Independent effect of weather, air pollutants, and seasonal influenza on risk of tuberculosis hospitalization: An analysis of 22-year hospital admission data.

BACKGROUND: While influenza infections and environmental factors have been documented as potential drivers of tuberculosis, no investigations have simultaneously examined their impact on tuberculosis at a population level. This study thereby made use of Hong Kong's surveillance data over 22 years to elucidate the temporal association between environmental influences, influenza infections, and tuberculosis activity. METHODS: Weekly total numbers of hospital admissions due to tuberculosis, meteorological data, and outdoor air pollutant concentrations in Hong Kong during 1998-2019 were obtained. All-type influenza-like illness positive (ILI+) rate and type-specific ILI+ rates were used as proxies for influenza activity. Quasi-Poisson generalized additive models together with distributed lag non-linear models were used to assess the association of interest. RESULTS: A total of 164,116 hospital admissions due to tuberculosis were notified in public settings over a period of 22 years. The cumulative adjusted relative risk (ARR) of hospital admission due to tuberculosis was 1.07 (95% CI, 1.00-1.14) when the mean ambient temperature increased from 15.1 °C (the 5th percentile) to 24.5 °C (median). Short-term exposure to air pollutants was not found to be statistically significantly related to tuberculosis hospitalization. Accounting for the environmental covariates in the analysis, the cumulative ARR of tuberculosis admission was elevated to 1.05 (95% CI, 1.01-1.08) when the rate of ILI+ total increased from zero to 19.9 per 1000 consultations, the 95th percentile. CONCLUSION: Our findings demonstrated that increased influenza activity and higher temperature were related to a higher risk of tuberculosis admissions. Stepping up the promotion of influenza vaccination, especially before the summer season, may lower the risk of tuberculosis infection/reactivation for vulnerable groups (e.g. elderly born before the launch of Bacillus Calmette-Guérin vaccination programme).

Association of weather, air pollutants, and seasonal influenza with chronic obstructive pulmonary disease hospitalization risks.

The influences of weather and air pollutants on chronic obstructive pulmonary disease (COPD) have been well-studied. However, the heterogeneous effects of different influenza viral infections, air pollution and weather on COPD admissions and re-admissions have not been thoroughly examined. In this study, we aimed to elucidate the relationships between meteorological variables, air pollutants, seasonal influenza, and hospital admissions and re-admissions due to COPD in Hong Kong, a non-industrial influenza epicenter. A total number of 507703 hospital admissions (i.e., index admissions) and 301728 re-admission episodes (i.e., episodes within 30 days after the previous discharge) for COPD over 14 years (1998-2011) were obtained from all public hospitals. The aggregated weekly numbers were matched with meteorological records and outdoor air pollutant concentrations. Type-specific and all-type influenza-like illness positive (ILI+) rates were used as proxies for influenza activity. Generalized additive models were used in conjunction with distributed-lag non-linear models to estimate the associations of interest. According to the results, high concentrations of fine particulate matter, oxidant gases, and cold weather were strong independent risk factors of COPD outcomes. The cumulative adjusted relative risks exhibited a monotone increasing trend except for ILI+ B, and the numbers were statistically significant over the entire observed range of ILI+ total and ILI+ A/H3N2 when the reference rate was zero. COPD hospitalization risk from influenza infection was higher in the elderly than that in the general population. In conclusion, our results suggest that health administrators should impose clean air policies, such as strengthening emissions control on petrol vehicles, to reduce pollution from oxidant gases and particulates. An extension of the influenza vaccination program for patients with COPD may need to be encouraged: for example, vaccination may be included in hospital discharge planning, particularly before the winter epidemic.

Relationship between acute kidney injury, seasonal influenza, and environmental factors: A 14-year retrospective analysis.

