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

Background

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.

Methods

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.

Results

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.

Conclusions

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.     

Changes in Streptococcus pneumoniae serotype distribution in invasive disease and nasopharyngeal carriage after the heptavalent pneumococcal conjugate vaccine introduction in Bogotá, Colombia

Background

In Bogotá, the Heptavalent Conjugate Vaccine (PCV7) was introduced into childhood immunization schedule since 2009. The aim of this study was to assess the changes in serotype distribution and penicillin susceptibility of Streptococcus pneumoniae isolates recovered from nasopharyngeal samples and invasive disease among children living in Bogotá, before and after PCV7 introduction.

Methods

Nasopharyngeal swabs were collected from healthy children aged between 12 and 18 months of age before (years 2005–2006) and after (2011) PCV7 introduction. Identification of S. pneumoniae was performed by multiplex PCR. Serotype was determined by PCR and Quellung reaction. Susceptibility to penicillin, ceftriaxone, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline and erythromycin was evaluated. In addition, distribution of serotypes and antimicrobial susceptibility before and after vaccine introduction among invasive isolates recovered from children ≤2 years old living in Bogotá was analyzed.

Results

Prevalence of pneumococcal nasopharyngeal carriage declined from 55.7% (137/246) in unvaccinated to 44.2% (87/197) (p = 0.01) in vaccinated children. The proportion of children carrying PCV7 serotypes decreased from 23.6% (58/246) to 7.6% (15/197) (p < 0.001). The decrease was counterbalanced by an increase in the proportion of non-PCV7 serotypes. The most prevalent among emerging serotypes were 15A, 15B, 15 C, 11A and 35B. Among IPD isolates, PCV7 serotypes decreased from 69.1% (235/340) in 2005/2009 to 38.0% (32/84) in 2010/2011 (p < 0.001). The increase of non-PCV7 serotypes was significant. Resistance to penicillin among invasive isolates recovered from meningitis decreased from 41.1% (30/73) in the pre-vaccine period to 14.2% (2/14) in post-vaccine period (p = 0.02).

Conclusions

A decrease in the prevalence of pneumococcal nasopharyngeal carriage following the introduction of PCV7 vaccine, have been overshadowed by an important surge in the prevalence of non-PCV7 serotypes. Systematic surveillance combining nasopharyngeal carriage surveys and IPD detection could help in evaluating the impact of conjugate vaccines.     

Immunogenicity and safety of heptavalent conjugate vaccine against Streptococcus pneumoniae in pre-term Polish infants

The purpose of the study was to assess post-vaccination immune response and occurrence of adverse events in the group of prematurely born infants. The study included 40 pre-term infants. Each child was vaccined four times (2, 4, 6 and 16 months) with the heptavalent conjugated pneumococcal vaccine (PCV7). Assessing of the level of antibodies was performed before vaccination, 4 weeks after primary series, before and 4 weeks after the booster dose. The research participants were qualified into 2 groups: group I - 19 children born before 30th gestational week, group II - 21 children born between the 30th and 34th gestational week. After the basic vaccination, an increase in the average antibody concentration in the area of all serotypes in most of the children tested was registered, with no significant differences observed between the groups. However, differences between individual serotypes were observed. The lowest values were found for serotype 6B. Before administering the booster dose, a significant drop in antibody titre in all of the children tested was noted. The last vaccination caused another significant increase in antibody concentration in both groups and the results obtained were markedly higher than those obtained after administering three vaccine doses. The majority of the children tested (with the exception of three from group II) achieved the preventive antibody level ≥0.35 μg/ml. In all of the children, no serious adverse events were observed. Our research showed, that heptavalent pneumococcal conjugate vaccine is immunogenic in children born before the completion of the 34th week of pregnancy. A booster dose of vaccine must be given at the right time to optimal response to the vaccine for all serotypes. Finally, any serious adverse events were observed.     

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

Background

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.

Methods

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.

Results

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.

Conclusions

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.     

