Short-Term Exposure to Ambient Air Pollution and Influenza: A Multicity Study in China.

BACKGROUND: Air pollution is a major risk factor for planetary health and has long been suspected of predisposing humans to respiratory diseases induced by pathogens like influenza viruses. However, epidemiological evidence remains elusive due to lack of longitudinal data from large cohorts. OBJECTIVE: Our aim is to quantify the short-term association of influenza incidence with exposure to ambient air pollutants in Chinese cities. METHODS: Based on air pollutant data and influenza surveillance data from 82 cities in China over a period of 5 years, we applied a two-stage time series analysis to assess the association of daily incidence of reported influenza cases with six common air pollutants [particulate matter with aerodynamic diameter ≤2.5µm (PM2.5), particulate matter with aerodynamic diameter ≤10µm (PM10), NO2, SO2, CO, and O3], while adjusting for potential confounders including temperature, relative humidity, seasonality, and holiday effects. We built a distributed lag Poisson model for one or multiple pollutants in each individual city in the first stage and conducted a meta-analysis to pool city-specific estimates in the second stage. RESULTS: A total of 3,735,934 influenza cases were reported in 82 cities from 2015 to 2019, accounting for 72.71% of the overall case number reported in the mainland of China. The time series models for each pollutant alone showed that the daily incidence of reported influenza cases was positively associated with almost all air pollutants except for ozone. The most prominent short-term associations were found for SO2 and NO2 with cumulative risk ratios of 1.094 [95% confidence interval (CI): 1.054, 1.136] and 1.093 (95% CI: 1.067, 1.119), respectively, for each 10 µg/m3 increase in the concentration at each of the lags of 1-7 d. Only NO2 showed a significant association with the daily incidence of influenza cases in the multipollutant model that adjusts all six air pollutants together. The impact of air pollutants on influenza was generally found to be greater in children, in subtropical cities, and during cold months. DISCUSSION: Increased exposure to ambient air pollutants, particularly NO2, is associated with a higher risk of influenza-associated illness. Policies on reducing air pollution levels may help alleviate the disease burden due to influenza infection. https://doi.org/10.1289/EHP12146.

Extreme cold weather and circulatory diseases of older adults: A time-stratified case-crossover study in jinan, China.

OBJECTIVES: We aimed to investigate the acute effect of extreme cold weather on circulatory disease mortality of older adults in Jinan, with individual and regional-scale characteristics as subgroup analyses to further identify vulnerable populations. METHODS: This study contained the death data of Jinan from 2011 to 2020 (Nov-Mar). A time-stratified case-crossover method was used to estimate the effects of extreme cold weather and lags 0-8 days, controlling for holiday and relative humidity. To evaluate the impact of different durations and thresholds of extreme cold weather, we considered 4 cold day and 12 cold wave definitions RESULTS: Our results showed an increase in circulatory disease deaths under several definitions. The number of older adults died of circulatory diseases totaled 92,119 during the study period. In the definitions of cold day, the maximum significant effect ranging from 1.08 (95% CI: 1.03,1.14) to 1.13 (95% CI: 1.04,1.24) and appeared on Lag5 or Lag6. In the definitions of cold wave, the maximum significant effect ranging from 1.07 (95% CI: 1.02, 1.12) to 1.14 (95% CI: 1.03, 1.25). The cold effect is mainly attributable to cold day rather than an added effect related to the duration. Our research confirmed that extreme cold weather had a stronger impact on women [maximum effects with an OR of 1.21 (95% CI: 1.08, 1.36) in P1, 1.19 (95% CI: 1.05, 1.36) in M12)], and the effect gradient increased with age. CONCLUSIONS: Our findings support the evidence on the impact of extreme cold weather on circulatory disease mortality and provide a basis for policymakers to select target groups to develop policies and reduce the public health burden.

Mapping the distributions of blood-sucking mites and mite-borne agents in China: a modeling study.

