Pneumococcal serogroups and serotypes in severe pneumococcal pneumonia in Belgian children: theoretical coverage of the 7-valent and 9-valent pneumococcal conjugate vaccines

BACKGROUND: Although the causative pneumococcal serotypes of invasive diseases are already extensively studied, few data are available about the pneumococcal serotypes additionally isolated from broncho-alveolar lavage samples in childhood pneumonia. STUDY AIM: To identify the causative pneumococcal serotypes in culture proven childhood community acquired pneumonia (CAP) and to calculate the effectiveness of the heptavalent and nonavalent pneumococcal vaccine (7- and 9-valent PnV) in severe pneumococcal pneumonia. METHODS: All pneumococcal isolates stored from broncho-alveolar lavage, blood culture and pleural fluid in healthy children with CAP were characterized. RESULTS: Seventy children (median age 2 years 3.5 months) could be included. The most prevalent serotypes were: SGT1 (21.4%), SGT6 (20.0%), SGT19 (12.8%), SGT23 (10.0%), and SGT14 (7.1%). SGT1 was especially prevalent in complicated cases and children >5 years. This first ranking of SGT1 is not reported in invasive pneumococcal disease studies. The overall theoretical coverage of the 7-valent PnV and the 9-valent PnV for pneumococcal pneumonia was 45.7% and 72.8%. The theoretical coverage of both vaccines was equal for non-invasive pneumonia (64%) but the theoretical coverage of the 9-valent PnV for invasive pneumonia was much higher (79% vs. 37.2%). Antibiotic susceptibility to penicillin was 84%, 70% to tetracycline and 61% to erythromycin; however only one strain (MIC = 4 mg/L) was highly resistant to penicillin. CONCLUSIONS: Based on this serotyping, the theoretical coverage of the 7-valent PnV for proven pneumococcal pneumonia is good but decreases with age. A 9-valent PnV containing SGT1 could significantly increase the coverage, especially for invasive pneumonia. According to these data, penicillin remains the first choice antibiotic treatment for childhood CAP in Belgium.     

Cost-effectiveness analysis of a universal vaccination programme with the 7-valent pneumococcal conjugate vaccine (PCV-7) in Sweden

The 7-valent pneumococcal conjugate vaccine (PCV-7) has proved to be highly effective against invasive pneumococcal disease and has also provided some protection against all-cause pneumonia and acute otitis media. The objective of this study was to evaluate the projected health benefits, costs and cost-effectiveness of vaccination with the 7-valent conjugated pneumococcal vaccine compared with no vaccination, in all infants in Sweden, taking herd immunity into account. A Markov model was used and a hypothetical birth cohort was simulated for a lifelong perspective. The results show that vaccination of 1 cohort could potentially prevent 9 cases of pneumococcal meningitis, 22 cases of pneumococcal septicaemia, 509 cases of hospitalized pneumonia, 7812 cases of acute otitis media, and 2.7 fatalities, among children 0-4 y of age and 6 episodes of pneumococcal meningitis and 167 cases of pneumococcal septicaemia among adults. The incremental cost per QALY and LY gained was estimated to euro29,200 and euro51,400, respectively. When herd immunity was accounted for, the cost per QALY and LY gained was estimated to euro5500 and euro6600, respectively. Thus, the health benefits of a national vaccination programmeme can be achieved within a 'moderate' or 'low' cost per QALY gained.     

Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001

Background  

In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV) given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV) at 18 months of age. This study presents carriage serotypes following this schedule.     

