•Zhejiang was the third worst-affected province of COVID-19 in China•This study monitored transmissibility of COVID-19, accounting transmission from imported cases•An interruption of local ...transmission was observed in early/mid-February 2020•Early response followed by large-scale measures was effective for the interruption
Owing to the frequent travel connections between Wuhan and Zhejiang, Zhejiang was the third worst-affected province in China with 1,205 cases confirmed before 26 February 2020. The transmissibility of the 2019 novel coronavirus disease was monitored in Zhejiang, accounting for the transmissions from imported cases. Even though Zhejiang was one of the worst-affected provinces, an interruption of disease transmission (i.e. instantaneous reproduction numbers <1) was observed in early/mid-February after a comprehensive set of interventions combating the outbreak.
Influenza virus continuously evolves to escape human adaptive immunity and generates seasonal epidemics. Therefore, influenza vaccine strains need to be updated annually for the upcoming flu season ...to ensure vaccine effectiveness. We develop a computational approach, beth-1, to forecast virus evolution and select representative virus for influenza vaccine. The method involves modelling site-wise mutation fitness. Informed by virus genome and population sero-positivity, we calibrate transition time of mutations and project the fitness landscape to future time, based on which beth-1 selects the optimal vaccine strain. In season-to-season prediction in historical data for the influenza A pH1N1 and H3N2 viruses, beth-1 demonstrates superior genetic matching compared to existing approaches. In prospective validations, the model shows superior or non-inferior genetic matching and neutralization against circulating virus in mice immunization experiments compared to the current vaccine. The method offers a promising and ready-to-use tool to facilitate vaccine strain selection for the influenza virus through capturing heterogeneous evolutionary dynamics over genome space-time and linking molecular variants to population immune response.
While many studies have focused on identifying the association between meteorological factors and the activity of COVID-19, we argue that the contribution of meteorological factors to a reduction of ...the risk of COVID-19 was minimal when the effects of control measures were taken into account. In this study, we assessed how much variability in COVID-19 activity is attributable to city-level socio-demographic characteristics, meteorological factors, and the control measures imposed. We obtained the daily incidence of COVID-19, city-level characteristics, and meteorological data from a total of 102 cities situated in 27 provinces/municipalities outside Hubei province in China from 1 January 2020 to 8 March 2020, which largely covers almost the first wave of the epidemic. Generalized linear mixed effect models were employed to examine the variance in the incidence of COVID-19 explained by different combinations of variables. According to the results, including the control measure effects in a model substantially raised the explained variance to 45%, which increased by >40% compared to the null model that did not include any covariates. On top of that, including temperature and relative humidity in the model could only result in < 1% increase in the explained variance even though the meteorological factors showed a statistically significant association with the incidence rate of COVID-19. In conclusion, we showed that very limited variability of the COVID-19 incidence was attributable to meteorological factors. Instead, the control measures could explain a larger proportion of variance.
Despite several immunization efforts, China saw a resurgence of measles in 2012. Monitoring of transmissions of individuals from different age groups could offer information that would be valuable ...for planning adequate disease control strategies. We compared the age-specific effective reproductive numbers (R) of measles during 2009-2016 in Guangdong, China.
We estimated the age-specific R values for 7 age groups: 0-8 months, 9-18 months, 19 months to 6 years, 7-15 years, 16-25 years, 26-45 years, and ≥46 years adapting the contact matrix of China. The daily numbers of laboratory and clinically confirmed cases reported to the Center for Disease Control and Prevention of Guangdong were used.
The peak R values of the entire population were above unity from 2012 to 2016, indicating the persistence of measles in the population. In general, children aged 0-6 years and adults aged 26-45 years had larger values of R when comparing with other age groups after 2012. While the peaks of R values for children aged 0-6 years dropped steadily after 2013, the peaks of R values for adults aged 26-45 years kept at a high range every year.
Although the provincial supplementary immunization activities (SIAs) conducted in 2009 and 2010 were able to reduce the transmissions from 2009 to 2011, larger values of R for children aged 0-6 years were observed after 2012, indicating that the benefits of the SIAs were short-lived. In addition, the transmissions from adults aged between 26 and 45 years increased over time. Disease control strategies should target children and adult groups that carry high potential for measles transmission.
Abstract
Background
Restrictive spirometry pattern (RSP), defined as reduced forced vital capacity (FVC) in absence of airflow obstruction (AFO), is associated with increased risk of mortality in ...general population. However, evidence in the patients with silicosis is limited. This study was aimed to investigate the relationship between RSP and the risk of death in a silicotic cohort.
