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1.  Excess Mortality Impact of Two Epidemics of Pandemic Influenza A(H1N1pdm09) Virus in Hong Kong 
Influenza and other respiratory viruses  2013;8(1):10.1111/irv.12196.
Hong Kong experienced two large epidemics of pandemic influenza A(H1N1pdm09). We used regression methods to estimate the excess mortality associated with each epidemic. The first epidemic of H1N1pdm09 peaked in September 2009 and was associated with 2.11 (95% confidence interval (CI): −8.03, 11.75) excess all-cause deaths per 100,000 population. The second epidemic of H1N1pdm09 in early 2011 was associated with 4.81 (95% CI: −0.72, 10.68) excess deaths per 100,000 population. More than half of the estimated excess all-cause deaths were attributable to respiratory causes in each epidemic. The reasons for substantial impact in the second wave remain to be clarified.
doi:10.1111/irv.12196
PMCID: PMC3877676  PMID: 24373289
excess mortality; impact; pandemic; influenza; H1N1pdm09
2.  Case fatality risk of influenza A(H1N1pdm09): a systematic review 
Epidemiology (Cambridge, Mass.)  2013;24(6):10.1097/EDE.0b013e3182a67448.
Background
During the 2009 influenza pandemic, uncertainty surrounding the seriousness of human infections with the H1N1pdm09 virus hindered appropriate public health response. One measure of seriousness is the case fatality risk, defined as the probability of mortality among people classified as cases.
Methods
We conducted a systematic review to summarize published estimates of the case fatality risk of the pandemic influenza H1N1pdm09 virus. Only studies that reported population-based estimates were included.
Results
We included 77 estimates of the case fatality risk from 50 published studies, about one-third of which were published within the first 9 months of the pandemic. We identified very substantial heterogeneity in published estimates, ranging from less than 1 to more than 10,000 deaths per 100,000 cases or infections. The choice of case definition in the denominator accounted for substantial heterogeneity, with the higher estimates based on laboratory-confirmed cases (point estimates= 0–13,500 per 100,000 cases) compared with symptomatic cases (point estimates= 0–1,200 per 100,000 cases) or infections (point estimates=1–10 per 100,000 infections). Risk based on symptomatic cases increased substantially with age.
Conclusions
Our review highlights the difficulty in estimating the seriousness of infection with a novel influenza virus using the case fatality risk. In addition, substantial variability in age-specific estimates complicates the interpretation of the overall case fatality risk and comparisons among populations. A consensus is needed on how to define and measure the seriousness of infection before the next pandemic.
doi:10.1097/EDE.0b013e3182a67448
PMCID: PMC3809029  PMID: 24045719
3.  Estimation of the Association Between Antibody Titers and Protection Against Confirmed Influenza Virus Infection in Children 
The Journal of Infectious Diseases  2013;208(8):1320-1324.
Antibody titers measured by hemagglutination inhibition (HAI) correlate with protection against influenza virus infection and are used to specify criteria for vaccine licensure. In a randomized, controlled trial of seasonal influenza vaccination in 773 children aged 6–17 years, we estimated that HAI titers of 1:40 against A(H1N1)pdm09 and B(Victoria lineage) were associated with 48% (95% confidence interval [CI], 30%–62%) and 55% (95% CI, 32%–70%) protection against PCR-confirmed infection with each strain. Our analysis accounted for waning in antibody titers over time, and could be particularly useful in settings where influenza activity is delayed or prolonged relative to measurement of antibody titers.
doi:10.1093/infdis/jit372
PMCID: PMC3778972  PMID: 23908481
antibody; immunity; influenza; vaccine; children
4.  Impact of live poultry market closure in reducing bird-to-human transmission of avian influenza A(H7N9) virus: an ecological study 
Lancet  2013;383(9916):541-548.
Background
A novel influenza A(H7N9) virus has emerged in China during the past few months. Inter-species zoonotic transmission appears to be the predominant route of spread. Live poultry markets (LPMs) in the major cities of Shanghai, Hangzhou, Huzhou and Nanjing, where the majority of cases have occurred, were swiftly closed as a precautionary public health measure. Our objective was to quantify the impact of LPM closure in reducing bird-to-human transmission of avian influenza A(H7N9) virus.
