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Background: Multidrug-resistant Neisseria gonorrhoeae strains are prevalent, threatening gonorrhoea treatment globally, and understanding of emergence, evolution, and spread of antimicrobial resistance (AMR) in gonococci remains limited. We describe the genomic evolution of gonococci and their AMR, related to the introduction of antimicrobial therapies, examining isolates from 1928 (preantibiotic era) to 2013 in Denmark. This is, to our knowledge, the oldest gonococcal collection globally. Methods: Lyophilised isolates were revived and examined using Etest (18 antimicrobials) and whole-genome sequencing (WGS). Quality-assured genome sequences were obtained for 191 viable and 40 non-viable isolates and analysed with multiple phylogenomic approaches. Results: Gonococcal AMR, including an accumulation of multiple AMR determinants, started to emerge particularly in the 1950s–1970s. By the twenty-first century, resistance to most antimicrobials was common. Despite that some AMR determinants affect many physiological functions and fitness, AMR determinants were mainly selected by the use/misuse of gonorrhoea therapeutic antimicrobials. Most AMR developed in strains belonging to one multidrug-resistant (MDR) clade with close to three times higher genomic mutation rate. Modern N. gonorrhoeae was inferred to have emerged in the late-1500s and its genome became increasingly conserved over time. Conclusions: WGS of gonococci from 1928 to 2013 showed that no AMR determinants, except penB, were in detectable frequency before the introduction of gonorrhoea therapeutic antimicrobials. The modern gonococcus is substantially younger than previously hypothesized and has been evolving into a more clonal species, driven by the use/misuse of antimicrobials. The MDR gonococcal clade should be further investigated for early detection of strains with predispositions to develop and maintain MDR and for initiation of public health interventions. [ABSTRACT FROM AUTHOR]

Background The epidemiology of nasopharyngeal (NP) pneumococcal carriage varies with geography and has changed in response to pneumococcal conjugate vaccine (PCV): a low prevalence (3% or less of colonizing isolates) of colonization by vaccine-type (VT) pneumococcal serotypes after PCV introduction has been reported. The primary goal of this study was to determine the VT serotype prevalence of NP pneumococcal colonization of children residing in the St. Louis, MO, USA metropolitan area following introduction of the 13-valent PCV in 2010. The secondary goal of this study was to identify characteristics associated with NP pneumococcal carriage of any serotype. Methods Between July 2013 and April 2016, we enrolled 397 healthy children, aged 0–17 years, who required sedation for procedures or minor surgeries at St. Louis Children’s Hospital. NP swabs were collected after sedation or anesthesia and cultured for pneumococcus. Vaccine records were obtained from primary care providers or from state immunization databases. Parents/guardians completed a questionnaire to provide demographics, past medical history and household characteristics. Results Of the 88 pneumococcal isolates recovered from 84 colonized subjects (21.2% of all enrolled subjects; 95% CI 17.2–25.2%), 16 were VT. Eleven isolates were serotype 19F (12.5%), four (4.5%) were 6A and one (1.1%) was 19A. Prevalence of VT among colonizing isolates was thus 18.2% (CI 10.1–26.1%) in our cohort, despite complete PCV vaccination in 87% of colonized children. Factors associated with pneumococcal colonization by any serotype included younger age and daycare attendance. Conclusion Children in St. Louis exhibit a higher prevalence of VT serotypes among pneumococcal carriage isolates than has been reported in other areas in the US, demonstrating the necessity of ongoing surveillance of local epidemiology and providing evidence that serotype 19F can remain prevalent in a pediatric population despite high vaccine uptake. [ABSTRACT FROM AUTHOR]