BACKGROUND: Emerging mite-borne pathogens and associated disease burdens in recent decades are raising serious public health concerns, yet their distributions and ecology remain under-investigated. We aim to describe the geographical distributions of blood-sucking mites and mite-borne agents and to assess their ecological niches in China. METHODS: We mapped 549 species of blood-sucking mites belonging to 100 genera at the county level and eight mite-associated agents detected from 36 species of blood-sucking mites in China during 1978-2020. Impacts of climatic and environmental factors on the ecology of 21 predominant vector mites and a leading pathogen, Orientia tsutsugamushi, were assessed using boosted regression tree (BRT) models, and model-predicted risks were mapped. We also estimated the model-predicted number, area and population size of affected counties for each of the 21 mite species in China. RESULTS: Laelaps echidninus is the leading mite species that potentially affects 744 million people, followed by La. jettmari (517 million) and Eulaelaps stabularis (452 million). Leptotrombidium scutellare is the mite species harboring the highest variety of mite-borne agents including four Rickettsia species and two viruses, followed by Eu. stabularis (2 agents), L. palpale (2) and La. echidninus (2). The top two agents that parasitize the largest number of mite species are O. tsutsugamushi (28 species) and hantavirus (8). Mammalian richness, annual mean temperature and precipitation of the driest quarter jointly determine the ecology of the mites, forming four clusters of major mite species with distinct geographic distributions. High-risk areas of O. tsutsugamushi are mainly distributed in southern and eastern coastal provinces where 71.5 million people live. CONCLUSIONS: Ecological niches of major mite species and mite-borne pathogens are much more extensive than what have been observed, necessitating expansion of current filed surveillance.

Variability in transmission risk of SARS-CoV-2 in close contact settings: A contact tracing study in Shandong Province, China.

BACKGROUND: Understanding the relative transmissibility of SARS-CoV-2 virus across different contact settings and the possibility of superspreading events is important for prioritizing disease control. Such assessment requires proper consideration of individual level exposure history, which is made possible by contact tracing. METHODS: The case-ascertained study in Shandong, China including 97 laboratory-confirmed index cases and 3158 close contacts. All close contacts were quarantined after their last exposure of index cases. Contacts were tested for COVID-19 regularly by PCR to identify both symptomatic and asymptomatic infections. We developed a Bayesian transmission model to the contact tracing data to account for different duration of exposure among individuals to transmission risk in different settings, and the heterogeneity of infectivity of cases. RESULTS: We estimate secondary attack rates (SAR) to be 39% (95% credible interval (CrI): 20-64%) in households, 30% (95% CrI: 11-67%) in healthcare facilities, 23% (95% CrI: 7-51%) at workplaces, and 4% (95% CrI: 1-17%) during air travel. Models allowing heterogeneity of infectivity of cases provided a better goodness-of-fit. We estimated that 64% (95% CrI: 55-72%) of cases did not generate secondary transmissions, and 20% (95% CrI: 15-26%) cases explained 80% of secondary transmissions. CONCLUSIONS: Household, healthcare facilities and workplaces are efficient setting for transmission. Timely identification of potential superspreaders in most transmissible settings remains crucial for containing the pandemic.

The effect of influenza A (H1N1) pdm09 virus infection on cytokine production and gene expression in BV2 microglial cells.

Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage. We performed reverse transcriptase droplet digital PCR (RT-ddPCR) and luminex assays to investigate virus proliferation and immune reactions in BV2 MGs infected with influenza A(H1N1)pdm09 virus. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to investigate the dynamic change in the protein expression profile in BV2 MGs to gain insight into the CNS response to influenza A (H1N1) pdm09 infection. Our results showed that the influenza A(H1N1)pdm09 virus was replicative and productive in BV2 MG cells, which produced cytokines such as interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. The expression of osteopontin (OPN) in the influenza A (H1N1) pdm09-infected BV2 MGs was upregulated at 16 and 32 h post-infection (hpi) compared to that in the control group, resulting in aggravated brain damage and inflammation. Our study indicates that OPN signalling might provide new insights into the treatment of CNS injury and neurodegenerative diseases in IAE.

