Post Hoc Analysis of a Randomized Double-Blind Trial of the Correlation of Functional and Binding Antibody Responses Elicited by 13-Valent and 7-Valent Pneumococcal Conjugate Vaccines and Association with Nasopharyngeal Colonization

In a randomized double-blind trial in healthy Israeli infants in Israel who received the 13-valent or 7-valent pneumococcal conjugate vaccine (PCV13 or PCV7, respectively) at 2, 4, 6, and 12 months, PCV13 significantly reduced nasopharyngeal (NP) colonization of serotypes 1, 6A, 7F, 19A, cross-reacting 6C, and the common PCV7 serotype 19F, from ages 7 to 24 months. No differences were observed between the vaccine groups for serotype 3 or for the remaining common PCV7 serotypes. For serotype 5, too few events were observed to draw an inference. Generally consistent with these findings, PCV13 elicited significantly higher enzyme-linked immunosorbent assay (ELISA) IgG-binding antibody responses than did PCV7 for the additional PCV13 serotypes 1, 3, 5, 6A, 7F, 19A, and for the common serotype 19F, with similar or lower responses for the remaining common serotypes. To further assess immunogenicity and colonization, we conducted a post hoc analysis of PCV13 functional antibody responses measured by opsonophagocytic activity (OPA) assays in a randomly selected subset of subjects. The pattern of functional antibody OPA responses elicited by PCV13 relative to PCV7 was similar to that of the ELISA anticapsular IgG-binding antibody responses described above. In addition, the OPA responses generally correlated positively with IgG responses for all 13 serotypes among the PCV13 recipients and for all 7 common serotypes and the additional serotype 6A but not for 19A or the other serotypes unique to PCV13 among the PCV7 recipients. This post hoc analysis supports an association between serum OPA functional and IgG-binding antibody levels, allowing for a transfer of inferred associations between IgG responses and NP colonization to OPA responses.     

The epidemiology of invasive Streptococcus pneumoniae infections in onco-haematology and haematopoietic stem cell transplant patients in France. Are the serotypes covered by the available anti-pneumococcal vaccines?

The pneumococcal antigens contained in the polysaccharide (PPV23) and conjugate (7-valent, PCV7; 13-valent, PCV13) vaccines have been chosen since they represent the serotypes that more frequently cause invasive pneumococcal disease. Whether these vaccines cover the serotypes most frequently isolated in haematology patients is unclear. The serotype distribution among Streptococcus pneumoniae in 25 consecutive pneumococcal infections that occurred over the last 3 years in two French haematology departments was investigated. The pneumococcal vaccines PCV7, PCV13 and PPV23 were found to cover 76, 84 and 92%, respectively, of the serotypes found.     

Baseline epidemiology of Streptococcus pneumoniae serotypes in Canada prior to the introduction of the 13-valent pneumococcal vaccine

Changes in the epidemiology of Streptococcus pneumoniae were reported worldwide after the introduction of the 7-valent pneumococcal vaccine, particularly an increase in multi-drug resistant (MDR) 19A strains. Subsequently, a 13-valent pneumococcal vaccine (PCV-13) has been introduced. This study assessed the incidence of S. pneumoniae serotypes in all age groups prior to the introduction of PCV-13 in Canada (2007-2009). Eight hundred S. pneumoniae isolates from respiratory specimens and blood cultures were collected as part of a Canadian surveillance study (CANWARD) from patients in 15 tertiary-care centers. Serotyping was performed by the Quellung method and antimicrobial susceptibility testing was performed by broth microdilution in accordance with the Clinical and Laboratory Standards Institute guidelines. The most common serotypes were 19A (8.6%), 3 (7.3%), 22F (6.0%), 4 (4.6%), 5 (4.4%), and 11A (4.4%); and the first serotype 6D isolate in Canada was identified. Serotypes 5, 7F, and 19A were significantly (p<0.001) more frequently isolated from bloodstream infections. Considerable serotype variability was noted for different age groups: 15B (p<0.01) and 19A (p<0.001) were more frequently isolated from children ≤2 years old. Overall, 46.4% of currently circulating S. pneumoniae serotypes in Canada are included in PCV-13. Notably, 87.5% of MDR-S. pneumoniae were covered by PCV-13. Accordingly, PCV-13 will provide coverage against a significant proportion of circulating S. pneumoniae strains in Canada, including the critical antimicrobial-resistant strains.     

