Incidence Of Invasive Pneumococcal Disease In Children Research Articles

What do you get? Transmission of pneumococcal pneumonia.

Streptococcus pneumoniae is a polysaccharide encapsulated bacterium responsible for the majority of cases of community acquired pneumonia. The upper respiratory tract of children becomes colonized with pneumococci early in life, from the first weeks of life up to 18 months. Factors which influence timing of colonization include geographical localization, socio-economic circumstances, and household conditions. Pneumococcal pneumonia to a degree is a seasonal disease, peaking in the winter months. One of the epidemiological determinants is that viral infections (in particular influenza) predispose for pneumococcal pneumonia. The infectious nature of pneumococcal pneumonia was underscored during the COVID-19 pandemic. Due to societal restrictions imposed (face masks, social distancing) the incidence of invasive pneumococcal disease (IPD) dropped, and returned to pre-COVID-19 numbers after lifting of the restrictions. There are 100 different S. pneumoniae serotypes, based on differences in the capsular polysaccharide. Introduction of protein conjugated polysaccharide vaccines (PCV) has reduced the incidence of IPD in children. Because children are the reservoir for other risk groups, in particular the elderly, introduction of PCV has indirectly also reduced the burden of IPD in latter risk group. The first generation of PCV consisted of the seven most prevalent pneumococcal serotypes. After implementation, replacement colonization of the upper respiratory tract with non-vaccine serotypes was observed and also replacement disease. Upcoming 24-valent PCVs will have a much broader coverage, but whether replacement disease now has been eliminated remains to be seen.

1309. Incidence and Epidemiology of Invasive Pneumococcal Disease due to Serotype 3 in South-Central Ontario

BackgroundIn our population, the most common serotype (ST) of S. pneumoniae causing invasive pneumococcal disease (IPD) is now ST 3. We undertook an analysis of population based surveillance for IPD to examine the incidence and epidemiology of ST 3 disease over the last 25 years.MethodsThe Toronto Invasive Bacterial Diseases Network has performed population-based surveillance for IPD in Toronto/Peel region (pop’n 4.5M) since 1995. All sterile site isolates of S. pneumoniae are reported to a central study laboratory, isolates are serotyped, and clinical and vaccination data are collected via patient and physician interview and chart review. Population data are obtained from Statistics Canada.ResultsFrom 1995-2020, 11032 episodes of IPD occurred; 10015 had STs available, and 10484 clinical data. Overall, ST 3 comprised 9.2% of cases (N=931). Compared to other patients with IPD, those with ST 3 IPD were older (median age 65 vs. 58.5, P< .001), more likely to have underlying lung (22.7% v 16.0%, P< .0001) and cardiac (21.7 v 18.4, P=.02) disease and less likely to be immunocompromised (IC) (23.1% v 29.0% P< .0001). ST3 episodes were more likely to be pneumonia (81% v 65%), less likely to be bacteremia without focus (7.6% v 18.9%), and more likely to require ICU admission (42.3% v 25.1%) and to die (27.1% v 16.6%). In multivariable analysis, patients with ST 3 disease remained more likely to die (OR 1.65; 95%CI1.3-2.0). Over time, the proportion of patients with ST 3 IPD who were nursing home (NH) residents (18/171 in 1995-2000 vs. 4/215 in 2016-2020, P=.0002), and who were IC (46/169 in 1995-2000 vs 39/204 in 2016-2020, P=.007) decreased significantly; in IPD due to other STs, the proportion who were NH residents declined, but the proportion IC increased significantly. The case fatality rate (CFR) declined significantly in IPD due to ST3 but not other STs (Figure 1). Changes in incidence are shown in Figure 2.Figure 2: Incidence of serotype 3 IPD over time, Toronto/Peel, 1995-2020 The incidence of ST3 IPD in children and adults under 65 did not change significantly from 1995/96 to 2019/20. In older adults, the annual incidence of disease declined from 4.98 per 100,000 per year in 1995-2000 to 3.53 per 100,000 per year in 2001-2010 (IRR 0.71, 95%CI 0.56-0.90), then to 2.23 per 100,000 per year in 2011-2020 (IRR compared to 2001-2010 0.63, 95%CI 0.50-0.79)FIgure 2: Case fatality rate of IPD due to serotype 3 and other serotypes over time, 1995-2020, Toronto-Peel The case fatality rate of IPD due to ST3 declined from 37.6% (56/149) in 1995-2000 to 50/235 (21.3%) in 2015-2020 (P<.0001). The CFR in other serotypes did not change.ConclusionThe epidemiology of IPD due to ST3 has changed significantly over time and the CFR has declined. The incidence of ST3 disease in children and younger adults has not changed significantly, although the power to detect change is low in children. In older adults the incidence of ST3 disease declined significantly after PPV23 introduction in 1995/6 and again after PCV13 introduction for children.Disclosures All Authors: No reported disclosures

