Invasive pneumococcal disease after implementation of a reduced three-dose pneumococcal conjugate vaccine program: a pediatric tertiary care center experience

Following the implementation of a government-sponsored reduced three-dose (2 + 1) heptavalent conjugate pneumococcal vaccine (PCV7) program, we report a 61.4% decrease in the number of cases of invasive pneumococcal diseases (IPD) treated at our institution. Four years after the implementation of the three-dose reduced vaccine program, only 7.4% of IPD were caused by PCV7 serotypes, and there was an increase in the proportion of IPD caused by nonPCV7 serotypes; serotype 19A represented 40.7% of the strains isolated during the last year of the study. These results, similar to those previously observed with a regular four-dose (3 + 1) PCV7 schedule, are reassuring as to the effectiveness of a reduced three-dose (2 + 1) PCV7 program. Increasing numbers of IPD caused by nonPCV7 serotypes warrant the use of a new conjugate pneumococcal vaccine that contains serotype 19A.     

Invasive pneumococcal disease in Danish children, 1996-2007, prior to the introduction of heptavalent pneumococcal conjugate vaccine

Aim: The aim of this study was to document the epidemiology, microbiology and outcome of invasive pneumococcal disease (IPD) among children <16 years with quality surveillance data, just prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the Danish routine immunization programme October 2007.
Methods: Clinical and microbiological records on cases of IPD in children <16 years admitted to Hvidovre Hospital, Denmark 1996–2007, were retrospectively reviewed.
Results: We identified 106 cases of IPD. The annual incidence of IPD was 11 per 100 000 in children <16 years, but considerably higher, 62 per 100 000, in children <2 years. Additionally, of the children with pneumococcal meningitis 86% were <2 years. We observed no fatalities. A total of 10% developed sequelae, but of the patients with pneumococcal meningitis 27% developed sequelae. Nine patients had known risk factors. The Streptococcus pneumoniae serotype was available for 81 cases. Seventy-five percent of the IPD cases in children aged <2 years were caused by one of the serotypes contained within PCV7, compared to only 24% in children ≥2 years.
Conclusion: Our data indicate that an estimated 75% of all IPD cases among children <2 years are caused by PCV7 serotypes and might therefore be prevented by PCV7 vaccination.     

Population-based surveillance for childhood invasive pneumococcal disease in the era of conjugate vaccine

BACKGROUND: Heptavalent pneumococcal conjugate vaccine was licensed in the United States in February 2000 and, following national guidelines, universally distributed in Massachusetts starting in July 2000 to children younger than 2 years of age and selected children 2-5 years of age. We performed statewide surveillance for all cases of invasive pneumococcal disease (IPD) in children younger than 18 years of age to determine risk features and contribution of vaccine failure to ongoing pneumococcal invasive disease. METHODS: Massachusetts pediatric IPD cases were identified via enhanced passive surveillance of microbiology laboratory reports of pneumococcal isolates from sterile body sites of children younger than 18 years for 2 years starting in October 2001. Serotyping was performed on isolates of Streptococcus pneumoniae from normally sterile body fluid. Case demographic and clinical data (including dates of prior doses of PCV7) were collected via follow-up telephone interviews with case primary care providers and/or parents. RESULTS: Between October 1, 2001 and September 30, 2003, 191 cases of IPD were identified statewide (138 in children younger than 5 years). Annual incidence rate for IPD was 17.4 per 100,000 children younger than 5 years, representing a decline of 69% when compared with annual incidence rate of 56.9 per 100,000 from Massachusetts statewide active surveillance performed 1990-1991. In 2001-2003, 30% of cases occurred in the first year of life (36.5 per 100,000), representing a 7.8-fold increased risk compared with children older than 1 year of age. Race-specific annual incidence rates in blacks and Hispanics were 2.3-fold (95% confidence interval, 1.21-4.42) and 1.9-fold (95% confidence interval, 1.06-3.37), greater than in whites. Fifty-nine cases were reported to have underlying comorbid conditions. Serotyping was available for 136 of 191 (71%) cases younger than 18 years; of isolates available for serotyping, 40 (29%) were vaccine serotype (ST), 31 (23%) vaccine-related ST and 65 (48%) nonvaccine ST. Seven of 40 cases with IPD caused by vaccine ST received at least 3 doses of PCV7 vaccine before IPD. CONCLUSIONS: Universal administration of PCV7 to children younger than 2 years of age and selective administration to children 2-5 years of age has resulted in a significant decline in IPD in Massachusetts. Children younger than 1 year of age, African American and Hispanic children and those with recognized comorbid illnesses (malignancy, human immunodeficiency virus, immune deficiency, nephrotic syndrome, etc.) continue to remain at risk for IPD. These risk features should be considered when evaluating febrile infants and children.     

