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Background: Bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) represent a significant disease burden worldwide. However, a comprehensive analysis of the mortality rates and global epidemiology across different ARB species associated with BSIs is currently lacking. Methods: We conducted a systematic review by searching multiple databases (PubMed, Web of Science, and Embase) for studies reporting ARB-related BSIs data up to June 19, 2023. Additionally, we performed genomic analyses of all the publicly available bacterial genomes associated with BSIs to elucidate their molecular characteristics. Results: A total of 322 articles (N = 90,672 patients) were included in this study. For 28 or 30-day mortality, the overall mortality rate for all ARB species was 32.0%. Among them, antibiotic-resistant A. baumannii exhibited the highest rate (54.2%). And the top three ARB types with the highest mortality rates at 28 or 30-day were CefeR-PA (cefepime-resistant P. aeruginosa), CREC (carbapenem-resistant E. coli), and CRAB (carbapenem-resistant A. baumannii), all exceeding 50%, whereas the mortality rates of CRKP (carbapenem-resistant K. pneumoniae), CRPA (carbapenem-resistant P. aeruginosa), and VREfm (vancomycin-resistant E. faecium) were at least 40%. A total of 9,289 ARB genomes related to BSIs were acquired from the NPDIB database and are predominantly distributed in North America, Asia, and Europe. Antibiotic resistance gene (ARG) analysis identified a total of 613 ARG subtypes from the top six ARB species, with numbers ranging from 48 for E. faecium to 253 for K. pneumoniae. Furthermore, specific clones of ARB species were strongly associated with BSIs, such as ST131 in E. coli, ST8, and ST5 in S. aureus, ST2 in A. baumannii, and ST11 and ST258 in K. pneumoniae. Conclusion: ARB contributed to the burden of BSIs, with a 30-day all-cause mortality rate as high as 32.0%. ARB strains causing BSIs display high genetic diversity, highlighting the importance of continuing to monitor high-risk clones to control the development of antibiotic resistance. Differences in ARGs patterns require tailored antibiotic management strategies for each ARB species. [ABSTRACT FROM AUTHOR]

Background: Vaccination is a highly effective strategy for the prevention of enterovirus A71 (EV-A71)—hand, foot, and mouth disease (HFMD). Three inactivated EV-A71 vaccines in China have demonstrated remarkable efficacy against EV-A71-HFMD during clinical trials, exhibiting vaccine effectiveness (VE) exceeding 90% and few adverse events (AEs). However, the effectiveness of vaccines in the real world and its impact on the epidemiological characteristics of HFMD after the use of EV-A71 inactivated vaccine are uncertain. Methods: The odd ratio (OR) and 95% confidence (CI) were used as the effect estimates of the meta-analysis in the test-negative design (TND), and the OR was used to calculate VE: VE = (1 − OR) × 100%. Results: According to the literature search strategy, a comprehensive search was conducted in PubMed, Web of Science (including Chinese Science Citation Database and MEDLINE), and Embase, and 18 records were ultimately included in this study. Subsequently, the overall VE and 95% CI of different vaccine doses were analyzed, with the one-dose vaccine at 66.9% (95% CI: 45.2–80.0%) and the two-dose vaccine at 84.2% (95% CI: 79.4–87.9%). Additionally, the most reported AEs were mild general reactions without any rare occurrences. Simultaneously, the widespread use of the EV-A71 vaccine would lead to a reduction in both the incidence of EV-A71-associated HFMD and severe cases caused by EV-A71. Conclusion: The administration of the two-dose EV-A71 vaccine is highly effective in preventing HFMD in the real world, and the widespread use of the EV-A71 vaccine leads to a reduction in the incidence of EV-A71-associated HFMD and that of severe cases caused by EV-A71. The findings suggest that administering the two-dose EV-A71 inactivated vaccine to children aged 6 months to 71 months can be effective in preventing EV-A71-associated HFMD, highlighting the need for developing a multivalent HFMD vaccine for preventing cases not caused by EV-A71. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) is an acute infectious illness primarily caused by enteroviruses. The present study aimed to describe the epidemiological characteristics of hospitalized HFMD patients in a hospital in Henan Province (Zhengzhou, China), and to predict the future epidemiological parameters. In this study, we conducted a retrospective analysis of general demographic and clinical data on hospitalized children who were diagnosed with HFMD from 2014 to 2023. We used wavelet analysis to determine the periodicity of the disease. We also conducted an analysis of the impact of the COVID‐19 epidemic on the detection ratio of severe illness. Additionally, we employed a Seasonal Difference Autoregressive Moving Average (SARIMA) model to forecast characteristics of future newly hospitalized HFMD children. A total of 19 487 HFMD cases were included in the dataset. Among these cases, 1515 (7.8%) were classified as severe. The peak incidence of HFMD typically fell between May and July, exhibiting pronounced seasonality. The emergence of COVID‐19 pandemic changed the ratio of severe illness. In addition, the best‐fitted seasonal ARIMA model was identified as (2,0,2)(1,0,1)12. The incidence of severe cases decreased significantly following the introduction of the vaccine to the market (χ2 = 109.9, p < 0.05). The number of hospitalized HFMD cases in Henan Province exhibited a seasonal and declining trend from 2014 to 2023. Non‐pharmacological interventions implemented during the COVID‐19 pandemic have led to a reduction in the incidence of severe illness. [ABSTRACT FROM AUTHOR]