Background. The capsular polysaccharide of group B meningococci (GBM) is structurally identical to a polysaccharide found on neural cell adhesion molecules in humans. This structural identity has raised concern that a vaccine based on the GBM capsular polysaccharide might induce autoimmune disease in vaccinated persons. Because systemic infection with GBM induces serum antibody in adults, we investigated whether persons with a history of GBM disease are at increased risk of developing autoimmune diseases. Methods. The entire Danish population constituted our study cohort of 7,467,001 individuals, who were observed for autoimmune diseases from 1977 through 2004. At-risk years were counted as the number of uninfected years prior to the first recorded diagnosis of meningococcal disease but changed to person-years at risk at the diagnosis of GBM disease (2984 subjects) or group C meningococcal disease (914 patients). Ratios of incidence rates of autoimmune disease served as measures of the relative risk. Results. Persons with a history of GBM disease experienced a total of 37,290 person-years at risk, ranging from 11 days to 31 years at risk after the onset of GBM disease, during which 49 cases of autoimmune disease occurred. Persons with GBM disease had no increased risk of autoimmune diseases, either compared with persons with a history of group C meningococcal disease (incidence rate ratio, 0.9; 95% confidence interval, 0.5–1.4) or compared with persons without a history of meningococcal disease (incidence rate ratio, 1.1; 95% confidence interval, 0.8–1.5). Conclusions. Our findings suggest that invasive disease caused by GBM is not associated with autoimmune diseases in humans for up to 31 years after meningococcal disease and should lessen concerns regarding the development of a capsular-based GBM vaccine. [ABSTRACT FROM AUTHOR]

Background. The human immune response to a Chlamydia trachomatis serovar D lysate was investigated in patients with urogenital C. trachomatis infection, to identify novel T cell targets. Methods. A C. trachomatis lysate was fractionated on the basis of molecular mass, and each fraction was used to stimulate peripheral-blood mononuclear cells from patients with C. trachomatis infection. In frequently recognized fractions, proteins were identified by mass spectrometry, recombinantly expressed, and tested for T cell recognition. Results. T cell recognition of the fractions was highly heterogeneous in patients with C. trachomatis infection (n = 16). Four patients exhibited responses that were strongly targeted to antigens of 16–20-kDa molecular mass. Three proteins were identified in this fraction: CT043, CT511, and CT521. The T cell response to the individual recombinant proteins were investigated, and CT521 was found to induce the highest level of interferon (IFN)—γ. The recognition of CT521 was investigated in a larger study population (n = 41), and a positive IFN-γ response was measured in 83% of the patients. Several T cell epitopes were identified in CT521; in particular, peptide 5 in the central part of the protein was frequently recognized by T cells (63%). Conclusion. We have identified a novel C. trachomatis antigen, CT521, that is frequently recognized in patients with urogenital C. trachomatis infection. [ABSTRACT FROM AUTHOR]

In this study, we investigated the seminal inflammatory response to egg infestation of the urogenital organs in 240 semen-donating men aged 15–49 years living in a Schistosoma haematobium-endemic area of Madagascar. In 29 subjects (12%) with excretion of &ges;5 ova/ejaculate, leukocytospermia (>106 leukocytes/mL) and the presence of seminal lymphocytes and eosinophil leukocytes were each significantly more prevalent than in 74 subjects (31%) who were S. haematobium negative (P<.01). In addition, seminal levels of interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor-α were significantly higher among seminal egg-excreting subjects than among infection-negative subjects (P<.001). Sexually transmitted infection (STI) with Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and/or Trichomonas vaginalis did not act as a confounding factor for the observed associations. At follow-up, 6 months after systematic antischistosomiasis and STI syndrome treatment at baseline, the prevalence of seminal leukocytes decreased significantly among the previously seminal egg-positive subjects. The same tendency was observed for the posttreatment levels of cytokines. Numerous studies have already shown an association between STI-associated genital inflammation and human immunodeficiency virus (HIV) propagation. Therefore, the results of the present study suggest that male urogenital schistosomiasis may constitute a risk factor for HIV transmission, as a result of egg-induced inflammation in the semen-producing pelvic organs. [ABSTRACT FROM AUTHOR]

Background: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated.Methods: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility.Results: Antimicrobial susceptibility category agreement in each year was ≥91%. Discrepancies in susceptibility categories were generally because the MICs for EQA panel isolates were on or very close to the susceptibility or resistance breakpoints. A high proportion of isolates tested over the 10 years were within one (≥90%) or two (≥97%) MIC log2 dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods.Conclusions: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing. [ABSTRACT FROM AUTHOR]

