Borrow R, Caugant DA, Clark SA
… +10 more, Dinleyici EÇ, Hall I, Harrison LH, Hausdorff WP, Ladhani SN, Lucidarme J, Sáfadi MAP, Smith V, Taha MK, Vázquez J
This review outlines recent trends on invasive meningococcal disease (IMD) discussed at the latest meeting of the Global Meningococcal Initiative (GMI). There has been a re-emergence of the Hajj strain sublineage (serogr...This review outlines recent trends on invasive meningococcal disease (IMD) discussed at the latest meeting of the Global Meningococcal Initiative (GMI). There has been a re-emergence of the Hajj strain sublineage (serogroup W; ST-11 clonal complex), with travel to the Kingdom of Saudi Arabia being a critical factor in transmission. The epidemiology of IMD has also changed following the COVID-19 pandemic, with annual IMD cases increasing in many countries. For example, the highest number of IMD cases since 2014 was reported in the USA in 2023-2024. Atypical presentations of IMD have been prominent irrespective of the pandemic. For instance, an increase in cases of meningococcal epiglottitis has been reported in France in 2022-2023 (serogroups W and Y). When considering vaccination, the GMI has identified a need for broader meningococcal serogroup B (MenB) immunisation owing to the potential impact of the vaccines on reducing IMD incidence caused by other serogroups than MenB. There is also a case for using MenB vaccination to protect against Neisseria gonorrhoeae infection based on initial evidence, albeit further studies will need to be conducted.
Sedik S, Egger M, Wolfgruber S
… +37 more, Salmanton-García J, Bassetti M, Mikulska M, Özenci V, Arikan-Akdagli S, Akova M, Gangneux JP, Bandera A, Alastruey-Izquierdo A, Barac A, Rautemaa-Richardson R, de Jonge NA, Loughlin L, Blennow O, Lanternier F, Meijer EFJ, Khanna N, Garcia-Vidal C, Dávila-Valls J, Klimko N, Khostelidi SN, White PL, Akalin H, Rogers B, Ruiz M, García-Rodríguez J, Akyol D, Longval T, Danion F, Prattes J, Krause R, Biswas SK, Arendrup MC, Koehler P, Cornely OA, Hoenigl M, ECMM Candida III study group
OBJECTIVES: Candidemia is a severe complication in critically ill and immunocompromised patients, and is associated with high morbidity and mortality. While early fungal clearance may improve outcomes, the association be...OBJECTIVES: Candidemia is a severe complication in critically ill and immunocompromised patients, and is associated with high morbidity and mortality. While early fungal clearance may improve outcomes, the association between follow-up blood culture (FUBCs) results and clinical outcomes remains insufficiently explored. This sub-analysis of the ECMM Candida III study investigates predictors of persistent candidemia and the impact of positive FUBC results on clinical outcomes. METHODS: The multicenter ECMM Candida III study enrolled adults with culture-proven candidemia from 60 European centers (2018-2019). This sub-analysis included patients with at least one FUBC result reported (n = 258; 40.8%). Statistical analysis used SPSS 29 and R. Binary logistic regression was used to identify predictors of persistent candidemia. To assess mortality risk factors, Cox proportional hazards regression models were constructed. RESULTS: Of 258 patients, 52 (20.2%) had persistent candidemia based on positive FUBCs (median duration of candidemia 6 days). Utilization of echinocandins as first line treatment was less frequent (61.5% vs. 78.2%; p=0.014) in those with positive FUBCs. Mortality was significantly higher in the FUBC-positive group (50% vs. 32%; p=0.016). In the multivariable logistic regression model, lower EQUAL Candida Scores, reflecting reduced adherence to guideline-recommended management, were independently associated with persistent candidemia (OR 0.003, 95% CI 0.0002-0.07; p<0.001). Univariable Cox regression identified persistent candidemia ≥5 days (HR 2.16; 95% CI 1.33-3.53; p= 0.002) as a significant predictor of mortality. In the multivariable Cox regression model, intensive care unit (ICU) admission (HR 1.59, 95% CI 1.02-2.50; p= 0.039) and persistent candidemia ≥5 days (HR 2.06, 95% CI 1.26-3.37; p= 0.004) remained independent predictors of mortality. CONCLUSION: Persistent candidemia was predicted by poor adherence to treatment guidelines, as shown by low EQUAL Candida Scores, particularly due to the lack of initial echinocandin use. After controlling immortal time bias, persistent candidemia ≥5 days and ICU admission remained independent predictors of mortality in the multivariable model.
