Pediatric Invasive Pneumococcal Disease Research Articles

Study of pediatric invasive pneumococcal disease in the 13-pneumococcal conjugated vaccine era

BackgroundInvasive pneumococcal disease (IPD) remains a significant concern among children under 5, despite vaccination efforts. This study assessed IPD prevalence and associated risks in pediatric population. MethodsAn observational, retrospective, multicenter study in Comunidad Valenciana, Spain, of IPD cases in children under 13 from January 2012 to September 2022. Data from the CV Microbiology Surveillance Network (RedMIVA) and medical records were reviewed. ResultsA total of 379 IPD cases in 377 patients were analyzed, predominantly males (54.11 %) under 5 (81.17 %). PCV13 vaccination notably reduced PCV13-serotypes IPD (p=0.0002), except serotype 3. Pneumonia was common, with half having underlying conditions (50.40 %). Worse outcomes occurred in patients with neurological disorders (ANOVA, p=0.57). Vaccine failures often involved underlying conditions (63 %) and serotypes 3 and 19A. Immunodeficiencies may relate to recurrent IPD, but evidence is limited. ConclusionDespite vaccination, IPD still impacts children, influenced by immunological status, affecting severity and mortality.

Serotype distribution, clinical characteristics, and antimicrobial resistance of pediatric invasive pneumococcal disease in Colombia during PCV10 mass vaccination (2017-2022).

Invasive Pneumococcal Disease (IPD) causes significant morbidity and mortality in children under 5 y. Colombia introduced PCV10 vaccination in 2012, and the Neumocolombia network has been monitoring IPD in pediatric patients since 2008. This study is a secondary analysis of a prospective cohort involving pediatric patients with IPD admitted to 17 hospitals in Colombia, from January 1st, 2017, to December 31st, 2022. We present data on serotypes (Spn), clinical characteristics, and resistance patterns. We report 530 patients, 215 (40.5%) were younger than 24 months. Among these, 344 cases (64.7%) presented with pneumonia, 95 (17.9%) with primary bacteremia, 53 (10%) with meningitis, 6 (1.1%) had pneumonia and meningitis, and 32 (6%) had other IPD diagnosis. The median hospital stay was 12 days (RIQ 8-14 days), and 268 (50.6%) were admitted to the ICU, of whom 60 (11.3%) died. Serotyping was performed in 298 (56.1%). The most frequent serotypes were Spn19A (51.3%), Spn6C (7.7%), Spn3 (6.7%), Spn6A (3.6%), and Spn14 (3.6%). Of 495 (93%) isolates with known susceptibility, 46 (9.2%) were meningeal (M) and 449 (90.7%) non-meningeal (NM). Among M isolates, 41.3% showed resistance to penicillin, and 21.7% decreased susceptibility to ceftriaxone. For NM isolates, 28.2% had decreased susceptibility to penicilin, and 24.2% decreased susceptibility to ceftriaxone. Spn19A showed the highest resistant to penicillin at 47% and was linked to multiresistance. The prevalence of PCV10-included serotypes decreased, while serotypes 19A and 6C increased, with Spn19A being associated with multiresistance. These findings had played a crucial role in the decision made by Colombia to modify its immunization schedule by switching to PCV13 in July 2022.

Molecular epidemiology of paediatric invasive pneumococcal disease in Andalusia, Spain.