Early Changes in the Serotype Distribution of Invasive Pneumococcal Isolates from Children after the Introduction of Extended-valent Pneumococcal Conjugate Vaccines in Korea, 2011-2013

This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored.     

Distribution of Streptococcus pneumoniae Serotypes That Cause Parapneumonic Empyema in Turkey

Streptococcus pneumoniae is the most common etiological cause of complicated pneumonia, including empyema. In this study, we investigated the serotypes of S. pneumoniae that cause empyema in children. One hundred fifty-six children who were diagnosed with pneumonia complicated with empyema in 13 hospitals in seven geographic regions of Turkey between 2010 and 2012 were included in this study. Pleural fluid samples were collected by thoracentesis and tested for 14 serotypes/serogroups using a Bio-Plex multiplex antigen detection assay. The serotypes of S. pneumoniae were specified in 33 of 156 samples. The mean age ± the standard deviation of the 33 patients was 6.17 ± 3.54 years (range, 0.6 to 15 years). All of the children were unvaccinated according to the vaccination reports. Eighteen of the children were male, and 15 were female. The serotypes of the non-7-valent pneumococcal conjugated vaccine (non-PCV-7), serotype 1, serotype 5, and serotype 3, were detected in eight (14.5%), seven (12.7%), and five (9.1%) of the samples, respectively. Serotypes 1 and 5 were codetected in two samples. The remaining non-PCV-7 serotypes were 8 (n = 3), 18 (n = 1), 19A (n = 1), and 7F/A (n = 1). PCV-7 serotypes 6B, 9V, 14, 19F, and 23F were detected in nine (16.3%) of the samples. The potential serotype coverages of PCV-7, PCV-10, and PCV-13 were 16.3%, 45.4%, and 60%, respectively. Pediatric parapneumonic empyema continues to be an important health problem despite the introduction of conjugated pneumococcal vaccines. Active surveillance studies are needed to monitor the change in S. pneumoniae serotypes that cause empyema in order to have a better selection of pneumococcal vaccines.     

Changes in Molecular Epidemiology of Streptococcus pneumoniae Causing Meningitis following Introduction of Pneumococcal Conjugate Vaccination in England and Wales

The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in September 2006 has markedly reduced the burden of invasive pneumococcal disease (IPD) including meningitis in England and Wales. This study examined changes in the molecular epidemiology of pneumococcal isolates causing meningitis from July 2004 to June 2009. The Health Protection Agency conducts enhanced pneumococcal surveillance in England and Wales. In addition to serotyping, pneumococcal isolates causing meningitis were genotyped by multilocus sequence typing (MLST). A total of 1,030 isolates were both serotyped and genotyped over the 5-year period. Fifty-two serotypes, 238 sequence types (STs), and 87 clonal complexes were identified, with no significant difference in the yearly Simpson''s diversity index values (range, 0.974 to 0.984). STs commonly associated with PCV7 serotypes declined following PCV implementation, with a proportionally greater decline in ST124 (commonly associated with serotype 14). No other ST showed significant changes in distribution, even within individual serotypes. Replacement disease following PCV7 introduction was mainly due to serotypes 1, 3, 7F, 19A, 22F, and 33F through clonal expansion. A single instance of possible capsule switching was identified where one ST4327 clone expressed a serotype 14 capsule in 2005 and a serotype 28A capsule in 2009. In 2008 to 2009, ST191 (7F) became the most prevalent clone causing meningitis (10.3%). Case fatality (145 fatalities/1,030 cases; 14.1%) was high across all age groups and serotype groups. Thus, the introduction of PCV7 resulted in an increase in non-PCV7 serotypes, including some not covered by the 13-valent vaccine, such as serotypes 22F and 33F, emphasizing the importance of long-term epidemiological and molecular surveillance.     

