Streptococcus pneumoniae colonization after introduction of 13-valent pneumococcal conjugate vaccine for US adults 65 years of age and older, 2015–2016

Background

Vaccination of children with 13-valent pneumococcal conjugate vaccine (PCV13) led to declines in vaccine-type pneumococcal nasopharyngeal carriage among adults through indirect effects. In August 2014, PCV13 immunization of all U.S. adults ≥65?years of age was recommended. This study sought to define prevalence and serotype distribution of pneumococcal carriage among adults ≥65?years of age and to describe risk factors for colonization soon after introduction of PCV13 in adults.

Invasive disease potential of Streptococcus pneumoniae serotypes before and after 10-valent pneumococcal conjugate vaccine introduction in a rural area,southern Mozambique

BackgroundInvasive pneumococcal disease (IPD) is a significant cause of morbidity and mortality among children worldwide. In April 2013, Mozambique introduced 10-valent PCV (PCV10) into the National Expanded Program on immunization using a three-dose schedule at 2, 3, and 4 months of age. We aimed to evaluate the invasive disease potential of pneumococcal serotypes among children in our region before and after PCV10 introduction.MethodsWe used data from ongoing population-based surveillance for IPD and cross-sectional pneumococcal carriage surveys among children aged <5 years in Manhiҫa, Mozambique. To determine the invasive disease potential for each serotype pre- and post-PCV10 introduction, odds ratios (OR) and 95% confidence intervals (95% CI) were calculated comparing serotype-specific prevalence in IPD and in carriage. For each serotype, OR and 95% CI > 1 indicated high invasive disease potential and OR and 95% CI < 1 indicated low invasive disease potential.ResultsIn the pre-PCV10 period, 524 pneumococcal isolates were obtained from 411 colonized children and IPD cases were detected in 40 children. In the post-PCV10 period, 540 pneumococcal isolates were obtained from 507 colonized children and IPD cases were detected in 30 children. The most prevalent serotypes causing IPD pre-PCV10 were 6A (17.5%), 6B (15.0%), 14 (12.5%), 23F (10.0%) and 19F (7.5%), and post-PCV10 were 6A (36.7%), 13 (10%), 1 (10.0%), 6B (6.7%) and 19A (6.7%). Serotypes associated with high invasive disease potential pre-PCV10 included 1 (OR:22.3 [95% CI 2.0; 251.2]), 6B (OR:3.1 [95% CI 1.2; 8.1]), 14 (OR: 3.4 [95% CI 1.2; 9.8]) and post-PCV10 included serotype 6A (OR:6.1[95% CI 2.7; 13.5]).ConclusionThe number of serotypes with high invasive disease potential decreased after PCV10 introduction. Serotype 6A, which is not included in PCV10, was the most common cause of IPD throughout the study and showed a high invasive potential in the post-PCV10 period.     

Pneumococcal carriage in young children after introduction of PCV13 in Hong Kong

ObjectivesPneumococcal conjugate vaccine (PCV) has been included in Hong Kong’s Childhood Immunization Programme since 2009. This study aimed to assess nasopharyngeal pneumococcal carriage rate, serotypes and antimicrobial resistance pattern in young children after the introduction of 13-valent PCV (PCV13).Study designA community-based, cross-sectional surveillance study was performed on healthy infants attending eleven Maternal and Child Health Centres across different parts of Hong Kong. Nasopharyngeal swabs were obtained from healthy children aged 2, 12 and 18 months during their visit to the centers for immunization from June 2013 to June 2014. Pneumococcal isolates were serotyped and tested for antimicrobial resistance. Details of the demographics, family composition, vaccination history and medical history was obtained through interview of the guardians.Results1541 children were recruited. The overall carriage rate was 5.5%. Children aged 12 and 18 months were more likely to have pneumococcal colonization (12 months OR: 2.88; 95% CI: 1.41–5.87 and 18 months OR: 2.19, 95% CI: 1.05–4.57). Recent respiratory symptoms and presence of siblings younger than 6 years were independently associated with pneumococcal carriage. Eighty-four pneumococcal isolates were serotyped. The most prevalent serogroup/types were 15 (15B/C, 16.7%; 15A/F, 9.5%), 6C (15.5%) and 23A (13.1%). Overall, 2.4% of the isolates were heptavalent PCV serotypes, 10.7% were PCV13 serotypes and 89.3% were non-PCV13 serotypes. The proportions of penicillin, cefotaxime and erythromycin non-susceptible isolates were 7.3%, 13.4% and 79.3% respectively.ConclusionThe rate of pneumococcal carriage was low in young children in Hong Kong and compared to previous local studies there appears to have been an overall reduction in the carriage rate after the introduction of PCV. Likely serotype replacement was noted with a predominance of non-vaccine serotypes in pneumococcal carriage with the emergence of serogroup/type 15 and 6C.     