Methods
We used data on the illness onset dates and geographical locations of laboratory-confirmed influenza A(H7N9) cases that were officially announced by 7 June 2013. We constructed a statistical model to explain the patterns in incident cases reported in each city based on the assumption of a constant force of infection prior to closure, and a different constant force of infection after closure. We fitted the model using Markov chain Monte Carlo methods.
Findings
There were 85 confirmed influenza A(H7N9) cases in Shanghai, Hangzhou, Huzhou and Nanjing out of a total of 130 confirmed cases in mainland China by 7 June 2013. Closure of LPMs in those four cities reduced the risk of human infections by 97%–99% (range 68%–100%) in each city. Given that LPMs were the predominant source of influenza A(H7N9) exposure in those locations, we estimated the mean incubation period to be 3.3 days.
Interpretation
LPM closures were extremely effective in controlling human risk of influenza A(H7N9). If the influenza A(H7N9) epizootic/epidemic continues, LPM closure should be sustained in at-risk areas and implemented in any urban areas where influenza A(H7N9) reappears in future. In the longer term, evidence-based discussions and deliberations about the role of central slaughtering of all live poultry should be renewed.
Funding
Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.
doi:10.1016/S0140-6736(13)61904-2
PMCID: PMC3946250  PMID: 24183056
5.  The epidemiological and public health research response to 2009 pandemic influenza A(H1N1): experiences from Hong Kong 
Background
In recent years Hong Kong has invested in research infrastructure to appropriately respond to novel infectious disease epidemics. Research from Hong Kong made a strong contribution to the international response to the 2009 influenza A(H1N1) pandemic (pH1N1). Summarizing, describing and reviewing the Hong Kong's response to the 2009 pandemic, this article aimed to identify key elements of a real-time research response.
Methods
A systematic search in PubMed and EMBASE for research into the infection dynamics and natural history, impact or control of pH1N1 in Hong Kong. Eligible articles were analyzed according to their scope.
Results
55 articles were included in the review. Transmissibility of pH1N1 was similar in Hong Kong to elsewhere, and only a small fraction of infections were associated with severe disease. School closures were effective in reducing pH1N1 transmission, oseltamivir was effective for treatment of severe cases while convalescent plasma therapy has the potential to mitigate future pandemics.
Conclusions
There was a rapid and comprehensive research response to pH1N1 in Hong Kong, providing important information on the epidemiology of the novel virus with relevance internationally as well as locally. The scientific knowledge gained through these detailed studies of pH1N1 is now being used to revise and update pandemic plans. The experiences of the research response in Hong Kong could provide a template for the research response to future emerging and reemerging disease epidemics.
doi:10.1111/j.1750-2659.2012.00420.x
PMCID: PMC3705741  PMID: 22883352
6.  Responses to Threat of Influenza A(H7N9) and Support for Live Poultry Markets, Hong Kong, 2013 
Emerging Infectious Diseases  2014;20(5):882-886.
We conducted a population survey in Hong Kong to gauge psychological and behavioral responses to the threat of influenza A(H7N9) and support for closure of live poultry markets. We found low anxiety and low levels of exposure to live poultry but mixed support for permanent closure of the markets.
doi:10.3201/eid2005.131859
PMCID: PMC4012820  PMID: 24750988
avian influenza A(H7N9); influenza; viruses; Hong Kong; public health; behavioral response; psychological response; community; H7N9; survey; respiratory infections; live poultry markets; poultry; birds
7.  Infection Fatality Risk of the Pandemic A(H1N1)2009 Virus in Hong Kong 
American Journal of Epidemiology  2013;177(8):834-840.
