An outbreak of hepatitis E virus genotype 4d caused by consuming undercooked pig liver in a nursing home in Zhejiang Province, China.

Hepatitis E infection is typically caused by contaminated water or food. In July and August 2022, an outbreak of hepatitis E was reported in a nursing home in Zhejiang Province, China. Local authorities and workers took immediate actions to confirm the outbreak, investigated the sources of infection and routes of transmission, took measures to terminate the outbreak, and summarized the lessons learned. An epidemiological investigation was conducted on all individuals in the nursing home, including demographic information, clinical symptoms, history of dietary, water intake and contact. Stool and blood samples were collected from these populations for laboratory examinations. The hygiene environment of the nursing home was also investigated. A case-control study was conducted to identify the risk factors for this outbreak. Of the 722 subjects in the nursing home, 77 were diagnosed with hepatitis E, for an attack rate of 10.66 %. Among them, 18 (23.38 %, 18/77) individuals had symptoms such as jaundice, fever, and loss of appetite and were defined as the population with hepatitis E. The average age of people infected with hepatitis E virus (HEV) was 59.96 years and the attack rate of hepatitis E among women (12.02 %, 59/491) was greater than that among men (7.79 %, 18/231). The rate was the highest among caregivers (22.22 %, 32/144) and lowest among logistics personnel (6.25 %, 2/32); however, these differences were not statistically significant (P > 0.05). Laboratory sequencing results indicated that the genotype of this hepatitis E outbreak was 4d. A case-control study showed that consuming pig liver (odds ratio (OR) = 7.50; 95 % confidence interval [CI]: 3.84-16.14, P < 0.001) and consuming raw fruits and vegetables (OR = 5.92; 95 % CI: 1.74-37.13, P = 0.017) were risk factors for this outbreak of Hepatitis E. Moreover, a monitoring video showed that the canteen personnel did not separate raw and cooked foods, and pig livers were cooked for only 2 min and 10 s. Approximately 1 month after the outbreak, an emergency vaccination for HEV was administered. No new cases were reported after two long incubation periods (approximately 4 months). The outbreak of HEV genotype 4d was likely caused by consuming undercooked pig liver, resulting in an attack rate of 10.66 %. This was related to the rapid stir-frying cooking method and the hygiene habit of not separating raw and cooked foods.

Intensity and drivers of subtypes interference between seasonal influenza viruses in mainland China: A modeling study.

Subtype interference has a significant impact on the epidemiological patterns of seasonal influenza viruses (SIVs). We used attributable risk percent [the absolute value of the ratio of the effective reproduction number (Rₑ) of different subtypes minus one] to quantify interference intensity between A/H1N1 and A/H3N2, as well as B/Victoria and B/Yamagata. The interference intensity between A/H1N1 and A/H3N2 was higher in southern China 0.26 (IQR: 0.11-0.46) than in northern China 0.17 (IQR: 0.07-0.24). Similarly, interference intensity between B/Victoria and B/Yamagata was also higher in southern China 0.14 (IQR: 0.07-0.24) than in norther China 0.10 (IQR: 0.04-0.18). High relative humidity significantly increased subtype interference, with the highest relative risk reaching 20.59 (95% CI: 6.12-69.33) in southern China. Southern China exhibited higher levels of subtype interference, particularly between A/H1N1 and A/H3N2. Higher relative humidity has a more pronounced promoting effect on subtype interference.

An anoikis-related lncRNA signature is a useful tool for predicting the prognosis of patients with lung adenocarcinoma.

