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.     

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.     

Re-emergence of pneumococcal colonization by vaccine serotype 19F in persons aged ≥5 years after 13-valent pneumococcal conjugate vaccine introduction—Alaska, 2008–2013

BackgroundThe pneumococcal conjugate vaccine (PCV) was introduced in 2001. Widespread PCV use nearly eradicated pneumococcal colonization by vaccine serotypes. Since 2008, however, colonization by PCV-serotype 19F has increased in Alaska residents. We describe the epidemiology of re-emerging serotype 19F colonization.MethodsWe conducted annual cross-sectional colonization surveys from 2008 to 2013. We recruited children aged <5 years at 2 urban clinics and participants of all ages from Region-A (2 villages), Region-B (4 villages), and Region-C (2 villages). We interviewed participants and reviewed their medical records to obtain demographic information and determine PCV status. We obtained nasopharyngeal swab specimens from participants to identify pneumococci and to determine the pneumococcal serotype, antimicrobial resistance, and multilocus sequence type. We used the Cochran-Armitage test to assess for significant trends in colonization across time periods.ResultsAmong participants aged <5 years, pneumococcal serotype 19F colonization remained unchanged from 2008–2009 (0.7%) to 2012–2013 (0.5%; P-value [P] = .54). Serotype 19F colonization increased from 2008–2009 to 2012–2013 among participants aged 5–11 years (0.3% to 3.2%; P < .01), participants 12–17 years (0.0% to 2.0%; P < .01), and participants aged ≥18 years (0.1% to 0.5%; P < .01). During 2012–2013, 85 (93%) of 91 pneumococcal serotype 19F isolates were identified among participants from Region B; the majority of serotype 19F isolates belonged to an antimicrobial nonsusceptibility pattern corresponding to a novel multilocus sequence type 9074.ConclusionsPCV continues to protect against serotype 19F colonization in vaccinated children aged <5 years. The direct PCV impact on serotype 19F colonization in persons aged 5–11 years and indirect impact in persons aged ≥12 years is waning, possibly because of a newly introduced genotype in Region-B.     

The impact of private use of PCV7 in 2009 and 2010 on serotypes and antimicrobial resistance of Streptococcus pneumoniae carried by young children in Portugal: Comparison with data obtained since 1996 generating a 15-year study prior to PCV13 introduction

In Portugal, the 7-valent pneumococcal conjugate vaccine (PCV7) was not introduced in the national immunization plan but was commercially available between 2001 and 2010. We studied serotype distribution and antibiotic susceptibility of Streptococcus pneumoniae carried by children in 2009 and 2010. Vaccination with PCV7 was extracted from children's immunization bulletins and information on recent antimicrobial consumption was obtained through a questionnaire. For comparison, we included data from previous studies conducted since 1996: 1996–1999, 2001–2003, 2006–2007. Pneumococci were isolated from nasopharyngeal samples of 1092 children up to six years old attending day-care in an urban area. Among these, 76% (819/1070) were vaccinated and 62% (677/1092) carried pneumococci. In 2009–2010, serotype replacement was extensive. Carriage of PCV7 serotypes was 4.9% and 5.8%, in 2009 and 2010, respectively, with the majority being of serotype 19F (carried by 4.3% and 4.6% of all participants, respectively). Colonization by serotype 19F was associated with vaccine status (7.7% (19/248) of non-vaccinees vs. 3.5% (29/818) of PCV7-vaccinees, p = 0.010). Carriage of serotype 19A was high in 2009 and 2010 (8.6% of all participants) consistent with values already observed in 2007; carriage of serotype 6A was <1% (10/1092), indicating a major decline after 2007 (5.8% or 31/538, p < 0.001). Non-vaccine serotypes increased and serotype 6C became the most frequently carried serotype in 2010 (11.2% (54/481)). High-level resistance to penicillin (MIC ≥2 mg/L) showed a decreasing trend (p < 0.001), whereas resistance to both penicillin and erythromycin increased (p < 0.001) and was detected in 15–20% of all isolates in 2009–2010, most of which were non-vaccine serotypes. Antimicrobial use decreased over time (p < 0.001). In conclusion, widespread private use of PCV7 has impacted on colonization leading to near elimination of all PCV7 serotypes except for serotype 19F. Antimicrobial consumption declined but it may be too soon to observe generalized changes in antimicrobial resistance rates.     