A surge in gonorrhoea in Denmark has occurred since 2022, a 46% increase from 2021. National surveillance, leveraging mandatory reporting and epidemiological data, highlights three distinct clades linked to heterosexual transmission. Despite the rise, these exhibit high susceptibility, contrasting MSM-associated strains. Geographical hotspots and age-specific patterns further illuminate transmission dynamics. The combination of genomic and epidemiological data provides novel insights into the evolving landscape of gonorrhoea, indicating potential shifts in infection dynamics and transmissibility.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Background: The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic., Methods: For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere., Findings: Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories., Interpretation: COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies., Funding: Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization., Competing Interests: Declaration of interests The UK Health Security Agency's Immunisation and Vaccine Preventable Diseases Division has provided vaccine manufacturers (GSK, Pfizer, and Sanofi) with post-marketing surveillance reports, which the Marketing Authorization Holders are required to submit to the UK Licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. The UK Health Security Agency's Respiratory and Vaccine Preventable Bacteria Reference Unit has received unrestricted research grants from Pfizer to participate in pneumococcal surveillance projects. CHI de Créteil (France) received research grants from the French Public Health Agency, Pfizer, and MSD. University Hospitals Leuven (Belgium) received research grants from Merck-MSD and Pfizer, and consulting fees from Merck-MSD. SD received personal payments or honoraria from Pfizer. The Swiss National Reference Center for Invasive Pneumococci received funding from the Federal Office of Public Health. MH has received grants from Pfizer and personal fees (for being on an advisory board) from Pfizer and Merck Sharp & Dohme. The National Medicines Institute (Warsaw, Poland) received funding from the Polish Ministry of Health, the Polish Ministry of Science and Higher Education, Pfizer, and MSD. AS received payments from MSD and Pfizer for lectures, and from MSD, Pfizer, and Sanofi Pasteur for participation in advisory boards. AS is the unpaid Vice President of the European Meningococcal and Haemophilus Disease Society. The Finnish Institute for Health and Welfare (Finland) received research funding from Pfizer. ABB is an unpaid adviser to WHO, providing expertise related to vaccines and antimicrobial resistance. ABB is an unpaid General Assembly member (2022 onwards), and has been a board member (2016–22) and Secretary (2018–22), of the International Society of Pneumonia and Pneumococcal Diseases (ISPPD). MD has received financial support from Pfizer to attend national scientific meetings. MdP received grant funding from the National Research Foundation (South Africa) and the Bill & Melinda Gates Foundation to support the International Pathogenic Neisseria Conference (IPNC) 2022 meeting. MdP received personal support from the ISPPD to participate in the ISPPD conference in 2022, and was a member of the organising and scientific committee for the IPNC meeting in 2022. HH and MC received a grant from Pfizer (W1243730) to investigate Irish pneumococcal serotypes by whole-genome sequencing. HH received payment from Scottish Hospitals Enquiry for expert testimony. HH was the President of the Healthcare Infection Society (2018–22). KAJ received personal royalties from GlaxoSmithKline, and personal honoraria from the Wellcome Trust. SL performs contract research on behalf of St George's University of London for pharmaceutical companies (GlaxoSmithKline, Pfizer, and Sanofi), including vaccine manufacturers, but does not receive any personal remuneration. T-TL received consulting fees from the Trond Mohn Foundation. T-TL is an unpaid board member of the European Meningococcal and Haemophilus Disease Society and the German Society for Hygiene and Microbiology, committee for microbial systematics, population genetics and infection epidemiology. SM participated on an unpaid advisory board for Pfizer for the meningococcal type B vaccine in South Africa in 2020. WM received funding from GlaxoSmithKline and Pfizer for investigator-initiated research on meningitis B (MenB) strain vaccine coverage. CS received financial support for flights, accommodation, and registration to attend the 2022 ISPPD meeting in Canada. H-CS received funding from Pfizer for a pneumococcal carriage project. H-CS received funding for participation on a data safety monitoring board or advisory board for MSD. LS received personal support from the European Centre for Disease Prevention and Control for attending the European Scientific Conference on Applied Infectious Disease Epidemiology in 2022. MPGvdL received consulting fees from Pfizer, Merck, and GlaxoSmithKline; payment or honoraria from Pfizer and Merck; and support for attending meetings or travel, or both, from Pfizer. AvG is the chairperson for the National Advisory Group on Immunization of South Africa. NMvS received fees for services and consulting fees from MSD and GlaxoSmithKline, and research funding from the Dutch Health Counsel, US National Institutes of Health, and Amsterdam University Medical Centers, and from MSD and GlaxoSmithKline, which are all directly paid to the institution. NMvS holds a patent (WO 2013/020090 A3) on vaccine development against Streptococcus pyogenes. NMvS is an unpaid scientific adviser to the ItsME foundation, and a scientific adviser to the StrepAotearoa New Zealand project but fees are paid to the University of Amsterdam. NMvS holds personal stocks in Genmab. JY received payments for lectures given at scientific meetings organised by MSD and Pfizer; received support from MSD and Pfizer to attend national and international scientific meetings; and participated in advisory boards for MSD and Pfizer. DS is supported by an Oxford Clarendon Scholarship. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus .

The world has seen numerous infectious disease outbreaks in the past decade. In many cases these outbreaks have had considerable perinatal health consequences including increased risk of preterm delivery (e.g., influenza, measles, and COVID-19), and the delivery of low birth weight or small for gestational age babies (e.g., influenza, COVID-19). Furthermore, severe perinatal outcomes including perinatal and infant death are a known consequence of multiple infectious diseases (e.g., Ebola virus disease, Zika virus disease, pertussis, and measles). In addition to vaccination during pregnancy (where possible), pregnant women, are provided some level of protection from the adverse effects of infection through community-level application of evidence-based transmission-control methods. This review demonstrates that it takes almost 2 years for the perinatal impacts of an infectious disease outbreak to be reported. However, many infectious disease outbreaks between 2010 and 2020 have no associated pregnancy data reported in the scientific literature, or pregnancy data is reported in the form of case-studies only. This lack of systematic data collection and reporting has a negative impact on our understanding of these diseases and the implications they may have for pregnant women and their unborn infants. Monitoring perinatal health is an essential aspect of national and global healthcare strategies as perinatal life has a critical impact on early life mortality as well as possible effects on later life health. The unpredictable nature of emerging infections and the potential for adverse perinatal outcomes necessitate that we thoroughly assess pregnancy and perinatal health implications of disease outbreaks and their public health interventions in tandem with outbreak response efforts. Disease surveillance programs should incorporate perinatal health monitoring and health systems around the world should endeavor to continuously collect perinatal health data in order to quickly update pregnancy care protocols as needed., Competing Interests: Author PH held an unpaid position at Brazen Bio. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Malange, Hedermann, Lausten-Thomsen, Hoffmann, Voldstedlund, Aabakke, Eltvedt, Jensen, Breindahl, Krebs, Christiansen and Hedley.)

Background: This study aimed to investigate what impact the COVID-19 pandemic and its associated restrictions had on Chlamydia trachomatis and Neisseria gonorrhoeae infections in Sweden, Denmark and Norway, countries with very different governmental strategies for handling this pandemic., Methods: Retrospective analysis of data collected via requests to Swedish regions and to health authorities in Denmark and Norway. The data were collected for the years 2018-2020 and the data from Sweden were more detailed., Results: When the pandemic restrictions were installed in 2020, the number of reported chlamydia cases decreased. The decline was most pronounced in Norway 10.8% (2019: n  = 28,446; 2020: n  = 25,444) while it was only 3.1% in Denmark (2019: n  = 35,688; 2020: n  = 34,689) and 4.3% in Sweden (2019: n  = 34,726; 2020: n  = 33,339). Nucleic acid amplifications tests for chlamydia decreased in Sweden (10%) and Norway (18%) in 2020 compared to 2019, while in Denmark a 21% decrease was noted in April 2020 but thereafter increased to a higher level than 2019. The number of reported gonorrhoea cases decreased in Sweden (17%) and in Norway (39%) in 2020 compared to 2019, while a 21% increase was noted in Denmark., Conclusions: Pandemic restrictions had an impact on the number of reported chlamydia infections in all three countries, but only temporarily and did not seem to be correlated to the restriction levels. The number of reported gonorrhoea infections in Sweden and Norway significantly decreased but not in Denmark. Pandemic restrictions appear to have had a limited effect on the spread of chlamydia and gonorrhoea.