Increase in invasive nonvaccine pneumococcal serotypes at two hospitals in Barcelona: was replacement disease to blame?

Aim: To describe an increase in the incidence of invasive pneumococcal disease (IPD) caused by serotypes not contained in the heptavalent pneumococcal conjugate vaccine (PCV7) in children in two hospitals in Barcelona with different vaccine uptake. Methods: Cumulative incidences of IPD, vaccine and nonvaccine serotypes (NVSTs), and main clinical presentations before (1998–2001) and after vaccine introduction (2005–2008) were compared. Results: The incidence of IPD in children aged <2 years at Hospital Germans Trias i Pujol covering a population in which PCV7 was not widely used showed a nonsignificant increase from 29.9 to 58.8 per 100 000 child‐years between both periods. Following vaccine introduction, there was a 2.5‐fold increase in IPD caused by NVSTs in children aged <5 years. Analysis of trends in the almost fully vaccinated population of Hospital de Barcelona revealed a nonsignificant reduction in IPD incidence in children aged <2 years from 63.1 to 26.0 per 100 000 child‐years. NVSTs in children aged <5 years showed a nonsignificant 1.7‐fold increase in the vaccine period at this centre. Conclusions: The paradoxical increase in invasive infections caused by NVSTs in these populations with different vaccine use suggests that these changes were not driven only by PCV7.     

Program Szczepień Ochronnych w 2017 roku − powszechne szczepienia przeciwko pneumokokom u dzieci

In Poland, starting from 2017, mandatory vaccination against pneumococcus in children will be financed. There are two conjugate vaccines: PCV10 and PCV13 for children from 2 months of age. PCV10 vaccine was purchased for mandatory vaccination programme. In 2011?2015, PCV13 vaccine in children provided more than 20% broader serotypes coverage than the PCV10 vaccine (www.koroun.edu.pl). PCV13 is the only vaccine that demonstrated protection against invasive and non-invasive diseases caused by serotype 19A, which is the most common multi-drug resistant serotype in the population (approximately 80% of the isolates of 19A are MDR). Serotype 19A was the third most common serotype after 6B and 14, responsible for invasive pneumococcal disease (IPD) in children up to 2 years of age. The vaccine PCV10 does not include antigen of serotype 19A.In Kielce, over the last 10 years of the universal immunization programme, PCV7 / PCV13 in children showed reduction in carriage of penicillin-resistant serotypes of Streptococcus pneumoniae. Indirect effect as a decrease in pneumonia in non-vaccinated elderly population has been observed.Pediatric Group of Experts on the Immunization Programme by the Ministry of Health, based on the Polish data KOROUN, recommended vaccine PCV13 for the implementation as universal immunization for children. The arguments for the recommendation take into account the broadest serotype coverage, reducing the carriage of antibiotic-resistant serotypes and the impact of PCV13 vaccine to reduce pneumonia in non-vaccinated population.Vaccination in high-risk groups, including preterm newborns, remains unchanged. For this group, PCV13 is recommended.In the assessment of the effective prevention of pneumococcal disease, serotype coverage, real-world effectiveness of vaccines and health benefits for the entire population should be taken into account.     

