Effectiveness of nirsevimab immunoprophylaxis against respiratory syncytial virus-related outcomes in hospital and primary care settings: a retrospective cohort study in infants in Catalonia (Spain).

BACKGROUND: In Catalonia, infants under 6 months old were eligible to receive nirsevimab, a novel monoclonal antibody against respiratory syncytial virus (RSV). We aimed to analyse nirsevimab's effectiveness across primary and hospital care outcomes. METHODS: Retrospective cohort study from 1 October 2023 to 31 January 2024, including all infants born between April and September 2023. We established two cohorts based on nirsevimab administration (immunised and non-immunised). We followed individuals until the earliest moment of an outcome-RSV infection, primary care attended bronchiolitis and pneumonia, hospital emergency visits due to bronchiolitis, hospital admission or intensive care unit (ICU) admission due to RSV bronchiolitis-death or the end of the study. We used the Kaplan-Meier estimator and fitted Cox regression models using a calendar time scale to estimate HRs and their 95% CIs. RESULTS: Among 26 525 infants, a dose of nirsevimab led to an adjusted HR for hospital admission due to RSV bronchiolitis of 0.124 (95% CI: 0.086 to 0.179) and an adjusted HR for ICU admission of 0.099 (95% CI: 0.041 to 0.237). Additionally, the adjusted HRs observed for emergency visits were 0.446 (95% CI: 0.385 to 0.516) and 0.393 (95% CI: 0.203 to 0.758) for viral pneumonia, 0.519 (95% CI: 0.467 to 0.576) for bronchiolitis attended in primary care and 0.311 (95% CI: 0.200 to 0.483) for RSV infection. CONCLUSION: We demonstrated nirsevimab's effectiveness with reductions of 87.6% and 90.1% in hospital and ICU admissions, respectively. These findings offer crucial guidance for public health authorities in implementing RSV immunisation campaigns.

Comparison of next generation technologies and bioinformatics pipelines for capsular typing of Streptococcus pneumoniae.

Whole genome sequencing (WGS)-based approaches for pneumococcal capsular typing have become an alternative to serological methods. In silico serotyping from WGS has not yet been applied to long-read sequences produced by third-generation technologies. The objective of the study was to determine the capsular types of pneumococci causing invasive disease in Catalonia (Spain) using serological typing and WGS and to compare the performance of different bioinformatics pipelines using short- and long-read data from WGS. All invasive pneumococcal pediatric isolates collected in Hospital Sant Joan de Déu (Barcelona) from 2013 to 2019 were included. Isolates were assigned a capsular type by serological testing based on anticapsular antisera and by different WGS-based pipelines: Illumina sequencing followed by serotyping with PneumoCaT, SeroBA, and Pathogenwatch vs MinION-ONT sequencing coupled with serotyping by Pathogenwatch from pneumococcal assembled genomes. A total of 119 out of 121 pneumococcal isolates were available for sequencing. Twenty-nine different serotypes were identified by serological typing, with 24F (n = 17; 14.3%), 14 (n = 10; 8.4%), and 15B/C (n = 8; 6.7%) being the most common serotypes. WGS-based pipelines showed initial concordance with serological typing (>91% of accuracy). The main discrepant results were found at the serotype level within a serogroup: 6A/B, 6C/D, 9A/V, 11A/D, and 18B/C. Only one discrepancy at the serogroup level was observed: serotype 29 by serological testing and serotype 35B/D by all WGS-based pipelines. Thus, bioinformatics WGS-based pipelines, including those using third-generation sequencing, are useful for pneumococcal capsular assignment. Possible discrepancies between serological typing and WGS-based approaches should be considered in pneumococcal capsular-type surveillance studies.

Impact of SARS-CoV-2 infection in pregnant women and their babies: clinical and epidemiological features.

