Changing Epidemiology of TB in Shandong, China Driven by Demographic Changes.

Tuberculosis (TB) incidence has been in steady decline in China over the last few decades. However, ongoing demographic transition, fueled by aging, and massive internal migration could have important implications for TB control in the future. We collated data on TB notification, demography, and drug resistance between 2004 and 2017 across seven cities in Shandong, the second most populous province in China. Using these data, and age-period-cohort models, we (i) quantified heterogeneities in TB incidence across cities, by age, sex, resident status, and occupation and (ii) projected future trends in TB incidence, including drug-resistant TB (DR-TB). Between 2006 and 2017, we observed (i) substantial variability in the rates of annual change in TB incidence across cities, from -4.84 to 1.52%; (ii) heterogeneities in the increments in the proportion of patients over 60 among reported TB cases differs from 2 to 13%, and from 0 to 17% for women; (iii) huge differences across cities in the annual growths in TB notification rates among migrant population between 2007 and 2017, from 2.81 cases per 100K migrants per year in Jinan to 22.11 cases per 100K migrants per year in Liaocheng, with drastically increasing burden of TB cases from farmers; and (iv) moderate and stable increase in the notification rates of DR-TB in the province. All of these trends were projected to continue over the next decade, increasing heterogeneities in TB incidence across cities and between populations. To sustain declines in TB incidence and to prevent an increase in Multiple DR-TB (MDR-TB) in the future in China, future TB control strategies may (i) need to be tailored to local demography, (ii) prioritize key populations, such as elderly and internal migrants, and (iii) enhance DR-TB surveillance.

Modelling the skip-and-resurgence of Japanese encephalitis epidemics in Hong Kong.

Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne virus, persisting in pigs, Ardeid birds and Culex mosquitoes. It is endemic to China and Southeastern Asia. The case-fatality ratio (CFR) or the rate of permanent psychiatric sequelae is 30% among symptomatic patients. There were no reported local JEV human cases between 2006 and 2010 in Hong Kong, but it was followed by a resurgence of cases from 2011 to 2017. The mechanism behind this "skip-and-resurgence" patterns is unclear. This work aims to reveal the mechanism behind the "skip-and-resurgence" patterns using mathematical modelling and likelihood-based inference techniques. We found that pig-to-pig transmission increases the size of JEV epidemics but is unlikely to maintain the same level of transmission among pigs. The disappearance of JEV human cases in 2006-2010 could be explained by a sudden reduction of the population of farm pigs as a result of the implementation of the voluntary "pig-rearing licence surrendering" policy. The resurgence could be explained by of a new strain in 2011, which increased the transmissibility of the virus or the spill-over ratio from reservoir to host or both.

Unsynchronized influenza epidemics in two neighboring subtropical cities.

OBJECTIVE: The aim of this study was to examine the synchrony of influenza epidemics between Hong Kong and Shenzhen, two neighboring subtropical cities in South China. METHODS: Laboratory-confirmed influenza data for the period January 2006 to December 2016 were obtained from the Shenzhen Center for Disease Control and Prevention and the Department of Health in Hong Kong. The population data were retrieved from the 2011 population censuses. The weekly rates of laboratory-confirmed influenza cases were compared between Shenzhen and Hong Kong. RESULTS: Unsynchronized influenza epidemics between Hong Kong and Shenzhen were frequently observed during the study period. Influenza A/H1N1 caused a more severe pandemic in Hong Kong in 2009, but the subsequent seasonal epidemics showed similar magnitudes in both cities. Two influenza A/H3N2 dominant epidemic waves were seen in Hong Kong in 2015, but these epidemics were very minor in Shenzhen. More influenza B epidemics occurred in Shenzhen than in Hong Kong. CONCLUSIONS: Influenza epidemics appeared to be unsynchronized between Hong Kong and Shenzhen most of the time. Given the close geographical locations of these two cities, this could be due to the strikingly different age structures of their populations.