Using genomics to examine the persistence of Streptococcus pneumoniae serotype 19A in Ireland and the emergence of a sub-clade associated with vaccine failures

BackgroundStreptococcus pneumoniae serotype 19A remains a significant cause of invasive pneumococcal disease (IPD) in Ireland despite the successful introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 which reduced the overall incidence of IPD in children. MethodsInvasive Streptococcus pneumoniae serotype 19A isolates from the Irish reference laboratory between 2007–08 and 2017–18 were analysed using whole genome sequencing (WGS) to investigate the persistence of this vaccine-preventable serotype. We compared the entire national 19A collection to other international collections using a standardised nomenclature of Global Pneumococcal Sequencing Clusters (GPSC). ResultsExpansion of GPSCs and clonal complexes (CCs) may have been associated with vaccine introduction and antimicrobial prescribing policies. A sub-clade of GPSC1-CC320 (n = 25) unique to Ireland, included five of the ten vaccine failures/breakthrough cases identified (p = 0.0086). This sub-clade was not observed in a global GPSC1-CC320 collection. All isolates within the sub-clade (n = 25) contained a galE gene variant rarely observed in a global pneumococcal collection (n = 37/13454, p < 0.001) nor within GPSC1-CC320 (n = 19/227) (p < 0.001). The sub-clade was estimated to have emerged at the start of the PCV-vaccine era (ancestral origin 2000, range 1995–2004) and expanded in Ireland, with most isolated after PCV13 introduction (n = 24/25). ConclusionsThe identification of a sub-clade/variant of serotype 19A highlights the benefit of using WGS to analyse genotypes associated with persistence of a preventable serotype of S. pneumoniae. Particularly as this sub-clade identified was more likely to be associated with IPD in vaccinated children than other 19A genotypes. It is possible that changes to the galE gene, which is involved in capsule production but outside of the capsular polysaccharide biosynthesis locus, may affect bacterial persistence within the population. Discrete changes associated with vaccine-serotype persistence should be further investigated and may inform vaccine strategies.

Impact of pneumococcal conjugate vaccine on invasive pneumococcal disease in children under 5 years of age in the Czech Republic.

IntroductionThe aim of this study is to analyse the impact of vaccination of infants with pneumococcal conjugate vaccine (PCV) on the incidence of invasive pneumococcal disease (IPD) in children under 5 years of age in the Czech Republic.Material and methodsThe present study includes all IPD cases reported in children aged 0–4 years within the surveillance program in 2007–2017. The impact of PCV is analysed for five categories of IPD: cases caused by all serotypes, cases caused by PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), cases caused by three additional PCV10 serotypes (1, 5, and 7F), cases caused by three additional PCV13 serotypes (3, 6A, and 19A), and cases caused by non-PCV serotypes. To assess the impact of PCV, the study period was divided into the pre-vaccination period 2007–2008 and post-vaccination period 2009–2017, which was divided into three three-year parts: 2009–2011, 2012–2014, and 2015–2017. Analysis of differences between periods was based on the Poisson regression model where the population numbers were handled as an offset.ResultsThe annual incidence of IPD in children under 5 years of age caused by all serotypes has had a downward trend since 2007: it dropped from 8.52/100 000 in 2007 to 2.67/100 000 in 2017, with slight increases in 2010 and 2013. All three post-vaccination periods show significantly lower (p<0.001) incidences in comparison to the pre-vaccination period, but they do not statistically significantly differ from each other.ConclusionsIPD surveillance data in the Czech Republic show that after the introduction of PCV vaccination of infants, there has been a significant decrease in the IPD incidence of children under 5 years of age. Continued IPD surveillance is essential to monitor for possible post-vaccination serotype replacement.

Impact of Switch Options on the Economics of Pneumococcal Conjugate Vaccine (PCV) Introduction in Indonesia.

