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SummaryBackgroundThe Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused byStreptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidisandStreptococcus agalactiae. Here we analyse the incidence and distribution of disease during the first two years of the pandemic.MethodsLaboratories in 30 countries/territories representing five continents submitted case data from 2018-2021 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/group were examined. Interrupted time series analyses quantified the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models estimated effect sizes and forecasted counterfactual trends by hemisphere.FindingsOverall, 116,841 cases were analysed: 76,481 (2018-2019, pre-pandemic) plus 40,360 (2020-2021, pandemic). During the pandemic there was a significant reduction in the risk of disease caused byS pneumoniae(risk ratio: 0.47; 95% confidence interval: 0.40-0.55),H influenzae(0.51; 0.40-0.66) andN meningitidis(0.26; 0.21-0.31), whereas no significant changes were observed for the non-respiratory-transmitted pathogenS agalactiae(1.02; 0.75-1.40). No major changes in the distribution of cases were observed when stratified by patient age or serotype/group. An estimated 36,289 (17,145-55,434) cases of invasive bacterial disease were averted during the first two years of the pandemic among IRIS participating countries/territories.InterpretationCOVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused byS pneumoniae, H influenzaeandN meningitidisduring the first two years of the pandemic, but cases began to increase in some countries as pandemic restrictions were lifted.Research in contextEvidence before this studyEarly in the COVID-19 pandemic the IRIS Consortium reported a significant reduction in invasive disease due to respiratory-transmitted bacterial pathogens, which was associated with the implementation of COVID-19 stringency measures and changes in human social behaviour. All 26 countries/territories participating in IRIS at the time experienced a significant reduction in infections between January and May 2020, compared with the previous two years. In particular,S pneumoniaeinfections decreased by 68% at four weeks after COVID-19 containment measures were imposed, and by 82% at eight weeks.Added value of this studyThese new data from the expanded IRIS Consortium across 30 countries/territories demonstrated a sustained reduction in invasive disease throughout the first two years of the COVID-19 pandemic. Using time series modelling, we estimated that over 36,000 cases of invasive bacterial disease were averted in 2020-2021 among the countries participating in IRIS; however, minor increases in disease in the latter half of 2021 require close monitoring to understand the nature of re-emerging cases.Implications of all the available evidenceFuture epidemics and pandemics will occur, and we need to understand not only the pathogen that is directly responsible for the pandemic, but also that population-level responses to an epidemic or pandemic more broadly affect overall human health and other microbes. IRIS provides evidence for the effects of such public health responses on severe invasive bacterial infections across many countries. Moreover, these IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to healthcare service planning and provision of policies.

Background Bacterial meningitis (BM) is a rare but severe infection. Few population-based studies have characterised BM episodes and sequelae over long periods. Methods This was a population-based observational cohort study with national coverage, using data on aetiological pathogens, sex, premorbid conditions, steroid pretreatment, severe sequelae and birth, death and diagnosis dates collected from 10,339 patients with BM reported to the National Board of Health and Welfare in Sweden between 1964 and 2014. Results During the 50-year study period, the incidence of BM decreased in young children, but not in the elderly. The most common cause of BM was pneumococci (34%), followed by Haemophilus influenzae (26%), and meningococci (18%), mainly community acquired. Premorbid conditions were found in 20%. After the H. influenzae type b vaccine was introduced in 1993, the BM incidence decreased by 36%. Following pneumococcal conjugated vaccine introduction in 2009, the incidence and 30-day mortality from pneumococcal meningitis decreased by 64% and 100%, respectively, in previously healthy children, and the 30-day mortality decreased by 64% among comorbid adults. The BM incidence in immunosuppressed patients increased by 3% annually post vaccine introduction. The 30-day mortality was 3% in children and 14% in adults, and the rate of severe sequelae was 44%. On average, patients lost 11 years of healthy life due to BM. Conclusion The introduction of conjugated vaccines into the childhood vaccination program has reduced the incidence of BM in young children, but not in adults. Post vaccine introduction, patients present with more premorbid conditions and other bacterial causes of BM, emphasising the need for a correct diagnosis when treating these infections.

