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To determine invasive group A Streptococcus trends in Canada, we characterized emm1 isolates collected during 2018–2023. The percentage of hypervirulent M1UK lineage isolates increased significantly, from 22.1% in 2018 to 60.2% in 2023. Genomic analysis identified geographically and temporally associated clusters and genes associated with virulent bacteriophage acquisition.

Background: While Streptococcus agalactiae (Group B Streptococcus [GBS]) infections in infants usually result from maternal transmission, healthcare-associated cases, particularly in the neonatal intensive care unit (NICU), can occur. Whole genome sequencing (WGS) can aid in investigating GBS outbreaks among infants in hospital settings. The aim of the study is to describe the investigation of GBS infections in NICU using WGS. Methods: Infection prevention and control (IPAC) at our hospital monitors the occurrence of late-onset GBS disease (LOD) in our 57-bed NICU, which consists of all private rooms. The occurrence of 2 cases of LOD within 2 weeks triggered an investigation, including WGS of the two isolates and isolates causing invasive GBS during the last 6 months in the unit. GBS isolates underwent WGS using Illumina at Canada’s National Microbiology Laboratory. All affected patients underwent chart-review. Outbreak description and investigation: In August 2023, two NICU neonates (patients 2,3) experienced LOD two weeks apart, one with bacteremic meningitis and the other with two bacteremic episodes three weeks apart. While WGS was pending two additional cases of late-onset GBS bacteremia (patients 4,5) occurred. Isolates from Pts 2,3 and 5 were indistinguishable from each other and from an isolate from an infant admitted to the NICU with early onset bacteremia on July 27, 2023 (day 1 of life) (patient 1). Weekly point prevalence for throat and rectal colonization over 3 weeks identified five infants colonized with unrelated strains. An additional long-stay infant (patient 6) developed GBS conjunctivitis due to a strain indistinguishable from (patient 4) by pulse field gel electrophoresis, WGS for the second cluster is pending. IPAC interventions: Lapses in IPAC practices were observed, with no commonalities among cases other than similar geographic location within the unit. We hypothesized transmission was due to horizontal transmission between babies due to these lapses. Basic IPAC measures, including hand hygiene and environmental cleaning, were reinforced; Additional Precautions were not used due to private rooms’ unit structure. No environmental samples were taken due to lack of an obvious environmental point or common source. Point prevalence monitoring persisted until no new cases related to the outbreak strains were further identified in three consecutive weekly point prevalence. Conclusions: Increased awareness of healthcare-associated transmission is crucial in NICU as LOD GBS emerges. WGS plays a key role in identifying transmission. Detecting a multi-strain outbreak can appropriately redirect investigations. Legend: Figure 1: Timeline of stay at NICU and infection timing for patients 1-6

BackgroundThe treatment of minimal change disease (MCD) consists of a high dose of steroids for several months, implying significant drug toxicity. Nevertheless, relapses of steroid-sensitive MCD usually respond to lower doses of steroids.MethodsThe objective of this study was to analyze whether a low dose of steroids (LDS) is effective for the treatment of MCD relapses. Since 2018, new relapses of steroid-sensitive adult patients with MCD in three Spanish centers have been treated with LDS. The cumulative dose of steroids, the time to remission, and the relapse-free time were compared between relapses treated with LDS and previous relapses of the same patients treated with a standard dose of steroids (SDS).ResultsA total of 51 relapses in 31 patients were treated with LDS and compared with 48 historical relapses of the same patients treated with SDS. The mean doses of prednisone adjusted by weight for the initial treatment were 0.45 mg/kg (0.40–0.51 mg/kg) in the relapses treated with LDS and 0.88 mg/kg (0.81–1.00 mg/kg) in those treated with SDS. The mean cumulative doses of prednisone in LDS- and SDS-treated relapses were 1,191 mg (801–1,890 mg) and 3,700 mg (2,755–5,800 mg), respectively. The duration of treatment was 63 days (42–117 days) in the LDS group and was 140 days (65–195 days) in the SDS group. All patients achieved complete remission within 1 month after steroid therapy in both groups. The times to remission of the LDS and SDS groups were 19.10 ± 12.80 and 18.93 ± 12.98 days, respectively (p = 0.95).ConclusionAmong the steroid-sensitive patients with MCD, relapse therapy with LDS (0.5 mg/kg) appears effective and allows minimization of the steroid cumulative dose.

