Controlling Pneumococcal Disease around the Globe

South Africa introduced the seven-valent pneumococcal protein-polysaccharide conjugate vaccine (PCV-7) in 2009 using a novel 3-dose infant schedule (6, 14 and 36 weeks). We assessed PCV-7 impact using national disease surveillance data, accounting for HIV prevention effects. We conducted active, national, laboratorybased surveillance for invasive pneumococcal disease (IPD) from 2005 through 2012, including serotyping and susceptibility testing. We calculated the percentage change in IPD incidence, focusing on individuals aged <2 and 25-44 years, between post-vaccine (2011 and 2012) and pre-vaccine years (average of 2005 through 2008). From 2005 through 2012, 35,192 IPD cases were identified. Rates of PCV-7 vaccine-serotype IPD among children <2 years declined by 89% in 2012, from 32.1 cases per 100,000 person-years to 3.4/100,000 (95% confidence interval [CI], -92% to -86%) while nonvaccine-serotype IPD increased non-significantly from 8.9/100,000 to 9.5/100,000 (+6%; 95% CI, -16% to +23%). Among adults age 25 to 44 years, vaccine serotype IPD declined by 57% (95% CI, -63% to-50% [3.7/100,000 to 1.6/100,000]), compared with smaller nonvaccine serotype IPD declines (3.9/100,000 to 3.5/100,000; -11%, 95% CI, -21% to +4%). Among children <2 years, penicillin-nonsusceptible IPD rates decreased (34.1/100,000 to 6.1/100,000 [-82%; 95% CI, -85% to-78%]). The large reduction in disease caused by vaccine serotypes among both children and adults likely reflects substantial direct and indirect benefits from PCV-7 introduction. The smaller reduction in nonvaccine-serotype IPD suggests HIV prevention efforts are also playing a role in prevention of serious pneumococcal disease.

Background: PCV7 was introduced as universal childhood vaccination in Israel on Jul 2009 and was gradually replaced by PCV13 from Nov 2010. Here we report data on adult IPD, two years post PCV13 implementation. Methods: An ongoing nationwide active surveillance (all 27 laboratories performing blood cultures in Israel), providing all blood/CSF pneumococci from persons >18y initiated on Jul2009. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. Medical history and outcomes were recorded in ~90%. Results: Overall VT7/VT13 serotypes decreased by 69%/55% within 4 years. This was accompanied by a 47% increase in nonVT13 strains. These changes were most apparent in winter season (Fig.1) and were seen in all age groups (Fig2), including in individuals with comorbidities. Non-VT serotypes that significantly increased were 12F, 15A and 10A. A continuous reduction in isolates with penicillin MIC>0.06 was observed (26% to 11%, p<0.001).  Conclusion: Four years after PCV universal implementation in children, incidence of adult IPD caused by VT7 and VT13 decreased in all age groups. Despite increase in non-VT IPD, overall pneumococcal IPD decreased. However, additional follow-up is still needed to determine the long-term impact on adult IPD. Background: In 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10). The schedule included primary doses at 2, 4 and 6 months plus a booster at 12 months. A single dose was offered for catch-up of unvaccinated children 12-23 months old. We conducted a case-control study to evaluate PCV10 effectiveness. Methods: Invasive pneumococcal disease (i.e., isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid or other normally sterile site) was identified in children age-eligible for ≥1 PCV10 dose through laboratory-and hospital-based surveillance in 10 Brazilian states. We aimed to identify 4 age-and neighborhood-matched controls for each case. We calculated effectiveness ([1-adjusted matched odds ratio] x 100%) for vaccine-type and vaccinerelated serotypes (i.e., in the same serogroup as a vaccine serotype). Results: Among 316 cases with available serotype and 1219 matched controls, the effectiveness of an ageappropriate PCV10 schedule was 83.8% (95% confidence interval [CI] 65.9-92.3) against vaccine serotypes and 77.9% (95% CI 4.0-91.7) against vaccine-related serotypes. Serotype-specific effectiveness was demonstrated for the two most common vaccine serotypes, 14 (VE: 87.7%, 95% CI 60.8-96.0) and 6B (82.8%, 95% CI 23.8-96.1), as well as serotype 19A (82.2%,), a serotype related to vaccine serotype 19F. A single catch-up dose among children aged 12-23 months was effective against vaccine-type disease (68.0%, . No significant effectiveness was found against non-vaccine serotypes. Conclusion: In the context of the routine immunization program in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes and may provide cross-protection against some vaccine-related serotypes. Results: Among all Alaska children <5 years, PCV13 serotypes comprised 65% of IPD in the pre-vaccine period; 94.8% of AN children 19-35 months of age had received 3 or more doses of PCV during the post-vaccine period. Among Alaska children <5 years, IPD rates decreased from 57.5 (pre) to 20.8 (post) per 100,000/yr (p < 0.001); PCV13 serotype IPD decreased 81% from 35.6 to 6.5 (p < 0.001). Among AN children <5 years, IPD rates decreased from 156.6 to 57.3 (p < 0.001); PCV13 serotype IPD decreased 76% from 91.4 to 21.5 (p < 0.001); non-PCV13 serotype IPD did not decline significantly (54.1to 31.0, p = 0.09). Conclusion: 33 months after introduction of PCV13, PCV13-serotype IPD rates decreased in Alaska Native and non-Native children <5 years of age. There is no evidence of non-PCV13 serotype replacement IPD at this time. Further surveillance is needed. A priori estimates of pneumococcal conjugate vaccine (PCV) impact are complicated by serotype replacement. The impact of PCVs on invasive pneumococcal disease varies between settings; the sources of that variability are not entirely clear. Prediction models usually rely on disease incidence data, which in most of the developing world is unavailable and few have tested their predictive ability against surveillance data. Assuming PCV use results in a) vaccine serotype (VT) elimination in colonization, b) full serotype replacement in colonization and c) unchanged invasiveness of non vaccine serotypes (NVT) after vaccination, the incidence risk ratio (IRR) of IPD is: IRR=(Cvt/Cnvt + 1) / (Dvt/Dnvt + 1), where C and D are the proportion of VT and NVT carriage and disease respectively. The predictive ability of this method was tested by comparing predictions employing the serotype distributions in IPD1 and carriage 2-15 to respective IPD impact surveillance estimates after 3 years of PCV use in children under 5 years of age 1 using weighted linear regression. The predictive value for the observed impact of PCV7 on IPD in children was good (adjusted R 2 = 0.97) and the predictions accounted for the observed heterogeneity (see Figure). The relative disease impact of PCVs can be estimated a priori from the serotype distribution of a representative sample of carriers and IPD cases. The observed heterogeneity in disease impact likely arises mostly from differences in serotype distribution of disease and colonization before vaccination.

No conflict of interest
Background and Aims: Children with sickle cell disease (SCD) have a significantly increased risk of invasive pneumococcal disease and mortality. Previously we reported immunogenicity data from a 2-dose regimen of PCV13 given 6-months apart to 6-17 year-old children with SCD who had previously received PPSV23. Herein, we present data collected 1 year after dose 2. Methods: Anti-pneumococcal polysaccharide immunoglobulin (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) titers (GMTs) were determined for each blood draw. Newly diagnosed chronic medical conditions and serious adverse events (SAEs) were recorded. Results: 158 subjects 13.3 (±3.08) year-old were enrolled and vaccinated; 146 received dose 2; 87 continued for 1 year. Antibody levels after doses 1 and 2 were generally comparable. Antibody levels declined over the year after dose 2; however, OPA GMTs for all serotypes (Table 1) and IgG GMCs (except serotype 3) remained above prevaccination levels. Background and Aims: A conjugate vaccine targeting 10 pneumococcal serotypes was licensed for young children in 2010 in Brazil. The aim of this study was to determine among adults aged 50 years or older whether incidence of invasive pneumococcal disease (IPD) have changed over the 3 years since pneumococcal conjugate vaccine licensure. Methods: Prospective laboratory surveillance for IPD was performed from 2008 to 2013 in Salvador, Brazil. Incidence was compared for the 2 and 3 year period preceding and following pneumococcal vaccination. Capsular serotype was determined by multiplex PCR and/or Quellung reaction. Results: Incidence of invasive pneumococcal disease among adults aged 50 years or older declined 20% from 0.36 cases/100.000 in 2008-2012 to 0.29 in 2010-2013. Among those aged 60 years or older, the incidence decreased 23% from 0.26 to 0.20 per 100,000/inhabitants in pre-and post-PCV10 period. The most frequent pneumococcal vaccine related serotypes in the post-PCV10 were: 6A/B (17%), 14 (5.9%) and 19F (5.9%). The non-PCV10 serotypes causing IPD in the period following vaccine implementation were: 7C (17%), 3 (13%), 19A (8.7%) and 12F (8.7%). Conclusion: Our findings indicate that use of conjugate vaccine in children may be reducing the rate of disease in older adults. Policy makers would consider the benefits seen in older adults to recommend pneumococcal conjugate vaccine in this age group. Acknowledgments: Conselho Nacional de Desenvolvimento Científico e Tecnológico (#482755/2010-5), Programa Estratégico de Apoio à Pesquisa em Saúde (PAPES#407551/2012-3) and Fundação Oswaldo Cruz.

7-VALENT PNEUMOCOCCAL CONJUGATE VACCINE: IMPACT ON EPIDEMIOLOGY OF PNEUMOCOCCAL MENINGITIS IN AUSTRALIA
S. Bag 1 , S. Jayasinghe 1 , H. Wang 1 , H. Gidding 2 , F. Beard 1 , P. McIntyre 3 1 Immunisation research, National Centre for Immunisation Research and Surveillance, Westmead, Australia; 2 Immunisation research, National Centre for Immunisation Research and Surveillance and University of New South Wales, Sydney, Australia; 3 Immunisation research, National Centre for Immunisation Research and Surveillance and University of Sydney, Sydney, Australia Background: Following the introduction of a 7-valent pneumococcal conjugate vaccine (7vPCV) program in Australia for all infants in 2005, the incidence of invasive pneumococcal disease (IPD) decreased significantly. 7vPCV was replaced with 13-valent pneumococcal conjugate vaccine (13vPCV) in July 2011. The most severe form of IPD is pneumococcal meningitis, which has a high case-fatality rate. Significant decreases in pneumococcal meningitis caused by 7vPCV serotypes have been reported in the United States and the United Kingdom, both in children and older age groups, following introduction of universal infant 7vPCV programs. Aims: To assess the impact of 7vPCV on pneumococcal meningitis epidemiology in Australia. Methods: We examined trends in pneumococcal meningitis from 2004 to 2010 using Australian notification data. Analysis was stratified by age and serotype. Results: In the <5 year age group, there was a 96% decrease in the number of meningitis cases caused by 7vPCV serotypes between the periods before (2004; 36 cases) and after7vPCV introduction (2007-2010; annual average 1.3 cases) (p<0.0001). A non-significant 71% decrease (7 to 2 cases; p=0.06) was observed in the ≥65 year old group over this period. There was a moderate increase in meningitis caused by non-7vPCV serotypes in both age groups (<5year olds: 5 to 16, p=0.0001; ≥65 year olds: 1.3 to 7.8, p=0.0001), predominantly due the extra serotypes found in 13vPCV. Conclusion: Our study documents a significant decrease in pneumococcal meningitis in young children in Australia following introduction of the 7vPCV program. Ongoing surveillance is important to assess the impact of 13vPCV introduction.