This study aimed to assess the impact of the introduction of pneumococcal conjugate vaccine 13 (PCV13) on the molecular epidemiology of invasive pneumococcal disease (IPD) in children from Andalusia. A population-based prospective surveillance study was conducted on IPD in children aged <14 years from Andalusia (2018-2020). Pneumococcal invasive isolates collected between 2006 and 2009 in the two largest tertiary hospitals in Andalusia were used as pre-PCV13 controls for comparison of serotype/genotype distribution. Overall IPD incidence rate was 3.55 cases per 100 000 in 2018; increased non-significantly to 4.20 cases per 100 000 in 2019 and declined in 2020 to 1.69 cases per 100 000 (incidence rate ratio 2020 vs. 2019: 0.40, 95% confidence interval (CI) 0.20-0.89, P = 0.01). Proportion of IPD cases due to PCV13 serotypes in 2018-2020 was 28% (P = 0.0001 for comparison with 2006-2009). Serotypes 24F (15%) and 11A (8.3%) were the most frequently identified non-PCV13 serotypes (NVT) in 2018-2020. Penicillin- and/or ampicillin-resistant clones mostly belonged to clonal complex 156 (serotype 14-ST156 and ST2944 and serotype 11A-ST6521). The proportion of IPD cases caused by PCV13 serotypes declined significantly after the initiation of the PCV13 vaccination programme in 2016. Certain NVT, such as serotypes 24F and 11A, warrant future monitoring in IPD owing to invasive potential and/or antibiotic resistance rates.

Association of Nonpharmaceutical Interventions During the COVID-19 Pandemic With Invasive Pneumococcal Disease, Pneumococcal Carriage, and Respiratory Viral Infections Among Children in France

An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections. To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France. This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France. Implementation of NPIs during the COVID-19 pandemic. The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model. During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, -82% to -43%; P < .001) and was similar for non-13-valent pneumococcal conjugate vaccine serotypes with both high disease potential (-63%; 95% CI, -77% to -48%; P < .001) and low disease potential (-53%; 95% CI, -70% to -35%; P < .001). The overall pneumococcal carriage rate did not significantly change after NPI implementation (-12%; 95% CI, -37% to 12%; P = .32), nor did the carriage rate for non-PCV13 serotypes with high disease potential (-26%; 95% CI, -100% to 52%; P = .50) or low disease potential (-7%; 95% CI, -34% to 20%; P = .61). After NPI implementation, the estimated number of influenza cases decreased by 91% (95% CI, -74% to -97%; P < .001), and the estimated number of RSV cases decreased by 74% (95% CI, -55% to -85%; P < .001). Overall, the decrease in influenza and RSV cases accounted for 53% (95% CI, -28% to -78%; P < .001) and 40% (95% CI, -15% to -65%; P = .002) of the decrease in IPD incidence during the NPI period, respectively. The decrease in IPD incidence was not associated with pneumococcal carriage, with carriage accounting for only 4% (95% CI, -7% to 15%; P = .49) of the decrease. In this cohort study of data from multiple national continuous surveillance systems, a decrease in pediatric IPD incidence occurred after the implementation of NPIs in France; this decrease was associated with a decrease in viral infection cases rather than pneumococcal carriage rate. The association between pneumococcal carriage and IPD was potentially modified by changes in the number of RSV and influenza cases, suggesting that interventions targeting respiratory viruses, such as immunoprophylaxis or vaccines for RSV and influenza, may be able to prevent a large proportion of pediatric IPD cases.

Decrease in Pediatric Invasive Pneumococcal Disease During the COVID-19 Pandemic.

Measures to limit SARS-CoV-2 transmission in 2020 reduced other viral infections. Among 7 US children’s hospitals, invasive pneumococcal disease cumulative incidence decreased by 46% in 2020 vs 2017-2019. Limited droplet transmission of pneumococci and preceding viral pathogens may be responsible.

Clinical characteristics, antimicrobial resistance, and risk factors for mortality in paediatric invasive pneumococcal disease in Beijing, 2012\u20132017