ABSTRACT The International Circumpolar Surveillance (ICS) program is a population-based surveillance network for invasive bacterial diseases throughout Arctic countries and territories. The ICS quality control program for Streptococcus pneumoniae serotyping and antimicrobial susceptibility testing has been ongoing since 1999. Current participating laboratories include the Provincial Laboratory for Public Health in Edmonton, Alberta; Laboratoire de santé publique du Québec in Sainte-Anne-de-Bellevue, Québec; the Centers for Disease Control’s Arctic Investigations Program in Anchorage, Alaska; the Neisseria and Streptococcus Reference Laboratory at Statens Serum Institut in Copenhagen, Denmark; the Department of Clinical Microbiology, Landspitali in Reykjavik, Iceland; and Public Health Agency of Canada’s National Microbiology Laboratory in Winnipeg, Manitoba. From 2009 to 2020, 140 isolates of S. pneumoniae were distributed among the six laboratories as part of the quality control program. Overall serotype concordance was 96.9%, with 99.3% concordance to pool level. All participating laboratories had individual concordance rates >92% for serotype and >97% for pool. Overall concordance by modal minimum inhibitory concentration (MIC) for testing done by broth microdilution or Etest was 99.1%, and >98% for all antimicrobials tested. Categorical concordance was >98% by both CLSI and EUCAST criteria. For two laboratories performing disc diffusion, rates of concordance by modal MIC were >97% for most antimicrobials, except chloramphenicol (>93%) and trimethoprim/sulfamethoxazole (>88%). Data collected from 12 years of the ICS quality control program for S. pneumoniae demonstrate excellent (≥95%) overall concordance for serotype and antimicrobial susceptibility testing results across six laboratories.IMPORTANCEArctic populations experience several social and physical challenges that lead to the increased spread and incidence of invasive diseases. The International Circumpolar Surveillance (ICS) program was developed to monitor five invasive bacterial diseases in Arctic countries and territories. Each ICS organism has a corresponding interlaboratory quality control (QC) program for laboratory-based typing, to ensure the technical precision and accuracy of reference testing services for these regions, and identify and correct potential problems. Here, we describe the results of the ICS Streptococcus pneumoniae QC program, from 2009 to 2020. Excellent overall concordance was achieved for serotype and antimicrobial susceptibility testing results across six laboratories. Ongoing participation in these QC programs ensures the continuation of quality surveillance systems within Arctic populations that experience health disparities.

Antarctica is one of the most outstanding analogs of Mars, and cyanobacterial mats are considered one of the most resilient biological consortia. The purpose of this study is to find out the effect of the Martian conditions on an Antarctic cyanobacterial mat. We exposed an Antarctic microbial mat to Martian conditions in a simulating chamber (MARTE) for 15 d and investigated the variations in the consortium by the use of 16S rRNA gene expression as an indicator of the biological activity. Metabarcoding using the V3-V4 regions of the 16S rRNA gene was used to determine the succession of the active members of the microbial consortium during the experiment. The results showed that the microbial mat, far from collapsing, can survive the stringent conditions in the simulating chamber. Different behaviors were displayed depending on the metabolic capabilities and physiological characteristics of every taxon. The main conclusion is that the Martian conditions did not impair growth in some of the groups, and thus, the investigated Antarctic community would be able to survive in a Martian environment at least during the short experimental period, although elements of the community were affected in different ways.

Photoreduction of CO2 to solar fuels and chemicals offers a sustainable method to produce net zero energy vectors. For large-scale applications, it is crucial to develop an improved understanding of the influence of reaction conditions on the design and optimisation of the photoreactor. The performance of CuO impregnated on BaTiO3 photocatalyst was investigated and compared to pristine BaTiO3, and CuO impregnated on commercial P25 (CuO/P25) and ZnO. The influence of irradiance, CO2 and H2O flow and partial pressure, and CO2/H2O ratio on the product yield and selectivity were examined. Using Design of Experiments and Computational Fluid Dynamic modelling, the optimised reaction conditions were irradiance of 125 mW cm−2, with a CO2 flow of 0.09 mL min−1, and water bubbler temperature of 25 °C. At these conditions, a 2 and 10-fold increase of CO and CH4 production, respectively, were obtained, compared to baseline conditions as well as exhibited the highest CO and CH4 production rate compared to previous reports. Among the earth-abundant photocatalysts, CuO/P25 had the highest quantum yield for CH4 (φCH4: 0.47), whilst CuO/BaTiO3 exhibited highest φCO (0.09) and stability for CO production. The under-performing of BaTiO3 and CuO/BaTiO3 was attributed to the presence of amorphous phase in BaTiO3. This work reveals that the combination of catalyst design, reaction engineering, and modelling can improve the efficiencies of CO2 photoreduction.

Summary: 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.

