Journal of Infection最新文献

{"title":"Risk of unintended consequences from lower antibiotic prescribing for respiratory tract infections in primary care","authors":"","doi":"10.1016/j.jinf.2024.106255","DOIUrl":"10.1016/j.jinf.2024.106255","url":null,"abstract":"<div><h3>Objectives</h3><p>About 60% of antibiotic prescribing in primary care is for respiratory tract infections (RTIs), some of which is likely unnecessary. There is limited evidence on the association between reduced antibiotic prescribing and adverse events. We aimed to identify associations between practice-level prescribing rates for RTIs in general practice, and patient-level adverse outcomes.</p></div><div><h3>Methods</h3><p>We included 1471 English General Practitioner (GP) practices, linked to hospital admissions in England, from the Clinical Practice Research Datalink for 2005 to 2019. Outcomes were hospitalisations, RTI-related re-consultations and additional antibiotic prescriptions, adjusted for practice level case-mix prescribing.</p></div><div><h3>Results</h3><p>Prescribing rates for practices falling within the lowest and highest prescribing quintiles were 52 and 139 prescriptions per 1000 RTI-related consultations. Patients from practices in the lowest prescribing quintile did not have significantly higher risk of hospitalisation, adjusted odds ratio 0·99 (95% CI 0·96 to 1·02). Re-consultations within 30 days were significantly higher for the lowest prescribing practices, adjusted odds ratio 1·209 (1·206 to 1·212). Additional antibiotic prescriptions and subsequent prescriptions upon re-consultation were significantly lower for the lowest prescribing practices, adjusted odds ratio 0·317 (0·314 to 0·321) and 0·706 (0·699 to 0·712), respectively.</p></div><div><h3>Conclusions</h3><p>Our results contribute to evidence on the safety of reduced antibiotic prescribing for RTIs in primary care. Results suggest that for the majority of practices, further reductions in RTI-related antibiotic prescribing should be possible without an increase in hospitalisation for pneumonia.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001890/pdfft?md5=6dc6ef2c1dd3c0a0c02e529e92fa08a5&pid=1-s2.0-S0163445324001890-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-packaged cold-chain ready-to-eat food as a source of sporadic listeriosis in Beijing, China","authors":"","doi":"10.1016/j.jinf.2024.106254","DOIUrl":"10.1016/j.jinf.2024.106254","url":null,"abstract":"<div><h3>Objectives</h3><p>Using a sporadic case of listeriosis suspected to have been caused by consuming a pre-packaged cold-chain ready-to-eat (RTE) food in Beijing, China in 2021 as an exemplar, this study demonstrated the importance of thoroughly investigating the source of listeriosis up to the production point for mitigating infection risk during routine monitoring of <em>Listeria</em> in food facilities and national surveillance program using whole-genome sequencing (WGS).</p></div><div><h3>Methods</h3><p>Epidemiological, laboratory, traceback, and plant investigations were used to identify the source of infection.</p></div><div><h3>Results</h3><p>WGS showed the isolate from the patient was genetically indistinguishable from that of the implicated food. During a plant investigation, <em>L. monocytogenes</em> was detected in 26% (9/35) of the environmental samples and one of two raw material samples, confirming the source.</p></div><div><h3>Conclusion</h3><p>To our knowledge, this is the first investigation in China linking a case of <em>L. monocytogenes</em> infection to a suspected food and its production environment. This report highlights the risk of <em>L. monocytogenes</em> contamination of RTE food and demonstrates the role of food safety risk monitoring in identifying potential sources of infection. Reinforcing control programs in RTE processing plants, intensified surveillance of microorganisms in food products and targeted health education is required to mitigate the infection risk.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001889/pdfft?md5=1bf63864efcbaf923016171073fd0cfc&pid=1-s2.0-S0163445324001889-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global temporal trends and projections of acute hepatitis E incidence among women of childbearing age: Age-period-cohort analysis 2021","authors":"","doi":"10.1016/j.jinf.2024.106250","DOIUrl":"10.1016/j.jinf.2024.106250","url":null,"abstract":"<div><h3>Background &amp; aims</h3><p>Acute hepatitis E (AHE) poses a significant threat to global public health, particularly among women of childbearing age (WCBA), who are at heightened risk for severe pregnancy-related complications. This study aimed to delineate the temporal trends and project future incidence of AHE in WCBA, providing insights crucial for targeted prevention and control strategies.