BackgroundTo analyse clinical characteristics, antibiotic susceptibility, and risk factors for mortality in paediatric invasive pneumococcal disease (IPD) in Beijing.MethodsPaediatric IPD patients in our hospital were retrospectively collected from 2012 to 2017. Clinical manifestations, laboratory tests, antimicrobial susceptibility and serotype of isolates, and risk factors for mortality of IPD were analysed.ResultsOverall, 186 IPD cases were enrolled. The major manifestations were meningitis (76), pneumonia with bacteraemia (60), bacteraemia without focus (21), and pneumonia with empyaema (22). Of 72 cases with underlying diseases, leukaemia (18.0%), congenital heart disease (15.3%), primary immunodeficiency disease (12.5%), nephrotic syndrome (12.5%), and cerebrospinal fluid leakage (12.5%) were most common. In total 96.9% of isolates would have been covered by the pneumococcal conjugate vaccine (PCV13), including 19F (32.8%), 19A (23.4%), 4 (17.2%), and 23F (9.4%). Nonsusceptibility rates of penicillin, cefotaxime, and cefepime among nonmeningitis patients increased between 2012 and 2017; The mortality rate was 21.5%. Meningitis, respiratory failure, multiple organ failure, and white blood cell count < 4000 cells/μL were independent risk factors for mortality.ConclusionMeningitis was the most common clinical manifestation of IPD, and was frequently associated with death. Strains in the PCV13 vaccine would cover most of the cases, and so wider use of PCV13 should be considered.

Epidemiological characteristics in serotype 24 paediatric invasive pneumococcal disease according to an 11-year population-based study in Japan.

After the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), serotype replacement has occurred in Japan, and serotype 24 has become the most common serotype in paediatric invasive pneumococcal disease (IPD). To understand the characteristics of serotype 24-IPD in Japanese children in the post-PCV13 era, we conducted a retrospective study in children aged ≤15 years from 2010 to 2020 using a database of paediatric IPD surveillance in Chiba prefecture, Japan. We identified a total of 357 IPD cases and collected clinical information on 225 cases (24: 32 cases, non-24: 193 cases). Compared with the non-serotype 24-IPD, serotype 24-IPD was independently related to be <2 years of age [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.47-10.44; P = 0.0064] and bacteremia (OR 2.28, 95% CI 1.01-5.13; P = 0.0475), as a result of the multivariate regression analysis. We also conducted a bacterial analysis, and the isolates of serotype 24-IPD had tendencies of PCG-susceptible (24: 100.0%, non-24: 61.3%; P < 0.0001) and macrolide-resistance (24: 100.0%, non-24: 87.3%; P = 0.0490). Their multilocus sequence typing was mostly ST2572 and the variants, which were unique to Japan. This tendency might have been a result of the progress made in the Japanese PCV13 immunisation programme.

183. Decrease in Invasive Pneumococcal Disease in 7 United States Children’s Hospitals during the COVID-19 Pandemic

BackgroundDuring the 2020 SARS-CoV-2 pandemic, physical distancing and mask use guidelines were implemented resulting in a decline in the number of infections caused by influenza, respiratory syncytial virus and otitis media. A surveillance analysis from England and Taiwan showed a decline in invasive pneumococcal disease (IPD) (Clin Infect Dis. 2021;72: e65-75 and J Infect. 2021;82:296-297). We hypothesized that COVID mitigation efforts resulted in a decrease in incidence of pediatric IPD within the U.S. during 2020 compared to previous years.MethodsWe reviewed all cases of IPD among 7 children’s hospitals from the U.S. Pediatric Multicenter Pneumococcal Surveillance Group from 2017-2020. IPD was defined by the isolation of Streptococcus pneumoniae from normally sterile sites (eg. blood, cerebrospinal, pleural, synovial or peritoneal fluid). Pneumococcal pneumonia was defined as an abnormal chest radiograph in the presence of a positive blood, pleural fluid or lung culture. Mastoiditis was identified by positive middle ear, subperiosteal abscess or mastoid bone culture. Serotypes were determined by the capsular swelling method. Hospital admission numbers were obtained for incidence calculations. Statistical analyses were performed using STATA11. A p< 0.05 was considered significant.ResultsA total of 410 IPD cases were identified. The cumulative incidence of IPD (0-22 years of age) decreased from 99.2/100,000 admissions in 2017-2019 to 53.8/100,000 admissions in 2020 (risk ratio 0.54, CI: 0.40-0.72, p< 0.00001). Pneumococcal bacteremia and pneumonia decreased significantly in 2020 (p< 0.05), and although not statistically significant, there were fewer cases of meningitis and mastoiditis when compared to previous years (p=0.08) (Figure 1). Sex, race, age or presence of comorbidities were not significantly different between groups. Most common serotypes in 2020 were 35B, 3 and 15B/C (Figure 2). ConclusionThe observed decline in IPD cases during the first year of the SARS-CoV-2 pandemic is likely associated with mask use and physical distancing limiting transmission of S. pneumoniae via droplets and viral infections frequently preceding IPD. These precautions might be useful in the future to decrease IPD, especially in high-risk patients.Disclosures Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Tina Q. Tan, MD, GSK (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; ILiAD (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; Moderna (Individual(s) Involved: Self): Advisor or Review Panel member; Pfizer (Individual(s) Involved: Self): Advisor or Review Panel member Pia S. Pannaraj, MD, MPH, Pfizer (Grant/Research Support)Sanofi-Pasteur (Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Larry Givner, MD, AstraZeneca (Advisor or Review Panel member) Kristina G. Hulten, PhD, Pfizer (Research Grant or Support)

