Maternal Streptococcus agalactiae colonization in Europe: data from the multi-center DEVANI study.

INTRODUCTION: Despite national guidelines and use of intrapartum antibiotic prophylaxis (IAP), Streptococcus agalactiae (group B streptococci (GBS)) is still a leading cause of morbidity and mortality in newborns in Europe and the United States. The European DEVANI (Design of a Vaccine Against Neonatal Infections) program assessed the neonatal GBS infection burden in Europe, the clinical characteristics of colonized women and microbiological data of GBS strains in colonized women and their infants with early-onset disease (EOD). METHODS: Overall, 1083 pregnant women with a GBS-positive culture result from eight European countries were included in the study. Clinical obstetrical information was collected by a standardized questionnaire. GBS strains were characterized by serological and molecular methods. RESULTS: Among GBS carriers included in this study after testing positive for GBS by vaginal or recto-vaginal sampling, 13.4% had at least one additional obstetrical risk factor for EOD. The five most common capsular types (i.e., Ia, Ib, II, III and V) comprised ~ 93% of GBS carried. Of the colonized women, 77.8% received any IAP, and in 49.5% the IAP was considered appropriate. In our cohort, nine neonates presented with GBS early-onset disease (EOD) with significant regional heterogeneity. CONCLUSIONS: Screening methods and IAP rates need to be harmonized across Europe in order to reduce the rates of EOD. The epidemiological data from eight different European countries provides important information for the development of a successful GBS vaccine.

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.

Incidence and severity of pertussis hospitalisations in infants aged less than 1 year in 37 hospitals of six EU/EEA countries, results of PERTINENT sentinel pilot surveillance system, December 2015 to December 2018.

IntroductionPERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites).AimThis observational study aimed to estimate annual pertussis incidence per site from 2016 to 2018 and respective trends between 2017 and 2018. Pertussis cases were described, including their severity.MethodsWe developed a generic protocol and laboratory guidelines to harmonise practices across sites. Cases were hospitalised infants testing positive for Bordetella pertussis by PCR or culture. Sites collected demographic, clinical, laboratory data, vaccination status, and risk/protective factors. We estimated sites' annual incidences by dividing case numbers by the catchment populations.ResultsFrom December 2015 to December 2018, we identified 469 cases (247 males; 53%). The median age, birthweight and gestational age were 2.5 months (range: 0-11.6; interquartile range (IQR): 2.5), 3,280 g (range: 700-4,925; IQR: 720) and 39 weeks (range: 25-42; IQR: 2), respectively. Thirty cases (6%) had atypical presentation either with cough or cyanosis only or with absence of pertussis-like symptoms. Of 330 cases with information, 83 (25%) were admitted to intensive care units including five deceased infants too young to be vaccinated. Incidence rate ratios between 2018 and 2017 were 1.43 in Czech Republic (p = 0.468), 0.25 in Catalonia (p = 0.002), 0.71 in France (p = 0.034), 0.14 in Ireland (p = 0.002), 0.63 in Italy (p = 0.053), 0.21 in Navarra (p = 0.148) and zero in Norway.ConclusionsIncidence appeared to decrease between 2017 and 2018 in all but one site. Enhanced surveillance of hospitalised pertussis in Europe is essential to monitor pertussis epidemiology and disease burden.