One measure of the severity of a pandemic influenza outbreak at the individual level is the risk of death among people infected by the new virus. However, there are complications in estimating both the numerator and denominator. Regarding the numerator, statistical estimates of the excess deaths associated with influenza virus infections tend to exceed the number of deaths associated with laboratory-confirmed infection. Regarding the denominator, few infections are laboratory confirmed, while differences in case definitions and approaches to case ascertainment can lead to wide variation in case fatality risk estimates. Serological surveillance can be used to estimate the cumulative incidence of infection as a denominator that is more comparable across studies. We estimated that the first wave of the influenza A(H1N1)pdm09 virus in 2009 was associated with approximately 232 (95% confidence interval: 136, 328) excess deaths of all ages in Hong Kong, mainly among the elderly. The point estimates of the risk of death on a per-infection basis increased substantially with age, from below 1 per 100,000 infections in children to 1,099 per 100,000 infections in those 60–69 years of age. Substantial variation in the age-specific infection fatality risk complicates comparison of the severity of different influenza strains.
doi:10.1093/aje/kws314
PMCID: PMC3658096  PMID: 23459950
death; human influenza; severity
8.  Effect of the One-Child Policy on Influenza Transmission in China: A Stochastic Transmission Model 
PLoS ONE  2014;9(2):e84961.
Background
China's one-child-per-couple policy, introduced in 1979, led to profound demographic changes for nearly a quarter of the world's population. Several decades later, the consequences include decreased fertility rates, population aging, decreased household sizes, changes in family structure, and imbalanced sex ratios. The epidemiology of communicable diseases may have been affected by these changes since the transmission dynamics of infectious diseases depend on demographic characteristics of the population. Of particular interest is influenza because China and Southeast Asia lie at the center of a global transmission network of influenza. Moreover, changes in household structure may affect influenza transmission. Is it possible that the pronounced demographic changes that have occurred in China have affected influenza transmission?
Methods and Findings
To address this question, we developed a continuous-time, stochastic, individual-based simulation model for influenza transmission. With this model, we simulated 30 years of influenza transmission and compared influenza transmission rates in populations with and without the one-child policy control. We found that the average annual attack rate is reduced by 6.08% (SD 2.21%) in the presence of the one-child policy compared to a population in which no demographic changes occurred. There was no discernible difference in the secondary attack rate, −0.15% (SD 1.85%), between the populations with and without a one-child policy. We also forecasted influenza transmission over a ten-year time period in a population with a two-child policy under a hypothesis that a two-child-per-couple policy will be carried out in 2015, and found a negligible difference in the average annual attack rate compared to the population with the one-child policy.
Conclusions
This study found that the average annual attack rate is slightly lowered in a population with a one-child policy, which may have resulted from a decrease in household size and the proportion of children in the population.
doi:10.1371/journal.pone.0084961
PMCID: PMC3916292  PMID: 24516519
9.  Excess mortality impact of two epidemics of pandemic influenza A(H1N1pdm09) virus in Hong Kong 
Hong Kong experienced two large epidemics of pandemic influenza A(H1N1pdm09). We used regression methods to estimate the excess mortality associated with each epidemic. The first epidemic of H1N1pdm09 peaked in September 2009 and was associated with 2·13 [95% confidence interval (CI): −8·08, 11·82] excess all-cause deaths per 100 000 population. The second epidemic of H1N1pdm09 in early 2011 was associated with 4·72 [95% CI: −0·70, 10·50] excess deaths per 100 000 population. More than half of the estimated excess all-cause deaths were attributable to respiratory causes in each epidemic. The reasons for substantial impact in the second wave remain to be clarified.
doi:10.1111/irv.12196
PMCID: PMC3877676  PMID: 24373289
Excess mortality; H1N1pdm09; impact; influenza; pandemic
10.  Poultry Market Closures and Human Infection with Influenza A(H7N9) Virus, China, 2013–14 
Emerging Infectious Diseases  2014;20(11):1891-1894.
Closure of live poultry markets was implemented in areas affected by the influenza virus A(H7N9) outbreak in China during winter, 2013–14. Our analysis showed that closing live poultry markets in the most affected cities of Guangdong and Zhejiang provinces was highly effective in reducing the risk for H7N9 infection in humans.
doi:10.3201/eid2011.140556
PMCID: PMC4214308  PMID: 25340354
Avian influenza A(H7N9); viruses; live poultry markets; public health; China
11.  Excess Mortality Associated With Influenza A and B Virus in Hong Kong, 1998–2009 
The Journal of Infectious Diseases  2012;206(12):1862-1871.
Background. Although deaths associated with laboratory-confirmed influenza virus infections are rare, the excess mortality burden of influenza estimated from statistical models may more reliably quantify the impact of influenza in a population.
