Low transmission of SARS-CoV-2 derived from children in family clusters: An observational study of family households in the Barcelona Metropolitan Area, Spain.

BACKGROUND: Family clusters offer a good opportunity to study viral transmission in a stable setting. We aimed to analyze the specific role of children in transmission of SARS-CoV-2 within households. METHODS: A prospective, longitudinal, observational study, including children with documented acute SARS-CoV-2 infection attending 22 summer-schools in Barcelona, Spain, was performed. Moreover, other patients and families coming from other school-like environments that voluntarily accessed the study were also studied. A longitudinal follow-up (5 weeks) of the family clusters was conducted to determine whether the children considered to be primary cases were able to transmit the virus to other family members. The household reproduction number (Re*) and the secondary attack rate (SAR) were calculated. RESULTS: 1905 children from the summer schools were screened for SARS-CoV-2 infection and 22 (1.15%) tested positive. Moreover, 32 additional children accessed the study voluntarily. Of these, 37 children and their 26 households were studied completely. In half of the cases (13/26), the primary case was considered to be a child and secondary transmission to other members of the household was observed in 3/13, with a SAR of 14.2% and a Re* of 0.46. Conversely, the SAR of adult primary cases was 72.2% including the kids that gave rise to the contact tracing study, and 61.5% without them, and the estimated Re* was 2.6. In 4/13 of the paediatric primary cases (30.0%), nasopharyngeal PCR was persistently positive > 1 week after diagnosis, and 3/4 of these children infected another family member (p<0.01). CONCLUSIONS: Children may not be the main drivers of the infection in household transmission clusters in the study population. A prolonged positive PCR could be associated with higher transmissibility.

Safety and effectiveness of bubble continuous positive airway pressure as respiratory support for bronchiolitis in a pediatric ward.

The results of several clinical trials suggest that continuous positive airway pressure (CPAP) for acute bronchiolitis can be more effective than high-flow nasal cannula (HFNC). The use of HFNC involved a minimum reduction (5%) in admissions to the pediatric intensive care unit (PICU) in our hospital. Our main aim was to evaluate its safety and effectiveness as respiratory support for patients with bronchiolitis in a pediatric general ward. A secondary goal was to compare the admissions to PICU and the invasive mechanical ventilation (IMV) rate of patients treated with HFNC and those treated with HFNC/b-CPAP during the 2018-2019 and 2019-2020 epidemic seasons, respectively. Two prospective single-centre observational studies were performed. For the main aim, a cohort study (CS1) was carried out from 1st of November 2019 to 15th of January 2020. Inclusion criteria were children aged up to 3 months with bronchiolitis treated with b-CPAP support when HFNC failed. Epidemiological and clinical parameters were collected before and 60 min after the onset of CPAP and compared between the responder (R) and non-responders (NR) groups. NR was the group that required PICU admission. One hundred fifty-eight patients were admitted to the ward with bronchiolitis and HFNC. Fifty-seven out of one hundred fifty-eight required b-CPAP. No adverse events were observed. Thirty-two out of fifty-seven remained in the general ward (R-group), and 25/57 were admitted to PICU (NR-group). There were statistically significant differences in respiratory rate (RR) and heart rate (HR) between both groups before and after the initiation of b-CPAP, but the multivariable models showed that the main differences were observed after 60 min of therapy (lower HR, RR, BROSJOD score and FiO2 in the R-group). For the secondary aim, another cohort study (CS2) was performed comparing data from a pre-b-CPAP bronchiolitis season (1st of November 2018 to 15th January 2019) and the b-CPAP season (2019-2020). Inclusion criteria in pre-b-CPAP season were children aged up to 3 months admitted to the same general ward with moderate-severe bronchiolitis and with HFNC support. Admissions to PICU during the CPAP season were significantly reduced, without entailing an increase in the rate of IMV. CONCLUSION: The implementation of b-CPAP for patients with bronchiolitis in a pediatric ward, in whom HFNC fails, is safe and effective and results in a reduction in PICU admissions. WHAT IS KNOWN: • Bronchiolitis is one of the most frequent respiratory infections in children and one of the leading causes of hospitalization in infants. • Several studies suggest that the use of continuous positive airway pressure (CPAP) for acute bronchiolitis can be more effective than the high flow nasal cannula (HFNC). CPAP is a non-invasive ventilation (NIV) therapy used in patients admitted to pediatric intensive care unit (PICU) with progressive moderate-severe bronchiolitis. There is little experience in the literature on the use of continuous positive airway pressure (CPAP) for acute bronchiolitis in a general ward. WHAT IS NEW: • CPAP could be safely and effectively used as respiratory support in young infants with moderate-severe bronchiolitis in a general ward and it reduced the rate of patients who required PICU admission. • Patients' heart and respiratory rate and their FiO2 needs in the first 60 minutes may help to decide whether or not to continue the CPAP therapy in a general ward.