Introduction: Endothelial dysfunction and platelet activation have been highlighted as possible mediators in Takotsubo syndrome (TTS). Nevertheless, to date, evidence on the usefulness of antiplatelet therapy in TTS remains controversial. The aim of our study is to evaluate long-term prognosis in TTS patients treated with antiplatelet therapy (APT) at hospitalization discharge. Material and methods: An ambispective cohort study from the Spanish National Takotsubo Registry database was performed (June 2002 to March 2017). Patients were divided into two groups: those who received APT at hospital discharge (APT cohort) and those who did not (non-APT cohort). Primary endpoint was all-cause death. Secondary endpoints included the composite of recurrence or readmission and a composite of death, recurrence or readmission. Results: From a total of 741 patients, 728 patients were alive at discharge. Follow-up was performed in 544 patients, who were included in the final analysis: 321 patients (59.0%) in the APT cohort and 223 patients (41.0%) in the non-APT cohort. The APT cohort had a better clinical presentation and received more heart failure and acute coronary syndrome-like therapies (angiotensin converting enzyme inhibitors/angiotensin receptor blockers: 75.1% vs. 51.1%; p

Contexte : Le programme de surveillance circumpolaire internationale assure la surveillance de cinq maladies bactériennes invasives : les pneumococcies invasives, les infections invasives à streptocoque du groupe A, l’Haemophilus influenzae, les infections invasives à méningocoque et les streptocoques du groupe B. Les maladies bactériennes invasives ont une charge de morbidité plus élevée dans les populations nordiques que dans le reste du Canada. Méthodologies : Afin de décrire l’épidémiologie des maladies bactériennes invasives dans le nord du Canada de 1999 à 2018, les données relatives aux pneumococcies invasives, aux infections invasives à streptocoque du groupe A, à l’Haemophilus influenzae, aux infections invasives à méningocoque et aux streptocoques du groupe B ont été extraites du programme de surveillance circumpolaire internationale et du Système canadien de surveillance des maladies à déclaration obligatoire (SSMDO) et analysées. Résultats : Les taux d’incidence annualisés des pneumococcies invasives, des infections invasives à streptocoque du groupe A, de l’Haemophilus influenzae, des streptocoques du groupe B et des infections invasives à méningocoque étaient respectivement de 23,3, 10,5, 8,9, 1,9 et 1,1 pour 100 000 habitants. L’incidence de la pneumococcie invasive, de l’infection invasive à streptocoque du groupe A et de l’Haemophilus influenzae de type b (Hib) était respectivement 2,8, 3,2 et 8,8 fois plus élevée dans le Nord du Canada que dans le reste du pays. Les taux de maladie ont diminué de manière statistiquement significative pour la pneumococcie invasive (β = -0,02) et ont augmenté de manière statistique pour l’infection invasive à streptocoque du groupe A (β = 0,08) et l’Haemophilus influenzae sérotype a (β = 0,04) pendant la période d’étude. Dans le Nord du Canada, les taux d’incidence annualisés des pneumococcies invasives, des infections invasives à streptocoque du groupe A et de l’Haemophilus influenzae étaient statistiquement plus élevés chez les résidents autochtones que chez les résidents non autochtones. Les taux d’incidence les plus élevés ont été enregistrés dans les groupes d’âge très jeunes et plus âgés. Conclusion : Les maladies bactériennes invasives représentent une charge de morbidité importante pour les populations nordiques du Canada. Les peuples autochtones, les enfants et les personnes âgées sont particulièrement exposés.

Background: The International Circumpolar Surveillance (ICS) program conducts surveillance on five invasive bacterial diseases: pneumococcal disease (IPD), group A streptococcus (iGAS), Haemophilus influenzae (Hi), meningococcal disease (IMD) and group B streptococcus (GBS). Invasive bacterial diseases have a higher burden of disease in northern populations than the rest of Canada. Methods: To describe the epidemiology of invasive bacterial diseases in northern Canada from 1999 to 2018, data for IPD, iGAS, Hi, IMD and GBS were extracted from the ICS program and the Canadian Notifiable Diseases Surveillance System (CNDSS) and analyzed. Results: The annualized incidence rates for IPD, iGAS, Hi, GBS and IMD were 23.3, 10.5, 8.9, 1.9 and 1.1 per 100,000 population, respectively. The incidence of IPD, iGAS and Hi serotype b were 2.8, 3.2 and 8.8 times higher, respectively, in northern Canada than in the rest of Canada. Rates of disease decreased statistically significantly for IPD (β=−0.02) and increased statistically for iGAS (β=0.08) and Hi serotype a (β=0.04) during the study period. In Northern Canada, the annualized incidence rates for IPD, iGAS and Hi were statistically higher for Indigenous residents than for non-Indigenous residents. The highest incidence rates were among the very young and older age groups. Conclusion: Invasive bacterial diseases represent a high burden of disease in Canada’s northern populations. Indigenous peoples, children and seniors are particularly at risk.

