Abstract
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 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,
< 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.
•To provide a quantified understanding of the proportion of asymptomatic individuals among cases with COVID-19 infection.•To describe the specific population that is asymptomatic.•Findings could help ...to develop prevention and control strategies for asymptomatic individuals.
The role of asymptomatic infections in the transmission of COVID-19 have drawn considerable attention. Here, we performed a meta-analysis to summarize the epidemiological and radiographical characteristics of asymptomatic infections associated with COVID-19.
Data on the epidemiological and radiographical characteristics of asymptomatic infections were extracted from the existing literature. Pooled proportions with 95% confidence intervals were then calculated using a random effects model.
A total of 104 studies involving 20,152 cases were included. The proportion of asymptomatic individuals among those with COVID-19 was 13.34% (10.86%–16.29%), among which presymptomatic and covert infections accounted for 7.64% (4.02%–14.04%) and 8.44% (5.12%–13.62%), respectively. The proportions of asymptomatic infections among infected children and healthcare workers were 32.24% (23.08%–42.13%) and 36.96% (18.51%–60.21%), respectively. The proportion of asymptomatic infections was significantly higher after 2020/02/29 than before (33.53% vs 10.19%) and in non-Asian regions than in Asia (28.76% vs 11.54%). The median viral shedding duration of asymptomatic infections was 14.14 days (11.25–17.04). A total of 47.62% (31.13%–72.87%) of asymptomatic infections showed lung abnormalities, especially ground-glass opacity (41.11% 19.7%–85.79%).
Asymptomatic infections were more commonly found in infected children and healthcare workers and increased after 2020/02/29 and in non-Asian regions. Chest radiographical imaging could be conducive to the early identification of asymptomatic infections.
•The global influenza vaccination rates (IVRs) were overall low, especially in the general population.•Compared to middle-income, IVRs were higher in high-income countries/regions.•Compared to the ...other period, IVRs increased during the COVID-19 pandemic.•Free vaccination policies was the positive factor for the higher IVR.
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.
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.
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).
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.
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.
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.
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.
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.
Long-term follow-up data indicates that 1/4 patients with acute kidney injury (AKI) will develop to chronic kidney disease (CKD). Our previous studies have demonstrated that enhancer of zeste homolog ...2 (EZH2) played an important role in AKI and CKD. However, the role and mechanisms of EZH2 in AKI-to-CKD transition are still unclear. Here, we demonstrated EZH2 and H3K27me3 highly upregulated in kidney from patients with ANCA-associated glomerulonephritis, and expressed positively with fibrotic lesion and negatively with renal function. Conditional EZH2 deletion or pharmacological inhibition with 3-DZNeP significantly improved renal function and attenuated pathological lesion in ischemia/reperfusion (I/R) or folic acid (FA) mice models (two models of AKI-to-CKD transition). Mechanistically, we used CUT & Tag technology to verify that EZH2 binding to the PTEN promoter and regulating its transcription, thus regulating its downstream signaling pathways. Genetic or pharmacological depletion of EZH2 upregulated PTEN expression and suppressed the phosphorylation of EGFR and its downstream signaling ERK1/2 and STAT3, consequently alleviating the partial epithelial-mesenchymal transition (EMT), G2/M arrest, and the aberrant secretion of profibrogenic and proinflammatory factors in vivo and vitro experiments. In addition, EZH2 promoted the EMT program induced loss of renal tubular epithelial cell transporters (OAT1, ATPase, and AQP1), and blockade of EZH2 prevented it. We further co-cultured macrophages with the medium of human renal tubular epithelial cells treated with H
O
and found macrophages transferred to M2 phenotype, and EZH2 could regulate M2 macrophage polarization through STAT6 and PI3K/AKT pathways. These results were further verified in two mice models. Thus, targeted inhibition of EZH2 might be a novel therapy for ameliorating renal fibrosis after acute kidney injury by counteracting partial EMT and blockade of M2 macrophage polarization.
Previous studies have reported that temperature is the main meteorological factor associated with influenza activity. This study used generalized additive models (GAMs) to explore the relationship ...between temperature and influenza activity in China. From the national perspective, the average temperature (AT) had an approximately negative linear correlation with the incidence of influenza, as well as a positive rate of influenza H1N1 virus (A/H1N1). Every degree that the monthly AT rose, the influenza cases decreased by 2.49% (95%CI: 1.24%–3.72%). The risk of influenza cases reached a peak at −5.35 °C with RRs of 2.14 (95%CI: 1.38–3.33) and the monthly AT in the range of −5.35 °C to 18.31 °C had significant effects on the incidence of influenza. Every degree that the weekly AT rose, the positive rate of A/H1N1 decreased by 5.28% (95%CI: 0.35%–9.96%). The risk of A/H1N1 reached a peak at −3.14 °C with RRs of 4.88 (95%CI: 1.01–23.75) and the weekly AT in the range of −3.14 °C to 17.25 °C had significant effects on the incidence of influenza. Our study found that AT is negatively associated with influenza activity, especially for A/H1N1. These findings indicate that temperature could be integrated into the current influenza surveillance system to develop early warning systems to better predict and prepare for the risks of influenza.