Background Demography is changing, with people living longer with comorbidities. In this nationwide population-based study, we investigated the serotype-specific invasive pneumococcal disease (IPD) risk in individuals with comorbidities, and effects of the pneumococcal conjugated vaccine (PCV) child immunization program. Methods Cases included 14 096 IPD episodes in Sweden during 2006–2015. Controls (n = 137 289), matched to cases by age, sex, region, and calendar time, were selected from the general population. Comorbidity data was obtained through health registers and grouped as immunocompromising (IC) or chronic medical conditions (CMC). Results The prevalence of CMC and IC among elderly cases was 33.9% and 39.4%. New risks identified for IPD were sarcoidosis, inflammatory polyarthropathies, systemic connective tissue, and neurological diseases. The odds ratio (OR) for IPD caused by non-PCV13 compared with PCV13 serotypes was higher in individuals with CMC/IC. Serotypes associated with the highest risk were 16F, 15C, 35F, 19F, and 23A (OR 3–5 for CMC, >10 for IC). Most comorbidities increased post-vaccination, and absolute increases of IPD caused by non-PCV13, PPV23–non-PCV13, and non-PCV13/non-PPV23 serotypes were higher in individuals with IC/CMC compared with healthy persons. Non-PCV13 serotypes 6C, 9N, 11A, 22F, 23A and 35F increased more in those with comorbidities. Mortality due to non-PCV13 serotypes increased in individuals with IC/CMC, while remaining stable in persons without comorbidities. Conclusions The PCV child immunization program associates with an increased disease burden of non-vaccine serotypes in individuals with comorbidities. These data are important for vaccine design and optimization of current vaccination strategies.

BackgroundStreptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis are leading causes of invasive diseases including bacteraemic pneumonia and meningitis, and of secondary infections post-viral respiratory disease. They are typically transmitted via respiratory droplets. We investigated rates of invasive disease due to these pathogens during the early phase of the COVID-19 pandemic.MethodsLaboratories in 26 countries across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae and N meningitidis from 1 January 2018 to 31 May 2020. Weekly cases in 2020 vs 2018-2019 were compared. Streptococcus agalactiae data were collected from nine laboratories for comparison to a non-respiratory pathogen. The stringency of COVID-19 containment measures was quantified by the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed by Google COVID-19 Community Mobility Reports. Interrupted time series modelling quantified changes in rates of invasive disease in 2020 relative to when containment measures were imposed.FindingsAll countries experienced a significant, sustained reduction in invasive diseases due to S pneumoniae, H influenzae and N meningitidis, but not S agalactiae, in early 2020, which coincided with the introduction of COVID-19 containment measures in each country. Similar impacts were observed across most countries despite differing stringency in COVID-19 control policies. There was no evidence of a specific effect due to enforced school closures.InterpretationThe introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of these bacterial respiratory pathogens, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.

Background Streptococcus pneumoniae is a major human pathogen, and nasopharyngeal colonization is the first step for transmission and pathogenesis of pneumococcal diseases. Ethiopia introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in October 2011. Here we studied nasopharyngeal carriage rates of pneumococci in children and analyzed the serotype and genetic diversity of pneumococcal isolates before first dose and after completion of the vaccine. Method A longitudinal study was conducted from February 2013 to November 2016. Totally 789 infants were enrolled at the age of 6 weeks before first dose of PCV10 vaccination, 206 were re-sampled at the age of 9 months, and 201 at 2 years of age after the final dose of PCV10 at the age of 14 weeks. One hundred sixteen children were followed during all the three sampling periods. A total of 422 nasopharyngeal isolates were serotyped using gel diffusion and the Quellung reaction, 325 were typed with pulsed field gel electrophoresis (PFGE), and 12 were selected for multi locus sequence typing (MLST). Results Pneumococcal carriage rates at the age of 6 weeks, 9 months and 2 years of age were 26.6% (210/789), 56.8% (117/206) and 48.3% (97/201), respectively. Out of 116 children none of them carried the same strain during the three period and the carriage rate at the age of 6 weeks, 9 months and 2 years were 32.7% (38/116), 59.% (69/116) and 49.1% (57/116) respectively. Totally 59 pneumococcal serotypes were identified among 422 isolates. Serotype 6A (5.0%) dominated followed by 34 (4.5%), 10A (4.0%), 11A (4.0%), 19F (3.8%), 15B (3.8%), 23F (3.6%), and 15A (3.6%). The proportion of non-PCV10 serotypes among the isolates recovered at 6 weeks, 9 months and 2 years was 79.4, 88.9 and 89.7% respectively. Molecular typing of 325 isolates collected at 6 weeks and 9 months of age showed a high genetic diversity. Conclusion This study highlights the presence of very diverse serotypes in Ethiopia where non-vaccine serotypes were predominant. Completion of the PCV10 schedule was associated with an approximately 50% reduction of vaccine-type carriage and increase of non-vaccine types. PCV13 would potentially reduce vaccine-type carriage by further 10%. Electronic supplementary material The online version of this article (10.1186/s12879-019-4024-1) contains supplementary material, which is available to authorized users.

