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.

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.

[Invasive community-acquired infections in children]. / Lasten kotisyntyiset invasiiviset infektiot.

The study group consisted of 180 patients who had 186 community-acquired blood-culture positive infections during 2007-June 2013. Three of them died of meningitis caused by S. pneumoniae or N. meningitidis. A ten-valent conjugated pneumococcal vaccine was introduced in the Finnish National Vaccine Program in 2010. After that the incidence of invasive pneumococcal infections decreased markedly. The numbers of resistant S. pneumoniae appeared to decrease slightly, as did also hospitalization due to pneumonia in age group 0 to 2 years. No evidence for serotype replacement was found. The situation requires constant monitoring as the time passes, since the introduction of vaccination is quite recent.

Association between anti-capsular IgG levels at birth and risk of invasive group B streptococcus disease in Finnish newborns: a retrospective case-control study.

BACKGROUND: Group B streptococcus is a major cause of neonatal disease. Natural history studies have linked maternally transferred anti-group B streptococcus capsular polysaccharide antibodies with protection against infant group B streptococcus disease. Previous studies of capsular polysaccharide antibody concentration in European populations have used maternal (not infant) sera and a non-standardised assay. This study aimed to evaluate anti-capsular polysaccharide IgG concentrations associated with protection against invasive group B streptococcus disease in Finnish infants. METHODS: In this retrospective case-control study, we used cord sera from the Finnish DIPP study repository, which was obtained between Jan 1, 1995, and Dec 31, 2017. We included infants aged 6 months or younger with group B streptococcus infection (cases) and healthy infants (controls). We enrolled infants with invasive neonatal group B streptococcus (55 cases) and matched controls (229 controls) aged 6 months or younger after identification from Finnish health registers. We measured anti-capsular polysaccharide IgG (serotypes Ia-V) concentration using a standardised immunoassay and we estimated its relationship to disease risk using a Bayesian model. We used the derived risk-concentration curve to predict potential efficacy of six-valent group B streptococcus capsular polysaccharide vaccine (GBS6) based on previously reported immunogenicity data. FINDINGS: Most (32 [58%] of 55 cases) group B streptococcus cases were due to serotype III and anti-serotype III streptococcus capsular IgG concentrations were higher in serotype III-matched controls than in cases (p<0·001). 0·120-0·266 µg/mL serotype III-specific IgG was estimated to confer 75-90% risk reduction against serotype III disease. A universal risk-concentration curve, aggregating results across all six serotypes, yielded similar results. Application of this curve to GBS6 immunogenicity data predicted maternal immunisation to be more than 80% efficacious for prevention of infant group B streptococcus disease. INTERPRETATION: Higher neonatal anti-capsular polysaccharide serum IgG concentration at birth correlated with reduced risk of infant group B streptococcus disease in Finland. Based on these results, a maternal group B streptococcus capsular conjugate vaccine currently in development is predicted to be efficacious. FUNDING: Pfizer.

Pneumococcemia in children--a retrospective study before universal pneumococcal vaccinations.

AIM: To evaluate the incidence and characteristics of blood culture-positive occult pneumococcemia compared with blood culture-positive pneumococcal pneumonia in children. METHODS: In years 2001-2010, 105 children with positive blood cultures for Streptococcus pneumoniae were identified from hospital electronic files. The patient cards were retrospectively charted for clinical and laboratory data, and 38 patients had and 67 had not pneumonia. RESULTS: The annual incidence of pneumococcemia was, on average, 29.0/10 000 at 0-12 months, 5.3/10 000 at 13-24 months and 1.9/10 000 at 2-4 years of ages, with no increasing or decreasing trend. The incidence of bacteraemic pneumococcal pneumonia increased (p = 0.022) during the study period. The duration of fever before hospitalization (<24 h 73.9% vs. 25.0%, p = 0.022) and the duration of intravenous antibiotics, usually G-penicillin (median 72 vs. 96 h, p = 0.021) was shorter in pneumococcemia patients. On admission, blood leucocyte count was higher in pneumococcemia (mean 26.6 vs. 21.9 × 10E9/L, p = 0.012), but serum CRP was higher in pneumonia (median 160 vs. 67.4 mg/L, p < 0.001). The serotypes 6B and 14 caused 53.2% of pneumococcemia cases. CONCLUSION: The incidence of pneumococcemia was highest in 1-2-year-old children, and typical for pneumococcemia was rapid onset of fever, high blood leucocyte count and a modestly elevated CRP on admission.