SURVEILLANCE OF INVASIVE PNEUMOCOCCAL DISEASES IN VENETO REGION, ITALY
T. Baldovin 1 , F. Russo 2 , R. Lazzari 1 , C. Bertoncello 1 , P. Furlan 1 , S. Cocchio 1 , V. Baldo 1 1 University of Padova Dept. of Molecular Medicine, Section of Public Health Laboratory of Hygiene and Public Health, Padova, Italy; 2 Veneto Region Direction of Prevention, Promotion and Development of Hygiene and Public Health Service, Venice, Italy Background and Aims: Streptococcus pneumoniae is characterized by >90 serotypes and it is a major cause of morbidity and mortality worldwide, especially in children <5 years old and the elderly. It occurs mostly as meningitis, pneumonia and bacteremia. This study aims to describe the epidemiology of invasive pneumococcal disease (IPD) in the Veneto Region (Northeast Italy). Methods: Data were collected through a system of active surveillance of invasive bacterial diseases based on microbiology laboratories of the hospitals and local health authorities. Results: In January 2007-June 2013 period, the Surveillance System of the Veneto Region received 963 IPD notifications. The notification rate was 3.0/100,000. The age distribution show a higher incidence in subjects <5 y old (7.4/100,000) and in ≥65 y old age group (7.2/100,000). A decreased IPD incidence in children <5 y old is pointed out from the last quarter of 2009, declining from 5.4 to 1.7/100,000 in the first quarter of 2013 (p<0.001); for the ≥65 y old age group, the notification rate trend shows a slow increase in the analyzed period (p=n.s.). A total number of 499 isolates were typified: 69.3% belongs to PCV13 serotypes, 17.6% to the additional PPSV23 serotypes; 13.0% of remaining isolates belongs to strains not included in the available vaccines. In the analyzed period, 68 deaths occurred, with a lethality rate of 7.1%; the 67.6% of deaths occurred in subjects ≥65 y old Conclusion: Current strategies have significantly reduced the IPD burden in subjects <5 y old Instead in the elderly, it is necessary a change of the vaccination strategy. Background: We wanted to explore PCV13's effect in reducing IPD-attributable morbidity and mortality, and whether serotype-specific changes were attributable to PCV13's introduction. Methods: Population-based cohort study based on the linkage of national laboratory surveillance data on IPD and several national registries. We measured changes in IPD-incidence and mortality during baseline (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007), PCV7 (2008( -2010( ) and PCV13 (2011( -2012 periods. Results: We observed a 17% (95% CI, 13%-22%) reduction in the total incidence of IPD in the PCV-13 period. We estimated a 85 (95% CI, 64%-95%) reduction in the incidence of the six additional PCV13-serotypes and 74% (95% CI, 63%-82%) for IPD caused by all serotypes in children <2 years. We observed a 28% (95% CI, 18%-27%) reduction in IPD-attributable 30-day mortality, from 3.4 deaths (95% CI, 3.2-3.6) to 3.1 (95% CI, 2.8-3.4) and 2.4 (95% CI, 2.2-2.7) per 100.000 population in the PCV7 and PCV13-periods. The decline in mortality was observed across all age groups, but mainly in the non-vaccinated population. For serotypes 1 and 3, there were no significant changes in incidence beyond what would be expected from the natural cyclical patterns. There was a significant increase in 19A-incidence following PCV7, but by 2012, the incidence declined towards baseline levels.

Conclusion:
We observed a further decline on the incidence of IPD shortly after the shift from PCV-7 to PCV-13 in the national immunization programme. There was a substantial population-level decline in pneumococcalattributable mortality of nearly 30% among non-vaccinated persons.

SEROTYPE-SPECIFIC PCV7/PCV13 EFFECT ON INVASIVE PNEUMOCOCCAL DISEASE (IPD) IN CHILDREN <5 YEARS IN ISRAEL, JULY 2004 -JUNE 2013
S. Ben-Shimol 1 , D. Greenberg 1 , N. Givon-Lavi 1 , R. Dagan 1 1 Pediatric Infectious Disease Unit, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel Background and Aims: Seven-valent pneumococcal conjugate vaccine (PCV7) Introduction to the Israeli national immunization plan (NIP) in Jul-2009 resulted in a fast reduction of PCV7 serotype-specific IPD rate. Since Nov-2010, PCV13 gradually replaced PCV7 without catch-up. We assessed PCV7/PCV13 impact on serotype-specific IPD in children <5 years in Israel. Methods: Methods were previously described (Ben-Shimol et-al, 50th IDSA, Abstr. 442, 2013). Results: Overall-IPD incidence (per 100,000 children<5 years) declined by 63%, from a mean of 50.6±2.3 in the pre-PCV period (Jul-2004through Jun-2008) to 18.8 in 2012-2013 Comparing the last study year (Jul-2012through Jun-2013 to the pre-PCV period: PCV7+6A serotypes disease incidences declined by ≥91%; the 5 additional PCV13 serotypes (PCV5) decreased significantly by 70%; single serotypes 1, 5 and 19A decreased significantly, while serotypes 7F and 3 IPD were not significantly reduced. Non-PCV13 serotypes IPD rates increased overall by 140% (p < 0.001). Conclusion: Substantial and significant reduction of overall IPD and IPD caused by 10 of PCV13 serotypes was observed shortly after PCV13 introduction to NIP. Disease caused by serotypes 3, 4 and 7F was rare and was not significantly reduced. Non-PCV13 IPD increased, but this had only moderate effect on overall-IPD.  Objective: To evaluate the level and the persistence of maternal antibodies in infants after maternal immunization with pneumococcal polysaccharide vaccine. Methods: A total of 100 pregnant women without relevant obstetric clinical conditions was included in the study between May 2005 and January 2006. The pregnant women were assigned to two groups, based on a randomized list during routine low-risk pre-natal visits. The first Group (VAC) received the 23V non-conjugate pneumococcal polysaccharide vaccine (Pn23V) shortly after enrolment (pregnant women at 28 weeks or later) and the second Group (NO_VAC) received no vaccine to investigate the antibody persistence, we collected blood samples from the mothers after 1 month of delivery and from the infants at 1 month and 6 months of age. Antibody titers were measured for serotypes 1, 6B and 14. Results: Mother's immunization induced antibody responses to all serotypes tested. GMC's of specific IgG were significantly higher in the vaccinated group compared to unvaccinated controls for all 3 serotypes tested. A significantly higher proportion of vaccinated mothers achieved protective concentrations of IgG to serotype 1 compared to unvaccinated controls. However, proportions above both 0.35 and 1.0 µg/ml were relatively high for serotypes 6B and 14 in unvaccinated mothers. For the infants at one month of age, GMC's and proportions above 0.35 and 1.0 µg/ml were significantly higher in the infants born from mothers who received vaccine compared to infants born from unvaccinated mothers. At one month of age infant IgG to serotypes 1, 6B and 14 were 19.6%, 20.8% and 20.8% of the maternal levels. By 6 months of age antibody levels had dropped by >90% to all 3 serotypes. Despite this rapid decline in antibody, at 6 months of age proportions > 0.35 µg/ml remained higher in the infants of vaccinated mothers than controls for all three serotypes although proportions >1.0 µg/ml were not significant for any serotype.

IMMUNOGENICITY AND SAFETY OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HIV INFECTED CHILDREN AND ADULTS NOT PREVIOUSLY IMMUNIZED WITH PNEUMOCOCCAL VACCINE
A. Bhorat 1 , S. Madhi 2 , F. Laudat 3 , V. Sundaraiyer 4 , A. Gurtman 3 , K. Jansen 3 , D. Scott 3 , E. Emini 3 , W. Gruber 3 , B. Schmoele-Thoma 3 1 Family Physician, Soweto Clinical Trials Centre, Johannesburg, South Africa; 2 Department of Science/National Research Foundation, University of Witwatersrand, Johannesburg, South Africa; 3 Vaccine Research, Pfizer Vaccine Research, Collegeville, USA; 4 Statistics, InVentiv Health Clinical LLC, Princeton, USA Background and Aims: HIV-infected individuals, including those on highly active antiretroviral therapy (HAART), are at increased risk of pneumococcal disease. This open-label, single-arm study assessed safety, tolerability, and immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent polysaccharide vaccine (PPSV23) in pneumococcal vaccine-naive, HIV-infected subjects. Methods: Subjects aged ≥6 years received 3 PCV13 doses followed by 1 PPSV23 dose at 1 month intervals. Blood samples were obtained before and 1 month after each vaccination; serotype-specific anti-capsular IgG and antipneumococcal opsonophagocytic activity (OPA) were measured. Local and systemic reactions were collected for 14 days after PCV13; adverse events, graded for severity, relation to PCV13, and seriousness, were collected for 6 months after PPSV23. Results: 150 subjects aged 6-17 years and 151 subjects ≥18 years were enrolled and vaccinated; 97% were on HAART; 71% had viral loads <50 copies/mL. Mean CD4 count was 717±381 cells/µL. After one PCV13 dose, IgG geometric mean fold-rises (GMFRs) and OPA GMFRs were 1. 15-15.79 and 4.8-89.4, respectively, in 6-17-year-olds and 1.62-8.29 and 4.1-52.2, respectively, in ≥18-year-olds. OPA GMFRs were similar or higher following doses 2 and 3; IgG GMFRs were mostly higher in the younger age group. Injection site pain (mostly mild to moderate) was the most frequent local reaction. There were no PCV13-related serious adverse events. Conclusion: PCV13 appeared safe and immunogenic in pneumococcal vaccine-naive, HIV-infected subjects aged ≥6 years with CD4 cell counts ≥200 cells/µL. Vaccine serotype-specific increases in OPA were observed after one PCV13 dose; and similar or higher after subsequent PCV13 doses. Background and Aims: In 2010, Brazil introduced the PCV10 into the National Immunization Program in a 3+1 dose schedule (2,4,6 and 12-18m of age), and in a catch-up campaign for children aged 12-<24m. In 2011/2012, the PCV10 coverage for <1y old was ~80%. After two years of PCV10-introduction, we investigated the vaccination effect on the PCV10-serotypes in vaccinated and unvaccinated population. Methods: We used data from the national Streptococcus pneumoniae laboratory based surveillance. The mean number of PCV10-types and non-vaccine types were compared between the pre-(Jan/2008-Dec/2009) and post-(Jan/2011-Dec/ 2012) vaccination periods and used to assess the PCV10-effectiveness (1-Odd ratio). Results: During 2008-2012, 2,399 invasive S. pneumoniae were studied. Annual number of PCV10-types in preand post-vaccination by age group is shown in table 1. PCV10-types were significantly less prevalent in the postvaccination period compared to the pre-vaccination for all age groups. Conclusion: Two-years after PCV10 introduction, vaccine-serotypes reduced significantly in vaccinated population and a significant herd effect was observed in all age-group but ≥65y old. Acknowledgment: SIREVAII-PAHO for supplying the pneumococcal antisera; CNPQ for grant support to MCCBrandileone(#302175/2010-5) and ALA(#306096/2010-2). Pneumococcal conjugated vaccines (PCVs) have recently been introduced in the childhood vaccination program in several countries, including Sweden showing a protective effect against invasive disease (IPD) caused by vaccine types, and an increase of non-vaccine type disease in both vaccinated children and non-vaccinated adults. It is not known to what extent non-vaccine serotypes provide the same ability to cause IPD and whether the disease manifestations are the same as for vaccine types. Here we used a large collection (n=2288) of patient data and corresponding pneumococcal isolates from IPD in adults (n=2096) and children (n=192) to explore correlations of clinical manifestations to vaccine and non-vaccine types. Additional 165 invasive and 550 pneumococcal carriage isolates from children were used to calculate the invasive disease potential for different serotypes. The odds ratio for causing IPD in children was lower for non-PCV13 strains as compared to vaccine type strains. Children infected with non-PCV13 strains had more underlying diseases and tended to have meningitis more often (47%) and to have a higher OR for intensive care attendance (33%) than children infected with PCV13 serotypes (33% and 23% respectively). Adult IPD patients infected with non-PCV13 strains showed bacteremia more often, more underlying diseases but less pneumonia, while the OR for meningitis, death and age did not differ between infections with non-PCV13 or PCV13 strains. Childhood vaccination with PCV will likely not change the clinical manifestation of IPD in non-vaccinated adults even though there will be a replacement with non-vaccine type strains due to herd immunity.

