post-PCV13 Period Research Articles

Early impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis—Burkina Faso, 2014–2015

ObjectivesWe evaluate early impact of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in Burkina Faso. MethodsNationwide surveillance gathered demographic/clinical information and cerebrospinal fluid (CSF) results for meningitis cases. Pneumococcal cases were confirmed by culture, polymerase chain reaction (PCR), or latex agglutination, and strains serotyped using PCR. We compared incidence (cases per 100,000) in the early post-PCV13 period (2014 and 2015) to average pre-PCV13 incidence (2011–2013). ResultsIn 2015, age-specific pneumococcal meningitis incidences were 8.7 (<1 year), 2.4 (1–4 years), 6.5 (5–14 years), and 2.6 (≥15 years). Compared to 2011–2013, PCV13-serotype incidence among all ages decreased by 32% (95%CI: 23%–39%), with significant decreases among children aged <1 year (76%; 95%CI: 64%–84%) and 1–4 years (58%, 95%CI: 40%–71%). Among all ages, incidence of PCV13 serotypes besides serotype 1 decreased (68%; 95%CI: 59%–75%), but serotype 1 incidence did not. Incidence of non-PCV13 serotypes also decreased (47%; 95%CI: 29%–60%). Among children aged <1 year, serotypes 12F/12A/12B/44/46 (17%), 1 (12%), and 5 (10%) predominated. ConclusionsFollowing PCV13 introduction, PCV13-serotype meningitis incidence in young children significantly decreased. PCV13 impact on serotype 1 and disease in older children and adults requires continued monitoring.

Paediatric invasive pneumococcal disease on the island of Gran Canaria: 16-year prospective study (2001–2016)

ObjectivesTo calculate the incidence of invasive pneumococcal disease (IPD) in the paediatric population of Gran Canaria (Spain), its clinical and epidemiological characteristics, serotype distribution, antibiotic resistance, and variations in these variables before and after the introduction of the PCV13 vaccine. MethodsProspective hospital-based study including all patients (190) aged 0–14 years admitted with confirmed IPD between January 2001–May 2010 (152 cases) and June 2010–December 2016 (38 cases). Patients were divided into 3 age groups (<2 years; 2–5 years; and >5 years). Clinical symptoms were mutually-exclusively classified as meningitis, bacteraemic pneumonia, pleural effusion (PE), empyema or bacteraemia without a focus. ResultsMost cases occurred in boys (59.47%), during autumn-winter (65.79%), in children aged <2 years (55.79%) and with mean age increasing from the pre-PCV13 to the post-PCV13 period (2.5 vs 3.1 years). Incidence between periods reduced by 66.4% (p<0.001): from 13.1/100,000 to 4.4/100,000. PEs (3.9% vs 18.4%, p<0.005) and empyemas (1.5% vs 16.7%, p=NS) increased in the post-PCV13 period whereas all other symptoms decreased, although this was not statistically significant. Vaccine serotypes (77% vs 40.6%, p=0.000), particularly serotypes 19A (23.9% vs 12.5%) and 14 (14.2% vs 9.4%), as well as erythromycin resistance (57.2% vs 7.9%, p=0.000) decreased in the post-PCV13 period. ConclusionIPD incidence, vaccine serotypes and erythromycin resistance decreased in the post-PCV13 period whereas PEs increased.

Impact of infant pneumococcal conjugate vaccination on community acquired pneumonia hospitalization in all ages in the Netherlands.

The long-term impact of pneumococcal conjugate vaccines on pneumonia hospitalizations in all age-groups varies between countries. In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV7) was implemented for newborns in 2006 and replaced by PCV10 in 2011. We assessed the impact of PCVs on community-acquired pneumonia (CAP) hospitalization rates in all age-groups. A time series analysis using Poisson regression was performed on 155,994 CAP hospitalizations. Hospitalization rates were calculated using the total number of hospitalizations as denominator. The time trend in the pre-PCV period (1999-2006) was extrapolated to predict the hospitalization rate in the post-PCV period (2006-2014) if PCV had not been implemented. Rate ratios over time were calculated by comparing observed and predicted time trends. In children <5 years of age, the observed hospitalization rates during the post-PCV period were significantly lower than predicted if PCV had not been implemented (0-6 months: 0.62, 95% CI: 0.41-0.96; 6 months - 1 year: 0.67, 95% CI: 0.50-0.90; 2-4 years: 0.78, 95% CI: 0.61-0.97). In all other age-groups, rate ratios declined over time but did not reach statistical significance. After introduction of PCV, CAP hospitalizations declined in young children but no clear impact of PCV on CAP hospitalizations was seen in other age-groups.