Burden of invasive pneumococcal disease and serotype distribution among Streptococcus pneumoniae isolates in young children in Europe: impact of the 7-valent pneumococcal conjugate vaccine and considerations for future conjugate vaccines

ObjectivesThe overall reported burden of invasive pneumococcal disease (IPD) varies among countries in Europe. This review describes the epidemiology and serotype distribution of IPD in European children from studies published from 1990 to 2008.MethodsAverages were derived from all studies from all countries that had available data.ResultsBefore widespread immunization with 7-valent pneumococcal conjugate vaccine (PCV7), the overall mean annual incidence of IPD in children aged <2 years was 44.4/100 000. The mean case fatality rate for IPD was 3.5%, and resistant rates were approximately 23% for penicillin G (minimum inhibitory concentration ≥2 mg/l), 41% for erythromycin, and 9% (≤5 years) for third-generation cephalosporins. The most common serotypes causing IPD were 14, 6B, 19F, and 23F, all of which are included in PCV7. Vaccine serotype coverage ranged from 37% to 100% for PCV7, with mean increases in coverage of 7% and 16% for investigational 10- and 13-valent pneumococcal conjugate vaccines, respectively. The most common IPD isolates since PCV7 introduction in Belgium, France, Germany, Greece, Norway, Portugal, Spain, and the UK were serotypes 1, 19A, 3, 6A, and 7F.ConclusionsWith routine effective use of PCV7, a general decline in IPD, antibiotic non-susceptibility, and vaccine serotypes has been observed. The most common IPD isolates since PCV7 introduction are serotypes 1, 19A, 3, 6A, and 7F, highlighting the need for inclusion of these serotypes in future vaccine formulations.     

Epidemiology of pneumococcal diseases in Spain after the introduction of pneumococcal conjugate vaccines

In Spain, the use of pneumococcal conjugate vaccines (PCVs) has led to a decrease in the incidence of vaccine serotypes causing invasive and non-invasive disease in vaccinated and unvaccinated children and adults. Further, the coverage of most of the resistant serotypes by vaccines resulted in an overall decline in antibiotic resistance.As an undesirable effect, there was an increase in the non-vaccine serotypes causing infection, especially serotypes 1, 7F and 19A after PCV7 and serotype 8 after PCV13 approval, this making the beneficial effect of vaccination less apparent.The inclusion of PCVs in childhood vaccination schedules, its approval for use in healthy adults and the increasing number of serotypes covered by the vaccines in development are strong strategies in the fight against pneumococcal disease. Nonetheless, the epidemiology of Streptococcus pneumoniae infections must be still under surveillance to detect new changes, given the high capacity for recombination and adaptability of this always-surprising microorganism.     

Cost-effectiveness of combined outreach for the pneumococcal and influenza vaccines

BACKGROUND: We conducted a cost-effectiveness analysis as part of a randomized, controlled trial of a community-based outreach initiative to promote the pneumococcal and influenza vaccines for people aged 65 years or older. METHODS: The analysis was based on primary data from the trial on the increase in vaccination rates and cost of the intervention, and published estimates of the effectiveness of the vaccines and cost of treatment. We performed partial stochastic analyses based on the confidence intervals (CIs) of the effectiveness of the intervention and of the vaccines. RESULTS: The cost-effectiveness ratio of the combined-outreach initiative as implemented was $35 486 per quality-adjusted life-year (QALY), whereas it was $53 547 per QALY for the pneumococcal vaccine and $130 908 per QALY for the influenza vaccine. In partial stochastic analyses, the quasi-CI of the combined-outreach initiative ranged from $15 145 to $152 311 per QALY. The cost-effectiveness ratio of the intervention targeted to people who had never received the pneumococcal vaccine or who had not received the influenza vaccine in the previous year was $11 771 per QALY, with a quasi-CI of $3330 to $46 095 per QALY. With the use of the projected cost of replicating the intervention, the cost-effectiveness ratio was $26 512 per QALY for the initiative as implemented and $7843 per QALY for a targeted initiative. CONCLUSIONS: The community-based outreach initiative to promote the pneumococcal and influenza vaccines was reasonably cost-effective. Further improvements in cost-effectiveness could be made by targeting the initiative or through lessons learned during the first year that would reduce the cost of the initiative in subsequent years.     

Proportion of invasive pneumococcal infections in German children preventable by pneumococcal conjugate vaccines.

