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Population genomics of pneumococcal carriage in Massachusetts children following introduction of PCV-13.

ABSTRACT: The 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced in the United States in 2010. Using a large paediatric carriage sample collected from shortly after the introduction of PCV-7 to several years after the introduction of PCV-13, we investigate alterations in the composition of the pneumococcal population following the introduction of PCV-13, evaluating the extent to which the post-vaccination non-vaccine type (NVT) population mirrors that from prior to vaccine introduction and the effect of PCV-13 on vaccine type lineages. Draft genome assemblies from 736 newly sequenced and 616 previously published pneumococcal carriage isolates from children in Massachusetts between 2001 and 2014 were analysed. Isolates were classified into one of 22 sequence clusters (SCs) on the basis of their core genome sequence. We calculated the SC diversity for each sampling period as the probability that any two randomly drawn isolates from that period belong to different SCs. The sampling period immediately after the introduction of PCV-13 (2011) was found to have higher diversity than preceding (2007) or subsequent (2014) sampling periods {Simpson's D 2007: 0.915 [95?% confidence interval (CI) 0.901, 0.929]; 2011:? 0.935 [0.927, 0.942]; 2014?:? 0.912 [0.901, 0.923]}. Amongst NVT isolates, we found the distribution of SCs in 2011 to be significantly different from that in 2007 or 2014 (Fisher's exact test P=0.018, 0.0078), but did not find a difference comparing 2007 to 2014 (Fisher's exact test P=0.24), indicating greater similarity between samples separated by a longer time period than between samples from closer time periods. We also found changes in the accessory gene content of the NVT population between 2007 and 2011 to have been reduced by 2014. Amongst the new serotypes targeted by PCV-13, four were present in our sample. The proportion of our sample composed of PCV-13-only vaccine serotypes 19A, 6C and 7F decreased between 2007 and 2014, but no such reduction was seen for serotype 3. We did, however, observe differences in the genetic composition of the pre- and post-PCV-13 serotype 3 population. Our isolates were collected during discrete sampling periods from a small geographical area, which may limit the generalizability of our findings. Pneumococcal diversity increased immediately following the introduction of PCV-13, but subsequently returned to pre-vaccination levels. This is reflected in the distribution of NVT lineages, and, to a lesser extent, their accessory gene frequencies. As such, there may be a period during which the population is particularly disrupted by vaccination before returning to a more stable distribution. The persistence and shifting genetic composition of serotype 3 is a concern and warrants further investigation.

SUBMITTER: Mitchell PK

PROVIDER: S-EPMC6421351 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Population genomics of pneumococcal carriage in Massachusetts children following introduction of PCV-13.

Mitchell Patrick K PK Azarian Taj T Croucher Nicholas J NJ Callendrello Alanna A Thompson Claudette M CM Pelton Stephen I SI Lipsitch Marc M Hanage William P WP

Microbial genomics 20190219 2

The 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced in the United States in 2010. Using a large paediatric carriage sample collected from shortly after the introduction of PCV-7 to several years after the introduction of PCV-13, we investigate alterations in the composition of the pneumococcal population following the introduction of PCV-13, evaluating the extent to which the post-vaccination non-vaccine type (NVT) population mirrors that from prior to vaccine introduction and t ...[more]

PMID: 30777813

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Project description:BackgroundThirteen-valent pneumococcal conjugate vaccine (PCV13) was introduced in Malawi in November 2011 and is offered to infants at 6, 10 and 14?weeks of age as part of routine immunisation. PCV13 is expected to reduce vaccine type (VT) nasopharyngeal carriage, leading to reduced transmission and herd protection.MethodsWe compared pneumococcal carriage in rural Karonga District, Malawi, pre-vaccine in 2009-2011 and post-vaccine in 2014 using a combination of cross-sectional and longitudinal analyses. Nasopharyngeal swabs were collected from a cohort of mother-infant pairs and household members <16?years. Pneumococci from 2009 to 2011 were serogrouped using latex agglutination and serotyped by Quellung reaction. In 2014, latex agglutination was used for both steps. Carriage prevalence ratios using prevalence data from before and after vaccine introduction were calculated by log-binomial regression, adjusted for age, seasonality and household composition. Participating infants in 2014 received PCV13 as part of routine immunisation.ResultsVT carriage prior to PCV-13 introduction was 11.4%, 45.1%, 28.2%, 21.2% and 6.6% for 6-week old infants, 18-week old infants, children 1-4?years, children 5-15?years and mothers, respectively. After vaccine introduction, VT carriage decreased among vaccinated 18-week old infants (adjusted prevalence ratio 0.24 (95%CI 0.08-0.75)), vaccinated children 1-4?years (0.54 (0.33-0.88)), unvaccinated children 5-15?years (0.37 (0.17-0.78)) and mothers (0.34 (0.15-0.79)). No decrease in VT carriage was observed for 6-week old infants too young to be vaccinated (1.07 (0.38-3.02)) and PCV-13 ineligible children 1-4?years (0.84 (0.53-1.33)). Non-VT carriage increased only among vaccinated children 1-4?years (1.58 (1.21-2.06)).ConclusionsThere is evidence of reduced VT pneumococcal carriage three years after vaccine introduction in this rural Malawian population with good vaccine coverage using a 3?+?0 schedule. However carriage was sustained among 6-week-old infants and PCV13 ineligible 1-4?year olds, and there was some indication of serotype replacement in vaccinated 1-4?year olds.