The impact of PCV7/13 on the distribution of carried pneumococcal serotypes and on pilus prevalence; 14 years of repeated cross-sectional surveillance

BackgroundS. pneumoniae carriage by children is a major source of pneumococcal transmission, and the initial step prior to infection. Pilus type 1, reported in ~30% of pneumococcal strains in the pre-vaccine era, contributes to pneumococcal colonization and virulence. In this study, we report the impact of the pneumococcal conjugate vaccine (PCV), PCV7/PCV13 sequential implementation on serotype distribution, and on the prevalence of piliated strains among carried pneumococci during the pre- and post-vaccine eras.MethodsDuring 2002-2016, 12 repeated cross-sectional surveillances of nasopharyngeal S. pneumoniae carriage were conducted among 8,473 children <5.5 years old visiting primary care physicians in Central Israel. Seven biannual surveillances in the pre-PCV period, 2 surveillances after PCV7 was licensed but before implementation in the National Immunization Plan, and 3 additional surveillances in the post-PCV period. S. pneumoniae serotype distribution and prevalence of piliated strains were assessed.ResultsCarriage of S. pneumoniae was relatively stable (45.4%). The prevalence of serotypes included in PCV13 was 65.7%, in the pre-vaccine period and the pilus was present in 26.4% of isolates. The distribution of serotypes and the pilus prevalence in the pre-PCV period was relatively stable except for a decrease in prevalence of piliated 19F, observed following the first study year. Following PCV7/PCV13 implementation, vaccine type 13 (VT13) strains were nearly eliminated to 3.3% by 2016. Piliated strains, which were primarily of VT13 serotypes, initially followed a similar trend and were nearly eliminated by 2014 (1.7%). Yet, two years later, pilus prevalence re-emerged among non-VT strains to 12.8% of all pneumococci.ConclusionsFollowing PCV implementation, a dramatic and rapid decrease in VT strains prevalence was observed with a concomitant increase in non-VT strains. Piliated strains were nearly eliminated, yet re-emerged 7 years following PCV7/PCV13 implementation in various non-VT strains. This suggests that the pilus confers an advantage in colonization.     

Impact of the 13-valent pneumococcal conjugate vaccine on Streptococcus pneumoniae multiple serotype carriage

IntroductionPneumococcal multiple serotype carriage is important for evolution of the species and to understand how the pneumococcal population is changing with vaccination. We aimed to determine the impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on multiple serotype carriage.Methods and materialsNasopharyngeal samples from fully vaccinated pneumococcal carriers (4 doses of PCV13, n = 141, aged 18–72 months) or from non-vaccinated pneumococcal carriers (0 doses of any PCV, n = 140, same age group) were analyzed. Multiple serotype carriage was evaluated by DNA hybridization with a molecular serotyping microarray that detects all known serotypes.ResultsVaccinated children had a lower prevalence of multiple serotype carriage than the non-vaccinated group (20.6% vs 29.3%, p = 0.097), and a significantly lower proportion of PCV13 serotypes (6.4% vs 38.5%, p = 0.0001). PCV13 serotypes found among vaccinated children were mostly detected as a minor serotype in co-colonization with a more abundant non-vaccine serotype. Vaccinated children were colonized by a significantly higher proportion of commensal non-pneumococcal Streptococcus spp. (58.2% vs 42.8%, p = 0.012). In vaccinated children there were significantly less non-vaccine type (NVT) co-colonization events than expected based on the distribution of these serotypes in non-vaccinated children.ConclusionsThe results suggest that vaccinated children have lower pneumococcal multiple serotype carriage prevalence due to higher competitive abilities of non-vaccine serotypes expanding after PCV13 use. This might represent an additional benefit of PCV13, as decreased co-colonization rates translate into decreased opportunities for horizontal gene transfer and might have implications for the evolution and virulence of pneumococci.     