Objective To evaluate the carriage prevalence, serotype distribution, and antibiotic resistance for pneumococcal carriage isolates collected 4–8 years after introduction of pneumococcal conjugate vaccines (PCVs) in Stockholm, Sweden, and to identify risk factors for carriage and calculate the invasive disease potential for emerging serotypes. Methods Nasopharyngeal aspirates were collected from 3024 children aged 0–

The effects of pneumococcal conjugated vaccines (PCVs) need to be investigated. In Stockholm County, Sweden, PCV7 was introduced in the childhood immunisation programme in 2007 and changed to PCV13 in 2010. Over 90% of all invasive isolates during 2005–2014 (n=2336) and carriage isolates, 260 before and 647 after vaccine introduction, were characterised by serotyping, molecular typing and antibiotic susceptibility, and serotype diversity was calculated. Clinical information was collected for children and adults with invasive pneumococcal disease (IPD). The IPD incidence decreased post-PCV7, but not post-PCV13, in vaccinated children. Beneficial herd effects were seen in older children and adults, but not in the elderly. The herd protection was more pronounced post-PCV7 than post-PCV13. PCV7 serotypes decreased. IPD caused by PCV13 serotypes 3 and 19A increased post-PCV7. Post-PCV13, serotypes 6A and 19A, but not serotype 3, decreased. The serotype distribution changed in carriage and IPD to nonvaccine types, also in nonvaccinated populations. Expansion of non-PCV13 serotypes was largest following PCV13 introduction. Serotype diversity increased and nonvaccine clones emerged, such as CC433 (serotype 22F) in IPD and CC62 (serotype 11A) in carriage. In young children, meningitis, septicaemia and severe rhinosinusitis, but not bacteraemic pneumonia, decreased. Pneumococcal vaccination leads to expansion of new or minor serotypes/clones, also in nonvaccinated populations., New or minor serotypes/clones expanded, also in nonvaccinated populations, affecting future vaccine strategies http://ow.ly/VA9EO

An external quality assessment (EQA) scheme for pneumococcal serotype identification has been performed over a period of 11 years, by a network of European pneumococcal reference laboratories. We report the results from the EQA, and present an assessment of the acceptability and utility of the EQA scheme. Reports from 22 EQA panels distributed in 2005–2016 were analysed. Each EQA panel consisted of seven isolates. A questionnaire including seven questions related to the acceptability and utility of the EQA scheme was distributed to all participating laboratories. Altogether, 154 pneumococcal isolates were tested. Of the 92 serologically distinct serotypes currently defined, 49 serotypes were included in the rounds. Discrepant results were observed in eight EQA rounds, involving 11 isolates (7.1%, 95% CI: 4% to 12%). All participating laboratories reported that the EQA scheme was useful for quality assurance purposes. Our results show that comparable serotyping data can be obtained in different laboratories. The EQA participation helps to keep the typing procedures at a high standard and provides data for accreditation purposes. The EQA is helpful when new technologies are introduced, and reveal limitations of both genotypic and phenotypic methods. Continuation of the presented EQA scheme is planned.

