Epidemiological and molecular characterization of invasive Streptococcus pneumoniae isolated following introduction of 7-valent conjugate vaccine in Kinki region, Japan, 2008-2013.

Streptococcus pneumoniae is one of the most common bacteria causing community-acquired pneumonia and meningitis. The use of 7-valent pneumococcal conjugate vaccine (PCV7) has reduced the incidence of pneumococcal disease while changing pneumococcal population through herd immunity and non-vaccine pneumococci replacement. This study investigated molecular epidemiologic characteristics of pneumococcal strains in the Kinki region of Japan from 2008 to 2013. A total of 159 invasive pneumococcal isolates were characterized by serotyping, antibiotic susceptibility testing, PCR analysis of penicillin-binding protein genes, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). In adult populations, pediatric PCV7 introduction decreased isolates expressing PCV7 serotypes via herd immunity and increased isolates expressing non-PCV7 serotypes. The rate of penicillin resistance and isolates with alterations in all three pbp genes was higher in PCV7 type isolates than in non-PCV7 type isolates. In MLST analysis, all of serotype 19F isolates were of the same sequence type, ST236, which is the antimicrobial-resistant clone Taiwan19F-14, and the majority of serotypes 23F and 19A isolates were of ST1437 and ST3111 respectively, which are the predominant clones of antimicrobial-resistant pneumococci in Japan. In PFGE profiles, serotype 6B-ST2224, serotype 19F-ST236, serotype 19A-ST3111, and serotype 23F-ST1437 formed six separate clusters composed of genetically identical strains, and genetically identical serotype 22F-ST433 formed two different clusters between the pre- and post-PCV7 period. The results of molecular analysis suggest the spread and persistence of these identical antimicrobial resistant clones in the Kinki region and genetic changes of epidemic clone serotype 22F-ST433 before and after pediatric PCV7 introduction.

Application of pharmacokinetic/pharmacodynamic analysis to evaluate the adequacy of antimicrobial therapy for pediatric acute otitis media in Spain before and after the introduction of the PCV7 vaccine.

OBJECTIVE: To evaluate, by applying pharmacokinetic/pharmacodynamic (PK/PD) analysis, if the change in antibiotic susceptibility after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Spain had any influence on the usefulness of the antimicrobials more frequently used as empirical treatment of pediatric acute otitis media (AOM). METHODS: PK parameters and susceptibility of Streptococcus pneumoniae and Haemophilus influenzae were obtained from bibliography. Monte Carlo simulation was used to estimate the cumulative fraction of response (CFR), understood as the expected probability of therapy success. For amoxicillin and amoxicillin/clavulanate, the target was free antibiotic concentration remaining above the minimum inhibitory concentration (MIC) for ≥50% of the dosing interval (fT>MIC≥50%), whereas for cefuroxime axetil and cefotaxime, the target was fT>MIC≥60%. CFR values ≥90% were considered successful. RESULTS: When all serotypes of S. pneumoniae are considered, amoxicillin and cefotaxime turned out to reach a high probability of success, and difference before and after vaccination was scarce. For H. influenzae, CFR values were higher with amoxicillin/clavulanate than with amoxicillin. For both microorganisms, cefuroxime axetil resulted in low probability of success in the two periods of study. CONCLUSIONS: We have shown that the introduction of the PCV7 vaccination did not lead to changes in the probability of success of the current empiric treatments of the AOM. Integrated PK/PD analysis has demonstrated to be a useful tool to identify changes in antimicrobial activity after the implantation of a vaccination program, providing complementary information to the simple assessment of MIC values.

Predominance of Serogroup 19 CC320/271 among Penicillin-Nonsusceptible Streptococcus pneumoniae Isolates after Introduction of the PCV7 Vaccine in Several Regions of Japan.