Emergence of 19A as virulent and multidrug resistant Pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine

BACKGROUND: The long-term effects of selective pressure from conjugate pneumococcal vaccine on the serotype distribution and antimicrobial resistance of carriage and invasive isolates of Streptococcus pneumoniae are unknown. Early changes demonstrate a reduction in vaccine serotypes and an increase in nonvaccine serotypes (NVT) among both carriage and invasive isolates. Ongoing surveillance is necessary to identify emerging invasive serotypes and antimicrobial susceptibilities. METHODS: Enhanced surveillance of invasive pneumococcal disease in Massachusetts began in October 2001 and remains ongoing. Isolates from children less than 5 are sent to the Massachusetts Department of Public Health and subsequently to the Maxwell Finland laboratory for serotyping and determination of antimicrobial susceptibility. Annual incidence rates for vaccine serotype and NVT disease are calculated using 2000 census data. RESULTS: NVT caused 72%-91% of invasive pneumococcal disease annually in children less than 5 years of age between 2002 and 2005. Serotype 19A has emerged as the most frequent cause of IPD in Massachusetts. A multidrug-resistant clone (ceftriaxone, amoxicillin, azithromycin and trimethoprim-sulfamethoxazole) (MLST 320) was first identified in Massachusetts in 2005. CONCLUSIONS: Three years after the introduction of pneumococcal conjugate vaccine for universal administration to children less than 2 in Massachusetts, a significant increase in invasive disease due to serotype 19A was observed. Although MLST 199 remains the most frequent sequence type among invasive isolates (of 19A), a multidrug-resistant sequence type, not previously identified in Massachusetts, has become an important cause of invasive disease. Further surveillance of the changing ecology of S. pneumoniae is necessary as a 4-year time period is not sufficient to fully evaluate the impact of PCV of pneumococcal infections.     

The future of pneumococcal conjugate vaccines for prevention of pneumococcal diseases in infants and children

Seven-valent pneumococcal conjugate vaccine (PCV7) was licensed in February 2000. In June 2000, the Advisory Committee on Immunization Practices and the American Academy of Pediatrics recommended the universal administration of pneumococcal conjugate vaccine for all children 23 months of age and younger and for children 24 to 59 months of age who are at high risk for serious pneumococcal disease. Since then, >23 million doses have been administered in the United States. Postlicensure surveillance of invasive pneumococcal disease (IPD) in the United States from the Active Bacterial Core Surveillance program at the Centers for Disease Control and Prevention and the Northern California Kaiser Permanente Vaccine Study Center has reported a decline in IPD and in pneumococcal disease incidence as a result of vaccine serotypes, respectively. During this period, issues critical to the long-term success of PCV7 have become more relevant: Will PCV7 be as effective in groups of children who are at high risk for IPD as in healthy children? Will nonvaccine types replace vaccine serotypes in the nasopharynx and in disease? Why are the results of the clinical trials different for IPD and for acute otitis media? How many doses of PCV7 and what concentrations of antibody are necessary for protection? Will universal administration of PCV7 to children younger than 2 years reduce antimicrobial drug resistance and alter prescribing patterns of physicians for febrile infants? Have there been unanticipated adverse events or benefits observed? The purpose of this report is to review the current data available to address these questions and to identify gaps that will require additional knowledge to determine the ultimate value of pneumococcal conjugate vaccines in reducing the burden of pneumococcal disease in infants and children.     