Methods:
We performed a 5-year (2008-2012) hospital-based surveillance at a reference hospital for infectious diseases in Salvador. All pneumococcal isolates were serotyped by multiplex PCR and/or Quellung method. Results: A total of 104 cases of pneumococcal meningitis were identified. The incidence of pneumococcal meningitis decreased from 0.71 (pre-PCV10) to 0.46 (post-PCV10) cases per 100,000 persons for all age groups (p < 0.03). A significantly decline was observed in children with < 2 years of age (p < 0.058). The overall case-fatality rate decreased from 24% (pre-PCV10) to 17.6% (post-PCV10). Overall, the incidence of disease by PCV10 serotypes decreased from 0.31 (pre-PCV10) to 0.15 cases (post-PCV10) per 100,000 persons (p <0.03). The most prevalent serotypes were 14 (14%), 23F (10,55), 6B (8.8%) and 3 (7%) (pre-PCV10) and, 18C (11.8%), 23F (8.8%) and 12F (8.8%) (post-PCV10). Conclusion: There was a decline in the incidence of pneumococcal meningitis after PCV10 introduction. The distribution of serotypes showed a normal fluctuation without predominance of any serotype. Continued surveillance studies will be essential to evaluate the benefits of the vaccination and serotype dynamics in Brazil. Background and Aims: Several hospital and community based studies on invasive pneumococcal disease (IPD) had been conducted for the past 20 years. In all the studies Streptococcus pneumoniae was one of the most prevalent etiologic agents. Only serogrouping was performed among isolates. This study aims to describe the serotype distribution, age distribution and antibiotic resistance patterns of S. pneumoniae isolates from hospitalized patients. Methods and Results: This study was conducted from June 2010 to September 2012. A total of 301 S. pneumoniae isolates were confirmed from 311 sample isolates collected from 42 tertiary hospital laboratories nationwide. These were collected from blood, CSF, pleural fluid and peritoneal fluid. The age range of patients were from 2 days to 87 years old. Pediatric patients comprised 41.5% whereas adult patients 56.4%. Serotype distribution of S. pneumoniae and vaccine coverage for PCV13 for all age groups 68.4%; Pediatrics 71.2% and adult age group 65.5%. Antibiotic resistance patterns of S. pneumoniae from hospitalized patients was significantly low except resistance to co-trimoxazole. Conclusion: Information on the serotypes distribution included in this study has implications for future pneumococcal immunization program in the country.
No conflict of interest pneumonia 2014 Volume 3 160 ISPPD-9 / pneumonia 2014 Mar 9-13;3:1-286 Background and Aims: The Tijuana, Mexico and San Diego, California, is the world's most transited frontier. We have previously published and presented pneumococcal serotype replacement following 7-valent pneumococcal conjugated vaccine, especially by serotypes 19-A, 3 and 6A/C. Since May/2012 universal vaccination with the 13-valent pneumococcal conjugated vaccine (PCV-13) was introduced for all children. This study analyzes the effectiveness of PCV-13 following 16 months after PCV-13 implementation in the region. Methods: Since October/2005 until September/2013 (8 years) we underwent an active surveillance for all Invasive Pneumococcal Diseases (IPD) in children < 16 years admitted at the Tijuana General Hospital. Only cultureconfirmed cases were included. Following identification, serotyping was performed using the Quellung Reaction (Statens Serum Institute® Copenhagen, Denmark). Descriptive analysis was performed using Excel®. Results: 48 cases of confirmed IPD were found. Clinical diagnosis were pleural empyemas (48%), sepsis with/ without other conditions (27%), meningitis (25%), otomastoiditis (18.75%) and bacteremic pneumonia (4.15%). From eight confirmed IPD cases during 2011-12, there were only two cases during 2012-13 (75% reduction in overall IPD's following PCV-13 introduction). From an average of 1.75 yearly cases due to pneumococcal serotype 19-A, and pneumococcal meningitis in the last three years, there were no cases of neither serotype 19-A S. pneumoniae associated IPD's and pneumococcal meningitis during 2012-13. Conclusion: This is the first Mexican study based on active surveillance, and second in Latin America, that shows early findings of effectiveness of PCV-13 on reduction of overall IPD, and disappearance of pneumococcal serotype 19-A and pneumococcal meningitis in children.

STREPTOCOCCUS PNEUMONIAE
S. Chhibber 1 , A. Saini 2 , K. Harjai 3 1 Microbiology, Panjab University Chandigarh, Chandigarh, India; 2 Microbiology, National Institute of Immunology, New Delhi, India; 3 Microbiology, Panjab University, Chandigarh, India Aims and Background: In the present study, effect of extended feeding of flaxseed and sea-cod oil and their effect on lung infection by Streptococcus pneumoniae was evaluated. Methods: Animals were given flaxseed and sea-cod oil for a period of 90 days enterally and challenged intratracheally with S. pneumoniae D39 serotype2. Survival of animals and various inflammatory parameters i.e. myeloperoxidase, malondialdehyde, nitric oxide, leukotriene B4, cytokines (IL-1β, TNF-α, IL-10), ICAM-1 levels and fatty acid analysis in the lung homogenates were determined. Results: Increased survival of mice accompanied with reduction in bacterial load and inflammatory parameters was observed. Maximum decrease in lung bacterial load was observed in sea-cod fed animals. Pathological evaluation of lung tissue showed that supplementation of diet with ω-3 PUFA oils resulted in lowering the severity of infection from severe pneumonia to moderate pneumonia.

ISPPD-0175
No conflict of interest pneumonia 2014 Volume 3 163 ISPPD-9 / pneumonia 2014 Mar 9-13;3:1-286 Background: In Quebec, Canada, a PCV program was implemented in December 2004 and the recommended schedule is 2+1 doses for low-risk infants. PCV-7 was first used (including catch-up for children up to age 5 years), replaced by PCV-10 in June 2009, and by PCV-13 in January 2011 (no catch-up in both instances). From the beginning, vaccine uptake has been high: > 90% of children are receiving the recommended number of doses. Objective: To estimate the effectiveness of PCVs. Methods: IPD cases in children 2-59 months and reported during the years 2005-2012 were eligible and controls randomly identified in the provincial health insurance registry. Parents were interviewed by telephone and immunization records reviewed. Vaccine effectiveness (VE) was computed using logistic regression models. Results: Out of 830 IPD cases reported, full participation was obtained for 480 cases (58%) and for 1,647 controls. Increased IPD risk was associated with year, colder seasons, younger age, lower maternal education and family income, day-care attendance, comorbidity and influenza immunization whereas PCV vaccination was protective. VE estimates (≥ 1 dose) are shown in the Table (*p<0.05).

EFFECTIVENESS OF THREE PNEUMOCOCCAL CONJUGATE VACCINES (PCVs) TO PREVENT INVASIVE PNEUMOCOCCAL DISEASE (IPD) IN QUEBEC, CANADA
All serotypes 53%* 75%* 79% Conclusion: Results suggest that PCV10 and PCV13 are more effective than PCV7 thanks to the higher number of serotypes, and a high level of cross-protection against 19A for PCV10.

Conclusion:
In France, presence of comorbidities is associated with increased IHMR and LOS for most study conditions. These data are useful for establishing vaccination policy.  Background and Aims: In Jan/2012, PCV13 was introduced into routine immunization program, in 2+1 schedule for children <2 years, in Argentina. The coverage rates were 75.7% and 43.0% for the 1st and 2nd dose in infants <1 year. Objectives: to estimate the burden and clinical-epidemiological pattern of community-acquired pneumonia (CAP) through hospital-based surveillance at pediatric sentinel units before and after PCV13 vaccine introduction in Argentina. Methods: We compare population characteristics, annual hospitalized incidence (per 10.000 discharges) for CAP and pneumococcal-CAP (P-CAP) between pre-vaccine years: 2007-2008 (1st period)) and vaccine introduction 2012 (2nd period). Three years prospective active surveillance of CAP conducted at 10 pediatric hospital sentinel units. First year report (January-December/12). Results: Significant reduction was observed for CAP incidence in the 10 hospitals, between both periods from 623 (5441/87331) CI95% 607-640 to 495 (4051/82027) CI95% 479-509 with an effectiveness of 20.73% CI95% 17.44-23.89. In 6 hospitals, the P-CAP rates decreased 23.4%, from 10.2 (65/63441) (95%CI 8-13 to 7.8) (47/59890) (95%CI 6-10) without statistical significance. Out of 277 culture confirmed CAP cases of the 1st period, 196 (70.8%) were P-CAP, while in the 2nd period 59.3% (99/167) corresponded to P-CAP (p = 0.017). The percentage of children <2 years with P-CAP was reduced 45.4% (95%CI 14.2-65.2) from 44.4% (87/196) to 24.2% (24/99) for 2nd period (p = 0.001). No significant associations were found in other population characteristics between both periods. Conclusion: In the 1st year after PCV13 introduction, there was a significant reduction in CAP incidences and in the percentage of children <2 years with pneumococcal-CAP. Epidemiology, R. Gutierrez Children Hospital, Bs As, Argentina; 2 Pediatrics, F. Falcon Pediatric Hospital, Bs As, Argentina; 3 Pediatrics, J. Sanguinetti Hospital, Bs As, Argentina; 4 Diagnostic Imaging, R. Gutierrez Children Hospital, Bs As, Argentina Background and Aims: In Jan/2012, PCV13 was introduced into routine immunization program, in 2+1 schedule for children <2 years, in Argentina. Pilar vaccination coverage was 85% and 94% for the 1st and 2nd in <1 year; and 61% for 3rd dose. Objective: to evaluate the effectiveness of PCV13 in Pilar Department. Methods: Prospective population-based study after PCV13 introduction. Inclusion criteria: all children <5 y with clinical signs of pneumonia living in Pilar, assisted in references hospitals, between Jan/12-Dec 2013 Comparison of population characteristics, and annual consolidated pneumonia (CP) incidence (per 10.0000 discharges) between pre-vaccine years (2003)(2004)(2005)   Results: Of 38 patients in 20 (53%) was determined Spn serotype. 5 of them, of patients with meningitis were detected serotypes 5, 3, 7F, 23F and 18C. The 15 patients: bacteremic pneumonia (13), 3 with pleural effusion, peritonitis (1) and occult bacteremia (1) serotypes detected: 5 (1), 4 (5), 2 (23F), 2 (14), 1 (3) and one (11A). 5 and 1 serotypes accounted for 50%. The Pen and Cro MICs could not be performed in 3 strains, 34 strains were sensitive to Cro and Pen, 1 strain of meningitis had Pen MICs of 2 mg/ml (R). Of the 38 patients in 8 without evidence of vaccine, no vaccine 24 and 6 with insufficient doses, including here 3 patients affected by serotype 23F. We found patients affected with Spn vaccine serotypes, as 1, 5, 7F, 14 with high invasiveness. 1 and 5 are almost never nasopharyngeal colonizers therefore usually are susceptible to antibiotics. After two doses of primary vaccination between 20% and 40% of children do not achieve protective titers against serotype 23 F, which would explain the infection in vaccinated patients Background & Aims: Indirect effects of widespread pediatric use of pneumococcal conjugate vaccines (PCVs) influence the frequency of serotype-specific pneumococcal disease among adults. Methods: To characterize the effect of PCVs on adult pneumococcal serotype distribution, we systematically reviewed the literature. From all eligible papers, differences in serotype distribution for invasive pneumococcal disease (IPD) isolates matching the 23-valent pneumococcal polysaccharide vaccine (PPSV23) or PCV13 were assessed. Similarly, differences in IPD rates corresponding to PPSV23 and PCV13 serotypes were evaluated. Reports were stratified by pre-and post-introduction of childhood PCV programs. Results: For IPD serotype distribution among adults in 21 reports before widespread pediatric use of PCV, the median differential between the 23 and 13 vaccine serotypes was 16% (interquartile range, IQR, 12-22). For 8 studies after widespread pediatric PCV7 use, the median differential was 25% (IQR 19-29) (p<0.0002, compared to 16%). For serotype-specific IPD incidence rates among adults in 10 reports before widespread pediatric PCV7 use, the median 23-vs-13 differential was 0.5 cases per 100,000 population (IQR 0.3-4.9). For 5 studies after widespread pediatric PCV use, the median differential was 4.6 cases per 100,000 (IQR 2.8-5.7) (p<0.01, compared to 0.5).