After the introduction of pneumococcal conjugate vaccines for children, invasive pneumococcal disease caused by Streptococcus pneumoniae serotype 4 declined in all ages in Alberta, Canada, but it has reemerged and spread in adults in Calgary, primarily among persons who are experiencing homelessness or who use illicit drugs. We conducted clinical and molecular analyses to examine the cases and isolates. Whole-genome sequencing analysis indicated relatively high genetic variability of serotype 4 isolates. Phylogenetic analysis identified 1 emergent sequence type (ST) 244 lineage primarily associated within Alberta and nationally distributed clades ST205 and ST695. Isolates from 6 subclades of the ST244 lineage clustered regionally, temporally, and by homeless status. In multivariable logistic regression, factors associated with serotype 4 invasive pneumococcal disease were being male, being

We assessed antimicrobial resistance (AMR) in Neisseria gonorrhoeae in Nunavut, Canada, using remnant gonorrhea nucleic acid amplification test–positive urine specimens. This study confirms the feasibility of conducting N. gonorrhoeae AMR surveillance and highlights the diversity of gonococcal sequence types and geographic variation of AMR patterns in the territory.

Aorto-ventricular tunnels are rare, congenital extracardiac connections arising from the tubular ascending aorta, above the sinotubular junction, which communicate directly with the ventricular cavity. We present long-term follow-up in a series of five adults undergoing pediatric repair and describe the cardiovascular features and outcomes. Significant aortic regurgitation, ascending aortic aneurysm and left ventricular noncompaction were found to be highly prevalent, emphasizing the need for ongoing surveillance following repair of this anomaly.

Abstract Background Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. Methods Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch ( https://pathogen.watch/ngonorrhoeae ). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. Results AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. Conclusions The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.

Residual learning is known for being a learning framework that facilitates the training of very deep neural networks. Residual blocks or units are made up of a set of stacked layers, where the inputs are added back to their outputs with the aim of creating identity mappings. In practice, such identity mappings are accomplished by means of the so-called skip or shortcut connections. However, multiple implementation alternatives arise with respect to where such skip connections are applied within the set of stacked layers making up a residual block. While residual networks for image classification using convolutional neural networks (CNNs) have been widely discussed in the literature, their adoption for 1D end-to-end architectures is still scarce in the audio domain. Thus, the suitability of different residual block designs for raw audio classification is partly unknown. The purpose of this article is to compare, analyze and discuss the performance of several residual block implementations, the most commonly used in image classification problems, within a state-of-the-art CNN-based architecture for end-to-end audio classification using raw audio waveforms. Deep and careful statistical analyses over six different residual block alternatives are conducted, considering two well-known datasets and common input normalization choices. The results show that, while some significant differences in performance are observed among architectures using different residual block designs, the selection of the most suitable residual block can be highly dependent on the input data.

Pulmonary arterial hypertension (PAH) is a severe condition with a high mortality rate despite advances in diagnostic and therapeutic strategies. In recent years, significant scientific progress has been made in the understanding of the underlying pathobiological mechanisms. Since current available treatments mainly target pulmonary vasodilation, but lack an effect on the pathological changes that develop in the pulmonary vasculature, there is need to develop novel therapeutic compounds aimed at antagonizing the pulmonary vascular remodeling. This review presents the main molecular mechanisms involved in the pathobiology of PAH, discusses the new molecular compounds currently being developed for the medical treatment of PAH and assesses their potential future role in the therapeutic algorithms of PAH.

Summary: Background: Gonorrhoea and antimicrobial resistance (AMR) in Neisseria gonorrhoeae are major health concerns globally. Increased global surveillance of gonococcal AMR is essential. We aimed to describe the 2017–18 data from WHO's global gonococcal AMR surveillance, and to discuss priorities essential for the effective management and control of gonorrhoea. Methods: We did a retrospective observational study of the AMR data of gonococcal isolates reported to WHO by 73 countries in 2017–18. WHO recommends that each country collects at least 100 gonococcal isolates per year, and that quantitative methods to determine the minimum inhibitory concentration of antimicrobials, interpreted by internationally standardised resistance breakpoints, are used. Findings: In 2017–18, 73 countries provided AMR data for one or more drug. Decreased susceptibility or resistance to ceftriaxone was reported by 21 (31%) of 68 reporting countries and to cefixime by 24 (47%) of 51 reporting countries. Resistance to azithromycin was reported by 51 (84%) of 61 reporting countries and to ciprofloxacin by all 70 (100%) reporting countries. The annual proportion of decreased susceptibility or resistance across countries was 0–21% to ceftriaxone and 0–22% to cefixime, and that of resistance was 0–60% to azithromycin and 0–100% to ciprofloxacin. The number of countries reporting gonococcal AMR and resistant isolates, and the number of examined isolates, have increased since 2015–16. Surveillance remains scarce in central America and the Caribbean and eastern Europe, and in the WHO African, Eastern Mediterranean, and South-East Asian regions. Interpretation: In many countries, ciprofloxacin resistance was exceedingly high, azithromycin resistance was increasing, and decreased susceptibility or resistance to ceftriaxone and cefixime continued to emerge. WHO's global surveillance of gonococcal AMR needs to expand internationally to provide imperative data for national and international management guidelines and public health policies. Improved prevention, early diagnosis, treatment of index patients and partners, enhanced surveillance (eg, infection, AMR, treatment failures, and antimicrobial use or misuse), and increased knowledge on antimicrobial selection, stewardship, and pharmacokinetics or pharmacodynamics are essential. The development of rapid, accurate, and affordable point-of-care gonococcal diagnostic tests, new antimicrobials, and gonococcal vaccines is imperative. Funding: None.