Method
This retrospective cohort study used data from the Pneumoconiosis Clinic, Hong Kong Department of Health that containing 4315 patients aged 18–80 years and diagnosed with silicosis during 1981–2019, with a follow-up till 31 December 2019. Spirometry was carried out at the diagnostic examination of silicosis. Lung function categories were classified as normal spirometry (FEV
1
/FVC ≥ 0.7, FVC ≥ 80% predicted), RSP only (FEV
1
/FVC ≥ 0.7, FVC < 80% predicted), AFO only (FEV1/FVC < 0.7, FVC ≥ 80% predicted), and RSP&AFO mixed (FEV
1
/FVC < 0.7, FVC < 80% predicted). The hazard ratio (HR) and 95% confidence intervals (95% CI) were computed using a Cox proportional hazards model adjusting for age, body mass index, history of tuberculosis, smoking status, pack-years, and radiographic characteristics of silicotic nodules.
Results
Among the 4315 patients enrolled in the study, the prevalence of RSP was 24.1% (n = 1038), including 11.0% (n = 473) with RSP only and 13.1% (n = 565) with mixed RSP and AFO. During the follow-up period, a total of 2399 (55.6%) deaths were observed. Compared with the silicotics with normal spirometry, those with RSP only had significantly increased risk of all-cause mortality (HR = 1.63, 95% CI 1.44–1.85) and respiratory-related mortality (HR = 1.56, 95% CI 1.31–1.85). Notably, a higher risk of mortality was observed in silicotics with mixed ventilatory defects of both RSP and AFO (all-cause mortality: HR = 2.22, 95% CI 1.95–2.52; respiratory-related mortality: HR = 2.59, 95% CI 2.18–3.07) than in those with RSP only.
Conclusion
RSP is significantly associated with increased risk of all-cause and respiratory-related mortality in the silicotics, and patients with mixed restrictive and obstructive ventilatory defect have higher risk of mortality than those with single RSP or AFO. These findings emphasize the importance of recognizing RSP in the occupational settings, especially for the silicotic patients with mixed ventilatory defect.
Krüppel-like Factor 4 (KLF4), a target gene of miR-145, can negatively regulate lung fibrosis. However, the potential role of KLF4 and miR-145 in hepatic stellate cells (HSCs) activation or in ...hepatic fibrosis keeps unclear. This study aims to characterize miR-145 and KLF4 in activated HSCs and liver cirrhotic, and the underlying molecular basis. miR-145 was significantly up-regulated, while KLF4 was dramatically down-regulated during the activation of rat primary HSCs and TGF-βtreated HSCs. Furthermore, miR-145 mimics induced and inhibition of miR-145 reduced α-SMA and COL-I expression in primary HSCs. Additionally, the mRNA and protein levels of KLF4 in the liver of cirrhotic patients and rats were significantly down-regulated. α-SMA and COL-I were increased after inhibition of KLF4 by specific shRNA in primary HSCs. Forced KLF4 expression led to a reduction of α-SMA and COL-I expression in HSCs. miR-145 promotes HSC activation and liver fibrosis by targeting KLF4.
Abstract
Background
The elderly healthcare voucher (EHCV) scheme is expected to lead to an increase in the number of elderly people selecting private primary healthcare services and reduce reliance ...on the public sector in Hong Kong. However, studies thus far have reported that this scheme has not received satisfactory responses. In this study, we examined changes in the ratio of visits between public and private doctors in primary care (to measure reliance on the public sector) for different strategic scenarios in the EHCV scheme.
Methods
Based on comments from an expert panel, a system dynamics model was formulated to simulate the impact of various enhanced strategies in the scheme: increasing voucher amounts, lowering the age eligibility, and designating vouchers for chronic conditions follow-up. Data and statistics for the model calibration were collected from various sources.
Results
The simulation results show that the current EHCV scheme is unable to reduce the utilization of public healthcare services, as well as the ratio of visits between public and private primary care among the local aging population. When comparing three different tested scenarios, even if the increase in the annual voucher amount could be maintained at the current pace or the age eligibility can be lowered to include those aged 60 years, the impact on shifts from public-to-private utilization were insignificant. The public-to-private ratio could only be marginally reduced from 0.74 to 0.64 in the first several years. Nevertheless, introducing a chronic disease-oriented voucher could result in a significant drop of 0.50 in the public-to-private ratio during the early implementation phase. However, the effect could not be maintained for an extended period.