OBJECTIVE: Assess the risk associated with COVID-19 in pregnant women on maternal and neonatal outcomes in Catalonia (Spain) in 2020, before the beginning of COVID-19 vaccination campaign. METHOD: Cross-sectional descriptive study with all pregnant women (41,560) and their live newborns (42,097) (1st March to 31st December 2020). Women were classified: positive and negative COVID-19 diagnosis during pregnancy. The outcomes analysed were complications during pregnancy, gestational age, admission of newborns to neonatal intensive care unit (NICU) and birth weight. Associations among positive COVID-19 and maternal and infant variables were measured with logistic regression models. Results were expressed as odds ratios and 95% confidence intervals. Models were adjusted for nationality, maternal age, socioeconomic status, type of pregnancy and type of centre where the delivery occurred (public or private management hospital). RESULTS: A total of 696 women (1.7%) were diagnosed with COVID-19 during pregnancy. Women with COVID-19 were 4.37 times more likely to have complications during pregnancy (4.37; 3.52-5.40). A total of 713 newborns (1.7%) were from mothers with COVID-19. A positive diagnosis of COVID-19 increased the risk of preterm birth (1.41; 1.03-1.89), admission to NICU (1.40; 1.06-1.82) and low birth weight (1.35; 0.99-1.80) in babies. CONCLUSIONS: Pregnant women with COVID-19 had higher risk of developing complications during pregnancy and their newborns were more likely to be admitted to NICU and had prematurity.

Changes in Invasive Pneumococcal Disease in the Paediatric Population in the Second COVID-19 Pandemic Year.

Incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020, coinciding with the implementation of measures to reduce COVID-19 transmission. We evaluated the impact of the COVID-19 pandemic on healthcare demand and IPD in children in 2021 compared to the pre-pandemic period (2018-2019) and the early pandemic period (2020) in a study carried out during 2018-2021 in Catalonia. Incidence rates were compared by calculating the incidence rate ratio (IRR), and expressing percentage changes in IRR as (1-IRR)x100. Compared to 2018-2019, emergency room (ER) visits declined by 21% in 2021 (p < 0.001), mainly in the first quarter (-39%), and compared to 2020, ER visits increased by 22% in 2021 (p < 0.001), except in the first quarter. IPD incidence overall was 11.0 in 2018-2019 and 4.6 in 2021 (-58%, p < 0.001); the reduction in incidence was similar in the 0-4 age group and was higher in the first quarters. Compared to 2020, in 2021, IPD incidence decreased during the first quarter (-86%, p < 0.001), but increased from 0.0 to 1.2 in the second quarter (p = 0.02) and from 0.6 to 2.1 (p=0.03) in the fourth quarter. The decreased IPD incidence observed in 2021 compared to 2018-2019 (most especially in the first quarter) was greater than the decrease in healthcare demand and PCR test requests. Compared to 2020, IPD incidence decreased in the first quarter when a second state of alarm was in force. In 2021, compared to 2018-2019, there was a greater reduction in PCV13 serotypes than in non-PCV13 serotypes.

Epidemiology and antimicrobial resistance profile of Neisseria gonorrhoeae in Catalonia, Spain, 2016-2019.

Antimicrobial resistance data for Neisseria gonorrhoeae is globally sparse and resistant strains are emerging in Catalonia. We aim to describe epidemiological and antimicrobial resistance in all patients infected with N. gonorrhoeae during the period from 2016 to 2019, using available antimicrobial susceptibility data. We retrospectively analysed confirmed N. gonorrhoeae cases notified to Catalonia's microbiological reporting system. Antibiotic susceptibility testing (azithromycin, cefixime, ceftriaxone, ciprofloxacin, penicillin, spectinomycin, and tetracycline) was assessed using clinical breakpoints published by the European Committee on Antimicrobial Susceptibility Testing. Incidence rates were calculated and proportions were compared using the χ2 test or Fisher's exact test, and analysed using the Statistical Package for Social Sciences (SPSS 18.0). A total of 14,251 confirmed cases of N. gonorrhoeae were notified. Incidence increased from 30.7 cases/100,000 person-years (p < 0.001) in 2016 to 64.7 in 2019. Culture was available in 6,292 isolates (44.2%), of which 5,377 (85.5%) were resistant to at least one of the antibiotics tested. Azithromycin resistance rose from 6.1% in 2016 to 16% in 2019 (p < 0.001). Only 1.0% (45 cases) were resistant to ceftriaxone. Multidrug-resistant N. gonorrhoeae increased from 0.25% in 2016 to 0.42% in 2019 (p = 0.521). One case presented extensively drug-resistant N. gonorrhoeae. In Catalonia, 10% of the N. gonorrhoeae isolates were resistant to azithromycin in the 2016-2019 period. According to World Health Organization guidelines, resistance above 5% indicates an alert to review treatment guidelines. Antimicrobial susceptibility testing in clinical practice followed by surveillance and interventions are essential to monitor trends and prevent the spread of antimicrobial resistance.