Nasopharyngeal carriage of Streptococcus pneumoniae in healthy children aged less than five years

PurposeIn Turkey, pneumococcal conjugate vaccine (PCV) was introduced to the national immunization program as PCV7 in 2008, and was replaced with PCV13 in 2011. The aim of the study was to demonstrate the pneumococcal carriage rate and the serotype distribution in healthy children under 5 years in Turkey who were vaccinated with PCV13.MethodsWe conducted a cross-sectional study including the collection of questionnaire data and nasopharyngeal (NP) specimens among children aged <5 years from five centers from March 2019 to March 2020. Pneumococcal isolates were identified using optochin sensitivity and bile solubility. Serotyping was performed using a latex agglutination kit and Quellung reaction.ResultsNP swab samples were collected from 580 healthy children. The observed overall carriage rate was 17.8%. None of the hypothesised predictors of S. pneumoniae carriage, except maternal education level was statistically significant (p = 0.017). High maternal education level appeared to decrease the risk (lower vs. higher maternal education OR: 1.992 [95% CI; 1.089–3.643], p = 0.025). The overall NP S. pneumoniae carriage prevalence for the PCV13-vaccinated children was 17.8% (103/580). The most common serotypes detected were serotype 15B (n = 10, 9.7%), serotype 23F (n = 9, 8.7%), serotype 23A (n = 9, 8.7%), serotype 11A (n = 7, 6.7%), serotype 19F (n = 5, 4.8%) and serotype 15F (n = 5, 4.8%). Of the isolates, 28 (27.2%) were in PCV13 vaccine strains (VSs), and 75 (72.8%) strains were non-VS. The serotype coverage rate was 27.2% for PCV13.ConclusionThe overall S. pneumoniae carriage rate was higher than in earlier studies from Turkey. Post-vaccine era studies from around the world have reported a decrease in VS serotypes and a ‘serotype replacement’ to non-VS serotypes, as we determined in our study.     

Association of serotype with respiratory presentations of pneumococcal infection,Ontario, Canada, 2003–2011

BackgroundPneumococcal disease burden is difficult to quantify due to limited data regarding non-bacteremic disease. We assessed serotype-specific differences in pneumococcal disease presentations in adults in Toronto, Canada.MethodsFrom 2003 to 2011, population-based surveillance for invasive pneumococcal disease was conducted and respiratory pneumococcal isolates collected in Metropolitan Toronto/Peel Region, Canada. Episodes of care were classified into disease categories.ResultsOf 3105 eligible cases of IPD, 2060 cases were bacteremic pneumonia, and 1045 bacteremia without pneumonia. Of 2751 eligible respiratory cases, 1542 (56.0%) were non-bacteremic pneumonia (NBPP), 467 (17.0%) were other acute respiratory infection (oARI), and 742 (27.0%) were isolates representing colonization. Serotypes 3 (11.3%), 19A (8.4%) and 22F (6.2%) were the most common; serotypes 1,5, and 8 were rare. Serotypes 4, 14, 7F, 9V, 12F, 14, 19A and 6C were over-represented in bacteremic disease, and serotypes 3, 6A, 11A, 19F, 23A, 23F, 35B, 35F were more common in NBPP. The proportion of cases due to PCV7 serotypes declined from 48.7% to 8.7% in bacteremic pneumonia, from 35.3% to 10.9% in NBPP, from 34.2% to 7.5% in oARI, and from 38.7% to 12.2% in colonizing isolates. In 2010–2011, PCV13 serotypes accounted for 62.6% of isolates associated with bacteremic pneumonia, 42.0% of bacteremia without pneumonia, 41.1% of NBPP, 25.7% of oARI, and 32.9% of colonizing isolates.ConclusionsSerotype distributions differ significantly in different presentations of pneumococcal disease. Herd protection due to PCV7 has changed serotype distribution, but PCV13 serotypes remain important in all categories of disease.     

