Changes in the incidence of Streptococcus pneumoniae bacteremia and its serotypes over 10 years in one hospital in South Korea

Here, we examined the distribution of pneumococcal serotypes and the antibiotic susceptibility of Streptococcus pneumoniae in clinical blood isolates. The serotypes of 91 S. pneumoniae blood isolates, collected from January 2003 to March 2014, were identified by multiplex PCR and sequencing. The most common serotypes were 19F, 19A, 3, 4, and 14, accounting for 53.8% of the total. The serotype coverage rates of pneumococcal conjugated vaccine (PCV) 7, PCV10, and PCV13 were different during three test periods: 38.7%, 70.9%, and 93.5% in period I (2003–2005), 46.8%, 50.0%, and 75.0% in period II (2006–2008), and 28.5%, 32.1%, and 64.2% in period III (2009–2014), respectively. By contrast, the number of non-PCV13 serotypes increased from 6.4% in period I to 25% and 35.7% in periods II and III, respectively. The susceptibility of non-PCV13 serotypes to antimicrobial agents (penicillin, erythromycin, cefotaxime, and meropenem) was higher than that of PCV serotypes. In particular, non-PCV13 serotypes showed 100% and 95% susceptibility to penicillin and cefotaxime, respectively. Serotypes 19A and 19F showed high prevalence (79.1%) among 24 multi-drug resistant (MDR) isolates. Notably, all serotype 19A isolates were MDR. From January 2003 to March 2014, the proportion of non-PCV13 serotype pneumococci in blood isolates increased whereas the coverage rate of PCV13 decreased. Effective pneumococcal vaccines are required to protect against MDR serotype 19A isolates and the increasing number of non-PCV13 serotypes.     

Serotype distribution and antibiotic resistance of 140 pneumococcal isolates from pediatric patients with upper respiratory infections in Beijing, 2010

In the present study, the serotype distribution and antibiotic resistance of S. pneumoniae from pediatric patients with upper respiratory infections in Beijing, 2010 were described. 140 pneumococcal isolates were obtained, and the prevailing five serotypes were 19F (18.6%), 23F (9.3%), 14 (9.3%), 15 (9.3%), and 6A (7.1%). The vaccine coverage of PCV7, PCV10, and PCV13 were 43.6%, 43.6%, and 60.0%, respectively. According to the CLSI 2010 criteria, 99.3% of the S. pneumoniae isolates were susceptible to penicillin. The resistance rates to erythromycin and azithromycin were 96.4% and 97.1%, respectively. Meanwhile, 64.3% (90/140) of all pneumococcal isolates were multidrug-resistant S. pneumoniae (MDRSP). PCV13 covered 68.9% (62/90) of MDRSP strains, whereas it was 47.8% (43/90) for PCV7. ErmB was the dominant macrolide-resistance gene, whereas 30.4% pneumococcal isolates expressed both ermB and mefA. No isolate expressed ermTR. The potential coverage of PCV13 is higher than PCV7 and PCV10 because high rates of serotypes 6A and 19A, and the conjugate vaccines could prevent the spread of MDRSP. S. pneumoniae is still sensitive to penicillin. The resistance rate of S. pneumoniae to macrolides is high and ermB is the dominant macrolide-resistance gene in China, so continued surveillance of the antimicrobial susceptibility of S. pneumoniae may be necessary.     

Distribution, dynamics and antibiotic resistance patterns of Streptococcus pneumoniae serotypes causing acute otitis media in children in southern Israel during the 10 year-period before the introduction of the 7-valent pneumococcal conjugate vaccine

Objectives

To determine the dynamics of serotype prevalence, potential coverage by pneumococcal conjugate vaccines (PCV) and antibiotic resistance patterns of Streptococcus pneumoniae causing acute otitis media (AOM) in children in southern Israel before PCV7 introduction in the routine immunization program in Israel.

Methods

All S. pneumoniae isolates from middle ear fluid from children with AOM during 1999-2008 were included. Prospectively collected demographic data on S. pneumoniae serotypes and antibiotic resistance patterns were analyzed.