Multidrug-resistant Streptococcus pneumoniae serogroup 19, including serotypes 19A and 19F, associated with clonal complex 320/271 (CC320/271), has been previously shown to be predominant in many countries after introduction of a 7-valent pneumococcal conjugate vaccine (PCV7). However, in Japan there has been no epidemiological research focused on penicillin-nonsusceptible isolates after this event. Therefore, we aimed to characterize penicillin-nonsusceptible S. pneumoniae (PNSSP; penicillin minimum inhibitory concentration [MIC] ≥ 4.0 µg/ml) after the introduction of PCV7 in Japan. Throughout Japan, we collected 1,057 pneumococcal isolates from 2010 to 2014. We then evaluated MICs and performed serotyping, multilocus sequence typing, and sequencing of penicillin-binding protein genes in 51 isolates (penicillin MIC ≥ 2.0 µg/ml). Twenty-three isolates (2.2%) showed penicillin nonsusceptibility (penicillin MIC ≥ 4.0 µg/ml). Serotypes 19F (14 isolates, 60.9%) and 23F (4 isolates, 17.4%), which are covered by the vaccine, were predominant among PNSSP strains. Only 3 isolates belonged to nonvaccine serotype 19A. Among the PNSSP isolates, CC320/271 (16/23 strains, 69.6%) was the most prevalent clone. Moreover, CC320/271 clones showed high MIC values of a third-generation cephalosporin. Thus, we demonstrated clonal predominance of serogroup 19 CC320/271 with strong resistance to ß-lactams including a third-generation cephalosporin among PNSSP isolates.

Serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae strains isolated in Japan after introduction of the routine immunization program.

Pneumococcal vaccines have reduced the incidences of Streptococcus pneumoniae infections among children and adults, but a relative increase in the prevalence of non-vaccine serotypes has been reported. To follow the changing epidemiology of pneumococcal diseases, capsular serotyping and antimicrobial susceptibility testing was performed on 534 pneumococcal isolates obtained from a hospital in Japan after routine immunization was launched, between October 2014 and May 2016. Serotype distributions and antimicrobial susceptibilities were evaluated among the total patient population, and were compared by age and sample groups and by serotype group, respectively. Serotypes targeted by the 13-valent pneumococcal conjugate vaccine (PCV13) were identified in 14.6%, 44.5%, and 40.2% of the samples from the <5, 5-64, and ≥65 year age groups, respectively. The 23-valent pneumococcal polysaccharide vaccine serotypes (PPSV23) were identified in 42.4%, 68.2%, and 63.1% of the samples, respectively; whereas non-PCV13 serotypes or non-PPSV serotypes (NVT) comprised 46.8% of all isolates. Among NVT, strain 35B was the most frequently isolated, followed by 15A, particularly in sputum samples collected from children <5 years old. Meanwhile, serotype 3, which is targeted by the PCV13 and PPSV23, was the most prevalent among patients aged ≥65 and 5-64 years. Antimicrobial susceptibility testing revealed that 88.9% and 81.0% of serotype 35B was non-susceptible to penicillin and meropenem, respectively, and 89.4% of 15A was non-susceptible to penicillin. Our data suggest rapid effects of pneumococcal vaccines and progression of serotype replacement. Besides invasive potential, the increased prevalence of non-vaccine serotypes with highly non-susceptible to penicillin was a concern. Continuous monitoring of pneumococcal serotypes and antimicrobial susceptibility is necessary for developing optimal preventive strategies.

Emergence of antibiotic-resistant non-vaccine serotype pneumococci in nasopharyngeal carriage in children after the use of extended-valency pneumococcal conjugate vaccines in Korea.

