Serotypes and Clonal Composition of Streptococcus pneumoniae Isolates Causing IPD in Children and Adults in Catalonia before 2013 to 2015 and after 2017 to 2019 Systematic Introduction of PCV13

Clones; Invasive pneumococcal disease; SerotypesClones; Enfermedad neumocócica invasiva; SerotiposClons; Malaltia pneumocòcica invasiva; SerotipsThe goal of this study was to investigate the distribution of serotypes and clonal composition of Streptococcus pneumoniae isolates causing invasive pneumococcal disease (IPD) in Catalonia, before and after systematic introduction of PCV13. Pneumococcal strains isolated from normally sterile sites obtained from patients of all ages with IPD received between 2013 and 2019 from 25 health centers of Catalonia were included. Two study periods were defined: presystematic vaccination period (2013 and 2015) and systematic vaccination period (SVP) (2017 to 2019). A total of 2,303 isolates were analyzed. In the SVP, there was a significant decrease in the incidence of IPD cases in children 5 to 17 years old (relative risk [RR] 0.61; 95% confidence interval [CI] 0.38 to 0.99), while there was a significant increase in the incidence of IPD cases in 18- to 64-year-old adults (RR 1.33; 95% CI 1.16 to 1.52) and adults over 65 years old (RR 1.23; 95% CI 1.09 to 1.38). Serotype 8 was the major emerging serotype in all age groups except in 5- to 17-year-old children. In children younger than 5 years old, the main serotypes in SVP were 24F, 15A, and 3, while in adults older than 65 years they were serotypes 3, 8, and 12F. A significant decrease in the proportions of clonal complexes CC156, CC191, and ST306 and an increase in those of CC180, CC53, and CC404 were observed. A steady decrease in the incidence of IPD caused by PCV13 serotypes indicates the importance and impact of systematic vaccination. The increase of non-PCV13 serotypes highlights the need to expand serotype coverage in future vaccines and rethink vaccination programs for older adults. IMPORTANCE We found that with the incorporation of the PCV13 vaccine, the numbers of IPD cases caused by serotypes included in this vaccine decreased in all of the age groups. Still, there was an unforeseen increase of the serotypes not included in this vaccine causing IPD, especially in the >65-year-old group. Moreover, a significant increase of serotype 3 included in the vaccine has been observed; this event has been reported by other researchers. These facts call for the incorporation of more serotypes in future vaccines and a more thorough surveillance of the dynamics of this microorganism

Failures of 13-Valent Conjugated Pneumococcal Vaccine in Age-Appropriately Vaccinated Children 2-59 Months of Age, Spain

Vaccination with the 13-valent conjugated pneumococcal disease (PCV13) has reduced invasive pneumococcal disease (IPD), but there have been reports of vaccine failures. We performed a prospective study in children aged 2-59 months who received diagnoses of IPD during January 2012-June 2016 in 3 pediatric hospitals in Catalonia, Spain, a region with a PCV13 vaccination coverage of 63%. We analyzed patients who had been age-appropriately vaccinated but who developed IPD caused by PCV13 serotypes. We detected 24 vaccine failure cases. The serotypes involved were 3 (16 cases); 19A (5 cases); and 1, 6B, and 14 (1 case each). Cases were associated with children without underlying conditions, with complicated pneumonia (OR 6.65, 95% CI 1.91-23.21), and with diagnosis by PCR (OR 5.18, 95% CI 1.84-14.59). Vaccination coverage should be increased to reduce the circulation of vaccine serotypes. Continuous surveillance of cases of IPD using both culture and PCR to characterize vaccine failures is necessary

Effectiveness of the 13-valent pneumococcal conjugate vaccine in preventing invasive pneumococcal disease in children aged 7-59 months. A matched case-control study