Teunis G, Dallman TJ, Zając M
… +22 more, Skarżyńska M, Petrovska L, Pista A, Silveira L, Clemente L, Thépault A, Bonifait L, Kerouanton A, Chemaly M, Alvarez J, Söderlund R, Nielsen EM, Chattaway M, Burgess K, Byrne W, Zomer AL, van den Beld M, Hendrickx APA, Franz E, Pires S, Hald T, Mughini-Gras L
Non-typhoidal Salmonella is the second most frequently reported zoonotic pathogen in the European Union and European Economic Area. Most human infections are caused by serovars Enteritidis and Typhimurium. Genomic charac...Non-typhoidal Salmonella is the second most frequently reported zoonotic pathogen in the European Union and European Economic Area. Most human infections are caused by serovars Enteritidis and Typhimurium. Genomic characterisation of Salmonella isolates from humans and animals has become a routine public health surveillance tool in many countries. In this study, the relative contributions of several potential sources of human infection of the five frequently reported Salmonella serovars were estimated using machine-learning methods based on a large, cross-sectional collection of genomes from human cases, and animal and environmental sources, across ten European countries. To define the population structure, core-genome Multilocus Sequence Typing was performed. A supervised machine-learning approach was applied for source attribution in the form of a Random Forest classifier. The source and country attribution models achieved moderate accuracy (F1=0.6-0.9), which is lower than in previous studies using machine-learning on Whole Genome Sequencing data. However, attributions of human clinical isolates to different sources were generally in line with previous findings for these five serovars. While the lack of clonality in some sources hindered their prediction, it is also likely that certain sources (e.g., pets) do not serve as major contributors to human infection. Therefore, in most cases attributing these sources to the livestock species they are typically associated with, is likely appropriate. Country attributions showed that substantial human cases are attributable to countries other than their own, indicating geographical interrelatedness of sources. This highlights the value of internationally harmonised Salmonella-control policies in the food production chain.
OBJECTIVES: Although cases of nontuberculous mycobacteria (NTM) pulmonary disease (NTMPD) are rapidly increasing primarily in individuals over the age of 65, the host factors leading to higher occurrence in immunocompete...OBJECTIVES: Although cases of nontuberculous mycobacteria (NTM) pulmonary disease (NTMPD) are rapidly increasing primarily in individuals over the age of 65, the host factors leading to higher occurrence in immunocompetent older patients remain elusive. This study aims to elucidate host factors leading to higher nontuberculous mycobacterial pulmonary disease occurrence in older immunocompetent patients. METHODS: To address these challenges, we used a rhesus macaque model developed by our laboratory where macaques were infected via intrabronchial inoculation with M. avium subsp. hominissuis (MAH). Disease progression, bacterial load, microbial community compositions, and host responses were monitored longitudinally using computed tomography, culturing, 16S amplicon sequencing, histology, flow cytometry, and single cell RNA sequencing. RESULTS: Despite comparable kinetics of bacterial clearance, computed tomography scans indicated more severe radiological outcomes in older animals which mounted predominantly an inflammatory acute phase response rather than a Th1 response. Single cell RNA sequencing indicated a persistent inflammatory signature in aged animals. Microbial community analysis revealed an age-mediated loss of an uncultured Tropheryma species that was inversely correlated with severity of radiographic changes. CONCLUSIONS: These data reveal that nontuberculous mycobacterial pulmonary disease severity in the aged animals is driven by dysregulated inflammatory responses and dysbiosis of the lung microbiome.