Effect of childhood pneumococcal conjugate vaccination on invasive disease in older adults of 10 European countries: implications for adult vaccination.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) have the potential to prevent pneumococcal disease through direct and indirect protection. This multicentre European study estimated the indirect effects of 5-year childhood PCV10 and/or PCV13 programmes on invasive pneumococcal disease (IPD) in older adults across 13 sites in 10 European countries, to support decision-making on pneumococcal vaccination policies. METHODS: For each site we calculated IPD incidence rate ratios (IRR) in people aged ≥65 years by serotype for each PCV10/13 year (2011-2015) compared with 2009 (pre-PCV10/13). We calculated pooled IRR and 95% CI using random-effects meta-analysis and PCV10/13 effect as (1 - IRR)*100. RESULTS: After five PCV10/13 years, the incidence of IPD caused by all types, PCV7 and additional PCV13 serotypes declined 9% (95% CI -4% to 19%), 77% (95% CI 67% to 84%) and 38% (95% CI 19% to 53%), respectively, while the incidence of non-PCV13 serotypes increased 63% (95% CI 39% to 91%). The incidence of serotypes included in PCV13 and not in PCV10 decreased 37% (95% CI 22% to 50%) in six PCV13 sites and increased by 50% (95% CI -8% to 146%) in the four sites using PCV10 (alone or with PCV13). In 2015, PCV13 serotypes represented 20-29% and 32-53% of IPD cases in PCV13 and PCV10 sites, respectively. CONCLUSION: Overall IPD incidence in older adults decreased moderately after five childhood PCV10/13 years in 13 European sites. Large declines in PCV10/13 serotype IPD, due to the indirect effect of childhood vaccination, were countered by increases in non-PCV13 IPD, but these declines varied according to the childhood vaccine used. Decision-making on pneumococcal vaccination for older adults must consider the indirect effects of childhood PCV programmes. Sustained monitoring of IPD epidemiology is imperative.

Increase of invasive meningococcal serogroup W disease in Europe, 2013 to 2017.

BackgroundThe total incidence of invasive meningococcal disease (IMD) in Europe has been declining in recent years; however, a rising incidence due to serogroup W (MenW), predominantly sequence type 11 (ST-11), clonal complex 11 (cc11), was reported in some European countries.AimThe aim of this study was to compile the most recent laboratory surveillance data on MenW IMD from several European countries to assess recent trends in Europe.MethodsIn this observational, retrospective study, IMD surveillance data collected from 2013-17 by national reference laboratories and surveillance units from 13 European countries were analysed using descriptive statistics.ResultsThe overall incidence of IMD has been stable during the study period. Incidence of MenW IMD per 100,000 population (2013: 0.03; 2014: 0.05; 2015: 0.08; 2016: 0.11; 2017: 0.11) and the proportion of this serogroup among all invasive cases (2013: 5% (116/2,216); 2014: 9% (161/1,761); 2015: 13% (271/2,074); 2016: 17% (388/2,222); 2017: 19% (393/2,112)) continuously increased. The most affected countries were England, the Netherlands, Switzerland and Sweden. MenW was more frequent in older age groups (≥ 45 years), while the proportion in children (< 15 years) was lower than in other age groups. Of the culture-confirmed MenW IMD cases, 80% (615/767) were caused by hypervirulent cc11.ConclusionDuring the years 2013-17, an increase in MenW IMD, mainly caused by MenW cc11, was observed in the majority of European countries. Given the unpredictable nature of meningococcal spread and the epidemiological potential of cc11, European countries may consider preventive strategies adapted to their contexts.

Establishment of the European meningococcal strain collection genome library (EMSC-GL) for the 2011 to 2012 epidemiological year.

Invasive meningococcal disease surveillance in Europe combines isolate characterisation and epidemiological data to support public health intervention. A representative European Meningococcal Strain Collection (EMSC) of IMD isolates was obtained, and whole genome sequenced to characterise 799 EMSC isolates from the epidemiological year July 2011-June 2012. To establish a genome library (GL), the isolate information was deposited in the pubMLST.org/neisseria database. Genomes were curated and annotated at 2,429 meningococcal loci, including those defining clonal complex, capsule, antigens, and antimicrobial resistance. Most genomes contained genes encoding B (n = 525; 65.7%) or C (n = 163; 20.4%) capsules; isolates were genetically highly diverse, with >20 genomic lineages, five of which comprising 60.7% (n = 485) of isolates. There were >350 antigenic fine-types: 307 were present once, the most frequent (P1.7-2,4:F5-1) comprised 8% (n = 64) of isolates. Each genome was characterised for Bexsero Antigen Sequence Typing (BAST): 25.5% (n = 204) of isolates contained alleles encoding the fHbp and/or the PorA VR1 vaccine component, but most genomes (n = 513; 64.2%) did not contain the NadA component. EMSC-GL will support an integrated surveillance of disease-associated genotypes in Europe, enabling the monitoring of hyperinvasive lineages, outbreak identification, and supporting vaccine programme implementation.