Methods. We applied age-specific multiple linear regression models to all-cause and cause-specific mortality rates in Hong Kong from 1998 through 2009. The differences between estimated mortality rates in the presence or absence of recorded influenza activity were used to estimate influenza-associated excess mortality.
Results. The annual influenza-associated all-cause excess mortality rate was 11.1 (95% confidence interval [CI], 7.2–14.6) per 100 000 person-years. We estimated an average of 751 (95% CI, 488–990) excess deaths associated with influenza annually from 1998 through 2009, with 95% of the excess deaths occurring in persons aged ≥65 years. Most of the influenza-associated excess deaths were from respiratory (53%) and cardiovascular (18%) causes. Influenza A(H3N2) epidemics were associated with more excess deaths than influenza A(H1N1) or B during the study period.
Conclusions. Influenza was associated with a substantial number of excess deaths each year, mainly among the elderly, in Hong Kong in the past decade. The influenza-associated excess mortality rates were generally similar in Hong Kong and the United States.
doi:10.1093/infdis/jis628
PMCID: PMC3502382  PMID: 23045622
12.  Knowledge, attitudes and practices relating to influenza A(H7N9) risk among live poultry traders in Guangzhou City, China 
BMC Infectious Diseases  2014;14(1):554.
Background
Live poultry traders (LPTs) have greater risk to avian influenza due to occupational exposure to poultry. This study investigated knowledge, attitudes and practices of LPTs relating to influenza A (H7N9).
Methods
Using multi-stage cluster sampling, 306 LPTs were interviewed in Guangzhou by a standardized questionnaire between mid-May to June, 2013. Hierarchical logistic regression models were used to identify factors associated with preventive practices and attitudes towards various control measures implemented in live poultry markets against H7N9.
Results
Only 46.1% of the respondents recognized risks associated with contacts with bird secretions or droppings, and only 22.9% perceived personally “likely/very likely” to contract H7N9 infection. Around 60% of the respondents complied with hand-washing and wearing gloves, and only 20% reported wearing face masks. Only 16.3% of the respondents agreed on introducing central slaughtering of poultry. Being younger, involving in slaughtering poultry, having longer working hours, less access to H7N9-related information and poorer knowledge, and perceiving lower personal susceptibility to H7N9 infection were negatively associated with preventive practices. Comparing with previous studies conducted when human cases of H5N1 avian influenza infection was first identified in Guangdong, LPTs’ perceived susceptibility to novel influenza viruses increased significantly but acceptance for central slaughtering of poultry remained low.
Conclusions
Information on avian influenza provided through multiple communication tools may be necessary to promote knowledge among poultry traders. Familiarity with risk may have led to the lower perceived vulnerability to avian influenza and less protective actions among the LPTs particularly for those involving more risky exposure to live poultry. Reasons for the consistently low acceptance for central slaughtering of poultry await further exploration.
doi:10.1186/s12879-014-0554-8
PMCID: PMC4210513  PMID: 25324011
Live poultry trader; Avian influenza; Attitudes; Knowledge
13.  Years of Life Lost in the First Wave of the 2009 Influenza A(H1N1) Pandemic in Hong Kong 
American Journal of Epidemiology  2013;178(8):1313-1318.
The impact of influenza pandemics might be overestimated; the published studies of years of life lost (YLL) have typically ignored the presence of underlying chronic conditions or health risk behaviors in most deaths. We used data on deaths involving laboratory-confirmed 2009 influenza A(H1N1) virus infection that occurred between April 2009 and May 2010 in Hong Kong, China, to adjust for these underlying risk factors. Life expectancy was corrected with hazard-based modifications to the life tables. The excess hazards posed by underlying risk factors were added to the “baseline” age-specific hazards in the local life tables to reflect the life expectancy associated with each underlying risk factor. Of 72 deceased persons with laboratory-confirmed 2009 influenza A(H1N1) virus infection, 56% had underlying risk factors. We estimated that the 2009 pandemic was associated with 1,540 (95% confidence interval: 1,350, 1,630) YLL after adjustment for age and underlying risk factors. This figure is approximately 25% lower than the YLL estimate of 2,080 derived after adjustment for age but not for risk factors. Our analysis demonstrates the potential scale of bias in YLL estimation if underlying risk factors are ignored. The estimation of YLL with correction for underlying risk factors in addition to age could also provide a framework for similar calculations elsewhere.
doi:10.1093/aje/kwt120
PMCID: PMC3792731  PMID: 23978528
influenza; pandemics; underlying risk factors; years of life lost
14.  Modes of Transmission of Influenza B Virus in Households 
PLoS ONE  2014;9(9):e108850.