Surveillance for invasive pneumococcal disease during 2000-2005 in a population of children who received 7-valent pneumococcal conjugate vaccine

OBJECTIVES: To assess the incidence of invasive pneumococcal disease (IPD) in all children younger than 5 years of age in the Northern California Kaiser Permanente (NCKP) health care system during a 5-year surveillance period (2000-2005) after the introduction in April 2000 of routine use of 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: This was a laboratory-based surveillance study of all children younger than 5 years of age in the NCKP health care system from April 2000 to March 2005. The comparison group was all children younger than 5 years of age in the NCKP health care system from April 1996 to March 2000. Data obtained from clinical databases included microbiologic identification and susceptibility testing; serotyping of isolates; immunization records; and IPD diagnoses for inpatients and outpatients. IPD was defined as a positive culture of Streptococcus pneumoniae from a normally sterile body site. RESULTS: For all serotypes, the mean annual incidence of IPD during the postlicensure surveillance period was 15.3 cases/100,000 person-years (10(5) p-y) compared with 62.5 cases/10(5) p-y in the prelicensure years of 1996-2000. The average incidence of IPD caused by vaccine serotypes was reduced from 50.1 cases/10(5) p-y during the prelicensure years to 4.9 cases/10(5) p-y during the postlicensure period. The average incidences of IPD caused by cross-reactive and by nonvaccine serotypes were 5.8 and 5.3 cases/10(5) p-y, respectively, during the prelicensure years and 2.5 and 6.2 cases/10(5) p-y, respectively, during the postlicensure period. Of the 131 IPD cases observed during the postlicensure surveillance period, bacteremia (50.4%) and pneumonia (31.3%) were the most common diagnoses. During the 5-year postlicensure surveillance period, only 3 subjects who were identified to be fully vaccinated for age with PCV7 (3 doses by 7 months of age or 4 doses by 18 months of age) developed vaccine-serotype IPD. CONCLUSION: The incidence of IPD has significantly decreased in a large population of children after the introduction of PCV7. Vaccine-type IPD was rare in patients who received full 4-dose immunization with PCV7. There is no clear evidence of a significant increase in nonvaccine-serotype IPD. Introduction of a 4-dose infant schedule of PCV7 into this population has resulted in a marked and sustained reduction of IPD in children.     

Serotype distribution and antimicrobial susceptibility of <Emphasis Type="Italic"> Streptococcus pneumoniae </Emphasis>causing invasive infections and acute otitis media in children

A prospective study was conducted to determine the serotypes and antibiotic resistance patterns of pneumococcal isolates from children with invasive pneumococcal disease (IPD) and acute otitis media (AOM). From October 2001 to May 2002, 65 children with IPD (28 bacteraemic pneumonia, 24 bacteraemia without focus, 7 meningitis, 6 other infections) and 78 with AOM were identified. The most common serotypes causing IPD were 14 (32.3%), 6B (20.0%), 1 (18.5%) and 19F (7.7%) whereas the predominant serotypes causing AOM were 19F (35.9%), 14 (16.7%) and 23F (9.1%). Sixty-nine percent of IPD and 70.5% of AOM were caused by vaccine serotypes. The vaccine serotypes were more commonly encountered in meningitis cases and in children younger than 2 years of age. Intermediate resistance to penicillin was observed in 6 of 65 (9.2%) IPD isolates, one of which was intermediately resistant to cefotaxime (1.6%), whereas none exhibited high-level resistance to penicillin or other beta-lactam antibiotics. A higher proportion of antimicrobial resistance was noted in AOM isolates; 29 of 78 (37.4%) exhibited intermediate resistance and 8 (10.2%) high level resistance to penicillin, four of which had intermediate resistance to cefotaxime. Significant resistance was also noted to erythromycin; 38.5% of IPD and 48.7% of AOM isolates were resistant. Multidrug resistance was observed in one IPD and in eight AOM isolates. Conclusion:these findings have implications in the potential use of 7-valent conjugate vaccine in our region.Abbreviations AOM acute otitis media - IPD invasive pneumococcal disease - MIC minimal inhibitory concentration     

Current issues regarding the use of pneumococcal conjugate and polysaccharide vaccines in Australian children