BACKGROUND: This study was performed to assess the serotype distribution and antibiotic nonsusceptibility of pneumococcal carriage isolates from children in Korea following the introduction of extended-valency pneumococcal conjugate vaccines (PCVs). METHODS: From April to June 2014, nasopharyngeal swabs were collected from children who were attending daycare centers in Korea. The collection was conducted in accordance with the World Health Organization Pneumococcal Carriage Working Group standards. Isolates were identified based on colony morphology, the presence of alpha-hemolysis, and inhibition by optochin test. Serotype was determined by Quellung reaction and sequencing analysis (for serogroup 6). The E-test was performed to determine antibiotic susceptibility. RESULTS: A total of 267 pneumococcal isolates were collected from 734 children. Non-PCV13 serotypes accounted for 88.3% and 23A (12.6%), 15B (10.4%), and 15C (9.5%) were most common. Younger age was associated with higher carriage (65.6% vs. 31.2%, P<0.001), while completion of PCV vaccination was associated with lower carriage caused by PCV13 serotypes (7.4% vs. 20.8%, P=0.007). Overall, nonsusceptibility rates were 86.0% to penicillin and 90.5% to erythromycin, with a multidrug resistance rate of 81.5%. Among penicillin-nonsusceptible isolates, those caused by PCV13 serotypes were 11% and non-PCV13 serotypes were 89%. Frequent non-PCV13 serotypes (23A, 15B, and 15C) were all nonsusceptible to both penicillin and erythromycin except one. CONCLUSION: High rates of carriage caused by non-PCV13 serotypes such as 23A, 15B, and 15C that show nonsusceptibilities to penicillin and erythromycin were noted following the introduction of extended-valency PCVs in Korea.

The impact of a pneumococcal conjugate vaccination program on the nasopharyngeal carriage, serotype distribution and antimicrobial resistance of Streptococcus pneumoniae among healthy children in Turkey.

BACKGROUND: The 7-valent conjugate pneumococcal vaccine (PCV7) was introduced by the Turkey National Immunization Program in 2008 and replaced by the PCV13 in 2011. We assessed the impact of PCV vaccination on the nasopharyngeal (NP) carriage, serotype distribution and antimicrobial resistance of Streptococcus pneumoniae (SP) among healthy Turkish children. METHODS: A prospective surveillance study was performed between September 2011 and September 2013 in Istanbul, Turkey. NP swabs, demographic data, and vaccination statuses were obtained from 2165 healthy children aged 0-18years. Pneumococcal carriage was defined by a positive culture; serotyping was performed via multiplex conventional PCR, and the antibiotic susceptibilities of the isolates were determined based on the minimum inhibitory concentration (MIC) values of the Clinical Laboratory Standards Institute (CLSI). RESULTS: The prevalence of pneumococcal carriage was 6.4%. The carriage rates were 8%, 7%, and 5% in the following age groups: 0-24months, 25-60months, and >60months, respectively. The carriage rate was significantly higher in the 0-24month age group than in the >60months age group (p=0.03). Sixty percent of the children were not vaccinated with any PCV; 4%, 2%, and 4% received at least 1, 2 or 3 doses and 30% children received the full schedule (4 doses) of either PCV7 or PCV13. Among the isolated S. pneumoniae strains, 45% were of the non-vaccine type (NVT) and 55% were of the vaccine type (VT). The children who received at least a single PCV dose had significantly lower odds of colonization via VT serotypes than the non-vaccinated children [odds ratio: 0.61 (95% confidence interval=0.41-0.91), p=0.01]. The percentages of the serotypes covered by PCV7 and PCV13 were 51% and 56%, respectively. The most frequently isolated serotypes were 6A/B/C (n=22, 16.5%), 19F (n=18, 13.5%), 23F (n=15, 11.2%), serotype 9V/A (n=10, 7.5%), 12F (n=5, 4.5%), 15A/F (n=7, 4.5%) and 22 A/F (n=6, 4.5%). Using the meningitis criteria and the MIC, 62% of the isolates were resistant to penicillin and 13% were non-sensitive to ceftriaxone. Erythromycin and clindamycin resistance were 43% and 31%, respectively. CONCLUSION: We shown that following nation-wide PCV vaccination, S. pneumoniae NP carriage was decreased.

