Safety and Efficacy of the Modified Vaccinia Ankara-Bavaria Nordic Vaccine Against Mpox in the Real World: Systematic Review and Meta-Analysis.

In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated orthopoxvirus vaccine that has been authorized by the U.S. Food and Drug Administration as the vaccine of choice for the prevention of mpox. In this study, we conducted a meta-analysis of all currently published literature on the efficacy and safety of the MVA-BN vaccine in the real world, showing that the MVA-BN vaccine is effective and safe, with efficacy of up to 75% with a single dose and up to 80% with a two-dose vaccine. Meanwhile, we found that subcutaneous injection has lower local and systemic adverse events than intradermal injection, regardless of single- or two-dose vaccination, and subcutaneous injection is better tolerated in children, the elderly, or people with underlying medical conditions. These results have important reference value for clinical practice.

Efficacy, immunogenicity and safety of respiratory syncytial virus prefusion F vaccine: systematic review and meta-analysis.

OBJECTIVE: A notable research gap exists in the systematic review and meta-analysis concerning the efficacy, immunogenicity, and safety of the respiratory syncytial virus (RSV) prefusion F vaccine. METHODS: We conducted a comprehensive search across PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov to retrieve articles related to the efficacy, immunogenicity, and safety of RSV prefusion F vaccines, published through September 8, 2023. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 22 randomized controlled trials involving 78,990 participants were included in this systematic review and meta-analysis. The RSV prefusion F vaccine exhibited a vaccine effectiveness of 68% (95% CI: 59-75%) against RSV-associated acute respiratory illness, 70% (95% CI: 60-77%) against medically attended RSV-associated lower respiratory tract illness, and 87% (95% CI: 71-94%) against medically attended severe RSV-associated lower respiratory tract illness. Common reported local adverse reactions following RSV prefusion F vaccination include pain, redness, and swelling at the injection site, and systemic reactions such as fatigue, headache, myalgia, arthralgia, nausea, and chills. CONCLUSIONS: Our meta-analysis suggests that vaccines using the RSV prefusion F protein as antigen exhibit appears broadly acceptable efficacy, immunogenicity, and safety in the population. In particular, it provides high protective efficiency against severe RSV-associated lower respiratory tract disease.

Contraction and expansion dynamics: deciphering genomic underpinnings of growth rate and pathogenicity in Mycobacterium.

Background: Mycobacterium bacteria, encompassing both slow growth (SGM) and rapid growth mycobacteria (RGM), along with true pathogenic (TP), opportunistic pathogenic (OP), and non-pathogenic (NP) types, exhibit diverse phenotypes. Yet, the genetic underpinnings of these variations remain elusive. Methods: Here, We conducted a comprehensive comparative genomics study involving 53 Mycobacterium species to unveil the genomic drivers behind growth rate and pathogenicity disparities. Results: Our core/pan-genome analysis highlighted 1,307 shared gene families, revealing an open pan-genome structure. A phylogenetic tree highlighted clear boundaries between SGM and RGM, as well as TP and other species. Gene family contraction emerged as the primary alteration associated with growth and pathogenicity transitions. Specifically, ABC transporters for amino acids and inorganic ions, along with quorum sensing genes, exhibited significant contractions in SGM species, potentially influencing their distinct traits. Conversely, TP strains displayed contraction in lipid and secondary metabolite biosynthesis and metabolism-related genes. Across the 53 species, we identified 26 core and 64 accessory virulence factors. Remarkably, TP and OP strains stood out for their expanded mycobactin biosynthesis and type VII secretion system gene families, pivotal for their pathogenicity. Conclusion: Our findings underscore the importance of gene family contraction in nucleic acids, ions, and substance metabolism for host adaptation, while emphasizing the significance of virulence gene family expansion, including type VII secretion systems and mycobactin biosynthesis, in driving mycobacterial pathogenicity.

High Prevalence of Respiratory Co-Infections and Risk Factors in COVID-19 Patients at Hospital Admission During an Epidemic Peak in China.