OBJECTIVE: To present the results of child pneumococcal vaccination studies in the setting of current Australian disease epidemiology and immunization policy, and issues that clinicians should consider in discussions with families. METHODS: This paper includes a narrative review of randomized, controlled, double blind studies and systematic reviews which evaluated the efficacy of child pneumococcal vaccination. RESULTS: 7PCV is expected to prevent > 80% of childhood invasive pneumococcal disease (IPD, includes meningitis, septicaemia/bacteraemia) and the associated mortality. 7PCV may prevent 6% of all pneumonia, 18% of radiographically-defined pneumonia, 6% of all otitis media (OM) and 20%-40% of tympanostomy tube procedures. It may also reduce IPD due to antibiotic-resistant pneumococci, and prevent IPD in unvaccinated individuals. The impact of replacement disease caused by non-vaccine serotypes is not yet known. Pneumococcal polysaccharide vaccines given to 2-year-old children may prevent approximately 19% of all and 26% of recurrent OM. CONCLUSION: The Australian Standard Vaccination Schedule recommends universal infant immunization with seven-valent pneumococcal conjugate vaccine (7PCV). Universal infant 7PCV will prevent pneumococcal diseases and deaths. The potential for its impact to be reduced in the long-term by serotype replacement must be closely monitored. Information concerning disease epidemiology, vaccine efficacy and safety, disease risk perception and national costs may prove useful in discussions with families.     

儿童下呼吸道感染常见细菌病原分布及耐药现状

下呼吸道感染(LRTI)尤其肺炎,是主要的儿童杀手。在发展中国家儿童LRTI病原菌以细菌为主。肺炎链球菌是最重要的社区获得性LRTI细菌病原。随着7价肺炎链球菌结合疫苗的应用,非疫苗血清型菌株所致的侵袭性肺炎链球菌疾病增多,且对抗生素的耐药性增强。社区获得性耐甲氧西林金黄色葡萄球菌(CA-MRSA)和医院获得性耐甲氧西林金黄色葡萄球菌(HA-MRSA)有着不同的遗传背景,其耐药性也有明显差异。革兰阴性杆菌仍是医院获得性LRTI的重要病原菌。社区获得性LRTI与医院获得性LRTI常见细菌病原有区别,亦有重叠。了解儿童LRTI常见细菌病原的分布及耐药现状,对指导临床合理诊治至关重要。     

Impact of the pneumococcal conjugate vaccine on pneumococcal parapneumonic empyema

BACKGROUND: Pediatric pneumococcal parapneumonic empyema (PPE) has become increasingly common. In the last decade, Utah has had one of the highest rates of PPE in the United States, 14/100,000 children, attributed primarily to Streptococcus pneumoniae serotype 1. Our objective was to describe the temporal trends in PPE in Utah before and after the availability of the 7-valent pneumococcal conjugate vaccine (PCV-7). METHODS: The Intermountain Health Care (IHC) data warehouse was queried for all cases of empyema in children younger than 18 years, defined as International Classification of Diseases, 9th revision, Clinical Modification code 510.9, for the study period March 1996-June 2005. We also retrieved and serotyped all blood and pleural fluid isolates of S. pneumoniae from children younger than 18 years with a diagnosis of PPE at Primary Children's Medical Center (PCMC) between March 1996 and June 2005. The pre-PCV-7 period (PRE) included 57 months (March 1996-December 2000) and the post-PCV-7 period (POST) included 54 months (January 2001-June 2005). RESULTS: We identified 776 cases of pediatric empyema in the IHC system, and 478 (62%) were managed at PCMC. In the years 1996-2000, we managed a mean of 38 cases of empyema per year compared with 71.5 cases per year between 2001 and 2004 (P = 0.006). At PCMC, there were 295 cases of invasive pneumococcal disease (IPD), and 74 (25%) were PPE. During the PRE period, PPE represented 24 of 137 (17.5%) cases of IPD compared with 50 of 158 (32%) in the POST period (P = 0.008). One-half of the children with PPE required intensive care and 4 died. During the PRE and POST periods, PPE was most often caused by serotype 1 (46 and 34%, respectively), but in the POST period serogroups 3 (20%), and 19A (14%) were also prevalent. PPE in PCV-7-immunized children was caused exclusively by nonvaccine serotypes. CONCLUSIONS: PPE in the post-PCV-7 era is more common, representing one-third of the IPD in children in UT. PPE is associated with significant morbidity and mortality. Serotype 1 remains the most common cause of PPE, but serotypes 3 and 19A are emerging.     