Pediatric invasive pneumococcal disease in the United States in the era of pneumococcal conjugate vaccines

Invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide, especially in children under 5 years of age. In the United States, 90% of invasive pneumococcal infections in children are caused by 13 serotypes of S. pneumoniae. The licensure (in 2000) and subsequent widespread use of a heptavalent pneumococcal conjugate vaccine (PCV7) have had a significant impact on decreasing the incidence of serious invasive pneumococcal disease (IPD) in all age groups, especially in children under 2 years of age. However, the emergence of replacement non-PCV7 serotypes, especially serotype 19A, has resulted in an increase in the incidence of serious and invasive infections. In 2010, a 13-valent PCV was licensed in the United States. However, the impact that this vaccine will have on IPD remains to be seen. The objectives of this review are to discuss the epidemiology of serious and invasive pneumococcal infections in the United States in the PCV era and to review some of the pneumococcal vaccines that are in development.     

Experience with pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) in children and adults

Streptococcus pneumoniae-related infections are a major cause of morbidity and mortality in people of all ages worldwide. Pneumococcal vaccine development started in 1911 with a whole cell vaccine and more recently multivalent plain polysaccharide and polysaccharide conjugate vaccines have been developed. The recent vaccines rely on capsular polysaccharide antigens to induce serotype-specific immune responses. We summarize here the presentations on pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) given during the integrated symposium organized and funded by Pfizer International Operations during the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 31 March to 3 April 2012, London, UK. A dramatic reduction in the incidence of invasive pneumococcal diseases (IPD) due to vaccine serotypes (VST-IPD) has been reported since the introduction of a hepta-valent pneumococcal conjugate vaccine (PCV7). An indirect (herd) effect has been demonstrated to be associated with PCV7 infant vaccination programmes, with many studies reporting reductions in VST-IPD in populations that are not eligible for PCV7 vaccination. Since 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) has been introduced into national immunization programmes and results from early surveillance suggest that this vaccine also has an impact on the serotypes unique to PCV13, as well as continuing to protect against the PCV7 serotypes. Data from a passive surveillance system in Europe in 2009, for instance, showed that the highest incidence of IPD remains in those aged >65 years and in children <5 years. PCV13 has now been licensed for vaccination of adults >50 years based on safety and immunogenicity data; an efficacy trial is being conducted. Regardless of previous pneumococcal vaccination status, if the use of 23-valent polysaccharide is considered appropriate, it is recommended to give PCV13 first. Novel immunization strategies remain the only practical means to reduce significantly the remaining global mortality and morbidity due to S. pneumoniae in adults.     

Global prevailing and emerging pediatric pneumococcal serotypes

Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths among children younger than 5 years of age worldwide. The 7-valent pneumococcal conjugate vaccine (PCV7) is currently licensed in more than 90 countries and has contributed to significant declines in the incidence of invasive pneumococcal disease (IPD). Recent studies report an increased incidence of IPD caused by non-PCV7 vaccine serotypes (NVTs). Seroepidemiology of IPD caused by NVTs following the introduction of PCV7 is of interest, and this article provides a comprehensive global summary of the prevailing and emerging serotypes causing IPD in children. Currently, globally emerging or persistent NVTs include serotypes 1, 3, 5, 6A, 7F and 19A. Serotypes included in the recently licensed 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) account for pneumococcal disease burdens in most developed countries of 65-85% and 80-90%, respectively. The seroprevalence of NVTs after widespread use of PCV10 and PCV13 requires ongoing monitoring.     

Pediatric osteoarticular infections caused by Streptococcus pneumoniae before and after the introduction of the heptavalent pneumococcal conjugate vaccine

Streptococcus pneumoniae is an uncommon cause of osteoarticular infections (OAI) in children. The objective of this study was to investigate the clinical and laboratory characteristics of pneumococcal OAI before and after the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7). Data were retrospectively collected from children aged?<16?years who were hospitalized for pneumococcal OAI between 1997 and 2007 in four Parisian teaching hospitals. Forty-three children were included (32 with arthritis and 11 with osteomyelitis) and the median age of these children was 12.5?months (range 3?months to 14?years). Serotypes were available for 19/43 strains (44?%) from 1997 onwards and for 12/13 strains (92?%) from 2005 onwards. Seven unvaccinated children were infected with vaccine serotypes and we observed only one vaccine failure. After the introduction of PCV7, we noted an increase in short-term complications and the emergence of serotype 19A, which was penicillin-intermediate in 86?% of cases. After PCV7 introduction, serotype 19A was the most frequent serotype implicated in pediatric pneumococcal OAI. The 13-valent pneumococcal conjugate vaccine introduced in France in June 2010 should cover the emerging serotype.     