Background The 13-valent pneumococcal conjugate vaccine (PCV13) was licensed based on the results of immunogenicity studies and correlates of protection derived from randomized clinical trials of the 7-valent conjugate pneumococcal vaccine. We assessed the vaccination effectiveness (VE) of the PCV13 in preventing invasive pneumococcal disease (IPD) in children aged 7-59 months in a population with suboptimal vaccination coverage of 55%. Methods The study was carried out in children with IPD admitted to three hospitals in Barcelona (Spain) and controls matched by hospital, age, sex, date of hospitalization and underlying disease. Information on the vaccination status was obtained from written medical records. Conditional logistic regression was made to estimate the adjusted VE and 95% confidence intervals (CI). Results 169 cases and 645 controls were included. The overall VE of ≥1 doses of PCV13 in preventing IPD due to vaccine serotypes was 75.8% (95% CI, 54.1-87.2) and 90% (95% CI, 63.9-97.2) when ≥2 doses before 12 months, two doses on or after 12 months or one dose on or after 24 months, were administered. The VE of ≥1 doses was 89% (95% CI, 42.7-97.9) against serotype 1 and 86.0% (95% CI, 51.2-99.7) against serotype 19A. Serotype 3 showed a non-statistically significant effectiveness (25.9%; 95% CI, -65.3 to 66.8). Conclusions The effectiveness of ≥1 doses of PCV13 in preventing IPD caused by all PCV13 serotypes in children aged 7-59 months was good and, except for serotype 3, the effectiveness of ≥1 doses against the most frequent PCV13 serotypes causing IPD was high when considered individually

Impact of the 13-valent conjugated pneumococcal vaccine on the direct costs of invasive pneumococcal disease requiring hospital admission in children aged < 5 years. A prospective study

The lack of invasive pneumococcal disease (IPD) cost studies may underestimate the effect of pneumococcal polysaccharide conjugated vaccines (PCV). The objective of this study was to estimate the direct costs of hospitalized IPD cases. A prospective study was made in children aged <5 years diagnosed with IPD in two high-tech hospitals in Catalonia (Spain) between 2007-2009 (PCV7 period) and 2012-2015 (PCV13 period). Costs were calculated according to 2014 Catalan Health Service rates using diagnostic-related groups. In total, 319 and 154 cases were collected, respectively. Pneumonia had the highest cost (65.7% and 62.0%, respectively), followed by meningitis (25.8% and 26.1%, respectively). During 2007-2015, the costs associated with PCV7 serotypes (Pearson coeffcient (Pc) = 0.79; p = 0.036) and additional PCV13 serotypes (Pc = 0.75; p = 0.05) decreased, but those of other serotypes did not (Pc = 0.23 p = 0.62). The total mean cost of IPD increased in the PCV13 period by 31.4% (¿3016.1 vs. ¿3963.9), mainly due to ICU stay (77.4%; ¿1051.4 vs. ¿1865.6). During the PCV13 period, direct IPD costs decreased due to a reduction in the number of cases, but cases were more severe and had a higher mean cost. During 2015, IPD costs increased due to an increase in the costs associated with non-PCV13 serotypes and serotype 3 and this requires further investigation

Serotypes and Clonal Composition of Streptococcus pneumoniae Isolates Causing IPD in Children and Adults in Catalonia before 2013 to 2015 and after 2017 to 2019 Systematic Introduction of PCV13