Background: Anoikis-related long non-coding RNAs (ARLs) play a critical role in tumor metastasis and progression, suggesting that they may serve as risk markers for cancer. This study aimed to investigate the prognostic value of ARLs in patients with lung adenocarcinoma (LUAD). Methods: Clinical data, RNA sequencing (RNA-seq) data, and mutation data from the LUAD project were obtained from The Cancer Genome Atlas (TCGA) database. The Molecular Signatures Database (MSigDB) and the GeneCard database were used to collect an anoikis-related gene (ARG) set. Pearson correlation analysis was performed to identify ARLs. LASSO and Cox regression were then used to establish a prognostic risk signature for ARLs. The median risk score served as the basis for categorizing patients into high and low-risk groups. Kaplan-Meier analysis was utilized to compare the prognosis between these two groups. The study also examined the associations between risk scores and prognosis, clinicopathological characteristics, immune status, tumor mutation burden (TMB), and chemotherapeutic agents. LncRNA expression was assessed using quantitative real-time PCR (qRT-PCR). Results: A total of 480 RNA expression profiles, 501 ARGs, and 2698 ARLs were obtained from the database. A prognostic ARL signature for LUAD was established, consisting of 9 lncRNAs. Patients in the low-risk group exhibited significantly better prognosis compared to those in the high-risk group (P < 0.001). The 9 lncRNAs from the ARL signature were identified as independent prognostic factors (P < 0.001). The signature demonstrated high accuracy in predicting LUAD prognosis, with area under the curve values exceeding 0.7. The risk scores for ARLs showed strong negative correlations with stroma score (P = 5.9E-07, R = -0.23), immune score (P = 9.7E-09, R = -0.26), and microenvironment score (P = 8E-11, R = -0.29). Additionally, the low-risk group exhibited significantly higher TMB compared to the high-risk group (P = 4.6E-05). High-risk status was significantly associated with lower half-maximal inhibitory concentrations for most chemotherapeutic drugs. Conclusion: This newly constructed signature based on nine ARLs is a useful instrument for the risk stratification of LUAD patients. The signature has potential clinical significance for predicting the prognosis of LUAD patients and guiding personalized immunotherapy.

Characteristics of circulating immune cells in HBV-related acute-on-chronic liver failure following artificial liver treatment.

BACKGROUND AND AIM: Liver failure, which is predominantly caused by hepatitis B (HBV) can be improved by an artificial liver support system (ALSS). This study investigated the phenotypic heterogeneity of immunocytes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) before and after ALSS therapy. METHODS: A total of 22 patients with HBV-ACLF who received ALSS therapy were included in the study. Patients with Grade I according to the ACLF Research Consortium score were considered to have improved. Demographic and laboratory data were collected and analyzed during hospitalization. Immunological features of peripheral blood in the patients before and after ALSS were detected by mass cytometry analyses. RESULTS: In total, 12 patients improved and 10 patients did not. According to the immunological features data after ALSS, the proportion of circulating monocytes was significantly higher in non-improved patients, but there were fewer γδT cells compared with those in improved patients. Characterization of 37 cell clusters revealed that the frequency of effector CD8+ T (P = 0.003), CD4+ TCM (P = 0.033), CD4+ TEM (P = 0.039), and inhibitory natural killer (NK) cells (P = 0.029) decreased in HBV-ACLF patients after ALSS therapy. Sub group analyses after treatment showed that the improved patients had higher proportions of CD4+ TCM (P = 0.010), CD4+ TEM (P = 0.021), and γδT cells (P = 0.003) and a lower proportion of monocytes (P = 0.012) compared with the non-improved patients. CONCLUSIONS: Changes in effector CD8+ T cells, effector and memory CD4+ T cells, and inhibitory NK cells are associated with ALSS treatment of HBV-ACLF. Moreover, monocytes and γδT cells exhibited the main differences when patients obtained different prognoses. The phenotypic heterogeneity of lymphocytes and monocytes may contribute to the prognosis of ALSS and future immunotherapy strategies.

Prevalence of hepatitis E virus in China from 1997 to 2022: a systematic review and meta-analysis.

Introduction: Several studies have reported on hepatitis E virus (HEV) prevalence in various regions of China, but the results vary widely. Herein, we conducted a systematic review and meta-analysis to assess the seroprevalence, RNA-positive rate, genotype distribution of HEV in China, and its risk factors. Methods: We included 208 related studies involving 1,785,569 participants published between 1997 and 2022. Random-effects models were used to pool prevalence, and subgroup analyses were conducted by population, gender, age, study period, regions, and rural-urban distribution. The meta regression models and pooled odds ratios (OR) were performed to identify risk factors for HEV infections. Results: The pooled anti-HEV IgG, IgM, and Ag seroprevalence, and RNA detection rates in China from 1997 to 2022 were 23.17% [95% confidence interval (CI): 20.23-26.25], 0.73% (95% CI: 0.55-0.93), 0.12% (95% CI: 0.01-0.32), and 6.55% (95% CI: 3.46-12.05), respectively. The anti-HEV IgG seropositivity was higher in the occupational population (48.41%; 95% CI: 40.02-56.85) and older adult aged 50-59 years (40.87%; 95% CI: 31.95-50.11). The dominant genotype (GT) of hepatitis E in China was GT4. Notably, drinking non-tap water (OR = 1.82; 95% CI: 1.50-2.20), consumption of raw or undercooked meat (OR = 1.47; 95% CI: 1.17-1.84), and ethnic minorities (OR = 1.50; 95% CI: 1.29-1.73) were risk factors of anti-HEV IgG seroprevalence. Discussions: Overall, the prevalence of hepatitis E was relatively high in China, especially among older adults, ethnic minorities, and humans with occupational exposure to pigs. Thus, there is a need for preventive measures, including HEV infection screening and surveillance, health education, and hepatitis E vaccine intervention in high-risk areas and populations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023397036.

