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.

Background/Objectives: West Nile neuroinvasive disease (WNND) is a severe neurological illness that develops in approximately 1% of individuals infected with West Nile virus (WNV). Manifesting most frequently as encephalitis (WNE), meningitis (WNM), or acute flaccid paralysis (WNP), there is no cure for WNND beyond supportive care and rehabilitation, and death or permanent disability are common outcomes. As the virus arrived in North America less than 20 years ago, determinants of severe disease progression following infection are still being explored. This project is the first to examine comorbid conditions as risk factors of WNND in Ontario using a population-based study design. As prevention is the only avenue of defence against WNND, identifying comorbid risk factors of WNND would allow for public health prevention campaigns targeted to high-risk groups. The main objectives of this thesis were to explore whether pre-existing chronic diseases were associated with the development of WNND, or any of its three manifestations (i.e., encephalitis, meningitis, acute flaccid paralysis). Methods: This was a retrospective, population-based study including all Ontario residents with a confirmed diagnosis of WNV infection between January 1, 2002 and December 31, 2012. A cohort of individuals with WNV was identified from a provincial laboratory database and individually-linked to health administrative databases. In the WNV cohort, individuals with WNND and 13 comorbid conditions were identified using algorithms based on ICD-10-CA diagnostic codes. Incidence of WNND following WNV infection was then compared among individuals with and without comorbid conditions using relative risks estimated by log binomial regression. Additionally, risk ratios were calculated for associations between specific comorbid conditions and WNND neuroinvasive manifestation (i.e., encephalitis, meningitis, acute flaccid paralysis). Finally, associations between Charlson Comorbidity Index (CCI) scoring and development of WNND was examined through calculation of relative risk using log binomial regression. Results/Potential Impact: Risk factors for WNND included male sex (aRR: 1.21; 95% CI: 1.00-1.46) in addition to the combined effect of hypertension and increasing age (5-year intervals) (aRR: 1.16; 95% CI: 1.08-1.24); WNND was also associated with increasing CCI scores; individuals in low, medium, and high categories had increased risk compared to individuals with a score of zero, but the greatest risk was in the high CCI category (aRR: 3.45; 95% CI: 2.25-4.83) Male sex (aRR: 1.32; 95% CI: 1.00-1.76), increasing age (aRR: 1.02; 95% CI: 1.02-1.03), and being immunocompromised (aRR: 2.61; 95% CI: 1.23-4.53) were associated with development of WNE. No risk factors were identified for WNM and WNP. Identification of comorbid risk factors of WNND will allow public health officials to identify high-risk groups and to develop prevention strategies targeted for vulnerable individuals.