The Catalan Surveillance Network of SARS-CoV-2 in Sewage: design, implementation, and performance.

Wastewater-based epidemiology has shown to be an efficient tool to track the circulation of SARS-CoV-2 in communities assisted by wastewater treatment plants (WWTPs). The challenge comes when this approach is employed to help Health authorities in their decision-making. Here, we describe the roadmap for the design and deployment of SARSAIGUA, the Catalan Surveillance Network of SARS-CoV-2 in Sewage. The network monitors, weekly or biweekly, 56 WWTPs evenly distributed across the territory and serving 6 M inhabitants (80% of the Catalan population). Each week, samples from 45 WWTPs are collected, analyzed, results reported to Health authorities, and finally published within less than 72 h in an online dashboard ( https://sarsaigua.icra.cat ). After 20 months of monitoring (July 20-March 22), the standardized viral load (gene copies/day) in all the WWTPs monitored fairly matched the cumulative number of COVID-19 cases along the successive pandemic waves, showing a good fit with the diagnosed cases in the served municipalities (Spearman Rho = 0.69). Here we describe the roadmap of the design and deployment of SARSAIGUA while providing several open-access tools for the management and visualization of the surveillance data.

Effect of COVID-19 Pandemic on Invasive Pneumococcal Disease in Children, Catalonia, Spain.

We analyzed the effect of COVID-19 on healthcare demand and invasive pneumococcal disease in children in Catalonia, Spain. Compared with 2018-2019, we noted large reductions in healthcare activities and incidence of invasive pneumococcal disease in 2020. These changes likely resulted from nonpharmaceutical measures implemented during the COVID-19 pandemic.

Integrated genomic surveillance enables tracing of person-to-person SARS-CoV-2 transmission chains during community transmission and reveals extensive onward transmission of travel-imported infections, Germany, June to July 2021.

BackgroundTracking person-to-person SARS-CoV-2 transmission in the population is important to understand the epidemiology of community transmission and may contribute to the containment of SARS-CoV-2. Neither contact tracing nor genomic surveillance alone, however, are typically sufficient to achieve this objective.AimWe demonstrate the successful application of the integrated genomic surveillance (IGS) system of the German city of Düsseldorf for tracing SARS-CoV-2 transmission chains in the population as well as detecting and investigating travel-associated SARS-CoV-2 infection clusters.MethodsGenomic surveillance, phylogenetic analysis, and structured case interviews were integrated to elucidate two genetically defined clusters of SARS-CoV-2 isolates detected by IGS in Düsseldorf in July 2021.ResultsCluster 1 (n = 67 Düsseldorf cases) and Cluster 2 (n = 36) were detected in a surveillance dataset of 518 high-quality SARS-CoV-2 genomes from Düsseldorf (53% of total cases, sampled mid-June to July 2021). Cluster 1 could be traced back to a complex pattern of transmission in nightlife venues following a putative importation by a SARS-CoV-2-infected return traveller (IP) in late June; 28 SARS-CoV-2 cases could be epidemiologically directly linked to IP. Supported by viral genome data from Spain, Cluster 2 was shown to represent multiple independent introduction events of a viral strain circulating in Catalonia and other European countries, followed by diffuse community transmission in Düsseldorf.ConclusionIGS enabled high-resolution tracing of SARS-CoV-2 transmission in an internationally connected city during community transmission and provided infection chain-level evidence of the downstream propagation of travel-imported SARS-CoV-2 cases.