Direct effect of the 13-valent pneumococcal conjugate vaccine use on pneumococcal colonization among children in Brazil

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) has been commercially available in Brazil since 2010. We investigated the carriage prevalence, capsular types, and antimicrobial resistance among pneumococci isolated from children immunized with PCV13 in Brazil.MethodsWe analyzed 500 children < 6 years old attending public (n = 270) and private (n = 230) clinics in Niterói/RJ, Brazil, in 2014. We determined the antimicrobial susceptibility and capsular types for all isolates.ResultsThirty-eight (7.6%) of 500 children had received at least one PCV13 dose. Since only two (0.7%) of 270 children at the public clinic were vaccinated with PCV13, major analyses focused on 36 (15.7%) of 230 children attending private clinics. Nine (25%) of 36 children were pneumococcal carriers. Characteristics associated with carriage were age ≥ 2 years, cough/expectoration, and childcare center attendance (p ≤ 0.01). The capsular types found were 15B/C (n = 2), 6C, 11A/D, 16F, 23A, and 23F. Two isolates were non-typeable (NT). Three (33.3%) isolates were multidrug resistant. We found four (44.4%) penicillin non-susceptible pneumococci, with penicillin and ceftriaxone MICs ranging from 0.12 to 4.0 µg/ml and 0.023–0.5 µg/ml, respectively. We also detected two (22.2%) erythromycin-resistant isolates (MICs of 3.0 and 256 µg/ml).ConclusionsColonization with PCV13 serotype was rare among the vaccinated children. Increasing PCV13 coverage might help reduce the frequency of major serotypes currently associated with invasive pneumococcal diseases in Brazil, such as 3 and 19A. The isolation of multidrug-resistant serotype 6C and NT isolates in carriage, however, requires close monitoring.     

Unaltered pneumococcal carriage prevalence due to expansion of non-vaccine types of low invasive potential 8 years after vaccine introduction in Stockholm,Sweden

ObjectiveTo evaluate the carriage prevalence, serotype distribution, and antibiotic resistance for pneumococcal carriage isolates collected 4–8 years after introduction of pneumococcal conjugate vaccines (PCVs) in Stockholm, Sweden, and to identify risk factors for carriage and calculate the invasive disease potential for emerging serotypes.MethodsNasopharyngeal aspirates were collected from 3024 children aged 0–<5 years at regular visits at 23 Child Health Centers in Stockholm County in 2011–2015, and from 787 parents in 2014–2015. The invasive disease potential was calculated for serotypes using invasive disease isolates from 824 patients of all ages identified in the Stockholm County during the same time period as the carriage isolates.ResultsA total carriage prevalence of 30% did not change during the study period. Non-vaccine types (NVT) dominated (94% by 2015) and the most common serotypes in descending order were 11A, 23B, 35F and 21. Risk factors for carriage were: age ⩾3 months–<3 years, having siblings, attending day-care and having travelled abroad the last 3 months. Antibiotic resistance remained low. The invasive disease potential was high for NVT 8, 9N, 12F, and 22F, while low for a majority of emerging NVTs in carriage.ConclusionThe carriage prevalence remained the same 4–8 years after vaccine introduction, but serotype replacement became almost complete. A majority of emerging NVTs in carriage showed a low invasive disease potential. Carriage studies are an important complement to invasive disease surveillance to understand the full effect of PCV vaccine programs.     

Long-term effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae in children in Brazil

Brazil introduced the 10-valent pneumococcal vaccine (PCV10) to the routine national immunization program (NIP) in March 2010. In 2017, we investigated the effects of PCV10 on nasopharyngeal carriage of vaccine-types (VT) and non-vaccine-types (NVT) of Streptococcus pneumoniae (Spn) among children living in São Paulo city. We also compared the prevalence of VT and NVT with previous carriage surveys performed in 2010 (baseline) and 2013.MethodThe carriage survey was conducted among 531 children, aged 12 months to <24 months, recruited from public Primary Health Units during the immunization campaign, using previous surveys methodology, except for qPCR, which was performed in the 2017 survey only.ResultsNo statistical difference was found in the prevalence of Spn either by culture (59.7%) or by qPCR (61.2%). Spn carriage increased from 40.3% (baseline) to 59.7% (2017 survey) (p < 0.001). Colonization by VT isolates significantly decreased by 90.9% (19.8–1.8%) and 95.5% (19.8–0.9%) in the 2013 and 2017 surveys, respectively, compared to that at baseline. NVT isolates increased significantly by 128% (19.6–44.8%) and 185% (19.6–55.9%) in the respective post-PCV10 surveys, most led to high prevalence of serotypes 6C (27%), 15B (9.8%), 19A (9.2%), 15A (6.0%), and 16F (5.7%). In 2017, reduction in serotype 6A (4.2–0.6%, p < 0.001) and increase in serotype 19A (1.8–6.0%, p = 0.001) were found; serotype 3 isolate was not detected in the present survey. We identified the emergence of 19A isolates CC320, associated with high penicillin (MIC ≥ 2.0 mg/L) and cefotaxime (MIC ≥ 1.0 mg/L) values.ConclusionAfter 7 years of PCV10 introduction in the NIP, colonization by VT among toddlers decreased substantially to a residual level, along with substantial serotype replacement by novel serotypes not present in any current conjugated pneumococcal vaccine and serotype 19A. The present findings can assist policy decisions in Brazil.     