Invasive pneumococcal disease due to 22F and 33F in England: A tail of two serotypes

BackgroundA 15-valent pneumococcal conjugate vaccine (PCV15) aims to protect against serotype 22F and 33F in addition to the serotypes within the 13-valent PCV (PCV13) which was introduced to the UK childhood immunisation programme in April 2010. Little is known about the specific epidemiology, clinical features or outcomes of invasive pneumococcal disease (IPD) due to these two serotypes.MethodsPublic Health England (PHE) conducts enhanced IPD surveillance in England. Hospital laboratories routinely submit invasive pneumococcal isolates to PHE for serotyping and enhanced clinical information is collected through questionnaires sent to general practitioners. IPD due to serotypes 22F and 33F diagnosed during 2014/15–2018/19 were compared with IPD due to PCV13 serotypes and remaining serotypes.ResultsIn total, 25,415 isolates (93.4%) were serotyped and questionnaires were completed for 22,097 (86.9%) cases. Serotype 22F was responsible for 1,788 (7.0%) and serotype 33F for 893 (3.5%) cases compared to 19.9% (n = 5,047) for PCV13 and 69.6% (n = 17,687) for the remaining serotypes. IPD incidence increased for both serotypes since 2005/06, especially in older adults, but plateaued after PCV13 introduction. Comorbidity prevalence was 68.7% (n = 1,037) for serotype 22F and 67.2% (n = 505) for serotype 33F, with invasive pneumonia being the most common clinical presentation 1,067/1,482; 72.0%, and 514/755; 68.1%, respectively. There were 3,617 deaths within 30 days of disease onset, including 236 (CFR, 15.4%) among 22F, 128 (CFR, 16.5%) among 33F and 21.3% (925/4,350) among PCV13-type IPD cases. When compared with PCV13-type IPD, serotype 22F (aOR 0.58, 95%CI 0.49–0.68, p < 0.001) and 33F (aOR 0.73, 95%CI 0.59–0.91, p = 0.004) were independently associated with lower odds of death. The major circulating sequence types (STs) in 22F (ST 433, ST698) and 33F (ST717, ST100, ST673) were not associated with an increased risk of death compared to the other STs.ConclusionsSerotype 22F and 33F-type IPD are associated with a lower risk of death compared to PCV13-type, with those presenting with septicaemia more likely to have a fatal outcome compared to pneumonia. PCV15 has the potential to prevent up to an additional 10% of IPD cases in England.     

Immunogenicity of a 7-valent pneumococcal conjugate vaccine (PCV7) and impact on carriage in Venezuelan children at risk of invasive pneumococcal diseases

Background and aims

We evaluated the immunogenicity of the 7-valent pneumococcal conjugate vaccine (PCV7), and its impact on pneumococcal carriage in Venezuelan children at high risk for invasive pneumococcal disease (IPD).

Methods

82 children (age 2–59 months) with sickle cell anemia (n = 22), chronic heart disease (n = 19), HIV infection (n = 12), immune-suppressive therapy (n = 11) and other IPD-predisposing conditions (n = 18) were vaccinated with PCV7 according to CDC-recommended age-related immunization schedules. Blood samples were taken to determine the concentration of IgG antibody, and nasopharyngeal swabs were obtained to isolate Streptococcus pneumoniae, before the first vaccine dose and 1 month after completion of the vaccination schedule.

Results

Pneumococcal carriage prior to the first immunization was 27% (n = 22), with the most frequently carried serotypes being vaccine serotypes 6B (22%) and 14 (13%). One month after completion of the vaccination scheme pneumococcal carriage was 22% (n = 17), dominated by non-vaccine serotypes 19A (24%) and 7F (12%). Before immunization, 65% of the subjects had IgG antibody titers >0.35 μg/mL for five serotypes tested. Post-vaccination, 100% of the subjects showed titers >1.0 μg/mL for all PCV7 serotypes with geometric mean concentrations (GMC) ranging from 1.75 μg/mL (serotype 23F) to 17.16 μg/mL (serotype 14). Children previously colonized with serotype 6B had a significantly lower GMC to this serotype following immunization than children not carrying 6B prior to the first PCV dose (p < 0.05).

Conclusions

PCV7 is highly immunogenic in Venezuelan children at high-risk for IPD. Vaccination was associated with an immediate shift in nasopharyngeal carriage toward non-PCV7 serotypes. Finally, we observed serotype-specific hyporesponsiveness to immunization after natural carriage with the same serotype in high-risk children.     