Nasopharyngeal carriage of Streptococcus pneumoniae in healthy Turkish children after the addition of PCV7 to the national vaccine schedule

The aim of this study was to determine serotype distribution and investigate antimicrobial resistance patterns of Streptococcus pneumoniae in healthy Turkish children in the era of community-wide pneumococcal conjugate vaccine (PCV7). The study was conducted on 1,101 healthy children less than 18 years of age. Specimens were collected with nasopharyngeal swabs between April 2011 and June 2011. Penicillin and ceftriaxone susceptibilities were determined by E-test according to the 2008 Clinical Laboratory Standards Institute, and serotypes of the isolates were determined by Quellung reaction. The nasopharyngeal pneumococcal carriage rate was 21.9 % (241/1,101). Using the meningitis criteria of minimum inhibitory concentration values, 73 % of the isolates were resistant to penicillin and 47.7 % of them were resistant to ceftriaxone. Half of all pneumococcal isolates were serotyped as 19F (15.2 %), 6A (15.2 %), 23F (10.3 %), and 6B (9.3 %) and surprisingly, no serotype 19A was isolated. Serotype coverage rates of PCV7 and non-PCV7 were 46.2 and 53.8 %, respectively. The most common penicillin- and ceftriaxone-resistant serotypes were 6A, 6B, 14, 19F, and 23F. Penicillin- and ceftriaxone-resistant isolates were more prevalent in serotypes covered by PCV7 than the non-PCV7 serotypes. Conclusion: After the community-wide PCV7 vaccination, more non-PCV7 serotypes were isolated from the carriers compared to the time before PCV7 was used especially the serotype 6A, and the antimicrobial resistance of pneumococci was significantly increased.     

Increased antimicrobial resistance among nonvaccine serotypes of Streptococcus pneumoniae in the pediatric population after the introduction of 7-valent pneumococcal vaccine in the United States

BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the United States in February 2000. The PROTEKT US study evaluated serotype distribution, PCV7 coverage and antimicrobial susceptibility among Streptococcus pneumoniae isolates collected from children aged 0 to 14 years in 2000 through 2001 (year 1; n = 2033), 2002 through 2003 (year 3; n = 1740) and 2003 through 2004 (year 4; n = 1591). METHODS: Serotyping was performed by Neufeld Quellung reaction. Antimicrobial susceptibilities were determined centrally according to Clinical Laboratory Standards Institute methodology and interpretive breakpoints. RESULTS: The proportion of isolates covered by PCV7 (vaccine serotypes) decreased from 65.5% (year 1) to 34.7% (year 3) and to 27.0% (year 4) (P < 0.0001) with similar changes seen at regional and state levels. The most common serotypes in year 4 were nonvaccine serotypes (NVS) 19A (19.0% of all isolates), 6A (7.8%), 3 (7.6%), 15 (6.3%) and 35B (5.8%) and vaccine serotype 19F (12.7%). NVS 19A increased relative to vaccine serotype 19F among isolates expressing the erm(B) + mef(A) macrolide-resistant genotype (P < 0.0001) between year 1 (7.8% [19A] versus 86.7% [19F]) and year 4 (45.5% [19A] versus 51.7% [19F]). Antimicrobial resistance rates (year 1 versus year 4) among NVS from nonblood (respiratory tract) sources increased for penicillin (resistant: 12.7-16.1% [P = 0.0857]; intermediate susceptibility: 20.1-31.5% [P < 0.0001]), erythromycin (21.2-31.6% [P < 0.0001]), amoxicillin-clavulanate (1.4-5.8% [P < 0.0001]) and multidrug resistance (resistance to > or =2 antimicrobial classes) (24.6-31.6% [P = 0.0034]). CONCLUSIONS: The proportion of S. pneumoniae isolates from U.S. pediatric patients covered by PCV7 decreased substantially in the 4 years after vaccine introduction. However, resistance to commonly used antimicrobials, including beta-lactams and macrolides, as well as multidrug-resistant strains increased significantly among respiratory tract isolates of NVS.     