In recent years, the emergence of blaOXA-encoding Escherichia coli (E. coli) poses a significant threat to human health. Here, we systematically analyzed the global geographic distribution and genetic characteristics of 328 blaOXA-positive E. coli plasmids based on NCBI database. Twelve blaOXA variants have been discovered, with blaOXA−1 (57.93%) being the most common, followed by blaOXA−10 (11.28%) and blaOXA−48 (10.67%). Our results suggested that blaOXA-positive E. coli plasmids were widespread in 40 countries, mainly in China, the United States, and Spain. MLST analysis showed that ST2, ST43, and ST471 were the top three host STs for blaOXA-positive plasmids, deserving continuing attention in future surveillance program. Network analysis revealed a correlation between different blaOXA variants and specific antibiotic resistance genes, such as blaOXA−1 and aac (6')-Ib-cr (95.79%), blaOXA−181 and qnrS1 (87.88%). The frequent detection of aminoglycosides-, carbapenems- and even colistin-related resistance genes in blaOXA-positive plasmids highlights their multidrug-resistant potential. Additionally, blaOXA-positive plasmids were further divided into eight clades, clade I-VIII. Each clade displayed specificity in replicon types and conjugative transfer elements. Different blaOXA variants were associated with specific plasmid lineages, such as blaOXA−1 and IncFII plasmids in clade II, and blaOXA−48 and IncL plasmids in clade I. Overall, our findings provide a comprehensive insight into blaOXA-positive plasmids in E. coli, highlighting the role of plasmids in blaOXA dissemination in E. coli. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is a major human pathogen and can cause a wide range of diseases, including pneumonia, osteomyelitis, skin and soft tissue infections (SSTIs), endocarditis, mastitis, bacteremia, and so forth. Rats have been widely used in the field of infectious diseases due to their unique advantages, and the models of S. aureus infections have played a pivotal role in elucidating their pathogenic mechanisms and the effectiveness of therapeutic agents. This review outlined the current application of rat models in S. aureus infections and future prospects for rat models in infectious diseases caused by S. aureus. [ABSTRACT FROM AUTHOR]

Coxsackievirus A6 (CVA6) is currently considered as a predominant pathogen of hand, foot, and mouth disease (HFMD), and is occasionally linked to myocardial injury. We first established a mouse model of CVA6-induced myocardial injury. Next, we analyzed the immune cell phenotypes CVA6-infected mice hearts by fluorescence-activated cell sorting, and found that CVA6 led to massive neutrophils infiltration, suggesting their potential link with the occurrence of myocardial injury. We further used either αGr-1 or αLy6G antibody to deplete neutrophils, and found that neutrophil-depleted animals showed decreased cardiac enzymes, lower degree of pathology in hearts, and reduced inflammatory cytokine production compared to isotype controls. Finally, we confirmed the involvement of neutrophils in myocardial injury of clinical patients with severe HFMD. Our study suggests that excessive neutrophils contribute to myocardial injury caused by CVA6 infection, which provides new insights into myocardial injury during the development of HFMD severity and the outcome of immune cell-mediated therapies. [ABSTRACT FROM AUTHOR]

Author(s): Li Shi [sup.1], Jie Xu [sup.1], Guangcai Duan [sup.1], Haiyan Yang [sup.1], Yadong Wang [sup.2] Author Affiliations: (1) grid.207374.5, 0000 0001 2189 3846, Department of Epidemiology, College of Public [...]