Effectiveness of one and two doses of acellular pertussis vaccines against laboratory-confirmed pertussis requiring hospitalisation in infants: Results of the PERTINENT sentinel surveillance system in six EU/EEA countries, December 2015 - December 2019.

BACKGROUND: Monitoring effectiveness of pertussis vaccines is necessary to adapt vaccination strategies. PERTINENT, Pertussis in Infants European Network, is an active sentinel surveillance system implemented in 35 hospitals across six EU/EEA countries. We aim to measure pertussis vaccines effectiveness (VE) by dose against hospitalisation in infants aged <1 year. METHODS: From December 2015 to December 2019, participating hospitals recruited all infants with pertussis-like symptoms. Cases were vaccine-eligible infants testing positive for Bordetella pertussis by PCR or culture; controls were those testing negative to all Bordetella spp. For each vaccine dose, we defined an infant as vaccinated if she/he received the corresponding dose >14 days before symptoms. Unvaccinated were those who did not receive any dose. We calculated (one-stage model) pooled VE as 100*(1-odds ratio of vaccination) adjusted for country, onset date (in 3-month categories) and age-group (when sample allowed it). RESULTS: Of 1,393 infants eligible for vaccination, we included 259 cases and 746 controls. Median age was 16 weeks for cases and 19 weeks for controls (p < 0.001). Median birth weight and gestational age were 3,235 g and week 39 for cases, 3,113 g and week 39 for controls. Among cases, 119 (46 %) were vaccinated: 74 with one dose, 37 two doses, 8 three doses. Among controls, 469 (63 %) were vaccinated: 233 with one dose, 206 two doses, 30 three doses. Adjusted VE after at least one dose was 59 % (95 %CI: 36-73). Adjusted VE was 48 % (95 %CI: 5-71) for dose one (416 eligible infants) and 76 % (95 %CI: 43-90) for dose two (258 eligible infants). Only 42 infants were eligible for the third dose. CONCLUSIONS: Our results suggest moderate one-dose and two-dose VE in infants. Larger sample size would allow more precise estimates for dose one, two and three.

[Invasive meningococcal disease in the Czech Republic - analysis of the epidemiological situation and vaccination strategy recommendations]. / Invazivní meningokokové onemocnení v Ceské republice - analýza epidemiologické situace a doporucení k vakcinacní strategii.

AIMS: Analysis of invasive meningococcal disease (IMD) surveillance data including molecular epidemio-logy data. Vaccination strategy recommendations based on the current epidemiological situation of IMD in the Czech Republic and availability of meningococcal vaccines. MATERIAL AND METHODS: IMD surveillance data are compiled by the National Reference Laboratory for Meningococcal Disease (NRL) from routinely reported data and NRL data after clearing out duplicate data. Neisseria meningitidis (N.m.) isolates referred to the NRL are confirmed and characterized in detail according to internationally validated methods. RESULTS: The current epidemiological situation of IMD is relatively favourable - the incidence rates have been below 1/100,000 population for several years, but show a slightly upward trend over more than 40-year period (1970-2012). A return to the typical prevalence of serogroup B accounting for up to 75% of cases has recently been shown. In this context, the upward trend in IMD caused by serogroup Y associated with a high case fatality rate in the Czech Republic cannot be overseen or even underestimated. The hypervirulent clonal complex cc11 characteristic of N.m.C:2a:P1.2,5 prevailed in this country between 1993 and 2004, but decreased in the following years and currently, hypervirulent clonal complexes characteristic of N.m.B (cc18, cc32, cc41/44, and cc269) are the most common in the Czech Republic. The average overall case fatality rate in the Czech Republic is 10%, but varies between causative serogroups: the highest case fatality rate has been caused by serogroup Y (16.7% ), followed by serogroup C (12.3%), and serogroup W135 (11.7%), while serogroup B only accounts for a case fatality rate of 7.8%. In the age group under one year, the incidence of IMD caused by serogroup B remains three to five times as high as in the age groups 1-4 years and 15-19 years throughout the surveillance period. The highest numbers of IMD cases caused by serogroup B have been reported in 3-7-month-olds. CONCLUSION: Based on the IMD surveillance data from the Czech Republic, the NRL recommends a vaccination strategy to provide an adequate protection to individuals. To induce an immune response as wide as possible, the tetravalent meningococcal conjugate vaccine A,C,Y,W135 in combination with the newly registered MenB vaccine designed by reverse vaccinology should be given. To maintain immunity, subsequent booster doses are required at intervals depending on the primary vaccination age.