Conclusions
Our findings will assist officials in improving the design of the EHCV scheme, within the wider context of promoting primary care among the elderly. We suggest that an additional chronic disease-oriented voucher can serve as an alternative strategy. The scheme must be redesigned to address more specific objectives or provide a separate voucher that promotes under-utilized healthcare services (e.g., preventive care), instead of services designed for unspecified reasons, which may lead to concerns regarding exploitation.
Hong Kong is a high-income city with intermediate tuberculosis (TB) burden primarily driven by endogenous reactivations. A high proportion of remote latently infected people, particularly elderly, ...hinders the effectiveness of current strategies focusing on passive TB detection. In this study, we developed a mathematical model to evaluate the impact of treating latent TB infection (LTBI) in the elderly in addition to current TB control strategies. The model was calibrated using the annual age-stratified TB notifications from 1965-2013 in Hong Kong. Our results showed that at present, approximately 75% of annual new notifications were from reactivations. Given the present treatment completion rate, even if only a low to moderate proportion (approximately 20% to 40%) of elderly people were screened and treated for LTBI, the overall TB incidence could be reduced by almost 50%, to reach the 2025 milestone of the global End TB Strategy. Nevertheless, due to a high risk of hepatotoxicity in elderly population, benefit-risk ratios were mostly below unity; thus, intervention programs should be carefully formulated, including prioritising LTBI treatment for high-risk elderly groups who are closely monitored for possible adverse side effects.
Timely detection of an evolving event of an infectious disease with superspreading potential is imperative for territory-wide disease control as well as preventing future outbreaks. While the ...reproduction number (R) is a commonly-adopted metric for disease transmissibility, the transmission heterogeneity quantified by dispersion parameter k, a metric for superspreading potential is seldom tracked. In this study, we developed an estimation framework to track the time-varying risk of superspreading events (SSEs) and demonstrated the method using the three epidemic waves of COVID-19 in Hong Kong. Epidemiological contact tracing data of the confirmed COVID-19 cases from 23 January 2020 to 30 September 2021 were obtained. By applying branching process models, we jointly estimated the time-varying R and k. Individual-based outbreak simulations were conducted to compare the time-varying assessment of the superspreading potential with the typical non-time-varying estimate of k over a period of time. We found that the COVID-19 transmission in Hong Kong exhibited substantial superspreading during the initial phase of the epidemics, with only 1 % (95 % Credible interval CrI: 0.6–2 %), 5 % (95 % CrI: 3–7 %) and 10 % (95 % CrI: 8–14 %) of the most infectious cases generated 80 % of all transmission for the first, second and third epidemic waves, respectively. After implementing local public health interventions, R estimates dropped gradually and k estimates increased thereby reducing the risk of SSEs to approaching zero. Outbreak simulations indicated that the non-time-varying estimate of k may overlook the possibility of large outbreaks. Hence, an estimation of the time-varying k as a compliment of R as a monitoring of both disease transmissibility and superspreading potential, particularly when public health interventions were relaxed is crucial for minimizing the risk of future outbreaks.
•We developed an estimation framework to track the time-varying superspreading potential.•Only 1 to 10% of the infectious cases generated 80% of all transmissions for the first three epidemics in Hong Kong.•Simulations demonstrated traditional non-time-varying estimate of k may overlook the possibility of larger outbreaks.•We highlight the need of tracking transmission heterogeneity along with the viral transmissibility for guiding control.
In a new influenza pandemic, travel data such as arrival times of cases seeded by the originating country can be regarded as a combination of the epidemic size and the mobility networks of infections ...connecting the originating country with other regions. It can be a complete and timely source for estimating the basic reproduction number (R
), a key indicator of disease transmissibility.
In this study, we developed a likelihood-based method using arrival times of infected cases in different countries to estimate R
for influenza pandemics. A simulation was conducted to assess the performance of the proposed method. We further applied the method to the outbreak of the influenza pandemic A/H1N1 in Mexico.
In the numerical application, the estimated R
was equal to 1.69 with a 95% confidence interval (1.65, 1.73). For the simulation results, the estimations were robust to the decline of travel rate and other parameter assumptions. Nevertheless, the estimates were moderately sensitive to the assumption of infectious duration. Generally, the findings were in line with other relevant studies.
Our approach as well as the estimate is potential to assist officials in planning control and prevention measures. Improved coordination to streamline or even centralize surveillance of imported cases among countries will thus be beneficial to public health.
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