Declining serotype coverage of new pneumococcal conjugate vaccines relating to the carriage of Streptococcus pneumoniae in young children.

Asymptomatic carriage of the opportunistic pathogen Streptococcus pneumoniae is known to precede the development of invasive disease. Young children are one of the major reservoirs for pneumococci and worldwide over 700,000 children under two years old die due to invasive pneumococcal disease each year. Heptavalent conjugate vaccine (PCV-7) was introduced into the UK childhood immunisation schedule in September 2006. Our objective was to assess the emergence of colonising serotypes in young children in the three years following PCV-7 implementation. Time-series prevalence survey set in the paediatric outpatients department of a large UK teaching hospital. Participants were children aged four years and under attending the outpatients department during PCV-7 introduction (October 2006-February 2007) and in the same months of the two subsequent years. The main outcome measure was prevalence of pneumococcal carriage by serotype. The rate of pneumococcal nasopharyngeal carriage remained stable during the three year period. We observed a significant 69% (95% CI, -40% to -118%, p<0.0001) decrease in carriage of PCV-7 serotypes during PCV-7 implementation and a concomitant increase in the proportion of non PCV-7 serotypes. The most prevalent emerging non-vaccine serotypes were 6C, 11A, 19A and 22F. By March 2009, PCV-13 was predicted to cover only 33.3% (95% CI, 24.2-42.5%) of strains carried in the study population. Although the overall pneumococcal carriage rate remained stable between 2006 and 2009, we observed a significant decrease in the serotype coverage of PCV-7 and PCV-13. PCV-7 was highly successful in reducing carriage of vaccine serotypes. However, the increase in the proportion of non-vaccine serotypes found both in our study and causing invasive disease currently in the UK, underlines the importance of continued surveillance of carriage and disease.

Tocheva AS ，Jefferies JM ，Rubery H ，Bennett J ，Afimeke G ，Garland J ，Christodoulides M ，Faust SN ，Clarke SC ... -  《-》

The rise and fall of pneumococcal serotypes carried in the PCV era.

Streptococcus pneumoniae is a major cause of meningitis, sepsis and pneumonia worldwide. Vaccination using pneumococcal conjugate vaccines (PCV) has therefore been part of the UK's childhood immunisation programme since 2006. Here we describe pneumococcal carriage rates in children under five years of age attending the paediatric department of a large UK hospital in response to vaccine implementation over seven winter seasons from 2006 to 2013. S. pneumoniae (n=696) were isolated from nasopharyngeal swabs (n=2267) collected during seven consecutive winters, October to March, 2006/7 to 2012/13. This includes the period immediately following the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in 2006 in addition to pre- and post-PCV13 introduction in 2010. We show a decrease in PCV13 vaccine serotypes (VT) in the three years following PCV13 vaccine implementation (2010/11 to 2012/13). Serotype 6A represented the only observed VT following PCV13 implementation with all others (including PCV7 serotypes) absent from carriage. Overall pneumococcal carriage, attributable to non-VT (NVT), was consistent across all sampling years with a mean of 31·1%. The ten most frequently isolated NVTs were 6C, 11A, 15B, 23B, 15A, 21, 22F, 35F, 23A and 15C. Fluctuations in the prevalence of each were however noted. Comparing prevalence at 2006/07 with 2012/13 only 15A was shown to have increased significantly (p value of 0·003) during the course of PCV implementation. These data support the increasing evidence that the primary effect of PCVs is due to population immunity by reducing or eliminating the carriage of invasive VT serotypes. With IPD being increasingly attributed to non-vaccine serotypes, surveillance of carriage data continues to act as an early warning system for vaccine design and public health policy that require continual data of both carried pneumococcal serotypes and IPD attributed serotype data.

Devine VT ，Cleary DW ，Jefferies JM ，Anderson R ，Morris DE ，Tuck AC ，Gladstone RA ，O'Doherty G ，Kuruparan P ，Bentley SD ，Faust SN ，Clarke SC ... -  《-》

Nasopharyngeal carriage of Streptococcus pneumoniae in Taiwan before and after the introduction of a conjugate vaccine.

