Background / Hand, foot, and mouth disease (HFMD), in particular those associated with enterovirus 71 (EV71), has caused large outbreaks in the Western Pacific and Southeast Asian countries in the past three decades. There is currently no effective chemoprophylaxis or vaccination for HFMD or EV71 infection. Public health strategies rest on good understanding of the epidemiological features of HFMD. The present series of studies examined the epidemiological characteristics of HFMD in Hong Kong, with a view to better understand the disease epidemiology so as to guide public health actions. / Methods and results of individual studies / Study (1)--characterizing the changing epidemiological features identified from various surveillance systems for HFMD / The trend of HFMD activities from 2001-2009 was analyzed using the sentinel surveillance statistics and HFMD outbreaks. The type of institutions reporting HFMD over time, incidences of outbreaks in 18 districts, and age and sex distribution of affected persons of HFMD outbreaks were analyzed. The clinical presentation, hospitalization rate, complication rate and case fatality of outbreaks were examined. The circulating enterovirues each year were determined by laboratory surveillance findings from 2001-2009 and test for morbidity caused by EV71. Seasonal peak was detected from warmer months of May through July but a smaller winter peak was found from October to December since 2006. An increasing trend of more older children aged above 5 years were infected, from 25.4% in 2001 to 33.0% in 2009 (p=0.01, Mantel-Haenszel Chi-square test). Laboratory surveillance detected a cyclical high activity of EV71 in every 3 to 4 years, which was associated with a higher average hospitalization rate among patients of the HFMD outbreaks reported in corresponding year, although it was only marginally significant (p=0.09, linear regression test). / Study (2)--analyzing the characteristics of EV71 epidemic in 2008 / All EV71 cases diagnosed by PHLC from 1998-2008 were analyzed. The complication and case fatality rates, percentage requiring hospitalization, median duration of hospital care, and the likelihood of being associated with an HMFD outbreak in institution in 2008 were compared with the corresponding rates calculated from cases reported from 1998-2007. Phylogenetic tree was constructed by using the neighbour-joining method and the molecular epidemiology of EV71 detected in 2008 was compared with the past years’ trends. Ninety-eight EV71 cases were reported in 2008, highest in the past decade. The annual incidence was 1.4/100 000 in general population, with highest incidence reported in children aged 0-4 years old (27.9/100 000). 11.2% had complications including meningitis or encephalitis (6.1%), pneumonia (3.1%), acute flaccid paralysis (1.0%), and shock (1.0%). There was only one fatal case (CFR: 1.0%) attributed to interstitial pneumonitis. 45.9% had concurrent HFMD outbreaks in their schools or institutions, and six schools required temporarily class suspension for 14 days. Both the complication rate and CFR werenot significantly different from the corresponding rates of the past 10 years (p=0.12 and 1.00 respectively). Phylogenetic analysis found that most cases reported in 2008 were C4 strains, which were the predominant circulating strains in the past ten years. / Study (3)--examining the association between meteorological parameters and HFMD activity / The sentinel consultation rate of HFMD was tested for any association with the meteorological parameters obtained from the Hong Kong Observatory from 2000-2004. Different regression models were examined to find the best model for predicting HFMD consultation rates from 2005-2009. In multivariate regression analysis, model M2 (in which mean temperature, diurnal difference in temperature, relative humidity and wind speed were positively associated with HFMD) was found to have a higher R2 (0.119) than M0 and M1 models with an R2 of 0.079 and 0.062 respectively, indicating that HFMD consultation rates were better explained using meteorological parameters measured 2 weeks earlier. The predicted trend of HFMD consultation rates for 2005 to 2009 matched well with the observed one (Spearman’s rank correlation coefficient=0.276, P=0.000). Sensitivity analysis showed that the estimated HFMD consultation rates were mostly affected by varying the relative humidity and least affected by wind speed. / Study (4)--determining the basic reproduction number of coxsackievirus A16 and enterovirus 71 using mathematical