Clonality of Streptococcus pneumoniae in relation to antimicrobial resistance in Finland

Streptococcus pneumoniae, or the pneumococcus, is a bacterium of the human nasopharyngeal normal flora that also causes non-invasive respiratory tract infections, and serious infections, such as pneumonia, septicaemia, and meningitis. Globally, the rise in pneumococcal antimicrobial resistance over the past few decades is a worrying trend. The bacterium is covered by a polysaccharide capsule and over 90 different kinds of pneumococcal capsules can be recognised by serotyping. The most important serotypes are included in the available polysaccharide and conjugate vaccines. The 10-valent conjugate vaccine has been part of the Finnish national vaccination programme since September 2010. In this study, the serotype and genotype clonality of the invasive pneumococcal population in Finland was studied in relation to antimicrobial resistance. All invasive pneumococci (n=7,765) isolated in Finland during 2002-2011 and a subset of non-invasive multidrug-resistant isolates (n=12) from 2008 were serotyped and studied for antimicrobial susceptibility. The penicillin-resistant isolates were genotyped by multi locus sequence typing (MLST) and pilus-encoding virulence genes were detected by PCR. A sequential multiplex PCR assay for deducting the serotypes of pneumococci was set up tailored to the serotype distribution of invasive isolates recovered in Finland. Serotype 14 was the predominant serotype every year of the study, representing 17.5% of all the invasive isolates. The proportion of invasive isolates non-susceptible to penicillin or erythromycin was high, and it increased over the study period, reaching 22% and 26% for penicillin and erythromycin, respectively, in 2011. The proportion of non-susceptible isolates was particularly high among isolates from children and within serotype 14. Among the genotyped isolates, international resistant clones such as PMEN3 Spain9VST156 and PMEN14 Taiwan19FST236 dominated. However, novel genotypes were also found, which illustrates the continuous recombination of pneumococci. This study showed that in Finland multidrug-resistant serotype 19A pneumococci appeared among the non-invasive isolates prior to large-scale vaccination. In many countries, the clone has emerged following vaccination. Pilus-encoding gene carriage, which may serve as a competitive advantage for the bacterium by facilitating adherence to the epithelium, was frequent among the penicillin- and multidrug-resistant isolates. In the future, a vaccine targeting the pilus proteins might successfully help to control these clones. The serotyping scheme, which was set up, is useful in surveillance, as knowledge of the serotype distribution of the invasive pneumococci is essential for vaccine development and monitoring of the vaccination programme.Streptococcus pneumoniae, pneumokokki, on nenänielun normaaliflooran bakteeri, joka voi aiheuttaa hengitystieinfektioita sekä vakavia tauteja, kuten keuhkokuumetta, verenmyrkytystä ja aivokalvontulehdusta. Pneumokokkien mikrobilääkeresistenssi on maailmanlaajuisesti ollut huolestuttavassa kasvussa. Pneumokokilla tunnetaan yli 90 erilaista polysakkaridikapselia, jotka määritetään serotyypittämällä. Käytössä olevat rokotteet kattavat tärkeimmät vakavia tauteja aiheuttavat serotyypit. 