Sex Differences in Case Fatality Rate of Patients With Severe Fever With Thrombocytopenia Syndrome.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne disease with high mortality. However, detailed analysis is lacking to explore the complex effect of sex with age or comorbidities. Methods: A retrospective cohort study was performed among 2,938 SFTS patients entered during 2011-2020 in Xinyang, China. The case fatality rate (CFR) was estimated for their association with sex, age, and comorbidities by an interactive way. The difference of immune response between sex was explored in an age dependent way. Results: An overall CFR of 15.3% (450/2,938) was obtained, which appeared to be higher in males than in females [17.7% vs. 13.6%, adjusted odds ratio (aOR) = 1.24; 95% CI, 1.00-1.53; P = 0.048] and increased dramatically with age (P < 0.001). The associations between sex and SFTS fatal outcome were age-dependent and varied according to the status of comorbidities. The mortality-related risk conferred by older age was more pronounced in males, with aOR (95% CI) to be 5.76 (3.75-8.84) vs. 5.30 (3.54-7.95) in female. Sex-stratified analysis disclosed significant associations between death and comorbidities among female patients (aOR = 1.87, 95% CI: 1.40-2.49; P < 0.001), while none among males. Among females, the significant associations between presence of comorbidity and fatal outcome differed among age groups, with aOR (95% CI) decreased from 2.28 (1.16-4.46) in ≤60 years, to 2.06 (1.34-3.18) in 60-70 years and further to 1.55 (0.97-2.47) in >70 years. Altogether 194 SFTS patients were randomly selected for the test of B cells, natural killer (NK) cells, CD4 cells percentages, and anti-SFTSV IgM antibody level, the results revealed that males >60 years had significantly decreased percentages of B cells, CD4 cells, lower anti-SFTSV IgM antibody titer, and increased level of NK cells than male aged ≤60 years, while none of these age specific differences was observed in the females. This finding underlies the more pronounced age specific difference in CFR among male than female. Conclusions: Males had a significantly higher mortality of SFTS than did females, and more likely to be affected by aging for SFTS mortality. This difference can be explained by the effect from comorbidities and the host immunity. It is essential to take a sex- and age-based approach to SFTS treatment and management.

Non-linear relationships and interactions of meteorological factors on mumps in Jinan, China.

Although vaccination is available, mumps remains a public health concern in many countries including China. Previous studies have indicated the impact of meteorological factors and mumps, but findings vary across different regions with limited evidence to inform local public health responses. We aim to examine the impacts of meteorological variables on mumps in Jinan, a temperate city of China, and explore the interactions of temperature with humidity or wind speed. Weekly meteorological data and notified cases of mumps in Jinan were collected for 2014-2018. Regression analyses using the generalized additive model were performed with considerations of multicollinearity, lag effects, school holidays, long-term trend, and seasonality. A stratification model was applied to investigate the interaction. We found a non-linear relationship between weekly mean temperature and the number of cases. Between 1.2 and 24.5 °C, the excess risk (ER) of mumps for a 1 °C increase in weekly mean temperature was 3.08% (95% CI 1.32 to 4.87%) at 0-week lag. The lagged effects could last for 3 weeks. There were interactions between mean temperature and relative humidity or wind speed. The effect of mean temperature was enhanced in days with low relative humidity or high wind speed. This study suggests that temperature is positively associated with mumps cases with thresholds in the temperate city of China, and the effect can be modified by relative humidity and wind speed and is independent of vaccine coverage. Findings could be integrated into current early warning systems of mumps in order to protect people's health from the risk of changing climate.

Analyses of air pollution control measures and co-benefits in the heavily air-polluted Jinan city of China, 2013-2017.

China has made great efforts in air pollution control since 2013. However, there is a lack of evaluation of environmental, health and economic co-benefits associated with the national and local air pollution control measures at a city level. We analyzed local air pollution control policies and implementation in Jinan, one of the most heavily air-polluted cities in China between 2013 and 2017. We assessed the changes in exhaust emissions, air quality, mortality and morbidity of associated specific-diseases, and related economic benefits. We also projected the future scenarios of PM2.5 concentration dropped to 15 µg/m3. There were significant decreases in exhaust emissions of SO2 and NOx in Jinan during the study period. Annual reductions in ambient air pollution were 72.6% for SO2, 43.1% for PM2.5, and 34.2% for PM10. A total of 2,317 (95%CI: 1,533-2,842) premature deaths and 15,822 (95%CI: 8,734-23,990) related morbidity cases had been avoided in 2017, leading to a total of US$ 317.7 million (95%CI: 227.5-458.1) in economic benefits. Decreasing PM2.5 concentrations to 15 µg/m3 would result in reductions of 70% in total PM2.5-related non-accidental mortality and 95% in total PM2.5-related morbidity, which translates into US$ 1,289.5 million (95%CI: 825.8-1,673.6) in economic benefits. The national and local air pollution control measures have brought significant environmental, health and economic benefits to a previously heavy polluted Chinese city.

Personal black carbon exposure and its determinants among elderly adults in urban China.