Invasive pneumococcal disease in children under 60 months before and after availability of 13-valent conjugate vaccine.

BACKGROUND: Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). METHODS: Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). RESULTS: We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 casos per 100 000 habitantes ( -62%; P < .001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 casos/100 000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P = .00). The incidence of serotype 3 decreased from 10.4 to 6.9 casos per 100 000 population, although it was the serotype involved most frequently in patients with severe disease. CONCLUSIONS: After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD.

Necrotizing pneumonia due to Streptococcus pneumoniae in children during the period of non-systematic use of PCV13 in Catalonia, Spain.

BACKGROUND: Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain). METHODS: A prospective observational study was conducted in patients <18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%. RESULTS: 35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children <5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13. CONCLUSIONS: Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

Rapid Increase of Oral Bacteria in Nasopharyngeal Microbiota After Antibiotic Treatment in Children With Invasive Pneumococcal Disease.

Introduction: Antibiotics are commonly prescribed to young children for treating bacterial infections such as invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae. Despite the obvious benefits of antibiotics, little is known about their possible side effects on children's nasopharyngeal microbiota. In other ecological niches, antibiotics have been described to perturb the balanced microbiota with short- and long-term effects on children's health. The present study aims to evaluate and compare the nasopharyngeal microbiota of children with IPD and different degree of antibiotic exposure. Methods: We investigated differences in nasopharyngeal microbiota of two groups of children <18 years with IPD: children not exposed to antibiotics before sample collection (n=27) compared to children previously exposed (n=54). Epidemiological/clinical data were collected from subjects, and microbiota was characterized by Illumina sequencing of V3-V4 amplicons of the 16S rRNA gene. Results: Main epidemiological/clinical factors were similar across groups. Antibiotic-exposed patients were treated during a median of 4 days (IQR: 3-6) with at least one beta-lactam (100.0%). Higher bacterial richness and diversity were found in the group exposed to antibiotics. Different streptococcal amplicon sequence variants (ASVs) were differentially abundant across groups: antibiotic use was associated to lower relative abundances of Streptococcus ASV2 and Streptococcus ASV11 (phylogenetically close to S. pneumoniae), and higher relative abundances of Streptococcus ASV3 and Streptococcus ASV12 (phylogenetically close to viridans group streptococci). ASVs assigned to typical bacteria from the oral cavity, including Veillonella, Alloprevotella, Porphyromonas, Granulicatella, or Capnocytophaga, were associated to the antibiotic-exposed group. Common nosocomial genera such as Staphylococcus, Acinetobacter, and Pseudomonas were also enriched in the group exposed to antibiotics. Conclusion: Our results point toward a reduction of S. pneumoniae abundance on the nasopharynx of children with IPD after antibiotic treatment and a short-term repopulation of this altered niche by oral and nosocomial bacteria. Future research studies will have to evaluate the clinical implications of these findings and if these populations would benefit from the probiotic/prebiotic administration or even from the improvement on oral hygiene practices frequently neglected among hospitalized children.