As one of Gavi, the Vaccine Alliance (previously the Global Alliance for Vaccines and Immunization), graduating countries, Indonesia is still eligible to access Gavi price for PCV13, PCV10 A and B. This study aims to estimate the economic impact of switch from the existing product/presentation of PCV (single-dose of PCV13) to the new product/presentation of PCV (multi-dose of PCV13, PCV10 A and B) since PCV is one of the most expensive vaccines in the Expanded Program on Immunization (EPI) schedule. Assuming that Gavi-Advance Market Commitment (AMC) price for all PCVs can be accessed in 2021, the use of multi-dose PCV13, PCV10 A and PCV10 B with Gavi-AMC price in 2021–2024 were considered as respective scenarios. The result showed that the scenario assuming the use of single-dose of PCV13 with contract price in 2019–2020 that would be switched into multi-dose of PCV10 B with Gavi-AMC price in 2021–2024 resulted in the highest potential saving, compared with other scenarios. Our analysis suggests an economic advantage to switch from single-dose into a multi-dose presentation. Vaccination coverage, vaccine price, vaccine wastage and additional Gavi-AMC vaccine costs were considered to be the most influential parameter affecting the savings in all scenarios. Applying the effectiveness of PCV13 and PCV10 A on reducing the risk for invasive pneumococcal disease (IPD), potential averted incidence of IPD in children under one year of age during 2019–2024 would be 246,164 and 105,587 in both scenarios. Despite the result confirmed that PCV13 may provide an additional benefit, a more comprehensive economic evaluation study is required to investigate further the comparison of cost-effectiveness values among all PCVs in Indonesia.

Serotype and clonal distribution dynamics of invasive pneumococcal strains after PCV13 introduction (2011-2016): Surveillance data from 23 sites in Catalonia, Spain.

BackgroundThe objective of this study is to describe incidence and shifts of serotype and clonal distribution of invasive Streptococcus pneumoniae strains in four different age groups (<5 years, 5–17 years, 18–64 years and >65 years) during a period of intermediate PCV13 vaccination coverage (2011–2016) in Catalonia, Spain.MethodsWe included all pneumococcal strains systematically sent to the Catalan support laboratory for molecular surveillance of invasive pneumococcal disease (IPD) located at Hospital Sant Joan de Deu, Barcelona. Two study periods were considered: 2011–13, early PCV13 vaccination period (EVP) and 2014–2016, late vaccination period (LVP).ResultsA total of 2142 strains were included in the study. Five years after intermediate introduction of PCV13 in our population, a significant decrease of overall incidence of IPD in children <5 years was observed (incidence rate ratio 0.5, 95% confidence interval 0.4–0.8). However, in seniors older than 65 years, a significant increase of overall incidence of IPD was observed (IRR 1.4, 95% CI 1.1–1.7). The contribution of PCV13 vaccine serotypes to IPD declined significantly in all age groups: from 59% to 38.1% in <5 years; 82.7% to 59% in 5–17 years, 47.8% to 34.1% in 18–64 years and 48.2% to 37% in >65 years. Results found when comparing both periods were consistent with IRRs observed year by year. In children <5 years, the three major serotypes detected were 1, 24F and 19A in EVP vs 24F, 14 and 10A in LVP. Among patients 5–17 years the first three serotypes were 1, 12F and 14 both in EVP and LVP. Among adults 18–64, the three major serotypes detected were 1, 12F and 8 vs 8, 12F and 3, respectively. Finally, in patients >65 years the most frequently isolated serotypes were 3, 19A and 7F vs 3, 14 and 12F, respectively. Regarding clonal complexes (CCs) expressing mainly PCV13 serotypes, significant decreases of the proportions of CC306, CC191 and CC320 were observed, while CC156 showed a significant increase. As for CCs expressing mostly non-PCV13 serotypes, significant increases in ST989, CC53 and CC404 were showed.ConclusionsDespite low vaccine coverage in our setting a significant decrease of incidence of IPD was observed in children younger than 5 years. The modest indirect protection against vaccine serotypes causing IPD in elderly indicate the need for the inclusion of more serotypes in future high-valent PCV and vaccinating old adults should be considered.