From Quellung to multiplex PCR, and back when needed, in pneumococcal serotyping.

All currently available vaccines against Streptococcus pneumoniae are based on selections of the over 90 different serotypes, which underlines the importance of serotyping for surveillance and vaccine efficacy monitoring. In this study, we modified and validated a PCR-based scheme for deducing the serotypes of the invasive pneumococci isolated in Finland. For validation, 170 isolates were serotyped using the new protocol with six sequential multiplex PCRs for the deduction of serotypes, supplemented with Quellung testing when needed. The results were compared with those obtained by traditional serotyping methods. We found that 98.8% (168/170) of the isolates were correctly serotyped by the new protocol. Subsequently, the scheme was taken into regular use for serotyping the invasive pneumococci isolated in Finland for serotype-specific surveillance purposes and has been applied in the serotyping of more than 1,500 invasive isolates so far. The sequential multiplex PCRs (mPCRs) have given a result for over 99% of the isolates and allowed us to both handle samples in bulk and noticeably reduce the cost of reagents. While serotyping primarily by PCR is precise and effective, Quellung testing remains the most reliable way to discover possible discrepancies between the DNA deduced and the phenotypic serotype of an isolate. Since implementing the protocol for regular use, two serotype 19F PCR-positive isolates were found to be serotype 19A by the Quellung reaction. While a rare occurrence, this is an important observation, which prompted a revision of our serotyping protocol to prevent possible underreporting of serotype 19A, a potential replacement serotype following large-scale vaccination.

Genotypic and phenotypic characterization of carriage and invasive disease isolates of Neisseria meningitidis in Finland.

The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates.

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.

Long-term population effects of infant 10-valent pneumococcal conjugate vaccination on pneumococcal meningitis in Finland.

BACKGROUND: No previous studies have reported long-term follow-up of ten-valent pneumococcal conjugate vaccine (PCV10) program impact on pneumococcal meningitis (PM). We assessed the effects of infant PCV10 program on PM incidence, mortality and serotype distribution in children and adults during 7 years after introduction. METHODS: We conducted a population-based observational study. A case of PM was defined as isolation of Streptococcus pneumoniae from cerebrospinal fluid or, a patient with S. pneumoniae isolated from blood and an ICD-10 hospital discharge diagnosis of bacterial meningitis within 30 days before or after positive culture date.We compared age- and serotype-specific incidence and associated 30-day mortality rates in 2011-2017 (PCV10 period) with those in 2004-2010 (pre-PCV10 baseline) by using Poisson regression models. Absolute rate differences and 95% confidence intervals (CIs) were calculated from the parameter estimates by using delta method. RESULTS: During the PCV10 period, the overall incidence of PCV10 serotype meningitis decreased by 68% (95%CI 57%-77%), and the overall PM incidence by 27% (95%CI: 12%-39%). In age groups 0-4, 50-64, and ≥ 18 years, the overall PM incidence was reduced by 64%, 34% and 19%, respectively. In adults ≥ 65 years of age, a 69% reduction in PCV10 serotypes was offset by 157% (56%-342%) increase in non-PCV10 serotypes. The overall PM-related mortality rate decreased by 42% (95%CI 4%-65%). Overall case fatality proportion (CFP) was 16% in pre-PCV10 period and 12% in PCV10 period (p = 0.41); among persons 50-64 years the CFP decreased from 25% to 10% (p = 0.04). CONCLUSIONS: We observed substantial impact and herd protection for vaccine-serotype PM and associated mortality after infant PCV10 introduction. However, in older adults ≥ 65 years of age, PM burden remains unchanged due to serotype replacement.

Similar impact and replacement disease after pneumococcal conjugate vaccine introduction in hospitalised children with invasive pneumococcal disease in Europe and North America.