Introduction
While influenza A and B viruses can be transmitted via respiratory droplets, the importance of small droplet nuclei “aerosols” in transmission is controversial.
Methods and Findings
In Hong Kong and Bangkok, in 2008–11, subjects were recruited from outpatient clinics if they had recent onset of acute respiratory illness and none of their household contacts were ill. Following a positive rapid influenza diagnostic test result, subjects were randomly allocated to one of three household-based interventions: hand hygiene, hand hygiene plus face masks, and a control group. Index cases plus their household contacts were followed for 7–10 days to identify secondary infections by reverse transcription polymerase chain reaction (RT-PCR) testing of respiratory specimens. Index cases with RT-PCR-confirmed influenza B were included in the present analyses. We used a mathematical model to make inferences on the modes of transmission, facilitated by apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We estimated that approximately 37% and 26% of influenza B virus transmission was via the aerosol mode in households in Hong Kong and Bangkok, respectively. In the fitted model, influenza B virus infections were associated with a 56%–72% risk of fever plus cough if infected via aerosol route, and a 23%–31% risk of fever plus cough if infected via the other two modes of transmission.
Conclusions
Aerosol transmission may be an important mode of spread of influenza B virus. The point estimates of aerosol transmission were slightly lower for influenza B virus compared to previously published estimates for influenza A virus in both Hong Kong and Bangkok. Caution should be taken in interpreting these findings because of the multiple assumptions inherent in the model, including that there is limited biological evidence to date supporting a difference in the clinical features of influenza B virus infection by different modes.
doi:10.1371/journal.pone.0108850
PMCID: PMC4182555  PMID: 25268241
15.  Humoral Antibody Response after Receipt of Inactivated Seasonal Influenza Vaccinations one Year Apart in Children 
In a randomized controlled trial, we administered seasonal trivalent inactivated influenza vaccine (TIV) or placebo to subjects 6–15 years of age in two consecutive years. Receipt of TIV in year 2 induced seroprotection in most subjects. Among 39 children who received TIV in the second year, receipt of TIV in the first year was associated with lower antibody titer rises in the second year to seasonal influenza A(H1N1) and A(H3N2) strains for which the vaccine strains remained unchanged. Antibody response to a different influenza B strain in the second year was unaffected by receipt of TIV in the first year.
doi:10.1097/INF.0b013e318263280e
PMCID: PMC3422369  PMID: 22683675
vaccination; influenza; antibody response; children
16.  Absence of Detectable Influenza RNA Transmitted via Aerosol during Various Human Respiratory Activities – Experiments from Singapore and Hong Kong 
PLoS ONE  2014;9(9):e107338.
Two independent studies by two separate research teams (from Hong Kong and Singapore) failed to detect any influenza RNA landing on, or inhaled by, a life-like, human manikin target, after exposure to naturally influenza-infected volunteers. For the Hong Kong experiments, 9 influenza-infected volunteers were recruited to breathe, talk/count and cough, from 0.1 m and 0.5 m distance, onto a mouth-breathing manikin. Aerosolised droplets exhaled from the volunteers and entering the manikin’s mouth were collected with PTFE filters and an aerosol sampler, in separate experiments. Virus detection was performed using an in-house influenza RNA reverse-transcription polymerase chain reaction (RT-PCR) assay. No influenza RNA was detected from any of the PTFE filters or air samples. For the Singapore experiments, 6 influenza-infected volunteers were asked to breathe (nasal/mouth breathing), talk (counting in English/second language), cough (from 1 m/0.1 m away) and laugh, onto a thermal, breathing manikin. The manikin’s face was swabbed at specific points (around both eyes, the nostrils and the mouth) before and after exposure to each of these respiratory activities, and was cleaned between each activity with medical grade alcohol swabs. Shadowgraph imaging was used to record the generation of these respiratory aerosols from the infected volunteers and their impact onto the target manikin. No influenza RNA was detected from any of these swabs with either team’s in-house diagnostic influenza assays. All the influenza-infected volunteers had diagnostic swabs taken at recruitment that confirmed influenza (A/H1, A/H3 or B) infection with high viral loads, ranging from 105-108 copies/mL (Hong Kong volunteers/assay) and 104–107 copies/mL influenza viral RNA (Singapore volunteers/assay). These findings suggest that influenza RNA may not be readily transmitted from naturally-infected human source to susceptible recipients via these natural respiratory activities, within these exposure time-frames. Various reasons are discussed in an attempt to explain these findings.