Twelve years of pneumococcal conjugate vaccination in the Netherlands: Impact on incidence and clinical outcomes of invasive pneumococcal disease

IntroductionIn 2006, the Netherlands introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in their national immunisation programme. In 2011, PCV7 was replaced by the 10-valent vaccine (PCV10). We report on the impact of PCV on invasive pneumococcal disease (IPD) incidence, clinical syndromes and patient outcomes. MethodsPneumococcal isolates of hospitalised IPD patients between June 2004 and May 2018 were obtained from nine sentinel laboratories, covering 25% of the Dutch population. All isolates were serotyped. IPD incidence and clinical outcome were determined before and after introduction of PCV7 and after the switch to PCV10, stratified by age and serotype. ResultsCompared to before PCV7 introduction, significant declines in IPD incidence were observed in 2016–2018 in children <5 years (69%), 18–49 year olds (31%) and ≥65 year olds (19%). Compared to before PCV10 introduction, the IPD incidence in 2016–2018 declined in children <5 years (RR:0.68, 95%CI:0.42–1.11), 5–17 year olds (RR:0.58, 95%CI:0.29–1.14) and 18–49 year olds (RR:0.72, 95%CI:0.57–0.90), but not in 50–64 year olds (RR:0.94, 95%CI:0.81–1.10) and ≥65 year olds (RR:1.04, 95%CI:0.0.93–1.15). While the case fatality rate (CFR) decreased from 16.2% pre-PCV to 13.4% post-PCV10 (RR:0.83, 95%CI:0.70–0.99), the switch to PCV10 had no further impact on CFR (RR:1.14, 95%CI:0.96–1.36). ConclusionTwelve years of PCV in the Netherlands has resulted in a sustained reduction of IPD incidence in children and younger adults. The switch from PCV7 to PCV10 did not have additional impact on the IPD incidence in older adults and CFR due to emerging non-vaccine serotypes.

Persistent Circulation of Vaccine Serotypes and Serotype Replacement After 5 Years of Infant Immunization With 13-Valent Pneumococcal Conjugate Vaccine in the United Kingdom.

Following programmatic introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), there is residual carriage and disease due to PCV13-covered serotypes. PCV13-immunized children aged 13-48 months, N = 988, were enrolled between February 2014 and August 2015 ("late PCV13"), and had nasopharyngeal pneumococcal carriage compared with 7-valent pneumococcal conjugate vaccine (PCV7) immunized children, N = 567, enrolled between November 2010 and September 2011 ("early PCV13"). Nasopharyngeal pneumococci were molecular-serotyped by microarray. Invasive pneumococcal disease (IPD) cases were identified through enhanced national surveillance. Compared with PCV7-immunized children, carriage among PCV13-immunized children was significantly lower for serotypes 19A (odds ratio [OR], 0.08 [95% confidence interval {CI}, .02-.25]), 6C (OR, 0.11 [95% CI, .03-.32]), and 7F (8 vs 0 cases). IPD incidence in children <5 years was significantly lower for serotypes 1 (incidence rate ratio [IRR], 0.03 [95% CI, 0-.19]) and 7F (IRR, 0.13 [95% CI, .05-.36]) but not 19A (IRR, 0.6 [95% CI, .3-1.12]) or serotype 3 (IRR, 2.3 [95% CI, .86-6.15]) in the late PCV13 period than in the early PCV13 period. The most significant rises in IPD incidence were for serotypes 8, 12F, and 24F. PCV13 has reduced serotype 19A carriage among vaccinated children. We found no impact of PCV13 on serotype 3 carriage or disease, and emergence of non-PCV13-serotype disease.

Invasive pneumococcal disease in hospitalised children from Lima, Peru before and after introduction of the 7-valent conjugated vaccine.

The objective of this study was to determine the serotype distribution and antibiotic resistance of invasive pneumococcal disease (IPD) strains in children from Lima, Peru, before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), which was introduced in the national immunisation program on 2009. We conducted a prospective, multicentre, passive surveillance IPD study during 2006-2008 and 2009-2011, before and right after the introduction of PCV7 in Peru. The study was performed in 11 hospitals and five private laboratories in Lima, Peru, in patients &lt;18 years old, with sterile site cultures yielding Streptococcus pneumoniae. In total 159 S. pneumoniae isolates were recovered. There was a decrease in the incidence of IPD in children &lt;2 years old after the introduction of PCV7 (18.4/100 000 vs. 5.1/100 000, P = 0.004). Meningitis cases decreased significantly in the second period (P = 0.036) as well as the overall case fatality rate (P = 0.025), including a decreased case fatality rate of pneumonia (16.3% to 0%, P = 0.04). PCV7 serotypes showed a downward trend. Vaccine-preventable serotypes caused 78.9% of IPD cases, mainly 14, 6B, 5, 19F and 23F. A non-significant increase in erythromycin resistance was reported. Our findings suggest that the introduction of PCV7 led to a significant decrease of IPD in children under 2 years old and in the overall case fatality rate.