Pediatric Invasive Pneumococcal Disease Three Years after PCV13 Introduction in the National Immunization Plan—The Continued Importance of Serotype 3

The introduction of pneumococcal conjugate vaccines PCV7 and PCV13 led to decreases in incidence of pediatric invasive pneumococcal disease (pIPD) and changes in serotype distribution. We evaluated the consequences of higher vaccine uptake after the introduction of PCV13 in the National Immunization Plan (NIP) in 2015. Besides culture and conventional serotyping, the use of molecular methods to detect and serotype pneumococci in both pleural and cerebrospinal fluid samples contributed to 30% of all pIPD (n = 232) in 2015–2018. The most frequently detected serotypes were: 3 (n = 59, 26%), 10A (n = 17, 8%), 8 (n = 16, 7%) and 19A (n = 10, 4%). PCV13 serotypes still accounted for 46% of pIPD cases. Serotypes not included in any currently available conjugate vaccine (NVT) are becoming important causes of pIPD, with the increases in serotypes 8 and 33F being of particular concern given the importance of serotype 8 in adult IPD and the antimicrobial resistance of serotype 33F isolates. This study highlights the importance of using molecular methods in pIPD surveillance since these allowed a better case ascertainment and the identification of serotype 3 as the leading cause of pIPD. Even in a situation of vaccine uptake >95% for 3 years, PCV13 serotypes remain important causes of pIPD.

POS-199 STREPTOCOCCUS PNEUMONIAE-ASSOCIATED HEMOLYTIC UREMIC SYNDROME IN CANADIAN CHILDREN WITH INVASIVE PNEUMOCOCCAL DISEASE: FROM IMPACT NATIONAL SURVEILLANCE NETWORK

Hemolytic uremic syndrome (HUS) is typically a complication of enterocolitis from Shiga toxin-producing Escherichia coli. Streptococcus pneumoniae-associated HUS (SP-HUS) is less frequent, accounting for ~5% of HUS cases in children. It is most associated with invasive pneumococcal disease (IPD) that presents with pneumonia. Pediatric SP-HUS mortality has been reported as 3-12%. This study aimed to describe the epidemiology of pediatric SP-HUS in Canada by conducting a secondary analysis of the national pediatric IPD surveillance data from 1991-2019.

Health and economic burden of invasive pneumococcal disease associated with 15-valent pneumococcal conjugate vaccine serotypes in children across eight European countries