HIV epidemics in Shenzhen and Chongqing, China.

OBJECTIVE: Men who have sex with men (MSM) and heterosexuals are the populations with the fastest growing HIV infection rates in China. We characterize the epidemic growth and age patterns between these two routes from 2004 to 2015 in Chongqing and Shenzhen, China. DESIGN AND METHODS: Data were downloaded from the National HIV/ AIDS Comprehensive Response Information Management System. For the new HIV diagnoses of heterosexuals and MSM in both cities, we estimated the growth rates by fitting different sub-exponential models. Heat maps are used to show their age patterns. We used histograms to compare these patterns by birth cohort. RESULTS: The MSM epidemics grew significantly in both cities. Chongqing experienced quadratic growth in HIV reported cases with an estimated growth rate of 0.086 per week and a "deceleration rate" of 0.673. HIV reported cases of MSM in Shenzhen grew even more drastically with a growth rate of 0.033 per week and "deceleration rate" of 0.794. The new infections are mainly affecting the ages of 18 to 30 in Chongqing and ages of 20 to 35 in Shenzhen. They peaked in early 1990's and mid-1990's birth cohorts in Chongqing and Shenzhen respectively. The HIV epidemic among heterosexuals grew rapidly in both cities. The growth rates were estimated as 0.02 and 0.028 in Chongqing and Shenzhen respectively whereas the "deceleration rates" were 0.878 and 0.790 in these two places. It affected mostly aged 18 to 75 in males and 18 to 65 in females in Chongqing and aged 18 to 45 in males and 18 to 50 in females in Shenzhen in 2015. In Chongqing, the heterosexual female epidemics display two peaks in HIV diagnoses in the birth cohorts of early 1950's and early 1980's, with heterosexual male epidemics peaked in early 1940's and early 1960's. The heterosexual male and female epidemics display higher rates in the birth cohort 1940-1960, than the birth cohort 1960-1990. It peaked in birth cohorts of 1950's and 1980's in Shenzhen. CONCLUSIONS: We revealed striking differences in epidemic growth and age patterns of the HIV epidemics in these two cities. Our results may be used to inform age-targeted public health policies to curb their epidemic growth.

Anti-phase synchronization of influenza A/H1N1 and A/H3N2 in Hong Kong and countries in the North Temperate Zone.

OBJECTIVES: Influenza affects 10% of the global population annually. Hong Kong is a subtropical city close to the North Temperate Zone (NTZ). Influenza-associated mortality rates in Hong Kong were 27.53, 79.55, 36.94, and 48.72 per one million person-years in 2014, 2015, 2016, and January to July 2017, respectively. The aim of this study was to explore the temporal patterns of influenza A subtypes in both Hong Kong and the NTZ. METHODS: Weekly reported cases of influenza A/H1N1 and A/H3N2 from January 2010 to July 2017 were downloaded from the Centre for Health Protection in Hong Kong and FluNet (provided by the World Health Organization). The spatio-temporal patterns of A/H1N1 and A/H3N2 in Hong Kong and the NTZ were explored. Anti-phase synchronization between A/H1N1 and A/H3N2 is indicated by a high for A/H1N1 coinciding with a low for A/H3N2, and vice versa. RESULTS: Anti-phase synchronization was evident in both Hong Kong and the NTZ. It was found that A/H3N2 clearly dominated in the 2011/2012, 2014/2015, and 2016/2017 influenza seasons. CONCLUSIONS: These results are novel in identifying anti-phase synchronization in influenza A subtypes in Hong Kong and the NTZ. These findings should inform public health preparedness for future epidemics of A/H3N2, which are typically more severe than those of A/H1N1.

Analysing increasing trends of Guillain-Barré Syndrome (GBS) and dengue cases in Hong Kong using meteorological data.