The goal of this study was to investigate the distribution of serotypes and clonal composition of Streptococcus pneumoniae isolates causing invasive pneumococcal disease (IPD) in Catalonia, before and after systematic introduction of PCV13. Pneumococcal strains isolated from normally sterile sites obtained from patients of all ages with IPD received between 2013 and 2019 from 25 health centers of Catalonia were included. Two study periods were defined: presystematic vaccination period (2013 and 2015) and systematic vaccination period (SVP) (2017 to 2019). A total of 2,303 isolates were analyzed. In the SVP, there was a significant decrease in the incidence of IPD cases in children 5 to 17 years old (relative risk [RR] 0.61; 95% confidence interval [CI] 0.38 to 0.99), while there was a significant increase in the incidence of IPD cases in 18- to 64-year-old adults (RR 1.33; 95% CI 1.16 to 1.52) and adults over 65 years old (RR 1.23; 95% CI 1.09 to 1.38). Serotype 8 was the major emerging serotype in all age groups except in 5- to 17-year-old children. In children younger than 5 years old, the main serotypes in SVP were 24F, 15A, and 3, while in adults older than 65 years they were serotypes 3, 8, and 12F. A significant decrease in the proportions of clonal complexes CC156, CC191, and ST306 and an increase in those of CC180, CC53, and CC404 were observed. A steady decrease in the incidence of IPD caused by PCV13 serotypes indicates the importance and impact of systematic vaccination. The increase of non-PCV13 serotypes highlights the need to expand serotype coverage in future vaccines and rethink vaccination programs for older adults. IMPORTANCE We found that with the incorporation of the PCV13 vaccine, the numbers of IPD cases caused by serotypes included in this vaccine decreased in all of the age groups. Still, there was an unforeseen increase of the serotypes not included in this vaccine causing IPD, especially in the >65-year-old group. Moreover, a significant increase of serotype 3 included in the vaccine has been observed; this event has been reported by other researchers. These facts call for the incorporation of more serotypes in future vaccines and a more thorough surveillance of the dynamics of this microorganism

PsrP, a Protective Pneumococcal Antigen, Is Highly Prevalent in Children with Pneumonia and Is Strongly Associated with Clonal Type ▿

Invasive pneumococcal disease (IPD) is a major health problem worldwide. Due to ongoing serotype replacement, current efforts are focused in an attempt to identify the pneumococcal antigens that could be used in a next-generation multivalent protein vaccine. The objective of our study was to use real-time PCR to determine the distribution and clonal type variability of PsrP, a protective pneumococcal antigen, among pneumococcal isolates from children with IPD or healthy nasopharyngeal carriers. psrP was detected in 52.4% of the 441 strains tested. While no differences were determined when the prevalence of psrP in colonizing strains (n = 89) versus that in all invasive strains (n = 352) was compared, a strong trend was observed when the prevalence of psrP in all pneumonia isolates (n = 209) and colonizing isolates (P = 0.067) was compared, and a significant difference was observed when the prevalence in all pneumonia isolates and those causing bacteremia (n = 76) was compared (P = 0.001). An age-dependent distribution of psrP was also observed, with the incidence of psrP being the greatest in strains isolated from children >2 years of age (P = 0.02). Strikingly, the presence of psrP within a serotype was highly dependent on the clonotype, with all isolates of invasive clones such as clonal complex 306 carrying psrP (n = 88), whereas for sequence type 304, only 1 of 19 isolates carried psrP; moreover, this was inversely correlated with antibiotic susceptibility. This finding suggests that inclusion of psrP in a vaccine formulation would not target resistant strains. We conclude that psrP is highly prevalent in strains that cause IPD but is most prevalent in strains isolated from older children with pneumonia. These data support the potential use of PsrP as one component in a multivalent protein-based vaccine

Recurrent invasive pneumococcal disease in children: underlying clinical conditions, and immunological and microbiological characteristics.

Clinical, immunological and microbiological characteristics of recurrent invasive pneumococcal disease (IPD) in children were evaluated, differentiating relapse from reinfection, in order to identify specific risk factors for both conditions.All patients <18 years-old with recurrent IPD admitted to a tertiary-care pediatric center from January 2004 to December 2011 were evaluated. An episode of IPD was defined as the presence of clinical findings of infection together with isolation and/or pneumococcal DNA detection by Real-Time PCR in any sterile body fluid. Recurrent IPD was defined as 2 or more episodes in the same individual at least 1 month apart. Among recurrent IPD, we differentiated relapse (same pneumococcal isolate) from reinfection.593 patients were diagnosed with IPD and 10 patients died. Among survivors, 23 episodes of recurrent IPD were identified in 10 patients (1.7%). Meningitis was the most frequent form of recurrent IPD (10 episodes/4 children) followed by recurrent empyema (8 episodes/4 children). Three patients with recurrent empyema caused by the same pneumococcal clone ST306 were considered relapses and showed high bacterial load in their first episode. In contrast, all other episodes of recurrent IPD were considered reinfections. Overall, the rate of relapse of IPD was 0.5% and the rate of reinfection 1.2%. Five out of 7 patients with reinfection had an underlying risk factor: cerebrospinal fluid leak (n = 3), chemotherapy treatment (n = 1) and a homozygous mutation in MyD88 gene (n = 1). No predisposing risk factors were found in the remainder.recurrent IPD in children is a rare condition associated with an identifiable risk factor in case of reinfection in almost 80% of cases. In contrast, recurrent IPD with pleuropneumonia is usually a relapse of infection