Aims V114, a 15-valent pneumococcal conjugate vaccine (PCV15) currently approved in adults in the US, contains the 13 S. pneumoniae serotypes in PCV13 and two additional serotypes, 22 F and 33 F, which are important contributors to residual PD. This study quantified the health and economic burden of pediatric invasive pneumococcal disease (IPD) associated with V114 serotypes in eight countries in Europe. Materials and methods A Markov model estimated V114-type IPD cases and costs in hypothetical unvaccinated birth cohorts from Denmark, France, Germany, Italy, Norway, Spain, Switzerland, and the UK over 20 years. Inputs were obtained from published literature. IPD cases and costs were calculated for three time periods using time-specific epidemiological data: (a) pre-PCV7; (b) pre-PCV13; and (c) post-PCV13. Costs were estimated from a societal perspective (2018 Euros) and discounted at 3%. Results The model estimated that 4,649 IPD cases in the pre-PCV7 period, 3,248 cases in the pre-PCV13 period, and 958 cases in the post-PCV13 period were attributable to V114 serotypes. Total discounted costs associated with V114 serotypes were €109.1 million (pre-PCV7 period), €65.7 million (pre-PCV13 period), and €18.7 million (post-PCV13 period). Limitations Post-meningitis sequelae, acute otitis media, and non-bacteremic pneumonia were not considered. Direct non-medical costs were not included. Conclusions on effectiveness of V114 or added value over existing infant vaccination programs cannot be drawn. Conclusions IPD cases and costs were estimated in hypothetical birth cohorts in eight European countries followed for 20 years during three time periods. Serotypes included in V114 were associated with significant morbidity and costs in pre-PCV7, pre-PCV13, and post-PCV13 periods. Future pediatric pneumococcal vaccines should maintain protection against serotypes in licensed vaccines while extending coverage to additional serotypes to ensure reductions in IPD burden are maintained.

Dynamic changes in paediatric invasive pneumococcal disease after sequential switches of conjugate vaccine in Belgium: a national retrospective observational study

Ten-valent and 13-valent pneumococcal conjugate vaccines (PCVs) have shown important benefits by decreasing invasive pneumococcal disease caused by vaccine serotypes. Belgium had an uncommon situation with sequential use of PCV7, PCV13, and PCV10 in the childhood vaccination programmes between 2007 and 2018. We aimed to analyse the changes in incidence of invasive pneumococcal disease and serotype distribution in children throughout this period. Streptococcus pneumoniae isolates were obtained from patients with invasive pneumococcal disease in Belgium between 2007 and 2018 by the national laboratory-based surveillance. Paediatric invasive pneumococcal disease incidence, serotype distribution, and antimicrobial susceptibility were analysed in periods during which PCV7 (2009-10), PCV13 (2013-14), both PCV13 and PCV10 (2015-16), and PCV10 (2017-18) were used. Incidence rates and trends were compared. Vaccination status was collected. For a subset of serotype 19A isolates, multilocus sequence type was identified. After a decrease in PCV7 serotype invasive pneumococcal disease was observed during the PCV7 period, total paediatric invasive pneumococcal disease incidence significantly declined during the PCV13 period (-2·6% monthly, p<0·0001). During the PCV13-PCV10 period (2015-16), the lowest mean in paediatric invasive pneumococcal disease incidence was achieved, but the incidence increased again during the PCV10 period (2017-18), especially in children younger than 2 years (+1·7% monthly; p=0·028). This increase was mainly due to a significant rise in serotype 19A invasive pneumococcal disease incidence in the PCV10 period compared with the PCV13 period (p<0·0001), making serotype 19A the predominant serotype in paediatric invasive pneumococcal disease in the PCV10 period. Genetic diversity within the 2017-18 serotype 19A collection was seen, with two predominant clones, ST416 and ST994, that were infrequently observed before PCV10 introduction. In 2018, among children younger than 5 years with invasive pneumococcal disease who were correctly vaccinated, 37% (37 of 100) had PCV13 serotype invasive pneumococcal disease, all caused by serotype 19A and serotype 3. After a significant decrease during the PCV13 period, paediatric invasive pneumococcal disease incidence increased again during the PCV10 period. This observation mainly resulted from a significant increase of serotype 19A cases. During the PCV10 period, dominant serotype 19A clones differed from those detected during previous vaccine periods. Whether changes in epidemiology resulted from the vaccine switch or also from natural evolution remains to be further elucidated. The Belgian National Reference is funded by the Belgian National Institute for Health and Disability Insurance and the whole genome sequencing by an investigator-initiated research grant from Pfizer.

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.

Clonal spread of serotype 12F ST4846 Streptococcus pneumoniae.

