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.
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).
- MeSH
- analýza přerušované časové série MeSH
- bakteriální infekce epidemiologie přenos MeSH
- COVID-19 * prevence a kontrola MeSH
- Haemophilus influenzae MeSH
- incidence MeSH
- infekce dýchací soustavy epidemiologie MeSH
- lidé MeSH
- Neisseria meningitidis MeSH
- prospektivní studie MeSH
- Streptococcus agalactiae MeSH
- Streptococcus pneumoniae MeSH
- surveillance populace MeSH
- veřejné zdravotnictví - praxe MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and ≥25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.
- MeSH
- antigeny bakteriální imunologie MeSH
- bakteriální pouzdra imunologie MeSH
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- meningokoková meningitida imunologie mikrobiologie prevence a kontrola MeSH
- meningokokové vakcíny imunologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- multilokusová sekvenční typizace MeSH
- Neisseria meningitidis séroskupiny B imunologie MeSH
- Neisseria meningitidis imunologie izolace a purifikace MeSH
- předškolní dítě MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- věkové rozložení MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Most studies of bacterial pathogen populations have been based on isolates collected from individuals with disease, or their contacts, over short time periods. For commensal organisms that occasionally cause disease, such as Neisseria meningitidis, however, the analysis of isolates from long-term asymptomatic carriage is necessary to elucidate their evolution and population structure. Here, we use mathematical models to analyse the structuring and dynamics of three vaccine-candidate antigens among carried meningococcal isolates collected over nearly 30 years in the Czech Republic. The data indicate that stable combinations of antigenic alleles were maintained over this time period despite evidence for high rates of recombination, consistent with theoretical models in which strong immune selection can maintain non-overlapping combinations of antigenic determinants in the presence of recombination. We contrast this antigenic structure with the overlapping but relatively stable combinations of the housekeeping genes observed among the same isolates, and use a novel network approach to visualize these relationships.
- MeSH
- alely MeSH
- antigeny bakteriální genetika imunologie MeSH
- bakteriální proteiny genetika MeSH
- biologické modely MeSH
- genetická variace MeSH
- lidé MeSH
- meningokoková meningitida mikrobiologie MeSH
- molekulární evoluce * MeSH
- Neisseria meningitidis genetika imunologie MeSH
- poriny genetika imunologie MeSH
- přenašečství mikrobiologie MeSH
- proteiny vnější bakteriální membrány genetika imunologie MeSH
- rekombinace genetická MeSH
- selekce (genetika) MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Neisseria meningitis is a human commensal bacterium that occasionally causes life-threatening disease. As with a number of other bacterial pathogens, meningococcal populations comprise distinct lineages, which persist over many decades and during global spread in the face of high rates of recombination. In addition, the propensity to cause invasive disease is associated with particular "hyperinvasive" lineages that coexist with less invasive lineages despite the fact that disease does not contribute to host-to-host transmission. Here, by combining a modeling approach with molecular epidemiological data from 1,108 meningococci isolated in the Czech Republic over 27 years, we show that interstrain competition, mediated by immune selection, can explain both the persistence of multiple discrete meningococcal lineages and the association of a subset of these with invasive disease. The model indicates that the combinations of allelic variants of housekeeping genes that define these lineages are associated with very small differences in transmission efficiency among hosts. These findings have general implications for the emergence of lineage structure and virulence in recombining bacterial populations.
- MeSH
- alely MeSH
- dítě MeSH
- dospělí MeSH
- genetická variace MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- molekulární epidemiologie MeSH
- molekulární evoluce * MeSH
- Neisseria meningitidis klasifikace genetika izolace a purifikace patogenita MeSH
- předškolní dítě MeSH
- selekce (genetika) * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- virulence genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
The distribution of serogroups and multilocus sequence types (STs) in collections of disease-associated and carried meningococci from the period 1991 to 2000 in three European countries (the Czech Republic, Greece, and Norway) was investigated. A total of 314 patient isolates and 353 isolates from asymptomatic carriers were characterized. The frequency distributions of serogroups and clone complexes differed among countries and between disease and carrier isolate collections. Highly significant differentiation was seen at each housekeeping locus. A marked positive association of serogroup C with disease was evidenced. The ST-11 complex was strongly positively associated with disease; associations for other clone complexes were weaker. The genetic diversity of the clone complexes differed. A single ST dominated the ST-11 clone complex, while the ST-41/44 complex exhibited greater levels of diversity. These data robustly demonstrated differences in the distribution of meningococcal genotypes in disease and carrier isolates and among countries. Further, they indicated that differences in genotype diversity and pathogenicity exist between meningococcal clone complexes.
- MeSH
- genetická variace MeSH
- genotyp MeSH
- lidé MeSH
- meningokokové infekce epidemiologie mikrobiologie MeSH
- Neisseria meningitidis klasifikace genetika izolace a purifikace patogenita MeSH
- přenašečství epidemiologie mikrobiologie MeSH
- sérotypizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Norsko MeSH
- Řecko MeSH
The distribution of serogroups and multilocus sequence types (STs) in collections of disease-associated and carried meningococci from the period 1991 to 2000 in three European countries (the Czech Republic, Greece, and Norway) was investigated. A total of 314 patient isolates and 353 isolates from asymptomatic carriers were characterized. The frequency distributions of serogroups and clone complexes differed among countries and between disease and carrier isolate collections. Highly significant differentiation was seen at each housekeeping locus. A marked positive association of serogroup C with disease was evidenced. The ST-11 complex was strongly positively associated with disease; associations for other clone complexes were weaker. The genetic diversity of the clone complexes differed. A single ST dominated the ST-11 clone complex, while the ST-41/44 complex exhibited greater levels of diversity. These data robustly demonstrated differences in the distribution of meningococcal genotypes in disease and carrier isolates and among countries. Further, they indicated that differences in genotype diversity and pathogenicity exist between meningococcal clone complexes.
- MeSH
- genetická variace MeSH
- genotyp MeSH
- lidé MeSH
- meningokokové infekce * epidemiologie mikrobiologie MeSH
- Neisseria meningitidis * genetika izolace a purifikace klasifikace patogenita MeSH
- přenašečství * epidemiologie mikrobiologie MeSH
- sérotypizace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Norsko MeSH
- Řecko MeSH
The genetic diversity of porB genes from meningococcal isolates characterized as serotype 22 was investigated by gene sequencing. This procedure identified seven distinct porB sequences, demonstrating variation in the PorB protein recognized by the serotype 22 monoclonal antibody. This is consistent with the genetic heterogeneity of serotype 22 meningococci reported previously.