Results

A total of 14,911 tympanocenteses yielded 5281(35%) S. pneumoniae. Proportion of S. pneumoniae-AOM did not vary significantly (overall 35%; 33% in 2007; 38% in 2002 and 2003). The most frequent serotypes were 19F, 14, 23F and 19A; in both Jewish and Bedouin children; serotypes 6A and 19A contributed 6% and 10%, respectively, of all S. pneumoniae isolates. Serotypes included in PCV7, PCV10 and PCV13 represented 60%, 64%, 85% in Jewish children vs. 49%, 55% and 74%, respectively, in Bedouin children (P < 0.001). Nonsusceptibility to TMP/SMX decreased significantly, in parallel with a significant increase in the nonsusceptibility to erythromycin, clindamycin and in multidrug resistant (MDR) isolates. No changes were recorded in the proportion of S. pneumoniae isolates with penicillin MIC ≥ 1.0 μg/ml. The proportion of penicillin- and erythromycin-nonsusceptible and of MDR serotype 6A and 19A isolates increased significantly in Bedouin children.

Conclusions

1) No significant changes were recorded in the yearly proportions of serotypes 23F, 19F, 19A, 14 and 6A in both ethnic populations; 2) Potential coverage of the 3 PCVs was higher in Jewish children than in Bedouin children; 3) The relatively high coverage of macrolides- and multidrug-resistant S. pneumoniae by PCV13 and lack of increase in penicillin, erythromycin and multidrug nonsusceptibility among non-PCV13 isolates is encouraging.     

The changing phenotypes and genotypes of invasive pneumococcal isolates from children in Shenzhen during 2013–2017

BackgroundThe phenotypes and genotypes of Streptococcus pneumoniae isolated from invasive pneumococcal diseases (IPDs) were changing all the time. To monitor these changes of phenotypes and genotypes of S. pneumoniae isolates from children, we examined antibiotic susceptibility, serotype distribution and sequence types (STs) of S. pneumoniae, which were isolated before the 13-valent pneumococcal conjugate vaccine (PCV13) introduced into China.MethodsStrains were isolated from children less than 14 years old between January 2013 and May 2017 from Shenzhen Children’s Hospital. Serotypes, antibiotic resistance, and genotypes of these isolates were determined using capsular swelling, E-test, and multi-locus sequence typing, respectively.ResultsA total of 94 S. pneumoniae strains were isolated, which belonged to 15 serotypes. The five most prevalent serotypes were 19F (25.5%), 19A (19%), 14 (17%), 23F (7.5%), and 6B (9.6%). We found 42 STs for these isolates. The most abundant STs were ST271 (24.4%), ST876 (17%), and ST320 (10.6%), mainly related to 19F, 14, and 19A, respectively. The potential coverage of PCV13 was 87.2%. Among non-meningitis isolates, the resistance rates to penicillin and ceftriaxone were 0% and 2%. However, the meningitis isolates showed high resistance to penicillin (80%) and ceftriaxone (20%). Most of these isolates (95.7%) were resistant to erythromycin, and 66 (70.2%) strains carried the ermB gene and 24 (25.5%) strains carried both the ermB and mefA/E genes. Serotype 19A showed the highest mean minimum inhibitory concentration (MIC) for penicillin (MIC = 1.486) than the other serotypes, but no significant difference in penicillin MIC among the three main STs (ST271, ST320, and ST876).ConclusionsThe phenotypes and genotypes of invasive pneumococcal isolates from Shenzhen Children’s Hospital have changed with the passage of time. Compared with PCV7, PCV13 can more effectively protect Chinese children from IPDs. To some extent, these changes are possibly related to the usage of antibiotics and vaccines.     

Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high heptavalent pneumococcal conjugate vaccine coverage in Central Greece

In order to study whether the use of the heptavalent pneumococcal conjugate vaccine (PCV7) led to a shift in the Streptococcus pneumoniae serotypes distribution and whether it modified the resistance to antibiotics, 2649 nasopharyngeal samples were obtained between 2005 and 2009, from children attending day-care centers in Central Greece. The percentage of attendees vaccinated with ≥1 dose of PCV7 increased from 12.9% (2005) to 95.5% (2009). Non-PCV7 serotypes replaced those belonging to PCV7. In 2009, 19F was virtually the only PCV7 serotype that continued to circulate. A significant increase in the frequency of penicillin-intermediate (oral penicillin V breakpoints) isolates coincided with a marked reduction in isolates with high resistance to penicillin. Several non-PCV7 serotypes colonized the children, but their frequency varied substantially from year to year. Each one of 14 specific non-PCV7 serotypes, i.e. 6A, 11A, 15B, 23A, 10A, 16F, 38, 22F, 15C, 19A, 35F, 24F, 6C, and 7F, accounted for ≥2% of pneumococcal isolates in at least 2 annual surveillances. An increase in non-PCV7 serotypes with antibiotic resistance, beyond 6A and 19A, occurred. Intermediate resistance to penicillin was observed in serotype 23B, 15B, 15C, 15A, 35F, 6C, and 24F pneumococci. Their exact role in invasive and non-invasive disease remains to be seen in the years ahead.     

Phenotype,genotype, and serotype distribution of macrolide resistant invasive and non-invasive Streptococcus pneumoniae strains,in Sousse,Tunisia

ObjectiveWe determined the macrolide resistance phenotypes and genotypes in Streptococcus pneumoniae isolates in Sousse and assessed the serotype distribution.MethodsWe included S. pneumoniae strains isolated at our laboratory (2010–2013). The antimicrobial susceptibility was tested according to CA-SFM specifications. Serotyping was performed by agglutination of latex particles, to identify a subset of serotypes included in pneumococcal conjugate vaccines. The presence of macrolide resistance genes (ermB, mefA, mel) was detected by PCR.ResultsA total of 52.8% of 140 S. pneumoniae isolates were macrolide-resistant: MLSB (89.2%) and M (10.8%). The MLSB phenotypes were genotypically confirmed by ermB gene presence. 62% had decreased susceptibility to penicillin. The serotypes were: 14, 1, 23F, and 19A. Serotype coverage by PCV7, PCV10 and PCV13 was 44.2%, 73.6%, and 75.6% respectively.Conclusion50% of S. pneumoniae isolates were macrolide resistant. The MLSB phenotype encoded by the ermB gene was the most frequent. Serotype coverage seems inadequate.     

Serotype distribution of Streptococcus pneumoniae isolated from children hospitalized in Beijing children’s hospital (2013–2019)

BackgroundStreptococcus pneumoniae can cause many infectious diseases among children, and relevant vaccines have not been scheduled into the National Immunization Program in China. The serotype distribution of Streptococcus pneumoniae is essential information used to evaluate the value of pneumococcal vaccines and formulate immunization strategies.MethodsStreptococcus pneumoniae isolates, identified as the disease pathogens, were collected from children hospitalized in Beijing Children’s Hospital from 2013 to 2019. The serotype was detected by the Quellung reaction.ResultsA total of 903 isolates of Streptococcus pneumoniae were collected, among which 809 were from non-invasive infections and 94 were from invasive infections. The non-invasive isolates were mainly isolated from respiratory secretions (49.4%) and bronchoalveolar lavage fluid (38.9%), while invasive isolates were from venous blood (5.4%), cerebrospinal fluid (2.8%) and pleural effusion (2.8%). The leading serotypes were 19F (36.0%), 19A (13.6%), 23F (9.4%), 14 (8.9%), 6A (6.9%), and 6B (5.3%). The overall coverage rates of 10-, 13-, 15-, 20-valent pneumococcal conjugate vaccines (PCV10, PCV13, PCV15, PCV20) and 23-valent pneumococcal polysaccharide vaccine (PPV23) as well as Pneumosil (a 10-valent pneumococcal conjugate vaccine) were 61.6%, 83.2%, 83.4%, 88.0%, 82.4% and 81.6%, respectively. The coverage rates of PCV13, PCV15 and PPV23 in isolates from invasive infections were significantly higher than those from non-invasive infections. The coverage rates of Pneumosil, either on the whole or among different age groups or different infections, were significantly higher than those of PCV10.ConclusionsSerotypes 19F, 19A, 23F, 14, 6A and 6B were the most common types among the isolates. As for pneumococcal vaccines available now, the coverage rate of PCV13 was high, especially in isolates from invasive infections. The promotion of PCV13 or further high valent vaccines might be of greater benefit in preventing pneumococcal infections than other pneumococcal vaccines in children.     