Changes in the Nature and Severity of Invasive Pneumococcal Disease in Children Before and After the Seven-valent and Thirteen-valent Pneumococcal Conjugate Vaccine Programs in Calgary, Canada.

Since the introduction of childhood pneumococcal conjugate vaccines, invasive pneumococcal disease (IPD) incidence has decreased in children and the predominant serotypes causing disease have changed. This study describes changes in the clinical features of IPD in children (<18 years) before and after the conjugate vaccine introduction. The Calgary Area Streptococcus pneumoniae Epidemiology Research study collects information on all IPD cases in Calgary, Alberta, Canada. Descriptive and regression analyses were used to compare IPD in the pre-vaccine (January 2000 to August 2002), post-7-valent protein-polysaccharide conjugate vaccine (September 2002 to June 2010) and post-13-valent protein-polysaccharide conjugate vaccine (PCV13) (July 2010 to December 2015) periods; intensive care unit and inpatient admissions were outcome measures. The incidence of IPD in children (<18 years) decreased from an average of 17 cases/100,000/yr in 2000-2001 to 4 cases/100,000/yr in 2015. The median age of children presenting with IPD shifted from 2.0 years (interquartile range: 2.5) in the pre-vaccine period to 3.9 years (interquartile range: 6.2) in the post-PCV13 period. The proportion of children with a comorbidity that is an indication for pneumococcal vaccination did not change. Invasive disease with focus (meningitis, pneumonia, empyema, peritonitis) compared with invasive disease with bacteremia only increased from 44.6% in pre-vaccine to 64.0% and 61.4% in the post-7-valent protein-polysaccharide conjugate vaccine and post-PCV13 periods, respectively (P = 0.017). Having IPD in the post-PCV13 period compared with the pre-vaccine period was associated with an increased odds of hospitalization [Odds ratio (OR): 2.9; 95% Confidence Interval (CI): 1.4-6.2]. Clinical features of IPD have changed since pneumococcal conjugate vaccines were introduced, with a shift toward more focal infections requiring hospitalization. Although overall IPD cases have declined, disease that does occur appears to be more severe.

Invasive Pneumococcal Disease in Children With Sickle Cell Anemia

Research Article| November 01 2017 Invasive Pneumococcal Disease in Children With Sickle Cell Anemia AAP Grand Rounds (2017) 38 (5): 57. https://doi.org/10.1542/gr.38-5-57 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Invasive Pneumococcal Disease in Children With Sickle Cell Anemia. AAP Grand Rounds November 2017; 38 (5): 57. https://doi.org/10.1542/gr.38-5-57 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search toolbar search search input Search input auto suggest filter your search All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: invasive pneumococcal disease, sickle cell anemia Source: Martin OO, Moquist KL, Hennessy JM, et al. Invasive pneumococcal disease in children with sickle cell disease in the pneumococcal conjugate vaccine era. Pediatr Blood Cancer. 2017 4 July [published online ahead of print]; doi: https://doi.org/10.1002/pbc.26713Google Scholar Investigators from Michigan State University, Flint, MI, and Children’s Hospitals and Clinics of Minnesota (CHCM), Minneapolis, MN, conducted a retrospective study to assess trends in invasive pneumococcal disease (IPD) among children with sickle cell disease (SCD) in the era of universal pneumococcal immunization for young children. For the study, they reviewed medical records and microbiological databases at CHCM to identify cases of IPD in children with SCD between 2000 and 2014. IPD was defined as the presence of pneumococcus in a blood or cerebrospinal fluid culture. Data collected on study patients included age, pneumococcal immunization status, pneumococcus serotype, and penicillin susceptibility. On the basis of the number of cases identified and the population of patients with SCD followed up at CHCM, the investigators estimated the incidence of IPD per 100,000 person-years among children with SCD. In addition to describing clinical characteristics of cases of IPD over the entire study period, observations were divided into 2 periods on the basis of the type of pneumococcal conjugate vaccine available. Thus, in period 1, 2000–2010, the pneumococcal conjugate vaccine (PCV) against 7 serotypes (PCV7) was available, and in period 2, 2010–2014, the 13-valent PCV (PCV13) was used. During the overall study period, 11 cases of IPD in patients with SCD were identified, including 7 in period 1 and 4 in period 2. The mean age of study patients was 5 years, with a range of 6 months to 11 years. Two children with IPD died; information on pneumococcus serotype was available for the remaining 9 patients. PCV data were available for 8 of these 9 children, and data for all 8 were classified as being up to date. During period 1, all cases of IPD were caused by serotypes of pneumococcus not included in PCV7; during period 2, 1 patient (an 8-year-old boy) had IPD caused by serotype 7F (included in PCV13 but not PCV7). All isolates tested (n = 9) were sensitive to penicillin. The overall incidence of IPD in children with SCD in this study was estimated at 417 per 100,000 patient-years, with an incidence of 390 per 100,000 patient-years in period 1 and 450 per 100,000 patient-years in period 2. The authors conclude that even in the era of universal pneumococcal immunization, children with SCD remain at risk for IPD. Dr Winer has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. When considering a prophylactic intervention, one must take into account both the burden of the potential disease and the effect of the proposed intervention. In this brief report, the authors argue for both penicillin and PCV prophylaxis in patients with SCD <5 years of age, which is the... You do not currently have access to this content.