Whole genome analysis of Neisseria meningitidis isolates from invasive meningococcal disease collected in the Czech Republic over 28 years (1993-2020).

Invasive meningococcal disease belongs among the most dangerous infectious diseases in the world. Several polysaccharide conjugate vaccines against serogroups A, C, W and Y are available and two recombinant peptide vaccines against serogroup B (MenB vaccines) have been developed: MenB-4C (Bexsero) and MenB-fHbp (Trumenba). The aim of this study was to define the clonal composition of the Neisseria meningitidis population in the Czech Republic, to determine changes in this population over time and to estimate the theoretical coverage of isolates by MenB vaccines. This study presents the analysis of whole genome sequencing data of 369 Czech N. meningitidis isolates from invasive meningococcal disease covering 28 years. Serogroup B isolates (MenB) showed high heterogeneity and the most common clonal complexes were cc18, cc32, cc35, cc41/44, and cc269. Isolates of clonal complex cc11 were predominately serogroup C (MenC). The highest number of serogroup W isolates (MenW) belonged to clonal complex cc865, which we described as exclusive to the Czech Republic. Our study supports the theory that this cc865 subpopulation originated in the Czech Republic from MenB isolates by a capsule switching mechanism. A dominant clonal complex of serogroup Y isolates (MenY) was cc23, which formed two genetically quite distant subpopulations and which showed constant representation throughout the observed period. The theoretical coverage of isolates by two MenB vaccines was determined using the Meningococcal Deduced Vaccine Antigen Reactivity Index (MenDeVAR). Estimated Bexsero vaccine coverage was 70.6% (for MenB) and 62.2% (for MenC, W, Y). For Trumenba vaccine, estimated coverage was 74.6% (for MenB) and 65.7% (for MenC, W, Y). Our results demonstrated sufficient coverage of Czech heterogeneous population of N. meningitidis with MenB vaccines and, together with surveillance data on invasive meningococcal disease in the Czech Republic, were the basis for updating recommendations for vaccination against invasive meningococcal disease.

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

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.

Whole genome sequencing of Neisseria meningitidis Y isolates collected in the Czech Republic in 1993-2018.

INTRODUCTION: The study presents the analysis of whole genome sequencing (WGS) data for Neisseria meningitidis serogroup Y isolates collected in the Czech Republic and their comparison to other countries. The aim of the study was to determine whether there are lineages of N. meningitidis serogroup Y in the Czech Republic genetically related to foreign ones that have been causing an increase of the morbidity and the mortality of invasive meningococcal disease (IMD) world-wide recently. MATERIAL AND METHODS: The WGS data of 43 Czech N. meningitidis Y isolates, 35 from IMD and 8 from healthy carriers were analysed. Due to the potential of meningococcal B vaccines to induce protection against non-B serogroups, the coverage of Czech isolates of N. meningitidis Y by these vaccines was studied. The WGS data of Czech, European and non-European isolates of N. meningitidis serogroup Y were compared. RESULTS: WGS assigned 36 isolates of N. meningitidis Y to five clonal complexes: cc23, cc92, cc167, cc103, and cc174, while seven isolates remained unassigned to any clonal complexes (ccUA). Eighteen invasive isolates belonged to clonal complex cc23, which was detected throughout the studied years. The occurrence of cc23 was recorded in all age groups of IMD patients, with the highest found in those aged 15-19 years. On the phylogenetic network isolates of cc23 form a separate lineage, distinct from all other isolates of N. meningitidis Y. The remaining isolates were assigned to other clonal complexes and have very low relatedness to cc23 isolates and to each other. The comparison with foreign WGS data showed that within the main genetic lineages, which are defined by clonal complexes, Czech isolates of N. meningitidis Y, similar to European ones, mostly cluster together and form geographical sublineages. CONCLUSIONS: WGS analysis showed the population of Czech N. meningitidis Y isolates as relatively heterogeneous, containing a large number of genetic lineages. The Czech isolates of N. meningitidis Y follow the trend observed for European isolates. Our result was one of the bases for updating the recommended vaccination strategy in the Czech Republic.