Despite high incidence of acute kidney injury (AKI) among patients hospitalised for influenza, no previous work has attempted to analyse and quantify the association between the two. Herein, we made use of Hong Kong's surveillance data to evaluate the time-varying relationship between seasonal influenza and risk of AKI with adjustment for potential environmental covariates. Generalized additive model was used in conjunction with distributed-lag non-linear model to estimate the association of interest with daily AKI admissions as outcome and daily influenza admissions as predictor, while controlling for environmental variables (i.e. temperature, relative humidity, total rainfall, nitrogen dioxide, and ozone). Results suggested a positive association between risk of AKI admission and number of influenza hospitalisation cases, with relative risk reaching 1.12 (95% confidence interval, 1.10-1.15) at the 95th percentile. Using median as reference, an almost U-shaped association between risk of AKI admission and temperature was observed; the risk increased significantly when the temperature was low. While ozone was not shown to be a risk factor for AKI, moderate-to-high levels of nitrogen dioxide (50-95th percentile) were significantly associated with increased risk of AKI admission. This study mentioned the possibility that AKI hospitalisations are subject to environmental influences and offered support for a positive association between seasonal influenza and AKI occurrence in Hong Kong. Authorities are urged to extend the influenza vaccination program to individuals with pre-existing renal conditions to safeguard the health of the vulnerable. Given that adverse health effects are evident at current ambient levels of nitrogen dioxide, the government is recommended to adopt clean-air policies at the earliest opportunity to protect the health of the community.

Limited role for meteorological factors on the variability in COVID-19 incidence: A retrospective study of 102 Chinese cities.

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.

Targeted Profiling of Immunological Genes during Norovirus Replication in Human Intestinal Enteroids.

Norovirus is the leading cause of acute gastroenteritis worldwide. The pathogenesis of norovirus and the induced immune response remain poorly understood due to the lack of a robust virus culture system. The monolayers of two secretor-positive Chinese human intestinal enteroid (HIE) lines were challenged with two norovirus pandemic GII.4 Sydney strains. Norovirus RNA replication in supernatants and cell lysates were quantified by RT-qPCR. RNA expression levels of immune-related genes were profiled using PCR arrays. The secreted protein levels of shortlisted upregulated genes were measured in supernatants using analyte-specific enzyme-linked immunosorbent assay (ELISA). Productive norovirus replications were achieved in three (75%) out of four inoculations. The two most upregulated immune-related genes were CXCL10 (93-folds) and IFI44L (580-folds). Gene expressions of CXCL10 and IFI44L were positively correlated with the level of norovirus RNA replication (CXCL10: Spearman's r = 0.779, p < 0.05; IFI44L: r = 0.881, p < 0.01). The higher level of secreted CXCL10 and IFI44L proteins confirmed their elevated gene expression. The two genes have been reported to be upregulated in norovirus volunteer challenges and natural human infections by other viruses. Our data suggested that HIE could mimic the innate immune response elicited in natural norovirus infection and, therefore, could serve as an experimental model for future virus-host interaction and antiviral studies.

Short-term association among meteorological variation, outdoor air pollution and acute bronchiolitis in children in a subtropical setting.

OBJECTIVES: To examine the association among acute bronchiolitis-related hospitalisation in children, meteorological variation and outdoor air pollution. METHODS: We obtained the daily counts of acute bronchiolitis-related admission of children≤2 years old from all public hospitals, meteorological data and outdoor air pollutants' concentrations between 1 January 2008 and 31 December 2017 in Hong Kong. We used quasi-Poisson generalised additive models together with distributed lag non-linear models to estimate the associations of interest adjusted for confounders. RESULTS: A total of 29 688 admissions were included in the analysis. Increased adjusted relative risk (ARR) of acute bronchiolitis-related hospitalisation was associated with high temperature (ambient temperature and apparent temperature) and was marginally associated with high vapour pressure, a proxy for absolute humidity. High concentration of NO2 was associated with elevated risk of acute bronchiolitis admission; the risk of bronchiolitis hospitalisation increased statistically significantly with cumulative NO2 exposure over the range 66.2-119.6 µg/m3. For PM10, the significant effect observed at high concentrations appears to be immediate but not long lasting. For SO2, ARR increased as the concentration approached the 75th percentile and then decreased though the association was insignificant. CONCLUSIONS: Acute bronchiolitis-related hospitalisation among children was associated with temperature and exposure to NO2 and PM10 at different lag times, suggesting a need to adopt sustainable clean air policies, especially to target pollutants produced by motor vehicles, to protect young children's health.

Independent association between meteorological factors, PM2.5, and seasonal influenza activity in Hangzhou, Zhejiang province, China.