Incidence of pediatric invasive pneumococcal disease in the Island of Majorca (2008-2010), an area with non-universal vaccination, and estimations of serotype &amp; children population coverage by available conjugate vaccines

BackgroundThe World Health Organization reported in 2007 that inclusion of PCV7 in national immunization programs should be seen as a priority, also encouraging countries to conduct appropriate surveillances for monitoring the impact of vaccination. These analyses should be conducted in specific geographical areas and should be aimed to evolution of invasive pneumococcal disease (IPD), by age groups, clinical presentation, and vaccine serotypes (and non-vaccine serotypes to detect possible replacement). This study aimed to monitor the evolution of IPD incidence in children <15 years requiring hospitalization in the Island of Majorca.MethodsA prospective clinical surveillance of all culture and/or PCR-confirmed IPD in children <15 years was performed in all hospitals in the Island of Majorca (approximately 900,000 inhabitants) from January 2008 to December 2010. Incidence rate (IR) was calculated as cases/100000 inhabitants using children population data.Results66 IPDs were identified: 39 (59.1%) parapneumonic pneumococcal empyema (PPE), 16 (24.2%) bacteremic pneumonia (BP), 7 (10.6%) primary bacteremia, 3 (4.5%) meningitis, and 1 (1.5%) osteomyelitis. IRs in the three-year study period were: 64.22 for children 12- < 24 months, 37.21 for those 24-59 months, 22.62 for those <12 months, and 3.98 for children >59 months. By study year, IRs were 21.25 in 2008, 19.89 in 2009 and 9.80 in 2010. The reduction found in 2010 was significant and due to significant reductions in IRs of IPDs caused by serotypes included in PCV10 and PCV13. Overall, estimated serotype coverage by conjugate vaccines was 12.1% for PCV7, 37.9% for PCV10 and 65.2% for PCV13. Of the 66 hospitalized children with IPD, 20 had received at least one dose of PCV7 (13 cases with identified serotype). None of these 13 cases was caused by PCV7 serotypes, all were caused by PCV13 serotypes and only 53.8% by PCV10 serotypes.ConclusionsThe results of the present study evidence the importance of expanding the number of serotypes covered by PCV, and the added value of PCV13 with respect to PCV10 and PCV7, even in an area of low prevalence of 19A as the Island of Majorca.