Differential nasopharyngeal microbiota composition in children according to respiratory health status.

Acute respiratory infections (ARIs) constitute one of the leading causes of antibiotic administration, hospitalization and death among children <5 years old. The upper respiratory tract microbiota has been suggested to explain differential susceptibility to ARIs and modulate ARI severity. The aim of the present study was to investigate the relation of nasopharyngeal microbiota and other microbiological parameters with respiratory health and disease, and to assess nasopharyngeal microbiota diagnostic utility for discriminating between different respiratory health statuses. We conducted a prospective case-control study at Hospital Sant Joan de Deu (Barcelona, Spain) from 2014 to 2018. This study included three groups of children <18 years with gradual decrease of ARI severity: cases with invasive pneumococcal disease (IPD) (representative of lower respiratory tract infections and systemic infections), symptomatic controls with mild viral upper respiratory tract infections (URTI), and healthy/asymptomatic controls according to an approximate case-control ratio 1:2. Nasopharyngeal samples were collected from participants for detection, quantification and serotyping of pneumococcal DNA, viral DNA/RNA detection and 16S rRNA gene sequencing. Microbiological parameters were included on case-control classification models. A total of 140 subjects were recruited (IPD=27, URTI=48, healthy/asymptomatic control=65). Children's nasopharyngeal microbiota composition varied according to respiratory health status and infection severity. The IPD group was characterized by overrepresentation of Streptococcus pneumoniae, higher frequency of invasive pneumococcal serotypes, increased rate of viral infection and underrepresentation of potential protective bacterial species such as Dolosigranulum pigrum and Moraxella lincolnii. Microbiota-based classification models differentiated cases from controls with moderately high accuracy. These results demonstrate the close relationship existing between a child's nasopharyngeal microbiota and respiratory health, and provide initial evidence of the potential of microbiota-based diagnostics for differential diagnosis of severe ARIs using non-invasive samples.

[Invasive pneumococcal disease in children under 60 months before and after availability of 13-valent conjugate vaccine]. / Enfermedad neumocócica invasiva en niños menores de 60 meses, antes y después de la introducción de la vacuna conjugada 13-valente.

BACKGROUND: Invasive pneumococcal disease (IPD) is the most important bacterial infection in young children, and the introduction of pneumococcal conjugate vaccines has changed its presentation. This study compared the incidence, characteristics and serotype distribution of IPD before and after the introduction of the pneumococcal conjugate vaccine (PCV13). METHODS: Prospective enrolment of patients with IPD aged less than 60 months and admitted to either of 2 tertiary care hospitals between January 2007 and December 2009 (pre-PCV13 period) and January 2012 and June-2016 (PCV13 period). RESULTS: We identified 493 cases, 319 in the pre-PCV13 period and 174 in the PCV13 period. The incidence of IPD decreased from 89.7 to 34.4 cases per 100,000 population (-62%; P<.001). This decrease was observed in all forms of disease except necrotising pneumonia (increase from 0.8 to 3.7 cases/100,000 population). There was a significant reduction in all serotypes included in the PCV13 and not included in the PCV7. We did not find significant differences in length of stay, mortality or the frequency of sequelae between both periods, but in the PCV13 period, the length of stay in the paediatric intensive care unit and the duration of mechanical ventilation were longer (P=.00). The incidence of serotype 3 decreased from 10.4 to 6.9 cases per 100,000 population, although it was the serotype involved most frequently in patients with severe disease. CONCLUSIONS: After the introduction of the PCV13, there has been a significant decrease in IPD cases. Serotype 3 continues to be an important cause of severe IPD.

Necrotizing pneumonia due to Streptococcus pneumoniae in children during the period of non-systematic use of PCV13 in Catalonia, Spain.