Summary: 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).

In July 2018, a case of Neisseria gonorrhoeae associated with ceftriaxone treatment failure was identified in Alberta, Canada. We identified the isolate and nucleic acid amplification testing (NAAT) specimen as the ceftriaxone-resistant strain multilocus sequence type 1903/NG-MAST 3435/NG-STAR 233, originally identified in Japan (FC428), with the same penA 60.001 mosaic allele and genetic resistance determinants. Core single-nucleotide variant (SNV) analysis identified 13 SNVs between this isolate and FC428. Culture-independent surveillance by PCR for the A311V mutation in the penA allele and N. gonorrhoeae multiantigen sequence typing directly from NAAT transport media positive for N. gonorrhoeae by NAAT did not detect spread of the strain. We identified multiple sequence types not previously detected in Alberta by routine surveillance. This case demonstrates the benefit of using culture-independent methods to enhance detection, public health investigations, and surveillance to address this global threat.

The emergence of Neisseria gonorrhoeae strains with resistance (R) to extended-spectrum cephalosporins (ESCsR) represents a public health threat of untreatable gonococcal infections. This study was designed to determine the prevalence and molecular mechanisms of ESCR of Shanghai N. gonorrhoeae isolates. A total of 366 N. gonorrhoeae isolates were collected in 2017 in Shanghai. Susceptibility to ceftriaxone (CRO), cefixime (CFM), azithromycin (AZM), ciprofloxacin (CIP), spectinomycin, penicillin, and tetracycline was determined using the agar dilution method. A subset of 124 isolates was subjected to phylogenetic analysis for nine antimicrobial resistance-associated genes, i.e., penA, porB, ponA, mtrR, 23S rRNA, gyrA, parC, 16S rRNA, and rpsE. Approximately 20.0% of the isolates exhibited CFMR [minimum inhibitory concentration (MIC) >0.125 mg/L], and 5.5% were CROR (MIC > 0.125 mg/L). In total, 72.7% of ESCR isolates were clonal and associated with mosaic penA 10 and 60 alleles. Non-mosaic penA 18 allele and substitutions of PenA A501T, G542S, and PorB1b G213S/Y were observed in non-clonal ESCR. Approximately 6.8% of the isolates showed AZM MIC above the epidemiological cutoff (ECOFF, 1 mg/L), were associated with 23S rRNA A2059G mutation, and did not exhibit clonal distribution. Almost all isolates were CIPR (resistance to ciprofloxacin) and associated with GyrA-91/92 and ParC-85/86/87/88/89/91 alterations. Isolates with ParC S88P substitution were clustered into the ESCR clade. The Shanghai isolates exhibited a high level of ESCR and distinct resistant patterns.

Background In Canada, 13-valent pneumococcal conjugate vaccine (PCV13) is recommended in childhood, in individuals at high risk of invasive pneumococcal disease (IPD) and in healthy adults aged ≥65 years for protection against vaccine-type IPD and pneumococcal community-acquired pneumonia (pCAP). Since vaccine recommendations in Canada include both age-based and risk-based guidance, this study aimed to describe the burden of vaccine-preventable pCAP in hospitalised adults by age.Methods Surveillance for community-acquired pneumonia (CAP) in hospitalised adults was performed prospectively from 2010 to 2015. CAP was radiologically confirmed, and pCAP was identified using blood and sputum culture and urine antigen testing. Patient demographics and outcomes were stratified by age (16–49, 50–64, ≥65 and ≥50 years).Results Of 6666/8802 CAP cases tested, 830 (12.5%) had pCAP, and 418 (6.3%) were attributed to a PCV13 serotype. Of PCV13 pCAP, 41% and 74% were in adults aged ≥65 and ≥50 years, respectively. Compared with non-pCAP controls, pCAP cases aged ≥50 years were more likely to be admitted to intensive care units (ICUs) and to require mechanical ventilation. Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively.Conclusions Adults hospitalised with pCAP in the age cohort of 50–64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada.