doi:10.1371/journal.pone.0107338
PMCID: PMC4160257  PMID: 25208000
17.  Social contacts and the locations in which they occur as risk factors for influenza infection 
The interaction of human social behaviour and transmission is an intriguing aspect of the life cycle of respiratory viral infections. Although age-specific mixing patterns are often assumed to be the key drivers of the age-specific heterogeneity in transmission, the association between social contacts and biologically confirmed infection has not previously been tested at the individual level. We administered a questionnaire to participants in a longitudinal cohort survey of influenza in which infection was defined by longitudinal paired serology. Using a variety of statistical approaches, we found overwhelming support for the inclusion of individual age in addition to contact variables when explaining odds of infection: the best model not including age explained only 15.7% of the deviance, whereas the best model with age explained 23.6%. However, within age groups, we did observe an association between contacts, locations and infection: median numbers of contacts (or locations) reported by those infected were higher than those from the uninfected group in every age group other than the youngest. Further, we found some support for the retention of location and contact variables in addition to age in our regression models, with excess odds of infection of approximately 10% per additional 10 contacts or one location. These results suggest that, although the relationship between age and incidence of respiratory infection at the level of the individual is not driven by self-reported social contacts, risk within an age group may be.
doi:10.1098/rspb.2014.0709
PMCID: PMC4100506  PMID: 25009062
pandemic; influenza; contact patterns
18.  Aerosol transmission is an important mode of influenza A virus spread 
Nature communications  2013;4:1935.
Influenza A viruses are believed to spread between humans through contact, large respiratory droplets and small particle droplet nuclei (aerosols), but the relative importance of each of these modes of transmission is unclear. Volunteer studies suggest that infections via aerosol transmission may have a higher risk of febrile illness. Here we apply a mathematical model to data from randomized controlled trials of hand hygiene and surgical face masks in Hong Kong and Bangkok households. In these particular environments, inferences on the relative importance of modes of transmission are facilitated by information on the timing of secondary infections and apparent differences in clinical presentation of secondary infections resulting from aerosol transmission. We find that aerosol transmission accounts for approximately half of all transmission events. This implies that measures to reduce transmission by contact or large droplets may not be sufficient to control influenza A virus transmission in households.
doi:10.1038/ncomms2922
PMCID: PMC3682679  PMID: 23736803
19.  Increased Risk of Noninfluenza Respiratory Virus Infections Associated With Receipt of Inactivated Influenza Vaccine 
We randomized 115 children to trivalent inactivated influenza vaccine (TIV) or placebo. Over the following 9 months, TIV recipients had an increased risk of virologically-confirmed non-influenza infections (relative risk: 4.40; 95% confidence interval: 1.31-14.8). Being protected against influenza, TIV recipients may lack temporary non-specific immunity that protected against other respiratory viruses.
doi:10.1093/cid/cis307
PMCID: PMC3404712  PMID: 22423139
20.  Characterizing Influenza surveillance systems performance: application of a Bayesian hierarchical statistical model to Hong Kong surveillance data 
BMC Public Health  2014;14(1):850.
Background
Infectious disease surveillance is a process the product of which reflects both actual disease trends and public awareness of the disease. Decisions made by patients, health care providers, and public health professionals about seeking and providing health care and about reporting cases to health authorities are all influenced by the information environment, which changes constantly. Biases are therefore imbedded in surveillance systems; these biases need to be characterized to provide better situational awareness for decision-making purposes. Our goal is to develop a statistical framework to characterize influenza surveillance systems, particularly their correlation with the information environment.