The incidence and serotype distribution of Streptococcus pneumoniae as a cause of invasive diseases are unknown with regard to most European countries. From January 1997 through December 1998, population-based nationwide prospective surveillance was undertaken for invasive pneumococcal disease (IPD) in children in Germany, based on monthly independent reports from all pediatric hospitals and from clinical microbiology laboratories. On the basis of 896 reported IPD cases (including 404 with meningitis), the incidences per 10(5) children in different age groups were as follows: children aged <1 year, 18.9 (9.7 for meningitis); children aged <2 years, 16. 0 (7.2 for meningitis); for children aged <5 years, 8.9 (3.9 for meningitis); and for children aged <16 years, 3.2 (1.4 for meningitis). The proportions of cases involving strains (304 serotyped) included in conjugate vaccines were as follows: for the 7-valent vaccine, 52%; for the 9-valent, 62%; and for the 11-valent, 71%. None of the isolates were resistant to penicillin or cefotaxime. Although the rate for meningitis is similar, other manifestations of IPD are less commonly diagnosed in Germany than in other countries. The serotype distribution only partially matched that used in the recent development of pneumococcal conjugate vaccines.     

Streptococcus pneumoniae meningitis in Alberta pre- and postintroduction of the 7-valent pneumococcal conjugate vaccine

OBJECTIVE:

To describe the epidemiology, clinical characteristics, microbiology and outcomes of patients of all ages with Streptococcus pneumoniae meningitis two years pre- and postintroduction of a S pneumoniae 7-valent conjugate vaccine program in Alberta in children <2 years of age.

METHODS:

Between 2000 and 2004, all cases of invasive pneumococcal disease in Alberta were identified. From this cohort, patients with S pneumoniae meningitis were identified by chart review. Clinical data, laboratory data and in-hospital outcomes were collected.

RESULTS:

Of the 1768 cases of invasive pneumococcal disease identified between 2000 and 2004, 110 (6.2%) had S pneumoniae meningitis. The overall incidence was 0.7 per 100,000 persons and remained unchanged over the study period. The rate in children <2 years of age appeared to fall over time, from 10.5 per 100,000 persons in 2000 to five per 100,000 persons in 2004, although there was insufficient evidence of a statistically significant time trend within any age group. Overall, the mean age was 30 years and 47% were male. In-hospital mortality was 20%, ranging from 6% in those ≤2 years of age to 31% for those ≥18 years of age, despite appropriate antimicrobial therapy.

CONCLUSION:

The high mortality rate associated with S pneumoniae meningitis suggests that prevention by vaccination is critical. In children <2 years of age, there was a downward trend in the rate of S pneumoniae meningitis after implementation of the S pneumoniae 7-valent conjugate vaccine program, but rates were still high.     

Primary and booster salivary antibody responses to a 7-valent pneumococcal conjugate vaccine in infants

Salivary anticapsular antibody responses to a 7-valent pneumococcal conjugate vaccine (7VPnC) were measured in healthy infants. Infants received diphtheria-tetanus-pertussis/Haemophilus influenzae type b (DTP/Hib; group 1), DTP/Hib and 7VPnC (group 2), or DTP and 7VPnC/Hib (group 3) at ages 2, 3 and 4 months. All children received 23-valent pneumococcal polysaccharide vaccine at age 13 months. Salivary IgA and IgG responses to primary immunizations were generally poor. IgA mean concentrations at age 5 months were higher in the treatment groups than in control subjects for serotype 14 only (P<.001). At age 13-14 months, there were marked increases in IgA (mean fold difference, 3.7-4.9) and IgG (mean fold difference, 4. 1-11.7) levels for serotypes 4, 9V, 14, and 19F and serotypes 4, 18C, 19F, and 23F, respectively, in the treatment groups. This contrasts with low IgA (1.2 and 1.4) and IgG (1.3 and 2.2) mean fold differences for non-7VPnC serotypes 1 and 5. The results suggest that 7VPnC primes for mucosal memory responses in infants.     