Invasive Streptococcus pneumoniae isolates from pediatric population in Argentina for the period 2006–2019. Temporal progression of serotypes distribution and antibiotic resistance

Streptococcus pneumoniae is a major cause of severe invasive disease associated with high mortality and morbidity worldwide. A total of 2908 pneumococcal isolates were analyzed between 2006 and 2019. Gold standard pneumococcal serotyping (the Neufeld-Quellung reaction) was performed to identify the serotypes associated with infection in children < 5 years in Argentina and agar dilution method was carried out to determine their profiles to 14 antimicrobial agents.In 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) was included in the National Immunization Program. In this work we have analyzed the local epidemiology of invasive pneumococcal diseases before and after the introduction of this vaccine in order to understand the epidemiological relevance and impact of PCV13.During the periods compared in the present study there was a significant increase in the proportion of non-PCV13 serotypes, serogroup 24 (246.7%) and 12F (85.7%), and a significant decrease in PCV13 serotypes, including serotypes 14 (91.2%), 5 (95.6%) and 1 (84.6%) among others. Another observation was that serotypes 3 (7.4%) and 19A (4.9%) still remain among the most frequent serotypes despite being part of the PCV13 formulation. Regarding antimicrobial resistance, in the present study we observed an increase in erythromycin resistance during the period of study mainly associated to serotype 14 in the pre-PCV13 period and to serogroup 24 in the post-PCV13 period, which also was the major NVT serotype associated with antimicrobial resistance and MDR. Serotypes 14, 24A/B/F and 19A were in the first three places among isolates resistant to all the antibiotics tested.Our data highlight the importance of continuous surveillance to assess the impact of pneumococcal vaccines and the use of antibiotics in the dynamic of pneumococcal serotypes.     

河北省19F型和19A型侵袭性肺炎链球菌耐药性分析及多位点序列分型分析

目的 了解河北省侵袭性肺炎链球菌(Streptococcus pneumoniae,Spn)19F型和19A型的耐药特征及多位点序列分型(multilocus sequence type,MLST)分布.方法 19F 型和 19A 型采用多重聚合酶链式反应(multiplex polymerase chain reac...     

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.     

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.     

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.     

The current status of invasive pneumococcal disease in Poland

The objectives of this study were to assess the incidence of invasive pneumococcal disease (IPD) in Poland (2006-2009), where mass vaccination had not been implemented, and to determine the serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates. The IPD incidence rates were highest among children under 2 years of age (3.39/100,000 in 2009) and children 2-5 years old (2.44/100,000). The most common serotypes were 14, 3, 1, 4, 19F, 23F, 6B, and 12F (61.7% of all isolates). In children aged less than 5 years, isolates of serotypes 14, 6B, and 19F were most prevalent (52.7% of the IPD cases). The PCV7, PCV10, and PCV13 covered 43.3%, 54.8%, and 68.8% of all IPD cases, and 68.7%, 76.3%, and 86.3% of cases involving children under 5 years of age. Penicillin resistance was found in 21.3% of the isolates responsible for meningitis and in 1.2% of isolates responsible for other invasive infections.Introduction of antipneumococcal conjugated vaccines into the national immunisation programme would likely lead to a significant reduction of IPD-associated morbidity among Polish children in particular, as well as in the population as a whole, especially in cases involving pneumococci with a decreased susceptibility to antibiotics.     

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.     

Invasive disease potential of pneumococci before and after the 13-valent pneumococcal conjugate vaccine implementation in children

BackgroundChanges in serotype distribution have been induced after pneumococcal conjugate vaccines (PCV) implementation, and non-vaccine serotypes are now circulating. Among these latter serotypes, we aimed to distinguish those with high invasive disease potential before (2008–2009) and after PCV13 implementation (2012–2013).MethodsInvasive pneumococcal disease (IPD) serotypes isolated from children 6 to 24 months were compared with nasopharyngeal-colonizing serotypes in healthy children. To assess the invasive potential of a given serotype, odds ratios (ORs) were calculated. For each serotype, OR >1 indicated increased probability of association with IPD and OR <1 decreased probability.ResultsIn 2008/2009 and 2012/2013, 355 pneumococci were isolated from 1212 healthy children and from 569 IPD, including 166 meningitis, 114 pneumonia, and 289 other IPDs. In period 1, serotypes 7F, 3, 1, 24F, and 19A showed highly significant invasive disease potential whereas in period 2, only serotype 24F was associated with a significant high OR (6.6 [95% CI 2.6; 16.2]). Of note, for serotype 12F, OR could not be calculated because of no carrier recorded, however, if there had been a single 12F carrier, the OR would be among the highest, in period 2, 15.7 [95% 3.4; 73.0]). Only two serotypes appeared negatively associated with IPD, 11A and 23B in the period 2 as compared with nine in period 1. In the second period, pneumococcal penicillin non-susceptible isolates were mostly represented by serotypes 19A, 15A, 19F, 35B and 24F both in carriers and IPD. Only one strain was resistant to penicillin with MIC = 4 μg/ml (serotype 19A) during the first period.ConclusionIn children <2 years old, compared to the previous period, the number of serotypes having a high disease potential decreased after PCV13 implementation, only two non-vaccine serotypes, 24F and 12F, had high invasive disease potential.     