Project description:BackgroundThe study objective was to determine the carriage and serotype distribution of Streptococcus pneumoniae among children in Accra, Ghana, five years after the introduction of the pneumococcal conjugate vaccine (PCV-13) in 2012.MethodsNasopharyngeal swab samples were collected from 410 children below 5?years of age in Accra, Ghana, from September to December, 2016. Pneumococcal isolates were identified by optochin sensitivity and bile solubility. Serotyping was performed using the latex agglutination kit and Quellung reaction. The isolates were furthermore tested for antimicrobial susceptibility for different antimicrobials, including penicillin (PEN). Twelve isolates including seven non-typeable (NT) isolates were characterized using whole-genome sequencing analysis (WGS).ResultsThe overall carriage prevalence was found to be 54% (95% CI, 49-59%), and 20% (95% CI, 49-59%) of the children were carrying PCV-13 included serotypes, while 37% (95% CI, 33-42%) of the children were carrying non-PCV-13 serotypes. Based on the serotype distribution, 33% of all observed serotypes were included in PCV-13 while 66% were non-PCV-13 serotypes. The dominating non-PCV-13 serotypes were 23B, 16F, and 11A followed by PCV-13 serotypes 23F and 19F. The PCV-13 covers the majority of resistant isolates in Accra. A proportion of 22.3% of the isolates showed intermediate resistance to penicillin G, while only one isolate showed full resistance. Forty-five isolates (20.5%) were defined as multidrug-resistant (MDR) as they were intermediate/resistant to three or more classes of antimicrobials. Of the seven NT isolates characterized by WGS, four showed highest match to genotype 38, while the remaining three showed highest match to genotype 14. Four MDR serotype 19A isolates were found to be MLST 320.ConclusionPCV-13 introduced in Ghana did not eliminate PCV-13 covered serotypes, and the carriage rate of 54% in this study is similar to carriage studies from pre PCV-13 period. However, the penicillin non-susceptible isolates have been reduced from 45% of carriage isolates before PCV-13 introduction to 22.3% of the isolates in this study. Continuous monitoring of serotype distribution is important, and in addition, an evaluation of an alternative vaccination schedule from 3?+?0 to 2?+?1 will be important to consider.

Project description:BACKGROUND:Streptococcus pneumoniae carriage is often asymptomatic but can cause invasive pneumococcal disease. Pneumococcal carriage is a prerequisite for disease, with children as main reservoir and transmitters. Childhood carriage can therefore be used to determine which serotypes circulate in the population and which may cause disease in the non-vaccinated population. In 2006, a pneumococcal conjugate vaccine (PCV7) was introduced into the Norwegian Childhood Immunisation Programme, which was replaced by the more valent PCV13 in 2011. We investigated changes in pneumococcal carriage prevalence 4 years after switching to PCV13 compared to three previous surveys, and analysed factors associated with carriage in children. METHODS:We conducted a cross-sectional study in Norway, autumn 2015, among children attending day-care centres. We collected questionnaire data and nasopharyngeal swabs to identify pneumococcal serotypes. We compared the carriage prevalence in 2015 with surveys conducted in the same setting performed before widespread vaccination (2006; n = 610), 2 years after PCV7 introduction (2008; n = 600), and 2 years after switching to PCV13 (2013; n = 874). Using multilevel logistic regression we determined the association between pneumococcal carriage and previously associated factors. RESULTS:In 2015, 896 children participated, with age ranging from 8 to 80 months. The overall carriage prevalence was 48/100 children [95%CI 44-53] in 2015, 38% [29-46] lower than in 2006 pre-PCV7, and 23% [12-32] lower than in 2013, 2 years after switching to PCV13. The PCV13 carriage prevalence was 2.8/100 children [1.9-4.2] in 2015. Increasing age (p < 0.001), recent antimicrobial use (odds ratio = 0.42 [0.21-0.57]) and being vaccinated (odds ratio = 0.37 [0.29-0.47]) were negatively associated with carriage. CONCLUSIONS:Our study showed a continued decrease in overall pneumococcal carriage, mainly fuelled by the decline in vaccine serotypes after vaccine introduction. Childhood vaccination with PCV13 should be continued to keep low PCV13 carriage, transmission and disease. Furthermore, the low prevalence of PCV13-type carriage in children endorse the choice of not recommending PCV13 in addition to the 23-valent pneumococcal polysaccharide vaccine to most medical risk groups in Norway, as little disease caused by these serotypes can be expected.

Dataset Information

Population genomics of pneumococcal carriage in Massachusetts children following introduction of PCV-13.

Publications

Population genomics of pneumococcal carriage in Massachusetts children following introduction of PCV-13.

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