Background: Risk of invasive meningococcal disease (IMD) is increased in patients with complement deficiency and human immunodeficiency virus (HIV) infection. Risk associated with comorbidity is not well described., Methods: This was a nationwide adult case-control study. Cases for the period 1977-2018 were identified by the national meningococcus reference laboratory. Matched controls were identified by registry linkage. Comorbidities diagnosed prior to IMD were based on the International Classification of Diseases, Eighth or Tenth Revision. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated by logistic regression after adjustment for sex, age, and other comorbidities., Results: We identified 1221 cases (45% male), with a median age of 45 years (interquartile range, 22-64 years). The dominant meningococcal serogroups were B (n = 738) and C (n = 337). Increased risk of IMD was associated with solid organ transplantation (SOT) (OR 40.47 [95% CI: 4.84-337.23]), hemolytic anemia (OR 7.56 [95% CI: 2.63-21.79]), renal disease (OR 2.95 [95% CI: 1.77-4.92]), liver disease (OR 2.54 [95% CI: 1.58-4.08]), cancer (OR 2.31 [95% CI: 1.85-2.89]), diabetes (OR 1.74 [95% CI: 1.27-2.39]), neurological disease (OR 1.72 [95% CI: 1.20-2.46]), and autoimmune disease (OR 1.70 [95% CI: 1.63-2.11]). Having 1, 2, and ≥3 comorbidities was associated with increased risk of IMD (ORs 1.6-3.5). Increased risk was not associated with specific serogroups., Conclusions: This study of adults with IMD over 4 decades showed increased risk of IMD associated with renal disease, immunological disorders, liver disease, cancer, and SOT ranging from a 2- to 40-fold increased risk. Vaccination may be warranted in these populations., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We aimed to descriptively analyse the possible impact of the national COVID-19 interventions on the incidence of common infectious diseases in Denmark during spring and summer 2020. This observational study focused on national register data on infections caused by 16 different bacterial and viral pathogens. We included new cases registered between 1 January 2016 and 31 July 2020. The weekly number of new cases were analysed with respect to the COVID-19-related interventions introduced during 2020. We found a marked decrease in infections associated with droplet transmission coinciding with the COVID-19 interventions in spring and summer 2020. These included decreases in both viral and bacterial airway infections and also decreases in invasive infections caused by Streptococcus pneumoniae , Haemophilus influenzae and Neisseria meningitidis . There was also a reduction in cases associated with foodborne transmission during the COVID-19 lockdown period. We found no effect of the lockdown on infections by invasive beta-haemolytic streptococci group B, C and G, Staphylococcus aureus bacteraemia, Neisseria gonorrhoeae or Clostridioides difficile . In conclusion, we found that the widespread interventions such as physical distancing, less travel, hygiene measures and lockdown of schools, restaurants and workplaces together coincided with a marked decline in respiratory infections and, to a smaller extent, some foodborne-transmitted infections.

The aim of this study was to determine whether COVID-19 restrictions had an impact on Chlamydia trachomatis infections compared with 2018 and 2019. A retrospective nationwide observational study was performed using monthly incidences of laboratory-confirmed chlamydia cases and number of tests, obtained from Danish national surveillance data. Testing rates and positivity rates were compared using Poisson and logistic regression. The first Danish COVID-19 lockdown (12 March to 14 April 2020) resulted in a reduction in the number of chlamydia tests performed (rate ratio 0.72, 95% confidence interval  0.71-0.73) and a consequent reduction in the number of laboratory-identified cases (66.5 vs 88.3 per 100,000 population during the same period in 2018 to 2019). This period was followed by a return of testing and test positivity close to the level seen in 2018 to 2019. The second Danish COVID-19 lockdown (17 December to 31 March 2021) resulted in crude incidence rates of laboratory-confirmed chlamydia infection that were similar to the crude incidence rates seen during same period in 2018 to 2019. In conclusion, the Danish COVID-19 restrictions have had negligible effects on laboratory-confirmed C. trachomatis transmission.