Emergence of antibiotic-resistant non-vaccine serotype pneumococci in nasopharyngeal carriage in children after the use of extended-valency pneumococcal conjugate vaccines in Korea

BackgroundThis study was performed to assess the serotype distribution and antibiotic nonsusceptibility of pneumococcal carriage isolates from children in Korea following the introduction of extended-valency pneumococcal conjugate vaccines (PCVs).MethodsFrom April to June 2014, nasopharyngeal swabs were collected from children who were attending daycare centers in Korea. The collection was conducted in accordance with the World Health Organization Pneumococcal Carriage Working Group standards. Isolates were identified based on colony morphology, the presence of alpha-hemolysis, and inhibition by optochin test. Serotype was determined by Quellung reaction and sequencing analysis (for serogroup 6). The E-test was performed to determine antibiotic susceptibility.ResultsA total of 267 pneumococcal isolates were collected from 734 children. Non-PCV13 serotypes accounted for 88.3% and 23A (12.6%), 15B (10.4%), and 15C (9.5%) were most common. Younger age was associated with higher carriage (65.6% vs. 31.2%, P < 0.001), while completion of PCV vaccination was associated with lower carriage caused by PCV13 serotypes (7.4% vs. 20.8%, P = 0.007). Overall, nonsusceptibility rates were 86.0% to penicillin and 90.5% to erythromycin, with a multidrug resistance rate of 81.5%. Among penicillin-nonsusceptible isolates, those caused by PCV13 serotypes were 11% and non-PCV13 serotypes were 89%. Frequent non-PCV13 serotypes (23A, 15B, and 15C) were all nonsusceptible to both penicillin and erythromycin except one.ConclusionHigh rates of carriage caused by non-PCV13 serotypes such as 23A, 15B, and 15C that show nonsusceptibilities to penicillin and erythromycin were noted following the introduction of extended-valency PCVs in Korea.     

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.     

Nationwide surveillance of paediatric invasive and non-invasive pneumococcal disease in Japan after the introduction of the 13-valent conjugated vaccine, 2015–2017

Streptococcus pneumoniae is still one of the major causes of morbidity and mortality worldwide. In Japan, pneumococcal conjugate vaccine (PCV)7 and PCV13 were licensed in 2010 and 2013, respectively. We conducted a nationwide paediatric invasive pneumococcal disease (IPD) and non-IPD surveillance study in Japan between 2015 and 2017. We collected 498 IPD isolates and 231 non-IPD isolates from a total of 187 medical institutions in Japan. We performed serotyping, antimicrobial susceptibility testing and multi-locus sequencing typing (MLST) for the collected isolates. Among the 498 IPD isolates, the most prevalent serotype was 24F, followed by 12F, 15A and 15B/C. However, 12F increased and 24F significantly decreased during the study period (p < 0.001), resulting in 12F becoming the most prevalent serotype in 2017. Among the IPD isolates, the PCV7 and PCV13 coverage rates were 0.8% and 9.2%, respectively. The most prevalent serotype among the non-IPD isolates was 15A, followed by 35B, 15B/C and 19A. The overall resistance rates to penicillin (PG), cefotaxime (CTX), meropenem (MEM), erythromycin (EM) and levofloxacin (LFX) were 40.5%, 12.2%, 19.4%, 91.8% and 0.5%, respectively. PG, CTX and MEM resistance rates were significantly higher in non-IPD isolates than in IPD isolates (p < 0.001). Serotype 15A-CC63 and serotype 35B-CC558 tended to be multi-drug resistant. In conclusion, the PCV13 coverage rate was significantly lower than that in a previous surveillance study in Japan between 2012 and 2014, and IPD cases attributable to serotype 19A also decreased. We should note the rapid increase in the prevalence of serotype 12F in IPD cases and the spread of the multi-drug resistant serotype 15A-CC63 and 35B-CC558 lineages.     

