance of characterizing the immune response against similar viruses and will inform the development of human vaccines for both viruses.

Objective: The purpose of this investigation was to describe the long-term effects and functional outcomes of patients in Virginia who were reported to the Virginia Department of Health with West Nile virus (WNV) non-neuroinvasive and neuroinvasive disease. The study identified the duration of symptoms after initial illness, the number of persons who fully recovered versus the number who continue to be symptomatic and how patients' quality of life differed after illness.Methods: The study population was drawn from 60 human cases that met the surveillance case definition for non-neuroinvasive and neuroinvasive WNV illness in Virginia between 2002-2004. Information was collected during personal interviews using a standard questionnaire. The questionnaire included questions on demographics, clinical signs and symptoms, existing medical conditions and the respondents' personal assessment of health. Statistical analysis were used to compare pre and post illness symptoms, respondents vs. non-respondents, and non-neuroinvasive respondents vs. neuroinvasive respondents. Results: Thirty-four patients were enrolled in the study. Five (14.7%) respondents had non-neuroinvasive disease and 29 (85.2%) had neuroinvasive disease. Thirty respondents (88.2%) reported being hospitalized. Respondents with non-neuroinvasive disease spent a median of 3.5 (range, 0-7) days in the hospital and were unable to resume normal activities for a median of 17 (range, 7-365) days. Respondents with neuroinvasive disease spent a median of 7.5 (range, 0-82) days in the hospital and were unable to resume normal activities for a median of 127.50 days (range, 0-1023). Two (40%) of the respondents that suffer from non-neuroinvasive illness were unable to resume normal activities for at least 90 days. Fifteen (51.7%) respondents with neuroinvasive disease were unable to resume normal activities for at least 90 days. At the time of the interview, 20% of respondents with non-neuroinvasive disease reported fatigue, tremors, arthralgia, paralysis and memory problems. Respondents with neuroinvasive disease reported fatigue (58.5%), weakness (51.7%), myalgias (37.9%), confusion (41.4%), and memory loss (55.2%). Conclusion: WNV illness, including non-neuroinvasive illness, may be more serious and prolonged than generally thought. Neuroinvasive disease resulted in long-term morbidity and non-neuroinvasive disease resulted in work absenteeism and extended recovery periods. The mortality rates and potential long-term effects associated with non-neuroinvasive and neuroinvasive illness emphasizes the importance of continuing to develop effective methods of targeting preventive education to high-risk populations while continuing to pursue longer-term solutions such as vaccines to prevent emerging infection. Further research is needed to document the long-term effects of WNV, especially in areas with a high number of WNV human cases with more non-neuroinvasive patients. WNV is an emerging infectious disease with a wide clinical spectrum and variable long-term effects; thus a public health concern.

L'émergence de maladies telles que le SRAS et le SIDA au cours des dernières décennies a fait prendre conscience des liens étroits existant entre santé animale, santé humaine et santé des écosystèmes. En effet, les pathogènes émergents ont pour la plupart une origine zoonotique (i.e. ils circulaient à l'origine au sein des populations animales). Les risques sanitaires associés à ces émergences sont en constante évolution sous l'influence des changements globaux qui modifient les écosystèmes et les contacts entre les hôtes. La prévention et le contrôle des maladies infectieuses émergentes nécessitent la compréhension de leur dynamique dans l'ensemble des compartiments dans lesquels elles circulent. Le travail présenté ici avait pour objectif d'améliorer cette compréhension au sein des zones humides méditerranéennes en ce concentrant sur deux pathogènes émergents : les virus Influenza A (VIA) et le virus West Nile. Il a été structuré selon trois axes de recherche : i) Utiliser la surveillance épidémiologique de l'avifaune sauvage pour comprendre la circulation du virus West Nile dans le bassin méditerranéen ii) Comprendre la dynamique des VIA au sein des différents compartiments où ils circulent et à leur interface iii) Comprendre le rôle des conditions environnementales dans la dynamique des VIA notamment au sein des populations humaines. Nos résultats mettent en évidence l'intérêt de mener des études multidisciplinaires sur le long terme pour comprendre l'épidémiologie des maladies émergentes. Ils soulignent également le rôle des activités anthropiques et des conditions environnementales dans la dynamique de ces maladies. Nos études apportent des éléments de réflexion pour allier gestion des risques d'émergence et gestion des écosystèmes et des populations. Elles encouragent à développer ce type d'approche afin de relever le défi de la prévention et du contrôle des pathogènes émergents. / During the last decades, the emergence of numerous infectious diseases such as SARS and AIDS has raised awareness of the close links that exist between animal health, human health and ecosystem health. Many of the emerging pathogens have a zoonotic origin (i.e. they originally circulated among animal populations). The health risks associated with the emergence of these diseases are progressing under the influence of global changes that affect ecosystems and contacts between hosts. The prevention and control of emerging infectious diseases require an in-depth understanding of their dynamics in all the compartments in which they occur. The aim of the present work is to improve our understanding of these phenomena within the context of Mediterranean wetlands by focusing on two emerging pathogens: Influenza A viruses (IAV) and West Nile virus. The thesis is structured around three research axes i) Using epidemiological surveillance of wild birds to investigate the circulation of West Nile virus in the Mediterranean Basin ii) Exploring IAV dynamics in the different compartments in which they circulate and at their interface iii) Determining the role of environmental conditions in IAV dynamics, especially within human populations. Our results highlight the value of long-term interdisciplinary studies for the understanding of the epidemiology of emerging diseases. They also emphasize the role of human activities and environmental conditions in the dynamics of these diseases. Our studies open up perspectives for combining emerging disease risk management and the management of ecosystems and populations. They also argue in favour of further developing this type of approach in order to meet the challenge of emerging pathogen prevention and control.