Influence of pneumococcal conjugate vaccines on acute otitis media in Japan

ObjectiveThis study investigated: (i) changes in the incidence of acute otitis media (AOM) following introduction of public funding for free inoculation with 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13, respectively) and (ii) changes in the rate of myringotomies for AOM (MyfA) in children 1year following the publication of the first edition of the clinical practice guidelines for the diagnosis and management of AOM in children in Japan. MethodsPCV7 was launched on the Japanese market in 2010 and gained public funding in 2011. PCV7 was replaced with PCV13 in November 2013. Using the Japan Medical Data Center Claims Database, an 11-year study conducted between January 2005 and December 2015 investigated the decline in the incidence of visits to medical institutions (VtMI) due to all-cause AOM in children <15years. The rate of MyfA from January 2007 to December 2015was also investigated and changes before and after introduction of public funding for PCV7 (pfPCV7) and PCV13 (pfPCV13) for children were examined. Statistical data for the age group between 10 years and <15years served as the control. An analysis was conducted to examine changes for each age group, from infants that had received PCVs to children <5years. Statistical analysis was performed using the chi-square test and Ryan’s multiple comparison tests. Ryan’s multiple comparison tests were applied at a 5% level of significance. Due to significant changes in the guidelines on the indications for myringotomy introduced in 2013, statistical analysis of the rate of MyfA was limited to the pre- and post-PCV7 period. ResultsAfter introduction of pfPCV7 and pfPCV13, no significant suppression of the incidence of VtMI was observed in any age group. There was a gradual decline in the rate of MyfA after 2011. Compared to the control group, significant differences in all age groups from infants to children <5years were observed (p<0.009, chi-square test). Within 2 years after the introduction of PCV7, a significant decline in the rate of MyfA was observed in 1- and 5-year-olds using Ryan’s multiple comparison tests at a 5% level of significance. ConclusionThe preventative effect of PCVs on AOM was not established in this study. There was, however, a significant decline in the rate of MyfA among 1- and 5-year-olds. Taking into consideration past studies, PCV7 may play a role in preventing the aggravation of AOM in 1-year-olds. When evaluating the effectiveness of PCVs, measures to evaluate severity may be as important as evaluating disease prevention.

Changes in the epidemiology and clinical features of acute mastoiditis following the introduction of the pneumococcal conjugate vaccine

ObjectivesSeven years after the introduction of the pneumococcal conjugate vaccines (PCV) in Israel, its effect on the incidence and severity of episodes of acute mastoiditis (AM) remains unclear. The primary objective of this study was to determine the incidence of AM and describe its clinical features in children during the years that followed the introduction of the PCV13 in comparison with the pre-PCV period. MethodsIncluded in this retrospective comparative case series were all pediatric patients diagnosed with AM between Jan. 2007 and Dec. 2015 in one tertiary medical center. The patients were divided into 3 groups: pre-PCV, post-PCV7 (July 2009 through Dec. 2010) and post-PCV13 (Jan. 2011 through Dec. 2015). The patients' medical records were reviewed, and data on age at presentation, gender, presenting signs, bacterial ear cultures, hospitalization course, complications, surgical interventions, inflammatory response and outcome were retrieved and compared between the groups. Comparison was made between the pre-PCV and the post-PCV13 groups. Results216 children were identified for analysis, 80 children in the pre-PCV period, 31 in the post-PCV7 period and 105 in the post-PCV13 period. Their mean age was 2.6 years. The number of AM cases per 1000 visits at the emergency room decreased by 46% in the post-PCV13 period compared to the pre-PCV period. There was no difference in the rate of AM between the post-PCV7 and post-PCV13 periods. No differences were found in age, gender, hospitalization length, C-reactive protein level, white blood cell count, rate of surgical interventions (mastoidectomy and incision and drainage) and rate of complications between the 3 groups. ConclusionThe incidence of AM was lower in the post-PCV13 period compared to the pre-PCV period. The rate of AM complications, however, has not changed, nor has the number of mastoidectomies.

Direct and Indirect Impact of 13-valent Pneumococcal Conjugate Vaccine (PCV13) on Invasive Pneumococcal Disease (IPD) Among Children and Adults in the U.S.