10-valenttinen pneumokokkikonjugaattirokote on syyskuusta 2010 lähtien ollut osa kansallista rokotusohjelmaa. Tutkimuksessa tarkasteltiin invasiivisten pneumokokkien klonaalisuutta sekä serotyyppi- että genotyyppitasolla suhteessa mikrobilääkeherkkyyteen. Serotyyppi ja mikrobilääkeherkkyys määritettiin kaikille Suomessa vuosina 2002-2011 verestä tai selkäydinnesteestä eristetyille invasiivisille kannoille sekä osalle vuonna 2008 eristetyille ei-invasiivisille moniresistenteille pneumokokeille. Penisilliiniresistenttien kantojen perimää tarkasteltiin edelleen määrittämällä niiden genotyyppi ja pilusgeenien läsnäolo. Lisäksi tutkimuksessa pystytettiin Suomen pneumokokkipopulaatioon räätälöity bakteerin perimää havaitseva serotyypitysmenetelmä. Serotyyppi 14 oli tärkein, se kattoi 17,5 % kaikista tutkimuksen invasiivisista pneumokokeista. Penisilliinille herkkyydeltään alentuneiden kantojen osuus kasvoi tutkimusjaksona ja oli 22 % vuonna 2011. Herkkyydeltään alentuneiden kantojen osuus oli erityisen korkea lapsilta eristettyjen kantojen keskuudessa sekä serotyypillä 14. Myös erytromysiinille herkkyydeltään alentuneiden kantojen osuus oli korkea. Suurin osa genotyypitetyistä kannoista oli sukua maailmanlaajuisille resistenteille pneumokokkiklooneille mutta myös uusia genotyyppejä havaittiin, mikä kuvastaa resistenttien kloonien jatkuvaa kehitystä. Havaittiin, että serotyypin 19A moniresistentti pneumokokkikanta on esiintynyt Suomessa ei-invasiivisissa kannoissa jo ennen laajamittaisia rokotuksia, vaikka se on useassa maassa yleistynyt vasta rokotusten myötä. Valtaosa tutkituista resistenteistä kannoista kantoi limakalvoon tarttumista edistäviä pilusgeenejä. On todennäköistä, että mahdollinen pilusproteiineja sisältävä rokote kykenisi tulevaisuudessa torjumaan tällaisia kantoja. Pystytetyllä serotyypitysmenetelmällä voidaan selvittää invasiivisen pneumokokkipopulaation serotyyppijakauma, jonka tunteminen on ensiarvoisen tärkeää rokoteseurannassa ja rokotekehittämistyössä.Streptococcus pneumoniae, eller pneumokocken, är en bakterie som finns i människans normalflora men också orsakar allt från milda luftvägsinfektioner till svåra invasiva sjukdomar som lunginflammationer, sepsis och hjärnhinne-inflammationer. Globalt sett har antibiotikaresistensen bland pneumokocker ökat oroväckande under de senaste decennierna. Fler än 90 olika polysackaridkapslar har beskrivits; dessa bestäms genom serotypning. De viktigaste serotyperna finns med i de vaccin som utvecklats mot pneumokocksjukdomar. I september 2010 blev det 10-valenta konjugatvaccinet en del av det nationella vaccinationsprogrammet i Finland. I den här undersökningen granskades de invasiva pneumokockernas klonalitet både på sero- och genotypnivå i förhållande till antibiotikaresistensen i Finland. Serotyper och antibiotikakänslighet bestämdes för alla invasiva pneumokocker som isolerades i Finland under åren 2002-2011 och för ett sampel av multiresistenta icke-invasiva pneumokocker från år 2008. De penicillinresistenta stammarna genotypades och deras gener för piluskodande virulensfaktorer utreddes. Ett nytt serotypnings-protokoll baserat på multiplex-PCR sattes också upp. Bland serotyperna var serotyp 14 den viktigaste, den utgjorde 17,5% av alla invasiva stammar. Andelen isolat med nedsatt känslighet mot penicillin eller erytromycin var hög och ökade under forskningsperioden till 22 %, respektive 26 %, av stammarna. Andelen stammar med nedsatt antibiotikakänslighet var speciellt hög bland isolat från barn och inom serotyp 14. Internationella resistenta kloner dominerade bland de genotypade stammarna. Nya genotyper hittades också vilket beskriver de resistenta klonernas fortsatta utveckling. Resultaten visar också att den multiresistenta serotyp 19A-klon som på många håll i världen ökat markant efter vaccinering, hade fått fotfäste i Finland redan före storskalig vaccinering inletts. Majoriteten av de penicillin- och multiresistenta pneumokockerna bar på piluskodande gener, vilket tyder på att ett vaccin som innehåller pilusprotein i framtiden kunde begränsa dessa viktiga kloners framfart. Det nya serotypningsprotokollet möjliggör också i fortsättningen granskningen av pneumokockernas serotypfördelning för vaccin-uppföljning och vaccinutvecklingsbehov