West Nile Virus (WNV), a vector-borne disease continues to be a serious threat to public health in the United States, particularly in the Southwest region. While all the states in the U.S. experienced a decreasing trend of WNV disease in 2010, the state of Arizona experienced a sharp increase from 20 in 2009 to 166 cases the following year. This dissertation endeavored to develop forecasting models to predict future cases of disease and identify counties with increased propensity for WNV. Furthermore, this study aimed to identify environmental and economic factors that contributed to the increase in WNV cases in Maricopa County, Arizona. A spatiotemporal stochastic regression model was developed using Bayesian principles and was successful in calculating the annual mean cases of disease from 2003 to 2011 for all counties. The model was also able to predict future cases of disease by fitting historical data. The model-based inference identified counties in the southern region of Arizona as having an elevated propensity for disease compared to counties in the northern region. A Seasonal Autoregressive Integrated Moving Average (SARIMA) model was developed and effectively forecasted monthly cases of human WNV in Maricopa County, Arizona. By fitting the SARIMA model to monthly historical disease data from 2005 to 2011, the temporal model presented a decreasing trend of monthly incidence of disease for 2012. The impact of home foreclosures, climate variability, and population growth on the resurgence of human WNV disease cases in Maricopa County during the 2010 epidemic was investigated. These factors were found to have contributed to the resurgence of the disease by creating the optimal environmental conditions that allowed the amplification of mosquito populations, thus increasing the risk of disease transmission to humans. As spatiotemporal disease data become readily available, forecasting models can be an important and viable risk assessment tool for public health practitioners. Forecasting models allow the mobilization and distribution of limited resources to areas with elevated propensity for disease, and the timely deployment of intervention programs to reduce the overall risk of disease. / Graduation date: 2013

L'épidémie de West-Nile en Amérique du Nord en 2002, qui a touché plus de quarante états aux Etats-Unis, a conduit les Agences de santé à s'interroger sur le risque d'émergence, à l'extérieur de la zone intertropicale, de zoonoses vectorielles. Cette épidémie associée au changement climatique, a bien mis en évidence le rôle central de l'avifaune migratrice dans la diffusion du virus. La biologie des oiseaux, tout particulièrement le phénomène migratoire, permet un transport des virus sur de longues distances et entre espèces très diversifiées. Le Moyen-Orient, qui est situé au carrefour de différents continents, est extrêmement propice à la propagation des virus émergents dans les pays du Nord. La circulation du virus West Nile a été rapportée dans différents pays de la région, tels que l'Egypte, Israël, Liban, Irak, Emirats Arabes Unis et Iran. Saidi et al. (1970) ont montré la présence d'anticorps anti-virus du Nil occidental au sein de la population de la côte caspienne (Nord de l'Iran), des provinces du Khorassan (Nord-Est) et du Khuzestan (Sud-Ouest). Notre étude, conduite dans le cadre d'un programme associant TIMC-IMAG UMR 5525 UJF CNRS VetAgroSup, le Réseau International des Instituts Pasteurs et le Centre National d'Etudes Spatiales, vise: (i) à caractériser la circulation du virus de West-Nile au sein des populations équines d'Iran ; et (ii) et à modéliser l'impact sanitaire de l'environnement et du climat sur la transmission. Les résultats acquis permettent d'apprécier le risque associé à la dissémination spatio-temporelle du virus par les oiseaux migrateurs. Une attention toute particulière est portée à l'étude des déterminants environnementaux et climatiques susceptibles d'accroitre le potentiel de transmission du virus. / The outbreak of West Nile in North America in 2002, which affected more than forty states in the United States, has led Public Health Agencies to adress the risk of emergence of vectorial zoonosis, outside of the area tropical. This epidemic events associated with climate change, has highlighted the central role of migratory birds in spreading the virus. The biology of birds, especially the migratory phenomenon, ensures a transport of viruses over long distances and across very diverse species. The Middle East, located at the crossroad between different continents, is extremely prone to the spread of zoonotic diseases, like West-Nile, in the Northern countries. The circulation of WN virus has reported from different countries in the region; such as Egypt, Israel, Lebanon, Iraq, United Arab Emirates and Iran. Saidi et al. (1970) have established the presence of antibodies to West Nile among the population of the Caspian coast (northern Iran), the provinces of Khorasan (Northeast) and Khuzestan (Southwest). Our study, in the framework of a collaborative programme associating TIMC-IMAG UMR CNRS UJF VetAgroSup, International Network of Institut Pasteur and Centre National d'Etudes Spatiales, aim to: (i) characterizing the circulation of the virus from West Nile in the equine population of Iran, and (ii) and modelling the health impact of the environment and climate on the transmission. The results obtained allow us to assess the risk associated with spatial and temporal spread of the virus by migratory birds. Particular attention is given to the study of environmental and climatic determinants that may increase the potential for transmission.