BACKGROUND: Guillain-Barré Syndrome (GBS) is a severe paralytic neuropathy associated with virus infections such as Zika virus and Chikungunya virus. There were also case reports of dengue fever preceding GBS. With the aim to understand the mechanisms of GBS and dengue outbreaks, this ecological study investigates the relationships between GBS, dengue, meteorological factors in Hong Kong and global climatic factors from January 2000 to June 2016. METHODS: The correlations between GBS, dengue, Multivariate El Niño Southern Oscillation Index (MEI) and local meteorological data were explored by Spearman's Rank correlations and cross-correlations. Three Poisson regression models were fitted to identify non-linear associations among GBS, dengue and MEI. Cross wavelet analyses were applied to infer potential non-stationary oscillating associations among GBS, dengue and MEI. FINDINGS AND CONCLUSION: We report a substantial increasing of local GBS and dengue cases (mainly imported) in recent year in Hong Kong. The seasonalities of GBS and dengue are different, in particular, GBS is low while dengue is high in the summer. We found weak but significant correlations between GBS and local meteorological factors. MEI could explain over 17% of dengue's variations based on Poisson regression analyses. We report a possible non-stationary oscillating association between dengue fever and GBS cases in Hong Kong. This study has led to an improved understanding about the timing and ecological relationships between MEI, GBS and dengue.

Patterns of influenza vaccination coverage in the United States from 2009 to 2015.

BACKGROUND: Globally, influenza is a major cause of morbidity, hospitalization and mortality. Influenza vaccination has shown substantial protective effectiveness in the United States. METHODS: We investigated state-level patterns of coverage rates of seasonal and pandemic influenza vaccination, among the overall population (six months or older) in the U.S. and specifically among children (aged between 6 months and 17 years) and the elderly (aged 65 years or older), from 2009/10 to 2014/15, and associations with ecological factors. We obtained state-level influenza vaccination rates from national surveys, and state-level socio-demographic and health data from a variety of sources. We employed a retrospective ecological study design, and used both linear models and linear mixed-effect models to determine the levels of ecological association of the state-level vaccinations rates with these factors, both with and without region as a factor for the three populations. RESULTS AND CONCLUSIONS: Health-care access has a robust, positive association with state-level vaccination rates across all populations and models. This highlights a potential population-level advantage of expanding health-care access. We also found that prevalence of asthma in adults is negatively associated with mean influenza vaccination rates in the elderly populations.

News trends and web search query of HIV/AIDS in Hong Kong.

BACKGROUND: The HIV epidemic in Hong Kong has worsened in recent years, with major contributions from high-risk subgroup of men who have sex with men (MSM). Internet use is prevalent among the majority of the local population, where they sought health information online. This study examines the impacts of HIV/AIDS and MSM news coverage on web search query in Hong Kong. METHODS: Relevant news coverage about HIV/AIDS and MSM from January 1st, 2004 to December 31st, 2014 was obtained from the WiseNews databse. News trends were created by computing the number of relevant articles by type, topic, place of origin and sub-populations. We then obtained relevant search volumes from Google and analysed causality between news trends and Google Trends using Granger Causality test and orthogonal impulse function. RESULTS: We found that editorial news has an impact on "HIV" Google searches on HIV, with the search term popularity peaking at an average of two weeks after the news are published. Similarly, editorial news has an impact on the frequency of "AIDS" searches two weeks after. MSM-related news trends have a more fluctuating impact on "MSM" Google searches, although the time lag varies anywhere from one week later to ten weeks later. CONCLUSIONS: This infodemiological study shows that there is a positive impact of news trends on the online search behavior of HIV/AIDS or MSM-related issues for up to ten weeks after. Health promotional professionals could make use of this brief time window to tailor the timing of HIV awareness campaigns and public health interventions to maximise its reach and effectiveness.

Modelling the transmission and control strategies of varicella among school children in Shenzhen, China.