Serotypes,antimicrobial susceptibility,and molecular epidemiology of invasive and non-invasive Streptococcus pneumoniae isolates in paediatric patients after the introduction of 13-valent conjugate vaccine in a nationwide surveillance study conducted in Japan in 2012–2014

Pneumococcal infection in children is a major public health problem worldwide, including in Japan. The pneumococcal conjugate vaccine 7 (PCV7) was licensed for use in Japan in 2010 followed by PCV13 in 2013. This report includes the results of a nationwide surveillance of invasive pneumococcal disease (IPD) and non-IPD in paediatric patients from January 2012 to December 2014. We collected 343 isolates from 337 IPD patients and 286 isolates from 278 non-IPD patients. Of the IPD isolates, the most identified serotypes included 19A, 24F, and 15A. The prevalence of non-PCV13 serotype isolates increased significantly from 2012 to 2014 (51.6–71.4%, p = 0.004). Serotypes 19A, 15A and 35B were highly non-susceptible to penicillin, and the rates of non-susceptible isolates from IPD patients to penicillin and cefotaxime significantly declined during the study period (p = 0.029 and p = 0.013, respectively). The non-susceptible rate to meropenem increased, particularly for serotype 15A. The IPD isolates comprised clonal complex (CC) 3111 (93.8% was serotype 19A) followed by CC2572 (81.5% was serotype 24F) and CC63 (97.1% was serotype 15A). CC3111, CC63 and CC156 (33.3% was serotype 23A, 28.6% was serotype 6B, and 14.3% was serotype 19A) were highly non-susceptible to penicillin. Of the non-IPD isolates, the most identified serotypes included 19A, 15A, and 3. In conclusion, the introduction of PCV7 and PCV13 resulted in increasing non-PCV13 serotypes and clones, including antimicrobial resistant serotypes 15A and CC63 (Sweden^15A-25 clone).     

Pneumococcal serotype distribution and antimicrobial resistance in Chinese children hospitalized for pneumonia

A prospective study was performed to determine serotype distribution and antimicrobial resistance in Streptococcus pneumoniae (S. pneumoniae) from Chinese children <5 years old meeting pneumonia criteria. A total of 3865 children were enrolled and 338 S. pneumoniae isolates were obtained. The most frequent serotypes were 19F (55.6%), 19A (13.9%), 23F (10.1%), 6B (4.7%), and 14 (3.6%). The 7-, 10- and 13-valent conjugate vaccines, respectively, covered 76.3%, 76.9%, and 92.3% of isolates. Out of the isolates, six (1.8%) were penicillin resistant. All except 1 of the isolates were resistant to erythromycin. Serotype 19A showed the highest drug resistance. The use of PCV7 has the potential to prevent a substantial number of pneumococcal infections. However, PCV13 is likely to prevent more episodes of pneumococcal disease in China because of the high rates of 19A.     

Non-linear relationships between children age and pneumococcal vaccine coverage: Important implications for vaccine prevention strategies

BackgroundStreptococcus pneumoniae (S. pneumoniae) is an important pathogen causing both invasive and non-invasive infections in children, with significant morbidity and mortality worldwide. This study aimed to determine the potential relationships between age and vaccine coverage and between multiple phenotype-genotype characteristics of S. pneumoniae isolated from children.MethodsAll S. pneumoniae isolates were tested for antimicrobial susceptibility, virulence genes, serotypes, and sequence types. The restricted cubic spline models were used to reveal potential relationships between children age and pneumococcal vaccine coverage.ResultsFor capsular-based vaccines, we observed a high coverage rate of 13-valent pneumococcal conjugate vaccine (PCV13, 85.8%) and a significantly non-linear relationship between children age and vaccine coverage (including PCV7, PCV10, and PCV13), with marked fluctuations in children aged < 2 years. For protein-based and pilus-based vaccine candidates, we demonstrated dynamic non-linear relationships between age and vaccine coverage, maintaining a stable and high coverage rate of ply and lytA for all age groups. Moreover, there were significantly high-dimensional corresponding relationships among multiple phenotype-genotype characteristics of S. pneumoniae isolates (such as ST271 associated with serotype 19F, PI-2, and extensively drug-resistance).ConclusionsOur findings suggest that the age for high PCV coverage being children aged ≥ 2 years and also provide important evidence for supporting ply and lytA as priority candidate targets for the development of new-generation protein vaccines.     