The impact of private use of PCV7 in 2009 and 2010 on serotypes and antimicrobial resistance of Streptococcus pneumoniae carried by young children in Portugal: Comparison with data obtained since 1996 generating a 15-year study prior to PCV13 introduction.

In Portugal, the 7-valent pneumococcal conjugate vaccine (PCV7) was not introduced in the national immunization plan but was commercially available between 2001 and 2010. We studied serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae carried by children in 2009 and 2010. Vaccination with PCV7 was extracted from children's immunization bulletins and information on recent antimicrobial consumption was obtained through a questionnaire. For comparison, we included data from previous studies conducted since 1996: 1996-1999, 2001-2003, 2006-2007. Pneumococci were isolated from nasopharyngeal samples of 1092 children up to six years old attending day-care in an urban area. Among these, 76% (819/1070) were vaccinated and 62% (677/1092) carried pneumococci. In 2009-2010, serotype replacement was extensive. Carriage of PCV7 serotypes was 4.9% and 5.8%, in 2009 and 2010, respectively, with the majority being of serotype 19F (carried by 4.3% and 4.6% of all participants, respectively). Colonization by serotype 19F was associated with vaccine status (7.7% (19/248) of non-vaccinees vs. 3.5% (29/818) of PCV7-vaccinees, p=0.010). Carriage of serotype 19A was high in 2009 and 2010 (8.6% of all participants) consistent with values already observed in 2007; carriage of serotype 6A was <1% (10/1092), indicating a major decline after 2007 (5.8% or 31/538, p<0.001). Non-vaccine serotypes increased and serotype 6C became the most frequently carried serotype in 2010 (11.2% (54/481)). High-level resistance to penicillin (MIC ≥2mg/L) showed a decreasing trend (p<0.001), whereas resistance to both penicillin and erythromycin increased (p<0.001) and was detected in 15-20% of all isolates in 2009-2010, most of which were non-vaccine serotypes. Antimicrobial use decreased over time (p<0.001). In conclusion, widespread private use of PCV7 has impacted on colonization leading to near elimination of all PCV7 serotypes except for serotype 19F. Antimicrobial consumption declined but it may be too soon to observe generalized changes in antimicrobial resistance rates.

Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden.

The effects of pneumococcal conjugated vaccines (PCVs) need to be investigated. In Stockholm County, Sweden, PCV7 was introduced in the childhood immunisation programme in 2007 and changed to PCV13 in 2010.Over 90% of all invasive isolates during 2005-2014 (n=2336) and carriage isolates, 260 before and 647 after vaccine introduction, were characterised by serotyping, molecular typing and antibiotic susceptibility, and serotype diversity was calculated. Clinical information was collected for children and adults with invasive pneumococcal disease (IPD).The IPD incidence decreased post-PCV7, but not post-PCV13, in vaccinated children. Beneficial herd effects were seen in older children and adults, but not in the elderly. The herd protection was more pronounced post-PCV7 than post-PCV13. PCV7 serotypes decreased. IPD caused by PCV13 serotypes 3 and 19A increased post-PCV7. Post-PCV13, serotypes 6A and 19A, but not serotype 3, decreased. The serotype distribution changed in carriage and IPD to nonvaccine types, also in nonvaccinated populations. Expansion of non-PCV13 serotypes was largest following PCV13 introduction. Serotype diversity increased and nonvaccine clones emerged, such as CC433 (serotype 22F) in IPD and CC62 (serotype 11A) in carriage. In young children, meningitis, septicaemia and severe rhinosinusitis, but not bacteraemic pneumonia, decreased.Pneumococcal vaccination leads to expansion of new or minor serotypes/clones, also in nonvaccinated populations.

Impact of Pneumococcal Conjugate Universal Routine Vaccination on Pneumococcal Disease in Italian Children.