Although coinfection with influenza in COVID-19 patients has drawn considerable attention, it is still not completely understood whether simultaneously infected with these two viruses influences ...disease severity. We therefore aimed to estimate the impact of coinfected with SARS-CoV-2 and influenza on the disease outcomes compared with the single infection of SARS-CoV-2.
We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI) to identify relevant articles up to July 9, 2021. Studies that assessed the effect of SARS-CoV-2 and influenza coinfection on disease outcomes or those with sufficient data to calculate risk factors were included. Risk effects were pooled using fixed or random effects model.
We ultimately identified 12 studies with 9,498 patients to evaluate the risk effects of SARS-CoV-2 and influenza coinfection on disease severity. Results indicated that coinfection was not significantly associated with mortality (OR = 0.85, 95%CI: 0.51, 1.43;
= 0.55,
= 76.00%). However, mortality was found significantly decreased in the studies from China (OR = 0.51, 95%CI: 0.39, 0.68;
= 26.50%), while significantly increased outside China (OR = 1.56, 95%CI: 1.12, 2.19;
= 1.00%). Moreover, a lower risk for critical outcomes was detected among coinfection patients (OR = 0.64, 95%CI: 0.43, 0.97;
= 0.04,
= 0.00%). Additionally, coinfection patients presented different laboratory indexes compared with the single SARS-CoV-2 infection, including lymphocyte counts and APTT.
Our study revealed that coinfection with SARS-CoV-2 and influenza had no effect on overall mortality. However, risk for critical outcomes was lower in coinfection patients and different associations were detected in the studies from different regions and specific laboratory indexes. Further studies on influenza strains and the order of infection were warranted. Systematic testing for influenza coinfection in COVID-19 patients and influenza vaccination should be recommended.
Peritoneal dialysis (PD) is an effective replacement therapy for end-stage renal disease patients. However, long-term exposure to peritoneal dialysate will lead to the development of peritoneal ...fibrosis. Epigenetics has been shown to play an important role in peritoneal fibrosis, but the role of histone deacetylases 8 (HDAC8) in peritoneal fibrosis have not been elucidated. In this research, we focused on the role and mechanisms of HDAC8 in peritoneal fibrosis and discussed the mechanisms involved.
We examined the expression of HDAC8 in the peritoneum and dialysis effluent of continuous PD patients. Then we assessed the role and mechanism of HDAC8 in peritoneal fibrosis progression in mouse model of peritoneal fibrosis induced by high glucose peritoneal dialysis fluid by using PCI-34051. In vitro, TGF-β1 or IL-4 were used to stimulate human peritoneal mesothelial cells (HPMCs) or RAW264.7 cells to establish two cell injury models to further explore the role and mechanism of HDAC8 in epithelial-mesenchymal transition (EMT) and macrophage polarization.
We found that HDAC8 expressed highly in the peritoneum from patients with PD-related peritonitis. We further revealed that the level of HDAC8 in the dialysate increased over time, and HDAC8 was positively correlated with TGF-β1 and vascular endothelial growth factor (VEGF), and negatively correlated with cancer antigen 125. In mouse model of peritoneal fibrosis induced by high glucose dialysate, administration of PCI-34051 (a selective HDAC8 inhibitor) significantly prevented the progression of peritoneal fibrosis. Treatment with PCI-34051 blocked the phosphorylation of epidermal growth factor receptor (EGFR) and the activation of its downstream signaling pathways ERK1/2 and STAT3/HIF-1α. Inhibition of HDAC8 also reduced apoptosis. In vitro, HDAC8 silencing with PCI-34051 or siRNA inhibited TGF-β1-induced EMT and apoptosis in HPMCs. In addition, continuous high glucose dialysate or IL-4 stimulation induced M2 macrophage polarization. Blockade of HDAC8 reduced M2 macrophage polarization by inhibiting the activation of STAT6 and PI3K/Akt signaling pathways.
We demonstrated that HDAC8 promoted the EMT of HPMCs via EGFR/ERK1/2/STAT3/HIF-1α, induced M2 macrophage polarization via STAT6 and PI3K/Akt signaling pathways, and ultimately accelerated the process of peritoneal fibrosis.
•Global influenza virus circulation was characterized by seven influenza transmission zones (ITZs).•Influenza surveillance should be enhanced in Africa and Southern-America ITZs.•More attention ...should be given to Eastern & Southern-Asia and Africa ITZs.
This study aimed to investigate region-specific epidemiologic characteristics of influenza and influenza transmission zones (ITZs).
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.
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).
Global influenza virus circulation was significantly characterized by seven ITZs that could be applied to influenza surveillance and warning.
PDF