SARS-CoV-2 Catalonia contact tracing program: evaluation of key performance indicators.

BACKGROUND: Guidance on SARS-CoV-2 contact tracing indicators have been recently revised by international public health agencies. The aim of the study is to describe and analyse contact tracing indicators based on Catalonia's (Spain) real data and proposing to update them according to recommendations. METHODS: Retrospective cohort analysis including Catalonia's contact tracing dataset from 20 May until 31 December 2020. Descriptive statistics are performed including sociodemographic stratification by age, and differences are assessed over the study period. RESULTS: We analysed 923,072 contacts from 301,522 SARS-CoV-2 cases with identified contacts (67.1% contact tracing coverage). The average number of contacts per case was 4.6 (median 3, range 1-243). A total of 403,377 contacts accepted follow-up through three phone calls over a 14-day quarantine period (84.5% of contacts requiring follow-up). The percentage of new cases declared as contacts 14 days prior to diagnosis evolved from 33.9% in May to 57.9% in November. All indicators significantly improved towards the target over time (p < 0.05 for all four indicators). CONCLUSIONS: Catalonia's SARS-CoV-2 contact tracing indicators improved over time despite challenging context. The critical revision of the indicator's framework aims to provide essential information in control policies, new indicators proposed will improve system delay's follow-up. The study provides information on COVID-19 indicators framework experience from country's real data, allowing to improve monitoring tools in 2021-2022. With the SARS-CoV-2 pandemic being so harmful to health systems and globally, is important to analyse and share contact tracing data with the scientific community.

Estimation of the incidence of invasive meningococcal disease using a capture-recapture model based on two independent surveillance systems in Catalonia, Spain.

OBJECTIVES: Invasive meningococcal disease (IMD) is an urgent notifiable disease and its early notification is essential to prevent cases. The objective of the study was to assess the sensitivity of two independent surveillance systems and to estimate the incidence of IMD. DESIGN: We used capture-recapture model based on two independent surveillance systems, the statutory disease reporting (SDR) system and the microbiological reporting system (MRS) of the Public Health Agency of Catalonia, between 2011 and 2015. The capture-recapture analysis and 95% CIs were calculated using the Chapman formula. Multivariate vector generalised linear model was performed for adjusted estimation. MEASURES: The variables collected were age, sex, year of report, size of municipality (<10 000 and ≥10 000), clinical form, death, serogroup, country of birth and type of reporting centre (private and public). RESULTS: The sensitivity of the two combined surveillance systems was 88.5% (85.0-92.0). SDR had greater sensitivity than the MRS (67.9%; 62.7-73.1 vs 64.7%; 59.4-70.0). In 2014-2015, the sensitivity of both systems was higher (80.6%; 73.2-87.9 vs 73.4%; 65.2-81.6) than in 2011-2013 (59.3%; 52.6-66.0 vs 58.3%; 51.6-65.1). In private centres, the sensitivity was higher for SDR than for MRS (100%; 100-100 vs 4.8%; -4.4-13.9). The adjusted estimate of IMD cases was lower than that obtained using the Chapman formula (279; 266-296 vs 313; 295-330). The estimated adjusted incidence of IMD was 0.7/100 000 persons-year. CONCLUSIONS: The sensitivity of enhanced surveillance through the combination of two complementary sources was higher than for the sources individually. Factors associated with under-reporting in different systems should be analysed to improve IMD surveillance.

Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study.

BACKGROUND: Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet). METHODS: We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose. RESULTS: The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0-88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8-96.1) < 12 months to 85.1% (72.0-92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7-94.7) against fatal PCV13 IPD, 64.5% (43.7-77.6), 83.2% (73.7-89.3) and 85.1% (67.6-93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3-94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4-92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2-96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and -14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively. CONCLUSIONS: PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.