BackgroundIn February 2010, PCV13 was introduced for routine use among children aged < 5 years. In June 2012, PCV13 was recommended for use in series with 23-valent polysaccharide vaccine (PPSV23) for adults ≥19 years with select medical conditions, and in August 2014, for all adults ≥65 years. We evaluated the direct and indirect effects of PCV13 6 years post-introduction on invasive pneumococcal disease (IPD).MethodsIPD cases (isolation of pneumococcus from sterile sites) were identified among residents of Active Bacterial Core surveillance (ABCs) sites during July 2007–June 2016. Isolates were serotyped by Quellung, PCR, or whole genome sequencing and classified as PCV13 or non-vaccine type (NVT). Incidence changes were estimated as percent changes (one minus rate ratio) and 95% confidence intervals (95% CI) between pre-PCV13 (2007–2009) and two post-PCV13 periods (July 2014–June 2015 and July 2015–June 2016).ResultsABCs identified 31,190 IPD cases between 2007 and 2015, with 2,750 cases among children <5 years and 10,930 among those ≥65 years. During the two post-PCV13 periods, overall IPD rates were 33%-62% lower relative to 2007–2009 among all age groups, including <5 years and ≥65 years (Figure). Significant reductions in PCV13-type IPD incidence were observed for all age groups during both post-PCV13 periods, with incidence 84% (q95% CI 78, 88%) and 68% (95% CI 63, 73%) lower in 2015–2016 among children < 5 years and adults ≥65 years, respectively. PCV13-type IPD reductions were driven by serotypes 19A and 7F. IPD due to non-vaccine types also declined significantly among children < 5 years (−27%, 95% CI –42, –9%) and adults ≥65 years (-24%, 95% CI –34, –14%). PCV13-type IPD incidence did not differ significantly between the two post-PCV13 periods.ConclusionIPD incidence declined among children and adults in the U.S. following PCV13 introduction among children. The lack of difference in PCV13 rates between 2014–2015 and 2015–2016 suggests no measurable early impact of PCV13 introduction among adults ≥65 years. To date, we found no evidence of significant replacement disease with non-PCV13 types. Further work is needed to explain reductions in non-vaccine type disease observed in the post-PCV13 era.Disclosures W. Schaffner, Pfizer: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Novavax: Consultant, Consulting fee; Dynavax: Consultant, Consulting fee; Sanofi-pasteur: Consultant, Consulting fee; GSK: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee; L. Harrison, GSK: Scientific Advisor, Consulting fee

Antimicrobial resistance determinants and susceptibility profiles of pneumococcal isolates recovered in Trinidad and Tobago.

In Latin America and the Caribbean, pneumococcal infections are estimated to account for 12000-18000 deaths, 327000 pneumonia cases, 4000 meningitis cases and 1229 sepsis cases each year in children under five years old. Pneumococcal antimicrobial resistance has evolved into a worldwide health problem in the last few decades. This study aimed to determine the antimicrobial susceptibility profiles of pneumococcal isolates collected in Trinidad and Tobago and their associated genetic determinants. Whole-genome sequences were obtained from 98 pneumococcal isolates recovered at several regional hospitals, including 83 invasive and 15 non-invasive strains, recovered before (n=25) and after (n=73) introduction of pneumococcal conjugate vaccines (PCVs). A bioinformatics pipeline was used to identify core genomic and accessory elements conferring antimicrobial resistance phenotypes, including β-lactam non-susceptibility. Forty-one isolates (41.8%) were predicted as resistant to at least one antimicrobial class, including 13 (13.3%) resistant to at least three classes. The most common serotypes associated with antimicrobial resistance were 23F (n=10), 19F (n=8), 6B (n=6) and 14 (n=5). The most common serotypes associated with penicillin non-susceptibility were 19F (n=7) and 14 (n=5). Thirty-nine isolates (39.8%) were positive for PI-1 or PI-2 type pili: 30 (76.9%) were PI-1+, 4 (10.3%) were PI-2+ and 5 (12.8%) were positive for both PI-1 and PI-2. Of the 13 multidrug-resistant isolates, 10 belonged to globally distributed clones PMEN3 and PMEN14 and were isolated in the post-PCV period, suggesting clonal expansion.

Bacteremia in Children 3 to 36 Months Old After Introduction of Conjugated Pneumococcal Vaccines.

In June 2010, Kaiser Permanente Northern California replaced all 7-valent pneumococcal conjugate vaccine (PCV7) vaccines with the 13-valent pneumococcal conjugate vaccine (PCV13). Our objectives were to compare the incidence of bacteremia in children 3 to 36 months old by 3 time periods: pre-PCV7, post-PCV7/pre-PCV13, and post-PCV13. We designed a retrospective review of the electronic medical records of all blood cultures collected on children 3 to 36 months old at Kaiser Permanente Northern California from September 1, 1998 to August 31, 2014 in outpatient clinics, in emergency departments, and in the first 24 hours of hospitalization. During the study period, 57 733 blood cultures were collected in the population of children 3 to 36 months old. Implementation of routine immunization with the pneumococcal conjugate vaccine resulted in a 95.3% reduction of Streptococcus pneumoniae bacteremia, decreasing from 74.5 to 10 to 3.5 per 100 000 children per year by the post-PCV13 period. As pneumococcal rates decreased, Escherichia coli, Salmonella spp, and Staphylococcus aureus caused 77% of bacteremia. Seventy-six percent of all bacteremia in the post-PCV13 period occurred with a source. In the United States, routine immunizations have made bacteremia in the previously healthy toddler a rare event. As the incidence of pneumococcal bacteremia has decreased, E coli, Salmonella spp, and S aureus have increased in relative importance. New guidelines are needed to approach the previously healthy febrile toddler in the outpatient setting.