Meeting the challenge: prevention of pneumococcal disease with conjugate vaccines

Streptococcus pneumoniae is one of the leading causes of both invasive and noninvasive diseases in the pediatric population and continues to represent a significant public health burden worldwide. The increasing incidence of antibioticresistant strains of the pathogen has complicated treatment and management of the various pneumococcal disease manifestations. Thus, the best management strategy may be the prevention of pneumococcal diseases through vaccination. Although several pneumococcal conjugate vaccines have been clinically studied in infants and children, only a 7-valent conjugate vaccine (PNCRM7; Prevnar/Prevenar) is currently approved for the prevention of invasive disease. Vaccination with PNCRM7 is safe and effective in infants and young children. Routine vaccination with the conjugate vaccine could improve outcomes by safeguarding against the development of antibiotic-resistant strains of S. pneumoniae, thus simplifying the management of pneumococcal disease. Additionally, the overall costs associated with the treatment of pneumococcal diseases could be substantially reduced, particularly in developing countries. The time has come for fully applying this new advancement against S. pneumoniae, to benefit the children of the world. The English version of this paper is available at: http://www.insp.mx/salud/index.html     

Immunity to cross-reactive serotypes induced by pneumococcal conjugate vaccines in infants.

Infants were immunized with 1 of the 3 experimental pneumococcal conjugate vaccines that contain 6B and 19F but not 6A or 19A serotypes. Their sera were studied for the capacity to opsonize Streptococcus pneumoniae 6A, 6B, 19A, and 19F serotypes and the level of IgG antibody to the 4 serotypes. Significant increases were observed in the number of infants with detectable opsonophagocytic titers with 3 conjugate vaccines for 6B (vaccine) serotype but with only 2 vaccines for 6A (cross-reactive) serotype. Significant increases were observed with 2 conjugate vaccines for 19F serotype but with only 1 vaccine for 19A serotype. Thus, some conjugate vaccines may elicit cross-protection better than others. In addition, correlations between opsonophagocytic titers and IgG antibody levels by ELISA were high for 6B and 19F serotypes but low for 6A and 19A serotypes. Thus, ELISA may be an inadequate surrogate assay of vaccine response for cross-reactive serotypes.     

Efficacy of pneumococcal conjugate vaccines and their effect on carriage and antimicrobial resistance

Pneumococcal conjugate vaccines have shown a high degree of success in preventing pneumococcal bacteraemia in children. They also reduce the acquisition of carriage of vaccine serotypes in the nasopharynx, and reduce otitis media caused by those serotypes. Non-vaccine serotypes, which can colonise vaccinated infants, are associated with otitis media in these children and lower the overall effectiveness of the vaccine to this disorder. Longer term studies, however, could show that immunised children develop immunity to a broad range of pneumococcal serotypes at a younger age than non-immunised children. Preliminary data suggest that these vaccines could reduce the burden of radiologically confirmed pneumonia. Pneumococcal conjugate vaccines interrupt the transmission of antibiotic-resistant pneumococci and thus decrease the burden of antibiotic resistance in immunised children and in their contacts. Studies are underway to assess conjugate vaccine efficacy against invasive disease, pneumonia, and all-cause mortality in developing countries, and to assess the potential use of these vaccines in adults.     

Immune response to pneumococcal conjugate and polysaccharide vaccines in otitis-prone and otitis-free children.

We compared responses to pneumococcal conjugate and polysaccharide vaccines in 48 otitis-free and 64 otitis-prone children. Pre- and postimmunization concentrations of antibodies to pneumococcal serotypes 6B, 14, 19F, and 23F were measured by enzyme-linked immunosorbent assay. Postimmunization mean concentrations of antibodies to all four serotypes were significantly higher for children receiving conjugate vaccine than for those receiving polysaccharide vaccine; the difference in responses was primarily due to a better response to conjugate vaccine in the otitis-prone group. Significantly higher postimmunization concentrations of antibodies to all four serotypes and to one of the four serotypes were found in otitis-prone children and otitis-free children who received conjugate vaccine, respectively. Pneumococcal conjugate vaccine has the potential to reduce the incidence of disease due to vaccine serotypes, even among children with recurrent otitis media.