High incidence of childhood invasive pneumococcal disease (IPD) in the US declined steeply after 7-valent pneumococcal conjugate vaccine (PCV7) introduction, outweighing reductions observed elsewhere. We re-analysed aggregate published data and compared pre- and post-PCV IPD-incidence in different countries to explore PCV impact on hospitalised and outpatient IPD separately. The proportion of hospitalised IPD cases was consistently high (>80%) in England&Wales, Finland, the Netherlands, and Quebec/Canada, but only 32% in the US before PCV introduction, increasing to 69% during the PCV era. In the US, a higher reduction in outpatient IPD incidence (94% in 2015 versus 1998-99) was observed compared to hospitalised IPD (79%); a 51% reduction in the non-PCV13-type IPD incidence among outpatient cases was estimated compared to a >2-fold increase for hospitalised cases. After stratification by hospitalization status, PCV programmes resulted in similar impact and serotype replacement in hospitalised IPD in US when compared to other countries.

Effectiveness of 10-valent pneumococcal conjugate vaccine estimated with three parallel study designs among vaccine-eligible children in Finland.

BACKGROUND: Ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in 9/2010. We estimated the individual-level effectiveness (VE) of PCV10 in children during eight years of vaccine implementation. METHODS: Data on invasive pneumococcal disease (IPD) were collected from national, population-based surveillance, and vaccination status from the vaccination register. Vaccine-eligible children were followed from six months of age until end of 2018 (born 6/2010 or later, ages 6-102 months). VE was estimated with three parallel approaches: full cohort, nested case-control and indirect cohort designs adjusting with age-group, sex and calendar year. RESULTS: VE against PCV10 serotype IPD was estimated at 93% (95% credible interval 87-97%), 98% (90-100%) and 100% (98-100%), and against PCV10-related serotypes at 46% (-13-72%), 51% (-24-79%), and 78% (-7-97%), with the full cohort, nested case-control, and indirect cohort designs, respectively. The estimated VE against non-PCV10-related (neither PCV10 nor PCV10-related) serotypes was negative but included zero effectiveness (full cohort VE -67%, -711-52%; nested case-control VE -77%, -929-59%). VE against all IPD was estimated with these two methods at 54% (24-71%) and 61% (26-79%). Over time, VE against PCV10 IPD remained stable but VE against all IPD decreased. DISCUSSION: All designs provided estimates that were concordant with each other, but those with the full cohort design were usually the most precise. PCV10 offered sustained high VE against PCV10-serotype IPD on vaccinated children during the first decade after introduction into the programme.

Genomic Characterization of Invasive Meningococcal Serogroup B Isolates and Estimation of 4CMenB Vaccine Coverage in Finland.

Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a significant cause of morbidity and mortality worldwide. In Finland, the incidence rate of IMD is low, with meningococcal serogroup B (MenB) accounting for around one-third of IMD cases annually. The aim of this study was to investigate the genetic variability of invasive MenB isolates collected in Finland between 2010 and 2017 (n = 81), including the genes encoding the 4-component MenB vaccine (4CMenB; Bexsero; GSK) antigens and their promoters, and to evaluate the 4CMenB potential coverage. Whole-genome sequencing was performed. The meningococcal antigen typing system (MATS) was used to characterize MenB isolates and predict the potential coverage of 4CMenB. MATS was complemented by genetic MATS (gMATS) through association of antigen genotyping and phenotypic MATS results. Multilocus sequence typing revealed predominance of the ST-41/44 clonal complex among which sequence type (ST)-303 was the most common and was predicted to be covered by 4CMenB. Of the 4 major vaccine antigens, the factor H-binding protein variant 1, neisserial heparin binding antigen peptide 2, and the PorA P1.4 antigen were predominant, whereas Neisseria adhesin A was present in only 4% of the 81 isolates. MATS and gMATS 4CMenB strain coverage predictions were 78% and 86%, respectively, in a subpanel of 60 isolates collected during 2010 to 2014, with a gMATS prediction of 84% for all 81 isolates. The results suggest that 4CMenB could reduce the burden of IMD in Finland and that gMATS could be applied to monitor vaccine strain coverage and predict vaccine effectiveness.IMPORTANCE 4CMenB is a 4-component vaccine used against invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B (MenB). We investigated the genetic variability of MenB in Finland and evaluated 4CMenB strain coverage by 2 different methods: MATS (meningococcal antigen typing system) and gMATS (genetic MATS). In a set of MenB isolates, 78% (MATS) and 86% (gMATS) were predicted as covered by 4CMenB, suggesting that use of 4CMenB would help reduce IMD incidence in Finland. MATS has been used in 13 countries worldwide, generating information on phenotypic characteristics that could infer protection by 4CMenB. Based on these data and genetic information, gMATS coverage predictions can be made. gMATS predicts coverage consistent with MATS for about 94% of tested strains. Unlike MATS, gMATS does not require live isolates, thus allowing the analysis also of noncultivable strains, making the coverage predictions more accurate. Therefore, gMATS can replace MATS to assess 4CMenB coverage, including in regions with no prior MATS data.