model / The basic reproduction numbers (R0) of EV71 and CoxA16 from laboratory confirmed HFMD outbreaks reported to DH from 2004-2009 were determined using mathematical model. Thirty four outbreaks were analyzed, 27 due to CoxA16 and seven due to EV71. The median R0 of EV71 was 5.48 with an inter-quartile range of 4.206.51 while median R0 of CoxA16 was 2.50 with an inter-quartile range of 1.963.67. In the sensitivity analysis, R0 of EV71 was significantly higher than that of CoxA16 in whole range of incubation periods, p≦0.025. R0was not associated with outbreak setting, size of the institution or number of persons affected. / Study (5)--assessing the impact of SARS and pandemic influenza H1N1 on transmission of HFMD in Hong Kong / I compared the observed HFMD consultation rates and the projected rates, which were constructed using mathematical model, in defined periods of 2003 and 2009 during which territory-wide public health interventions (including school closure) against Severe Acute Respiratory Syndrome (SARS) and pandemic influenza H1N1 were implemented. There was a reduction of 57.2% (95% C.I.:53.0-60.7%) in observed HFMD consultation rates during SARS period in 2003 and a reduction of 26.7% (95% C.I.:19.5-32.7%) during pandemic influenza H1N1 period in 2009. In 2003, the projected rates were still lower than the observed rates beyond week 31 until almost the end of the year. On the contrary, in 2009, the observed HFMD consultation rates became comparable to that of the projected rates in August, before the end of the defined intervention period. / Conclusions / This thesis bridges the knowledge gaps regarding epidemiological characteristics of HFMD. The changing epidemiology of HFMD, including the cyclical high activity of EV71 warrants vigilant surveillance of its activity in order to guide preventive measures. I have demonstrated that climate parameters may help predict HFMD activity, which could assist in explaining the winter peak detected in recent years and issuing early warning in the future. The R0 of EV71 and CoxA16 were first determined in the literature and I found that R0 of EV71 was higher than R0 of CoxA16. The reduction of transmission of HFMD during the SARS and H1N1 periods suggested that public health measures are effective in reducing the transmission of enteroviruses. / Ma, Siu Keung. / Thesis (M.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 121-149). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Table of content --- p.ii / Acknowledgements --- p.iv / Abbreviations --- p.v / Caption for Tables --- p.vi / Caption for Figures --- p.viii / Précis --- p.1 / Chapter PART I: --- LITERATURE REVIEW ON HFMD --- p.5 / Chapter Chapter 1. --- Current Understanding of Epidemiology of HFMD --- p.6 / Chapter 1.1 --- Causative agents and virology --- p.6 / Chapter 1.2 --- Clinical presentation and management --- p.8 / Chapter 1.3 --- Geographical distribution and past epidemics --- p.14 / Chapter 1.4 --- Host susceptibility and molecular determinants of neruovirulence --- p.26 / Chapter 1.5 --- Routes of transmission and transmission dynamics --- p.27 / Chapter 1.6 --- Knowledge gap identified from literature review --- p.29 / Chapter PART II: --- STUDIES ON EPIDEMIOLOGY OF HFMD IN HONG KONG --- p.33 / Chapter Chapter 2. --- Study Objectives and Main data source for analysis --- p.34 / Chapter 2.1 --- Aim and objectives of this thesis --- p.34 / Chapter 2.2 --- Sentinel surveillance system for monitoring HFMD activity --- p.35 / Chapter 2.3 --- Institutional outbreaks of HFMD reported to DH . --- p.37 / Chapter 2.4 --- EV 71 infection reported to Department of Health --- p.37 / Chapter 2.5 --- Laboratory surveillance for monitoring enteroviruses --- p.37 / Chapter Chapter 3. --- Study (1)--Characterizing the changing epidemiological features identified from various surveillance systems for HFMD --- p.38 / Chapter Chapter 4. --- Study (2)--Analyzing the epidemic of enterovirus 71 in 2008 and its public health implication to Hong Kong --- p.52 / Chapter Chapter 5. --- Study (3)--Examining the association between meteorological parameters and HFMD activity --- p.67 / Chapter Chapter 6. --- Study (4)--Determining the basic reproduction number of coxsackievirus A16 and enterovirus 71 using mathematical model --- p.85 / Chapter Chapter 7. --- Study (5)--Impact of SARS and Pandemic Influenza H1N1 on transmission of HFMD in Hong Kong --- p.100 / Chapter Chapter 8. --- Conclusion --- p.111 / List of publications related to this thesis --- p.119 / References --- p.121