Introduction. In 2016-2017, there was an increase in the number of paediatric invasive pneumococcal disease (IPD) cases caused by Streptococcus pneumoniae serotype 12F in Chiba Prefecture, Japan. Serotype 12F is one of the major causative serotypes of IPD following the introduction of pneumococcal conjugate vaccine 13 (PCV13), and outbreaks of IPD caused by serotype 12F have recently been reported in several countries.Aim. Our goal here was to clarify the relationship among local outbreak strains and the outbreak strains in other countries, and for this we analysed clinical isolates of S. pneumoniae serotype 12F using several genetic identification methods.Methodology. All reported IPD cases caused by serotype 12F were reviewed and bacterial strains were collected and analysed. We also analysed S. pneumoniae serotype 12F strains isolated from other time periods, geographical areas, cases of adult IPD and respiratory specimens as control strains. Multi-locus sequence typing, PFGE and multi-locus variable number tandem repeat analysis (MLVA) were conducted on all isolates.Results. All 26 S. pneumoniae serotype 12F isolates, including control strains, belonged to a single sequence type (ST4846) that was the specific ST in Japan. All tested strains demonstrated five MLVA patterns and two PFGE patterns.Conclusion. We determined that the 2016-2017 outbreak of IPD in Chiba Prefecture was caused by clonally related isolates of serotype 12F. The continuous monitoring of IPD caused by serotype 12F is important for evaluating the impact of re-emerging pneumococcal serotypes following the PCV13 introduction era, and MLVA could be a useful tool for identification of outbreak strains.

The clinical implication of serotype distribution and drug resistance of invasive pneumococcal disease in children: A single center study in southern Taiwan during 2010-2016.

The regional study of pediatric invasive pneumococcal disease (IPD) is still limited in Taiwan. The aim of this study is to update the epidemiologic data of pediatric IPD in Taiwan, focusing on the trend of non-13-valent pneumococcal conjugate vaccines (PCV13)-specific serotypes and antimicrobial susceptibility. This was a single-center retrospective study by chart reviewing and recruited patients aged <18 years who were reported having IPD between January 2010 and December 2016. Clinical manifestations, serotypes of pneumococcus and antimicrobial susceptibility were compared and analyzed. A total of 46 patients were enrolled in this study. Serotype 19 A was the most common serotype (32.6%) in pediatric IPD and significantly correlated with empyema. Non-PCV13-specific serotypes such as serotype 15, 15B, 15C and 22 were reported during this period. There was no mortality or significant morbidity associated with these emerging strains. Using the meningitis breakpoint of minimum inhibitory concentration (MIC), although it showed no significant linear trend of the prevalence of ceftriaxone non-susceptible pneumococcus (CNSP) (p=0.392), the prevalence of CNSP increased from 50% (11 over 22) before 2013 to 83% (20 over 24) after 2013 with statistical significance (p=0.027). The increase in the prevalence of CNSP using meningitis breakpoint was observed since 2013. For treating pneumococcal meningitis, empirical therapy with vancomycin and ceftriaxone is warranted. Although the non-PCV13-specific serotypes reported in our study caused no morbidity and mortality, further monitoring and surveillance are still recommended.

The increasing importance of non-culture methods in diagnosis and serotyping of invasive pediatric pneumococcal infections revealed the continuous dominance of vaccine serotypes in the era of PCV13 vaccination