Background: Recent research highlights the contribution of co-infections to elevated disease severity and mortality among COVID-19 patients. Given China's decision to ease epidemic prevention policies in December 2022, a comprehensive exploration of the risks and characteristics of co-infections with respiratory pathogens becomes imperative. Methods: We conducted a retrospective analysis of 716 COVID-19 patients admitted to a primary hospital in China. The detection of twelve respiratory pathogens was conducted using qPCR, and the potential risk factors were analyzed through Cox regression analysis. Results: Within this cohort, 76.82% of cases exhibited co-infection involving eleven distinct pathogens. Among these, bacterial co-infections were observed in 74% of cases, with Streptococcus pneumoniae and Haemophilus influenzae emerging as the most prevalent bacterial co-infection agents. Additionally, 15% of cases presented with viral co-infections, predominantly involving influenza A virus and respiratory syncytial virus. Nevertheless, our investigation suggested that there might be some inappropriate antibiotic use in treatments. Furthermore, risk analysis unveiled dyspnea, hypoproteinemia, low lymphocyte counts, and co-infection with Mycoplasma pneumoniae as prominent risk factors for COVID-19 inpatients. Conclusion: Our findings underscore a significant occurrence of co-infections among COVID-19 patients during the epidemic, emphasizing the need for enhanced antibiotic stewardship. Effective management strategies should encompass respiratory status, nutritional aspects, and vigilance towards co-infections involving M. pneumoniae during COVID-19 treatment. This study underscores the significance of comprehensive management protocols to address the multifaceted challenges presented by co-infections in COVID-19 patients.

The temporal dynamics of antimicrobial-resistant Salmonella enterica and predominant serovars in China.

Salmonella enterica is one of the most common bacterial pathogens in humans and animals. Systematic studies on the trends and geographical distribution of antimicrobial-resistant Salmonella and dominant serovars have been well studied in European and American countries while not in China. Here, taking the One-Health strategy, we used >35 000 Salmonella enterica isolates to explore the temporal and spatial dynamics of dominant serovars in China. We found that Salmonella Typhimurium was the dominant serovar causing human infection in China, which was consistent with Australia but inconsistent with North American and European countries. The proportion of Salmonella serovars Typhimurium, London, Rissen, Corvallis, Meleagridis, Kentucky, and Goldcoast showed an increasing trend during 2006-2019. We randomly selected 1962 isolates for comparative genomics and antimicrobial resistance studies and found that the number of antibiotic resistance genes (ARGs) per isolate increased 1.84 and 2.69 times of human and non-human origins, respectively, spanning 14 years. The proportion of antimicrobial-resistant Salmonella isolates had an increasing trend during 2006-2019, especially beta-lactam, quinolone, tetracycline, and rifampicin resistance. Moreover, we found that higher diversity of sequence types (STs) in S. Typhimurium than in other serovars, ST34 from pig and ST19 from chicken origin, were mainly associated with isolates causing child and adult gastro-infection, respectively. Our results fill in the data gap on the trends of dominant serovars and antimicrobial resistance of Salmonella enterica in China. These data provide useful information for public health decision-makers prioritizing interventions for foodborne diseases and food safety.

Comparative Genomics Reveal the Utilization Ability of Variable Carbohydrates as Key Genetic Features of Listeria Pathogens in Their Pathogenic Lifestyles.

BACKGROUND: L. monocytogenes and L. ivanovii, the only two pathogens of Listeria, can survive in various environments, having different pathogenic characteristics. However, the genetic basis of their excellent adaptability and differences in pathogenicity has still not been completely elucidated. METHODS: We performed a comparative genomic analysis based on 275 L. monocytogenes, 10 L. ivanovii, and 22 non-pathogenic Listeria strains. RESULTS: Core/pan-genome analysis revealed that 975 gene families were conserved in all the studied strains. Additionally, 204, 242, and 756 gene families existed uniquely in L. monocytogenes, L. ivanovii, and both, respectively. Functional annotation partially verified that these unique gene families were closely related to their adaptability and pathogenicity. Moreover, the protein-protein interaction (PPI) network analysis of these unique gene sets showed that plenty of carbohydrate transport systems and energy metabolism enzymes were clustered in the networks. Interestingly, ethanolamine-metabolic-process-related proteins were significantly enriched in the PPI network of the unique genes of the Listeria pathogens, which can be understood as a determining factor of their pathogenicity. CONCLUSIONS: The utilization capacity of multiple carbon sources of Listeria pathogens, especially ethanolamine, is the key genetic basis for their ability to adapt to various environments and pathogenic lifestyles.