Ceftriaxone remains a first-line treatment for patients infected by Neisseria gonorrhoeae in most settings. We investigated the possible spread of a ceftriaxone-resistant FC428 N. gonorrhoeae clone in Japan after recent isolation of similar strains in Denmark (GK124) and Canada (47707). We report 2 instances of the FC428 clone in Australia in heterosexual men traveling from Asia. Our bioinformatic analyses included core single-nucleotide variation phylogeny and in silico molecular typing; phylogenetic analysis showed close genetic relatedness among all 5 isolates. Results showed multilocus sequence type 1903; N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) 233; and harboring of mosaic penA allele encoding alterations A311V and T483S (penA-60.001), associated with ceftriaxone resistance. Our results provide further evidence of international transmission of ceftriaxone-resistant N. gonorrhoeae. We recommend increasing awareness of international spread of this drug-resistant strain, strengthening surveillance to include identifying treatment failures and contacts, and strengthening international sharing of data.

Invasive Streptococcus pneumoniae disease is preceded by asymptomatic nasopharyngeal carriage. Measuring carriage in healthy populations provides data on what serotypes are present in communities, which is of interest in the era of polyvalent pneumococcal conjugate vaccines. Nasopharyngeal swabs from a survey of 682 and 800 healthy children in 2016 and 2018, respectively, were analyzed by culture and Quellung reaction to determine rates of carriage and serotypes. All swabs from 2016 and 300 randomly selected swabs from 2018 were then analyzed using real-time semi-quantitative PCR (qPCR) to detect S. pneumoniae gene targets lytA, piaA, and SP2020 and determine serotype. There were 71 (10.4%) and 68 (8.5%) culture positive samples in 2016 and 2018, respectively. All of these were also positive by qPCR except one that was equivocal. In total, 46.0% of 2016 swabs were positive by qPCR. In 2018, results from the selected sample extrapolated to the complete sample showed 49.0% positive by qPCR. PCV13 serotypes were detected in 29.3% and 21.7% of S. pneumoniae qPCR positive samples from 2016 and 2018, respectively; compared with only 8.4% and 6.0% PCV13 serotypes detected by Quellung reaction in culture positive samples. Compared with culture, qPCR detected S. pneumoniae more frequently. Further, qPCR serotyping detected PCV13 serotypes in a larger proportion of samples than culture and Quellung reaction did, showing that, despite established universal childhood PCV13 immunization, vaccine serotypes can still be detected in a large proportion of young children.

The incidence of group C and G Streptococcus (GCGS) bacteremia, which is associated with severe disease and death, is increasing. We characterized clinical features, outcomes, and genetic determinants of GCGS bacteremia for 89 patients in Winnipeg, Manitoba, Canada, who had GCGS bacteremia during 2012–2014. Of the 89 patients, 51% had bacteremia from skin and soft tissue, 70% had severe disease features, and 20% died. Whole-genome sequencing analysis was performed on isolates derived from 89 blood samples and 33 respiratory sample controls: 5 closely related genetic lineages were identified as being more likely to cause invasive disease than non-clade isolates (83% vs. 57%, p = 0.002). Virulence factors cbp, fbp, speG, sicG, gfbA, and bca clustered clonally into these clades. A clonal distribution of virulence factors may account for severe and fatal cases of bacteremia caused by invasive GCGS.

We identified a ceftriaxone-resistant Neisseria gonorrhoeae isolate in a patient in Canada. This isolate carried the penA-60 allele, which differs substantially from its closest relative, mosaic penA XXVII (80% nucleotide identity). Epidemiologic and genomic data suggest spread from Asia. Antimicrobial susceptibility surveillance helps prevent spread of highly resistant N. gonorrhoeae strains.

We recently showed that 37/600 (6.2%) invasive infections with group B Streptococcus (GBS) in Toronto, Ontario, Canada, were caused by serotype IV strains. We report a relatively high level of genetic diversity in 37 invasive strains of this emerging GBS serotype. Multilocus sequence typing identified 6 sequence types (STs) that belonged to 3 clonal complexes. Most isolates were ST-459 (19/37, 51%) and ST-452 (11/37, 30%), but we also identified ST-291, ST-3, ST-196, and a novel ST-682. We detected further diversity by performing whole-genome single-nucleotide polymorphism analysis and found evidence of recombination events contributing to variation in some serotype IV GBS strains. We also evaluated antimicrobial drug resistance and found that ST-459 strains were resistant to clindamycin and erythromycin, whereas strains of other STs were, for the most part, susceptible to these antimicrobial drugs.