In Italy, the effectiveness of pneumococcal universal vaccination in preventing vaccine-type invasive pneumococcal disease (IPD) in the PCV7/PCV13 shifting period was estimated to be 84.3% (95% CI: 84.0-84.6%) in children <5 years. This study aims at corroborating the estimation of both the effectiveness (VE) of PCVs and its impact in reducing pneumococcal diseases. A 1:3 matched-case-control study was conducted among children <5 years old hospitalized for IPD or pneumococcal pneumonia (PP) between 2006 and 2012 in the Puglia region. Moreover, hospitalizations for pneumococcal outcomes in the pre- and postvaccination period and the hospitalization risk ratios (HRRs) with 95% CIs were computed in Italy and in the first eight regions that introduced PCVs in 2006. The overall effectiveness of PCVs was 75% (95% CI: 61%-84%); it was 69% (95% CI: 30%-88%) against IPD and 77% (95% CI: 61%-87%) against PP. PCVs showed a significant impact on IPD and acute otitis media either at a national level or in those regions with a longer vaccination history, with a nearly 40% reduction of hospitalizations for both outcomes. Our findings provide further evidence of the effectiveness of PCVs against pneumococcal diseases and its impact on nasopharyngeal carriage in children <5 years, indicating the importance of maintaining high immunization coverage.

Response on Pneumococcal Vaccine in Preterm Infants After Neutral and Acidic Oligosaccharides Supplementation.

BACKGROUND: Supplementation of oligosaccharides in premature infants was shown to influence the immune system. We determined the effect of combined short-chain galacto-oligosaccharides (scGOS), long-chain fructo-oligosaccharides (lcFOS) and pectin-derived acidic oligosaccharides (pAOS) on antibody concentrations after pneumococcal conjugate vaccination in very preterm infants. METHODS: Very preterm infants with gestational age <32 weeks and/or birth weight <1500 g were randomized to receive enteral supplementation with scGOS/lcFOS/pAOS or placebo between days 3 and 30 of life. Blood samples were collected at birth, 5 and 12 months of age and compared with term samples from a Dutch cross-sectional population-based serosurveillance study. IgG antibody levels to pneumococcal capsular polysaccharides were determined by multiplex immunoassay. RESULTS: In total, 113 preterm infants were included with similar baseline and nutritional characteristics in both groups. After 3 primary pneumococcal vaccinations, the scGOS/lcFOS/pAOS-group had lower GMC antibody concentrations (µg/mL; serotype 4: 1.53, 6B:0.25, 9V: 1.19, 14: 2.39, 18C: 1.88, 19F: 7.42, 23F: 0.72) than the placebo group (serotype 4: 3.29, 6B: 0.79, 9V:2.64, 14: 4.52, 18C: 3.13, 19F: 14.64, 23F: 1.88; all P < 0.05), but comparable with those in the term control group (serotype 4: 0.97, 6B: 0.32, 9V: 1.67, 14: 3.24, 18C: 2.03, 19F: 5.06, 23F: 0.59; all P > 0.05). After the booster vaccination at 11 months, antibody levels were no longer different between the two preterm groups. CONCLUSION: Enteral supplementation of scGOS/lcFOS/pAOS has a regulatory effect on the response to conjugated polysaccharide pneumococcal vaccine with normalization of the enhanced responses in preterm infants toward levels similar to healthy term infants.

Pediatric invasive pneumococcal disease in Taiwan following a national catch-up program with the 13-valent pneumococcal conjugate vaccine.