OBJECTIVES: Varicella (chickenpox) is a highly transmissible childhood disease. Between 2010 and 2015, it displayed two epidemic waves annually among school populations in Shenzhen, China. However, their transmission dynamics remain unclear and there is no school-based vaccination programme in Shenzhen to-date. In this study, we developed a mathematical model to compare a school-based vaccination intervention scenario with a baseline (i.e. no intervention) scenario. METHODS: Data on varicella reported cases were downloaded from the Infectious Disease Reporting Information Management System. We obtained the population size, age structure of children aged 15 or under, the class and school distribution from Shenzhen Education Bureau. We developed an Agent-Based Susceptible-Exposed-Infectious-Recovered (ABM-SEIR) Model that considered within-class, class-to-class and out-of-school transmission modes. The intervention scenario was that school-wide vaccination intervention occurred when an outbreak threshold was reached within a school. We varied this threshold level from five to ten cases. We compared the reduction of disease outbreak size and estimated the key epidemiological parameters under the intervention strategy. RESULTS: Our ABM-SEIR model provided a good model fit to the two annual varicella epidemic waves from 2013 to 2015. The transmission dynamics displayed strong seasonality. Our results suggested that a school-based vaccination strategy could effectively prevent large outbreaks at different thresholds. CONCLUSIONS: There was a considerable increase in reported varicella cases from 2013 to 2015 in Shenzhen. Our modelling study provided important theoretical support for disease control decision making during school outbreaks and the development of a school-based vaccination programme.

Spatio-temporal patterns of proportions of influenza B cases.

We studied the spatio-temporal patterns of the proportions of influenza B cases out of all typed cases, with data from 139 countries and regions downloaded from the FluNet compiled by the World Health Organization, from January 2006 to October 2015. We restricted our analysis to 34 countries that reported more than 2,000 confirmations for each of types A and B over the study period. Globally, we found that Pearson's correlation is greater than 0.6 between effective distance from Mexico and the proportions of influenza B cases among the countries during the post-pandemic era (i.e. Week 1, 2010 to Week 40, 2015). Locally, in the United States, the proportions of influenza B cases in the pre-pandemic period (2003-2008) negatively correlated with that in the post-pandemic era (2010-2015) at the regional level. Our study limitations are the country-level variations in both surveillance methods and testing policies. The proportions of influenza B cases displayed wide variations over the study period. Our findings suggest that the 2009 influenza pandemic has an evident impact on the relative burden of the two influenza types. Future studies should examine whether there are other additional factors. This study has potential implications in prioritizing public health control measures.

Seasonality of Influenza A(H7N9) Virus in China-Fitting Simple Epidemic Models to Human Cases.

BACKGROUND: Three epidemic waves of influenza A(H7N9) (hereafter 'H7N9') human cases have occurred between March 2013 and July 2015 in China. However, the underlying transmission mechanism remains unclear. Our main objective is to use mathematical models to study how seasonality, secular changes and environmental transmission play a role in the spread of H7N9 in China. METHODS: Data on human cases and chicken cases of H7N9 infection were downloaded from the EMPRES-i Global Animal Disease Information System. We modelled on chicken-to-chicken transmission, assuming a constant ratio of 10-6 human case per chicken case, and compared the model fit with the observed human cases. We developed three different modified Susceptible-Exposed-Infectious-Recovered-Susceptible models: (i) a non-periodic transmission rate model with an environmental class, (ii) a non-periodic transmission rate model without an environmental class, and (iii) a periodic transmission rate model with an environmental class. We then estimated the key epidemiological parameters and compared the model fit using Akaike Information Criterion and Bayesian Information Criterion. RESULTS: Our results showed that a non-periodic transmission rate model with an environmental class provided the best model fit to the observed human cases in China during the study period. The estimated parameter values were within biologically plausible ranges. CONCLUSIONS: This study highlighted the importance of considering secular changes and environmental transmission in the modelling of human H7N9 cases. Secular changes were most likely due to control measures such as Live Poultry Markets closures that were implemented during the initial phase of the outbreaks in China. Our results suggested that environmental transmission via viral shedding of infected chickens had contributed to the spread of H7N9 human cases in China.