DISTRIBUTION OF SEROTYPES AND ANTIMICROBIAL SUSCEPTIBILITY OF STREPTOCOCCUS PNEUMONIAE IN PEDIATRIC PATIENTS WITH INVASIVE INFECTIONS
Corresponding values for settings with widespread pediatric PCV13 programs will be presented on site. Conclusion: The differential between the serotypes included in PPSV23 and PCV13 has widened, both as proportions of IPD isolates and clinical incidence rates. These differentials are relevant to vaccination strategies and vaccine formulation decision-making. These differences may widen further, with more extensive pediatric uptake of PCV10 or PCV13. Background and Aims: PNEUMOVAX® II (also called PNEUMOVAX® 23), a 23-valent polysaccharide pneumococcal vaccine (PPV23), covers 65% to 91% of the isolates responsible for invasive pneumococcal disease. Harboe and colleagues (PLoS Med 2009) showed 3.3-to 5.7-fold increased case-fatality rates associated with pneumococcal disease caused by serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A in comparison to serotype 1 as control. This study evaluated the immune response of PNEUMOVAX® II for four of these nine serotypes (10A, 11A, 15B, and 17F), that are included in PNEUMOVAX® II but not in pneumococcal conjugate vaccines. Methods: Serotype-specific IgG geometric mean concentrations (GMCs) for these four serotypes were measured by ELISA in 104 subjects >50 years old (mean 58, range 52-72) who were enrolled in a study evaluating the safety and immunogenicity of one dose of PNEUMOVAX® II. Results: For serotypes 10A, 11A, 15B and 17F, 1 month post-vaccination, GMCs were 6.5, 4.3, 14.7, and 5.1 mcg/ mL, respectively. GMC fold rises from baseline were 9.0, 4.5, 8.4, and 11.5, respectively. The percentage of subjects achieving a >2-fold increase of antibody concentration post-vaccination was 90%, 85%, 88% and 89%, respectively. Conclusion: PNEUMOVAX® II induces a robust immune response in adults to pneumococcal serotypes 10A, 11A, 15B, 17F, which were associated with elevated case-fatality rates. It has is the only pneumococcal vaccine that includes these Background and Aims: Streptococcus pneumoniae serotypes differ in their clinical manifestations among adults, varying in propensity for disease severity, invasiveness, and lethality. To characterize differentials in serious outcomes by various pneumococcal serotypes, we systematically reviewed the literature. Methods: After distilling 658 hits to 27 relevant articles, statistically significant differences in serotypes associated with empyema, meningitis, septic shock, necrotizing pneumonia, and case-fatality rates were assessed. Serotypes repeatedly associated with elevated risk of serious clinical outcomes were evaluated in terms of serotypes included in licensed adult pneumococcal vaccines (i.e., 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13)). Results: Among adult studies evaluating serious clinical outcomes, the following serotypes were repeatedly associated with elevated risk: Conclusion: Pneumococcal serotypes most often associated with a significant elevation in risk for serious clinical outcomes were included in both PPSV23 and PCV13. Four studies found elevated risk from serotype 6A (unique to PCV13). Thirteen studies found notably elevated risk from serotypes unique to PPSV23 (case-fatality: 11A and 9N, meningitis: 15B, 10A, 12F). Seven studies found elevated risk from serotypes not represented in any vaccine formulation. The pneumococcal serotypes repeatedly associated with elevated risk of serious outcomes in adults are an important consideration for vaccine policy making. Results: Among 836 IPD isolates, 97 were in children <5 and 739 in persons ≥5 years old. Of these, 785 were from blood, 35 from cerebrospinal fluid (CSF) and 90.3% could be serotyped. Predominant serotypes in children <5 were 6B (26.4%), 14 (22.0%) and 19F (9.9%). In persons ≥5 years, most common were serotypes 3 (10.7%), 6B (9.7%), 19A (8.7%) and 23F (8.7%). Among children <5, 74% and 82% of serotyped isolates were contained in 10-valent PCV (PCV10) and PCV13, respectively, compared to 48% and 70% in ≥5 year olds. Conclusion: Based on the largest reported sample of isolates in Thailand, PCV10 and PCV13 would cover >70% of IPD in children <5 years, and PCV13 would cover the majority of IPD in older individuals. Vaccine serotype coverage for young children is close to previous estimates, but the large number of isolates from older individuals and national scope of the sample contribute important data for vaccine policy considerations. Background: Streptococcus pneumoniae is a common pathogen of pneumonia and acute otitis media (AOM) in children. PCV-10 was introduced to the childhood immunization program in Iceland in 2011. The aim of the study was to evaluate the effect on hospital visits and admissions in a population not earlier vaccinated against pneumococci. Methods: The number of children <15 months of age visiting or admitted to The Children's Hospital for pneumonia or AOM from January 2008 through March 2013 were studied retrospectively. Children <15 months of age of each yearly birth cohort were included. Children born in 2011 (vaccinated) were compared to children born in 2008-2010 (unvaccinated) (odds ratio and likelihood ratio test). Results: The mean annual incidence/1000 children <15 months of age with AOM was 106 (standard deviation (SD):15.4) and for children born in 2011 the incidence was 85, significantly lower than for children born in the previous 3 years (mean = 113; SD:7.2; odds ratio (OR):0,720; 95% CI:0,632-0,820, p = 10-6). For pneumonia the mean annual incidence was 28 (SD:5.7), and for 2011 it was 20, significantly lower in the vaccinated group (mean = 31; SD:2.8; OR:0,652; 95% CI:0,508-0,837, p<0.006). For comparison, the incidence of acute bronchiolitis in 2008 -2011 was 30, 34, 52, and 47 respectively. Conclusion: A significant reduction in hospital visits and admissions due to AOM and pneumonia was seen in vaccinated children <15 months of age very soon after initiation of the immunisation with PCV-10. The early effect of the immunization in this young age group is encouraging. Background and Aims: Both extended valency pneumococcal conjugate vaccines (PCVs) in use today were originally licensed based on immunogenicity comparison with the heptavalent formulation. To understand how this has translated into public health impact, we reviewed the considerable amount of efficacy and effectiveness data generated with GlaxoSmithKline Vaccines' 10-valent PCV, PHiD-CV, since its licensure in 2008-2009. Methods: PHiD-CV efficacy and effectiveness data for invasive pneumococcal disease (IPD) and pneumonia from 2 double-blind randomized controlled trials (DBRCTs), FinIP and COMPAS (focusing on intent-to-treat analyses), and multiple post-marketing surveillance (PMS) studies were reviewed.

Results:
The DBRCTs and PMS studies demonstrated robust efficacy and effectiveness of infant and childhood immunization with PHiD-CV against IPD and pneumonia across a wide range of epidemiological, socio-economic and geographical settings (Table). In addition, decreases in IPD due to cross-reactive serotypes in the vaccineeligible age groups were evident from PMS studies in several countries. Significant reductions in vaccine-type IPD or nasopharyngeal carriage were also apparent in some vaccine-ineligible age groups in Finland and Brazil, suggestive of herd effects. Background and Aims: Flexible and extensible complex mathematical models provide an in silico laboratory for testing ideas about the factors that scale from individuals to populations and affect policy. Here we present a model of transmission and resistance applicable to Streptococcus pneumoniae and other clinically important bacteria that commonly colonize hosts and only occasionally cause disease. For these opportunistic pathogens, the colonizing bacteria (but usually not the bacteria in an infection) constitute the reservoir of contagion. Even as medicine focuses on managing invasive disease, public health and policy must also consider the reservoir dynamics that drive vaccineinduced strain replacement and the evolution of resistance to antibiotics. Methods: Our new Markov-chain model shows the reservoir and transmission dynamics of colonizing bacteria simultaneously considers several biological phenomena.

Results and Conclusion:
The effects of these biological factors on policy can lead to misleading conclusions if the wrong assumptions are made. We predict the effects of the factors in a flexible framework and identify the following to be important for bacterial reservoir dynamics and thus for policy: differences in the transmissibility, invasiveness, immunogenicity, and persistence of strains; strain-specific, cross-, or strain-transcending immunity; simultaneous colonization with multiple strains with no strain interaction, and with direct inhibition and competitive dominance; bacterial population responses to drug treatment and the evolution of drug resistance; and changes in immunity that are related to the host's age.