Methods
We identified Hong Kong influenza surveillance data systems covering healthcare providers, laboratories, daycare centers and residential care homes for the elderly. A Bayesian hierarchical statistical model was developed to examine the statistical relationships between the influenza surveillance data and the information environment represented by alerts from HealthMap and web queries from Google. Different models were fitted for non-pandemic and pandemic periods and model goodness-of-fit was assessed using common model selection procedures.
Results
Some surveillance systems — especially ad hoc systems developed in response to the pandemic flu outbreak — are more correlated with the information environment than others. General practitioner (percentage of influenza-like-illness related patient visits among all patient visits) and laboratory (percentage of specimen tested positive) seem to proportionally reflect the actual disease trends and are less representative of the information environment. Surveillance systems using influenza-specific code for reporting tend to reflect biases of both healthcare seekers and providers.
Conclusions
This study shows certain influenza surveillance systems are less correlated with the information environment than others, and therefore, might represent more reliable indicators of disease activity in future outbreaks. Although the patterns identified in this study might change in future outbreaks, the potential susceptibility of surveillance data is likely to persist in the future, and should be considered when interpreting surveillance data.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2458-14-850) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2458-14-850
PMCID: PMC4246552  PMID: 25127906
Influenza surveillance; Internet-based surveillance; Biosurveillance; Bayesian hierarchical modeling; Information environment; Public awareness
22.  A clinical prediction rule for diagnosing human infections with avian influenza A(H7N9) in a hospital emergency department setting 
BMC Medicine  2014;12(1):127.
Background
Human infections with avian influenza A(H7N9) virus are associated with severe illness and high mortality. To better inform triage decisions of hospitalization and management, we developed a clinical prediction rule for diagnosing patients with A(H7N9) and determined its predictive performance.
Methods
Clinical details on presentation of adult patients hospitalized with either A(H7N9)(n = 121) in China from March to May 2013 or other causes of acute respiratory infections (n = 2,603) in Jingzhou City, China from January 2010 through September 2012 were analyzed. A clinical prediction rule was developed using a two-step coefficient-based multivariable logistic regression scoring method and evaluated with internal validation by bootstrapping.
Results
In step 1, predictors for A(H7N9) included male sex, poultry exposure history, and fever, haemoptysis, or shortness of breath on history and physical examination. In step 2, haziness or pneumonic consolidation on chest radiographs and leukopenia were also associated with a higher probability of A(H7N9). The observed risk of A(H7N9) was 0.3% for those assigned to the low-risk group and 2.5%, 4.3%, and 44.0% for tertiles 1 through 3, respectively, in the high-risk group. This prediction rule achieved good model performance, with an optimism-corrected sensitivity of 0.93, a specificity of 0.80, and an area under the receiver-operating characteristic curve of 0.96.
Conclusions
A simple decision rule based on data readily obtainable in the setting of patients’ first clinical presentations from the first wave of the A/H7N9 epidemic in China has been developed. This prediction rule has achieved good model performance in predicting their risk of A(H7N9) infection and should be useful in guiding important clinical and public health decisions in a timely and objective manner. Data to be gathered with its use in the current evolving second wave of the A/H7N9 epidemic in China will help to inform its performance in the field and contribute to its further refinement.
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-014-0127-0) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-014-0127-0
PMCID: PMC4243192  PMID: 25091477
Avian influenza A(H7N9); Clinical prediction rule; Clinical diagnosis; Hospital emergency setting
23.  Human Exposure to Live Poultry and Psychological and Behavioral Responses to Influenza A(H7N9), China 
Emerging Infectious Diseases  2014;20(8):1296-1305.
Exposure was common in urban and rural areas and remains a potential risk factor for human infection.
To investigate human exposure to live poultry and changes in risk perception and behavior after the April 2013 influenza A(H7N9) outbreak in China, we surveyed 2,504 urban residents in 5 cities and 1,227 rural residents in 4 provinces and found that perceived risk for influenza A(H7N9) was low. The highest rate of exposure to live poultry was reported in Guangzhou, where 47% of those surveyed reported visiting a live poultry market >1 times in the previous year. Most (77%) urban respondents reported that they visited live markets less often after influenza A(H7N9) cases were first identified in China in March 2013, but only 30% supported permanent closure of the markets to control the epidemic. In rural areas, 48% of respondents reported that they raised backyard poultry. Exposure to live commercial and private poultry is common in urban and rural China and remains a potential risk factor for human infection with novel influenza viruses.
doi:10.3201/eid2008.131821
PMCID: PMC4111172  PMID: 25076186
influenza; viruses; influenza A(H7N9); live poultry; exposure; transmission; psychological; behavioral; survey; China; respiratory infections
24.  Age-Period-Cohort Projections of Ischaemic Heart Disease Mortality by Socio-Economic Position in a Rapidly Transitioning Chinese Population 
PLoS ONE  2013;8(4):e61495.