Background: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic., Methods: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed., Findings: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded., Interpretation: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide., Funding: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France)., Competing Interests: Declaration of interests The following authors received support for work unrelated to this study: MPGvdL has received grants from Pfizer, Merck, and the Robert Koch Institut; RB has done contract research on behalf of Public Health England for GlaxoSmithKline, Pfizer, and Sanofi Pasteur, but received no personal remuneration; MC has received grants from Pfizer; SAC has done contract research on behalf of Public Health England for GlaxoSmithKline, Pfizer, and Sanofi Pasteur, but received no personal remuneration; SD has received a grant from Pfizer; SJG did contract research (carriage studies) for vaccine manufacturers (GlaxoSmithKline and Pfizer) on behalf of Public Health England, but received no personal remuneration; MH has received grants from Pfizer and the Federal Office of Public Health, and personal fees (for being on an advisory board) from Pfizer and Merck Sharp & Dohme; HH has received grants from Astellas and Pfizer; KAJ has received a grant from Wellcome Trust and personal fees from GlaxoSmithKline; SNL has done contract research for vaccine manufacturers (GlaxoSmithKline, Pfizer, and Sanofi Pasteur) on behalf of St. George's University of London, but received no personal remuneration; DJL has received grants from GlaxoSmithKline and Pfizer; SM has received a grant from Sanofi Pasteur; CM-A has received grants from Quiastat, Roche, Pfizer, and Genomica, and personal fees from Roche, Pfizer, and Qiagen; LS has received a grant from GlaxoSmithKline; H-CS has received a grant from Pfizer; MI has received non-financial support from GlaxoSmithKline and Pfizer, personal fees from Pfizer (speaker fees) and Merck Sharp & Dohme (speaker fees), and grants from Merck Sharp & Dohme; M-KT has received grants from GlaxoSmithKline, Pfizer, and Sanofi Pasteur; ASk has received grants and non-financial support from Pfizer, and personal fees from Pfizer, Merck Sharp & Dohme, and Sanofi Pasteur; CLS has received grants from Pfizer and GlaxoSmithKline for investigator-led research; EV has received grants on behalf of her institution (Intercommunal Hospital of Créteil) from Pfizer and Merck Sharp & Dohme; MT has received grants from GlaxoSmithKline and Pfizer; NKF's institution (Public Health England) has received funding for investigator-initiated research from GlaxoSmithKline, Pfizer, and other vaccine manufacturers (GlaxoSmithKline, Pfizer, and Affinivax), but NKF received no personal remuneration; AvG has received a grant from Sanofi Pasteur; NMvS has received a grant from Pfizer, a fee for service paid to their institution from Merck Sharp & Dohme and GlaxoSmithKline, and also has a patent (WO 2013/020090 A3) on vaccine development against Streptococcus pyogenes, unrelated to this study, with royalties paid to University of California San Diego, CA, USA; and MKT has a patent (630133) for a vaccine for serogroup X meningococcus with GlaxoSmithKline. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Oculo-genital chlamydia caused by Chlamydia trachomatis is the most frequent sexually transmitted infection. The number of laboratory verified cases increases steadily in Denmark. This is due to an increased testing activity but also increased positivity rates. Men show substantially lower test rates than women albeit higher positivity rates and seem to constitute an important reservoir for a continued high prevalence of chlamydia. Screening and treatment of especially younger sexually active individuals, not at least men, is vital in controlling the disease.

Objectives: To determine the antimicrobial susceptibility and genotype distribution of Neisseria gonorrhoeae strains isolated from a cohort of patients in Nuuk, Greenland in order to assess the risk of rapid spread in the event of introduction of new strains., Methods: Gonococcal isolates (n=102) obtained from a prospective cohort study of ciprofloxacin resistance were collected between March 2012 and February 2013. Etest minimal inhibitory concentrations (MICs) were determined for ciprofloxacin, azithromycin, ceftriaxone, penicillin, tetracycline, spectinomycin and gentamicin. All isolates were subjected to molecular typing using N. gonorrhoeae multiantigen sequence typing (NG-MAST). After the introduction of a ciprofloxacin-resistant strain in early 2014, an additional 18 isolates were characterised., Results: During the study period, all 102 isolates were fully susceptible to ciprofloxacin (≤0.03 mg/L), azithromycin, spectinomycin, gentamicin and ceftriaxone. 10 different NG-MAST types circulated in Nuuk but 7 were found as single isolates, and 3 of the 7 belonged to 1 of the 3 major genogroups (G210, G9816 and G9817) together comprising 96% of the 102 isolates. ST210 accounted for 55% of the 102 strains. The newly introduced ciprofloxacin resistant strain belonged to ST2400 and dominated the population with 59% resistant strains within 6 months after its introduction. All G2400 strains had MICs≥2 mg/L., Conclusions: Introduction of a ciprofloxacin-resistant strain into a very homogeneous N. gonorrhoeae population led to an explosive spread of the resistant clone, probably as a result of large sexual networks suggested by the strain homogeneity. Careful surveillance of antimicrobial susceptibility is essential to avoid widespread treatment failure in closed populations., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Serological response to treatment of syphilis with orally administered doxycycline or intramuscularly administered penicillin was assessed in patients with concurrent HIV. All HIV-infected individuals diagnosed with syphilis attending 3 hospitals in Copenhagen, Denmark were included. Odds ratios (ORs) with 95% confidence intervals (CI) associated with serological outcome were modelled using propensity-score-adjusted logistic regression analysis. In total, 202 cases were treated with doxycycline or intramuscular penicillin. At 12 months, serological failure was observed in 12 cases (15%) treated with doxycycline and in 8 cases (17%) treated with penicillin (OR 0.78 (95% CI 0.16-3.88), p = 0.76). The serological cure rate at 12 months was highest in patients with primary syphilis (100%), followed by patients with secondary (89%), early latent (71%) and late latent (67%) syphilis (p = 0.006). In conclusion, this study provides evidence for the use of doxycycline as a treatment option when treating a HIV-infected population for syphilis.