Kinetics and avidity of antibodies evoked by heptavalent pneumococcal conjugate vaccines PncCRM and PncOMPC in the Finnish Otitis Media Vaccine Trial

The licensure of new pneumococcal conjugate vaccines (PCVs) relies on immunogenicity data. When defining correlates of protection, vaccine efficacy data must be included. In the FinOM Vaccine Efficacy Trial, the PncOMPC vaccine showed an efficacy profile similar to that of the licensed PncCRM vaccine despite different antibody responses after primary and booster vaccinations. We determined antibody kinetics and avidities in a subgroup of infants participating in the FinOM trial. A total of 166 infants in three vaccine groups were immunized at 2, 4, 6, and 12 months of age with 7-valent PCV, PncCRM or PncOMPC, or hepatitis B vaccine. Concentrations of serum immunoglobulin G (IgG) against pneumococcal capsular polysaccharides were determined at 2, 4, 6, 7, 12, 13, and 24 months of age, and the avidity index (AI) to serotypes 6B, 19F, and 23F were determined at 7, 12, 13, and 24 months of age by enzyme immunoassay. Both PCVs were highly immunogenic, but they demonstrated different kinetics of antibody response; the concentration of IgG against serotypes 6B, 19F, and 23F declined faster after the third and fourth doses of vaccine in the PncCRM group than in the PncOMPC group. For both PCVs, the mean AI of anti-6B and -23F, but not of anti-19F, increased during the follow-up, which is in line with serotype-specific protection in the FinOM trial. Our data suggest that the kinetics and avidities of antibodies should be considered, in addition to antibody responses, when defining correlates of protection.     

Changes in serotype distribution and antibiotic resistance of nasopharyngeal isolates of Streptococcus pneumoniae from children in Korea, after optional use of the 7-valent conjugate vaccine

We investigated serotype distribution and antimicrobial resistance of pneumococcal carriage isolates from children after optional immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) in Korea. From June 2009 to June 2010, 205 (16.5%) pneumococcal isolates were obtained from 1,243 nasopharyngeal aspirates of infants and children at Seoul National University Children's Hospital, Korea. Serotype was determined by Quellung reaction and antibiotic susceptibility was tested by E-test. The results were compared to previous studies done in the pre-PCV7 period. In this study, the most common serotypes were 6A (15.3%), 19A (14.7%), 19F (10.2%), 35B (7.3%), and 6D (5.6%). The proportion of PCV7 serotypes decreased from 61.9% to 23.8% (P < 0.001). The overall penicillin nonsusceptibility rate increased from 83.5% to 95.4% (P = 0.001). This study demonstrates the impact of optional PCV7 vaccination in Korea; the proportion of all PCV7 serotypes except 19F decreased while antimicrobial resistant serotypes 6A and 19A further increased.     

Impact of IgM Antibodies on Cross-Protection against Pneumococcal Serogroups 6 and 19 after Immunization with 7-Valent Pneumococcal Conjugate Vaccine in Children

Although it is well known that pneumococcal conjugate vaccines provide cross-protection against some vaccine-related serotypes, these mechanisms are still unclear. This study was performed to investigate the role of cross-protective IgM antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in children aged 12-23 months after immunization with 7-valent pneumococcal conjugate vaccine (PCV7). We obtained serum samples from 18 Korean children aged 12-23 months after a PCV7 booster immunization. The serum IgG and IgM concentrations of serotypes 6B and 19F were measured by enzyme-linked immunosorbent assay (ELISA) in serum. The opsonic indices (OIs) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were determined by an opsonophagocytic killing assay (OPA) in IgM-depleted and control serum. Both IgG and IgM antibodies in ELISA and opsonic indices in OPA against serotypes 6B and 19F were demonstrated in the immune serum. IgM depletion decreased the OIs against vaccine serotypes 6B (geometric means of OIs (GMIs) of 3,009 vs. 1,396, 38% reduction) and 19F (1,117 vs. 750, 36% reduction). In addition, IgM depletion markedly decreased the OIs against vaccine-related serotypes 6A (GMIs of 961 vs. 329, 70% reduction), 6C (432 vs. 185, 72% reduction), and 19A (301 vs. 166, 58% reduction). The booster immunization PCV7 induced protective antibodies in the form of both IgG and IgM isotypes. IgM antibodies contributed to eliciting cross-protection against vaccine-related serotypes as well as against vaccine serotypes.     

