Infection最新文献

Typhoid fever, a systemic disease caused by Salmonella enterica serovar Typhi (S. Typhi), remains a major global health problem, particularly in regions with poor sanitation. Despite advancements in diagnostics and treatment, S. Typhi continues to impose a heavy disease burden, worsened by the emergence of multidrug-resistant (MDR) strains. Chronic carriers, accounting for 2-5% of infections, play a crucial role in disease transmission. These carriers are often asymptomatic but intermittently shed bacteria, sustaining S. Typhi within the human population. Gallstones are strongly associated with the chronic carrier state, providing a niche for bacterial biofilm formation that enhances persistence and antibiotic resistance. Furthermore, long-term colonisation of the gallbladder is linked to an increased risk of gallbladder cancer, a condition common in typhoid-endemic areas. The pathogenesis of typhoid fever involves bacterial invasion of the gastrointestinal mucosa, evasion of innate immunity, and systemic spread. Biofilm formation on gallstones promotes long-term persistence within the gallbladder, while immune responses and intestinal microbiota dynamics influence disease progression and bacterial shedding. Current diagnostic methods, including culture and serology, often fall short in identifying carriers, necessitating the development of innovative approaches for effective surveillance and control. Treating chronic carriers remains difficult due to the biofilm-associated resistance of S. Typhi. Although cholecystectomy combined with targeted antimicrobial therapy shows promise, it does not guarantee the elimination of the carrier state. This review emphasises the importance of integrating strategies that combine improved diagnostic tools, targeted therapies, and public health interventions to reduce the burden of typhoid fever and its chronic carriers.

Purpose: Diphtheria is a re-emerging vaccine-preventable disease, mainly caused by toxigenic Corynebacterium diphtheriae.

Methods: Here, we report a fatal respiratory diphtheria infection in a Polish woman travelling to Germany possibly linked to a cutaneous diphtheria infection in a homeless man living in the same geographic area. Laboratory diagnostics involving MALDI-TOF MS, tox-gene PCR, Lateral Flow Immuno Assay, a modified Elek test and Next Generation Sequencing (NGS) identified the causative strain as cotrimoxazole-resistant toxigenic Corynebacterium diphtheriae biotype mitis, sequence type ST574. Moreover, a review on the diphtheria situation in Poland is presented.

Results: NGS data suggest a common source of infection in Poland and a possible link to the Europe-wide outbreak of imported diphtheria with C. diphtheriae since 2022. This is the first diphtheria case in Poland since 2000.

Purpose: Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. It is a major cause of morbidity and mortality. A contemporary overview of sepsis epidemiology in England is long overdue. This study provides an update on the incidence of sepsis-coded hospital admissions and mortality following the COVID-19 pandemic, focusing on the relative contribution of different bacterial pathogens to sepsis-coded admissions.

Methods: We undertook a descriptive study of all hospital admissions from April 1998 to March 2024 using routinely collected health data. Information on sepsis admission episodes, causative pathogens, age, sex, length-of-stay and mortality were collected.

Results: Sepsis-coded hospital admissions increased from 27.9 admissions per 100,000 in 1998 to 210.4 in 2023, a 7.5-fold increase. The incidence of sepsis-coded admissions due to most pre-specified pathogens of interest increased. The largest increases were seen for sepsis due to Enterococci, Streptococcus pyogenes, gram-negative bacteria, Streptococcus agalactiae, Staphylococcus aureus and Listeria spp. Sepsis due to meningococcus decreased. The percentage of patients aged ≥ 75 years admitted with sepsis increased from 32.4 to 52.5% of sepsis cases. Median length-of-stay was 6.1 days. Sepsis-coded admissions and mortality decreased during the COVID-19 pandemic. These have now returned to pre-pandemic levels.

Conclusion: The recorded incidence of sepsis-coded hospital admissions has risen. This may have been impacted by coding changes and improved disease recognition. The decrease in meningococcal sepsis may reflect the success of vaccination campaigns. Further research is needed to explore concurrent trends in sepsis severity, predict who is at greatest risk and improve prevention efforts.