Koronavilkku-projektin loppuraportti

Koronavilkku oli koronaviruksen tartuntaketjujen katkaisun tehostamiseen tarkoitettu tietojärjestelmä. Se auttoi informoimaan käyttäjiä mahdollisesta altistumisesta koronavirukselle ja antoi heille toimintaohjeita. Mahdollisesti altistunut henkilö ohjattiin Koronavilkusta terveydenhuollon palveluihin. Tartunnan saanut puolestaan sai positiivisen laboratoriotestin jälkeen terveydenhuollosta Koronavilkun avauskoodin. Syöttämällä sen sovellukseen hän lähetti ilmoituksen tartunnastaan Koronavilkun taustajärjestelmään, josta lähti tieto mahdollisesti altistuneille. Koronavilkku toteutettiin korkeiden tietosuoja ja -turva vaatimuksien mukaisesti. Sovellus oli käytössä 31.8.2020 1.6.2022. Koronavilkku oli sovelluskäyttäjille vapaaehtoinen ja maksuton. Tässä loppuraportissa kerrotaan Koronavilkku-projektin vaiheista ja opeista. Lisäksi annetaan ideoita mahdolliseen vastaavaan tilanteeseen tulevaisuudessa

Long-term population impact of infant 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in adults in Finland

Background: Limited data are available on long-term indirect effects of ten-valent pneumococcal conjugate vaccine (PCV10) programmes. We evaluated changes in invasive pneumococcal disease (IPD) incidence, mortality, and serotype distribution in adults up to 9 years after infant PCV10 introduction. Methods: Culture-confirmed IPD cases ≥18 years (n = 5610; 85% were pneumonia) were identified through national, population-based laboratory surveillance; data were linked with population registry to conduct nationwide follow-up study. In a time-series model, we compared serotype-specific IPD incidence and associated 30-day mortality rates before and after PCV10 by using negative binomial regression models. Results: During pre-PCV10 period (7/2004–6/2010), overall IPD incidence in adults ≥18 years increased yearly by 4.8%. After adjusting for trend and seasonality, the observed PCV10 serotype IPD incidence in 7/2018–6/2019 was 90% (12/100,000 person-years) lower than the expected rate without PCV10 program. Non-PCV10 serotype incidence was 40% (4.4/100,000 person-years) higher than expected; serotypes 3, 19A, 22F, and 6C accounted for most of the rate increase. However, incidence of non-PCV10 IPD levelled off by end of follow-up. The observed-expected incidence rate-ratio (IRR) was 0·7 (95 %CI 0·5–0.8) for all IPD and 0·7 (95 %CI 0·3–1·3) for IPD-associated 30-day mortality. Case-fatality proportion decreased from 11·9% to 10.0% (p < 0.01). In persons ≥65 years, the IRR was 0·7 (95 %CI 0·5–0.95). Conclusions: Significant indirect effects were seen for vaccine-serotype IPD and for overall IPD in all adult age groups. For non-vaccine IPD, the incidence stabilized 5 years after infant PVC10 program introduction, resulting in a steady state in which non-vaccine IPD accounted for nearly 90% of overall IPD. Substantial pneumococcal disease burden remains in older adults.publishedVersionPeer reviewe

Outbreak of invasive pneumococcal disease among shipyard workers, Turku, Finland, May to November 2019

We report an outbreak of invasive pneumococcal disease and pneumococcal pneumonia among shipyard workers, in Turku, Southwest Finland. In total, 31 confirmed and six probable cases were identified between 3 May and 28 November 2019. Streptococcus pneumoniae serotypes 12F, 4 and 8 were isolated from blood cultures of 25 cases. Occupational hygiene measures and vaccination of ca 4,000 workers are underway to control the outbreak at the shipyard.</p

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