Effectiveness of pertussis vaccination in pregnancy to prevent hospitalisation in infants aged <2 months and effectiveness of both primary vaccination and mother's vaccination in pregnancy in infants aged 2-11 months.

BACKGROUND: PERTINENT is an active hospital-based surveillance system for pertussis in infants. In 2019, four of the six participating European countries recommended pertussis vaccination in pregnancy. Among infants aged <2 months, we measured the vaccine effectiveness (VE) in pregnancy; among infants aged 2-11 months, VE of vaccination in pregnancy and of primary vaccination (PV). METHODS: From December 2015 to 2019, we included all infants aged <1 year presenting with pertussis-like symptoms. Using a test-negative-design, cases were infants testing positive for Bordetella pertussis by PCR or culture. Controls were those testing negative for all Bordetella species. Vaccinated mothers were those who received vaccine in pregnancy. Vaccinated infants were those who received ≥1 dose of PV > 14 days before symptom onset. We excluded infants with unknown maternal or PV status or with mothers vaccinated ≤14 days before delivery. We calculated pooled VE as 100 * (1-odds ratio of vaccination) adjusted for study site, onset date in quarters and infants' age group. RESULTS: Of 829 infants presenting with pertussis-like symptoms, 336 (41%) were too young for PV. For the VE in pregnancy analysis, we included 75 cases and 201 controls. Vaccination in pregnancy was recorded for 9 cases (12%) and 92 controls (46%), adjusted VE was between 75% [95%CI: 35-91%] and 88% [95%CI: 57-96%]. Of 493 infants eligible for PV, we included 123 cases and 253 controls. Thirty-one cases and 98 controls recorded both PV with ≥ 1 dose and vaccination in pregnancy, adjusted VE was between 74% [95%CI: 33-90] and 95% [95%CI: 69-99]; 27 cases and 53 controls recorded PV only, adjusted VE was between 68% [95%CI: 27-86] and 94% [95%CI: 59-99]. CONCLUSION: Our findings suggest that vaccination in pregnancy reduces pertussis incidence in infants too young for PV. In infants aged 2-11 months, PV only and both PV and vaccination in pregnancy provide significant protection against severe pertussis.

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.

Impact of pneumococcal conjugate vaccine on invasive pneumococcal disease in children under 5 years of age in the Czech Republic.

INTRODUCTION: The aim of this study is to analyse the impact of vaccination of infants with pneumococcal conjugate vaccine (PCV) on the incidence of invasive pneumococcal disease (IPD) in children under 5 years of age in the Czech Republic. MATERIAL AND METHODS: The present study includes all IPD cases reported in children aged 0-4 years within the surveillance program in 2007-2017. The impact of PCV is analysed for five categories of IPD: cases caused by all serotypes, cases caused by PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), cases caused by three additional PCV10 serotypes (1, 5, and 7F), cases caused by three additional PCV13 serotypes (3, 6A, and 19A), and cases caused by non-PCV serotypes. To assess the impact of PCV, the study period was divided into the pre-vaccination period 2007-2008 and post-vaccination period 2009-2017, which was divided into three three-year parts: 2009-2011, 2012-2014, and 2015-2017. Analysis of differences between periods was based on the Poisson regression model where the population numbers were handled as an offset. RESULTS: The annual incidence of IPD in children under 5 years of age caused by all serotypes has had a downward trend since 2007: it dropped from 8.52/100 000 in 2007 to 2.67/100 000 in 2017, with slight increases in 2010 and 2013. All three post-vaccination periods show significantly lower (p<0.001) incidences in comparison to the pre-vaccination period, but they do not statistically significantly differ from each other. CONCLUSIONS: IPD surveillance data in the Czech Republic show that after the introduction of PCV vaccination of infants, there has been a significant decrease in the IPD incidence of children under 5 years of age. Continued IPD surveillance is essential to monitor for possible post-vaccination serotype replacement.

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

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).

Genomic surveillance of invasive meningococcal disease in the Czech Republic, 2015-2017.