Personal exposure to air pollution is affected by its concentration in the microenvironment and individual time-activity patterns. To investigate personal black carbon (BC) exposure levels and identify their potential determinants, we conducted a panel study among 67 elderly residents aged 60-69 years in Jinan, China. Personal BC exposure was measured using portable real-time monitors, while corresponding ambient BC concentrations and meteorological conditions were also collected from the local central site. Time-activity and household characteristics were recorded. A linear mixed-effects model was used to identify potential determinants of personal BC exposure. The daily average personal BC exposure concentration was 4.1 ± 2.0 µg/m3 (±standard deviation, SD), which was significantly lower than the ambient concentration (4.6 ± 2.5 µg/m3) (p < 0.001). Strong correlation (Spearman's r = 0.63, p < 0.001) was found between personal and ambient BC concentrations. The fixed-site monitoring ambient concentration cannot fully reflect the actual personal exposure concentration. Ambient BC concentration, ambient temperature, relative humidity, education level and air purifier use were significant determinants of personal BC exposure. Our findings highlight the need for detailed assessment of personal exposure on health risk assessment of BC and also help develop strategies for targeted risk reduction.

The prevalence of non-GII.4 norovirus genotypes in acute gastroenteritis outbreaks in Jinan, China.

Noroviruses (NoVs) are the leading cause of acute viral gastroenteritis outbreaks. From June 2015 to March 2017, fifteen outbreaks of acute gastroenteritis (AGE) were reported to the Jinan Center for Disease Control and Prevention in China. To identify the circulating NoV genotypes associated with outbreaks in Jinan, China, 414 specimens from the 15 outbreaks were collected and analyzed for the causative viruses, and phylogenetic analysis was performed on the NoV-positive strains. The NoV detection rate was 57.5% (238/414), and a total of 14 outbreaks were caused by NoVs (eight by infection with genogroup II (GII), five by mixed infection with GI and GII, and one by mixed infection with GII and rotavirus (RoV)-A). A total of 75 NoV sequences were obtained from 13 NoV-positive outbreaks and classified into seven genotypes (38 GII.17, 13 GII.2, 4 GII.3, 4 GII.1, 10 GI.6, 5 GI.5 and 1 GI.3), while GII.4 was not identified. The most prevalent genotype changed yearly during the 2015-2017 period. Phylogenetic analysis demonstrated that these NoV genotypes had high homology with the strains circulating worldwide, especially strains from Asian countries and cities. Our study illustrated that multiple non-GII.4 NoV genotypes were prevalent in outbreaks of AGE in Jinan, China. Year-round surveillance of multiple NoV genotypes could help health authorities reduce the impact of NoV outbreaks on public health.

Impact of the China Healthy Cities Initiative on Urban Environment.

The China Healthy Cities initiative, a nationwide public health campaign, has been implemented for 25 years. As "Healthy China 2030" becomes the key national strategy for improving population health, this initiative is an important component. However, the effects of the initiative have not been well studied. This paper aims to explore its impact on urban environment using a multiple time series design. We adopted a stratified and systematic sampling method to choose 15 China healthy cities across the country. For the selected healthy cities, 1:1 matched non-healthy cities were selected as the comparison group. We collected longitudinal data from 5 years before cities achieved the healthy city title up to 2012. We used hierarchical models to calculate difference-in-differences estimates for examining the impact of the initiative. We found that the China Healthy Cities initiative was associated with increases in the proportion of urban domestic sewage treated (32 percentage points), the proportion of urban domestic garbage treated (30 percentage points), and the proportion of qualified farmers' markets (40 percentage points), all of which are statistically significant (P < 0.05). No significant change was found for increases in green coverage of urban built-up area (5 percentage points), green space per capita (2 square meter), and days with Air Quality Index/Air Pollution Index ≤ 100 (25 days). In conclusion, the China Healthy Cities initiative was associated with significant improved urban environment in terms of infrastructure construction, yet had little impact on green space and air quality.

Consistently low prevalence of syphilis among female sex workers in Jinan, China: findings from two consecutive respondent driven sampling surveys.

BACKGROUND: Routine surveillance using convenient sampling found low prevalence of HIV and syphilis among female sex workers in China. Two consecutive surveys using respondent driven sampling were conducted in 2008 and 2009 to examine the prevalence of HIV and syphilis among female sex workers in Jinan, China. METHODS: A face-to-face interview was conducted to collect demographic, behavioral and service utilization information using a structured questionnaire. Blood samples were drawn for serological tests of HIV-1 antibody and syphilis antibody. Respondent Driven Sampling Analysis Tool was used to generate population level estimates. RESULTS: In 2008 and in 2009, 363 and 432 subjects were recruited and surveyed respectively. Prevalence of syphilis was 2.8% in 2008 and 2.2% in 2009, while no HIV case was found in both years. Results are comparable to those from routine sentinel surveillance system in the city. Only 60.8% subjects in 2008 and 48.3% in 2009 reported a consistent condom use with clients during the past month. Over 50% subjects had not been covered by any HIV-related services in the past year, with only 15.6% subjects in 2008 and 13.1% in 2009 ever tested for HIV. CONCLUSIONS: Despite the low prevalence of syphilis and HIV, risk behaviors are common. Targeted interventions to promote the safe sex and utilization of existing intervention services are still needed to keep the epidemic from growing.