Background Pneumococcal conjugate vaccine 10 (PCV10) and pneumococcal conjugate vaccine 13 (PCV13), are used in childhood immunization programs worldwide, but direct comparisons of impacts against invasive pneumococcal disease (IPD) in equivalent populations have not been performed. We compared the vaccines (prevaccination 2007-2009 vs postvaccination 2013-2016) in Sweden, where the 21 counties use either PCV10 or PCV13 (introduced 2009-2010). Methods All IPD episodes (n = 16992) were recorded in Sweden during 2005-2016. Of 14 186 isolates from 2007-2016, 13 468 (94.9%) were characterized with serotyping and 12 235 (86.2%) with antibiotic susceptibility. Poisson models assessed changes in incidence over time. Results Invasive pneumococcal disease incidences decreased between 2005 and 2016 in vaccinated children (by 68.5%), and in the whole population (by 13.5%), but not among the elderly (increased by 2%) due to a substantial increase in nonvaccine types (NVTs). In 2016, NVTs constituted 72% of IPD cases in the elderly. Serotype 6A declined in PCV10 and PCV13 counties, whereas serotype 19A increased in PCV10 counties. There was no effect against serotype 3. Cross-protection was found between 6B and 6A but not between 19F and 19A. Serotype 6C increased in PCV10 counties, but not in PCV13 counties, suggesting cross-protection with 6A, which is included in PCV13. In the elderly, the increase in NVTs, excluding 6C, was more pronounced in PCV13 counties. Conclusions The overall impact of IPD incidences was not statistically different irrespective of vaccine used. The incidence of serotypes, where the effect of the vaccines differed, will influence the cost-effectiveness of which vaccine to use in immunization programs. The dominance of NVTs suggests a limited effect of current pediatric PCVs against IPD in the elderly.

Summary Background The Streptococcus pneumoniae Invasive Disease network (SpIDnet) actively monitors populations in nine sites in seven European countries for invasive pneumococcal disease. Five sites use 13-valent pneumococcal conjugate vaccine (PCV13) alone and four use the ten-valent PCV (PCV10) and PCV13. Vaccination uptake is greater than 90% in six sites and 67–78% in three sites. We measured the effects of introducing high-valency PCVs on the incidence of invasive pneumococcal disease in children younger than 5 years. Methods We compared the incidence of invasive pneumococcal disease in each of the 4 years after the introduction of PCV13 alone or PCV10 and PCV13 with the average incidence during the preceding period of heptavalent PCV (PCV7) use, overall and by serotype category. We calculated incidence rate ratios (IRRs) and 95% CIs for each year and pooled the values for all sites in a random effects meta-analysis. Findings 4 years after the introduction of PCV13 alone or PCV10 and PCV13, the pooled IRR was 0·53 (95% CI 0·43–0·65) for invasive pneumococcal disease in children younger than 5 years caused by any serotype, 0·16 (0·07–0·40) for disease caused by PCV7 serotypes, 0·17 (0·07–0·42) for disease caused by 1, 5, and 7F serotypes, and 0·41 (0·25–0·69) for that caused by 3, 6A and 19A serotypes. We saw a similar pattern when we restricted the analysis to sites where only PCV13 was used. The pooled IRR for invasive pneumococcal disease caused by non-PCV13 serotypes was 1·62 (1·09–2·42). Interpretation The incidence of invasive pneumococcal disease caused by all serotypes decreased due to a decline in the incidence of vaccine serotypes. By contrast, that of invasive pneumococcal disease caused by non-PCV13 serotypes increased, which suggests serotype replacement. Long-term surveillance will be crucial to monitor the further effects of PCV10 and PCV13 vaccination programmes in young children. Funding European Centre for Disease Prevention and Control, Czech National Institute of Public Health, French National Agency for Public Health, Irish Health Services Executive, Norwegian Institute of Public Health, Public Health Agency of Catalonia, Public Health Department of Community of Madrid, Navarra Hospital Complex, Public Health Institute of Navarra, CIBER Epidemiology and Public Health, Institute of Health Carlos III, Public Health Agency of Sweden, and NHS Scotland.