BACKGROUND: Seven-valent pneumococcal conjugate vaccine (PCV) has been available in Taiwan since late 2005. A national catch-up program was launched in Taiwan in 2013, providing 1 dose of 13-valent PCV to children aged 2-5 years. Here, we report the epidemiology of invasive pneumococcal disease (IPD) in children aged ≤5 years in this setting. METHODS: We collected demographic and clinical information for pediatric patients (≤5 years) with IPD between 2008 and 2013. The incidence of IPD was estimated. The logs for PCV import into Taiwan were obtained to evaluate the impact of PCV usage on IPD epidemiology. RESULTS: The overall incidence of IPD in children aged ≤5 years was 15.9 cases per 100,000 person-years. The IPD incidence caused by 7-valent PCV serotypes decreased significantly from 10.0 cases per 100,000 person-years in 2008 to 2.3 cases per 100,000 person-years in 2013. The incidence of IPD caused by serotype 19A increased substantially from 1.7 cases per 100,000 person-years in 2008 to 10.3 cases per 100,000 person-years in 2012, followed by a significant decrease to 5.6 cases per 100,000 person-years in 2013. The significant decrease in the incidence of serotype 19A IPD occurred primarily in children aged 2-5 years. CONCLUSIONS: The 13-valent PCV catch-up program was associated with a significant decrease in serotype 19A IPD incidence in 2013, primarily in children eligible for the 13-valent PCV immunization. Continued surveillance is necessary to assess the further impact of the national catch-up program on pediatric IPD epidemiology in Taiwan.

Medical prevention of recurrent acute otitis media: an updated overview.

Acute otitis media (AOM) is one of the most common pediatric diseases; almost all children experience at least one episode, and a third have two or more episodes in the first three years of life. The disease burden of AOM has important medical, social and economic effects. AOM requires considerable financial assistance due to needing at least one doctor visit and a prescription for antipyretics and/or antibiotics. AOM is also associated with high indirect costs, which are mostly related to lost days of work for one parent. Moreover, due to its acute symptoms and frequent recurrences, AOM considerably impacts both the child and family's quality of life. AOM prevention, particularly recurrent AOM (rAOM), is a primary goal of pediatric practice. In this paper, we review current evidence regarding the efficacy of medical treatments and vaccines for preventing rAOM and suggest the best approaches for AOM-prone children.

Microbiology of bacteria causing recurrent acute otitis media (AOM) and AOM treatment failure in young children in Spain: shifting pathogens in the post-pneumococcal conjugate vaccination era.

OBJECTIVE: To prospectively identify the bacterial aetiology and antimicrobial susceptibility of problematic (recurrent and treatment failure) acute otitis media in Spanish children several years after the introduction of 7-valent pneumococcal conjugate vaccine. METHODS: Tympanocentesis or careful sampling of spontaneous otorrhoea was performed on children aged 3 to <36 months with recurrent acute otitis media, acute otitis media treatment failure or unresolved acute otitis media. RESULTS: 105 acute otitis media episodes (77 sampled by tympanocentesis, 28 otorrhoea samples) were evaluated: 46 recurrent, 35 treatment failures, 24 unresolved acute otitis media. 74 episodes (70.4%) had at least one bacterium identified on culture: Streptococcus pneumoniae was identified in 21 episodes, Haemophilus influenzae (all non-typeable) in 44, Streptococcus pyogenes in 2, Moraxella catarrhalis in 2. No statistically significant difference in bacterial aetiology by episode type was detected. Non-typeable H. influenzae was the most commonly isolated pathogen in all acute otitis media types and in all age sub-groups. Forty percent of S. pneumoniae isolates were multi-drug resistant. Pneumococcal serotype 19A was the most frequently identified serotype (7/21 episodes). Multi-drug resistance was found in 56% of 19A isolates. Of non-typeable H. influenzae isolates, 15% were ampicillin resistant and 13% were amoxicillin/clavulanate resistant. S. pneumoniae and non-typeable H. influenzae DNA were each detected in 57% of samples culture negative for these pathogens, including 12 co-infections. CONCLUSION: Combining culture and polymerase chain reaction results, H. influenzae and S. pneumoniae may be implicated in 70% and 43% of clinically problematic bacterial acute otitis media episodes, respectively. The impact of new vaccines to prevent both S. pneumoniae and non-typeable H. influenzae acute otitis media may be substantial in this population and is worth investigating.