</p></div><div><h3>Methods</h3><p>Data on AHE incidence from the Global Health data 2021. The age-period-cohort (APC) model was applied to analyze trends across different age groups, periods, and birth cohorts, and the Bayesian APC model was utilized for forecasting future epidemiological trajectories.</p></div><div><h3>Results</h3><p>Globally, AHE incidence numbers among WCBA rose from 2,831,075 in 1992 to 3,420,786 in 2021, while the age-standardized incidence rate (ASIR) declined from 194.66 to 179.54 per 100,000 with a global net drift of −0.28%. However, high SDI regions showed a contrasting trend with a positive net drift of 0.02%. The age effect was consistent across SDI regions and globally, showing a decrease with advancing age, while unfavorable period and cohort effects were exhibited in high-SDI region. At the national level, locations exhibited varying trends of change. The BAPC model predicted a total of 3,759,384 AHE global cases in WCBA by 2030, with an expected mild increase in the ASIR. The outlook for the management and containment of AHE is grim in certain countries, including India.</p></div><div><h3>Conclusions</h3><p>The study revealed a complex epidemiological landscape of AHE in WCBA, with increasing global incidence numbers juxtaposed against a declining ASIR. The AHE burden by 2030 remain severe among WCBA. Young WCBA and high SDI region merit particular attention. The findings underscore the need for region-specific strategies to curb the projected rise in AHE incidence and align with the 2030 WHO goals.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001841/pdfft?md5=463be619e8e9d5d1fac08c8058c11da4&pid=1-s2.0-S0163445324001841-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibodies to PfEMP1 and variant surface antigens: Protection after controlled human malaria infection in semi-immune Kenyan adults","authors":"","doi":"10.1016/j.jinf.2024.106252","DOIUrl":"10.1016/j.jinf.2024.106252","url":null,"abstract":"<div><h3>Objectives</h3><p>Acquisition of antibodies to <em>Plasmodium falciparum</em> variant surface antigens (VSA) expressed on infected red blood cells (iRBCs) is associated with naturally acquired immunity to malaria. We have previously shown that antibodies to VSA on iRBCs are associated with protection against parasite growth in the context of controlled human malaria infection (CHMI). This study explored whether antibodies to recombinant antigens derived from <em>Pf</em>EMP1 domains were independently associated with protection during CHMI in semi-immune Kenyan adults.</p></div><div><h3>Methods</h3><p>We used a multiplex bead assay to measure levels of IgG antibody against a panel of 27 recombinant <em>Pf</em>EMP1 antigens derived from the <em>Pf</em>EMP1 repertoire of the 3D7 parasite clone. We measured IgG levels in plasma samples collected from the CHMI participants before inoculation with Sanaria® PfSPZ Challenge, on the day of diagnosis, and 35 days post-inoculation. Univariable and multivariable Cox regression analysis was used to evaluate the relationship between the levels of antibodies to the antigens and CHMI outcome. We also adjusted for previous data including antibodies to VSA on iRBCs, and we assessed the kinetics of antibody acquisition to the different <em>Pf</em>EMP1 recombinant antigens over time.</p></div><div><h3>Results</h3><p>All study participants had detectable antibodies to multiple <em>Pf</em>EMP1 proteins before inoculation. All <em>Pf</em>EMP1 antigens were associated with protection against parasite growth to the threshold criteria for treatment in CHMI, albeit with substantial collinearity. However, individual <em>Pf</em>EMP1 antigens were not independently associated with protection following adjustment for breadth of reactivity to VSA on iRBCs and schizont extract. In addition, antibodies to <em>Pf</em>EMP1 antigens derived from group B <em>Pf</em>EMP1 were induced and sustained in the participants who could not control parasite growth.</p></div><div><h3>Conclusion</h3><p>This study shows that the breadth of antibody response to VSA on iRBCs, and not to specific <em>Pf</em>EMP1 antigens, is predictive of protection against malaria in CHMI.