Background: Chagas disease and strongyloidiasis are endemic in Latin America, but both infections have become diseases of global concern due to migration flows. During the last fifteen years, these infections have become emerging infections in Italy as a consequence of the huge immigration from Latin American countries. The aim of this study is to assess the prevalence of Chagas disease, strongyloidiasis, and their co-infection in a cohort of Latin American migrants living in Rome. Additionally, it seeks to evaluate whether informational outreach campaigns-offered directly within communities and supported by local leaders-could represent a possible approach to reveal the hidden public health burden of these neglected infections among migrant populations.

Methods: Six community-based information campaigns on Chagas disease and strongyloidiasis were performed in Rome (Italy) in public events or in homes occupied by migrants from Latin America, inviting people to carry out screening tests at the National Institute for Health, Migration and Poverty clinic.

Results: 344 adults were tested for Chagas disease and strongyloidiasis. The overall prevalence of Trypanosoma cruzi infection was 7.8% (27/344). Of the positive results, 77.8% (21/27) were observed in persons originating from Bolivia. The prevalence of strongyloidiasis was 10.5% (36/344). Of the positive results, 69.4% (25/36)were among persons originating from Bolivia, out 27(22.2%) individuals tested positive for both Trypanosoma cruzi and Strongyloides stercoralis.

Conclusions: Our findings indicate that targeted informational outreach campaigns-particularly those embedded within cultural, recreational, and sporting events-can be an effective strategy for promoting systematic and combined screening for Chagas disease and strongyloidiasis. Such initiatives not only raise public health awareness among Latin American migrants in non-endemic settings but also help to uncover a largely overlooked public health issue.

Purpose: This study aimed to analyse COVID-19-related mortality during the pandemic, stratified by groups at risk of severe COVID-19.

Methods: Patients with COVID-19 between March 2020 and February 2023 were enrolled using the international multicentric Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS). The COVID-19 in-hospital mortality was calculated using a multivariable logistic regression model adjusted for age and sex.

Results: A total of 11,765 patients were included, with an overall mortality rate of 13.1% (N = 1541). Mortality decreased from 14.4% during the wildtype (wt) period to 10.6%, 9.5%, and 6.3% in the alpha (α), delta (δ), and omicron (Ω) periods, respectively. Patients aged 66-75, 76-85, and > 85 years had 11.4-, 19.3-, and 34.7-fold higher mortality odds than patients aged 26-35 years (p < 0.001 in all comparisons). This increase in mortality between younger and older patients decreased with the shift from wt (increase of 39.4%) to Ω (15.5%). The overall adjusted mortality rate in males (18.4%) was higher than in females (10.6%); however, this sex-specific difference levelled off with the shift from wt (m: 18.9%, f: 10.1%) to Ω (m: 5.9%, f: 5.3%). Referring to comorbidities, adjusted mortality increased significantly with the number of comorbidities in patients during the wt but remained stable in patients with Ω-period. Among severely immunosuppressed patients, mortality declined markedly throughout the pandemic (wt vs. Ω: p < 0.001).

Conclusion: Overall mortality decreased during the pandemic, even among severely immunosuppressed patients. Age, sex, and the number of comorbidities were key mortality risk factors, although their impact lessened as the pandemic progressed.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a major challenge in clinical settings due to high morbidity, mortality, and limited treatment options. In response, phage therapy has reemerged as a promising alternative to conventional antibiotics. In this study, two lytic bacteriophages, Kpn_PImp2 and Kpn_PImp3, were isolated from urban sewage, a rich source of phages owing to its diverse microbial community. These phages demonstrated remarkable pH stability and thermostability, ensuring their activity under a variety of environmental and physiological conditions. Genomic analysis suggests that both phages likely belong to the Webervirus genus within the Caudoviricetes class, characterized by tailed phages with double-stranded DNA. Importantly, neither phage harbors lysogenic, toxin, nor antimicrobial resistance genes, affirming their safety for therapeutic applications. Comparative studies of tail fiber proteins, which play a crucial role in host specificity, indicate that structural variations may account for the distinct host ranges of Kpn_PImp2 and Kpn_PImp3. Moreover, both phages exhibited the ability to inhibit and disrupt biofilm formation, a key factor in CRKP persistence and resistance. Their biofilm-disrupting properties could potentially enhance the penetration and efficacy of antibiotics in combination therapies. The in vivo efficacy of these phages was further validated using the Galleria mellonella infection model, where treatment led to a significant reduction in larval mortality. However, a cocktail combining both phages did not show synergistic benefits over monophage therapy, likely due to shared host-cell receptors. These findings highlight Kpn_PImp2 and Kpn_PImp3 as promising candidates for phage therapy against CRKP, warranting further research into resistance mechanisms, delivery methods, and combination therapies to fully realize their therapeutic potential. This study also expands the bacteriophage resources against K. pneumoniae and provides valuable insights for phage-based treatments.