Changes in serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates from adult patients in Asia: Emergence of drug-resistant non-vaccine serotypes

This study was performed to investigate the serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae in Asian countries. A prospective surveillance study on S. pneumoniae collected from adult patients (≥50 years old) with invasive pneumococcal disease or community-acquired pneumonia was performed at 66 hospitals in Asian countries (Korea, China, Malaysia, Singapore, the Philippines, and Thailand) in 2012-2017. Serotyping and antimicrobial susceptibility tests of 850 pneumococcal isolates were performed. The proportions of isolates with serotypes covered by 13-valent pneumococcal conjugate vaccine (PCV13) were 37.0% in Korea, 53.4% in China, 77.2% in Malaysia, 35.9% in the Philippines, 68.7% in Singapore, and 60.2% in Thailand. Major serotypes were 19F (10.4%), 19A (10.1%), and 3 (8.5%) in 2012-2017, with different serotype distributions in each country. Macrolide resistance in pneumococci was high (66.8%) and prevalence of multidrug resistance (MDR) also remained high (50.8%). MDR non-PCV13 serotypes such as 11A, 15A, 35B, and 23A have emerged in Asian countries. This study showed the persistent prevalence of 19F and 19A with a noteworthy increase of certain non-PCV13 serotypes in Asian countries. High prevalence of macrolide resistance and MDR was also found in pneumococcal isolates. These data emphasize the need for continued surveillance of pneumococcal epidemiology in Asia in the post-pneumococcal vaccine era.     

儿童侵袭性肺炎链球菌感染的血清型和耐药性

目的 了解某医院住院患儿侵袭性肺炎链球菌感染的临床特征以及菌株的血清型和耐药性,以期指导临床合理用药,寻找防治侵袭性肺炎链球菌感染的有效方法.方法 回顾性分析2014年1月—2018年12月该院明确诊断为侵袭性肺炎链球菌感染患儿的临床资料,肺炎链球菌的药敏结果、血清型,以及疫苗对其血清型覆盖情况.结果 74例侵袭性肺炎...     

Nasopharyngeal s. pneumoniae carriage and density in Belgian infants after 9 years of pneumococcal conjugate vaccine programme

BackgroundIn Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007–2011) to PCV13 (2011–2015) and to PCV10 (2015–2016). A 3-year nasopharyngeal carriage study was initiated during the programme switch in 2016. Main objective of the year 1 assessment was to obtain a baseline measurement of pneumococcal carriage prevalence, carriage density, serotype distribution and antibiotic resistance.Materials/methodsTwo infant populations aged 6–30 months and without use of antibiotics in the seven days prior to sampling were approached: (1) attending one of 85 randomly selected day-care centres (DCC); (2) presenting with AOM at study-trained general practitioners and paediatricians. Demographic and clinical characteristics were documented and a single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT-PCR) targeting LytA was performed.ResultsCulture-based (DCC: 462/760; 60.8% – AOM: 27/39; 69.2%) and LytA-based (DCC: 603/753; 80.1% – AOM: 32/39; 82.1%) carriage prevalence was high. Average pneumococcal DNA load in LytA-positive day-care samples was 6.5 × 10⁶ copies/µl (95%CI = 3.9–9.2 × 10⁶, median = 3.5 × 10⁵); DNA load was positively associated with signs of common cold and negatively with previous antibiotic use. Culture-based frequency of 13 pneumococcal vaccine (PCV) serotypes was 5.4% in DCC and 7.7% in AOM, with 19F and 14 being most frequent, and frequencies below 0.5% for serotypes 3, 6A, 19A in both populations. Predominant non-PCV serotypes were 23B and 23A in day-care and 11A in infants with AOM. In day-care, resistance to penicillin was rare (<0.5%) and absent against levofloxacin; 32.7% and 16.9% isolates were cotrimoxazole- and erythromycin-resistant respectively.ConclusionFour years after PCV13 introduction in the vaccination programme, PCV13 serotype carriage was rare in infants throughout Belgium and penicillin resistance was rare. Continued surveillance in the context of a PCV programme switch is necessary.     