Pneumococcal conjugated vaccines: impact of PCV-7 and new achievements in the postvaccine era

Pneumococcal disease is a major health problem worldwide. Large, rapid declines in overall invasive pneumococcal disease and mucosal disease in children, reductions in vaccine-type disease in unvaccinated children and adults (indirect effects) and significant drops in antibiotic-resistant infections were observed after the introduction of a safe, available and immunogenic seven-valent pneumococcal vaccine. The determination of vaccine efficacy is a complex process, which includes efficacy, immunogenicity, safety, cross-reactivity, indirect effects and substantial geographic variation in serotype coverage. In this report, we perform an overview of the literature on current, investigational and potential candidate pneumococcal conjugated vaccines (PCVs). Every country should have its own strong and sustained surveillance system implemented to monitor the effects of vaccination on the frequency of vaccine and nonvaccine serotypes for invasive or mucosal disease, nasopharyngeal carriage and the indirect effects before and after introduction of PCV. New PCVs (PHiD-CV and PCV-13) may provide even greater coverage worldwide, especially in developing countries. Vaccine experts' efforts are currently focused on developing alternative vaccine strategies against pneumococcal infections, especially the development of vaccines based on pneumococcal proteins.     

Epidemiology of Streptococcus pneumoniae in France before introduction of the PCV-13 vaccine

The purpose of this article was to describe the serotype incidence and antibiotic susceptibility of Streptococcus pneumoniae strains isolated from adults and children with invasive disease (IPD) or acute otitis media (AOM) before introduction of the 13-valent pneumococcal vaccine. During 2009, 494 strains of S. pneumoniae isolated were collected. Complete serotyping by latex antisera and molecular methods was performed. The most frequent serotypes isolated from children with IPD were 1 (26.2%), 19A (25%) and 7F (14.3%). Serotype 19A was predominant (42.1%) in children ≤ 2 years, whereas serotype 1 was predominant (63.3%) after the age of 5. Serotype 19A was the most frequently isolated serotype from AOM (62.3%). In adults, serotypes responsible for IPD were 7F (19.4%), 19A (13.7%), 1 (8.4%) and 3 (7.5%). The serotype 19A was predominant in adults older than 65 years (19.1%). The emergence of serotype 12F was observed in adults. Between 2007 and 2009, the introduction of PCV-7 has resulted in a significant decrease of IPD caused by serotypes included in the vaccine, in children as well as in adults, confirming the herd effect. Serotype coverage of PCV-13 was 70% and 80.9% for adult and children’s IPD, respectively. PCV-13 will be more efficient in preventing invasive diseases among children and adults.     

Routine infant immunization with the 7- and 13-valent pneumococcal conjugate vaccines: current perspective on reduced-dosage regimens

The 7 and 13-valent pneumococcal conjugate vaccines are mostly used in routine infant immunizations to prevent the development of pneumococcal disease. Currently, the dosing schedule approved and recommended for PCV7 and PCV13 in infants is 3 primary doses followed by a booster dose in the second year of life. However, a number of countries use a 2-dose only primary series with a booster dose in the second year of life. This review is aimed at providing the reader with a broad perspective on the currently available evidence which supports the clinical use of such reduced dosing schedules for the PCV7 and PCV13 vaccines. Recent evidence has been able to promulgate the immunogenicity and in some cases the effectiveness of the reduced dosing schedule for these vaccines. These findings may reduce costs as well as minimize supply and administration problems relating to the provision of the pneumococcal conjugated vaccines (PCVs). However, some caution is warranted since some inferior data have emerged with regards to the antibody immune response to certain pneumococcal serotypes following the implementation of such reduced dosing regimens. In addition, it is proposed that prospective surveillance be undertaken in all countries which have adopted the reduced-dosage immunization programs. This review may go some way in educating healthcare practitioners and healthcare policy decision makers at large.     