EARLY IMPACT OF 3+0 SCHEDULE OF 13VPCV IN AUSTRALIAN CHILDREN AND ADULTS
S. Jayasinghe 1 , C. Chiu 1 , R. Menzies 1 , C. Bareja 2 , V. Krause 3 , P. McIntyre 1 1 National Centre for Immunisation Research and Surveillance, The Children's Hospital at Westmead, Westmead, Australia; 2 Vaccine Preventable Diseases Surveillance Section Office of Health Protection, Department of Health, Canberra, Australia; 3 Centre for Disease Control, Department of Health Northern Territory Government, Darwin, Australia Background & Aims: On 1st July 2011, PCV13 replaced PCV7 in the childhood pneumococcal vaccination program in Australia. The unique schedule of 3 primary doses with no booster (3+0) was continued for 13vPCV. A single 13vPCV dose was offered, for one year, to children aged 12-35 months who had completed a 7vPCV course. This study compares impact of 13vPCV program in the first year with that in the same period post-7vPCV introduction. Methods: IPD notifications to the national passive surveillance system, NNDSS, were used in the study. Age and serotype specific incidence rate ratios (IRRs) of IPD due to 13-non-7v types were calculated for pre-(2009-10) vs. the first complete calendar year (2012) post-13vPCV introduction. The IRRs for 13v-non-7v were compared with those for 7v types in comparable pre-versus post-7vPCV periods.

Results:
In children <5 y of age, 66 isolates of 13v-non-7v IPD were identified in 2012 compared with the average for 2009-10 of 140.5, a significant reduction in total 13v-non-7v (54%) and in 19A (66%). There were non-significant decreases in 19A in those > 5 years, offset by increases in 7F. In the comparable period post-7vPCV introduction in 2005, vaccine type IPD decreased 79% and 27-36% in < 5 and >5 year ages respectively. Conclusion: A marked reduction in 13v-non-7v IPD was seen post-13vPCV introduction in the target age group and all young children. The impact of 13vPCV on IPD due to these 6 serotypes was less compared to that from 7vPCV on vaccine type IPD in a comparable period.

No conflict of interest
Background and Aims: In February 2010, PCV13 replaced 7-valent pneumococcal conjugate (PCV7) vaccine in the U.S. infant immunization schedule with catch-up for children <5 years. We evaluated the impact of PCV13 on adult disease. Methods: IPD cases (isolation of pneumococcus from sterile sites) among adults ≥ 18 years were identified through Active Bacterial Core surveillance (ABCs) during July 2004-June 2012. Isolates were serotyped by Quellung and classified as PCV5 (19A, 7F, 3, 5, 1) and non-PCV13 serotypes. We used pre-PCV13 observed cases in time-series models to forecast post-PCV13 incidence in the absence of PCV13 (counterfactual scenario). PCV13 impact was the difference between forecasted incidence and observed incidence. We derived incidence estimates and confidence intervals from the distribution of Monte-Carlo simulations. Results: ABCs identified 26,061 adult IPD cases. Average IPD incidence declined from 15.7/100,000 to 12.2/100,000. Incidence of PCV5-type IPD declined after PCV13 introduction (Table), driven primarily by serotypes 19A and 7F. Non-PCV13 serotype IPD incidence did not change. During January 2012-June 2012, 29% of IPD was due to PCV13 serotypes. Mortality was about 10%. > 90% isolates were susceptible to penicillin, cefotaxime but over 60 and 30 % isolates were resistant to trimethoprim-sulphamethoxazole, erythromycin respectively. Background: Changes in serotypes (STs) distribution have been observed, particularly following the pneumococcal conjugate vaccines (PCVs) implementation, and uncommon non vaccine STs so far are now circulating. There is a need to distinguish among these latter, those with higher invasive disease potential. Methods: Invasive pneumococcal disease (IPD) STs isolated from children 6 to 24 months were compared with nasopharyngeal (NP) colonizing STs. To assess the invasive potential of a given ST, odds ratio (OR) was calculated. For each ST, OR>1 indicated an increased probability to be associated with IPD, while OR<1 indicated a decreased probability. Pneumococcal strains were conventionally serotyped with antisera from Statens Seruminstitute. Results: Between 2011 and 2012, the pooled dataset included pneumococci isolated from 189 healthy carriers and 567 IPD (among which 143 meningitis and 73 pneumonia). Mean age ± SD was 12.9 months ± 5.1 (median 12.0) without any difference between the groups (healthy carriers and IPD). ST7F and ST19A were positively associated to IPD, meningitis and pneumonia with the highest ORs found for ST7F. ST24F was positively associated to IPD and meningitis, but not to pneumonia. Conversely, the lowest significant OR (0.1) was observed for ST23B in IPD and meningitis, and for ST15A in pneumonia. For two major invasive STs, case/carrier ratios were not calculated since no carrier was recorded (ST12F, ranking at the 2nd place in all invasive diseases and ST1, ranking at the 4th place for pneumonia).

Conclusion:
Our results suggest that 24F had the most important invasive disease potential among the non vaccine STs. Conversely ST 11A, 15A, 17F, 23A, 35F, 6C and 23B were poorly associated with IPD but for most of the other non vaccine STs, the risk was not assessed. Conclusion: During 13 years, 1.4% of PM caused by PCV ST occurred in PCV vaccinated children (adequately for age). Since PCV13 implementation, we observed, in vaccinated children, the disappearance of PCV7 STs except 19F, which represented 40% of overall cases.

REDUCED HOSPITALIZATION DUE TO SINUSITIS AND PNEUMONIA AFTER INTRODUCTION OF PCV7
A. Lindstrand 1 , R. Bennet 2 , I. Background: Streptococcus pneumoniae is the major cause of bacterial pneumonia and sinusitis. S. pneumoniae kills about 1.3 million children <5 years annually and sinusitis is a feared paediatric disease due to orbital and intracranial complications. Although effective against invasive pneumococcal disease, the effectiveness of pneumococcal conjugate vaccine (PCV) against pneumonia is less consistent and its effect on sinusitis is not known. Here, we compared hospitalizations rates due to sinusitis and pneumonia 4 years before and after introduction of PCV7 in 2007. Method: Retrospective study of hospital registry data on hospitalizations due to sinusitis and pneumonia in all children 0-<18 years. Trend analysis, incidence rates and relative risks were calculated comparing July 2003-June 2007 to July 2008-June 2012, excluding the year of PCV7 introduction. Results: Sinusitis hospitalizations decreased significantly in children 0-<2 years from 70 cases/100 000/year before the introduction of PCV7 to 25 cases/100 000/year (RR=0.35, P<0.001) after the introduction (Fig 1). Pneumonia hospitalizations decreased significantly in children 0-<2 years (RR 0.81, P<0,001) and 2-<5 years (RR=0.85, P=0.002) during the same period (Fig 2). Conclusion: Introduction of PCV led to a decreased risk of hospitalization due to sinusitis (65% decreased risk) and to pneumonia (19% decreased risk) in children 0-< 2 years. Background and Aims: In January 2012 PCV13 was introduced in Argentina using 2+1 schedule and catch-up program until 2 years of age. In 2012 vaccination coverage among infants <1 year of age was 89% and 59% for the first and the second dose, and among children 1 year old 41,8% and 28,3%, in Rosario city. We compared IPD epidemiology among hospitalized children 4 years prior to, with the transition year post PCV-13 introduction. Methods: Prospective observational study of laboratory confirmed IPD in hospitalized children younger than 13 years carried out from 2008 to 2011 vs 2012. We compared age group-specific, syndrome-specific and serogroupspecific IPD in both periods. Results: In children <2 years there was a trend toward reduction of hospitalizations for pneumococcal pneumonia, but statistical significance was yet not achieved (54.2% reduction from 68.9 to 31.5 cases/10 4 discharges, p = 0.1087). This rate decreased no significantly 66.1% from 55.2 to 18.7 cases/10 4 discharges in infants younger than 12 months of age (p = 0.146) and 40.4% from 97.4 to 58 cases/10 4 in children 12-23 months (p = 0.606). A nonsignificant 30.14% reduction in meningitis was seen in children younger than 2 years. Only one infant with IPD due to a vaccine serotype with 1 dose of vaccine and no one with 2 doses, were identified. No difference in hospitalizations for IPD was observed in older children.

Conclusion:
Just one year after introduction of PCV-13 in Argentina the hospitalization rates for pneumococcal pneumonia and meningitis show promisory decreases in children younger than 2 years old in Rosario. Background: The homeless state places individuals in living conditions that can result in a greater disposition to a variety of infectious diseases. Invasive pneumococcal disease (IPD) is one such disease that is becoming more recognized as being associated with the homeless population. Surveillance of IPD in Alberta has been performed by the Provincial Laboratory for Public Health (Provlab) since 2000. One of the metrics captured during this surveillance is homelessness. We report on the association of specific pneumococcal serotypes with the homeless in Alberta. Methods: IPD is a notifiable disease to Provincial Health Authorities. As such, the isolates from all cases of IPD are forwarded to the Provlab for serotyping. Cases of IPD identified through isolate submission were followed up by a study nurse to determine the cases place of residence. Results: Analysis of pneumococcal serotypes from 2000 to 2012 found an association of specific serotypes with the homeless population. Of 57 serotypes identified among over 5600 isolates, five serotypes accounted for 57% of invasive pneumococcal disease (IPD) from homeless people. These serotypes were 5, 8, 9N, 12F and 20. These five serotypes only made up 19% of serotypes found in cases of IPD from the non-homeless population. We also noticed temporal clustering. Serotype 20 was found in elevated numbers from 2011 to 2013 and serotype 5 from 2005 to 2008. Conclusion: Specific pneumococcal serotypes cause the majority of IPD in the homeless population. In addition, the temporal clustering events suggest successive outbreaks caused by these serotypes in this population.

Conflict of interest
pneumonia 2014 Volume 3 181 ISPPD-9 / pneumonia 2014 Mar 9-13;3:1-286 Background: The aim was to examine the evolving serotype epidemiology and antimicrobial susceptibility of Streptococcus pneumoniae isolates causing invasive pneumococcal disease (IPD) in children ≤14 y old following introduction of PCVs to the Greek National Immunization Programme (NIP). Methods: Data from a 4 year prospective study conducted between September 2008 and October 2012 in 10 pediatric hospitals are presented. Serotyping was performed by latex agglutination and Quellung reaction using anti-sera (SSI, Denmark). Antimicrobial susceptibility was determined by E-test. Results: Among 177 isolates collected (37.2% ≤2 y old) a 38% decrease of overall IPD cases was observed between pre-PCV13 (2008-2010) and post-PCV13 (2011-2012) periods; reaching 47.6% in children ≤2 y old. The decrease was more notable in meningitis cases (71.4%) followed by bacteremia (41.7%) and bacteremic pneumonia (26.3%) cases. The commonest IPD serotypes in the pre-PCV13 era were 7F (23.2%), 19A (20.2%), 1 (11.1%) and 3 (8.0%) while 1.5 years post-PCV13 were 7F and 19A (25.8% each) and 24F (9.7%). PCV7 serotypes became extinct while a substantial decrease (43.8%) of the 6 additional serotypes in PCV13 was recorded along with NVTs remaining at constant numbers. Resistance to penicillin (resistant or intermediate) exhibited 19.4% of isolates in the pre-PCV13 period vs. 9.7% in the post-PCV13 period. However, resistant isolates to erythromycin increased from 15.2% to 25.8% between the two periods. Conclusion: IPD cases decreased significantly after the introduction of PCV13 in the Greek NIP. Further reduction of residual burden of disease can be anticipated with the achievement of better compliance to the existing schedule. Objectives: To evaluate the impact of PCV7 and PCV13 on epidemiology, serotype distribution, and antimicrobial resistance of all Streptococcus pneumoniae isolates and the vaccine coverage rate in all age groups.