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001865/pdfft?md5=0622ed72b8bc70ec5f88c36e1e493fa2&pid=1-s2.0-S0163445324001865-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surveillance of avian influenza viruses in Hebei Province of China from 2021 to 2023: Identification of a novel reassortant H3N3","authors":"","doi":"10.1016/j.jinf.2024.106240","DOIUrl":"10.1016/j.jinf.2024.106240","url":null,"abstract":"<div><p>Avian influenza remains a global public health concern for its well-known point mutation and genomic segment reassortment, through which plenty of serum serotypes are generated to escape existing immune protection in animal and human populations. Some occasional cases of human infection of avian influenza viruses (AIVs) since 2020 posed a potential pandemic risk through human-to-human transmission. Both east-west and north-south migratory birds fly through and linger in the Hebei Province of China as a stopover habitat, providing an opportunity for imported AIVs to infect the local poultry and for viral gene reassortment to generate novel stains. In this study, we collected more than 6000 environmental samples (mostly feces) in Hebei Province from 2021 to 2023. Samples were screened using real-time RT-PCR, and virus isolation was performed using the chick embryo culture method. We identified 10 AIV isolates, including a novel reassortant H3N3 isolate. Sequencing analysis revealed these AIVs are highly homologous to those isolated in the Yellow River Basin. Our findings supported that AIVs keep evolving to generate new isolates, necessitating a continuous risk assessment of local avian influenza in wild waterfowl in Hebei, China.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001749/pdfft?md5=e9d7428d0e54aaa93103d78608505eb9&pid=1-s2.0-S0163445324001749-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency of antimicrobial-resistant bloodstream infections in 111 hospitals in Thailand, 2022","authors":"","doi":"10.1016/j.jinf.2024.106249","DOIUrl":"10.1016/j.jinf.2024.106249","url":null,"abstract":"<div><h3>Objectives</h3><p>To evaluate the frequency of antimicrobial-resistant bloodstream infections (AMR BSI) in Thailand.</p></div><div><h3>Methods</h3><p>We analyzed data from 2022, generated by 111 public hospitals in health regions 1 to 12, using the AutoMated tool for Antimicrobial resistance Surveillance System (AMASS), and submitted to the Ministry of Public Health, Thailand. Multilevel Poisson regression models were used.</p></div><div><h3>Results</h3><p>The most common cause of community-origin AMR BSI was third-generation cephalosporin-resistant <em>Escherichia coli</em> (3GCREC, 65.6%; 5101/7773 patients) and of hospital-origin AMR BSI was carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB, 51.2%, 4968/9747 patients). The percentage of patients tested for BSI was negatively associated with the frequency of community-origin 3GCREC BSI and hospital-origin CRAB BSI (per 100,000 tested patients). Hospitals in health regions 4 (lower central region) had the highest frequency of community-origin 3GCREC BSI (adjusted incidence rate ratio, 2.06; 95% confidence interval: 1.52–2.97). Health regions were not associated with the frequency of hospital-origin CRAB BSI, and between-hospital variation was high, even adjusting for hospital level and size.</p></div><div><h3>Conclusion</h3><p>The high between-hospital variation of hospital-origin CRAB BSI suggests the importance of hospital-specific factors. Our approach and findings highlight health regions and hospitals where actions against AMR infection, including antimicrobial stewardship and infection control, should be prioritized.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S016344532400183X/pdfft?md5=41896157f0d9108aa9468bb9d89e74fc&pid=1-s2.0-S016344532400183X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to doxycycline increases risk of carrying a broad range of enteric antimicrobial resistance determinants in an elderly cohort","authors":"","doi":"10.1016/j.jinf.2024.106243","DOIUrl":"10.1016/j.jinf.2024.106243","url":null,"abstract":"<div><h3>Objectives</h3><p>High rates of antibiotic prescription in residential aged care are likely to promote enteric carriage of antibiotic-resistant pathogens and increase the risk of antibiotic treatment failure. Despite their importance, relationships between antibiotic exposures and patterns of enteric resistance carriage in this population remain poorly understood.</p></div><div><h3>Methods</h3><p>We conducted a cross-sectional metagenomic cohort analysis of stool samples from residents of five long-term aged-care facilities in South Australia. Taxonomic composition was determined, and enteric carriage of antibiotic resistance genes (ARGs) was identified and quantified against the Comprehensive Antibiotic Resistance Database. Both the detection and abundance of stool taxa and ARGs were related to antibiotic exposures up to 12 months prior. Factors associated with the abundance of ARGs of high clinical concern were identified.