Expansion of Serotype Coverage in the Universal Pediatric Vaccination Calendar: Short-Term Effects on Age- and Serotype-Dependent Incidence of Invasive Pneumococcal Clinical Presentations in Madrid,Spain

In Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged <15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non-PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13 serotypes.     

Sustained high prevalence of pneumococcal serotype 1 in paediatric parapneumonic empyema in southern Spain from 2005 to 2009

The epidemiology and microbiological characteristics of paediatric parapneumonic empyema (PPE) before the introduction of the new generation of conjugate pneumococcal vaccines (10-valent and 13-valent) are described. All patients <14 years old admitted to a tertiary paediatric hospital with a diagnosis of PPE were prospectively enrolled from January 2005 to December 2009. Pneumococcal serotyping of culture-negative pleural fluid samples was performed using a multiplex real-time PCR assay. Overall, 219 patients had PPE. Incidence rates for PPE remained stable during the study period with a not significant increase in 2009 compared with 2005 (p 0.13), and were temporally associated with higher circulation of pandemic influenza A H1N1 during the last quarter in our population (p 0.001). Pneumococci were detected in 72% of culture-positive and 79% of culture-negative samples. Serotypes were determined in 104 PPE cases. Serotype 1 was the most prevalent serotype identified (42%) followed by serotypes 7F (20%), 3 (16%), 19A (8%) and 5 (7%). Serotype distribution remained similar during all time periods. Pneumococcal serotype 1 remained the most common cause of PPE during the 5-year study. The new generation of pneumococcal conjugate vaccines offers potential serotype coverage of 73% (10-valent) and 99% (13-valent) in the population studied suffering from PPE. Continuous epidemiological and molecular studies are paramount to monitor the impact of pneumococcal vaccines on the epidemiology of PPE.     

Serum IgM Antibodies Contribute to High Levels of Opsonophagocytic Activities in Toddlers Immunized with a Single Dose of the 9-Valent Pneumococcal Conjugate Vaccine

In immunogenicity trials of pneumococcal conjugate vaccines (PCVs), only IgG antibody concentrations to pneumococcal capsular polysaccharides (PPSs) are usually determined, along with the opsonophagocytic activity (OPA) of antipneumococcal antibodies. We aimed to determine the role of both IgG and IgM in OPA in toddlers receiving one dose of 9-valent PCV (PCV9). The IgG and IgM antibody concentrations to PPSs of serotypes 6A, 9V, 14, 19F, and 23F were measured by enzyme immunoassay in sera from toddlers (ages 18 to 35 months) 1 month after a single PCV9 dose. The OPA for the same serotypes was measured by multiplexed opsonophagocytosis assay (MOPA). Further, IgG and IgM concentrations and MOPA were measured to PPS of serotypes 6A, 14, and 19F in sera collected 12 months after vaccination. The detected MOPA titers were high in comparison to the IgG concentrations 1 month after immunization. The IgM concentrations were higher than IgG concentrations for serotypes 6A and 14 (P < 0.001) and as high as IgG for serotypes 9V, 19F, and 23F. Correlation of the IgM antibody concentrations with MOPA (r = 0.35 to 0.65) was stronger compared to that of the IgG antibodies (r = 0.07 to 0.41). The depletion of IgG antibodies in three sets of pooled sera only slightly decreased the OPA activity against serotype 14. At 12 months after immunization, 50 to 100% of serum samples still showed detectable MOPA activity against serotypes 6A, 14, and 19F. Our results suggest that IgM contributes to OPA 1 month after a single PCV9 vaccination in toddlers and that functionally active IgM and IgG antibodies persist for at least a year.     

Invasive pneumococcal disease caused by ceftriaxone-resistant Streptococcus pneumoniae in Taiwan

Background

Invasive pneumococcal disease (IPD) was associated with mortality, but the risk factors associated with mortality remains controversial.