Serotype distribution of invasive Streptococcus pneumoniae in Canada after the introduction of the 13-valent pneumococcal conjugate vaccine, 2010–2012

The introduction of the 7-valent pneumococcal vaccine (PCV7) in Canada was very effective in reducing invasive pneumococcal disease (IPD) in children; however, increases of non-PCV7 serotypes have subsequently offset some of these reductions. A 13-valent pneumococcal vaccine (PCV13) targeting additional serotypes was implemented between 2010 and 2011, and in 2012 changes in the incidence of disease and the distribution of IPD serotypes began to emerge. The incidence of IPD in children <5 years of age declined from 18.0 to 14.2 cases per 100 000 population between 2010 and 2012; however, the incidence in ages ≥5 years remained relatively unchanged over the 3-year period, at about 9.7 cases per 100 000 population. From 2010 to 2012, PCV13 serotypes declined significantly from 66% (224/339) to 41% (101/244, p < 0.001) in children <5 years of age, and from 54% (1262/2360) to 43% (1006/2353, p < 0.001) in children ≥5 years of age. Serotypes 19A, 7F, 3, and 22F were the most common serotypes in 2012, with 19A decreasing from 19% (521/2727) to 14% (364/2620, p < 0.001), 7F decreasing from 14% (389/2727) to 12% (323/2620, p = 0.04), and 22F increasing from 7% (185/2727) to 11% (279/2620, p < 0.001) since 2010. Serotype 3 increased from 7% (23/339) to 10% (24/244) in <5-year-olds (p = 0.22) over the 3-year period. The highest rates of antimicrobial resistance were observed with clarithromycin (23%), penicillin using meningitis breakpoints (12%), clindamycin (8%), and trimethoprim-sulfamethoxazole (6%). Shifts in the distribution of IPD serotypes and reductions in the incidence of disease suggest that current immunization programs in Canada are effective in reducing the burden of IPD in children. While we acknowledge the limited data on the effectiveness of the PCV13 vaccine, to our knowledge, this study represents one of the first descriptions of the potential impact of the PCV13 vaccine in the Canadian population. Continued surveillance will be important to recognize replacement serotypes, to determine the extent of herd immunity effects in nonpaediatric populations, and to assess the overall effectiveness of PCV13 in reducing IPD in Canada.

Changing epidemiology of invasive pneumococcal disease following increased coverage with the heptavalent conjugate vaccine in Navarre, Spain

The present study evaluated changes in the incidence of invasive pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre, Spain, after the introduction and increased coverage of the heptavalent pneumococcal conjugate vaccine (PCV7). All cases with isolation of pneumococcus from normally sterile bodily fluids were included. The incidence of IPD in children and adults was compared for the periods 2001–2002 and 2006–2007. By the end of 2002, only 11% of children aged <5 years had received any dose of PCV7, whereas, beginning in 2007, the proportion exceeded 50%. Among the cases of IPD aged <5 years, the percentage of those vaccinated increased from 7% during 2001–2002 to 53% during 2006–2007 (p <0.001). The incidence of IPD from PCV7-serotypes decreased by 85% in children <5 years (p <0.001), by 45% in the population aged 5–64 years (p 0.10) and by 68% in those ≥65 years (p 0.004). By contrast, the incidence of IPD from non-PCV7 serotypes increased by 40% overall (p 0.006). The incidence of IPD from all serotypes did not change significantly in children <5 years (from 83 to 72 per 100 000) or in the total population (from 15.8 to 16.3 per 100 000). The percentage of cases as a result of serotypes 7 and 19A increased significantly in both children and adults. No significant changes were seen in the clinical forms of IPD. The pattern of serotypes causing IPD has changed, in both children and adults, following the increased coverage of PCV7, although the incidence has been reduced only slightly.

Aspectos epidemiológicos de la enfermedad neumocócica invasiva antes y después del uso de la vacuna neumocócica conjugada en Gran Canaria

The introduction of pneumococcal conjugate vaccine (PCV-7) has modified the epidemiology of invasive pneumococcal disease (IPD). Our aim was to investigate the epidemiological features of IPD before and after implementing the use of PCV-7. All invasive Streptococcus pneumoniae strains isolated in our hospital from 2000 to 2006 were included. Serotypes were identified and antibiograms were performed in all cases. Data obtained before (2000-2001) and after (2004-2006) authorization of PCV-7 use in Spain were compared. There were 241 cases of IPD. None of the patients with IPD aged 2 years or younger had received PCV-7. PCV-7 coverage in children aged 5 or younger was about 48%. There was a non-significant increase in the incidence of IPD in children (from 53.8 to 57.8 cases/100 000 population), with no change in adults. When IPD incidence was adjusted by the number of blood samples collected, there was a non-significant decrease in both children and adults. Since PCV-7 came on the market, there has been a decrease in vaccine serotypes and an increase in non-vaccine serotypes. The emergent serotypes since that time include 3, 6A, 15, and 19A. Penicillin resistance decreased significantly (p<0.001) from the pre-vaccine period (87.3%) to 2003 (13.8%), and later rose from 2003 through 2006 (41.7%). Erythromycin resistance showed no changes during the study. The incidence of IPD in children aged 2 years and younger in Gran Canaria has not decreased despite the introduction of PCV-7. However, there has been a reduction in the number of cases related to vaccine serotypes and a significant decrease in penicillin resistance. In contrast, non-vaccine serotype IPD cases have increased. Universal vaccination and the use of new polyvalent vaccines may enhance these effects.