Mazzotta V, Matusali G, Cimini E
… +15 more, Caioli A, Esvan R, Colavita F, Tartaglia E, Paulicelli J, Micheli G, Bettini A, Notari S, Giacinta A, Bordi L, Gili S, Siddu A, Girardi E, Maggi F, Antinori A
Manzoni P, Riccò M, Nobili C
… +31 more, Tzialla C, Barera G, Del Barba P, De Franco S, Pellegrini G, Magri P, Crapanzano E, Nicolini G, Alba A, Fiocchi S, Vivalda M, Natta G, Casati A, Manzionna M, Rugolotto S, Saggioro L, Pesce S, Scavone M, Distilo A, Roseto V, Di Toro A, Pierri L, Scarpelli G, Bonanno E, Decembrino L, Felici E, Selvatico C, Saracco V, Morrone F, Giuffrè M, Italian Collaborative Network for surveillance and management of Neonatal and Infantile Infections (GdSIN)
INTRODUCTION: Metagenomic next-generation sequencing (mNGS) is an important tool for enhancing pathogen detection in infected patients. However, distinguishing between specimens that are infected or colonized is still a...INTRODUCTION: Metagenomic next-generation sequencing (mNGS) is an important tool for enhancing pathogen detection in infected patients. However, distinguishing between specimens that are infected or colonized is still a major challenge. OBJECTIVES: To explore the composition of bacteriophages in the blood and respiratory tract of the human body, the association between bacteriophage detection and bacterial infections, and whether bacteriophages can assist in differentiating infectious pathogens according to mNGS results. METHODS: Clinical samples from hospitalized patients were collected between January 2023 and February 2024. DNA and cell-free DNA were extracted from BALF and plasma retrospectively to identify the pathogens present, and bacteriophage annotations were conducted. RESULTS: A total of 299 samples, comprising 136 blood samples and 163 BALF samples, were obtained from 218 patients. Compared with the samples negative for bacteria, both blood and bronchoalveolar lavage fluid (BALF) samples infected with Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and S. aureus showed a corresponding increase in the proportions of phages related to these pathogens. In BALF samples with Acinetobacter baumannii infection, the proportions of Autographiviridae, Siphoviridae, and Myoviridae were significantly greater than those in the Acinetobacter baumannii colonization group. The sensitivity of Myoviridae for differentiating between infection and colonization was 86.36%, and the specificity was 52.94%. CONCLUSION: In sepsis, compared with conventional mNGS methods alone, the use of bacteriophages combined with mNGS was more effective in identifying causative pathogens and had higher specificity. These findings may provide new ideas and tools for improving clinical infection diagnosis.
Foulkes S, Munro K, Sparkes D
… +24 more, Khawam J, Russell S, Dunne A, Timeyin J, Hettiarachchi N, Cairns M, Bradley DT, De Lacy E, Wilson K, Andrews N, Charlett A, Respiratory Virus and Microbiome Initiative (RVI) team, Bellis K, Huang YL, Forbes M, Frick-Kretschmer A, Knoll M, Harrison EM, SIREN study group, Brown CS, Atti A, Islam J, Hopkins S, Hall V
BACKGROUND: During the winter, healthcare systems experience additional pressures due to increases in respiratory infections and staff absence. We aimed to determine the prevalence of respiratory viruses and impact on si...BACKGROUND: During the winter, healthcare systems experience additional pressures due to increases in respiratory infections and staff absence. We aimed to determine the prevalence of respiratory viruses and impact on sickness absence in the SIREN healthcare worker (HCW) cohort during winter 2023/24. METHODS: SIREN is a cohort study with linked testing, vaccination, demographic, symptoms and sick leave data. Participants undergo fortnightly multiplex PCR testing for SARS-CoV-2, influenza and RSV, regardless of symptoms. The proportion of participants who took sick leave, the total number and median of sick leave days taken was calculated, overall and stratified by viral infection and vaccination status. Logistic regression was used to estimate the association between sick leave and vaccination status. RESULTS: A total of 5287 participants were included, 78·3% female, median age 54 years. There were 1828 infections (1161 SARS-CoV-2; 387 RSV; 280 influenza infections) among 1659 participants. Influenza and RSV peaked in December (1·2%; 1·9%), SARS-CoV-2 peaked in September and December 2023 (4·0%; 4·3%). Regardless of a known infection, 35.8% (1892/5287) took sick leave, resulting in 10,168 days (median 5 days per person; range 1-98 days). DISCUSSION: Respiratory illness caused a substantial burden on the SIREN healthcare workforce over winter, with all three viruses contributing. Reduced number of staff at work and pressures to work through illness have implications for healthcare resilience.