Methods:
The study included all cases of invasive and non-invasive pneumococcal disease (IPD) in children and adults among all age groups from January 2004 to December 2011. The isolates were serotyped using Quellung reaction antisera and their susceptibility to penicillin was determined using the Etest method. Results: 645 pneumococcal isolates were included in the study. From January 2004 till July 2006, there were 250 isolates (22% were invasive and 27% were from children ≤5 years). From August 2006 till December 2011, there were 390 isolates (32% were invasive s and 35% were from children ≤5 years). The predominant invasive serotypes from 2004-2006 were 19F, 23F, 9V and 14, while from 2006-2011 were 19F, 8, 6A, 9V, 14, 3, 1, 19A, 5 and 15B. The percentage serotype coverage by PCV7 in children <2 years dropped from 75.0% in the first period to 34.6% in the second period. A positive impact of PCV7 on the incidence of IPD and drop in penicillin resistance was demonstrated in both children <5 years and adults >50 years. Conclusion: With the appearance of non-PCV7 pneumococcal serotypes, broader serotype coverage vaccines are needed for the prevention of IPD.

No conflict of interest
Background and Aims: World Health Organization (WHO) report that >1 million children's deaths annually are due to pneumococcal infection. Invasive pneumococcal disease (IPD) presents with high mortality in children less than 5 years of age, particularly in countries where anti-pneumococcal immunization has not been implemented as part of the national immunization schedule. In Ukraine vaccination with PCV is still available only for children with high risk of developing IPD patients and at some private hospitals. Methods: A retrospective chart review was conducted of 74 patients (1-17 y old) with cultural confirmed IPD. All patients were treated during 2003-2012 in Lviv Regional Infection Diseases Hospital. Results: Annual incidence rate of IPD in our region was 9.4 cases/100,000/year. The median of age of patients was 3.2 years. Bacterial pneumonias (27.1%), purulent meningitis (24.5%) and septicemias (16.6%) were the most frequent diagnoses. Mortality rate was 7.0% for IPD and 12.5% for pneumococcal meningitis. Long-term effects were reported in 12.0% of IPD cases. Serotypes were identified in 64.8%, and the leading was serotype 1 (20 cases), followed by serotypes 14 (17 cases) and 6B (11 cases). Conclusion: The rate pneunococcal disease in West region of Ukraine is still high. Prevaccination data on disease severity and outcome of IPD are important to determine the impact of vaccination strategies. The pneumoccocal vaccine must be included in national vaccination program. Background and Aims: In the present study we evaluated clinical profile, antimicrobial susceptibility, prevalent serotypes of pneumococcal isolates from children with suspected invasive pneumococcal disease (IPD) admitted to a tertiary care hospital. Methods: Hospitalized children, ≤5 years with fever (>38°C); increased respiratory rate or neurological symptoms were recruited,(as part of ASIP project 2011-2013). Ethical Approval was obtained. Identification of pneumococcal isolates from blood (Bactec) or cerebrospinal fluid (CSF) samples was done by routine culture methods and confirmed by multiplex -PCR. Confirmed isolates were analysed for antimicrobial susceptibility (MIC) and serotyping by Quellung's test. Results: Out of the 171 samples received in the lab, 17 grew pneumococci identified standard methods. Fourteen of them were confirmed by Multiplex -PCR. Maximum recruitment were seen in months of January and February (36.4%, 28.6%). Average age was 21 months. Common clinical feature were of pneumonia (42.8%) which included cough (78.5%), tachypnoea (42.8%), chest retraction (23.1%), auscultatory crepitations (38.4%). Radiological analysis showed consolidation and infiltration in 38.50. Prior antibiotics in the last 48 hours were given in 23.1% of children. Two isolates belonging to 19F and 19B serotype were resistant to penicillin. Serotype distribution was 6B and 19F (2 each) and 1, 2, 6A, 9V, 10A, 14, 15A, 19B, 21 and 35F (1 each). Conclusion: Based on the serotyped isolated from our paediatric cohort with IPD, current protection offered by the 10-valent and 13-valent pneumococcal conjugate vaccines were 33.3% and 41.6% respectively. Thus non-vaccine serotypes were featured prominently in our setting. Background and Aims: Pneumonia is responsible for approximately 1.2 million deaths each year in children less than 5 years old, with the bulk of those occurring in Southeast Asia and sub-Saharan Africa. Pneumococcal vaccines can prevent vaccine-type pneumococcal pneumonia. However the data pertaining to the use of pneumococcal vaccines in Asia is scarce. This is a phase II/III, open-labelled randomized controlled clinical trial. The overall aim of the study is to address the outstanding questions that will guide the identification of a new schedule for routine immunization in Asia to support the most efficient use of pneumococcal conjugate vaccines. This study will address two key questions regarding vaccine introduction into Asia: 1. What is the optimal schedule for provision of expanded programme of immunization (EPI) vaccines with the incorporation of Synflorix? 2. How do the responses to PCV vaccination with Synflorix or Prevnar-13 compare? Methods: 1200 infants aged between 60 to 74 days old will be recruited from 2 study sites located in District 4 and District 7 of Ho Chi Minh City. Subjects will be randomized to one of six vaccination schedules. Participants provide a series of blood samples for analysis of vaccine responses, and nasopharyngeal swabs for analysis of pneumococcal carriage. Conclusion: This clinical trial will provide answers to the two key questions that have inhibited introduction of routine pneumococcal vaccination into this region. This trial will provide critical evidence based research to guide policy regarding inclusion of these important vaccines into EPI in Asian countries

MATHEMATICAL MODELLING OF THE LONG-TERM POPULATION EFFECTS OF PNEUMOCOCCAL VACCINES ON CARRIAGE OF PNEUMOCOCCAL SEROTYPES IN KENYA
Background: In the nation-wide double-blind cluster-randomized Finnish Invasive Pneumococcal disease (FinIP) trial we assessed the indirect impact of 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) (GlaxoSmithKline Vaccines) on suspected IPD using hospital diagnoses. Methods: Children <19 months received PHiD-CV10 in 48 clusters or hepatitis B/A vaccine as control in 24 clusters according to infant 3+1 or 2+1 schedules or catch-up schedules. Hospitals' in/outpatient discharge reports with ICD-10 diagnoses compatible with IPD and unspecified sepsis and/or infection were collected from national Care Register for the whole population. Cases of IPD detected by culture or DNA/RNA detection were excluded. Annual incidences in the non-vaccinated population aged >5 years were compared between the PHiD-CV10 and control clusters. National vaccination programme for 3-month-old infants without catch-up started in Sep-2010. Results: Altogether, >41,000 children were enrolled from May-2009 to Oct-2010. Trial vaccination coverage varied from 29 to 61% in the PHiD-CV10 clusters. In 2011, 104 suspected, non-confirmed IPD episodes (ICD-10 A40.3/ B95.3/G00.1 /M00.1) were detected in the unvaccinated population aged >5 years. The table shows the preliminary results.

IMPACT OF PNEUMOCOCCAL VACCINE ON INVASIVE PNEUMOCOCCAL DISEASE AMONG YOUNG CHILDREN IN THE MID-WEST REGION OF IRELAND
R.K. Philip 1 , N. OConnell 2 , J. Powell 2 , R. Fitzgerald 3 Background and Aims: Pneumococcal vaccine (PCV 7) was included in the National immunisation schedule of Ireland in September 2008. Significant reduction in morbidity and case specific mortality was expected. We aimed to, 1. establish the reduction in hospital admission for children due to invasive pneumococcal disease (IPD) since the introduction of pneumococcal vaccine in the Mid-West region of Ireland, 2. to compare with the corresponding figures for the whole country, and 3. to determine the added clinical value of the extended spectrum vaccine (PCV13) that commenced in 2010. Methods: All admissions below five years of age registered on the hospital inpatient enquiry system (HIPE) with the confirmed diagnosis of IPD or recognised in the computerised laboratory data as a positive Streptococcus pneumoniae culture/PCR from blood, pleural effusion or cerebrospinal fluid were tabulated for 5 years before and 5 years after the HPV introduction to the National immunisation schedule. Number of cases against the birth cohort of the region (5000/year) was calculated. Results: There was reduction of 90% and 72% respectively for IPD below two years and two to five years age group after introduction of PCV. Our observations are similar to the National published figures. Since the introduction of HPV13 in late 2010 further reduction in hospital admission and incidence of complicated pneumonia was observed. Current PCV uptake in the region is 90%. Conclusion: In a developed health care setting, Immunisation with PCV offer significant reduction in hospital admission due to invasive pneumococcal disease. Methods: A prospective, laboratory-confirmed (culture and/or PCR) surveillance of all hospitalized IPDs in Madrid was performed. IR (no. cases/100,000 inhabitants) was calculated using data from the Spanish Instituto Nacional de Estadistica. The estimated vaccination coverage in 2012-3 (using data from IMS) was 70% for PCV13 (schedule) in children <12 mo (3+1) and 95% in those 12-59 mo (2+1+catch-up), and 50% for PCV7 in children ≥60 mo-<15 y (3+1). Comparisons of IR were performed (EPIDAT version 3.1). Conclusion: IRs of all IPD clinical presentations were markedly reduced in 2012-3 (with statistically significant reductions for respiratory presentations and meningitis) regardless withdrawal of pneumococcal vaccines from the vaccination calendar (high private uptake of PCV13). Background and Aims: Serotypes/susceptibility of Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi) isolates from otical/nasopharyngeal samples in children were explored in a well-defined area (400,000 inhabitants) of Barcelona (private market coverage: 50%). Methods: Nasopharyngeal and middle ear swabs from 238 children (2 mo-≤8 y) presenting otitis with spontaneous suppuration in a multicenter prospective study were sent to central laboratory. PCR detection (Sp, Hi) was performed in culture-negative ear samples. Results: 87 Sp, 97 Hi were identified in otical samples (both concomitant in 39). In nasopharynx, 112 Sp, 78 Hi were recovered. Non-typeable (by PCR) Sp: 39 (otical), 20 (nasopharyngeal). Tables show by origin PCV13 and non-PCV13 serotypes.

Results:
Conclusion: IR of IPD by PCV13 serotypes significantly decreased without increases in IRs of IPDs by non-PCV13 serotypes regardless withdrawal of pneumococcal vaccines from the vaccination calendar but with a high private uptake of PCV13. Methods: A prospective, laboratory-confirmed (culture and/or PCR) surveillance of all hospitalized IPDs was performed. All isolates (for serotyping) and culture-negative pleural/cerebrospinal fluids (for PCR detection) were sent to a central laboratory. IR (no. cases/100,000 inhabitants) was calculated using data from the Spanish Instituto Nacional de Estadistica. PCV13 vaccination in 2012-2013 was estimated using data from Intercontinental Marketing Services (IMS). Comparisons of IR were performed (EPIDAT version 3.1).   19F, 19A, 23F and 14 (2). · 3/5 were erythromycin resistant, 3/5 cotrimoxazole resistant, 2/5 chloramphenicol resistant and 1/5 penicillin resistant. ·

BY AGE GROUP INCIDENCE OF INVASIVE PNEUMOCOCCAL DISEASE AFTER WITHDRAWAL OF PCV13 FROM THE
The predictive value of having pneumococcal sepsis increases if fever >/= 101°F and leukocytosis > 15000 are taken together Acknowledgement: ASIP study for the laboratory services   Background and Aims: Worldwide, Streptococcus pneumoniae is the most commonly identifiable cause of Community Acquired Pneumonia (CAP) resulting in hospitalizations and deaths in high-risk adults and elderly. Incidence varies between 2-40 cases/1,000 elderly person-years, case fatality ratio between 7-35% in Europe/US. Little is known in Italy on the burden of this disease. Since 2000, 23-valent pneumococcal vaccine (PPV23) was offered in Apulia to individuals aged >64 years. Since 2011, 13-valent pneumococcal conjugate vaccine (PCV13) has been introduced targeting the same population. Overall (PPV23/PCV13) vaccination coverage was 10% (August 2013). We described the epidemiology of CAP in adults in Apulia.