Appraisal of evidence reliability and applicability of Paxlovid as treatment for SARS-COV-2 infection: A systematic review.

This study aimed to clarify the beneficial effect and the clinical application value of Paxlovid in the treatment of coronavirus disease-19 (COVID-19) through a systematic review. Databases including PubMed, Cochrane Library, Chinese Clinical Trial Registry, and ClinicalTrials.gov were systematically searched for interventional or observational studies on the efficacy and safety of Paxlovid in the treatment of SARS-COV-2. The relative and absolute effect sizes for the outcomes were calculated based on the data reported in the original intervention literature. The external applicability of the evidence was analysed in terms of clinical application scenarios, patient willingness, and cost utility. One interventional and three observational studies were conducted. Four studies published in 2022, had participation sample sizes ranging 1780-109,254. Based on the randomised controlled trial data, the risk of all-cause mortality, all-cause death, and hospitalisation was significantly reduced in the Paxlovid group. Serious adverse events were reduced during the study. Based on observational studies, Paxlovid can significantly reduce the risk of death and hospitalisation in older patients with COVID-19 (moderate certainty) and improve in-hospital disease progression, composite disease progression, and viral load (low certainty). Paxlovid did not improve the outcomes of death and hospitalisation (low certainty) in patients aged <65 years. As per the economic utility analysis, the economic cost of reducing one death dramatically decreased with increasing age. Early use of Paxlovid in the older adult population with COVID-19 is beneficial. However, in the setting of limited resources, Paxlovid should be prioritised for older patients.

Global burden and trends of respiratory syncytial virus infection across different age groups from 1990 to 2019: A systematic analysis of the Global Burden of Disease 2019 Study.

OBJECTIVE: Understanding the global patterns of respiratory syncytial virus (RSV) is crucial for developing effective prevention and control strategies. METHODS: Data on RSV-related burden were extracted from the Global Burden of Disease 2019. Joinpoint regression models were used to assess the global temporal trends of RSV and further stratified analyses were conducted according to the Socio-demographic Index (SDI), which is a composite measure of income, education, and total fertility. Age-period-cohort model was used to evaluate age, period, and cohort effects. RESULTS: In 2019, the global age-standardized rate of mortality (ASMR) and disability-adjusted life years (ASR-DALYs) of RSV were 4.79/100,000 (95% uncertainty interval [95% UI]: 1.82/100,000-9.32/100,000) and 218.34/100,000 (95% UI: 92.06/100,000-376.80/100,000), respectively. The burden of RSV was higher in men than women. The highest ASMR (10.26/100,000, 3.80/100,000-20.16/100,000) and ASR-DALYs (478.71/100,000, 202.40/100,000-840.85/100,000) were reported in low-SDI region. Although mortality and DALYs rates in all age groups declined globally, the pace of decline was not uniform across age groups. Mortality rate in the elderly over 70 years surpassed that in children under 5 years in 2019. CONCLUSION: This study highlights the need for targeted interventions to reduce the burden of RSV, particularly in low-SDI region, and among the elderly over 70 years.

Quantifying the rebound of influenza epidemics after the adjustment of zero-COVID policy in China.