Recurrent Invasive Pneumococcal Disease in Children: Underlying Clinical Conditions, and Immunological and Microbiological Characteristics

Purpose Clinical, immunological and microbiological characteristics of recurrent invasive pneumo- coccal disease (IPD) in children were evaluated, differentiating relapse from reinfection, in order to identify specific risk factors for both conditions. Methods All patients <18 years-old with recurrent IPD admitted to a tertiary-care pediatric center from January 2004 to December 2011 were evaluated. An episode of IPD was defined as the presence of clinical findings of infection together with isolation and/or pneumococcal DNA detection by Real-Time PCR in any sterile body fluid. Recurrent IPD was defined as 2 or more episodes in the same individual at least 1 month apart. Among recurrent IPD, we differentiated relapse (same pneumococcal isolate) from reinfection. Results 593 patients were diagnosed with IPD and 10 patients died. Among survivors, 23 episodes of recurrent IPD were identified in 10 patients (1.7%). Meningitis was the most frequent form of recurrent IPD (10 episodes/4 children) followed by recurrent empyema (8 episodes/4 chil- dren). Three patients with recurrent empyema caused by the same pneumococcal clone ST306 were considered relapses and showed high bacterial load in their first episode. In contrast, all other episodes of recurrent IPD were considered reinfections. Overall, the rate of relapse of IPD was 0.5% and the rate of reinfection 1.2%. Five out of 7 patients with rein- fection had an underlying risk factor: cerebrospinal fluid leak (n = 3), chemotherapytreatment (n = 1) and a homozygous mutation in MyD88 gene (n = 1). No predisposing risk factors were found in the remainder. Conclusions recurrent IPD in children is a rare condition associated with an identifiable risk factor in case of reinfection in almost 80% of cases. In contrast, recurrent IPD with pleuropneumonia is usually a relapse of infection

Microbiological characteristics of patients with recurrent invasive pneumococcal disease.

<p>P, patient identification; ST, sequence type by Multi-locus sequence typing; MDR, Multi-drug resistant strain; PCV-7, 7-valent polysaccharide-protein conjugate vaccine; PCV 13, 13-valent polysaccharide-protein conjugate vaccine; PPV-23, 23-valent pneumococcal polysaccharide vaccine; CSF, cerebrospinal fluid; NA, Not available; MIC, minimal inhibitory concentration; Pen, penicillin; Ery, erythromycin; Cm, chloramphenicol; Tet, tetracycline; Ctx, Cefotaxime; Bold text, resistant strain according to MICs for <i>Streptococcus pneumonia</i>. EUCAST Clinical Meningeal Breakpoints.</p><p>^aNA, ST were not available in episodes identified only by PCR.</p><p>Microbiological characteristics of patients with recurrent invasive pneumococcal disease.</p

Clinical characteristics of patients with recurrent invasive pneumococcal disease.

<p>P, patient identification; PCV-7, 7-valent polysaccharide-protein conjugate vaccine; PCV 13, 13-valent polysaccharide-protein conjugate vaccine; PPV-23, 23-valent pneumococcal polysaccharide vaccine.</p><p>Clinical characteristics of patients with recurrent invasive pneumococcal disease.</p