BACKGROUND: Some studies have observed an increased incidence of necrotizing pneumonia (NP) in recent years. This might be related to the emergence of non-vaccine S. pneumoniae serotypes after PCV7 introduction although it is suggested that evolutionary factors may have modified the virulence and the interactions of pneumococci. The aim of this study was to clinically and microbiologically define NP in the population served by the three major paediatric hospitals in Barcelona (Catalonia, Spain). METHODS: A prospective observational study was conducted in patients <18 years hospitalized due to invasive pneumococcal disease (January 2012-June 2016). Data of confirmed cases of pneumococcal NP (diagnosed by culture or DNA detection and serotyped) were collected. PCV13 was not systematically administered in Catalonia during the study period, but was available in the private market so the vaccination coverage in children increased from 48.2% to 74.5%. RESULTS: 35 cases of NP were identified. 77.1% of cases were associated with empyema. In the first 4 years, a trend to a decrease in NP incidence was observed (p=0.021), especially in children <5 years (p=0.006). Serotype 3 was responsible for 48.6% of NP cases. Five patients with NP due to serotype 3 were fully vaccinated for their age with PCV13. CONCLUSIONS: Serotype 3 has a preeminent role in pneumococcal NP and was associated with all PCV13 vaccination failures. Although in our series the incidence does not seem to be increasing, evolution of pneumococcal NP rates should be monitored after inclusion of PCV13 in the systematic calendar.

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.

Complicated pneumococcal pneumonia with pleural effusion or empyema in the 13-valent pneumococcal conjugate vaccine era.

AIM: The aim was to analyze the epidemiological, microbiological and clinical characteristics of patients with complicated pneumococcal pneumonia with pleural effusion (PE) or empyema. METHOD: Prospective study in three Catalan hospitals in persons aged <18 years diagnosed with complicated pneumonia with PE or empyema with isolation of Streptococcus pneumoniae in blood or pleural fluid by culture or real-time PCR between January 2012 and June 2016. Patients were divided into <2 years and 2-17 years age groups. Epidemiological, microbiological, and clinical data of patients were compared annually in both groups. PCV13 vaccination coverage increased from 48.2% in 2012 to 74.5% in 2015. RESULTS: We included 143 patients. The incidence of pneumococcal pneumonia was 6.83 cases × 10-5 persons/year in cases with PE or empyema and 2.09 cases × 10-5 person-years in cases without (rate ratio [RR]: 3.27; 2.25-4.86; P < 0.001). Empyema was more frequent than PE (79.7% vs 20.3%, P < 0.005). Of 143 cases studied, 93 (65.0%, P < 0.001) were diagnosed by real-time-PCR, 43 (30.1%) by culture and RT-PCR and 7 (4.9%) by culture only. PCV13 serotypes were more frequent in complicated than in uncomplicated pneumonia (116/142, 81.7% vs 27/45, 60.0%; P = 0.003), especially serotype 1 (41/142, 28.9% vs 6/45, 13.3%, P : 0.036). From 2012 to 2015 there was a significant reduction in serotype 1 (16/43, 37.2% vs 3/27, 11.1%, P = 0.026), and a trend to an increase in non-PCV13 serotypes (6/43, 14% vs 9/27, 33.3%, P = 0.054). CONCLUSIONS: A directly proportional relationship was observed between the reduction in pneumonia complicated with PE or empyema and a significant reduction in PCV13 serotypes, especially serotype 1, coinciding with increased PCV13 coverage.

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

PURPOSE: 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. 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 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. 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.

Are risk factors associated with invasive pneumococcal disease according to different serotypes?