Surveillance of SARS-CoV-2 virus circulation using Acute Respiratory Infections sentinel system of Catalonia (PIDIRAC) during the 2019-2020 season: A retrospective observational study.

BACKGROUND: In the context of COVID-19 pandemic in Catalonia (Spain), the present study analyses respiratory samples collected by the primary care network using Acute Respiratory Infections Sentinel Surveillance System (PIDIRAC) during the 2019-2020 season to complement the pandemic surveillance system in place to detect SARS-CoV-2. The aim of the study is to describe whether SARS-CoV-2 was circulating before the first confirmed case was detected in Catalonia, on February 25th, 2020. METHODS: The study sample was made up of all samples collected by the PIDIRAC primary care network as part of the Influenza and Acute Respiratory Infections (ARI) surveillance system activities. The study on respiratory virus included coronavirus using multiple RT-PCR assays. All positive samples for human coronavirus were subsequently typed for HKU1, OC43, NL63, 229E. Every respiratory sample was frozen at-80°C and retrospectively studied for SARS-CoV-2 detection. A descriptive study was performed, analysing significant differences among variables related to SARS-CoV- 2 cases comparing with rest of coronaviruses cases through a bivariate study with Chi-squared test and statistical significance at 95%. RESULTS: Between October 2019 and April 2020, 878 respiratory samples from patients with acute respiratory infection or influenza syndrome obtained by PIDIRAC were analysed. 51.9% tested positive for influenza virus, 48.1% for other respiratory viruses. SARS-CoV-2 was present in 6 samples. The first positive SARS-CoV-2 case had symptom onset on 2 March 2020. These 6 cases were 3 men and 3 women, aged between 25 and 50 years old. 67% had risk factors, none had previous travel history nor presented viral coinfection. All of them recovered favourably. CONCLUSION: Sentinel Surveillance PIDIRAC enhances global epidemiological surveillance by allowing confirmation of viral circulation and describes the epidemiology of generalized community respiratory viruses' transmission in Catalonia. The system can provide an alert signal when identification of a virus is not achieved in order to take adequate preparedness measures.

SARS-CoV-2 seroprevalence in blood donors before and after the first wave in Catalonia (Spain).

BACKGROUND: Due to the COVID-19 pandemic, a national lockdown was applied in Spain from March to May 2020. It is uncertain when SARS-CoV-2 started to circulate in Catalonia, and only a few cases were diagnosed in this period. We assessed the SARS-CoV-2 seroprevalence in blood donors before and after the first wave and compared it with public health service (PHS) data. MATERIALS AND METHODS: Retrospective archive or prospective fresh blood samples were obtained from blood donors aged 18 to 70 and anonymized after demographic data had been recorded (gender, age, place of residence, blood collection date). Two CE-marked enzyme-linked immunosorbent assays were used to test for anti-SARS-CoV-2. A SARS-CoV-2 IgM test was additionally performed in positive samples. Individuals aged 18 to 70 from among the general population diagnosed as having SARS-CoV-2 by the PHS were included for comparison with blood donor results. RESULTS: A total of 10,170 blood donations were included in the first period, between 24 February and 9 March 2020, and 6,829 in the second period, between 16 May and 17 June 2020. The observed SARS-CoV-2 seroprevalence among blood donors rose from 0.27% (95% CI: 0.18-0.39) before the first wave to 5.55% (95% CI: 5.03-6.12) after it, and was even higher (6.90% [95% CI: 5.64-8.41]) among blood donors aged 18 to 29. The seroprevalence among blood donors was higher in more populated areas (Barcelona: 7.69%). A comparison of blood donor data with officially diagnosed cases showed a global 87.44% underestimation of SARS-CoV-2 in June 2020. DISCUSSION: We analyzed the explosive 3-month increase in blood donor SARS-CoV-2 seroprevalence (from 0.27% to 5.55%) and show that more than 87% of cases went undiagnosed, despite the unprecedented deployment of testing measures. SARS-CoV-2 IgM results suggest that the virus was circulating among blood donors in February 2020. Blood donors are definitively proven to be a valuable resource for emerging disease surveillance studies.