Purpose: Antibiotic resistance (AR) is an escalating worldwide health emergency, requiring inventive strategies for antibiotic treatment. This review examines the tactics used in designing smart antibiotics, with a specific emphasis on the mechanism of action of lolamicin, a newly developed microbiome-sparing antibiotic.

Methods: We review the recent advances in smart antibiotic development, particularly those aiming to preserve the gut microbiome while effectively targeting pathogens. The study focuses on lolamicin's selective targeting mechanism, its inhibition of the LolCDE complex in Gram-negative bacteria.

Results: Lolamicin works by blocking the LolCDE complex, which is crucial for transporting lipoproteins in Gramnegative bacteria. It offers a significant improvement compared to conventional antibiotics and other microbiomesparing options by safeguarding the microbiome and reducing the development of resistance. However, its limited range of effectiveness - namely against certain harmful bacteria such as Pseudomonas aeruginosa - and the possibility of bacteria becoming resistant to it, remain areas of concern.

Conclusion: Lolamicin presents a hopeful resolution by selectively attacking Gram-negative bacteria while leaving the beneficial gut flora unharmed. Further investigation and rigorous clinical testing are essential to fully harness its promise and confirm its long-term utility in combating antibiotic resistance.

Purpose: This narrative review explores the multifaceted links between periodontal diseases (gingivitis and periodontitis) and systemic health conditions, including cardiovascular disease, diabetes, adverse pregnancy outcomes, Alzheimer's disease, cancers, rheumatoid arthritis, and respiratory infections. It aims to synthesize evidence on how local oral infections exert systemic effects and evaluate the potential of diagnostic technologies to monitor these interactions.

Methods: This narrative review synthesizes current scientific literature on periodontal disease pathogenesis, focusing on key pathogens (e.g., Porphyromonas gingivalis, Fusobacterium nucleatum) and their roles in driving local and systemic inflammation via virulence factors and microbial dysbiosis. It examines biomarker-based diagnostic approaches (e.g., IL-1β, TNF-α, microbial DNA) in saliva, blood, and gingival crevicular fluid (GCF) and evaluates current and emerging diagnostic tools (e.g., ELISA, PCR, lateral flow assays, biosensors, microfluidics).

Results: The review highlights that periodontal pathogens contribute to systemic disease through complex mechanisms including persistent inflammation (driven by cytokines like IL-1β, TNF-α), endotoxemia (via LPS, noting pathogen-specific structural variations impacting immune response), molecular mimicry, and immune modulation. Current diagnostic methods provide valuable information but often face limitations in speed, portability, and multiplexing capability needed for comprehensive point-of-care assessment. Emerging technologies, particularly multiplex platforms integrating biosensors or microfluidics, demonstrate significant potential for rapid, user-friendly analysis of multiple biomarkers, facilitating earlier detection and personalized risk stratification, especially in high-risk populations.

Conclusion: Periodontal diseases significantly impact systemic health via intricate microbial and inflammatory pathways. The complexity of these interactions necessitates moving beyond conventional diagnostics towards integrated, advanced technologies. Implementing rapid, multiplex biomarker detection platforms within a multidisciplinary healthcare framework holds the potential to revolutionize early detection of linked conditions, improve personalized management strategies, and ultimately reduce the systemic burden of periodontal disease.