Streptococcus pneumoniae serotypes isolated from the middle ear fluid of Costa Rican children following introduction of the heptavalent pneumococcal conjugate vaccine into a limited population

Background

The heptavalent pneumococcal conjugate vaccine (PCV-7) was introduced in high risk children and into the private market in Costa Rica in 2004 (<5% annual birth cohort). The aim of this study was to compare the Streptococcus pneumoniae serotype (ST) distribution, antibiotic resistance patterns and potential coverage before and after partial introduction of PCV-7.

Methods

A comparison between the S. pneumoniae isolates obtained and serotyped from the middle ear fluid (MEF) of Costa Rican children with otitis media between years 1999 and 2003 (before PCV-7 usage) and those isolates obtained from 2004 to 2008.

Results

A total of 145 and 218 MEF S. pneumoniae were serotyped between years 1999 and 2003 and 2004 and 2008, respectively. Considering a 19F outbreak observed between years 1999 and 2003, the following statistically significant changes in serotype distribution were detected between1999 and 2003 and 2004 and 2008: ST 3: 4.8–12.8% (P = 0.01); ST 11A: 0–4.1% (P = 0.01); ST 14: 3.5–21.1% (P < 0.001) and ST 19F: 52.4–18.3% (P < 0.05). Comparison of the two study periods demonstrated that during 2004 and 2008 a statistically significant decrease in penicillin non-susceptible serotypes (36.2–20.4% [P = 0.003]) and a statistically significant increase in trimethoprim-sulfametoxazole resistant serotypes (54.9–68.5%, respectively [P = 0.03]) was observed. Potential pneumococcal vaccines coverage between 1999 and 2003 and between 2004 and 2008 were: for PCV-7: 77.2–60.5%, respectively (P = 0.001); for the 10-valent conjugated vaccine (PCV-10): 78.6–61.4%, respectively (P = 0.0008) and for the 13-valent conjugated vaccine (PCV-13): 84.8–79.3%, respectively (P = 0.2).

Conclusions

Changes in the serotype distribution and antimicrobial susceptibility of MEF S. pneumoniae have been observed in Costa Rican children with OM. Because of the limited use of PCV-7 during the study period, these changes probably cannot be attributed to PCV-7 use. Between 2004 and 2008, PCV-13 offered the highest potential vaccine coverage.     

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.     

Poor potential coverage for 7-valent pneumococcal conjugate vaccine,Malawi

Streptococcus pneumoniae infections can be prevented by using new conjugate vaccines, but these vaccines have limited serogroup coverage. We report the first serogrouping data from carried and invasive isolates obtained from children and adults in Malawi. The 7-valent vaccine would cover 41% of invasive isolates from children and 25% from adults. A 9-valent vaccine, including types 1 and 5, would cover 66% of invasive isolates from children and 55% from adults.     

Dynamics of pneumococcal carriage among day-care center attendees during the transition from the 7-valent to the higher-valent pneumococcal conjugate vaccines in Greece

Background

In Greece recently, higher-valent pneumococcal conjugate vaccines (PCVs) replaced the 7-valent (PCV7); the 10-valent (PCV10) became available in May 2009 and the 13-valent (PCV13) in June 2010.

Methods

We investigated the nasopharyngeal colonization with Streptococcus pneumoniae in day-care center attendees in Athens and the prefecture of Viotia. Between December 2010 and June 2011, nasopharyngeal cultures were obtained 4 times, at enrollment and then every 6 to 8 weeks.

Results

Among the 233 children, 225 (96.6%) had been vaccinated with ≥1 dose of PCV7. One tenth of the PCV7 vaccinated attendees had also received ≥1 dose of PCV13 or PCV10. During the 4 samplings, 358 isolates were recovered from a total of 874 samples. Of the 233 children, 183 (78.5%) were found to carry S. pneumoniae at least once. The overall serotype distribution among carriers was similar regardless of the time lapsed since the last PCV7 dose. A high frequency of 19A (17.1%) coincided with a low frequency of 19F (1.4%). Non-PCV13 serotypes accounted for 73.1% of the isolates; 23B, 15B/C, 16F, 21, 11A, 15A, 6C, 10A, 22F and 23A were the most common. Among attendees aged 24–59 months (median age 42 months), prolonged carriage of a non-PCV13 serotype was relatively common, mainly for 21 and 16F. One out of 4 cases of colonization with the prevalent non-PCV13 serotypes was followed by persistent carriage for 5 to 14 weeks.