Changing trends in serotypes of S. pneumoniae isolates causing invasive and non-invasive diseases in unvaccinated population in Mexico (2000-2014)

ObjectiveIntroduction of pneumococcal conjugate vaccines (PCV) targeted against a limited number of serotypes substantially decreased invasive (IPD) and non-invasive pneumococcal diseases (NIPD) but it was accompanied by non-vaccine type replacement disease. After 9 years of introduction of PCV in Mexico, we analyze the evidence of the indirect effects on IPD and NIPD serotype distribution among groups not targeted to receive the vaccine. MethodsFrom January 2000 to December 2014, pneumococcal strains isolated from IPD and NIPD cases from patients ≥5 years of age from participant hospitals of the SIREVA II (Sistema Regional de Vacunas) network were serotyped. A regression analysis was performed considering year and proportion of serotypes included in the different vaccine formulations (PCV7, PCV10 and PCV13). The slope was obtained for each regression line and their correspondent p-value. The proportion of each serotype in the pre-PCV7 and post-PCV7 periods was evaluated by χ2 test. ResultsFrom a total of 1147 pneumococcal strains recovered, 570 corresponded to the pre-PCV7 and 577 to the post-PCV7 periods. The proportion of vaccine serotypes included in the three PCV formulations decreased by 2.4, 2.6 and 1.3%, respectively per year during the study period. A significant increase of serotype 19A was observed in the post-vaccine period in all age groups. ConclusionsA percentage of annual decline of serotypes causing IPD and NIPD included in PCV was detected among groups not targeted to receive the vaccine, probably due to herd effect. Considering pneumococcal serotype distribution is a dynamic process, we highlight the importance of surveillance programs.

PCV13 serotype decrease in Italian adolescents and adults in the post-PCV13 era: Herd protection from children or secular trend?

Background and aim of the workIn 2010 PCV13 replaced PCV7 in the pediatric vaccination schedule for Italian children. While a strong herd effect was demonstrated for PCV7, a possible herd effect due to PCV13 is still under debate. Our aim was to evaluate differences in the distribution of pneumococcal serotypes between the pre and post-PCV13 eras in unvaccinated Italian adolescents and adults with laboratory-confirmed pneumococcal infection from 3 Italian Regions with a high rate of PCV13 vaccination of children. Patients and methodsAdolescents and adults admitted with laboratory-confirmed pneumococcal infection in the hospitals of 3 Italian Regions (Friuli-Venezia Giulia, Emilia Romagna, and Tuscany) between April 2006 and June 2016 were included in the study. Diagnosis of pneumococcal infection and serotyping were performed with Real Time PCR directly on normally sterile fluids or on culture isolates. Results523 patients with laboratory-confirmed pneumococcal infection were enrolled (Male/Female ratio was 300/223, 1.3; median age 67.1, IQR 53.4–74.9). None of the patients had been vaccinated with any pneumococcal vaccine; 96.4% were serotyped. Overall, the most frequent serotypes were 3 (67/504, 13.3%), 8 (43/504, 8.5%), and 19A (38/504, 7.5%). Serotype distribution differed among age classes and clinical presentations.Overall, PCV13 serotypes accounted for 47.6% of cases: 62.3% in the pre-PCV13 era and 45.0% in the post-PCV13 era; (p=0.005 OR=2.03; CL 95%: 1.2–3.3). Serotype 7F accounted for 12/77 (15.6%) of all serotypes in the pre-PCV13 period and for 12/427 (2.8%) in the post-PCV13 period and was the only serotype significantly contributing to the difference in percentage between pre and post-PCV13 eras. ConclusionOur study demonstrated a difference in percentage in serotype distribution in adolescents and adults laboratory-confirmed pneumococcal infection between the pre and post-PCV13 eras. This difference is mainly due to the decrease of serotype 7F. Thus, in order to decrease disease burden, adults and in particular the elderly should be offered a specific vaccination program.