The main goal of thesis is to explore the changing global epidemiological situation depending on climate changes and to map trends of changes in epidemiological situation. A sub-objective is to find out if there are differences in the geographical distribution of the incidence of West Nile Virus (WNV) in the period 2004-2014 next to map surveillance, to propose options for improving prevention in a changing geographical distribution, to describe cases of the diseases reported in the Czech Republic, to determine whether in the Pilsen and Budweis medical facilities are routinely investigating also on detection of WNV infection and finally to chart the WNV infection rate and its causes in horse breeding. Influence of climate change on distribution of WNV can be very well observed. This change is mainly due to settlement of new countries by the originator and also reservoirs which are moving further to the north or south becouse of climate. Distribution of WNV to the new countries is also supported by the changing of landscape, mainly due to the changing climate. The changes of migration routes of migratory birds which are also affected by climate changes have also the effect on changing geographic distribution. The globalization of the world is also mostly responsible for change of distribution. The change of epidemiological situation is given by that the virus attacks organisms that did not meet with virus until now. Therefore, there is a change in the clinical picture and more serious forms of the disease appear in the greater degree than before. Official statistics numbers of diseases in the EU in 2008-2012 published by the ECDC revealed that number of illnesses depends on the global climate changes and also on the climate in a current year. Data for year 2010 clearly reveal how big influence extreme temperatures have on the number of reported illnesses. With regard to prevention in the Czech Republic, as a main step was to designed the informing of tourists. The substantial part of the repressive measures against WNV disease is to stop transmission of WNV blood transfusions. This deals with in annex 3of Decree no. 143/2008 Coll.. Currently the draft of methodological instruction which sets out the procedure for assessing the risk of WNV infection and the procedure to reduce the risk of transmission of the virus through blood transfusions is in the comment procedure. By the survey of health facilities was found out that it is according the legislation, specifically Decree 233/2011 Coll.. Private microbiology and serology laboratories in Pilsen and Budweis do not test on positivity of WNV. Targeted surveillance of horse WNV in Czech Republic is doing from 2011. In 2011 2013 it was 4 5 WNV positive horses, in 2014 it was already 13 horses from a total of 783 horses tested positive WNV. Various geographic distribution of horses and high specific antibody titers according to veterinarians indicate increasing activity of the virus in the Czech Republic and the possible expansion of WNV into new areas. The thesis also analyzes three cases of WNV disease that have been imported to the Czech Republic from the USA, Tanzania and from Cyprus. In thesis is also described the first autochthonous case of WNV infection in the Czech Republic in 2013 which demonstrates the changing epidemiological situation in the country. Based on the obtained data is appreciable that the virus will be with regard to a changing climate and increased globalization spread to new areas in which will be probably cause diseases with serious clinical course. Whereas the virus has a tends to mutation it is expected also a gradual change of the clinical picture. To stop the spread of the virus should be carried out surveillance at all levels. Insomuch as is not in current time human vaccine available to curb the spread of the The essential elements od prevention includes informing tourists traveling to high-risk countries and countries potentially risky.