Five winters of pneumococcal serotype replacement in UK carriage following PCV introduction

The seven-valent pneumococcal conjugate vaccine (PCV7) was added to the UK national immunisation programme in September 2006. PCV13 replaced PCV7 in April 2010. As carriage precedes disease cases this study collected carried pneumococci from children each winter from 2006/7 to 2010/11 over PCV introduction. Conventional microbiology and whole genome sequencing were utilised to characterise pneumococcal strains.Overall prevalence of pneumococcal carriage remained stable. Vaccine serotypes (VT) decreased (p < 0.0001) with concomitant increases in non-vaccine serotypes (NVT). In winter 2010/11 only one isolate of PCV7 VT was observed (6B). PCV13 unique VTs decreased between winters immediately preceding and following PCV13 introduction (p = 0.04). Significant decreases for VTs 6B, 19F, 23F (PCV7) and 6A (PCV13) and increases for NVT 21, 23B, 33F and 35F were detected. The serotype replacement was accompanied by parallel changes in genotype prevalence for associated sequence types with clonal expansion contributing to replacement. By winter 2010/11, serotype coverage of PCV7 and PCV13 was 1% and 11% respectively.VT replacement was observed for PCV7 and PCV13 serotypes. Conjugate vaccine design and use requires continuous monitoring and revision.     

Dynamic of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 introduction in France

To determine whether the use of seven valent pneumococcal conjugate vaccine (PCV7) caused a shift in the Streptococcus pneumoniae serotypes distribution and whether it modified the resistance to antibiotics, 3291 nasopharyngeal swabs were obtained between 2001 and 2006, from children aged 6–24 months with acute otitis media. Following the implementation of PCV7, we observed a slight reduction in the overall pneumococcal carriage, a marked decrease of vaccine serotypes, an increase in non-vaccine serotypes carriage and a reduction in the carriage of penicillin non-susceptible strains. Most of the serotype 19A replacement was related to the clonal expansion of ST276 which was found to be the predominant ST among penicillin non-susceptible isolates.     

Nasopharyngeal carriage of Streptococcus pneumoniae and other bacteria in the 7th year after implementation of the pneumococcal conjugate vaccine in the Netherlands

After introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the infant national immunization program (NIP) in the Netherlands in 2006, Streptococcus pneumoniae strains of the non-vaccine serotype 19A emerged and became the dominant serotype in carriage in children and their parents. Similar patterns were observed in other European countries and the United States. Increases in carriage rates of Staphylococcus aureus and non-typeable (NT) Haemophilus influenzae were also observed. After switching of PCV7 to 10-valent vaccine (PCV10) in 2011, a new carriage surveillance study was performed in the winter of 2012/2013. Nasopharyngeal carriage of S. pneumoniae, H. influenzae, S. aureus, and Moraxella catarrhalis was determined by conventional culture in 330 PCV10-vaccinated 11-month-old children, 330 PCV7-vaccinated 24-month-old children, and their parents. Carriage prevalence was compared with similar carriage studies conducted in 2005, 2009, and 2010/2011. Although serotype 19A remained the most frequently carried pneumococcal serotype in children, prevalence of 19A significantly declined in PCV7-vaccinated 24-month-old children (14% to 8%, p = 0.01), but less in PCV10-vaccinated 11-month-old children (12% to 9%, p = 0.31). Carriage of H. influenzae remained stable at an elevated level (65% in 11-month-olds and 69% in 24-month-olds), while the carriage of S. aureus returned to pre-PCV7 levels in 11-month-old children (14% in 2010/2011 to 7% in 2012/2013), but not in 24-month-olds (remained at 7%). Our results might indicate a new balance between replacing non-vaccine pneumococcal serotypes and other potential pathogenic bacteria in nasopharyngeal carriage. Carriage studies are valuable tools in assessing vaccine effects on pathogens circulating in the population, for evaluation of PCV impact, and in predicting changes in respiratory and invasive disease.     