Genetic Structures of Streptococcus pneumoniae Invasive Isolates from Korean Children Obtained Between 1995 and 2013

Understanding the population genetics of pneumococci will allow detection of changes in the prevalence of circulating genotypes and evidence for capsular switching after the use of pneumococcal conjugate vaccines (PCVs). We aimed to analyze the genetic structure of invasive pneumococcal isolates obtained from children before and after the optional use of PCV7 and PCV10/13 in Korea. A total of 285 invasive pneumococcal isolates obtained from children aged <18 years in multicenters during 1995–2013 were included. We classified the isolation year to pre-PCV7 (1995–2003; n = 70), post-PCV7 (2004–2010; n = 142), and post-PCV13 (2011–2013; n = 73) periods. Isolates were analyzed using serotyping, multilocus sequence typing, and antimicrobial susceptibility testing. Between pre-PCV7 and post-PCV13 periods, PCV7 serotypes decreased significantly (from 67.1% to 9.6%, P < 0.001) whereas non-vaccine serotypes (NVTs) showed a significant increase (from 2.9% to 53.9%, P < 0.001). Of the 10 clonal complexes (CCs), antibiotic-resistant international clones, CC320 (31.6%), CC81 (14.7%), and CC166 (6.7%) were the main complexes. Serotype 19A was the main serotype of CC320 throughout the periods. Serotype of CC81 mainly comprised of 23F (53.3%) in pre-PCV7 period and replaced by non-vaccine types (NVTs; 6C [10%], 13 [30%], 15A [40%], and 15B/C [20%]) in post-PCV13 period. The main serotype responsible for CC166 also changed from 9V (80%) in pre-PCV7 to NVT 11A (50%) in post-PCV13 periods. Non-susceptibility to penicillin (42.3%) was the highest in CC320, increasing from 0% to 76%. Genetic structure of IPD isolates in Korean children has changed after the PCV7 and PCV10/13 implementations, and the genotypes of PCV7 types during pre-PCV7 period were mostly disappeared and re-occupied by genotypes of PCV13 types/NVTs in post-PCV13 period. Serotype 19A/ST320 were expected to decrease rapidly after the use of PCV13 in national immunization program. All authors: No reported disclosures.

Impact of pneumococcal conjugate vaccine in children on the serotypic epidemiology of adult invasive pneumococcal diseases in Taiwan.

Invasive pneumococcal disease (IPD) causes significant morbidity and mortality, especially in children and older adults. Pneumococcal 7-valent and 13-valent conjugate vaccines (PCV7 and PCV13) were introduced in Taiwan in 2005 and 2011, respectively, for children. This study was conducted to evaluate the impact of PCV administered in children on adult IPD. From the logbooks of microbiology laboratories, we retrospectively retrieved Streptococcus pneumoniae isolates, collected from normally sterile sites in adult patients. One hundred and fifty-seven consecutive, nonduplicated isolates were collected from one hospital during 2001 and 2003 (pre-PCV period) and 150 isolates from three hospitals from July 2011 to June 2015 (post-PCV period). Serotypes were determined by Quellung test. Among the 307 isolates, 31 serotypes/serogroups were identified. PCV7 serotypes, particularly types 14 (31.2%), 23F (19.7%) and 6B (12.7%) dominated in the pre-PCV period (78.3%) but significantly decreased in the post-PCV period (36%) (p<0.01). PCV13 specific serotypes (PCV13-PCV7) significantly increased from 7% of the isolates in the pre-PCV period to 28.7% of the isolates in the post-PCV period (p<0.001), particularly type 19A (from 0.6% to 10%) and 6A (from 0 to 6.7%). Serotype 15B also increased significantly from 0.6% to 6.7% (p<0.01). Nonvaccine serotypes increased significantly in the post-PCV period (11.5% to 22.0%, p<0.05), particularly type 15A (from 0 to 4.4%, p<0.01). Serotype distribution of adult IPD in Taiwan has evolved after the introduction of PCV in children, indicating an indirect impact in adults. Continuous surveillance after the PCV13 vaccination program in children is needed.

Changes in empyema among U.S. children in the pneumococcal conjugate vaccine era

BackgroundParapneumonic empyema, a serious complication of pneumonia, started increasing among U.S. children before the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000, and continued afterwards. This increase was due in part to pneumococcal serotypes not included in PCV7 that were included in the new 13-valent (PCV13) vaccine introduced in 2010. We assessed changes in the incidence of empyema hospitalizations among U.S. children after PCV13 introduction. MethodsWe calculated annualized empyema hospitalization rates among U.S. children <18years using Nationwide Inpatient Sample and Census data (1997–2013) for four periods based on PCV7 and PCV13 introductions. Relative rates (RR) and 95% confidence intervals (CI) were calculated by age group and sex, comparing PCV7 [early-PCV7 (2001–2005) and late-PCV7 (2006–2009)] and PCV13 (2011–2013) periods with the pre-PCV7 period (1997–1999). Secondary analyses examined changes in pneumococcal, streptococcal, staphylococcal and unspecified empyema. ResultsAmong children <18years of age, annualized empyema hospitalization rates peaked at 3.6 per 100,000 in the late-PCV7 period compared with 2.1 per 100,000 in the pre-PCV7 period [RR: 1.70 (95% CI: 1.11–2.60)]. However, annualized rates in the post-PCV13 period declined to 2.0 per 100,000, similar to rates in the pre-PCV7 period. Empyema rates among children <2years were lower in the post-PCV13 period compared to the pre-PCV7 period [RR: 0.77 (95% CI: 0.61–0.96)], but rates in the two periods among children 2–4 and 5–17years were similar. Most empyema were of unspecified etiology. Pneumococcal and unspecified empyema declined after PCV13 introduction. ConclusionsAlthough empyema hospitalization rates among U.S. children peaked after PCV7 introduction, rates decreased substantially following the introduction of PCV13.