Changes in Streptococcus pneumoniae serotype distribution in invasive disease and nasopharyngeal carriage after the heptavalent pneumococcal conjugate vaccine introduction in Bogotá, Colombia.

BACKGROUND: In Bogotá, the Heptavalent Conjugate Vaccine (PCV7) was introduced into childhood immunization schedule since 2009. The aim of this study was to assess the changes in serotype distribution and penicillin susceptibility of Streptococcus pneumoniae isolates recovered from nasopharyngeal samples and invasive disease among children living in Bogotá, before and after PCV7 introduction. METHODS: Nasopharyngeal swabs were collected from healthy children aged between 12 and 18 months of age before (years 2005-2006) and after (2011) PCV7 introduction. Identification of S. pneumoniae was performed by multiplex PCR. Serotype was determined by PCR and Quellung reaction. Susceptibility to penicillin, ceftriaxone, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline and erythromycin was evaluated. In addition, distribution of serotypes and antimicrobial susceptibility before and after vaccine introduction among invasive isolates recovered from children ≤2 years old living in Bogotá was analyzed. RESULTS: Prevalence of pneumococcal nasopharyngeal carriage declined from 55.7% (137/246) in unvaccinated to 44.2% (87/197) (p=0.01) in vaccinated children. The proportion of children carrying PCV7 serotypes decreased from 23.6% (58/246) to 7.6% (15/197) (p<0.001). The decrease was counterbalanced by an increase in the proportion of non-PCV7 serotypes. The most prevalent among emerging serotypes were 15A, 15B, 15C, 11A and 35B. Among IPD isolates, PCV7 serotypes decreased from 69.1% (235/340) in 2005/2009 to 38.0% (32/84) in 2010/2011 (p<0.001). The increase of non-PCV7 serotypes was significant. Resistance to penicillin among invasive isolates recovered from meningitis decreased from 41.1% (30/73) in the pre-vaccine period to 14.2% (2/14) in post-vaccine period (p=0.02). CONCLUSIONS: A decrease in the prevalence of pneumococcal nasopharyngeal carriage following the introduction of PCV7 vaccine, have been overshadowed by an important surge in the prevalence of non-PCV7 serotypes. Systematic surveillance combining nasopharyngeal carriage surveys and IPD detection could help in evaluating the impact of conjugate vaccines.

Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model.

The incidence of invasive pneumococcal disease (IPD), caused by the approximately 91 serotypes of Streptococcus pneumoniae (PN), varies geographically and temporally as a result of changing epidemiology and vaccination patterns as well as due to regional measurement differences. Prevnar(®) (Pfizer), the first licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS) from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein, CRM197. In the United States and elsewhere, this vaccine has been highly efficacious in reducing the incidence of IPD caused by vaccine serotypes, however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has increased, resulting in the need for vaccines with higher valencies. In response, 10- and 13-valent PCVs have recently been licensed. To further increase serotype coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and formulated on aluminum phosphate adjuvant. Vaccine immunogenicity was evaluated in infant rhesus monkeys since they, like human infants, respond poorly to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three times with PCV-15 or Prevnar(®) at 2 month intervals, and serotype-specific IgG antibodies were measured using a multiarray electrochemiluminescence (ECL) assay. The results indicate that antibody responses to PCV-15 and Prevnar(®) were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were >10-fold higher than baseline for the 8 additional serotypes.

[Cost-effectiveness analysis of pneumococcal vaccination in Spain]. / Análisis de coste-efectividad de la vacunación antineumocócica en España.