Pneumococcal carriage in children in Ulaanbaatar,Mongolia before and one year after the introduction of the 13-valent pneumococcal conjugate vaccine

BackgroundNasopharyngeal carriage of Streptococcus pneumoniae precedes disease, is the source of pneumococcal community spread, and the mechanism for herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few PCV impact studies in low- and middle-income countries, particularly in Asia. In 2016, Mongolia introduced the 13-valent PCV (PCV13) in a phased manner using a 2 + 1 schedule, with catch-up. We aimed to assess the impact of PCV13 introduction on nasopharyngeal pneumococcal carriage and density in children in Mongolia.MethodsWe conducted two cross-sectional carriage surveys (pre- and one year post-PCV) at community health clinics in two districts of the capital city, Ulaanbaatar in both May-July 2015 and 2017. The study analysis included 961 children too young to be vaccinated (5–8 weeks old) and 989 children eligible for vaccination (12–23 months old). Pneumococci were detected by quantitative real-time PCR and molecular serotyping performed using DNA microarray.FindingsOne year post-PCV introduction, PCV13 serotype carriage reduced by 52% in 12–23 month olds (adjusted prevalence ratio [aPR] 0.48 [95% confidence interval [CI] 0.39–0.59]), with evidence of non-PCV13 serotype replacement (aPR 1.55 [95% CI 1.30–1.85]), compared with the pre-PCV period. In 5–8 week olds, PCV13 serotype carriage reduced by 51% (aPR 0.49 [95% CI 0.33–0.73]) with no significant change in non-PCV13 serotype carriage (aPR 1.10 [95% CI 0.83–1.46]). An increase was observed in both PCV13 and non-PCV13 pneumococcal density post-PCV introduction. Antimicrobial resistance (AMR) genes were common, with 82.3% of samples containing at least one of the 10 AMR genes assessed.ConclusionThis study demonstrates substantive PCV13 impact on pneumococcal carriage one year post-vaccine introduction in Mongolia. The reductions in PCV13 serotype carriage are likely to result in reductions in pneumococcal disease including indirect effects. Increases in non-PCV13 serotypes require further monitoring.     

Modeling the decline in pneumococcal acute otitis media following the introduction of pneumococcal conjugate vaccines in the US

We hypothesized that following the introduction of PCV7, the exchange of vaccine serotypes (VST) for non-vaccine serotypes (NVST) in the nasopharynx has resulted in fewer episodes of pneumococcal acute otitis media (AOM) due to the reduced capacity for common NVST strains to cause disease. We modeled the change in the proportion of children colonized with S. pneumoniae who would develop pneumococcal AOM that would occur due to serotype replacement, and projected the future impact of PCV13. Our model is based on observed changes in the nasopharyngeal pneumococcal serotype distribution from the pre- to post-PCV7 era, and an estimated capacity of each serotype to produce pneumococcal AOM given colonization; the latter was derived by dividing serotype-specific disease prevalence by serotype-specific carriage prevalence in the same population. Our results indicate a 12% (95% CI 0.5-26) decline in the number of AOM episodes attributable to S. pneumoniae in children less than 3 years of age between 2000 and 2007 due to the combined effects of PCV7 vaccine efficacy and vaccine-induced serotype replacement, and predicts that PCV13 will further decrease pneumococcal AOM an additional 27% (95% CI 13-40) from 2007 to 2013. Evaluation of changes in VST disease revealed a 91% (95% CI 83-97) decrease in PCV7-VST AOM from 2000 to 2007, and predicted an additional 65% (95% CI 57-74) decrease in PCV13-VST AOM from 2007 to 2013. Our model indicates that following vaccination, nasopharyngeal replacement of VST by NVST has led to a decrease in the amount of pneumococcal AOM despite a consistent rate of S. pneumoniae colonization, and that pneumococcal AOM may continue to decrease as pneumococcal serotypes with greater capacity to cause disease are replaced by less locally invasive serotypes.     