Serotype 3 Remains the Leading Cause of Invasive Pneumococcal Disease in Adults in Portugal (2012-2014) Despite Continued Reductions in Other 13-Valent Conjugate Vaccine Serotypes.

Since 2010 the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent vaccine (PCV7) as the leading pneumococcal vaccine used in children through the private sector. Although, neither of the PCVs were used significantly in adults, changes in adult invasive pneumococcal disease (IPD) were expected due to herd protection. We characterized n = 1163 isolates recovered from IPD in adults in 2012–2014 with the goal of documenting possible changes in serotype prevalence and antimicrobial resistance. Among the 54 different serotypes detected, the most frequent, accounting for half of all IPD, were serotypes: 3 (14%), 8 (11%), 19A (7%), 22F (7%), 14 (6%), and 7F (5%). The proportion of IPD caused by PCV7 serotypes remained stable during the study period (14%), but was smaller than in the previous period (19% in 2009–2011, p = 0.003). The proportion of IPD caused by PCV13 serotypes decreased from 51% in 2012 to 38% in 2014 (p < 0.001), mainly due to decreases in serotypes 7F and 19A. However, PCV13 serotype 3 remained relatively stable and the most frequent cause of adult IPD. Non-PCV13 serotypes continued the increase initiated in the late post-PCV7 period, with serotypes 8 and 22F being the most important emerging serotypes. Serotype 15A increased in 2012–2014 (0.7% to 3.5%, p = 0.011) and was strongly associated with antimicrobial resistance. However, the decreases in resistant isolates among serotypes 14 and 19A led to an overall decrease in penicillin non-susceptibility (from 17 to 13%, p = 0.174) and erythromycin resistance (from 19 to 13%, p = 0.034). Introduction of PCV13 in the NIP for children, as well as its availability for adults may further alter the serotypes causing IPD in adults in Portugal and lead to changes in the proportion of resistant isolates.

Comparative impact of pneumococcal conjugate vaccines on pneumococcal meningitis according to underlying conditions

BackgroundSeveral underlying conditions increase the risk of pneumococcal meningitis (PM) in childhood. Patients with these diseases are initially considered as an important target of pneumococcal conjugate vaccines (PCVs). Limited data are available for PM in children with underlying conditions. To understand the benefits of PCV7 followed by PCV13 in this vulnerable population, we analyzed the data for a large cohort of pediatric patients with PM in France from 2001 to 2014. MethodsWe conducted hospital-based active surveillance with 227 pediatric wards working with 168 microbiology departments throughout France. Standardized inclusion criteria for PM were used and data were analyzed by a pre-PCV7, post-PCV7 and post-PCV13 period. ResultsFrom 2001 to 2014, among the 1582 cases of PM, 62.5% were reported in children less than 2years old. Underlying conditions (n=255, 16.1%) accounted for 7.3% of the cases in these young children versus 30.8% for children ⩾2–18years old (p<0.001). After PCV13 implementation, PM cases decreased by 44.0% from 2009 to 2014, mainly in children without underlying conditions. Though the number of children with underlying conditions remained stable, their proportion among overall PM cases increased by 79.1%. Among children with underlying conditions, PCV7 serotypes, 6 additional PCV13 serotypes, additional 11 serotypes in PPV23 and other serotypes accounted for 24.5%, 14.7%, 25.0% and 35.8%, respectively (p<0.001). After PCV13 implementation, 50.0% of PM cases with underlying conditions and 37.9% without underlying conditions were caused by serotypes included in neither PCV13 nor PPV23. ConclusionBesides the reduced numbers of PM, its profile has changed, with an increase in cases in proportion of children with underlying conditions accompanied by a striking change in serotype distribution. This underlines the importance of detecting underlying conditions in children with PM in the PCV13 era.

Pneumonia hospitalisations in Scotland following the introduction of pneumococcal conjugate vaccination in young children.