Prevalence of pneumococcal nasopharyngeal colonization and serotypes circulating in Cameroonian children after the 13-valent pneumococcal conjugate vaccine introduction.

BACKGROUND: Streptococcus pneumoniae remains a major contributor to childhood infections and deaths globally. In Cameroon, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in July 2011, using a 3-dose Expanded programme on immunization (EPI) schedule administered to infants at 6, 10 and 14 weeks of age. To evaluate PCV13 effects, we assessed pneumococcal nasopharyngeal colonization and serotype distribution among Cameroonian children after PCV13 introduction. METHODS: Nasopharyngeal (NP) swabs were collected from eligible children aged 24-36 months in two cross-sectional surveys conducted from March to July: in 2013 (PCV13-unvaccinated), and in 2015 (PCV13-vaccinated). Using a systematic World Health Organization (WHO) cluster coverage sampling technique in 40 communities, NP swabs collected were processed following WHO recommendations. Standard bacterial culture techniques were used for the isolation of S. pneumoniae from gentamicin-blood agar plates and identification using optochin susceptibility testing. Serotyping was performed using sequential multiplex polymerase chain reaction, supplemented with Quellung test. RESULTS: Among the PCV13-vaccinated children, overall pneumococcal carriage prevalence was 61.8% (426/689) and PCV13 vaccine-type carriage prevalence was 18.0% (123/689). Eleven out of the 13 vaccine serotypes were detected in the vaccinated children. The most common serotypes were 19F (4.5%, 31/689) and 15B/C (7.3%, 50/689). CONCLUSION: In Cameroon, four years after infant vaccination nearly all of the PCV13-serotypes continued to circulate in the population. This suggests that the direct and indirect effects of the vaccination programme have not resulted in expected low levels of vaccine-type transmission. Continuous monitoring is needed to assess the long term effects of the PCV13 on nasopharyngeal carriage and disease.

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.

Pneumococcal Haemophilus influenzae protein D conjugate vaccine induces antibodies that inhibit glycerophosphodiester phosphodiesterase activity of protein D.

Haemophilus influenzae outer membrane protein D (PD) is a glycerophosphodiester phosphodiesterase (GlpQ) activity-possessing virulence factor and a promising vaccine antigen, providing 35.3% efficacy against acute otitis media caused by nontypeable H. influenzae (NTHI) when it was used as a carrier protein in a novel pneumococcal PD conjugate (Pnc-PD) vaccine. To study if PD-induced protection against NTHI could be due to antibodies that inhibit or neutralize its enzymatic activity, a GlpQ enzyme inhibition assay was developed, and serum samples collected from Finnish infants before and after Pnc-PD vaccination were analyzed for enzyme inhibition and anti-PD immunoglobulin G (IgG) antibody concentration. Before vaccination at age 2 months, the majority (84%) of infants (n = 69) had no detectable anti-PD IgG antibodies, and all were enzyme inhibition assay negative (inhibition index, <20). At age 13 to 16 months, all infants receiving three or four doses of Pnc-PD had detectable anti-PD IgG antibodies and 36% (8/22 infants) of the infants receiving three doses and 26% (6/23 infants) of the infants receiving four doses of Pnc-PD were inhibition assay positive (inhibition index, >/=20). No significant rise in anti-PD IgG antibodies or enzyme inhibition among control vaccinees (n = 24) receiving three doses of hepatitis B vaccine was detected. A modest correlation (r(s), approximately 0.66) between anti-PD IgG concentration and enzyme inhibition was detected; however, their kinetics were clearly different. These data suggest that measurement of antibody responses that inhibit PD's enzymatic activity could be a useful tool for assessing Pnc-PD vaccine-induced protective immunity against NTHI.