Background: Surveillance data on invasive pneumococcal disease (IPD) in Denmark (1999-2014) was analysed regarding the incidence and age-distribution due to ten selected non-PCV serotypes (10-Non-PCV). The effect of PCV-7 and PCV-13 vaccines on the 10-Non-PCV IPD incidence was examined., Methods: IPD cases caused by serotypes included in PCV-7, the additional six serotypes included in PCV-13 and 10-Non-PCV serotypes were identified (8, 9N, 11A, 12F, 15A, 22F, 24F, 20, 23B, 33F). The IPD incidence was stratified by three age groups: 0-4 years, 5-64 years and 65+ years., Results: The predominant IPD cases were caused by serotypes that are not included in PCV-13 (71%), followed by the six additional PCV-13 serotypes. The IPD incidence of serotypes included in the PCV-7 decreased markedly after PCV-7 introduction but are still diagnosed at a low level. The IPD incidence for the 10-Non-PCV serotypes was low for age groups 0-4 years and 5-64 years but high for 65+ years., Conclusion: Future vaccinations of the young age group alone with a vaccine targeting some of the 10-Non-PCV serotypes may not elicit the desired effect on herd protection since these serotypes are primarily causing IPD among the elderly. Future pneumococcal vaccination strategies in Denmark may therefore need carriage studies in order to identify among whom the pneumococcal serotypes causing IPD are carried., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

We sequenced the genomes of 3,615 strains of serotype Emm protein 1 (M1) group A Streptococcus to unravel the nature and timing of molecular events contributing to the emergence, dissemination, and genetic diversification of an unusually virulent clone that now causes epidemic human infections worldwide. We discovered that the contemporary epidemic clone emerged in stepwise fashion from a precursor cell that first contained the phage encoding an extracellular DNase virulence factor (streptococcal DNase D2, SdaD2) and subsequently acquired the phage encoding the SpeA1 variant of the streptococcal pyrogenic exotoxin A superantigen. The SpeA2 toxin variant evolved from SpeA1 by a single-nucleotide change in the M1 progenitor strain before acquisition by horizontal gene transfer of a large chromosomal region encoding secreted toxins NAD(+)-glycohydrolase and streptolysin O. Acquisition of this 36-kb region in the early 1980s into just one cell containing the phage-encoded sdaD2 and speA2 genes was the final major molecular event preceding the emergence and rapid intercontinental spread of the contemporary epidemic clone. Thus, we resolve a decades-old controversy about the type and sequence of genomic alterations that produced this explosive epidemic. Analysis of comprehensive, population-based contemporary invasive strains from seven countries identified strong patterns of temporal population structure. Compared with a preepidemic reference strain, the contemporary clone is significantly more virulent in nonhuman primate models of pharyngitis and necrotizing fasciitis. A key finding is that the molecular evolutionary events transpiring in just one bacterial cell ultimately have produced millions of human infections worldwide.

A mutant Chlamydia trachomatis variant was detected in Sweden in 2006 and has since also been diagnosed in Norway, but not in Ireland or the Netherlands. This paper describes a study aimed at assessing the presence of the new variant in Denmark. Between November 2006 and April 2007 we tested 3,770 specimens using methods capable of detecting the new variant and distinguishing it from the wild type. In late March 2007 we found one case of the new variant in a 19-year old Danish woman without any known relationship to Sweden. It is surprising that the spread of this sexually transmitted pathogen into Denmark and within Denmark has been so low in view of its rapid and substantial spread within Sweden.