Thesis (M. Nurs.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 83-96).

published_or_final_version / Community Medicine / Master / Master of Public Health

Respiratory infection is a major disease burden worldwide. Statistical reports revealed it is one of the main causes of mortality and morbidity especially in young children. Influenza infection is one of the predominant cause associate with respiratory infection. Traditionally, studies have been emphasized on the detection of influenza A and B virus owing to their significance in clinical and economic impact. Attention of influenza C virus is rarely recognized due to its difficulty in isolation. However, recently, increasing reports have been illustrated the co-circulation of influenza C virus globally. Serological studies also suggested majority of people worldwide acquired influenza C virus infection in their early childhood or adolescent stage, yet information regarding influenza C virus is still inadequate. Epidemiological and clinical impact of influenza C virus in pediatric patients in Hong Kong was examined by the approach of real-time PCR. From November 2007 to April 2011, a total of 1, 037 specimens were obtained from pediatric patients exhibited apparent respiratory tract illness in Hong Kong. Eleven strains of influenza C virus were detected by real-time PCR approach. All patients with influenza C virus infection were below 5 years of age with the youngest age of 11 months. The ratio of infection in male to female was approximately one to one. High grade fever appeared to be the most frequent clinical manifestations (10/11) of influenza C virus infection. Upper respiratory tract infection was also occasionally observed. The clinical presentation of influenza C virus was similar to its influenza counterpart. Phylogenetic analysis of influenza C virus was examined in 6/11 of the isolates to determine the lineages of co-circulating influenza C viruses in Hong Kong. Nucleotide sequencing was performed with primer targeting the hemagglutinin-esterase (HE) gene. Result revealed that most of the detected influenza C virus associate with the C/Sao Paulo/378/82 related lineage. Results from this study revealed the positive rate of influenza C was comparable to influenza B and resultant respiratory symptoms could be severe in pediatric patients It is suggested to consider the inclusion of influenza C virus detection in routine diagnostic panel and real-time PCR could be a desirable detection platform account for its sensitivity and rapidity. / published_or_final_version / Microbiology / Master / Master of Medical Sciences

Background Human infected with influenza virus commonly present with fever and cough. However, it is documented in the literature that a proportion of people with influenza infection remained afebrile or even asymptomatic. Understanding of the prevalence of febrile illness among people infected with influenza (the febrile proportion) could guide the public health response to influenza epidemics and pandemics. Methods A systematic review was conducted by a search of relevant articles published in peer-review journals using PubMed and Google. Two different approaches were adopted in the synthesis of the febrile proportion. Results Nine studies were included in the systematic review. The febrile proportion of influenza infection was estimated to lie between 32% and 83%, with the most plausible values in the range of approximately 50%. Pandemic and pre-pandemic strain of influenza A H1N1 subtype may have a higher febrile proportion than influenza A H3N2 subtype and influenza B. The febrile proportion among children was also higher than adults. Conclusion This systematic review consolidated evidence on the febrile proportion in influenza infection. Attributes were identified to be potentially associated with higher febrile proportion. These preliminary findings provide interesting hypothesis for future research and provide opportunities for changes in the public health response to influenza epidemics and pandemics, with particular implications for the use of body temperature screening at national borders. / published_or_final_version / Public Health / Master / Master of Public Health

Introduction: Seasonal influenza is believed to be a common attribution of morbidity and mortality in the children population, and it causes huge disease burden worldwide. Although seasonal influenza vaccination is recommended as the most effective prevention by the World Health Organization and vaccination programs for children have been introduced in many countries, vaccination coverage remains low. Parents are primary decision makers for their children's immunization, therefore it is important to understand the determinants that influence parents' decision-making to provide important information for promoting vaccination uptake against seasonal influenza among children. Objective: To synthesize factors that influence parental decision on children's vaccination against seasonal influenza from published literature. Method: Literature reported factors that influenced parental decision on children's vaccination against seasonal influenza published before/on 31th May, 2013 were searched in PubMed and Web of Science databases. Manual searching was also performed for the citations of the retrieved papers. Both qualitative and quantitative articles consistent with the objective were searched from PubMed and Web of Science databases on 31th May, 2013. Records were screened in the sequence of title, abstract and full text to identify eligible studies, and references of eligible studies were also scrutinized to avoid missing important articles. Influencing factors were extracted from included papers, and the identified factors that influenced parental decision making were then discussed based on theoretical behavioral models. Results: Totally 32 articles met the inclusion criteria. Factors associated with parental decision included demographic factors, which consisted of parental and children’s age, parental gender, ethnicity, household income, residence, insurance status, family characters, parental education level, and children’s health history; psychological factors, including attitudes towards influenza vaccination, knowledge of influenza and vaccination, perceived risk of seasonal influenza, and emotional factors; past behaviors comprising previous frequency of using health care services, children’s seasonal influenza vaccination history, previous absenteeism from school or work, social norm referring cues to action and subjective norms; and environmental factors, meaning access to vaccination facilities. Discussion: An integrated framework based on the Health Belief Model, Triandis’ Theory of Interpersonal Behavior and the Theory of Reasoned Action was constructed to explain the findings. The framework proposes that the parents’ intention to vaccinate their children against seasonal influenza is influenced by demographic variables, attitude towards seasonal influenza vaccination, knowledge and perception of influenza/influenza vaccine, social norms (cues to action and subjective norms), emotion, and past behavior/experience; easy access to vaccination providers as a facilitating condition additionally determine the possibility of turning intention into actual behavior. Interventions such as providing positive knowledge relevant to seasonal influenza vaccination, targeting less intended and more influential decision-makers, ensuring sufficient access to vaccination, and creating action cues may be implemented to promote uptake of seasonal influenza vaccination among children. / published_or_final_version / Public Health / Master / Master of Public Health