OBJECTIVE: To perform a cost-effectiveness analysis of pediatric pneumococcal vaccination in Spain. METHODS: A deterministic population-based model in the form of a decision-tree with a 1-year time horizon was used to estimate the impact of vaccination with Synflorix® or Prevenar13® in children aged less than 2 years in Spain from the perspective of the National Health System. Epidemiological data were obtained from the hospital discharge minimum data set (MDS) and the literature. Data on costs were obtained from national health costs databases. The main outcomes measured were the number of cases avoided of invasive pneumococcal disease, acute otitis media (AOM) and myringotomies, and hospital admissions for pneumonia. All costs were expressed in 2010 euros. Effectiveness was measured as the number of quality-adjusted life years (QALYs) gained. RESULTS: The efficacy of Synflorix® in preventing episodes of AOM caused by non-typeable Haemophilus influenzae could lead to additional prevention of 41,513 episodes of AOM, 36,324 antibiotic prescriptions and 382 myringotomy procedures and 143 QALYs gained compared with Prevenar13®. The total vaccination cost with Synflorix® would result in savings of 22 million euros. CONCLUSIONS: Pneumococcal vaccination with Synflorix® in comparison with Prevenar13® in children aged less than 2 years old in Spain could achieve a higher number of QALYs and a substantial cost offset. Vaccination with Synflorix® would be a dominant strategy in terms of cost-effectiveness.

The cost-burden of paediatric pneumococcal disease in Sweden and the potential cost-effectiveness of prevention using 7-valent pneumococcal vaccine.

AIMS: A cost-effectiveness model was used to estimate the change in disease burden that might be expected if PCV7 was included as part of the routine 3-dose vaccination schedule in Sweden. METHODS: An economic model was populated with data from the main clinical PCV7 efficacy trials, demographic data from government sources, surveillance and epidemiologic data from the US and Nordic region, and average treatment costs, considering the impact of disease on the whole national population. RESULTS: The model estimated that PCV7 would prevent 18,856 cases of AOM, 684 of pneumonia, 86 of pneumococcal bacteraemia and 21 cases of pneumococcal meningitis in children <10 years, further 221 cases of IPD would be avoided in older children and adults and 397 cases of pneumonia in adults aged 18-39 years. Annually, 4 childhood (<10 years) deaths and 39 deaths in older children and adults would be prevented, resulting in an annual saving of 632 life years. The reduction of cost for the society was estimated to 27.9 (-205, +160) million SEK. The sensitivity analysis showed that it was most sensitive to the efficacy of the vaccine against AOM, the cost of managing infections and the incidence of all disease. CONCLUSION: This model demonstrates that implementing a universal vaccine programme in Sweden with PCV7 would be cost-effective with an estimated net reduction of costs for the society.

Immunisation coverage in Australian Indigenous children: Time to move the goal posts.

Childhood immunisation coverage reported at 12 to <15 months and 2 years of age, may mask deficiencies in the timeliness of vaccines designed to protect against diseases in infancy. This study aimed to evaluate immunisation timeliness in Indigenous infants in the Northern Territory, Australia. Coverage was analysed at the date children turned 7, 13 and 18 months of age. By 7 months of age, 45.2% of children had completed the recommended schedule, increasing to 49.5% and 81.2% at 13 and 18 months of age, respectively. Immunisation performance benchmarks must focus on improving the timeliness in these children in the first year of life.

Has the licensing of respiratory quinolones for adults and the 7-valent pneumococcal conjugate vaccine (PCV-7) for children had herd effects with respect to antimicrobial non-susceptibility in invasive Streptococcus pneumoniae?

OBJECTIVES: The aim of the study was to analyse the evolution of antibiotic non-susceptibility in Spanish invasive Streptococcus pneumoniae after licensure of respiratory-quinolones for adults and 7-valent pneumococcal conjugate vaccine (PCV-7) for immunization of children. METHODS: All invasive pneumococci received in the Reference Laboratory (January 2000-August 2007; n = 12 957 isolates) were serotyped, and susceptibility to penicillin/erythromycin/levofloxacin was determined. Antibiotic consumption and PCV-7 doses/year were provided by IMS and the manufacturer, respectively. RESULTS: In 2000-07, PCV-7 distribution (doses/1000 inhabitants