Distribution of invasive Streptococcus pneumoniae serotypes before and 5 years after the introduction of 10-valent pneumococcal conjugate vaccine in Brazil

BackgroundIn March 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine immunization program in Brazil. We describe the pneumococcal serotypes that caused invasive pneumococcal diseases (IPD) before and after the introduction of PCV10 using data from a national laboratory-based surveillance system.MethodWe compared the prevalence of vaccine types (VT) and non-vaccine types (NVT) of Streptococcus pneumoniae in three periods, pre-PCV10 (January/2005-December/2009), early post-PCV10 (January/2010-December/2013), and late post-PCV10 (January/2014-December/2015), by episode in meningitis and non-meningitis cases and by age group. Changes in serotype prevalence in the early and late post-PCV10 periods were determined using pre-PCV10 period as a reference.ResultsA total of 8971 IPD isolates from patients aged 2 months to 99 years were analyzed. In the late post-PCV10 period, the VT-IPD reduction in the 2-month to 4-year age group was 83.4% for meningitis and 87.4% for non-meningitis cases; in the age groups 5–17 years, 18–64 years, and ≥65 years, VT declined by 56.1%, 54.1%, and 47.4%, respectively, in meningitis cases, and by 60.9%, 47.7%, and 53.4%, respectively, in non-meningitis cases. NVT-IPD increased throughout the study period, driven mainly by serotypes 3, 6C, and 19A, which remained the predominant types causing IPD in the late post-PCV10 period.ConclusionWe observed direct and indirect PCV10 protection against IPD caused by VT and a shift in the distribution of serotypes 5 years after the introduction of PCV10. Continued IPD surveillance is needed to evaluate the sustainability of the high prevalence of serotypes 3, 6C, and 19A, which were not included in PCV10.     

PCV13-vaccinated children still carrying PCV13 additional serotypes show similar carriage density to a control group of PCV7-vaccinated children

BackgroundIn addition to reducing vaccine-type nasopharyngeal carriage rates, pneumococcal conjugate vaccines (PCVs) may decrease carriage density in vaccinated individuals still carrying vaccine serotypes. However, reduction of carriage density has not been systematically studied. This study compared the effect of PCV13 versus PCV7 on carriage density of the serotypes in PCV13 that are not included in PCV7.MethodsThis randomized, double-blind study was conducted in southern Israel and included Jewish and Bedouin subjects. Per protocol, 881 and 873 infants received PCV13 and PCV7, respectively, at ages 2, 4, 6, and 12 months. Nasopharyngeal cultures at ages 7, 12, 13, 18, and 24 months were plated using the 4-quadrant semiquantitative method and graded 0 (negative) to 4 (growth in all plate quadrants). In this post hoc analysis, the least squares means of cumulative colonization densities per serotype and serotype combination of the total population and each ethnic subpopulation in each vaccine group were calculated, and differences between vaccine groups derived from a linear model.ResultsPCV13-vaccinated children still carrying the 6 additional PCV13 serotypes unique to PCV13 showed no significant differences in carriage density compared with the PCV7-vaccinated control group. No differences in carriage density were shown between Jewish and Bedouin subpopulations despite higher carriage rates among Bedouin subjects.ConclusionsAlthough PCV13 vaccination reduces vaccine-type carriage compared with PCV7 vaccination by reducing nasopharyngeal acquisition of the additional PCV13 serotypes as previously reported, the current study lacks evidence of a decrease in carriage density of these serotypes when acquired in vaccinated children. Despite the lack of effect on carriage density observed, surveillance data suggest a dramatic decrease in disease rates after PCV implementation. Thus, the current analysis suggests that PCV’s impact on carriage density has minimal or no impact on vaccine success. (www.ClinicalTrials.gov: NCT00508742)     

Evaluation of the impact of HIV-1 infection and density of common nasopharyngeal bacterial colonizers in South African children immunized with 7-valent pneumococcal conjugate vaccine