Next-Generation Probiotics: Microflora Intervention to Human Diseases.

With the development of human genome sequencing and techniques such as intestinal microbial culture and fecal microbial transplantation, newly discovered microorganisms have been isolated, cultured, and researched. Consequently, many beneficial probiotics have emerged as next-generation probiotics (NGPs). Currently, "safety," "individualized treatment," and "internal interaction within the flora" are requirements of a potential NGPs. Furthermore, in the complex ecosystem of humans and microbes, it is challenging to identify the relationship between specific strains, specific flora, and hosts to warrant a therapeutic intervention in case of a disease. Thus, this review focuses on the progress made in NGPs and human health research by elucidating the limitations of traditional probiotics; summarizing the functions and strengths of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, Eubacterium hallii, and Roseburia spp. as NGPs; and determining the role of their intervention in treatment of certain diseases. Finally, we aim to provide a reference for developing new probiotics in the future.

Gut Mycobiota Dysbiosis in Pulmonary Tuberculosis Patients Undergoing Anti-Tuberculosis Treatment.

Patients with pulmonary tuberculosis (TB) undergoing anti-tuberculosis (anti-TB) treatment were previously reported to present gut bacterial microbiota dysbiosis, but the role of the mycobiota has not been reported. Here, we conducted a follow-up study of 29 naive TB patients who received first-line anti-TB drug treatment; we collected their fecal samples at different time points, as well as 22 fecal samples from healthy subjects. Fungal ITS2 and bacterial 16S rRNA amplicon sequencing were used to analyze the effects of active TB and anti-TB treatment on the gut microbiota. We found that naive TB patients had bacterial and fungal dysbiosis with altered community composition and a decreased density of the transkingdom correlation network. Anti-TB drug treatment significantly decreased the diversity of bacteria and fungi with altered composition. Notably, we observed that the abundance of Purpureocillium lilacinum tended to decrease and Nakaseomyces spp. tended to increase in the anti-TB treatment, and all of them had increased proportions in the three TB groups compared with healthy subjects. We found that the fungal-bacterial transkingdom network was severely altered in TB patients after 2 months of treatment, and new fungal-enriched connections that were not observed in other groups after 6 months of treatment. This study provides the first detailed analysis of dysbiosis of the gut mycobiota due to active TB and anti-TB treatment. The results suggest that fungi play an important role in the balance of the gut microbiota and may be associated with the progression of TB, influencing the microbiota and immunity homeostasis in those receiving anti-TB treatment. IMPORTANCE Numerous studies have shown that the gut bacterial microbiota is altered in active TB patients and that anti-TB drugs have profound and long-term impacts. However, as an integral part of the microbiota, fungi have rarely been studied. The need to investigate both the bacterial and fungal microbiota, as well as the relationship between them is apparent. The significance of our study is in our examination of the changes in the bacterial and fungal microbiota simultaneously in both active TB and patients receiving anti-TB treatment. We found that fungi play an important role in the bacterial-fungal transkingdom network, especially during the anti-TB therapy. These findings underscore the importance of fungi in gut microbiota dysbiosis during active TB and anti-TB treatment processes. In addition, our findings suggest it is meaningful to research potential adjunctive therapies that reduce fungal expansion and increase commensal bacterial abundance after anti-TB treatment, which would help the recovery of TB patients.

The association between tuberculin skin test result and active tuberculosis risk of college students in Beijing, China: a retrospective cohort study.