The coexistence of coronavirus disease 2019 (COVID-19) and seasonal influenza epidemics has become a potential threat to human health, particularly in China in the oncoming season. However, with the relaxation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic, the rebound extent of the influenza activities is still poorly understood. In this study, we constructed a susceptible-vaccinated-infectious-recovered-susceptible (SVIRS) model to simulate influenza transmission and calibrated it using influenza surveillance data from 2018 to 2022. We projected the influenza transmission over the next 3 years using the SVIRS model. We observed that, in epidemiological year 2021-2022, the reproduction numbers of influenza in southern and northern China were reduced by 64.0 and 34.5%, respectively, compared with those before the pandemic. The percentage of people susceptible to influenza virus increased by 138.6 and 57.3% in southern and northern China by October 1, 2022, respectively. After relaxing NPIs, the potential accumulation of susceptibility to influenza infection may lead to a large-scale influenza outbreak in the year 2022-2023, the scale of which may be affected by the intensity of the NPIs. And later relaxation of NPIs in the year 2023 would not lead to much larger rebound of influenza activities in the year 2023-2024. To control the influenza epidemic to the prepandemic level after relaxing NPIs, the influenza vaccination rates in southern and northern China should increase to 53.8 and 33.8%, respectively. Vaccination for influenza should be advocated to reduce the potential reemergence of the influenza epidemic in the next few years.

The global region-specific epidemiologic characteristics of influenza: World Health Organization FluNet data from 1996 to 2021.

OBJECTIVES: This study aimed to investigate region-specific epidemiologic characteristics of influenza and influenza transmission zones (ITZs). METHODS: Weekly influenza surveillance data of 156 countries from 1996 to 2021 were obtained using FluNet. Joinpoint regression was used to describe global influenza virus trends, and clustering analyses were used to classify the ITZs. RESULTS: The global median average positive rate for total influenza virus was 16.19% (interquartile range: 11.62-25.70%). Overall, three major subtypes (influenza H1, H3, and B viruses) showed alternating epidemics. Notably, the proportion of influenza B viruses increased significantly from July 2020 to June 2021, reaching 62.66%. The primary peaks of influenza virus circulation in the north were earlier than those in the south. Global influenza virus circulation was significantly characterized by seven ITZs, including "Northern America" (primary peak: week 10), "Eastern & Southern-Asia" (primary peak: week 10), "Europe" (primary peak: week 11), "Asia-Europe" (primary peak: week 12), "Southern-America" (primary peak: week 30), "Oceania-Melanesia-Polynesia" (primary peak: week 39), and "Africa" (primary peak: week 46). CONCLUSION: Global influenza virus circulation was significantly characterized by seven ITZs that could be applied to influenza surveillance and warning.

Indoor relative humidity shapes influenza seasonality in temperate and subtropical climates in China.

OBJECTIVES: The aim of this study was to explore whether indoor or outdoor relative humidity (RH) modulates the influenza epidemic transmission in temperate and subtropical climates. METHODS: In this study, the daily temperature and RH in 1558 households from March 2017 to January 2019 in five cities across both temperate and subtropical regions in China were collected. City-level outdoor temperature and RH from 2013 to 2019 were collected from the weather stations. We first estimated the effective reproduction number (Rt) of influenza and then used time-series analyses to explore the relationship between indoor/outdoor RH/absolute humidity and the Rt of influenza. Furthermore, we expanded the measured 1-year indoor temperature and the RH data into 5 years and used the same method to examine the relationship between indoor/outdoor RH and the Rt of influenza. RESULTS: Indoor RH displayed a seasonal pattern, with highs during the summer months and lows during the winter months, whereas outdoor RH fluctuated with no consistent pattern in subtropical regions. The Rt of influenza followed a U-shaped relationship with indoor RH in both temperate and subtropical regions, whereas a U-shaped relationship was not observed between outdoor RH and Rt. In addition, indoor RH may be a better indicator for Rt of influenza than indoor absolute humidity. CONCLUSION: The findings indicated that indoor RH may be the driver of influenza seasonality in both temperate and subtropical locations in China.

Acceptance of the Human Papillomavirus Vaccine among General Men and Men with a Same-Sex Orientation and Its Influencing Factors: A Systematic Review and Meta-Analysis.