INTRODUCTION: The study presents the results of the genomic surveillance of invasive meningococcal disease (IMD) in the Czech Republic for the period of 2015-2017. MATERIAL AND METHODS: The study set includes all available IMD isolates recovered in the Czech Republic and referred to the National Reference Laboratory for Meningococcal Infections in 2015-2017, a total of 89 Neissseria meningitidis isolates-from 2015 (n = 20), 2016 (n = 27), and from 2017 (n = 42). All isolates were studied by whole genome sequencing (WGS). RESULTS: Serogroup B (MenB) was the most common, followed by serogroups C, W, and Y. Altogether 17 clonal complexes were identified, the most common of which was hypervirulent complex cc11, followed by complexes cc32, cc41/44, cc269, and cc865. Over the three study years, hypervirulent cc11 (MenC) showed an upward trend. The WGS method showed two clearly differentiated clusters of N. meningitidis C: P1.5,2:F3-3:ST-11 (cc11). The first cluster is represented by nine isolates, all of which are from 2017. The second cluster consisted of five isolates from 2016 and eight isolates from 2017. Their genetic discordance is illustrated by the changing nadA allele and subsequently by the variance in BAST type. Clonal complex cc269 (MenB) also increased over the time frame. WGS identified the presence of MenB vaccine antigen genes in all B and non-B isolates of N. meningitidis. Altogether 49 different Bexsero antigen sequence types (BAST) were identified and 10 combinations of these have not been previously described in the PubMLST database. CONCLUSIONS: The genomic surveillance of IMD in the Czech Republic provides data needed to update immunisation guidelines for this disease. WGS showed a higher discrimination power and provided more accurate data on molecular characteristics and genetic relationships among invasive N. meningitidis isolates.

Meningococcal serogroups and surveillance: a systematic review and survey.

BACKGROUND: Meningococcal disease continues to be a global public health concern due to its epidemic potential, severity, and sequelae. The global epidemiological data on circulating meningococcal serogroups have never been reviewed concurrently with the laboratory capacity for meningococcal surveillance at the national level. We, therefore, aimed to conduct a country-level review of meningococcal surveillance, serogroup distribution, and vaccine use. METHODS: We conducted a systematic literature review across six databases to identify studies (published January 1, 2010 to October 16, 2017) and grey literature reporting meningococcal serogroup data for the years 2010-2016. We performed independent random effects meta-analyses for serogroups A, B, C, W, X, Y, and other. We developed and circulated a questionnaire-based survey to surveillance focal points in countries (N = 95) with known regional bacterial meningitis surveillance programs to assess their surveillance capacity and summarized using descriptive methods. RESULTS: We included 173 studies from 59 countries in the final analysis. The distribution of meningococcal serogroups differed markedly between countries and regions. Meningococcal serogroups C and W accounted for substantial proportions of meningococcal disease in most of Africa and Latin America. Serogroup B was the predominant cause of meningococcal disease in many locations in Europe, the Americas, and the Western Pacific. Serogroup Y also caused many cases of meningococcal disease in these regions, particularly in Nordic countries. Survey responses were received from 51 countries. All countries reported the ability to confirm the pathogen in-country, while approximately 30% either relied on reference laboratories for serogrouping (N = 10) or did not serogroup specimens (N = 5). Approximately half of countries did not utilize active laboratory-based surveillance system (N = 22). Nationwide use of a meningococcal vaccine varied, but most countries (N = 36) utilized a meningococcal vaccine at least for certain high-risk population groups, in private care, or during outbreaks. CONCLUSIONS: Due to the large geographical variations in circulating meningococcal serogroups, each country should continue to be monitored for changes in major disease-causing serogroups in order to inform vaccine and control policies. Similarly, laboratory capacity should be appropriately scaled up to more accurately understand local epidemiology and disease burden, as well as the impact of vaccination programs.

Prevention and control of meningococcal disease: Updates from the Global Meningococcal Initiative in Eastern Europe.