BACKGROUND: About 10% latent tuberculosis infections (LTBI) would progress to active tuberculosis (TB), if left prophylactic therapy. Tuberculin skin test (TST) is the most widely used method for LTBI screening in the school of China. However, for college students, the association between TST reaction size and active TB risk was unclear. METHODS: We conducted a retrospective study to assess whether the TST reaction size would predict active TB during the next two years after TST screening for college students. Multivariable Cox regression was performed to identify the size of TST reaction and other factors associated with active TB risk. RESULTS: A total of 67292 college students in Beijing, China were included in this study; 8021 (11.92%) individuals were TST positive (≥10 mm), and 3879 (5.76%) of them were strong TST positive (≥15 mm). During the two years of follow-up, 26 active TB cases were reported in 134575 person-years with an incidence rate of 19.32 (95% CI: 12.61-28.32) per 100000 person-years. The adjusted hazard ratios (HR) (95% CI) were 1.094 (0.247~4.846), 3.644 (1.188~11.179), 6.832 (2.436~19.163) and 9.768 (2.203~43.315) of cohorts with the TST reaction size intervals 5~9, 10~14, 15~20 and ≥ 20 mm, respectively, compared to cohort with interval 0~4 mm. Besides, the adjusted HR (95% CI) was 3.593 (1.354~9.537) of males compared to females. CONCLUSIONS: This study indicated that the risk of active TB increased in college students when the TST reaction size was ≥10 mm, and males had a higher risk compared to females.

Genus-Wide Comparative Genomics Analysis of Neisseria to Identify New Genes Associated with Pathogenicity and Niche Adaptation of Neisseria Pathogens.

N. gonorrhoeae and N. meningitidis, the only two human pathogens of Neisseria, are closely related species. But the niches they survived in and their pathogenic characteristics are distinctly different. However, the genetic basis of these differences has not yet been fully elucidated. In this study, comparative genomics analysis was performed based on 15 N. gonorrhoeae, 75 N. meningitidis, and 7 nonpathogenic Neisseria genomes. Core-pangenome analysis found 1111 conserved gene families among them, and each of these species groups had opening pangenome. We found that 452, 78, and 319 gene families were unique in N. gonorrhoeae, N. meningitidis, and both of them, respectively. Those unique gene families were regarded as candidates that related to their pathogenicity and niche adaptation. The relationships among them have been partly verified by functional annotation analysis. But at least one-third genes for each gene set have not found the certain functional information. Simple sequence repeat (SSR), the basis of gene phase variation, was found abundant in the membrane or related genes of each unique gene set, which may facilitate their adaptation to variable host environments. Protein-protein interaction (PPI) analysis found at least five distinct PPI clusters in N. gonorrhoeae and four in N. meningitides, and 167 and 52 proteins with unknown function were contained within them, respectively.

Complete genome sequence and genomic characterization of Microcystis panniformis FACHB 1757 by third-generation sequencing.

The cyanobacterial genus Microcystis is well known as the main group that forms harmful blooms in water. A strain of Microcystis, M. panniformis FACHB1757, was isolated from Meiliang Bay of Lake Taihu in August 2011. The whole genome was sequenced using PacBio RS II sequencer with 48-fold coverage. The complete genome sequence with no gaps contained a 5,686,839 bp chromosome and a 38,683 bp plasmid, which coded for 6,519 and 49 proteins, respectively. Comparison with strains of M. aeruginosa and some other water bloom-forming cyanobacterial species revealed large-scale structure rearrangement and length variation at the genome level along with 36 genomic islands annotated genome-wide, which demonstrates high plasticity of the M. panniformis FACHB1757 genome and reveals that Microcystis has a flexible genome evolution.

Comparative Genomics of H. pylori and Non-Pylori Helicobacter Species to Identify New Regions Associated with Its Pathogenicity and Adaptability.

The genus Helicobacter is a group of Gram-negative, helical-shaped pathogens consisting of at least 36 bacterial species. Helicobacter pylori (H. pylori), infecting more than 50% of the human population, is considered as the major cause of gastritis, peptic ulcer, and gastric cancer. However, the genetic underpinnings of H. pylori that are responsible for its large scale epidemic and gastrointestinal environment adaption within human beings remain unclear. Core-pan genome analysis was performed among 75 representative H. pylori and 24 non-pylori Helicobacter genomes. There were 1173 conserved protein families of H. pylori and 673 of all 99 Helicobacter genus strains. We found 79 genome unique regions, a total of 202,359bp, shared by at least 80% of the H. pylori but lacked in non-pylori Helicobacter species. The operons, genes, and sRNAs within the H. pylori unique regions were considered as potential ones associated with its pathogenicity and adaptability, and the relativity among them has been partially confirmed by functional annotation analysis. However, functions of at least 54 genes and 10 sRNAs were still unclear. Our analysis of protein-protein interaction showed that 30 genes within them may have the cooperation relationship.