</p></div><div><h3>Results</h3><p>Stool samples were provided by 164 participants (median age: 88 years, IQR 81–93; 72% female). Sixty-one percent (n = 100) of participants were prescribed antibiotics at least once in the prior 12 months (median prescriptions: 4, range: 1–52), most commonly a penicillin (n = 55, 33.5%), cephalosporin (n = 53, 32.3%), diaminopyrimidine (trimethoprim) (n = 36, 22%), or tetracycline (doxycycline) (n = 21, 12.8%). More than 1100 unique ARGs, conferring resistance to 38 antibiotic classes, were identified, including 20 ARGs of high clinical concern. Multivariate logistic regression showed doxycycline exposure to be the greatest risk factor for high ARG abundance (adjusted odds ratio [aOR]=14.8, q&lt;0.001) and a significant contributor to inter-class selection, particularly for ARGs relating to penicillins (aOR=3.1, q=0.0004) and cephalosporins (aOR=3.4, q=0.003). High enteric ARG abundance was associated with the number of separate antibiotic exposures (aOR: 6.4, q&lt;0.001), exposures within the prior 30 days (aOR: 4.6, q=0.008) and prior 30–100 days (aOR: 2.6, q=0.008), high duration of antibiotic exposure (aOR: 7.9, q&lt;0.001), and exposure to 3 or more antibiotic classes (aOR: 7.4, q&lt;0.001). Carriage of one or more ARGs of high clinical concern was identified in 99% of participants (n = 162, median: 3, IQR: 2–4), involving 11 ARGs conferring resistance to aminoglycosides, four to beta-lactams, one to glycopeptides, three to fluoroquinolones, and one to oxazolidinones. Carriage of ARGs of high clinical concern was positively associated with exposure to doxycycline (aminoglycoside, fluoroquinolone, and oxazolidinone ARGs) and trimethoprim (fluoroquinolone and beta-lactam ARGs). Analysis of doxycycline impact on microbiota composition suggested that observed resistome changes arose principally through direct ARG selection, rather than through the antibiotic depletion of sensitive bacterial populations.</p></div><div><h3>Conclusions</h3><p>The gut microbiome of aged care residents is ","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001774/pdfft?md5=66bc62ff1df7f53a6670b6a0499a4a28&pid=1-s2.0-S0163445324001774-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in invasive Haemophilus influenzae serotype b (Hib) disease in England: 2012/13 to 2022/23","authors":"","doi":"10.1016/j.jinf.2024.106247","DOIUrl":"10.1016/j.jinf.2024.106247","url":null,"abstract":"<div><h3>Introduction</h3><p><em>Haemophilus influenzae</em> serotype b (Hib) conjugate vaccines have been highly successful in reducing the Hib disease worldwide. Recently, several European countries have reported an increase in invasive Hib disease. We aimed to describe the epidemiology, clinical characteristics, genomic trends, and outcomes of invasive Hib disease over the past 11 years in England.</p></div><div><h3>Methods</h3><p>The UK Health Security Agency (UKHSA) conducts national surveillance of invasive <em>H influenzae</em> disease and hosts a national reference laboratory for confirmation and serotyping. General practitioners are contacted to complete a surveillance questionnaire for confirmed Hib cases. Invasive Hib isolates routinely undergo whole genome sequencing.</p></div><div><h3>Results</h3><p>During 2012/13–2022/23, there were 6881 invasive <em>H. influenzae</em> infections, of which 5852 (85%) were serotyped; most isolates (4881, 83%) were non-typeable <em>H. influenzae</em>, followed by Hif (591, 10%), Hie (189, 3%), Hib (118, 2%) and Hia (54, 1.0%). The median age for invasive Hib disease was 51 years, and most cases (84%, 99/118) were in adults. Children accounted for 19 cases (16%), including 13 (11%) in &lt;1 year-olds and 6 (5%) in 1–5-year-olds. Bacteraemic pneumonia was the most common diagnosis (66/118, 56%). Hib case-fatality rate was 5.9% (7/118), with the last fatality reported in 2016. Among 64 sequenced strains during 2016/17–2022/2023, most (56/64, 88%) belonged to the CC6 lineage (representing ST6 and single locus variants of ST6).</p></div><div><h3>Conclusions</h3><p>In England, invasive Hib disease remains rare with no evidence of any increase in incidence and is rarely fatal, affecting mainly adults with underlying conditions, who typically develop pneumonia.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001816/pdfft?md5=00e269ebe89a68d03f5f926116f4ac1a&pid=1-s2.0-S0163445324001816-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BCG vaccination of healthcare workers for protection against COVID-19: 12-month outcomes from an international randomised controlled trial","authors":"","doi":"10.1016/j.jinf.2024.106245","DOIUrl":"10.1016/j.jinf.2024.106245","url":null,"abstract":"<div><h3>Objectives</h3><p>Bacille Calmette-Guérin (BCG) vaccine has immunomodulatory effects that may provide protection against unrelated infectious diseases. We aimed to determine whether BCG vaccination protects adults against COVID-19.</p></div><div><h3>Design</h3><p>Phase III double-blind randomised controlled trial.</p></div><div><h3>Setting</h3><p>Healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom during the COVID-19 pandemic.