BackgroundDue to limitations in standard culture methods, the impact of pneumococcal conjugate vaccine (PCV) immunization on nasopharyngeal bacterial carriage density is unclear, including among HIV-infected children.MethodsThe prevalence and density of serotype/serogroup-specific pneumococcal and other nasopharyngeal colonizing bacteria were investigated in archived swabs of HIV-infected and HIV-uninfected, PCV-7 immunized (at 6, 10 and 14 weeks of age) South African children collected at 9 and 16 months of age. During the course of the study, PCV-immunization of children in Soweto was limited to study-participants, as the vaccine had not been introduced into the public immunization program.ResultsAt 9 months of age, the prevalence of overall pneumococcal colonization was lower in HIV-infected (58.6%) than HIV-uninfected children (69.9%, p = 0.02), mainly due to lower prevalence of non-vaccine-serotype colonization (27.8% vs. 40%, respectively; p = 0.047). The mean-log₁₀ density of pneumococcal colonization was, however, higher in HIV-infected (4.81 CFU/ml) than HIV-uninfected pneumococcal colonized children (4.44 CFU/ml; p = 0.014); mainly due to higher mean-log₁₀ density of PCV7-serotype colonization (4.21 vs. 3.72 CFU/ml; p = 0.014). No difference in the prevalence or density of overall pneumococci was found at 16 months of age. The prevalence of non-vaccine serotype colonization remained 1.7 fold higher in HIV-uninfected (60.4%) than HIV-infected children (50.9%, p = 0.049). Other differences included a lower prevalence of H. influenzae colonization in HIV-infected (42.3% and 56%) than HIV-uninfected children (64.2% and 73.4%) at both 9 and 16 months of age respectively; however, the density of colonization was similar.ConclusionIncreased carriage density of residual PCV7-serotypes might cause HIV-infected children to have a higher risk of pneumococcal disease. The higher carriage density observed in HIV-infected children could be attributed to a combination of factors, including HIV treatment and impaired host immunity. Additional studies are needed.     

Pneumococcal carriage,serotype distribution,and antimicrobial susceptibility in Papua New Guinean children vaccinated with PCV10 or PCV13 in a head-to-head trial

BackgroundChildren in Papua New Guinea (PNG) are at high risk of pneumococcal infections. We investigated pneumococcal carriage rates, serotype distribution, and antimicrobial susceptibility in PNG children after vaccination with 10-valent or 13-valent pneumococcal conjugate vaccines (PCV10; PCV13).MethodsInfants (N = 262) were randomized to receive 3 doses of PCV10 or PCV13 at 1-2-3 months of age, followed by pneumococcal polysaccharide vaccination (PPV) or no PPV at 9 months of age. Nasopharyngeal swabs (NPS) collected at ages 1, 4, 9, 10, 23 and 24 months were cultured using standard bacteriological procedures. Morphologically distinct Streptococcus pneumoniae colonies were serotyped by the Quellung reaction. Antimicrobial susceptibility was determined by Kirby-Bauer disc diffusion and minimum inhibitory concentration (MIC).ResultsS. pneumoniae was isolated from 883/1063 NPS collected at 1–23 months of age, including 820 serotypeable (64 different serotypes) and 144 non-serotypeable isolates. At age 23 months, 93.6% (95%CI 86.6–97.6%) of PCV10 recipients and 88.6% (95%CI 80.1–94.4%) of PCV13 recipients were pneumococcal carriers, with higher carriage of PCV10 serotypes by PCV10 recipients (19.8%, 95%CI 12.2–29.5) than PCV13 recipients (9.3%, 95%CI 4.1–17.3) (p = 0.049). There were no other statistically significant differences between PCV10 and PCV13 recipients and children receiving PPV or no PPV. Nearly half (45.6%) of carried pneumococci were non-susceptible to penicillin based on the meningitis breakpoint (MIC ≥ 0.12 µg/mL), but resistance was rare (1.1%) using the non-meningitis cut-off (MIC ≥ 8 µg/mL). Non-susceptibility to trimethoprim-sulfamethoxazole (SXT) was common: 23.2% of isolates showed intermediate resistance (MIC 1/19–2/38 µg/mL) and 16.9% full resistance (MIC ≥ 4/76 µg/mL). PCV serotypes 14 and 19A were commonly non-susceptible to both penicillin (14, 97%; 19A, 70%) and SXT (14, 97%; 19A, 87%).ConclusionEven after PCV10 or PCV13 vaccination, children living in a high-risk setting such as PNG continue to experience high levels of pneumococcal colonization, including carriage of highly antimicrobial-resistant PCV serotypes.The study is registered with ClinicalTrials.gov (CTN NCT01619462).