Methods:
We implemented a two-year active sentinel surveillance system involving thirty physicians (general practitioners (GPs)/pneumologists) to identify patients with CAP signs and/or symptoms and collect: clinical information, vaccination history, nasopharyngeal swabs, sputum and/or blood specimens. Specimens were tested for S. pneumoniae identification and PCR serotyping. We analysed data using Stata/MP 11.2. Results: In January-September 2013, 76 CAP were identified. Median age was 79 years (range 64-95); 60.5% were males; vaccination history was available for 61 (80%) patients. Physicians collected 182 specimens. We identified 29 (29/76; 38%) CAP positive (in either blood or sputum) for S. pneumoniae. Mostly isolated serotypes were: 23F (8/29), 14 (4/29), 3 (3/29), 4 (3/29), 12F (2/29), 9V (2/29). Serotyping was not possible for three sputum. Conclusion: We are lightening the regional lack of longitudinal data on S. pneumoniae CAP. Most cases were due to vaccine-contained serotypes suggesting how paramount PCV13 vaccination uptake is to benefit of a substantial vaccine impact. Background and Aims: Streptococcus pneumoniae is the most commonly identifiable cause of community acquired pneumonia (CAP) resulting in hospitalization and death in the elderly worldwide. Since 2000, 23-valent pneumococcal vaccine (PPV23) was offered in Apulia to individuals aged >64 years. Since 2011, 13-valent pneumococcal conjugate vaccine (PCV13) has been introduced targeting the same population. Overall (PPV23/ PCV13) vaccination coverage was 10% (PCV13:6%-August 2013). In January 2013, we implemented a two-year CAP surveillance among adults targeted by the vaccination program to monitoring the S.pneumoniae serotypes circulating in the region. We estimated preliminarily PCV13 effectiveness. Methods: We conducted a test-negative design study using the information collected on patients with signs and/ or symptoms of CAP enrolled in the surveillance system. Cases were pneumonia patients with a specimen (sputum, blood) PCR positive for a PCV13-contained serotype. Controls were non-PCV13-serotypes pneumonia patients. The exposure of interest was PCV13 vaccination (regardless of previous PPV23 vaccination). We computed the test-negative estimate of vaccine effectiveness (VE) as 1-OR and calculated its exact 95% confidence interval. We analysed data using Stata/MP 11.2. Results: We included 22 cases and 3 controls. Most cases and controls had at least one co-morbidity (i.e. chronic pulmonary or cardiovascular disease); two and one respectively were vaccinated for PCV13. Crude Vaccine Effectiveness was 80% (-1660%;99.3%). Conclusion: The test-negative design provides relatively accurate VE estimates. However, due to the small number of patients, our findings, although suggestive of good vaccine effectiveness, should be interpreted with extreme caution. Significant efforts should be oriented to increase PCV13 vaccine uptake. Results: The incidence of IPD cases in children decreased from an average of 14 cases/100,000/year in 2000/2001 to 4 cases/100,000/year in 2011. The median age of cases increased from 2.0 y to 3.3 y (p = 0.06). The proportion with a risk factor (apart from age) that is an indication for pneumococcal vaccine did not change. The proportion of cases hospitalized increased from 59% to 83% (P<0.001). The proportion admitted to ICU increased from 14% to 25% (p = 0.06). Focal disease (meningitis, peumonia, empyema) compared to bacteremia without focus increased from 43% to 66% (p < 0.001). Having IPD in the post-vaccine period increased odds of hospitalization (OR: 2.9; 95% CI: 1.6-5.8). In the post-vaccine period, serotypes in PCV13 but not PCV7 caused most cases (42%). Conclusion: Clinical features of IPD have changed since PCV7 was introduced, with a shift towards more focal infections requiring hospitalization. Thus, although overall IPD cases have declined, disease that does occur is more severe. Background: After the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2002, IPD caused by PCV7 serotypes has been nearly eliminated at all ages. The purpose of this analysis is to describe recent trends in IPD (post-PVC7) in all age groups, as well as early trends following the introduction of the PCV13 in July 2010. Methods: We looked at overall and age-specific incidence of IPD caused by PCV7, PCV13 (less PCV7) and other serotypes from 1998-2012 in all age groups in Calgary. We also looked at changes in the proportion of IPD caused by specific serotypes and serotype groups. Results: IPD has declined in the youngest and oldest age groups since PCV7 was introduced. The average incidence of 11 cases/100,000 people/year in 1998-2001 declined to 8 cases/100,000 people in 2012. Serotype distributions have also changed.

Conclusion:
In the most vulnerable age groups, the very young and very old, there has been a decline in overall IPD since the introduction of conjugate vaccines. Overall incidence in the Calgary area has declined since 2007. PCV13 serotypes still cause IPD, especially in the older age groups. Background and Aims: Pneumococcal serotypes that affect adults are changing throughout time. The objective is to describe pneumococcal serotypes from patients with invasive disease and associate them with theoretical vaccine coverage. Methods: Epidemiological study of pneumococcal serotypes obtained from adults by the National Surveillance System (SIREVA), 1999 to 2012. Data obtained from the National Institute of Hygiene. Descriptive epidemiology of gender, age (adolescents 15-19; Young adults 20-49, adults 50-64, and elderly 65 and more years), type of sample, serotypes, an theoretical vaccine coverage. Estimation of potential vaccine coverage for VPP23v, VPC10v VPC13v. Definitions for maximum coverage includes any serotype incorporated in each vaccine; meanwhile, minimum coverage excludes non-specific identification of serotype among groups. Results: 133 samples; 82 from males, with similar gender distribution among age groups. 68% samples were from Cerebrospinal fluid, 13,5% pleural fluid, 13.5% blood and others, Most frequent serotypes were: 3 (14:10,5%), 7F (11;8.3%), and 19A, 19F, 23F, Group 12 (each 8;6%). Other serotypes found were: 14, 9V, 18C, 4, 5, 6B, POOL H (between 5.5 and 3% each), and the rest, less than 3% each, only 7 were not typed. During the last 4 years the number of specimens has increased (46.6%). Serotype changes within age groups were: Serotypes 3 and 19A in first positions among all age groups. Vaccine coverage are PPV23v 81-71%, and PCV13v 69-67% Conclusion: Pneumococcal serotypes from invasive samples differ more among adult groups of age. Surveillance for adults is increasing. Vaccines provide good coverage of invasive pneumococcal serotypes in Venezuela. Background and Aims: In 2012, Fiji introduced the 10-valent pneumococcal conjugate vaccine (PCV10) using a 3+0 schedule with AusAID support. After 3 years, the Ministry of Health will absorb all vaccine costs. Our impact evaluation will measure the direct and indirect effects of PCV10 on carriage, invasive pneumococcal disease (IPD), and pneumonia. To further understand the ethnic differences in disease rates, we will model carriage transmission. Methods: Annual community carriage surveys are being undertaken pre-and post-PCV10 introduction to measure direct and indirect effects in young infants, vaccinated children, and their caregivers. The frequency and intensity of social contact will be measured and the effect this has on pneumococcal carriage between ethnic groups will be compared. IPD surveillance will evaluate the impact of PCV10 on IPD and monitor invasive serotypes in all ages. An interrupted time series analysis will be undertaken pre/post PCV10 using inpatient and outpatient pneumonia data in all ages, identified by ICD10 codes. Radiological pneumonia and very severe pneumonia rates will be compared pre/post PCV10 in children less than two years old. Conclusion: IPD surveillance data and special studies are required to fully measure the effect of PCV10 on IPD and pneumonia. This impact evaluation will provide the necessary data to justify the ongoing cost of the PCV10 program, ensure sustainability, and shed light on the reasons for ethnic differences in disease rates. In addition, the results will guide other countries in the region on the value of PCV10 on common childhood diseases.  Background and Aims: Despite pneumonia being the commonest cause of childhood admissions and deaths globally, there are very little data on the impact of PCV on pneumonia, and even less data on its indirect effects, particularly in resource-limited settings. In 2012, the Fiji Ministry of Health introduced PCV10. To prepare for an evaluation of the direct and indirect effects of PCV10, this study describes the epidemiology of hospitalised pneumonia in all ages, prior to PCV10 introduction. Methods: All-cause pneumonia admissions for all ages were extracted using ICD10 codes from 2007-2011, from the Fiji national computerised hospital database and the manual reporting system, for those hospitals that are not computerised. The population denominators were sourced from the 2007 Census. Results: There were 14,826 admissions of all-cause pneumonia. The age distribution followed a U-shaped curve with the highest annual incidence occurring in <5 year olds (2,404 per 100,000) followed by the 65+ year old age group (1,004 per 100,000). The incidence rate was up to 3.1 fold higher in the i-Taukei (Indigenous) population compared with Fijians of Indian ethnicity. Of those with a fatal outcome, 30.2% (n = 292) occurred in children aged <5 years (CFR 3.1%) and 34% (n = 329) of all deaths occurred in 65+ year olds (CFR 21.5%). Conclusion: Pneumonia admissions and deaths were more common in young children and the elderly. For unknown reasons, pneumonia is more common in the Indigenous population. This data provides a good baseline to evaluate the direct and indirect effects of PCV10 on hospitalised pneumonia. Background and Aims: The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Brazilian Immunization Program in a 3 + 1 schedule for children < 2 years of age in mid 2010. Coverage for the primary three doses schedule of the vaccine among infants reached 80% in late 2011. The aim of this study was to evaluate the early effects of immunization on the incidence of invasive pneumococcal disease (IPD) and serotype distribution in São Paulo. Methods: We performed a 9-year (2004 -2012) surveillance, at a large sentinel hospital in Sao Paulo, including all children <2 years admitted due to IPD. Isolates were sent to a reference laboratory (Adolfo Lutz Institute) for serotyping and testing for antimicrobial susceptibility Results: We identified 94 cases of IPD in children aged <2 years during the study period. The annual number of PCV10-types IPD and all-types IPD in children aged <2 years declined 89% and 77%, respectively, in the postvaccination period. Serotype 14, responsible in the pre-vaccination period for 38% of the IPD cases, disappeared in the post-vaccination period. No increase in overall non-PCV10 type IPD was observed. Reduction in the rates of penicillin resistance was also demonstrated. Conclusion: The introduction of PCV10 into the routine vaccination program provided a rapid and significant reduction in IPD cases among children aged <2 years, the age group targeted for vaccination. These encouraging results highlight the need of continued surveillance studies to assess the long term impact of this vaccination program. Background and Aims: There is a paucity of vaccine impact studies in the Asia-Pacific region. Fiji introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in 2012. Our 'New Vaccine Evaluation Project' will measure the impact of PCV10 on nasopharyngeal carriage, invasive pneumococcal disease, and pneumonia. Annual community carriage surveys are being undertaken pre-and post-PCV10 introduction to measure direct and indirect effects in children (5-8 wk, 12-23 mo, 2-<7 y) and their caregivers. Methods: Nasopharyngeal swabs were collected from a representative sample of 500 healthy children aged 12-23 mth pre-PCV10 introduction. Swabs were collected, transported, stored and processed according to the new WHO guidelines. The dominant α-haemolytic morphology, and an example of each morphological variant, were identified as pneumococci using standard methods and serotyped by latex agglutination/Quellung. Results: Preliminary analysis of the pre-PCV10 swabs found 236 contained pneumococci, and 213 did not. Additional testing is underway for 51 swabs. The pneumococcal-positive swabs contained 249 serotypes, of which 103 were vaccine-types; 13 swabs contained more than one serotype. Soon we will examine swabs taken one year post-PCV10 introduction, and present these results compared to the pre-PCV10 data. Conclusion: Future analyses will examine the bacterial load in specimens and the genetic relatedness of the pneumococcal isolates. Ongoing surveys will assess the direct effects of PCV10 up to three years post-introduction and will be compared with carriage data from children with pneumonia; forming part of a comprehensive study to examine total vaccine impact, including direct and indirect effects on carriage and disease, in Fiji. Background: Prophylactic antipyretics (PAP) are often used during routine vaccination of infants and toddlers to prevent fever. However, recent research suggests that PAP may reduce immune response to some pediatric vaccines. This study evaluated the effect of different PAP on immune response to the 13-valent pneumococcal conjugate vaccine (PCV13) and other routinely recommended vaccine antigens. Methods: 908 healthy infants were enrolled and randomized to receive either paracetamol (P) or ibuprofen (I) in 1 of 4 PAP regimens, or to no PAP (control), after each vaccine dose: All subjects received PCV13 and DTaP/IPV/Hib/HBV at 2, 3, 4, and 12 months; blood was drawn at 5 and 13 months.