Purpose: We evaluated the role of non-culture methods for diagnosis in evaluating the impact of continued 13-valent pneumococcal conjugate vaccine (PCV13) use in the private market in pediatric invasive pneumococcal disease (pIPD) in Portugal (2012-2015). Methods & Materials: The pIPD cases were identified and isolates were submitted to a central laboratory for further characterization. In possible pIPD cases where culture of pleural or cerebrospinal fluid was negative, real-time PCR reactions targeting conserved (lytA and cpsA) genes and capsule specific genes were used to detect and serotype pneumococci. Results: The most frequently detected serotypes were: 3 (n = 32, 13.8%), 14 (n = 23, 9.9%), 1 (n = 23, 9.9%), 7F (n = 15, 6.4%), 19A (n = 13, 5.6%), 6B and 15B/C (both n = 12, 5.2%), and 24F, 10A and 12B (all with n = 10, 4.3%). The use of PCR to detect and serotype pneumococci in both pleural and cerebrospinal fluid samples contributed to 20% (n = 47) of all pIPD. Serotype 3 was mostly detected by PCR (n = 21/32, 65.6%) and resulted from a relevant number of vaccine failures. The incidence of pIPD varied in the different age groups but without a clear trend. There were no obvious declines of the incidence of pIPD due to serotypes included in any of the PCVs, and PCV13 serotypes still accounted for the majority of pIPD (53%). Conclusion: Our study indicates that a higher vaccination uptake may be necessary to realize the full benefits of PCVs, even after 15 years of use, and highlights the importance of using molecular methods in pIPD surveillance, since these can lead to substantially increased case ascertainment and the identification of particular serotypes as causes of pIPD.

Dominance of vaccine serotypes in pediatric invasive pneumococcal infections in Portugal (2012\u20132015)

We evaluated the impact of continued 13-valent pneumococcal conjugate vaccine (PCV13) use in the private market (uptake of 61%) in pediatric invasive pneumococcal disease (pIPD) in Portugal (2012–2015). The most frequently detected serotypes were: 3 (n = 32, 13.8%), 14 (n = 23, 9.9%), 1 (n = 23, 9.9%), 7F (n = 15, 6.4%), 19A (n = 13, 5.6%), 6B and 15B/C (both n = 12, 5.2%), and 24F, 10A and 12B (all with n = 10, 4.3%). Taken together, non-PCV13 serotypes were responsible for 42.2% of pIPD with a known serotype. The use of PCR to detect and serotype pneumococci in both pleural and cerebrospinal fluid samples contributed to 18.1% (n = 47) of all pIPD. Serotype 3 was mostly detected by PCR (n = 21/32, 65.6%) and resulted from a relevant number of vaccine failures. The incidence of pIPD varied in the different age groups but without a clear trend. There were no obvious declines of the incidence of pIPD due to serotypes included in any of the PCVs, and PCV13 serotypes still accounted for the majority of pIPD (57.8%). Our study indicates that a higher vaccination uptake may be necessary to realize the full benefits of PCVs, even after 15 years of moderate use, and highlights the importance of using molecular methods in pIPD surveillance, since these can lead to substantially increased case ascertainment and identification of particular serotypes as causes of pIPD.

Epidemiology of invasive pneumococcal disease in the city of Kenora, Ontario, Canada, and surrounding area (2010-2016)

Introduction: Streptococcus pneumoniae is a recognized important pathogen in Indigenous populations in the Sioux Lookout area of Northwestern Ontario, Canada. This study investigates the current epidemiology of invasive pneumococcal disease (IPD) in the Kenora area of Northwestern Ontario, which has a relatively large Indigenous population (30%). Methods: Data from January 2010 to December 2016 were retrieved from retrospective chart review at a hospital servicing a population of 19,380. Results: Thirty-one cases of IPD were identified. Regional incidence (26.6/100,000/year) is nearly three times the national rate (9.0/100,000/year). In adults, 66.7% of cases were caused by serotypes included in the 23-valent pneumococcal polysaccharide vaccine. All pediatric IPD cases were caused by serotypes not included in the 13-valent pneumococcal conjugate vaccine. Ninety per cent of cases had confirmed underlying disease. Conclusions: In the Kenora area, IPD incidence is comparable to incidence in the Sioux Lookout area. Improvement of pneumococcal vaccination uptake in senior and high-risk populations is required.