Conclusions

During this period of transition to the higher-valent PCVs in the day-care center setting, non-PCV13 serotypes dominated and exhibited prolonged colonization. The frequency and the duration of prolonged carriage tends to be increased, if sampling frequency increases and the carriage time before and after positive cultures is taken into consideration. Further studies regarding the fitness of the colonizing non-PCV13 serotypes will likely to be seen in the future.     

Serotypes and antimicrobial susceptibilities of invasive Streptococcus pneumoniae before and after introduction of 7-valent pneumococcal conjugate vaccine, Hong Kong, 1995-2009

This study analyzed 828 isolates causing invasive pneumococcal disease (IPD) before (1995-2001, n = 265) and after (2007-2009, n = 563) the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in Hong Kong. In children <5 years, serotype 14 had declined (36-15.7%, P < 0.01) while 19A had increased (0-12.9%, P < 0.01) in the before and after periods, respectively. In children aged <5 years, the proportion of PCV7 serotypes declined from 89.5% to 65.7% (72.8% if included cross protection against 6A) with time but that of PCV13 serotypes remained stable (91.4-93.2%). In elderly ≥65 years, 9V and 23F decreased from 3.8% to 0.3% (P = 0.01) and from 18.9% to 7.4% (P <0.01), respectively while 7F increased significantly from 0% to 4.1% (P = 0.04) over the same periods. Among isolates from aged <5 years, dual penicillin/erythromycin resistance increased from 44.1% to 64.2% (P = 0.01). The types that often had dual penicillin/erythromycin resistance were 6B, 14, 19F, 23F, 6A and 19A. The emergence of serotype 19A was associated with expansion of sequence type 320.     

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 antibodies in a child with type 14 pneumococcal conjugate vaccine failure

We measured the concentration, opsonic activity, and avidity of serotype-specific serum antibodies in a pneumococcal conjugate vaccine (PnCRM7) efficacy trial participant who contracted serotype 14 pneumococcal bacteremia following dose 3 of PnCRM7. Controls included 18 PnCRM7- and 10 MnCC-vaccinated children without invasive pneumococcal disease (IPD). The child with vaccine failure had 4.98 mcg/mL of serotype 14 antibodies 10 days before disease onset; these antibodies had greater opsonic activity and lower avidity than those of control PnCRM7 recipients. The child had no booster response to a fourth dose of PnCRM7 for most vaccine serotypes. We conclude that antibody concentration, functional activity and avidity do not predict individual protection against IPD, and immunological correlates of protection are only useful at the population level.     

Streptococcus pneumoniae serotype 19A in children, South Korea

Despite the concern of replacement disease, notably by serotype 19A after 7-valent conjugate vaccine (PCV7) use, serotype 19A was increasingly recognized in Korean children before the introduction of PCV7. To understand the dynamics of serogroup 19 prevalence from 1991-2006, we serotyped 538 pediatric pneumococcal isolates. Serogroup 19 isolates (n = 126) were characterized by antimicrobial drug susceptibility, presence of mefA/ermB, and multilocus sequence typing. Overall, the proportion of serotype 19A isolates increased but serotype 19F decreased. Among children <5 years of age, the proportion of serotype 19A isolates in invasive pneumococcal disease increased from 0% in 1991-1994 to 8%-10% in 1995-2000, reached 26% in 2001-2003, and remained at 20% in 2004-2006 when vaccine coverage did not exceed 25% (p = 0.005 for trend). This study demonstrates that the expansion of multidrug-resistant ST320 was responsible for the increase in serotype 19A before PCV7 use.     