The human papillomavirus (HPV) vaccine reduces the prevalence of genital warts and the cancers they are associated with in males. However, the vaccination of males has always been neglected. Here, we performed a meta-analysis to comprehend the acceptability of the HPV vaccine in men and the factors impacting vaccination intentions. We searched PubMed, Web of Science, Embase, Ovid, CNKI, and Wan Fang up to 5 July 2023 for studies that reported HPV vaccine acceptance among men. A random effects model was used to obtain the pooled acceptance rate, and subgroup analysis was performed. Then, the influencing factors of HPV vaccination in males were analyzed. A total of 57 studies with 32,962 samples were included in the analysis. The overall acceptance rate of the HPV vaccine in general men was 47.04% (95% confidence interval [95%CI]: 39.23-54.93%), and 62.23% (95% CI: 52.93-71.10%) among those whose sexual orientation contained men. HPV vaccine acceptance rates differed significantly between the two populations (p = 0.01). The population with a medical background (46.23%, 95% CI: 40.28-52.24%) was more willing to be vaccinated. In comparison to the employed population (66.93%, 95% CI: 48.79-82.81%) and the unemployed (68.44%, 95% CI: 52.82-82.23%), vaccination acceptance rates were lower among students (47.35%, 95% CI: 37.00-57.81%) (p = 0.04). The most significant barriers to vaccination were perceived low risk of infection for themselves (45.91%, 95% CI: 31.73-60.43%), followed by vaccine cost (43.46%, 95% CI: 31.20-56.13%). Moreover, the recommendations from medical professionals (60.90%, 95%CI: 44.23-76.37%) and sexual partners (60.09%, 95%CI: 27.11-88.67%) were significant factors in promoting vaccination. Overall, acceptance of the HPV vaccine among general men was at a lower level, despite being slightly higher among men with a same-sex orientation. Popularizing knowledge about diseases and vaccines, encouraging medical professionals to recommend vaccines to men, or reducing the cost of vaccines may promote HPV vaccination.

Global influenza vaccination rates and factors associated with influenza vaccination.

OBJECTIVES: Influenza vaccination is an effective method for preventing influenza virus infection. Herein, we performed a meta-analysis to quantify global influenza vaccination rates (IVRs) and the factors influencing its uptake in the general population, individuals with chronic diseases, pregnant women, and healthcare workers. METHODS: Related articles were obtained from online databases and screened according to the inclusion criteria. The pooled IVRs were calculated using the random effects model. Subgroup analyses and multivariate meta-regression were performed to determine the factors associated with influenza vaccine uptake. RESULTS: We included 522 studies from 68 countries/regions. Most studies were conducted in the European region (247 studies), followed by the Western Pacific (135 studies) and American regions (100 studies). The IVRs with 95% confidence intervals (CIs) in the general population were lower (24.96%, 23.45%-26.50%) than in individuals with chronic diseases (41.65%, 40.08%-43.23%), healthcare workers (36.57%, 33.74%-39.44%), and pregnant women (25.92%, 23.18%-28.75%). The IVRs in high-income countries/regions were significantly higher than that in middle-income countries/regions. A free national or regional vaccination policy, perception of influenza vaccine efficacy and disease severity, a recommendation from healthcare workers, and having a history of influenza vaccination were positive factors for vaccine uptake (P <0.01). CONCLUSION: Overall, global IVRs were low, especially in the general population. The studies on the IVRs, especially for priority populations, should be strengthened in Eastern Mediterranean, South-East Asian, and African regions. Free vaccination policies and the dissemination of continuous awareness campaigns are effective measures to enhance vaccination uptake.

Global burden and trends of rotavirus infection-associated deaths from 1990 to 2019: an observational trend study.

BACKGROUND: Rotavirus is the leading global pathogen of diarrhea-associated mortality and poses a great threat to public health in all age groups. This study aimed to explore the global burden and 30-year change patterns of rotavirus infection-associated deaths. METHODS: Based on the Global Burden of Disease 2019 Study (GBD 2019), we analyzed the age-standardized death rate (ASDR) of rotavirus infection by sex, geographical region, and sociodemographic index (SDI) from 1990 to 2019. A Joinpoint regression model was used to analyze the global trends in rotavirus infection over the 30 years, SaTScan software was used to detect the spatial and temporal aggregations, and a generalized linear model to explore the relationship between sociodemographic factors and death rates of rotavirus infection. RESULTS: Globally, rotavirus infection was the leading cause of diarrheal deaths, accounting for 19.11% of deaths from diarrhea in 2019. Rotavirus caused a higher death burden in African, Oceanian, and South Asian countries in the past three decades. The ASDR of rotavirus declined from 11.39 (95% uncertainty interval [95% UI] 5.46-19.48) per 100,000 people in 1990 to 3.41 (95% UI 1.60-6.01) per 100,000 people in 2019, with an average annual percentage change (AAPC) (- 4.07%, P < 0.05). However, a significant uptrend was found in high-income North America (AAPC = 1.79%, P < 0.05). The death rate was the highest among children under 5 years worldwide. However, the death rates of elderly individuals over 70 years were higher than those of children under 5 years in 2019 among high, high-middle, middle, and low-middle SDI regions. Current health expenditure, gross domestic product per capita, and the number of physicians per 1000 people were significantly negatively correlated with death rates of rotavirus. CONCLUSIONS: Although the global trends in the rotavirus burden have decreased substantially over the past three decades, the burden of rotavirus remained high in Africa, Oceania, and South Asia. Children under 5 years and elderly individuals over 70 years were the populations most at risk for rotavirus infection-associated deaths, especially elderly individuals over 70 years in relatively high SDI regions. More attention should be paid to these areas and populations, and effective public health policies should be implemented in the future.