</p></div><div><h3>Participants</h3><p>3988 healthcare workers with no prior COVID-19 and no contraindication to BCG.</p></div><div><h3>Intervention</h3><p>Randomised 1:1 using a web-based procedure to receive a single 0.1 mL intradermal dose of BCG-Denmark (BCG group, n = 1999) or saline (placebo group, n = 1989).</p></div><div><h3>Main outcome measures</h3><p>Difference in incidence of (i) symptomatic and (ii) severe COVID-19 during the 12 months following randomisation in the modified intention to treat (mITT) population (confirmed SARS-CoV-2 naïve at inclusion).</p></div><div><h3>Results</h3><p>Of the 3988 participants randomised, 3386 had a negative baseline SARS-CoV-2 test and were included in the mITT population. The 12-month adjusted estimated risk of symptomatic COVID-19 was higher in the BCG group (22.6%; 95% confidence interval [CI] 20.6 to 24.5%) compared with the placebo group (19.6%; 95% CI 17.6 to 21.5%); adjusted difference +3.0% points (95% CI 0.2 to 5.8%; p = 0.04). The 12-month adjusted estimated risk of severe COVID-19 (mainly comprising those reporting being unable to work for ≥3 consecutive days) was 11.0% in the BCG group (95% CI 9.5 to 12.4%) compared with 9.6% in the placebo group (95% CI 8.3 to 11.1%); adjusted difference +1.3% points (95% CI −0.7 to 3.3%, p = 0.2). Breakthrough COVID-19 (post COVID-19 vaccination) and asymptomatic SARS-CoV-2 infections were similar in the two groups. There were 18 hospitalisations due to COVID-19 (11 in BCG group, 7 in placebo group; adjusted hazard ratio 1.56, 95% CI 0.60 to 4.02, p = 0.4) and two deaths due to COVID-19, both in the placebo group.</p></div><div><h3>Conclusions</h3><p>Compared to placebo, vaccination with BCG-Denmark increased the risk of symptomatic COVID-19 over 12 months among healthcare workers and did not decrease the risk of severe COVID-19 or post-vaccination breakthrough COVID-19.</p></div><div><h3>Trial registration</h3><p>ClinicalTrials.gov NCT04327206.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001798/pdfft?md5=65bcee0b4f66914d5673151fbc41be54&pid=1-s2.0-S0163445324001798-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fourth dose bivalent COVID-19 vaccines outperform monovalent boosters in eliciting cross-reactive memory B cells to Omicron subvariants","authors":"","doi":"10.1016/j.jinf.2024.106246","DOIUrl":"10.1016/j.jinf.2024.106246","url":null,"abstract":"<div><p>Bivalent COVID-19 vaccines comprising ancestral Wuhan-Hu-1 (WH1) and the Omicron BA.1 or BA.5 subvariant elicit enhanced serum antibody responses to emerging Omicron subvariants. Here, we characterized the RBD-specific memory B cell (Bmem) response following a fourth dose with a BA.1 or BA.5 bivalent vaccine, in direct comparison with a WH1 monovalent fourth dose. Healthcare workers previously immunized with mRNA or adenoviral vector monovalent vaccines were sampled before and one month after a fourth dose with a monovalent or a BA.1 or BA.5 bivalent vaccine. Serum neutralizing antibodies (NAb) were quantified, as well as RBD-specific Bmem with an in-depth spectral flow cytometry panel including recombinant RBD proteins of the WH1, BA.1, BA.5, BQ.1.1, and XBB.1.5 variants. Both bivalent vaccines elicited higher NAb titers against Omicron subvariants compared to the monovalent vaccine. Following either vaccine type, recipients had slightly increased WH1 RBD-specific Bmem numbers. Both bivalent vaccines significantly increased WH1 RBD-specific Bmem binding of all Omicron subvariants tested by flow cytometry, while recognition of Omicron subvariants was not enhanced following monovalent vaccination. IgG1⁺ Bmem dominated the response, with substantial IgG4⁺ Bmem only detected in recipients of an mRNA vaccine for their primary dose. Thus, Omicron-based bivalent vaccines can significantly boost NAb and Bmem specific for ancestral WH1 and Omicron variants and improve recognition of descendent subvariants by pre-existing, WH1-specific Bmem beyond that of a monovalent vaccine. This provides new insights into the capacity of variant-based mRNA booster vaccines to improve immune memory against emerging SARS-CoV-2 variants and potentially protect against severe disease.</p></div><div><h3>One-sentence summary</h3><p>Omicron BA.1 and BA.5 bivalent COVID-19 boosters, used as a fourth dose, increase RBD-specific Bmem cross-recognition of Omicron subvariants, both those encoded by the vaccines and antigenically distinct subvariants, further than a monovalent booster.</p></div>","PeriodicalId":50180,"journal":{"name":"Journal of Infection","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0163445324001804/pdfft?md5=280d5ad7f22bbcf847012a77ebd4f750&pid=1-s2.0-S0163445324001804-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}