DOES USE OF PROPHYLACTIC ANTIPYRETICS (PAP) AFFECT IMMUNE RESPONSE TO VACCINATION IN INFANTS
Results: 800 subjects (88.1%) were included in the primary analysis. Pneumococcal anticapsular IgG geometric mean concentration (GMCs) were significantly (p < 0.0125) lower in G3 versus G5 (control) for 5 of 13 serotypes after the primary series. Pertussis FHA and tetanus IgG GMC were significantly lower among G4 versus G5 after the primary series. No differences were observed for any antigens after the toddler dose. Conclusion: Prophylactic paracetamol may interfere with primary series immune response to pneumococcal antigens. Ibuprofen did not interfere with pneumococcal responses, but may reduce response to pertussis FHA and tetanus antigens. These effects were not observed following the toddler dose. The clinical significance of these findings is unclear but suggests that PAP should be given careful consideration in the setting of infant vaccination.

IMPACT OF INTRODUCTION OF PNEUMOCOCCAL CONJUGATE VACCINE (PCV) INTO THE NATIONAL IMMUNIZATION PROGRAM ON THE RATE OF INVASIVE PNEUMOCOCCAL DISEASE (IPD) AND PENICILLIN NON-SUSCEPTIBLE STREPTOCOCCUS PNEUMONIAE (PRSP) IN SAUDI ARABIA
A. Shibl 1 , Z. memish 2 , A. senok 3 1 Microbiology, King saud university, Riyadh, Saudi Arabia; 2 infectious diseses, Ministry of health, Riyadh, Saudi Arabia; 3 Microbiology, Alfaisal university, Riyadh, Saudi Arabia Background and Aims: Between 2006 and 2012, a total of 1265 invasive pneumococcal disease (IPD) isolates from children under 5 years of age were collected from hospital laboratories around Saudi Arabia. These included 603 isolates before the introduction of PCV (2006 -2008), 378 isolates during the introduction of PCV7 (2009 -2010) and 284 isolates from the introduction of PCV13 (2011 -present). Methods: All isolates were screened for serotyping using pneumococcal capsule-specific sera obtained from Statens Serum Institute (Copenhagen, Denmark).Penicillin susceptibility was determined using the E-test. The predominant IPD serotypes, before introduction of PCV7, were 23F, 19F, 4, 6B and 14. Following the introduction of PCV7, the predominant isolates belonging to serotypes were 1, 7F, 5 and 19A. After the introduction of PCV13, a reduction in serotypes 3, 19A, and 6A were observed. Results and Conclusion: Compared to previous years, lower numbers of IPD isolates were obtained in 2013. In children under the age of five years, a significant reduction in the detection of penicillin non-susceptible Streptococcus pneumoniae (PRSP) isolates was observed from 49. 7% in 2009, 27.3% in 2010, 19.2% in 2011 and 10.6% in 2012. Similarly in this age group, based on the number of invasive isolates received, the proportion of invasive pneumococcal disease due to vaccine serotypes, declined from 21% to about 4% in 2012. These findings indicate that the introduction of the pneumococcal conjugate vaccine has had a positive impact in the country based on the reduction in the proportion of vaccine serotype IPD and a reduction in the frequency of PRSP.

Background and Aims:
Clinical studies in adults from the United States and Europe have shown that the T-cell dependent 13-valent pneumococcal conjugate vaccine (PCV13) is safe and induces a greater functional immune response than the unconjugated T-cell independent 23-valent pneumococcal polysaccharide (PPSV23) vaccine for the majority of PCV13-serotypes. A similar comparison of PCV13 with PPSV23 was conducted for the first time in a Japanese study population ≥65 years of age. Methods: In a phase 3, randomized, modified double-blind, active-controlled trial, eligible subjects were randomized 1:1 to receive PCV13 or PPSV23 intramuscularly. Blood samples were collected immediately before and 1 month after vaccination for measurement of serotype specific anti-pneumococcal opsonophagocytic activity (OPA) titers.

Results:
The evaluable analysis population included 366 PCV13 and 367 PPSV23 recipients. OPA geometric mean titers (GMTs) in the PCV13 group were statistically significantly higher than in the PPSV23 group for 9 of the 12 common serotypes and for serotype 6A, a serotype unique to PCV13; GMTs were similar for serotypes 1 and 14 and significantly lower for serotype 3 in the PCV13 group. Local reactions were more common in the PCV13 group but mainly mild to moderate; systemic and adverse events were similar across groups. There were no related serious adverse events. Conclusion: As observed in global studies, PCV13 was safe and well tolerated and induced a greater functional immune response than PPSV23 for the majority of PCV13-serotypes in Japanese subjects. Japanese adults showed a similar pattern of responses as adults in the United States and Europe.
incidence rates of pneumococcal meningitis in Tashkent city in 2008 were 2.3 cases per 100,000 children aged <14 years, 2009 were 2.0, 2010 were 3.9 and in 2011 were 4.2 and 2012-5.2 cases per 100,000 children aged <14 years. In 2012 the detected incidence rates of pneumococcal meningitis by age group were 2.6 cases per 100,000 children aged <1 year, 5.7 cases per 100,000 children aged 1 -6 year, 5.1 cases per 100,000 children aged 7 -14 years. Of the 108 patients with pneumococcal meningitis 24% had the adverse outcome and 1 (0.9%) died during hospitalization. Conclusion: The surveillance system detected a substantial burden of pneumococcal meningitis among children in Tashkent. S. pneumoniae was detected among 51.4% of investigated patients. The use of vaccines against this pathogen could prevent a substantial portion of disease and deaths in Uzbekistan. Background: Streptococcus pneumoniae (SP) is a common cause of bacterial meningitis in Greece. PCV7 was introduced for children <5 years of age in 2006 and PCV13 in 2010. The aim of this study was to describe the epidemiology of pneumococcal meningitis (SPM) following the introduction of PCV13 in comparison with previous years. Methods: Data of notified cases were reviewed retrospectively and were compared between three periods: A (prevaccine, 2000-2005), B (post PCV-7, 2006(post PCV-7, -2010 and C (post PCV13, 2011(post PCV13, -2012. Three multiplex PCR (mPCR) assays were performed; one genus-specific and two for serotype identification. Results: Of 598 SPM cases notified, 549 (91.8%) were confirmed by culture (n=220 40%) and/or PCR (n=418, 76.2%). Overall annual incidence was estimated for the 2 periods (A&B) at 0.54/100,000 while a reductionwas observed for period C (0.41/100 000). During period C, the overall incidence decreased in all age groups compared to period B with a significant difference among the 0-4 year olds (3.17 vs 2.2 vs 1.38/100,000 for A, B and C respectively, p<0.05). Most prevalent serotypes in period A were 14 (50%), 23F (13.4%) and 6 (12.3%), while in B 3 (31.3%), 19F (26.8%), 6 (21.9%) and 19A (12.5%). A considerable decrease in period C was observed for all serotypes especially 3 (6.5%) and 19A (2.6%) mainly found in older ages (>40 years). Conclusion: Incidence of SPM decreased significantly among younger children after the introduction of PCV13. The persistence of 3 and 19A in older ages is currently closely monitored.

EFFECTS OF 5 YEARS OF IMMUNIZATION WITH HIGHER VALENT PNEUMOCOCCAL CONJUGATE VACCINES IN GERMAN CHILDREN
M. van der Linden 1 , S. Perniciaro 1 , M. Imöhl 1 1 National Reference Center for Streptococci Department of Medical Microbiology, University Hospital Aachen, Aachen, Germany Background and Aims: A general recommendation for vaccination with pneumococcal conjugate vaccine (PCV) was issued for German children up to the age of 2 years in July 2006. In 2009, PCV10 and PCV13 were introduced in Germany. Here, we present data on cases of IPD from children collected in the eight years following the start of vaccination. Methods: Pneumococcal isolates recovered from children with IPD were collected at the German National Reference Center for Streptococci (GNRCS). Identification of the isolates was confirmed and serotyping was performed using the Neufeld-Quellung reaction. Results: In 2012-2013, IPD cases in children <2 years with PCV7 serotypes (n=4) decreased by over 96% (compared to 1997-2006), while cases with non-PCV7 serotypes (n=94) more than doubled. Particularly, serotypes 1, 3, 5, 6A, 7F, 19A increased following PCV7 introduction, but decreased after higher-valent PCVs were introduced. In 2012-2013 only 20 cases with PCV13nonPCV7 serotypes were reported, as compared to 59 in 2009-2010 (-66%). Reduction was observed for serotypes 1 (-66%), 3 (-50%), 6A (-100%), 7F (-82%) and 19A (-50%). IPD cases due to Non-PCV13 serotypes increased strongly from 32 to 74 (+124%), resulting in an increase in overall cases compared to 2011-2012. Conclusion: Eight years and five years following introduction of PCV7 and PCV13 for children in Germany, respectively, PCV7 serotypes have almost disappeared and PCV13 serotypes have strongly diminished among children <2 years. The strong increase in non-PCV13 serotypes might be related to a strong winter and influenza season. First data of 2013-2014 do not show a continuation of the high case numbers.