BackgroundScotland introduced PCV7 and PCV13 immunisation in young children in 2006 and 2010 respectively. One recent study from the United States reported a decrease in hospitalisation rates for all-cause pneumonia most notably in adults older than 75 years of age following PCV7 introduction in the US child population. We aimed to examine the effect of PCV7 and PCV13 on hospitalisation rates for all-cause pneumonia across all age groups in Scotland.MethodsWe linked hospital records and death certification datasets for the entire Scottish population for the period 2000 to 2012. We included all cases where the primary / secondary diagnosis was pneumonia. Differences in hospital admission rates for pneumonia by age group were calculated using the difference in average annual rates for each period.ResultsWe estimated that all-cause pneumonia hospitalisation rates in children <2 years decreased by about 30 % in the post-PCV-13 period compared with the pre-PCV period. However, in adults aged 75–84 years and ≥85 years, all-cause pneumonia hospitalisation rates increased by 63 and 46 % respectively in the post-PCV 13 period compared to the pre-PCV period. This resulted in an additional 7000 hospitalisations across all age groups in Scotland in 2012 about half of which were in adults >75 years. At the same time, the median length of hospital stay decreased by a third in children <2 years and by about 20 % in adults >75 years in the post-PCV13 period compared to the pre-PCV period. Additionally, there was an 11 % reduction in deaths due to all-cause pneumonia, and 30 % reduction in pneumococcal hospitalisations across all age groups in the post-PCV13 period compared with pre-PCV period.DiscussionThe modest and sustained decline in the rates of hospitalisation for all-cause pneumonia in children and the reduction in proportion of pneumonia hospitalisations in children coded as pneumococcal disease in the post-PCV period should alleviate concerns that pneumococcal serotype replacement may have resulted in an increased pneumonia burden in this age group. The indirect impact of child PCV immunisation in those not vaccinated (in terms of reduction in all-cause pneumonia hospitalisations in the elderly) has not been seen in Scotland. Our results are likely to be confounded by changes in clinical coding and healthcare practices over the same period.ConclusionsOur results illustrate that health care planners cannot, with confidence, predict indirect PCV vaccine impacts on hospitalisations. IPD surveillance across all age groups is needed to assess the indirect effects of PCV in the community.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1693-x) contains supplementary material, which is available to authorized users.

Influence of Childhood Pneumococcal Conjugate Vaccines on Invasive Pneumococcal Disease in Adults With Underlying Comorbidities in Calgary, Alberta (2000-2013).

Pneumococcal conjugate vaccine (PCV) was introduced into Alberta, Canada's routine childhood immunization programs in 2002 (7-valent [PCV7]) and 2010 (13-valent [PCV13]). We assessed the effect of these programs on the epidemiology of invasive pneumococcal disease (IPD) to determine if PCV-associated indirect protection was relatively reduced in adults with underlying comorbidities. Demographic and clinical data were collected by a prospective, population-based surveillance system in Calgary, Alberta, Canada, from January 2000 to December 2013. An indirect cohort study design was used to assess for changes in the proportion of IPD cases with underlying comorbidities. There were 1598 overall and 1346 adult IPD cases from 1 January 2000 to 31 December 2013. Overall IPD incidence decreased 33% (age 0-5 months), 86% (6-23 months), 67% (2-4 years), 26% (5-17 years), 22% (18-64 years), 36% (65-84 years), and 42% (≥85 years) from the prevaccine (January 2000-July 2002) to the post-PCV13 (July 2010-December 2013) period. Over the same timeframe, PCV7 serotype disease incidence declined to ≤1 case per 100 000 persons in all age groups. Neither the proportion of adult cases with immunocompetent comorbidities (relative risk ratio [RRR], 0.93; 95% confidence interval [CI], .62-1.40) nor immunocompromising comorbidities (RRR, 0.99; 95% CI, .61-1.61) differed between the pre-PCV period and post-PCV era. Childhood PCV programs have provided considerable benefit, with substantial declines in overall and vaccine-serotype IPD in vaccinated children and in unvaccinated persons. Conjugate vaccine-associated indirect protection for adults with comorbidities was similar to that for healthy adults.

Antibiotic susceptibility rates of invasive pneumococci before and after the introduction of pneumococcal conjugate vaccination in Germany

Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. A total of 22,208 isolates from invasive pneumococcal disease were collected between July 1, 1992 and June 30, 2013. The present study was conducted to analyze changes in antimicrobial susceptibility and pneumococcal vaccine coverage after the introduction of pneumococcal conjugate vaccination in Germany.Most of the isolates originated from adults ≥16 years (82.5%), while 17.5% were obtained from children <16 years. Penicillin resistance was observed in 7.2% of meningitis cases both among children and adults during the entire study period. In the post-PCV13 period, the resistance rate was 11.3% in children and 10.0% in adults, which is higher than in the pre-PCV7 and post-PCV7 periods. In the non-meningitis group, an overall penicillin nonsusceptibility rate (intermediate resistance and resistance) of 0.5% was detected both among children and adults. Nonsusceptibility rates among children were 6.3% (pre-PCV7), 7.6% (post-PCV7) and 9.0% (post-PCV13). The corresponding nonsusceptibility rates among adults were 4.4%, 6.0% and 7.9%, respectively. Concerning cefotaxime, in meningitis cases 0.8% of all isolates were intermediate and 0.5% resistant among children, while among adults, 0.9% were intermediate and 0.2% resistant. In non meningitis cases, cefotaxime nonsusceptibility rates were 0.5% in children and 0.3% in adults. Macrolide nonsusceptibility rates were lower in the post-PCV13 period (children 8.2%; adults 8.8%) than in the post-PCV7 period (children 17.3%; adults 13.0%) and the pre-PCV7 period (children 24.8%; adults 13.3%). In the pre-PCV7 period, macrolide resistance was mainly caused by M-phenotype clones carrying the mefA gene. In the post-PCV7/13 period, ermB (MLSb-phenotype) was the dominant resistance marker. Overall nonsusceptibility rates were 5.5% for clindamycin (intermediate 0.3%, resistant 5.2%), 0.7% for levofloxacin (intermediate 0.4%, resistant 0.3%), 8.5% for tetracycline (intermediate 0.6%, resistant 7.9%) and 11.0% for trimethoprim-sulfamethoxazole (SXT) (intermediate 5.7%, resistant 5.3%).In summary, childhood pneumococcal conjugate vaccination has had a strong effect on the pneumococcal population in Germany, both among vaccinated children as well as among non-vaccinated children and adults. Serotypes included in the pneumococcal conjugate vaccines have strongly diminished, while some non-vaccine serotypes have gained importance, particularly with respect to antibiotic resistance. However, concerning antibiotic non-susceptibility the most outstanding change over the years is the decline in macrolide resistance, especially among children.

Impact of the 13-valent pneumococcal conjugate vaccine (pcv13) on invasive pneumococcal disease and carriage in Alaska

BackgroundAlaska Native (AN) children have experienced high rates of invasive pneumococcal disease (IPD). In March 2010, PCV13 was introduced statewide in Alaska. We evaluated the impact of PCV13 on IPD in children and adults, 45 months after introduction. MethodsPneumococcal sterile site isolates, reported through state-wide surveillance, were serotyped using standard methods. We defined a pre-PCV13 time period 2005–2008 and post-PCV13 time period April 2010–December 2013; excluding Jan 2009–March 2010 because PCV13 was introduced pre-licensure in one high-risk region in 2009. ResultsAmong Alaska children <5 years, PCV13 serotypes comprised 65% of IPD in the pre-PCV13 period and 26% in the PCV13 period. Among all Alaska children <5 years, IPD rates decreased from 60.9 (pre) to 25.4 (post) per 100,000/year (P<0.001); PCV13 serotype IPD decreased from 37.7 to 6.4 (P<0.001). Among AN children <5 years, IPD rates decreased from 149.2 to 60.8 (P<0.001); PCV13 serotype IPD decreased from 87.0 to 17.4 (P<0.001); non-PCV13 serotype IPD did not change significantly. Among persons 5–17 and ≥45 years, the post-vaccine IPD rate was similar to the baseline period, but declined in persons 18–44 years (39%, P<0.001); this decline was similar in AN and non-AN persons (38%, P=0.016, 43%, P=0.014, respectively). ConclusionsForty-five months after PCV13 introduction, overall IPD and PCV13-serotype IPD rates had decreased 58% and 83%, respectively, in Alaska children <5 years of age when compared with 2005–2008. We observed evidence of indirect effect among adults with a 39% reduction in IPD among persons 18–44 years.

Impact of the 13-valent pneumococcal conjugate vaccine on the incidence of pneumococcal meningitis in children.

The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of pneumococcal meningitis (PM) in children is unknown. To determine this impact, a descriptive multicentre retrospective cohort study was conducted from 2008 to 2013 in northern France. All laboratory-confirmed PM in children aged <18 years in all hospitals of the area with paediatric units were included. Two independent databases were used for exhaustive identification of cases: medical plus laboratory records at each hospital and discharge codes. The corrected incidence of PM was determined by a capture-recapture analysis using these two databases. Sixty-two cases were found over the 6-year period. A decrease of the PM corrected incidence was observed in the global population (P = 0·07), significant only for children aged <2 years, from 11·9/100 000 in 2008 in 1·9/100 000 in 2013 [6·4 fold-decrease, 95% confidence interval (CI) 1·4-41, P = 0·01] between years 2008 and 2013. When comparing the pre- and post-PCV13 periods, this decrease was still statistically significant for children aged <2 years [7·32/100 000 (95% CI 4·39-10·25) to 2·78/100 000 (95% CI 0·96-4·60), P = 0·01]. Only three (5%) cases of PM caused by vaccine serotypes could have been prevented. After the introduction of the PCV13 vaccine, a decrease in the incidence of PM cases in children in northern France was observed.