Streptococcus pneumoniae is one of the major causes of pneumonia, meningitis and other pneumococcal infections in young children and elders. Determination of circulating S. pneumoniae serotypes is an essential service by public health laboratories for the monitoring of putative serotype replacement following the introduction of pneumococcal conjugate vaccines (PCVs) and of the efficacy of the immunization program. The Quellung method remains the gold standard for typing S. pneumoniae. Although this method is very effective, it is also costly, time consuming and not totally reliable due to its subjective nature. The objectives of this study were to test and evaluate the efficiency of 3 different molecular methods compared to the Quellung method. Sequential multiplex PCR, sequetyping and whole genome sequencing (WGS) were chosen and tested using a set of diverse S. pneumoniae. One-hundred and eighteen isolates covering 83 serotypes were subjected to multiplex PCR and sequetyping while 88 isolates covering 53 serotypes were subjected to WGS. Sequential multiplex PCR allowed the identification of a significant proportion (49%) of serotypes at the serogroup or subset level but only 27% were identified at the serotype level. Using WGS, 55% to 60% of isolates were identified at the serotype level depending on the analysis strategy used. Finally, sequetyping demonstrated the lowest performance, with 17% of misidentified serotypes. The use of Jin cpsB database instead of the GenBank database slightly improved results but did not significantly impact the efficiency of sequetyping. Although none of these molecular methods may currently replace the Quellung method, WGS remains the most promising molecular pneumococcal serotyping method.

Since implementation of the 13-valent polyvalent conjugate vaccine (PCV13) in Canada during 2010, the proportion of PCV13 serotypes causing invasive pneumococcal disease (IPD) has declined from 55% (n = 1492) in 2010 to 31% (n = 764) in 2014. A concurrent increase of non-PCV13 serotypes has occurred and 22F has become the most prevalent serotype in Canada increasing from 7% (n = 183) to 11% (n = 283). Core single nucleotide variant phylogenetic analysis was performed on 137 Streptococcus pneumoniae serotype 22F isolates collected across Canada from 2005-2015. Six phylogenetic lineages (n = 117) were identified among a serotype 22F/ST433 clonal complex (CC), including a recently expanding erythromycin-resistant clone. Erythromycin-resistance was observed in 25 isolates possessing ermB, mef or a 23S rRNA A2061G point mutation; 2 penicillin-resistant isolates had recombinant pbp1a, pbp2a and/or pbp2x; 3 tetracycline-resistant isolates contained tetM; and 1 isolate was multidrug-resistant. Virulence factor analysis indicated a high level of homogeneity among the 22F/ST433 clonal complex strains. A group of 6 phylogenetic outlier strains had differing MLST, antimicrobial resistance and molecular profiles suggestive of capsule switching events. While capsule switch events among S. pneumoniae serotype 22F has been observed, increasing prevalence of S. pneumoniae serotype 22F can be attributed to an evolving homogenous clone expanding nationally through local transmission events.

Indication of oxygen therapy in fibrotic interstitial lung diseases is not standardized and its specific requirements are not well defined. The objective of this study was to evaluate ambulatory oxygen therapy features in lung fibrotic patients. Clinical and exploratory data, including 6-minute walking test and pulmonary hypertension, from one hundred and seven patients with fibrotic interstitial lung disease that received ambulatory oxygen treatment were studied. In up to 40% of cases the prescription of oxygen therapy was made after performing a 6-minute walking test. Patients who required ambulatory oxygen only during exercise presented a mild to moderate reduction of the predicted % FVC (62.1 ± 19) and DLCO (49 ± 14.4) while patients who had respiratory failure at rest (mean PaO2 51.9 ± 6.7) presented a moderate reduction of %FVC (56.8 ± 15.6) but a severe decrease of %DLCO (31.67 ± 12). Pulmonary hypertension (PH) was evaluated in 47.7% of patients and occurred in 60.8% of them. In conclusion, there is no pulmonary functional predictor of oxyhaemoglobin desaturation during exercise. PH is frequently associated with interstitial lung diseases, mainly when respiratory failure at rest appears. The heterogeneity of the patients and limitation of retrospective studies could be the cause of the tributes for potential benefits of oxygen treatment in interstitial lung diseases.

Two genetically dissimilar sequence type 1 clades dominate the serotype VI group B Streptococcus population of strains causing invasive disease in Canada. Isolates of this rare serotype, recovered mainly from adult patients, were all susceptible to penicillin and vancomycin. However, we observed resistance to erythromycin and clindamycin.