Elimination of racial differences in invasive pneumococcal disease in young children after introduction of the conjugate pneumococcal vaccine

BACKGROUND: Racial differences in the epidemiology of invasive pneumococcal disease (IPD) have been widely recognized, but the impact of conjugate pneumococcal vaccine (PCV) introduction in 2000 on these differences has not been extensively studied. METHODS: IPD episodes in 5 Tennessee counties from January 1995 through December 2002 were collected prospectively using the Centers for Disease Control and Prevention's Active Bacterial Core Surveillance system (ABCs). Trained nurses collected clinical data, and antibiotic susceptibility testing was performed on available isolates. RESULTS: Before vaccine licensure, IPD rates were highest in children younger than 2 years and in blacks. The disparity in IPD rates between blacks and whites younger than 2 years of age substantially diminished after PCV introduction. In 1999, the IPD rate in black children younger than 2 years was 340.2 per 100,000, representing 176.5 more events per 100,000 than in white children (P < 0.001). In 2002, this rate had decreased 83% to 57.4 per 100,000, similar to the rate in white children (39.6 per 100,000; P = 0.31). Before vaccine licensure, a higher percentage of isolates from whites were antibiotic-nonsusceptible. In 2002, the proportion of antibiotic-nonsusceptible pneumococcal isolates was similar in whites and blacks of all ages for the first time during the study period (P > 0.05 for separate comparisons of penicillin, cephalosporin and erythromycin nonsusceptibility). These changes occurred despite a lower PCV vaccination coverage in Tennessee in blacks than in whites (31.2% versus 47.6%). CONCLUSIONS: With conjugate pneumococcal vaccine introduction in Tennessee, racial differences in the incidence rates of IPD have largely been eliminated, particularly in young children.     

Clinical effectiveness of seven-valent pneumococcal conjugate vaccine (Prevenar) against invasive pneumococcal diseases: prospects for children in France]

A seven-valent pneumococcal polysaccharide-CRM197 carrier protein conjugate vaccine (PNC7V; Prevenar, Wyeth, Paris) targets the serotypes (belonging to serogroups 14, 6, 19, 18, 23, 9, and 4) most often responsible for invasive pneumococcal disease (IPD) among children. A randomized, controlled, double-masked study among 37,868 children in northern California (Northern California Kaiser Permanente, USA) provided a per protocol vaccine efficacy value of 97.7% against invasive pediatric IPD due to the vaccine serotypes. The PNC7V vaccine was registered by the European Agency for the Evaluation of Medicinal Products (EMEA) in October 2000; a favorable "Community Marketing Decision" under the Centralized Procedure was granted in February 2001. PNC7V was recommended for most infants by the Conseil Supérieur d'Hygiène Publique de France in March 2002, on the advice of the Comité Technique des Vaccinations, as S. pneumoniae in children less than 2 years of age is the primary cause of bacterial meningitis and of mortality associated with community-acquired bacterial infections. The theoretical coverage of the vaccine towards pneumococcal invasive disease in France is about 80%, which represents one of the best serotype coverage estimates in Europe, and vaccines serotypes account for 90% of penicillin-nonsusceptible strains. Distinctive characteristics in France in terms of epidemiology, life style, and therapeutic attitudes justify a precise follow up of the consequences of the vaccination on a national level during the coming years. Hence, surveillance programs have been established: (i) to ascertain the future impact of large-scale PNC7V vaccination on invasive pneumococcal disease incidence, (ii) to follow the evolution of carriage and ecology of the pneumococcus, and (iii) to establish an active "vaccinovigilance".     