Background The dynamics of influenza virus transmission are not yet fully understood, hindering the appropriate development and implementation of control and mitigation strategies. One major uncertainty relates to the profile of infectiousness over time in humans infected by influenza virus, and how variation in infectiousness might contribute to the risk of transmission in households. Methods In 2008 and 2009, two large community-based studies were conducted to study the household transmission of influenza viruses in Hong Kong. I analyzed data on viral shedding and disease in participants, and used statistical models to examine how viral shedding patterns and other factors might affect the risk of influenza virus transmission in households, both within individuals over time, and between individuals with different patterns in viral shedding. Results The patterns of viral shedding relative to the time of illness (acute respiratory illness; ARI) onset in naturally acquired infections were found to be largely comparable to the patterns observed in experimental infections. Viral shedding detected by RT-PCR peaks around the day of ARI onset after which levels of shedding declined over around 7 days, and viral shedding tended to be greater in children than adults. The patterns of viral shedding in cases of seasonal A subtypes were similar, although the trends of shedding in cases of seasonal B differed with some indication of a plateau in shedding for up to 5 days after illness onset. The risk of household influenza transmission was significantly associated with log10 viral shedding, though not with influenza related signs and symptoms such as cough. Conclusions The patterns of viral shedding observed in naturally-acquired influenza A virus infections correlated with the pattern of infectiousness over time after onset of illness. The majority of infectiousness was estimated to occur within 2-3 days of illness onset, with implications for isolation strategies. The heterogeneous nature of individual viral shedding suggests the possibility of substantial variation in infectiousness, particularly among children. / published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

Introduction: Influenza is one of the commonest infectious diseases among human beings. The annual attack rates were 5-10% and 20-30% in adult and children respectively around the world. Fortunately, this is a vaccine preventable disease. Vaccinating health care workers can reduce risk of infection among themselves so as to maintain the availability of health care services. This can also prevent nosocomial infections and associated morbidity and mortality of their patients. The World Health Organization recommended 60% influenza vaccination coverage by 2006 in high risk groups and targeted 75% by 2010. However, the vaccine uptake rate among health care workers is still low globally. The vaccination coverage is in Western Europe 20-40%, in Hong Kong 30%, in Australia 16-60% and in the United States 63.5%. This systematic review aims at identifying the factors influencing influenza vaccine uptake among health care workers which can help formulation of future vaccination strategies so as to protect health care workers themselves and their patients. Methods: Electronic databases (PubMed, MEDLINE and eKG) of journal articles published after January 2011 using title and keywords related to health care workers and influenza vaccination uptake were searched. Predefined inclusion and exclusion criteria were applied. Data were extracted and quality was assessed from the eligible studies using individualized data extraction form and quality assessment form by two reviewers. The reasons of vaccination acceptance and declination were divided into different categories. A score was given to each category according to the percentage of respondents stating that as an important influencing factor. The factor with higher score indicated the more important it is. The predictive factors positively associated with vaccination acceptance were retrieved from results of multivariate logistic regression models of the studies which had an odd ratio greater than one. The PRISMA statement is used to guide the methodology and reporting of the studies. Results: Nine eligible studies were finally identified. The studies reviewed found that the reasons behind low seasonal influenza vaccination uptake rate among health care workers are complex and made up by both perceptual and organizational factors. For factors of influenza vaccination acceptance, self protection, risk perception, and protection of patients were identified as the most important. For factors of influenza declination, concern of vaccine side effects, lack of concern, and doubts of vaccine safety and efficacy showed the greatest influence. Convenient vaccination location and time was suggested to be the strongest predictive factor which positively associated with future vaccination uptake. Conclusion: As influenza vaccination is an effective measure to prevent infection among health care workers and nosocomial infection of their patients, annual seasonal influenza vaccination program is essential in health care settings. In order to promote annual seasonal influenza vaccination among health care worker, multipronged approach is recommended. Targeted educational intervention can be used to overcome the perceptual barriers on misconception about influenza and influenza vaccines. The organizational barriers can be fixed by introducing mobile vaccination team which provide services in flexible period of time around the workplace. / published_or_final_version / Public Health / Master / Master of Public Health