Acute bacterial, nonnecrotizing cellulitis in Finland: microbiological findings.

BACKGROUND: Bacterial, nonnecrotizing cellulitis is a localized and often recurrent infection of the skin. The aim of this study was to identify the beta-hemolytic streptococci that cause acute nonnecrotizing cellulitis infection in Finland. METHODS: A case-control study of 90 patients hospitalized for acute cellulitis and 90 control subjects was conducted during the period of April 2004-March 2005. Bacterial swab samples were obtained from skin lesions or any abrasion or fissured toe web. Blood culture samples were taken for detection of bacteremia. The patients, their household members, and control subjects were assessed for pharyngeal carrier status. beta-Hemolytic streptococci and Staphylococcus aureus were isolated and identified, and group A and G streptococcal isolates were further analyzed by T serotyping and emm and pulsed-field gel electrophoresis typing. RESULTS: beta-Hemolytic streptococci were isolated from 26 (29%) of 90 patients, 2 isolates of which were blood-culture positive for group G streptococci, and 24 patients had culture-positive skin lesions. Group G Streptococcus (Streptococcus dysgalactiae subsp. equisimilis) was found most often and was isolated from 22% of patient samples of either skin lesions or blood, followed by group A Streptococcus, which was found in 7% of patients. Group G streptococci were also carried in the pharynx of 7% of patients and 13% of household members but was missing from control subjects. Several emm and pulsed-field gel electrophoresis types were present among the isolates. Six patients (7%) had recurrent infections during the study. In 2 patients, the group G streptococcal isolates recovered from skin lesions during 2 consecutive episodes had identical emm and pulsed-field gel electrophoresis types. CONCLUSIONS: Group G streptococci, instead of group A streptococci, predominated in bacterial cellulitis. No clear predominance of a specific emm type was seen. The recurrent nature of cellulitis became evident during this study.

Long-term impact of 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease among children in Finland.

BACKGROUND: The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010. The impact of PCV10 vaccination against invasive pneumococcal disease (IPD) in vaccine-eligible children has been high. We evaluated the long-term impact of PCV10 vaccination against IPD in vaccine-eligible and older, unvaccinated children six years after PCV10 introduction with a special focus on cross-protection against PCV10-related serotypes (serotypes in the same serogroups as the PCV10 types). METHODS: We used data on IPD from the national, population-based surveillance. A target cohort of vaccine-eligible children (born June 2010 or later) was followed from 3 months of age until the end of 2016. For the indirect effect, another cohort of older PCV10-ineligible children was followed from 2012 through 2016. IPD rates were compared with those of season- and age-matched reference cohorts before NVP introduction. RESULTS: Among vaccine-eligible children, the incidence of all IPD decreased by 79% (95% CI 74-83%). There was a statistically significant reduction in the incidence of 6A IPD, but for 19A, the reduction was non-significant and the incidence of 19A increased towards the end of the study period in the older vaccine-eligible children. The increase in non-PCV10 related serotypes was non-significant. In the unvaccinated older children, the incidence of all IPD decreased by 33% (95% CI 8-52%) compared to the reference cohort, and there was no impact on serotype 6A or 19A IPD. CONCLUSION: Overall, the impact of PCV10 vaccination on IPD was high in vaccine-eligible children, with a major reduction in vaccine-type disease, and without notable replacement by other serotype groups. Our data suggest that PCV10 results in long-lasting direct cross-protection against 6A IPD. For 19A, no net reduction was observed six years after NVP introduction in the vaccine-eligible cohort. The indirect impact on IPD in unvaccinated children sustained.