Invasive pneumococcal disease in children under 60 months before and after availability of 13-valent conjugate vaccine.

BACKGROUND: Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). METHODS: Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). RESULTS: We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 casos per 100 000 habitantes ( -62%; P < .001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 casos/100 000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P = .00). The incidence of serotype 3 decreased from 10.4 to 6.9 casos per 100 000 population, although it was the serotype involved most frequently in patients with severe disease. CONCLUSIONS: After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD.

Serotype Replacement after Introduction of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccines in 10 Countries, Europe.

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011-2014 but increased during 2015-2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children <5 years of age, 32% in persons 5-64 years of age, and 7% in persons >65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. In 2018, serotypes in the 15-valent and 20-valent PCVs represented one third of cases in children <5 years of age and two thirds of cases in persons >65 years of age. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.

Clonal Spread and Intra- and Inter-Species Plasmid Dissemination Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacterales During a Hospital Outbreak in Barcelona, Spain.

Objectives: The study aimed to characterize the clonal spread of resistant bacteria and dissemination of resistance plasmids among carbapenem-resistant Enterobacterales at a tertiary hospital in Catalonia, Spain. Methods: Isolates were recovered from surveillance rectal swabs and diagnostic samples. Species identification was by matrix-assisted laser desorption ionization-time time of flight mass spectrometry (MALDI-TOF MS). Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). Antimicrobial susceptibility was assessed by gradient-diffusion and carriage of bla genes was detected by PCR. Plasmid typing, conjugation assays, S1-PFGE studies and long-read sequencing were used to characterize resistance plasmids. Results: From July 2018 to February 2019, 125 Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales were recovered from 101 inpatients from surveillance (74.4%) or clinical samples (25.6%), in a tertiary hospital in Barcelona. Clonality studies identified a major clone of Klebsiella pneumoniae belonging to sequence type ST15 and additional isolates of K. pneumoniae, Escherichia coli and Enterobacter sp. from different STs. All isolates but one carried the bla KPC-2 allelic variant. The bla KPC-2 gene was located in an IncFIIk plasmid of circa 106 Kb in a non-classical Tn4401 element designated NTEKPC-pMC-2-1. Whole-genome sequencing revealed different rearrangements of the 106 Kb plasmid while the NTEKPC-pMC-2-1 module was highly conserved. Conclusion: We report a hospital outbreak caused by the clonal dissemination of KPC-producing ST15 K. pneumoniae but also the intra- and inter-species transmission of the bla KPC-2 gene associated with plasmid conjugation and/or transposon dissemination. To our knowledge, this is the first report of an outbreak caused by KPC-producing Enterobacterales isolated from human patients in Catalonia and highlights the relevance of surveillance studies in the early detection and control of antibiotic resistant high-risk clones.

Necrotizing pneumonia due to Streptococcus pneumoniae in children during the period of non-systematic use of PCV13 in Catalonia, Spain.

BACKGROUND: Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain). METHODS: A prospective observational study was conducted in patients <18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%. RESULTS: 35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children <5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13. CONCLUSIONS: Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

[Invasive pneumococcal disease in children under 60 months before and after availability of 13-valent conjugate vaccine]. / Enfermedad neumocócica invasiva en niños menores de 60 meses, antes y después de la introducción de la vacuna conjugada 13-valente.

BACKGROUND: Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). METHODS: Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). RESULTS: We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 cases per 100,000 population (-62%; P<.001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 cases/100,000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P=.00). The incidence of serotype 3 decreased from 10.4 to 6.9 cases per 100,000 population, although it was the serotype involved most frequently in patients with severe disease. CONCLUSIONS: After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD.

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.