BACKGROUND: Due to variations in climatic conditions, the effects of meteorological factors and PM2.5 on influenza activity, particularly in subtropical regions, vary in existing literature. In this study, we examined the relationship between influenza activity, meteorological parameters, and PM2.5 . METHODS: A total of 20 165 laboratory-confirmed influenza cases in Hangzhou, Zhejiang province, were documented in our dataset and aggregated into weekly counts for downstream analysis. We employed a combination of the quasi-Poisson-generalized additive model and the distributed lag non-linear model to examine the relationship of interest, controlling for long-term trends, seasonal trends, and holidays. RESULTS: A hockey-stick association was found between absolute humidity and the risk of influenza infections. The overall cumulative adjusted relative risk (ARR) was statistically significant when weekly mean absolute humidity was low (<10 µg/m3 ) and high (>17.5 µg/m3 ). A slightly higher ARR was observed when weekly mean temperature reached over 30.5°C. A statistically significantly higher ARR was observed when weekly mean relative humidity dropped below 67%. ARR increased statistically significantly with increasing rainfall. For PM2.5 , the ARR was marginally statistically insignificant. In brief, high temperature, wet and dry conditions, and heavy rainfall were the major risk factors associated with a higher risk of influenza infections. CONCLUSIONS: The present study contributes additional knowledge to the understanding of the effects of various environmental factors on influenza activities. Our findings shall be useful and important for the development of influenza surveillance and early warning systems.

Detection of Norovirus Variant GII.4 Hong Kong in Asia and Europe, 2017-2019.

We report a new norovirus GII.4 variant, GII.4 Hong Kong, with low-level circulation in 4 Eurasia countries since mid-2017. Amino acid substitutions in key residues on the virus capsid associated with the emergence of pandemic noroviruses suggest that GII.4 Hong Kong has the potential to become the next pandemic variant.

A 21-year retrospective analysis of environmental impacts on paediatric acute gastroenteritis in an affluent setting.

BACKGROUND: Extreme weather events happen more frequently along with global warming and they constitute a challenge for public health preparedness. For example, many investigations showed heavy rainfall was associated with an increased risk of acute gastroenteritis. In this study, we examined the associations between different meteorological factors and paediatric acute gastroenteritis in an affluent setting in China controlling for pollutant effects. METHODS: Aggregated total weekly number of intestinal infection-related hospital admissions, and meteorological and air pollution data during 1998-2018 in Hong Kong were collected and analysed by a combination of quasi-Poisson generalized additive model and distributed lag nonlinear model. Study population was restricted to children under 5 years of age at the time of admission. RESULTS: While heavy rainfall did not exhibit a statistically significant association with the risk of paediatric admission due to intestinal infections, low temperature and humidity extremes (both relative humidity and vapour pressure) did. Compared with the temperature at which the lowest risk was detected (i.e. 22.5 °C), the risk was 6.4% higher (95% confidence interval: 0.0% to 13.0% at 15.1 °C (i.e. the 5th percentile)). We also found the risk of paediatric admission was statistically significantly associated with an increase in the number of extreme cold days in a week over the study period. CONCLUSION: Cold condition may have greater impact on disease transmission through increased stability and infectivity of enteric viruses in affluent settings like Hong Kong and thus resulted in an increased risk for paediatric acute gastroenteritis. On the contrary, an insignificant impact from heavy rainfall and high temperature may indicate a minor effect on disease transmission through bacterial growth in contaminated food and water. With the identified impacts of weather factors, extreme weather events are likely to distort the prevalence and seasonal pattern of diarrhoeal diseases in the future.

Transmissibility of coronavirus disease 2019 in Chinese cities with different dynamics of imported cases.