1432. County-Wide Pediatric IPD Experience Following Prevnar 13 Implementation

BackgroundAlthough invasive pneumococcal disease (IPD) has declined following pneumococcal conjugate vaccines, both respiratory (R-IPD; e.g., pneumonias +/− empyema) and nonrespiratory IPD (NR-IPD) remain concerning. We evaluate 13-valent pneumococcal conjugate vaccine (PCV13) impact on county-wide IPD, serotypes involved and patients affected since its 2010 introduction.MethodsProspective analysis of culture confirmed pediatric IPD was conducted in Orange County, CA following PCV13 vaccine implementation comparing 2010–2013 (transition; Era 1) to 2014–2017 (full implementation; Era 2). We reviewed age, ethnicity, health status, immunizations, immune work up, site of infection, and serotype distribution.ResultsThere were 135 IPD cases (78[58%] male; 63[47%] Hispanic, 38[28%] White, 14[10%] Asian, 9[7%] other and 11[8%] unknown). IPD decreased by 37.3% (Era 1 = 83 cases vs. Era 2 = 52). R-IPD (41.5%) and NR-IPD (58.5%) exhibited a similar decrease. Serotype was known for 116 (86%) cases. Overall PCV13 serotype incidence rate (IR) per 100,000 population decreased by 44.7%; of note non-PCV13 decreased by 14.8%. The largest change was seen in PCV13 serotype NR-IPD (−60%) (Figure 1). As a percentage of PCV13 serotypes, 19A and 3 increased from 32 and 21% to 46% (+44%) and 27% (+29%), respectively. Meanwhile, 7F decreased from 36 to 7% (−81%). R-IPD due to PCV13 serotype in children <5 years old did not decrease during the study (Figure 2). By Era 2 PCV13 immunization was broadly implemented (Figure 3). Despite being fully immunized, 12 patients (5[42%] male; 7[58%] White, 4[33%] Asian, 1[8%] other) developed PCV13 serotype IPD. The majority (10/12) were previously healthy, with R-IPD (83%) and affected by serotypes 19A (58%) or 3 (25%). No immune deficiency was identified among these subjects.ConclusionPediatric IPD continues to decrease post PCV13 implementation, most notably due to a decrease in PCV13 serotype NR-IPD and disappearance of 7F. We did not see an increase in non-PCV13 IPD. Serotypes 19A and 3 remain a significant proportion of a lower number of cases. Children <5 remain at highest risk for IPD, particularly R-IPD. A notable proportion of PCV13 serotype R-IPD occurred in fully immunized and previously healthy children. Disclosures A. Arrieta, Melinta Therapeutics: Investigator, Research support.

Paediatric invasive pneumococcal disease on the island of Gran Canaria: 16-year prospective study (2001–2016)

ObjectivesTo calculate the incidence of invasive pneumococcal disease (IPD) in the paediatric population of Gran Canaria (Spain), its clinical and epidemiological characteristics, serotype distribution, antibiotic resistance, and variations in these variables before and after the introduction of the PCV13 vaccine. MethodsProspective hospital-based study including all patients (190) aged 0–14 years admitted with confirmed IPD between January 2001–May 2010 (152 cases) and June 2010–December 2016 (38 cases). Patients were divided into 3 age groups (<2 years; 2–5 years; and >5 years). Clinical symptoms were mutually-exclusively classified as meningitis, bacteraemic pneumonia, pleural effusion (PE), empyema or bacteraemia without a focus. ResultsMost cases occurred in boys (59.47%), during autumn-winter (65.79%), in children aged <2 years (55.79%) and with mean age increasing from the pre-PCV13 to the post-PCV13 period (2.5 vs 3.1 years). Incidence between periods reduced by 66.4% (p<0.001): from 13.1/100,000 to 4.4/100,000. PEs (3.9% vs 18.4%, p<0.005) and empyemas (1.5% vs 16.7%, p=NS) increased in the post-PCV13 period whereas all other symptoms decreased, although this was not statistically significant. Vaccine serotypes (77% vs 40.6%, p=0.000), particularly serotypes 19A (23.9% vs 12.5%) and 14 (14.2% vs 9.4%), as well as erythromycin resistance (57.2% vs 7.9%, p=0.000) decreased in the post-PCV13 period. ConclusionIPD incidence, vaccine serotypes and erythromycin resistance decreased in the post-PCV13 period whereas PEs increased.