BACKGROUND: Shotgun metagenomics (SMg) promises to significantly improve the microbiological diagnosis of infectious diseases. However, the prospective evaluation of its clinical utility in different infectious syndromes...BACKGROUND: Shotgun metagenomics (SMg) promises to significantly improve the microbiological diagnosis of infectious diseases. However, the prospective evaluation of its clinical utility in different infectious syndromes remains poorly documented. METHODS: We conducted a prospective study including all patients who underwent SMg as part of their care at the French Henri Mondor Hospital National Reference Laboratory for accredited SMg between February 2018 and January 2020. Patients were categorized as having either a "high likelihood" or "low likelihood" of infection based on their clinical presentation. The contribution of the SMg to the final diagnosis was assessed by a multidisciplinary team of infectious disease specialists. FINDINGS: 202 patients were enrolled in the study. Of the 123 patients considered to have a high likelihood of infection, SMg confirmed the cause of infection in 38 cases (30.9%), including 12 cases (9.8%) diagnosed exclusively by this method. In the 79 patients classified as having a "low likelihood" of infection, SMg did not detect any microorganisms compatible with an infectious cause. In particular, patients undergoing immunosuppressive treatment within the latter group showed no deterioration after 6 months. INTERPRETATION: SMg facilitated microbiological diagnosis in over 30% of complex cases, regardless of sample type or site of infection. Compared with conventional techniques, SMg provided diagnoses in 10% more cases, highlighting its broad utility across different infectious diseases. Our results suggest that SMg is a promising tool for documenting complex infectious diseases alongside traditional microbiology tools. Furthermore, negative SMg results are useful for the management of patients with a low likelihood of infection.
OBJECTIVES: To determine the association between viral species and odds of severe lower respiratory tract illnesses (sLRI) versus upper respiratory illness (URI) among children under 2 years of age. METHODS: Infants (n=2...OBJECTIVES: To determine the association between viral species and odds of severe lower respiratory tract illnesses (sLRI) versus upper respiratory illness (URI) among children under 2 years of age. METHODS: Infants (n=2061) enrolled in the Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes were surveilled for respiratory illnesses until age 2 years (March 2020 to April 2024). Nasal swabs from 1363 illnesses (774 participants) were screened for 21 pathogens. RESULTS: RSV infections occurred in 23% of sLRIs and increased odds of sLRI vs URI (OR=9.28; 95% CI, 5.43-15.85). Metapneumovirus, parainfluenza, and non-SARS-CoV-2 coronavirus also increased odds of sLRIs, while SARS-CoV-2 was associated with lower risk of sLRIs. Rhinovirus (43%) and bocavirus (16.1%) were commonly detected, but were not associated with sLRI risk. Co-infection with multiple viral species was associated with 2.92-fold greater odds of sLRI (95% CI, 2.05-4.16) compared to single viral species infections. Rhinovirus-bocavirus was the most common co-infection, and interaction between these viruses was associated with increased odds of sLRI. CONCLUSIONS: Diverse viral pathogens drive early-life sLRIs. Some (e.g. RSV and metapneumovirus) have an intrinsic propensity to cause sLRIs, while other viruses' lower airway pathogenicity depends on other factors, including co-infection.
Respiratory syncytial virus (RSV) is a leading cause of infant death across the globe. Age is a significant factor that contributes to the severity of infection in young children. RSV primarily infects the ciliated cells...Respiratory syncytial virus (RSV) is a leading cause of infant death across the globe. Age is a significant factor that contributes to the severity of infection in young children. RSV primarily infects the ciliated cells of the airway epithelium, induces mucus hypersecretion, and impaired mucociliary clearance. Better understanding of RSV infection at the cellular level is needed for the development of effective therapeutic interventions. To investigate the age difference and comprehensively understand gene signatures associated with RSV infection, we performed single-cell transcriptomic analysis of adult and pediatric human nose organoids (HNOs) infected with RSV. Our analysis revealed a significant difference in transcriptomic signature associated with cellular differentiation and proliferative pathways between the adult and pediatric HNOs. Moreover, we found a distinct innate immune response to RSV infection, with pediatric HNO revealing a lower and dysregulated response. Through sub-clustering analysis of the ciliated cell population, we identified the primary ciliary cell as a novel and prominent susceptible ciliary cell type to RSV infection. Intriguingly and unexpectedly, we found that in the pediatric more than in the adult, HNO RSV infects other novel airway cells, including basal cells, and ionocytes/tuft cells, as demonstrated by increased RSV-gene counts and induction of interferon-related pathways. Together, our study provides the first HNO cell atlas dissecting the heterogeneity of RSV infection in airway epithelium between adult versus pediatric HNOs and identifies novel cell types that are susceptible to RSV infection, which altogether provides a key resource for research on RSV pathogenesis, therapeutics and vaccines.