BACKGROUND: Monitoring the reproduction number (Rt ) of the disease could help determine whether there is sustained transmission in a population, but areas with similar epidemic trends could have different transmission dynamics given the risk from imported cases varied across regions. In this study, we examined the Rt of coronavirus disease 2019 (COVID-19) by taking different dynamics of imported cases into account and compared the transmissibility of COVID-19 at different intervention periods in Hangzhou and Shenzhen. METHODS: We obtained the daily aggregated counts of laboratory-confirmed imported and local cases of COVID-19 infections in Hangzhou and Shenzhen from January 1 to March 13, 2020. Daily Rt and piecewise Rt before and after Wuhan lockdown were estimated, accounting for imported cases. RESULTS: Since the epidemic of COVID-19 in Shenzhen was dominated by imported cases, Rt was around 0.1 to 0.7 before the Wuhan lockdown. After the lockdown of Wuhan and the initialization of measures in response to the outbreak, local transmission was well-controlled as indicated by a low estimated value of piecewise Rt , 0.15 (95% CI [0.09-0.21]). On the contrary, Rt obtained for Hangzhou ranged from 1.2 to 4.9 with a piecewise Rt of 2.55 (95% CI [2.13-2.97]) before the lockdown of Wuhan due to the surge in local cases. Because of the Wuhan lockdown and other outbreak response measures, Rt dropped below unity in mid-February. CONCLUSIONS: Even though Shenzhen had more cases than Hangzhou, local transmission did not sustain probably due to limited transmission from imported cases owing to the reduction in local susceptibles as residents left the city during Chunyun. The lockdown measures and local outbreak responses helped reduce the local transmissibility.

Changes in Measles Seroprevalence in China After the Launch of Two Provincial Supplementary Immunization Activities During 2009 to 2013.

BACKGROUND: Supplementary immunization activities (SIAs) have been demonstrated being effective in reducing measles incidence within a short period of time in China, but the effects are short-lived if there is no follow-up SIA with high routine immunization coverage. OBJECTIVES: To assess the change in measles seroprevalence from 2009 to 2013 after the launch of 2 large-scale SIAs within the period. METHODS: Three population-based cross-sectional serologic surveys of measles antibodies were conducted in 2009, 2011 and 2013 in Zhejiang, a province in eastern China, with serologic samples collected from 1541, 896 and 1474 subjects, respectively. The serum levels of immunoglobulin G antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: We found that the seropositivity rate among infants 0-7 months of age, a group having no vaccination benefit, was below 80% throughout the study period. In addition, the seropositivity rate among adults 30-49 years of age decreased significantly from 96.0% (95% confidence interval: 93.7%-98.3%) in 2011 to 88.5% (95% confidence interval: 84.3%-92.8%) in 2013. CONCLUSION: We showed that large-scale SIAs were effective, but their effects were not long lasting. Given the drop in seropositivity among adults, their susceptibility should be carefully monitored. While older individuals could benefit from the immunization activities, children who were too young to be vaccinated still have a weak seropositivity profile and the optimal age for the administration of the first dose of vaccine should be reconsidered.

Monitoring disease transmissibility of 2019 novel coronavirus disease in Zhejiang, China.

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.

Ambient temperature, seasonal influenza and risk of cardiovascular disease in a subtropical area in Southern China.

BACKGROUND: Given the regular winter recurrence of influenza epidemics and the biologically plausible association between seasonal influenza and cardiovascular events, researchers assumed a valid and reliable influenza forecast could envision the timing and burden of winter surge in cardiovascular (CVD) hospitalizations. This, however, is well justified only in temperate regions. In this study, we aim to investigate the temporal association between ambient temperature, seasonal influenza and risk of cardiovascular events in a subtropical city. METHODS: Generalized additive model was used in conjunction with distributed-lag non-linear model of quasi-Poisson family to estimate the association of interest with daily CVD admissions as outcome and daily influenza admissions as predictor, while controlling for meteorological factors (i.e. temperature, relative humidity, wind speed and total rainfall) and respiratory pollutants (i.e. nitrogen dioxide, sulphur dioxide, ozone and PM10). Results were expressed in the form of relative risk (RR). RESULTS: Using median as the reference value, a U-shaped association was observed between CVD admissions and temperature. A slight decrease in RR was detected mainly towards the lower end of the temperature scale after adjusting for influenza admissions. Risk of CVD admission was found to be positively associated with the number of influenza hospitalization cases; this association remained consistent and statistically significant across subgroups of age except for those aged 5-49 years. CONCLUSION: The slight reduction in CVD admission risk towards the lower end of the temperature scale after controlling for influenza activity might be attributed to the winter peaks of influenza, meaning that the effect of low temperature on CVD admissions might be partly mediated by influenza infection. In summary, this study reassures us that ambient temperature is independently associated with CVD hospital admissions and offers support for a positive association between seasonal influenza activity and cardiovascular events in Hong Kong.