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).     

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.     

In-depth analysis of pneumococcal serotypes in Belgian children (2015–2018): Diversity,invasive disease potential,and antimicrobial susceptibility in carriage and disease

BackgroundChanges in serotype distribution have been described after the switch from the 13-valent pneumococcal conjugate vaccine (PCV13) to the 10-valent pneumococcal conjugate vaccine (PCV10) in Belgium.AimTo describe serotype’s invasive disease potential and the detailed evolution of serotype distribution and antimicrobial susceptibility of pneumococcal isolates (carriage and IPD) in children up to 30 months of age over a period during and after the vaccine switch (2015–2018).MethodsS. pneumoniae strains isolated from the nasopharynx of healthy children attending day-care centres (DCCs) and strains from normally sterile sites of children with IPD were serotyped (Quellung-reaction) and antimicrobial susceptibility testing was performed. Invasive disease potential was defined as the serotype-specific odds ratio (OR).ResultsThe highly invasive (OR > 1) serotypes 12F, 1, 3, 24A/B/F, 33F, 19A, and 9N were not frequently carried (<7.5% of carriage strains). Different serotypes dominated in carriage (23B, 23A, 11A, 15B) versus IPD (12F, 19A, 10A, 33F). PCV13 vaccine serotypes increased in carriage (5.4% (25/463) in period 1 vs 10.3% (69/668) in period 3) and in IPD (7.3% (8/110 in period 1 vs 23.9% (34/142) in period 3) due to an increase (p < 0.01) in serotype 19A. The penicillin non-susceptibility of 19A was lower (p = 0.02) in carriage (6.8%) than in IPD (23.5%). Erythromycin and tetracycline non-susceptibility were more frequent (p < 0.01) in IPD (26.0%; 23.0%) compared to carriage strains (18.2%; 14.5%) and penicillin non-susceptibility increased over the three year study period (carriage: 13.4%, 19.8%, 18.5%, p = 0.05; IPD: 11.8%, 15.0%, 20.4%, p = 0.02).ConclusionOnly some of the serotypes with high invasive disease potential (serotype 1, 3, 19A) in Belgium are included in PCV10 and/or PCV13. This reinforces the need for continuous monitoring, both in healthy children as in children with IPD, to better understand the dynamics of pneumococcal disease, to optimise the composition and implementation of PCVs.     

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).     

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.     

Pneumococcal serotypes and antibiotic resistance in healthy carriage children after introduction of PCV13 in Lima,Peru

ObjectiveTo determinate the frequency of Streptococcus pneumoniae nasopharyngeal carriers, serotypes and antimicrobial resistance in healthy children in Lima, Peru, post-PCV13 introduction and to compare the results with a similar study conducted between 2006 and 2008 before PCV7 introduction (pre-PCV7).MethodsA cross-sectional multicenter study was conducted between January 2018 and August 2019 in 1000 healthy children under two years of age. We use standard microbiological methods to determinate S. pneumoniae from nasopharyngeal swab, Kirby Bauer and minimum inhibitory concentration methods to determinate antimicrobial susceptibility and whole genomic sequencing to determinate pneumococcal serotypes.ResultsThe pneumococcal carriage rate was 20.8 % vs. 31.1 % in pre-PCV7 (p < 0.001). The most frequent serotypes were 15C, 19A and 6C (12.4 %, 10.9 % and 10.9 % respectively). The carriage of PCV13 serotypes after PCV13 introduction decreased from 59.1 % (before PCV7 introduction) to 18.7 % (p < 0.001). Penicillin resistance was 75.5 %, TMP/SMX 75.5 % and azithromycin 50.0 %, using disk diffusion. Penicillin resistance rates using MIC breakpoint for meningitis (MIC ≥ 0.12) increased from 60.4 % to 74.5 % (p = 0.001).ConclusionThe introduction of PCV13 in the immunization program in Peru has decreased the pneumococcal nasopharyngeal carriage and the frequency of PCV13 serotypes; however, there has been an increase in non-PCV13 serotypes and antimicrobial resistance.