Predictors of consistent condom use based on the Information-Motivation-Behavioral Skills (IMB) model among female sex workers in Jinan, China.

BACKGROUND: Female commercial sex workers (FSWs) are at high risk of human immunodeficiency virus (HIV) transmission in China. This study was designed to examine the predictors of condom use with clients during vaginal intercourse among FSWs based on the Information-Motivation-Behavioral Skills (IMB) model and to describe the relationships between IMB model constructs. METHODS: A cross-sectional study was conducted in Jinan of Shandong Province, from May to October, 2009. Participants (N = 432) were recruited using Respondent-Driven Sampling (RDS). A self-administered questionnaire was used to collect data. Structural equation modeling was used to assess the IMB model. RESULTS: A total of 427 (98.8%) participants completed their questionnaires. Condom use was significantly predicted by social referents support, experiences with and attitudes toward condoms, self-efficacy, and health behaviors and condom use skills. Significant indirect predictors of condom use mediated through behavioral skills included HIV knowledge, social referents support, and substance use. CONCLUSIONS: These results suggest that the IMB model could be used to predict condom use among Chinese FSWs. Further research is warranted to develop preventive interventions on the basis of the IMB model to promote condom use among FSWs in China.

Which Chinese men who have sex with men miss out on HIV testing?

OBJECTIVES: To describe socio-demographic, behavioural and other characteristics associated with HIV testing behaviour among men who have sex with men (MSM) in Jinan, China. METHODS: A cross-sectional survey was conducted among MSM (N=500) in Jinan in 2008 using respondent-driven sampling--a method used worldwide to reach hidden high-risk populations. Bivariate and multivariate analyses, adjusted for the sampling method, were conducted to identify correlates of not having an HIV test. RESULTS: Overall, 80.7% (95% CI 75.0% to 85.0%) of MSM in Jinan have not had an HIV test in the past 12 months. In the multivariate analyses, having not visited the local Centers for Disease Control and Prevention's website (AOR 5.59, 95% CI 2.62 to 11.95), being over the age of 35 years (AOR 3.77, 95% CI 1.19 to 11.93) and self-identified as bisexual or unsure (AOR 3.85, 95% CI 2.16 to 6.85) are significantly associated with having not had an HIV test. In addition, married men are slightly less likely to have not been tested compared to single men (AOR 0.38, 95% CI 0.17 to 0.85). Those who report meeting their sex partners at high-risk venues are two times more likely to have not had an HIV test (AOR 2.02, 95% CI 0.97 to 4.21). CONCLUSIONS: Targeted, culturally appropriate and innovative interventions to increase HIV testing uptake should be a top priority for HIV prevention among MSM in China.

Rising HIV prevalence among married and unmarried among men who have sex with men: Jinan, China.

We report on two waves of bio-behavioral surveillance of MSM in Jinan, Shandong Province, China. HIV prevalence rose from 0.05% in 2007 to 3.1% in 2008. Differences in the two waves of surveys were noted, particularly with respect to marital status, requiring stratified analysis. In multivariable analysis, unmarried, homosexually identified MSM who do not have female sex partners have a greater than sixfold greater chance of being infected with HIV compared to married, non-homosexually identified MSM who do have female partners. Carefully targeted and population-specific messages will be needed for homosexually identified and non-identified MSM in China.

HIV prevalence and correlates of unprotected anal intercourse among men who have sex with men, Jinan, China.

China's HIV epidemic may be shifting towards predominantly sexual transmission and emerging data point to potential increases in HIV prevalence among men who have sex with men (MSM). There is particular need to assess the extent of risk behavior among MSM outside of China's most cosmopolitan cities. We conducted a respondent-driven sampling survey (N = 428) to measure HIV seroprevalence and risk behavior among MSM in Jinan, China, the provincial capital of Shandong. HIV prevalence was 0.5% (95% confidence interval [CI] 0.1-1.0). Unprotected anal intercourse (UAI) in the last 6 months (reported by 61.4%) was associated with buying or selling sex to a man in the last 6 months, syphilis infection, multiple partners in the last month, low HIV knowledge and migrant status. No participant had previously tested for HIV. Risk for HIV transmission is widespread among MSM throughout China; basic prevention programs are urgently needed.