Long-term impact of pneumococcal polysaccharide vaccination on nasopharyngeal carriage in children previously vaccinated with various pneumococcal conjugate vaccine regimes

Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV.Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n = 194) were obtained from healthy children who participated in FiPP (now aged 5–7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR.There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children.Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23vPPV in children under two years of age are appropriate.     

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.     

Impact of a single dose of the 7-valent pneumococcal conjugate vaccine on colonization

The impact of the 7-valent pneumococcal conjugate vaccine (PCV7) on the pneumococcal flora has been mostly studied without evaluating multiple colonization and the mechanism(s) leading to serotype replacement. These issues are addressed here, while assessing the effect of a single PCV7 dose. A group of children received one PCV7 dose just after nasopharyngeal sampling, with the control receiving no vaccine and both groups being sampled again a month later. Up to 10 pneumococcal isolates were recovered per colonized child—1224 isolates were serotyped and representative ones characterized by pulsed-field gel electrophoresis. In vaccinated children, serotype replacement between vaccine (VT) and non-vaccine (NVT) types occurred in single and multiple carriers, and VTs were less prone to be de novo acquired. NVT unmasking was only detected in the vaccinated group. One month after vaccination with a single dose, PCV7 prevents VT de novo acquisition and promotes NVT unmasking.     

7-Valent pneumococcal conjugate vaccine and otitis media: Effectiveness of a 2-dose versus 3-dose primary series

Background

Seven-valent pneumococcal conjugate vaccination (PCV7) has been shown to reduce rates of otitis media (OM) when given as a 2- or 3-dose primary series followed by a booster dose. However, data on the 2- or 3-dose primary series’ relative effectiveness against OM is very limited. Using data from the United States after the 2000 introduction of PCV7, we compared the effectiveness of a 2- versus a 3-dose primary series against acute otitis media (AOM).

Methods

We examined the 2002 birth cohort from the Medstat MarketScan insurance claims database and compared the incidence of AOM in children that received two or three doses in the primary PCV7 series using propensity score matching. We assessed AOM rates after completion of the primary series and before the booster dose, and after the booster dose until four years of age.

Results

Among the 2002 birth cohort captured by MarketScan, we identified 38,786 children we could match with immunization data; of these 8515 (22%) received a 2-dose primary series and 10,152 (26%) received a 3-dose primary series. After matching, cumulative AOM incidence between 6 and 12 months among children who did not receive a PCV7 dose between the primary series and the booster dose was 37.6% for the 2-dose series and 35.0% for the 3-dose series. This difference was not statistically significant (p = 0.22). Cumulative AOM incidence between one and four years, i.e., after the booster dose, was 104.4% for the 2-dose primary series and 102.5% for the 3-dose primary series, and the difference between them was also statistically insignificant.

Conclusion

In a population of highly-insured children, a 2-dose primary series of PCV7 appears to provide similar protection against AOM as a 3-dose primary series. These data have important implications for national immunization programs where AOM is an important driver of cost-effectiveness.     

Colonization with 19F and other pneumococcal conjugate vaccine serotypes in children in St. Louis,Missouri, USA