Background Globally, epidemics of obesity and influenza are always two major public health issues that require immediate actions for human. After the outbreak of pandemic influenza A (H1N1) in 2009, the relationship between obesity and influenza was widely recognized due to severe illness and reported death with obesity among infected cases. We still doubted whether obesity is a risk factor for influenza infection or not. So I conducted this systemic review to explore the association between obesity and influenza A morbidity or mortality. Method PubMed, Google scholar, and HKU library were searched using a prepared strategy for all items in English up to 31 July 2014. Search strategy, exclusion and inclusion criteria, assessment of quality, as well as data analysis were established for screening all relevant publications. Findings Through careful screening, 17 relevant studies were adopted into this review. There were 9 case control studies of all observational studies. Obesity and morbid obesity in influenza A infected adults (below 60 years old) could be regarded as a risk factor for hospitalization and severe sickness. Morbid obesity would be related with higher risk for mortality and ICU admission. Conclusion From my review, there was a strong association between obesity and influenza A infection had been confirmed. However, we need to carry out further research to explore the details of impacts. Obese people, as the high-risk population, should take vaccine during influenza season to protect themselves effectively. / published_or_final_version / Public Health / Master / Master of Public Health

The impact of the 2009 influenza pandemic and other recent epidemics are still being assessed. Appropriate allocation of protection and control strategies depend on accurate estimation of disease burden, with high risk groups generally being a key focus especially for distribution of influenza vaccine to maximize the disease burden prevented per vaccine when resource is limited. Therefore, better understanding the impact of influenza and control of influenza among the high risks groups with greater burden is particularly important. In this thesis, I estimated the years of life lost (YLL) associated with influenza correcting for underlying risk factors in addition to age and provided a new methodology for disease burden estimation of influenza. I focused on three vaccine target groups - healthcare workers (HCWs), cancer patients and obese people - to estimate the influenza impact and control among them using multiple approaches. I applied a new comprehensive method to take into account the shorten life expectancy for influenza deaths with underlying risk factors compared to general population by adding excess hazards of these risk factors in the baseline life tables, finally correcting for 25% overestimation of YLL associated with 2009 pandemic. For vaccine target groups, I analyzed the serum data from a cross-sectional study and found there was no occupation-related excess infection risk for unvaccinated HCWs following the first wave of the 2009 pandemic, supporting the effectiveness of the intensive protection and control strategies in Hong Kong. However, the reasons for the unexpectedly poor immune response observed in this study for HCWs with receipt of the 2009 pandemic influenza vaccine requires further exploration. In a large elderly cohort study with follow-up period of 1998-2012, I identified substantial impact of influenza on cancer mortality and several risk factors particularly aggravating effect of influenza on cancer mortality. With the data from this elderly cohort study, I also found that obesity was an independent risk factor for increased respiratory mortality associated with seasonal influenza. The findings from this research have provided new evidence on high risk groups who were more vulnerable to severe outcomes after influenza infection. The insights gained suggest that effective protection policy, including an influenza vaccine program, should be prudently applied for HCWs, cancer patients (especially those with certain risk factors), and obese people during epidemics and pandemics. / published_or_final_version / Public Health / Doctoral / Doctor of Philosophy

Influenza is a common and potentially life threatening infection. The constant evolution of the virus poses challenges on the cross-reactive response of the immune system, and emergence of new strains renders the antibody-mediated protection insufficient. Cellmediated immunity (CMI) may attenuate the severity of illness and provide better heterosubtypic coverage. A myriad of underlying comorbidities affect the outcomes of influenza infection; however, such known risk factors fail to explain a significant proportion of severe influenza infections. To investigate cross reactive antibody and cell-mediated responses and predictors of disease severity we employed several projects and distinct cohorts- after natural infection; live- attenuated vaccine and inactivated vaccine. The main contributions of this project were the development of assays to measure antibody responses to multiple influenza strains, using a microbead based assay and application of phenotypic and functional assays to the study of influenza specific responses. Using these methods in healthy volunteers it was shown that repeated vaccination using a recurring strain failed to elicit increased antibody or cytotoxic T cell (CTL) responses. The administration of live attenuated influenza vaccine (LAIV) resulted in generation of measurable cross-reactive antibody responses. The study showed that even in a vaccine naïve adult population, LAIV resulted in limited generation of CD4 or CD8 responses. Furthermore, the microbead assay was applied to the study of prevalence rates of 2009 H1N1 pandemic during the first wave, demonstrating acceptable specificity with increased sensitivity along with the added benefits of high throughput and ability to simultaneously study responses to multiple strains of influenza. The study of severe influenza infection during II the 2009 pandemic was able to characterize the profile of several pro-inflammatory cytokines and chemokines that trended towards higher concentrations in those individuals that succumbed to pandemic H1N1 infection. This adds to the accumulating evidence suggesting that a cytokine storm together with inability to contain it are involved in determining the outcome of pandemic H1N1 infection. This may potentially aid in early identification of patients with poor prognosis and provide targets for tailored antiinflammatory interventions. In addition the study identified, for the first time, the association between CCR5 deletion and pandemic influenza severity, illustrating the importance of this polymorphism beyond HIV and flaviviral infections.