Impact of the pediatric 13-valent pneumococcal conjugate vaccine on serotype distribution and clinical characteristics of pneumococcal pneumonia in adults: The Japan Pneumococcal Vaccine Effectiveness Study (J-PAVE)

BackgroundThe pediatric 13-valent pneumococcal conjugate vaccine (PCV13) was included in the pediatric immunization programme in Japan in late 2013. The impact of vaccination on the serotype distribution and clinical characteristics of pneumococcal pneumonia has not been described.MethodsThe first phase of this multicentre prospective study was conducted at community-based hospitals in Japan from 2011 to 2014. The second phase was conducted from 2016 to 2017. Pneumococcal isolates and clinical data were collected from patients with community-acquired pneumonia who were ≥15 years of age. Patients were classified by pneumococcal serotype to PCV13 serotype, 23-valent pneumococcal polysaccharide vaccine (PPV23) non-PCV13 serotype, and non-vaccine serotype.ResultsA total of 484 patients were enrolled, 241 in the first phase and 243 in the second. The proportion of PCV13 serotypes decreased from 53% to 33% (p < 0.001), whereas PPV23 non-PCV13 serotypes did not change (p = 0.754). PCV13 serotypes were associated with increased risk of elevated blood urea nitrogen (adjusted odds ratio 2.49; 95% confidence interval: 1.49–4.16) and hospitalization (adjusted odds ratio 1.74; 95% confidence interval: 1.02–2.95). These associations were not observed in patients with PPV23 non-PCV13 serotypes.ConclusionsThe occurrence of pneumococcal pneumonia caused by vaccine-covered serotypes dramatically decreased following the introduction of pediatric PCV13. The PCV13 serotypes were associated with pneumonia severity.     

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.     

Hospital-based sentinel surveillance for bacterial meningitis in under-five children prior to the introduction of the PCV13 in India

IntroductionA hospital-based sentinel surveillance network for bacterial meningitis was established in India to estimate the burden of bacterial meningitis, and the proportion of major vaccine-preventable causative organisms. This report summarises the findings of the surveillance conducted between March 2012, and September 2016 in eleven hospitals.MethodsWe enrolled eligible children with bacterial meningitis in the age group of one to 59 months. CSF samples were collected and processed for biochemistry, culture, latex agglutination, and real-time PCR. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility.ResultsAmong 12 941 enrolled suspected meningitis cases, 586 (4.5%) were laboratory confirmed. S. pneumoniae (74.2%) was the most commonly detected pathogen, followed by H. influenzae (22.2%), and N. meningitidis (3.6%). Overall 58.1% of confirmed bacterial meningitis cases were children aged between one, and 11 months. H. influenzae meningitis cases had a high (12.3%) case fatality rate. The serotypes covered in PCV13 caused 72% pneumococcal infections, and the most common serotypes were 14 (18.3%), 6B (12.7%) and 19F (9.9%). Non-susceptibility to penicillin was 57%. Forty-five (43.7%) isolates exhibited multidrug resistance, of which 37 were PCV13 serotype isolates.ConclusionsThe results are representative of the burden of bacterial meningitis among under-five children in India. The findings were useful in rolling out PCV in the National Immunization Program. The non-susceptibility to penicillin and multidrug resistance was an important observation. Timely expansion of PCV across India will significantly reduce the burden of antimicrobial resistance. Continued surveillance is needed to understand the trend after PCV expansion in India.     

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.