Background
With economic development and population aging, ischaemic heart disease (IHD) is becoming a leading cause of mortality with widening inequalities in China. To forewarn the trends in China we projected IHD trends in the most economically developed part of China, i.e., Hong Kong.
Methods
Based on sex-specific IHD mortality rates from 1976 to 2005, we projected mortality rates by neighborhood-level socio-economic position (i.e., low- or high-income groups) to 2020 in Hong Kong using Poisson age-period-cohort models with autoregressive priors.
Results
In the low-income group, age-standardized IHD mortality rates among women declined from 33.3 deaths in 1976–1980 to 19.7 per 100,000 in 2016–2020 (from 55.5 deaths to 34.2 per 100,000 among men). The rates in the high-income group were initially higher in both sexes, particularly among men, but this had reversed by the end of the study periods. The rates declined faster for the high-income group than for the low-income group in both sexes. The rates were projected to decline faster in the high-income group, such that by the end of the projection period the high-income group would have lower IHD mortality rates, particularly for women. Birth cohort effects varied with sex, with a marked upturn in IHD mortality around 1945, i.e., for the first generation of men to grow up in a more economically developed environment. There was no such upturn in women. Birth cohort effects were the main drivers of change in IHD mortality rates.
Conclusion
IHD mortality rates are declining in Hong Kong and are projected to continue to do so, even taking into account greater vulnerability for the first generation of men born into a more developed environment. At the same time social disparities in IHD have reversed and are widening, partly as a result of a cohort effect, with corresponding implications for prevention.
doi:10.1371/journal.pone.0061495
PMCID: PMC3623955  PMID: 23593484
25.  Comparative epidemiology of human infections with avian influenza A(H7N9) and A(H5N1) viruses in China 
Lancet  2013;382(9887):129-137.
Background
The novel influenza A(H7N9) virus recently emerged, while influenza A(H5N1) virus has infected humans since 2003 in mainland China. Both infections are thought to be predominantly zoonotic. We compared the epidemiologic characteristics of the complete series of laboratory-confirmed cases of both viruses in mainland China to date.
Methods
An integrated database was constructed with information on demographic, epidemiological, and clinical variables of laboratory-confirmed A(H7N9) and A(H5N1) cases that were reported to the Chinese Center for Disease Control and Prevention up to May 24, 2013. We described disease occurrence by age, sex and geography and estimated key epidemiologic parameters.
Findings
Among 130 and 43 patients with confirmed A(H7N9) and A(H5N1) respectively, the median ages were 62y and 26y. In urban areas, 74% of cases of both viruses were male whereas in rural areas the proportions were 62% for A(H7N9) and 33% for A(H5N1). Among cases of A(H7N9) and A(H5N1), 75% and 71% reported recent exposure to poultry. The mean incubation periods of A(H7N9) and A(H5N1) were 3.1 and 3.3 days, respectively. On average, 21 and 18 contacts were traced for each A(H7N9) case in urban and rural areas respectively; compared to 90 and 63 for A(H5N1). The hospitalization fatality risk was 35% (95% CI: 25%, 44%) for A(H7N9) and 70% (95% CI: 56%, 83%) for A(H5N1).
Interpretation
The sex ratios in urban compared to rural cases are consistent with poultry exposure driving the risk of infection. However the difference in susceptibility to serious illness with the two different viruses remains unexplained, given that most A(H7N9) cases were in older adults while most A(H5N1) cases were in younger individuals.
Funding
Ministry of Science and Technology, China; Research Fund for the Control of Infectious Disease and University Grants Committee, Hong Kong Special Administrative Region, China; and the US National Institutes of Health.
doi:10.1016/S0140-6736(13)61171-X
PMCID: PMC3777567  PMID: 23803488

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