BackgroundThe epidemiology of nasopharyngeal (NP) pneumococcal carriage varies with geography and has changed in response to pneumococcal conjugate vaccine (PCV): a low prevalence (3% or less of colonizing isolates) of colonization by vaccine-type (VT) pneumococcal serotypes after PCV introduction has been reported. The primary goal of this study was to determine the VT serotype prevalence of NP pneumococcal colonization of children residing in the St. Louis, MO, USA metropolitan area following introduction of the 13-valent PCV in 2010. The secondary goal of this study was to identify characteristics associated with NP pneumococcal carriage of any serotype.MethodsBetween July 2013 and April 2016, we enrolled 397 healthy children, aged 0–17 years, who required sedation for procedures or minor surgeries at St. Louis Children’s Hospital. NP swabs were collected after sedation or anesthesia and cultured for pneumococcus. Vaccine records were obtained from primary care providers or from state immunization databases. Parents/guardians completed a questionnaire to provide demographics, past medical history and household characteristics.ResultsOf the 88 pneumococcal isolates recovered from 84 colonized subjects (21.2% of all enrolled subjects; 95% CI 17.2–25.2%), 16 were VT. Eleven isolates were serotype 19F (12.5%), four (4.5%) were 6A and one (1.1%) was 19A. Prevalence of VT among colonizing isolates was thus 18.2% (CI 10.1–26.1%) in our cohort, despite complete PCV vaccination in 87% of colonized children. Factors associated with pneumococcal colonization by any serotype included younger age and daycare attendance.ConclusionChildren in St. Louis exhibit a higher prevalence of VT serotypes among pneumococcal carriage isolates than has been reported in other areas in the US, demonstrating the necessity of ongoing surveillance of local epidemiology and providing evidence that serotype 19F can remain prevalent in a pediatric population despite high vaccine uptake.     

Serotypes 1, 7F and 19A became the leading causes of pediatric invasive pneumococcal infections in Portugal after 7 years of heptavalent conjugate vaccine use

We characterized 353 isolates responsible for pediatric invasive pneumococcal infections (IPD) in Portugal between 2006 and 2008. Serotypes included in the seven-valent conjugate vaccine (PCV7) accounted for 17% of IPD. Serotypes 1, 7F and 19A were the most frequent causes of IPD and the later consolidated as the most frequent serotype among erythromycin and penicillin non-susceptible isolates. Serotype 1 was associated with older children and empyemas, while serotype 19A was associated with IPD in younger (<2 years) children. The higher valency vaccines PCV10 and PCV13 have a potentially superior coverage, 55% and 83% respectively, but non-vaccine serotypes are emerging as important causes of IPD. A decline of resistance with patient age was noted. Comparing with previous data from Portugal, this study showed a continued decline of PCV7 serotypes and that overall resistance has stabilized following the initial decline of the first post-PCV7 years.     

Pneumococcal carriage in children and adults two years after introduction of the thirteen valent pneumococcal conjugate vaccine in England

Background/Aims

In April 2010 the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 13-valent PCV. We investigated pneumococcal carriage in children eligible for PCV7 or PCV13 and their household contacts.

Methods

Eligible families in Hertfordshire and Gloucester were identified and a nasopharyngeal swab obtained from consenting household members between July 2012 and March 2013. Samples were cultured for Streptococcus pneumoniae and serotyped by standard methods. For each serotype the ratio of its prevalence in invasive pneumococcal disease (IPD) to its carriage prevalence (case:carrier ratio, CCR) was calculated. Results were compared with previous carriage studies in 2001/2002 and 2008/2009, before and after PCV7 introduction.

Results

217 households were included. Among <5-year olds 47.7% (95% confidence interval 41.8–53.5) were carrying a pneumococcus compared with 51.0% (95% CI: 44.0–58.0) in 2008/2009 and 48.4% (95% CI: 44.1–52.7) in 2001/2002. The odds of carrying a PCV7 serotype was significantly reduced in 2008/2009 (0.07, 95% CI: 0.03–0.16) and 2012/2013 (0.01 95% CI: 0.00–0.07) relative to 2001/2002, while the odds of carrying any of the extra six PCV13 serotypes increased after PCV7 introduction (1.38, 95%CI: 0.73–2.59) but declined significantly after PCV13 introduction (0.05, 95%CI: 0.01–0.37). The CCRs for the frequently carried serotypes were relatively low, with the highest CCR observed for serotypes 7F, 19A, 3, 8, and 33F. Across the three carriage studies, CCR estimates were stable for nearly all serotypes.

Conclusion

Carriage of additional PCV13 serotypes has rapidly reduced post-PCV13 introduction in both vaccinated and unvaccinated individuals with a continued decline in transmission of PCV7 serotypes. Carriage rates in children remain unchanged, but the low CCRs of replacing serotypes would be expected to further reduce overall IPD across all age groups.     

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.