Meteorological Factors Affecting Infectious Diarrhea in Different Climate Zones of China.

Meteorological factors and the increase in extreme weather events are closely related to the incidence rate of infectious diarrhea. However, few studies have explored whether the impact of the same meteorological factors on the incidence rate of infectious diarrhea in different climate regions has changed and quantified these changes. In this study, the time series fixed-effect Poisson regression model guided by climate was used to quantify the relationships between the incidence rate of various types of infectious diarrhea and meteorological factors in different climate regions of China from 2004 to 2018, with a lag of 0-2 months. In addition, six social factors, including per capita Gross Domestic Product (GDP), population density, number of doctors per 1000 people, proportion of urbanized population, proportion of children aged 0-14 years old, and proportion of elderly over 65 years old, were included in the model for confounding control. Additionally, the intercept of each province in each model was analyzed by a meta-analysis. Four climate regions were considered in this study: tropical monsoon areas, subtropical monsoon areas, temperate areas and alpine plateau areas. The results indicate that the influence of meteorological factors and extreme weather in different climate regions on diverse infectious diarrhea types is distinct. In general, temperature was positively correlated with all infectious diarrhea cases (0.2 ≤ r ≤ 0.6, p < 0.05). After extreme rainfall, the incidence rate of dysentery in alpine plateau area in one month would be reduced by 18.7% (95% confidence interval (CI): -27.8--9.6%). Two months after the period of extreme sunshine duration happened, the incidence of dysentery in the alpine plateau area would increase by 21.9% (95% CI: 15.4-28.4%) in that month, and the incidence rate of typhoid and paratyphoid in the temperate region would increase by 17.2% (95% CI: 15.5-18.9%) in that month. The meta-analysis showed that there is no consistency between different provinces in the same climate region. Our study indicated that meteorological factors and extreme weather in different climate areas had different effects on various types of infectious diarrhea, particularly extreme rainfall and extreme sunshine duration, which will help the government develop disease-specific and location-specific interventions, especially after the occurrence of extreme weather.

Global Burden and Trends of Norovirus-Associated Diseases From 1990 to 2019: An Observational Trend Study.

Introduction: As an important pathogen causing diarrheal diseases, the burden and change in the death rate of norovirus-associated diseases (NADs) globally are still unknown. Methods: Based on global disease burden data from 1990 to 2019, we analyzed the age-standardized death rate (ASDR) of NADs by age, region, country, and Socio-Demographic Index (SDI) level. The discrete Poisson model was applied in the analysis of NADs' spatiotemporal aggregation, the Joinpoint regression model to analyze the trend of death burden of NADs over 30 years, and a generalized linear model to identify the risk factors for the death rate from NADs. Results: The ASDR of NADs significantly decreased by a factor of approximately 2.7 times, from 5.02 (95% CI: 1.1, 11.34) in 1990 to 1.86 (95% CI: 0.36, 4.16) in 2019 [average annual percent change (AAPC) = -3.43, 95% CI: -3.56, -3.29]. The death burden of NADs in 2019 was still highest in African regions despite a great decline in recent decades. However, the ASDR in high SDI countries presented an uptrend [0.12 (95% CI: 0.03, 0.26) in 1990 and 0.24 (95% CI: 0.03, 0.53) in 2019, AAPC = 2.52, 95% CI: 2.02-3.03], mainly observed in the elderly over 70 years old. Compared to children under 5 years old, the 2019 death rate of elderly individuals over 80 years old was much higher in high SDI countries. The generalized linear model showed that factors of the number of physicians (RR = 0.67), the proportions of children under 14 years old (RR = 1.21), elderly individuals over 65 years old (RR = 1.13), educational level (RR = 1.03) and urbanization proportion (RR = 1.01) influenced the ASDR of NADs. Conclusions: The death burden of NADs has remained high in developing regions over the last three decades and has increased among the elderly in countries with high SDI levels, even though the global trend in NAD-associated deaths has decreased significantly in the past three decades. More effective public health policies against NADs need to be implemented in high SDI regions and for the elderly.