Nonvaccine Streptococcus pneumoniae serotypes causing acute bacterial meningitis

The pneumococcal heptavalent conjugate vaccine protects children aged less than 2 years old from invasive pneumococcal disease (IPD). Efficacy is 89-93% in the US population and 71-86% in European studies. The vaccine confers active immunization against the main serotypes causing IPD (4, 6B, 9V, 14, 18C, 19F y 23F). We describe 2 children who presented with pneumococcal meningitis caused by nonvaccine serotypes. As a result of the widespread use of the heptavalent vaccine, there may be a shift in the serotypes causing IPD.     

PneumococcaL meningitis in french children before and after the introduction of pneumococcal conjugate vaccine

In France, despite a high rate of pneumococcal conjugate vaccine coverage, the number of cases of pneumococcal meningitis in children did not decline signi?cantly between 2001–2002 (n = 264) and 2007–2008 (n = 244). A decline was observed among children < 2 years old (185 [70.1%] to 134 [54.9%] cases; P = 0.0004), but was counterbalanced by an increase among children ≥ 2 years old (79 [29.9%] to 110 [45.1%] cases). Mean age increased signi?cantly, from 2.3 (median 0.8) to 3.8 (median 1.5) years. After pneumococcal conjugate vaccine 7 implementation, a wide diversity of serotypes implicated in pneumococcalmeningitis was observed; serotypes 19A and 7F were the most frequent.     

Impact of pneumococcal conjugate vaccine and the severity of winter influenza-like illnesses on invasive pneumococcal infections in children and adults

BACKGROUND: Pneumococcal conjugate vaccine (PCV7), recommended in July 2000 for routine use in infants, has resulted in a reduction in the rate of invasive pneumococcal disease (IPD) in young children. We studied the impact of PCV7 and the possible contribution of the severity of influenza-like respiratory infection season on the rate of IPD on children and adults. METHODS: In 7 hospitals of a health system, episodes of IPD were identified by the microbiology laboratories during the 2-year period before July 2000 and the 4-year period after July 2000 during routine use of PCV7, and patient records were reviewed. Episodes of influenza-like illnesses during each winter in a local county were prospectively measured by reports from all acute care hospitals and episodes of absenteeism resulting from influenza-like illnesses from all schools. RESULTS: There were 720 patients with blood and/or cerebrospinal fluid isolates of Streptococcus pneumoniae. There were significant reductions in cases of IPD in children younger than 2 years, 68% reduction; children 2-4 years of age, 70%; adults 18-49 years of age, 42%; and adults older than 64 years, 30%. Annually, during the PCV7 period, there were significantly fewer episodes of influenza-like illnesses than during the pre-PCV7 years. CONCLUSIONS: PCV7 efficacy and resultant herd-type immunity resulted in a reduction in the rate of IPD not only in young children but also in young and elderly adults. Milder winter respiratory viral seasons may possibly have contributed to the observed reduction in the rate of IPD.     

Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy.

AIMS: To ascertain whether the reduction in nasopharyngeal carriage of vaccine serotypes induced by pneumococcal conjugate vaccine (PnCV) administered to infants persists beyond the age of 2 years. METHODS: Non-randomised, unblinded controlled study of 2-5 year old children who had received three doses of heptavalent PnCV (7VPnCV) in infancy and 23-valent pneumococcal polysaccharide vaccine at 13 months, and unimmunised controls. Nasopharyngeal swabs were taken in summer (150 vaccinated subjects, 126 controls) and winter (143 vaccinated subjects, 188 controls). The swabs were cultured and serotyped for Streptococcus pneumoniae. RESULTS: Carriage rates (vaccinated subjects: 24.7% and 43.4%; controls: 27.0% and 41.0%, in summer and winter respectively) and carriage of vaccine serotypes (subjects: 10.0% and 30.0%; controls: 13.5% and 31.5%, in summer and winter respectively) were similar in the two groups. CONCLUSIONS: Effects of vaccination in infancy on rates of nasal carriage of pneumococcus and serotype replacement in children living in a largely unvaccinated population are no longer evident by 2-5 years of age.