Bacterial meningitis in Finland, 1995-2014: a population-based observational study.

OBJECTIVES: Bacterial meningitis remains an important cause of morbidity and mortality worldwide. Its epidemiological characteristics, however, are changing due to new vaccines and secular trends. Conjugate vaccines against Haemophilus influenzae type b and Streptococcus pneumoniae (10-valent) were introduced in 1986 and 2010 in Finland. We assessed the disease burden and long-term trends of five common causes of bacterial meningitis in a population-based observational study. METHODS: A case was defined as isolation of S. pneumoniae, Neisseria meningitidis, Streptococcus agalactiae, Listeria monocytogenes or H. influenzae from cerebrospinal fluid and reported to national, population-based laboratory surveillance system during 1995-2014. We evaluated changes in incidence rates (Poisson or negative binomial regression), case fatality proportions (χ2) and age distribution of cases (Wilcoxon rank-sum). RESULTS: During 1995-2014, S. pneumoniae and N. meningitidis accounted for 78% of the total 1361 reported bacterial meningitis cases. H. influenzae accounted for 4% of cases (92% of isolates were non-type b). During the study period, the overall rate of bacterial meningitis per 1 00 000 person-years decreased from 1.88 cases in 1995 to 0.70 cases in 2014 (4% annual decline (95% CI 3% to 5%). This was primarily due to a 9% annual reduction in rates of N. meningitidis (95% CI 7% to 10%) and 2% decrease in S. pneumoniae (95% CI 1% to 4%). The median age of cases increased from 31 years in 1995-2004 to 43 years in 2005-2014 (p=0.0004). Overall case fatality proportion (10%) did not change from 2004 to 2009 to 2010-2014. CONCLUSIONS: Substantial decreases in bacterial meningitis were associated with infant conjugate vaccination against pneumococcal meningitis and secular trend in meningococcal meningitis in the absence of vaccination programme. Ongoing epidemiological surveillance is needed to identify trends, evaluate serotype distribution, assess vaccine impact and develop future vaccination strategies.

Direct and Indirect Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine Against Carriage in a Cluster Randomized Trial.

Finnish invasive pneumococcal disease (FinIP) vaccine trial was designed to evaluate effectiveness of 10-valent pneumococcal conjugate vaccine (PHiD-CV10; GSK; Rixensart, Belgium). We conducted 2 satellite studies to evaluate ten-valent Pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) effectiveness against pneumococcal carriage in FinIP-vaccinated children (long-term direct and indirect effectiveness combined) and in their unvaccinated siblings (indirect effectiveness within the family). FinIP was a cluster randomized trial, where >47,000 children <19 months of age were recruited in 2009-2010. Children received PHiD-CV10 in 2/3, and control vaccine in 1/3 of clusters according to age-specific infant and catch-up schedules. We obtained nasopharyngeal samples from subgroups of FinIP-vaccinated children at 3-5 years of age in 2013 and their unvaccinated older siblings in 2011 and 2013, and compared carriage in PHiD-CV10 clusters to control clusters in parallel. National Vaccination Programme with PHiD-CV10 for all 3-month-old children started in 2010 resulting in 92% vaccination coverage. To investigate indirect effects, over 2200 nasopharyngeal swabs were obtained during each round from unvaccinated older siblings. In 2011, we observed a 29% (95% confidence interval: 6-47) reduction in vaccine-type carriage in siblings of PHiD-CV10 participants vaccinated according to infant schedules. Vaccine-type carriage prevalences were low with no differences observed in 2013, 3 years after PHiD-CV10 introduction. For estimation of combined direct and indirect effectiveness, 1550 swabs from FinIP-vaccinated children were obtained in 2013. We observed a reduction of 54% (95% confidence interval: 34-68) in vaccine-type carriage in PHiD-CV10-vaccinated children. This study was the first randomized trial to show the indirect effect of extended valency pneumococcal conjugate vaccination on carriage. Also, long-term effectiveness against vaccine-type carriage was demonstrated in vaccinated children.