The Global Meningococcal Initiative (GMI) aims to prevent invasive meningococcal disease (IMD) worldwide through education, research and cooperation. In March 2019, a GMI meeting was held with a multidisciplinary group of experts and representatives from countries within Eastern Europe. Across the countries represented, IMD surveillance is largely in place, with incidence declining in recent decades and now generally at <1 case per 100,000 persons per year. Predominating serogroups are B and C, followed by A, and cases attributable to serogroups W, X and Y are emerging. Available vaccines differ between countries, are generally not included in immunization programs and provided to high-risk groups only. Available vaccines include both conjugate and polysaccharide vaccines; however, current data and GMI recommendations advocate the use of conjugate vaccines, where possible, due to the ability to interrupt the acquisition of carriage. Ongoing carriage studies are expected to inform vaccine effectiveness and immunization schedules. Additionally, IMD prevention and control should be guided by monitoring outbreak progression and the emergence and international spread of strains and antibiotic resistance through use of genomic analyses and implementation of World Health Organization initiatives. Protection of high-risk groups (such as those with complement deficiencies, laboratory workers, migrants and refugees) is recommended.

Genetic Meningococcal Antigen Typing System (gMATS): A genotyping tool that predicts 4CMenB strain coverage worldwide.

BACKGROUND: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine. METHODS: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping. Individual associations between antigen genotypes and MATS coverage for each 4CMenB component were used to define a genetic MATS (gMATS). gMATS estimates were compared with England and Wales human complement serum bactericidal assay (hSBA) data and vaccine effectiveness (VE) data from England. RESULTS: Overall, 81% of the strain panel had genetically predictable MATS coverage, with 92% accuracy and highly concordant results across national panels (Lin's accuracy coefficient, 0.98; root-mean-square deviation, 6%). England and Wales strain coverage estimates were 72-73% by genotyping (66-73% by MATS), underestimating hSBA values after four vaccine doses (88%) and VE after two doses (83%). The gMATS predicted strain coverage in other countries was 58-88%. CONCLUSIONS: gMATS can replace MATS in predicting 4CMenB strain coverage in four out of five cases, without requiring a cultivable isolate, and is open to further improvement. Both methods underestimated VE in England. Strain coverage predictions in other countries matched or exceeded England and Wales estimates.

Whole genome sequencing of Neisseria meningitidis W isolates from the Czech Republic recovered in 1984-2017.

INTRODUCTION: The study presents the analysis of whole genome sequence (WGS) data for Neisseria meningitidis serogroup W isolates recovered in the Czech Republic in 1984-2017 and their comparison with WGS data from other countries. MATERIAL AND METHODS: Thirty-one Czech N. meningitidis W isolates, 22 from invasive meningococcal disease (IMD) and nine from healthy carriers were analysed. The 33-year study period was divided into three periods: 1984-1999, 2000-2009, and 2010-2017. RESULTS: Most study isolates from IMD and healthy carriers were assigned to clonal complex cc22 (n = 10) in all study periods. The second leading clonal complex was cc865 (n = 8) presented by IMD (n = 7) and carriage (n = 1) isolates that emerged in the last study period, 2010-2017. The third clonal complex was cc11 (n = 4) including IMD isolates from the first (1984-1999) and third (2010-2017) study periods. The following clonal complex was cc174 (n = 3) presented by IMD isolates from the first two study periods, i.e. 1984-1999 and 2000-2009. One isolate of each cc41/44 and cc1136 originated from healthy carriers from the second study period, 2000-2009. The comparison of WGS data for N. meningitidis W isolates recovered in the Czech Republic in the study period 1984-2017 and for isolates from other countries recovered in the same period showed that clonal complex cc865, ST-3342 is unique to the Czech Republic since 2010. Moreover, the comparison shows that cc11 in the Czech Republic does not comprise novel hypervirulent lineages reported from both European and non-European countries. All 31 study isolates were assigned to Bexsero® Antigen Sequence Types (BAST), and seven of them were of newly described BASTs. CONCLUSIONS: WGS analysis contributed considerably to a more detailed molecular characterization of N. meningitidis W isolates recovered in the Czech Republic over a 33-year period and allowed for a spatial and temporal comparison of these characteristics between isolates from the Czech Republic and other countries. The most interesting finding of this study is that eight of 31 Czech isolates of N. meningitidis W belong to clonal complex cc865, which is uncommon for serogroup W. In addition, the WGS data precised the base for the update of the recommendation for vaccination in the Czech Republic.