Tuberculosis (TB), which caused by Mycobacterium tuberculosis, is the leading cause of death from a single infectious agent and continues to be a major public health burden for the global community. Despite being the only globally licenced prophylactic vaccine, Bacillus Calmette-Guérin (BCG) has multiple deficiencies, and effective diagnostic and therapeutic options are limited. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is an adaptive immune system that is found in bacteria and has great potential for the development of novel antituberculosis drugs and vaccines. In addition, CRISPR-Cas is currently recognized as a prospective tool for the development of therapies for TB infection with potential diagnostic and therapeutic value, and CRISPR-Cas may become a viable tool for eliminating TB in the future. Herein, we systematically summarize the current applications of CRISPR–Cas-based technology for TB detection and its potential roles in drug discovery and vaccine development. [ABSTRACT FROM AUTHOR]

With the continuous evolution of the coronavirus, the Omicron variant has gradually replaced the Delta variant as the prevalent strain. Their inducing epidemics last longer, have a higher number of asymptomatic cases, and are more serious. In this article, we proposed a nonautonomous time-delayed susceptible-infected-removed (NATD-SIR) model to predict them in different regions of China. We obtained the maximum and its time of current infected persons, the final size, and the end time of COVID-19 epidemics from January 2022 in China. The method of the fifth-order moving average was used to preprocess the time series of the numbers of current infected and removed cases to obtain more accurate parameter estimations. We found that usually the transmission rate β (t) was a piecewise exponential decay function, but due to multiple bounces in Shanghai City, β (t) was approximately a piecewise quadratic function. In most regions, the removed rate γ (t) was approximately equal to a piecewise linear increasing function of (a*t+b)*H(t-k), but in a few areas, γ (t) displayed an exponential increasing trend. For cases where the removed rate cannot be obtained, we proposed a method for setting the removed rate, which has a good approximation. Using the numerical solution, we obtained the prediction results of the epidemics. By analyzing those important indicators of COVID-19, we provided valuable suggestions for epidemic prevention and control and the resumption of work and production. [ABSTRACT FROM AUTHOR]

The aim is to elucidate the relationship between sickle cell disorder and severe COVID‐19. We systematically searched the required articles in three electronic databases, extracting and pooling effect sizes (ES) and 95% confidence interval (CI) from each eligible study to evaluate the effect of combined sickle cell disorder on adverse consequences in patients with COVID‐19. This meta‐analysis included 21 studies. Sickle cell disease (SCD) was a risk factor for mortality (pooled ES = 1.70, 95% CI: 1.00–2.92, p = 0.001), hospitalization (pooled ES = 6.21, 95% CI: 3.60–10.70, p = 0.000) and intensive care unit (ICU) admission (pooled ES = 2.29, 95% CI: 1.61–3.24, p = 0.099) in COVID‐19 patients. Patients with SCD had an increased risk of respiratory failure/mechanical ventilation, but a statistical association was not found (pooled ES = 1.21, 95%CI: 0.74‐1.98, p = 0.036). There was significant heterogeneity between SCD and death, hospitalization, and respiratory failure/mechanical ventilation. The results of meta‐regression of SCD and hospitalization suggested that the tested variables including Area (p = 0.642), study design (p = 0.739), sample size (p = 0.397), proportion of males (p = 0.708), effect type (p = 0.723), whether confounding factors are adjusted (p = 0.606) might not be the source of heterogeneity. In addition, sickle cell trait (SCT) was significantly associated with the mortality (pooled ES = 1.54, 95% CI: 1.28–1.85, p = 0.771) and hospitalization (pooled ES = 1.20, 95% CI: 1.07–1.35，p = 0.519) in patients with COVID‐19. But any increased risk of ICU admission/severe (pooled ES = 1.24, 95% CI: 0.95–1.62, p = 0.520) and mechanical ventilation (OR = 1.00, 95%CI:0.59‐1.69) in COVID‐19 patients with SCT was not observed. Sensitivity analysis demonstrated that the results were robust. The results of the funnel plot and Egger's test did not support the existence of publication bias. Current meta‐analysis indicated that sickle cell disorder has a meaningful impact on COVID‐19 progression to severe cases and associated deaths. However, further investigations and research to validate the current findings is indispensable. [ABSTRACT FROM AUTHOR]