The heptavalent pneumococcal conjugate vaccine was introduced in Taiwan in October 2005. To evaluate the effect of the vaccination, we conducted an active, prospective, large-scale, long-term, and multicenter study to assess the prevalence of nasopharyngeal Streptococcus pneumoniae carriage in Taiwanese children. This study was performed at three tertiary teaching hospitals in northern, central, and southern Taiwan. Questionnaires provided demographic, family/household, and medical history data. Pneumococcal isolates were tested for their susceptibility to various antimicrobial agents and serotypes. In addition, influenza virus and Staphylococcus aureus were recovered from nasopharyngeal and nasal swabs, respectively. Between July 2005 and July 2008, 857 pneumococcal strains were recovered from a total of 6057 children aged >2 months to 5 years (carriage rate, 14.1%). Carriage rates differed geographically and varied with subject age. In a multivariate analysis, having at least one sibling, attendance at day-care centers, a history of otitis media, and history of upper respiratory tract infection in the previous 2 weeks were each associated with a higher risk of pneumococcal colonization of the nasopharynx. Staphylococcus aureus nasal colonization was inversely associated with nasopharyngeal carriage of pneumococcus (p=0.000; odds ratio [OR]: 0.48; 95% CI: 0.39-0.58). Daycare attendance was the only risk factor for carriage of penicillin non-susceptible S. pneumoniae (OR: 2.37; 95% CI: 1.22-4.88). Although vaccination rates rose from 2005 to 2008, no concomitant decrease in S. pneumoniae carriage occurred. The rate of penicillin resistance among S. pneumoniae isolates was 92.8% (using the meningitis criteria). The prevalence of cefotaxime resistance (21.6%) was higher than that of penicillin (6.9%; non-meningitis criteria). Slightly more than half (57.4%) of the isolates belonged to strains covered by the heptavalent pneumococcal conjugate vaccine when both vaccine and vaccine-related serotypes were included. Although vaccination rates rose from 2005 to 2008, no concomitant decrease occurred in S. pneumoniae carriage. Interaction between S. aureus and S. pneumoniae may influence vaccination efficacy. These findings provide baseline data to further compare pneumococcal carriage rates and antibiotic resistance patterns in Taiwanese children as vaccination rates continue to increase.

Kuo CY ，Hwang KP ，Hsieh YC ，Cheng CH ，Huang FL ，Shen YH ，Huang YC ，Chiu CH ，Chen PY ，Lin TY ... -  《-》

Carriage of Streptoccoccus pneumoniae 7 years after implementation of vaccination program in a population with very high and long-lasting coverage, Italy.

To evaluate how the 7-valent pneumococcal vaccine (PCV7) programme and the very high vaccination coverage reached for over 4 years affected the prevalence of Streptoccoccus pneumoniae serotypes in the paediatric population and to evaluate demographic, behavioural and risk factors for carriage in the post-vaccination era, a cross-sectional study on nasopharyngeal carriage was performed. Six hundred sixty-nine children under the age of 5, representative of the open population, were enrolled by cluster sampling. High sensitive techniques for detection of multi-serotype carriage, i.e. broth enrichment and real-time PCR and sequential PCRs for detection and typing, respectively, were used. Of the 669 enrolled children, 97.8% were compliant with the recommended PCV7 vaccination schedule. Post-stratification adjustment for age was applied considering the Ligurian population as standard population. Age-weighted carriage rate was 50.1% and 78% of carriers were colonized by more than one serotype. The prevalence of carriage increased with age from 22% in the first year of life, to 48.6% in the second year of life and to 60% in the 25-59 month age group. Age-weighted prevalence of any of the PCV7, PCV10 or PCV13 serotypes was 10.3%, 20.3% and 27.5%, respectively. PCV7 serotypes were mainly represented by serotype 4 that was carried since the 3rd year of life and was responsible for invasive pneumococcal disease (IPD) and non-IPD in adults, but not in children confirming the high vaccine effectiveness. Among the serotypes included in recently available vaccines, serotypes 5 and 19A showed a higher prevalence, being carried by 15.2% and 8.8% of the population, respectively. A multivariate analysis showed that age, the presence of child siblings at home and day care attendance covariates were strongly associated with S. pneumoniae carriage. In conclusion, over 7 years of vaccination with PCV7 and very high coverage in the last 4 years has led to low carriage prevalence in the first year of life rapidly increasing in the following years and high prevalence of non-PCV7 serotypes carriage.

Ansaldi F ，de Florentiis D ，Canepa P ，Zancolli M ，Martini M ，Orsi A ，Durando P ，Icardi G ... -  《-》

Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian children who participated in a 9-valent pneumococcal conjugate vaccine trial and in their younger siblings.

Cheung YB ，Zaman SM ，Nsekpong ED ，Van Beneden CA ，Adegbola RA ，Greenwood B ，Cutts FT ... -  《-》