Were infections in migrants associated with the resurgence of measles epidemic during 2013-2014 in southern China? A retrospective data analysis.

OBJECTIVE: The 2009 province-wide and 2010 nationwide supplementary immunization activities (SIAs) greatly reduced measles prevalence in Guangdong, a province in southern China with the largest migrant population. However, during 2013-2014, Guangdong experienced a resurgence of the measles epidemic. This study was performed to examine the association between infections in migrants and the resurgence of the measles epidemic. METHODS: The records of 22 362 clinically and laboratory-confirmed measles cases from the years 2009 to 2014 were extracted from the National Infectious Disease Monitoring Information System. The epidemiological characteristics of infections in migrants during 2009-2012 were compared to those during 2013-2014. RESULTS: Infections in migrants were not significantly associated with the resurgence of the measles epidemic in 2013-2014 (p=0.98). Nevertheless, for infections among locals and migrants during 2009-2012 and 2013-2014, substantial increases in the proportion of infection were detected among children aged <8 months and the unvaccinated population (p<0.01). CONCLUSIONS: The study findings suggest that infections in migrants might not have been the major cause of the epidemic resurgence of measles. Instead, the resurgence was likely due to infections among children aged <8 months and the unvaccinated. Thus, officials are advised to give higher priority to appropriate populations when formulating control measures, and to strengthen routine surveillance of vaccination coverage among them.

Early Waning of Maternal Measles Antibodies in Infants in Zhejiang Province, China: A Comparison of Two Cross-Sectional Serosurveys.

In China, children aged <8 months, who were expected to be protected by maternal antibodies before receiving the first dose of measles vaccine, were the age group with the greatest risk of infection in recent years. In this study, we evaluated whether infants yet to be age-eligible for measles vaccine had a sufficient seropositive level of maternal measles antibodies in 2009 and 2013. Blood samples were collected from infants aged <8 months through population-based serological surveys conducted in Zhejiang, China. Serum levels of immunoglobulin G measles antibodies were quantified using enzyme-linked immunosorbent assay. In 2013, the mean geometric mean titres (GMTs) of infants aged 4 to 8 months were below the seropositivity threshold (<200 mIU/mL), decreasing from 118.6 mIU/mL (95% confidence interval [CI] 83.0, 169.3 mIU/mL) at 4 months to 28.6 mIU/mL (95% CI 15.6, 52.3 mIU/mL) at 7 months. Antibody levels were significantly lower in 2013 than in 2009 starting from 5 months of age. In conclusion, infants aged 4 to 8 months are susceptible to measles due to low levels of maternal measles antibodies. It is thus suggested to provide infants with a supplementary dose on top of the routine schedule, and/or launch catch-up vaccination campaigns among young women.

Use of Human Intestinal Enteroids to Detect Human Norovirus Infectivity.

Tools to detect human norovirus infectivity have been lacking. Using human intestinal enteroid cultures inoculated with GII.Pe-GII.4 Sydney-infected fecal samples, we determined that a real-time reverse transcription PCR cycle threshold cutoff of 30 may indicate infectious norovirus. This finding could be used to help guide infection control.

Higher Viral Load of Emerging Norovirus GII.P16-GII.2 than Pandemic GII.4 and Epidemic GII.17, Hong Kong, China.

We compared viral load of emerging recombinant norovirus GII.P16-GII.2 with those for pandemic GII.Pe-GII.4 and epidemic GII.P17-GII.17 genotypes among inpatients in Hong Kong. Viral load of GII.P16-GII.2 was higher than those for other genotypes in different age groups. GII.P16-GII.2 is as replication competent as the pandemic genotype, explaining its high transmissibility and widespread circulation.

Bimodal Seasonality and Alternating Predominance of Norovirus GII.4 and Non-GII.4, Hong Kong, China, 2014-20171.

We report emerging subtropical bimodal seasonality and alternating predominance of norovirus GII.4 and non-GII.4 genotypes in Hong Kong. GII.4 predominated in summer and autumn months and affected young children, whereas emergent non-GII.4 genotypes predominated in winter months and affected all age groups. This highly dynamic epidemiology should inform vaccination strategies.