Prevalence trends of latent tuberculosis infection at the global, regional, and country levels from 1990-2019.

OBJECTIVES: To track the prevalence trends of latent tuberculosis infection (LTBI) at the global, regional, and national levels. METHODS: Data on the prevalence of LTBI were extracted from the Global Burden of Disease database. The average annual percent change (AAPC) was estimated by joinpoint regression and was used to evaluate the epidemic of the disease. RESULTS: Globally, the prevalence rate of LTBI decreased from 30.66% in 1990 to 23.67% in 2019, with an AAPC of -0.9%. The prevalence rate of LTBI varied from 5.02% (Jordan) to 48.35% (Uganda) in 1990 and from 2.51% (Jordan) to 43.75% (Vietnam) in 2019 at the country level. The prevalence decreased in all the six World Health Organization (WHO) regions and in most countries, with the AAPC ranging from -0.5% in the Western Pacific Region to -2.1% in the European Region and from -4.3% (Bhutan) to -0.1% (Malaysia, Myanmar, South Africa, Tokelau, and Vietnam), respectively. Disparities were also observed among different sex and age groups. CONCLUSION: The prevalence of LTBI decreased slightly worldwide in the last three decades, but the decrease is slow and not sufficient to meet the targets of WHO tuberculosis elimination. Much more effort and progress should be made in order to decrease the prevalence of LTBI.

Exhausted phenotype of circulating CD8+ T cell subsets in hepatitis B virus carriers.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is characterized by the presence of dysfunctional exhausted CD8+ T cells that hamper viral control. We investigated the phenotypic heterogeneity of exhausted CD8+ T cells in HBV carriers. METHODS: We enrolled 31 HBV carriers and 23 healthy controls (HCs) in our study. Peripheral blood mononuclear cells (PBMCs) were isolated, and flow cytometry was used to determine the phenotypic distribution of CD8+ T cell subsets. Expression of cytokines such as TNF-α and IFN-γ was detected by quantitative reverse transcription-PCR, a fluorescence flow cytometry-based immunomicrobead assay and flow cytometry. RESULTS: There were no significant differences in the baseline characteristics between the 31 HBV carriers and the 23 sex- and age-matched HCs. CD8+ T cells exhibited higher levels of inhibitory receptors (TIM3 and PD1) in the HBV carriers than in the HCs (P < 0.05); in particular, Tfc cells (CXCR5+CD25-) expressed higher levels of TIM3 and PD1 than non-Tfc cells in the HBV carriers. In addition, among the subsets of Tc cells, the Tc17 (CXCR5-CD25-CCR6+) subset displayed increased expression of TIM3 and LAG3 in the HBV carriers. Our findings further showed that CD8+ T cells produced lower levels of IFN-γ, TNF-α, and Granzyme B. Paired analysis of the Tfc subset and the Tc subset indicated that higher levels of cytokines (IFN-γ and TNF-α) were produced by the Tfc subset in the HBV carriers. Among the Tc subsets, the Tc17 subset produced lower levels of cytokines. CONCLUSION: The Tfc subset exhibited an enhanced exhausted phenotype but possessed some functional properties during chronic HBV infection, while the Tc subset showed a lower functional level. The identification of these unique subsets may provide a potential immunotherapeutic target in chronic HBV infection.

Psychological stress; knowledge, attitude and practice and acceptance of antiviral therapy in pregnant women with hepatitis B in Zhejiang, China: a case comparison study.