The aim of this study was to investigate risk factors for the most common serotypes of invasive pneumococcal disease (IPD). A total of 293 IPD cases were analyzed in children aged 3-59 mo in a community with intermediate vaccination coverage with the 7-valent pneumococcal vaccine (PCV7). IPD cases were reviewed during 2007-2009 in two pediatric hospitals in Catalonia (Spain). A multivariate analysis using unconditional logistic regression was performed to estimate the adjusted odds ratio. PCV7 coverage was 45.4%. Pneumonia with empyema (64.5%) was the most frequent clinical manifestation. The most common serotypes were: serotype 1 (21.2%), 19A (16.0%), 3 (12.6%) and 7F/A (6.8%). 70.0% of serotypes found were included in the 13-valent conjugate vaccine (PCV13), 39.2% in the 10-valent conjugate vaccine and 8.1% in the PCV7. PCV7 was protective in IPD cases due to PCV7-serotypes (aOR: 0.15, 95% CI:0.04-0.55). Serotype 1 was positively associated with attending day care or school (aOR: 3.55, 95% CI: 1.21-10.38) and age 24-59 mo (aOR: 7.70, 95% CI:2.70-21.98). Serotype 19A was positively associated with respiratory infection in the previous month (aOR: 2.26, 95% CI: 1.03-4.94), non-penicillin susceptible IPD (aOR: 1.89, 95% CI:1.13-3.16) and negatively associated with age 24-59 mo (aOR: 0.19, 95% CI:0.09-0.41). Serotype 3 was positively associated with vaccination (aOR: 4.87, 95% CI:2.05-11.59). No factors were associated with serotype 7F/A. Vaccination with pneumococcal vaccines including more serotypes may reduce the risk of disease in our setting.

Risk factors for invasive pneumococcal disease in a community with a high proportion of non vaccine serotypes.

The aim of this study was to investigate factors associated with vaccination with 7-pneumococcal conjugate vaccine (PCV7) and risk factors for invasive pneumococcal disease (IPD) and for penicillin-nonsusceptible strains in a community with intermediate vaccination coverage. We conducted a prospective, matched case-control study in children aged 3-59 months with IPD admitted to two hospitals in Catalonia. Three controls matched by hospital, age, sex, date of hospitalization and risk medical conditions were selected for each case. We calculated odds ratios for potential risk factors using logistic regression. Of the 1075 children included, 46.6% were considered fully vaccinated by age. 91.1% of cases were caused by non-PCV7 serotypes. Vaccination with PCV7 was positively associated with attending day care or school and negatively associated with age 24-59 months, >4 cohabitants and low social class. Attending day care or school and >4 cohabitants were risk factors for IPD. Previous antibiotic treatment in children aged 24-59 months was a protective factor for IPD; however, antibiotic use in the previous month and age <24 months were associated with penicillin-nonsusceptible IPD. In a community where IPD in children aged <5 years is caused mainly by non-PCV7 Streptococcus pneumoniae serotypes and where vaccine coverage is only intermediate, attending day care or school, age <24 months, >4 cohabitants and social class were associated with vaccination. Attending day care or school was a strong risk factor for IPD, while vaccination was protective in children aged <24 months. Age and antibiotic use in the previous month were associated with penicillin-nonsusceptible IPD.

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

The aim of this study was to evaluate the effectiveness of the administration of the 7-valent pneumococcal conjugate vaccine in a region with an intermediate vaccination coverage. A matched case-control study was carried out in children aged 7-59 months with invasive pneumococcal disease (IPD) admitted to two university hospitals in Catalonia. Three controls matched for hospital, age, sex, date of hospitalization and underlying disease were selected for each case. Information on the vaccination status of cases and controls was obtained from the vaccination card, the child's health card, the hospital medical record or the vaccination register of the primary healthcare center where the child was attended for non-severe conditions. A conditional logistic regression analysis was made to control for the effect of possible confounding variables. The adjusted vaccination effectiveness of the complete vaccination schedule (3 doses at 2, 4 and 6 months and a fourth dose at 15 months, 2 doses at least two months apart in children aged 12-23 months or a single dose in children aged >24 months) in preventing IPD caused by vaccine serotypes was 93.7% (95% CI 51.8-99.2). It was not effective in preventing cases caused by non-vaccine serotypes. The results of this study carried out in a population with intermediate vaccination coverage confirm those of other observational studies showing high levels of effectiveness of routine 7-valent pneumococcal conjugate vaccination.

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.