Introduction . The International Circumpolar Surveillance network is a population-based surveillance system that collects data on invasive pneumococcal disease (IPD) in Northern Canada. A 7-valent pneumococcal conjugate vaccine was first introduced in some regions of Northern Canada in 2002, followed by 10-valent (2009) and 13-valent (PCV-13) vaccines (2010). A 23-valent polysaccharide (PPV-23) vaccine was first introduced in 1988 for special populations and adults aged 65 years and older. To describe the epidemiology in the context of pneumococcal vaccination programs, we analysed surveillance data from Northern Canada from 1999 to 2010. Methods . A standardized case report form capturing demographic and clinical information was completed for all IPD cases in Northern Canada meeting the national case definition. Isolates were sent to a reference laboratory for confirmation, serotyping and antimicrobial resistance testing. Both laboratory and epidemiological data were sent to the Public Health Agency of Canada for analysis. Population denominators were obtained from Statistics Canada. Results . From 1999 to 2010, 433 IPD cases were reported (average 36 cases per year). Incidence was greatest among infants aged 1 manifestation. Pneumonia was the most common (70%), followed by bacteremia/septicaemia (30%) and meningitis (8%). Approximately, 42% of cases aged

Background. Streptococcus pneumoniae can cause a wide spectrum of disease, including invasive pneumococcal disease (IPD). From 2005 to 2009 an outbreak of IPD occurred in Western Canada, caused by a S. pneumoniae strain with multilocus sequence type (MLST) 289 and serotype 5. We sought to investigate the incidence of IPD due to this S. pneumoniae strain and to characterize the outbreak in British Columbia using whole-genome sequencing. Methods. IPD was defined according to Public Health Agency of Canada guidelines. Two isolates representing the beginning and end of the outbreak were whole-genome sequenced. The sequences were analyzed for single nucleotide variants (SNVs) and putative genomic islands. Results. The peak of the outbreak in British Columbia was in 2006, when 57% of invasive S. pneumoniae isolates were serotype 5. Comparison of two whole-genome sequenced strains showed only 10 SNVs between them. A 15.5 kb genomic island was identified in outbreak strains, allowing the design of a PCR assay to track the spread of the outbreak strain. Discussion. We show that the serotype 5 MLST 289 strain contains a distinguishing genomic island, which remained genetically consistent over time. Whole-genome sequencing holds great promise for real-time characterization of outbreaks in the future and may allow responses tailored to characteristics identified in the genome.

To increase understanding of drug-resistant Vibrio cholerae, we studied selected molecular mechanisms of antimicrobial drug resistance in the 2010 Haiti V. cholerae outbreak strain. Most resistance resulted from acquired genes located on an integrating conjugative element showing high homology to an integrating conjugative element identified in a V. cholerae isolate from India.

Eleven primer pairs were developed for the identification of Neisseria gonorrhoeae. The sensitivity and specificity of these primers were evaluated by Real Time (RT)-PCR melt curve analyses with DNA from 145 N. gonorrhoeae isolates and 40 other Neisseria or non-Neisseria species. Three primer pairs were further evaluated in a hydrogel-based RT-PCR detection platform, using DNA extracted from 50 N. gonorrhoeae cultures. We observed 100% sensitivity and specificity in the hydrogel assay, confirming its potential as a point-of-care test (POCT) for N. gonorrhoeae diagnosis.

Alberta established a surveillance system in 2001 to monitor resistance to antibiotics used for the treatment of gonorrhea. A retrospective review of gonorrhea cases during the last five years was conducted. All cases of gonorrhea were reportable to public health by testing laboratories and clinicians. Specimens were primarily submitted for nucleic acid amplification testing (NAAT); three sentinel sites obtained specimens for culture and NAAT. The Provincial Laboratory for Public Health conducted E-tests on isolates for multiple antibiotics. A proportion of isolates and NAAT specimens were submitted to the National Microbiology Laboratory for sequence typing (ST). Data were combined and analyzed using SAS version 9.4. Between 2012 and 2016, 13,132 gonorrhea cases were reported; 22.0% (n = 2891) had isolates available for susceptibility testing. All culture positive isolates were susceptible to ceftriaxone. Decreased susceptibility (0.5 ug/mL) to cefixime was reported in four cases in 2014. Resistance to azithromycin (≥2 ug/mL) ranged between 0.4% and 1.8%. Many (n = 509) unique STs were identified; the most prevalent sequence groups (SG) were SG-7638 (n = 367), SG-5985 (n = 145), and SG-11299 (n = 127). The Alberta model for maintaining surveillance for antimicrobial resistance in gonorrhea employs culture and NAAT specimens, providing information crucial to informing provincial treatment guidelines.