OBJECTIVES: To determine knowledge, attitude and practice (KAP) and antiviral therapy's acceptance during pregnancy of pregnant women with hepatitis B and influencing factors. DESIGN: Case-comparison study. SETTING: The study was conducted in Zhejiang province, China, from September 2019 to December 2020. PARTICIPANTS: Pregnant and postpartum women with chronic hepatitis B. PRIMARY AND SECONDARY OUTCOME MEASURES: The stress scores, self-assessed health score, KAP, antiviral therapy's acceptance rate during pregnancy and influencing factors were analysed. The Perceived Stress Scale-10 was used to assess stress. Logistic regression was used to analyse influencing factors on antiviral therapy. RESULTS: The self-assessed health score of pregnant women without liver diseases (82.4±9.3) was significantly higher than that of pregnant women with chronic hepatitis B (75.5±9.5) and postpartum (75.1±14.1). Psychological stress of pregnant women with chronic hepatitis B was significantly high with a 14.9±3.6 score, but there was no significant difference between hepatitis B postpartum and non-liver disease women (12.7±3.5 vs 12.9±3.5, p=0.75). The acceptance rate of pregnant women with hepatitis B for antiviral therapy was 84.2%, while that of postpartum women was even higher. Logistic regression analysis showed that patients with positive hepatitis B e antigen (HBeAg) (OR, 3.35; 95% CI, 1.21 to 9.26) and higher scores on hepatitis B-related knowledge (OR, 3.52, 95% CI, 2.18 to 5.69) were more likely to accept antiviral therapy during pregnancy. CONCLUSIONS: Pregnant women with hepatitis B in Zhejiang have heavy psychological stress and a high antiviral therapy acceptance rate during pregnancy. Acceptance is related to HBeAg status and level of understanding of hepatitis B during pregnancy. It is necessary to provide education on hepatitis B to reduce psychological stress and increase acceptance of antiviral therapy during pregnancy.

Genetic Risk and Chronic Obstructive Pulmonary Disease Independently Predict the Risk of Incident Severe COVID-19.

Rationale: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods: We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results: Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P < 0.001) than those at low genetic risk and without COPD. Conclusions: The polygenic risk score, which combines multiple risk alleles, can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of preexisting COPD.

Global burden and trends of sexually transmitted infections from 1990 to 2019: an observational trend study.

BACKGROUND: Sexually transmitted infections (STIs) are a major public health issue worldwide, but there is a paucity of literature on their burden and trends globally. We aimed to assess the global disease burden and trends of STIs from 1990 to 2019. METHODS: In this observational trend study, we collected data on incident cases, age-standardised incidence rate, and disability-adjusted life-years (DALYs), and calculated age-standardised DALY rates, for five STIs (syphilis, chlamydia, gonorrhoea, trichomonas, and genital herpes) between 1990 and 2019, by sex, geographical region, and cause using data exclusively from the Global Burden of Disease study 2019. The estimated annual percentage changes in the age-standardised incidence rate and age-standardised DALY rate were calculated to quantify the changing trend. FINDINGS: Globally, the age-standardised incidence rate of STIs showed a decreasing trend with an estimated annual percentage change of -0·04 (95% uncertainty interval [UI] -0·08 to 0·00) from 1990 to 2019, reaching 9535·71 per 100 000 person-years (8169·73 to 11 054·76) in 2019. The age-standardised DALY rate showed a decreasing trend with an estimated annual percentage change of -0·92 (-1·01 to -0·84) and reached 22·74 per 100 000 person-years (14·37 to 37·11) in 2019. The sub-Saharan African region had the highest age-standardised incidence rate (19 973·12 per 100 000 person-years, 17 382·69 to 23 001·57) and age-standardised DALY rate (389·32 per 100 000 person-years, 154·27 to 769·74). Adolescents had the highest incidence rate (18 377·82 per 100 000 person-years, 14 040·38 to 23 443·31) and showed stable total STI trends, except for an upward trend of syphilis between 2010 (347·65 per 100 000 person-years, 203·58 to 590·69) and 2019 (423·16 per 100 000 person-years, 235·70 to 659·01). Male individuals had a higher age-standardised incidence rate (10 471·63 per 100 000 person-years, 8892·20 to 12 176·10) than female individuals (8602·40 per 100 000 person-years, 7358·00 to 10001·18), whereas female individuals had a higher age-standardised DALY rate (33·31 per 100 000 person-years, 21·05 to 55·25) than male individuals (12·11 per 100 000 person-years, 7·63 to 18·93). INTERPRETATION: Although most countries showed a decrease in age-standardised rates of incidence and DALYs for STIs, the absolute incident cases and DALYs increased from 1990 to 2019. Therefore, STIs still represent a global public health challenge, especially in sub-Saharan Africa and Latin America, which warrants more attention and health prevention service. FUNDING: Mega-Project of National Science and Technology for the 13th Five-Year Plan of China and the National Natural Science Foundation of China.