Rapid Decrease of 7-Valent Conjugate Vaccine Coverage for Invasive Pneumococcal Diseases in Pediatric Patients in Japan
1 Laboratory of Molecular Epidemiology for Infectious Agents, Kitasato Institute for Life Sciences, Kitasato University , Tokyo, Japan .Microbial drug resistance (Larchmont, N.Y.) (Impact Factor: 2.49). 03/2013; 19(4). DOI: 10.1089/mdr.2012.0180
In Japan, the heptavalent pneumococcal conjugate vaccine (PCV7) has been introduced on a voluntary basis since February 2010, and official financial support for children under 5 years started in November 2010. The impact of PCV7 on invasive pneumococcal diseases (IPD) in children is unknown. There are 340 medical institutions that actively participated in our surveillance project throughout Japan. We collected 252 strains from patients with IPD in 2006 (pre-PCV7), 280 strains in 2010 (under 10% immunization achieved), and 128 strains in 2011 (50% to 60% immunization). Serotypes and penicillin-resistance genotypes (g) were compared between these years. Multilocus sequence typing was also carried out on these strains. Due to the official promotion, IPD significantly decreased in 2011 (p<0.001). In particular, meningitis and sepsis caused by vaccine type (VT) strains declined (p=0.033, p<0.001). In less than 2 years, among nonvaccine types (NVT), 15A and 22F increased in 2011 (p=0.015, p=0.015). Coverage by PCV7 decreased from 71.8% in 2006 to 51.6% in 2011. Sequence-type diversities accompanied by evolution to gPRSP occurred in both VT and NVT strains. Reduction of IPD caused by VT strains was accomplished, but a rapid increase of NVT raises concern about a future decrease in the efficacy of PCV7.
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ABSTRACT: 13-valent pneumococcal vaccine (PCV13) provides broader protection against pneumococcal disease than 7-valent pneumococcal vaccine (PCV7). This study in Japan compared the safety and immunogenicity of PCV13 with PCV7. Healthy Japanese infants received PCV13 and diphtheria, tetanus, acellular pertussis vaccine (DTaP), PCV7 and DTaP, or DTaP alone subcutaneously as a 3-dose infant series, with a fourth dose at 12 months of age. Antigen-specific immunoglobulin G (IgG) serum concentrations and opsonophagocytic activity (OPA) and DTaP antibodies were measured 1 month after dose 3 and dose 4. After 3 and 4 doses, the proportion of subjects in the PCV13+DTaP group achieving IgG concentrations >0.35 µg/mL to the 7 serotypes common to PCV13 and PCV7 was noninferior to that of the PCV7+DTaP group. IgG geometric mean concentrations (GMCs) in the PCV13+DTaP group were lower than but noninferior to the PCV7+DTaP group GMCs. For the 6 additional pneumococcal serotypes, the proportion of PCV13+DTaP group responders achieving IgG concentrations >0.35 µg/mL and IgG GMCs (except serotype 3 after dose 4) were noninferior to the lowest PCV7+DTaP group pneumococcal response in PCV7 recipients, and responses to the 6 additional antigens were significantly higher. The majority of subjects achieved prespecified antibody levels to DTaP antigens. GMCs to DTaP antigens were comparable among groups, except filamentous hemagglutinin (numerically higher in the DTaP alone group after dose 4). PCV13+DTaP was as immunogenic as PCV7 for the 7 common pneumococcal antigens, and elicited significantly higher responses to the 6 additional antigens. DTaP responses were comparable across groups. PCV13 given with DTaP was safe and well tolerated. NCT01200368.
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ABSTRACT: We constructed a new real-time PCR method to detect causative pathogens in cerebrospinal fluid (CSF) from patient due to bacterial meningitis. The eight pathogens targeted in the PCR are Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus agalactiae, Staphylococcus aurues, Neisseria meningitides, Listeria monocytogenes, Esherichia coli, and Mycoplasma pneumoniae. The total time from DNA extraction from CSF to PCR analysis was 1.5 hour. The pathogens were detected in 72% of the CSF samples (n=115) by real-time PCR, but in only 48% by culture, although the microorganisms were completely concordant. The detection rate of pathogens with PCR was significantly better than that with cultures in patients with antibiotic administration.In conclusion, detection with real-time PCR is useful for rapidly identifying the causative pathogens of meningitis and for examining the clinical course of chemotherapy.
Article: Changes in nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis among healthy children attending a day-care centre before and after official financial support for the 7-valent pneumococcal conjugate vaccine and H. influenzae type b vaccine in Japan[Show abstract] [Hide abstract]
ABSTRACT: The 7-valent pneumococcal conjugate vaccine (PCV7) and Haemophilus influenzae type b (Hib) vaccine reduce nasopharyngeal carriage of vaccine-type bacteria, which may in turn influence the presence of other nasopharyngeal bacterial pathogens. To investigate this possibility, nasopharyngeal carriage of potential pathogens was examined before and after official financial support was provided to offer the PCV7 and Hib vaccines in healthy children attending a day care centre in Japan during 2011-2012. Despite a virtual disappearance of PCV7 serotypes over time, the overall pneumococcal carriage rate remained unchanged. Although others have reported an increase in PCV13 serotypes following PCV7 vaccination, only non-PCV13 serotypes were observed to have increased in this study. The majority of H. influenzae isolates were non-typeable and Hib was not found. Our data identified an unexpected pattern of pneumococcal serotype replacement following PCV7. Continuous monitoring of pneumococcal carriage is important for decisions regarding the future of national vaccination policy in Japan.
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