Molecular detection methods and serotyping performed directly on clinical samples improve diagnostic sensitivity and reveal increased incidence of invasive disease by Streptococcus pneumoniae in Italian children

The aims of this study were to evaluate the incidence of invasive pneumococcal disease (IPD) in Italian children and perform serotyping by PCR-based assays directly on clinical samples. A 1-year paediatric (0–14 years) population-based surveillance study was designed to evaluate the incidence of IPD in the province of Florence, Italy, by cultural and molecular methods. Among 92 children (80 with pneumonia, 8 with meningitis/sepsis, 4 with arthritis), 4 cases of IPD were diagnosed both by culture and real-time PCR and 18 cases exclusively by molecular methods. The sensitivity of molecular methods was significantly higher than that of cultural methods (Cohen’s κ 0.41; McNemar P=0.000008). The incidence of IPD in children below 2 years of age was 11.5/100 000 and 51.8/100 000 by cultural and molecular methods, respectively. Pneumococcal serotyping by multiplex sequential PCR was obtained in 19/22 samples. Real-time PCR and multiplex sequential PCR can be used directly on biological samples, improving the ability to diagnose IPD. The incidence of IPD appears 5–10 times higher by PCR than by cultural methods.

Impact of Capsular Switch on Invasive Pneumococcal Disease Incidence in a Vaccinated Population

BackgroundDespite the dramatic decline in the incidence of invasive pneumococcal disease (IPD) observed since the introduction of conjugate vaccination, it is feared that several factors may undermine the future effectiveness of the vaccines. In particular, pathogenic pneumococci may switch their capsular types and evade vaccine-conferred immunity.Methodology/Principal FindingsHere, we first review the literature and summarize the available epidemiological data on capsular switch for S. pneumoniae. We estimate the weekly probability that a persistently carried strain may switch its capsule from four studies, totalling 516 children and 6 years of follow-up, at 1.5×10−3/week [4.6×10−5–4.8×10−3/week]. There is not enough power to assess an increase in this frequency in vaccinated individuals. Then, we use a mathematical model of pneumococcal transmission to quantify the impact of capsular switch on the incidence of IPD in a vaccinated population. In this model, we investigate a wide range of values for the frequency of vaccine-selected capsular switch. Predictions show that, with vaccine-independent switching only, IPD incidence in children should be down by 48% 5 years after the introduction of the vaccine with high coverage. Introducing vaccine-selected capsular switch at a frequency up to 0.01/week shows little effect on this decrease; yearly, at most 3 excess cases of IPD per 106 children might occur due to switched pneumococcal strains.ConclusionsBased on all available data and model predictions, the existence of capsular switch by itself should not impact significantly the efficacy of pneumococcal conjugate vaccination on IPD incidence. This optimistic result should be tempered by the fact that the selective pressure induced by the vaccine is currently increasing along with vaccine coverage worldwide; continued surveillance of pneumococcal populations remains of the utmost importance, in particular during clinical trials of the new conjugate vaccines.

Editorial Commentary:Replacement Pneumococcal Disease in Perspective

Bender et al. [1] describe 33 patients with pneumococcal necrotizing pneumonia who were admitted to Primary Children's Medical Center (Salt Lake City, Utah) from January 2001 through March 2006. One-third of all hospitalized cases of pneumococcal pneumonia in the period after the introduction of 7-valent pneumococcal conjugate vaccine (PCV-7) were complicated by radiographic evidence of necrosis (evidence of necrotic lung, lung abscess, or pneumatocele), compared with 13% of cases before 2001. This group has also reported an increase in pediatric parapneumonic empyema beginning the same year [2]. The number of cases of parapneumonic empyema among children also increased in Spain and France during the period following the introduction of PCV-7. At Primary Children's Medical Center, 88% of cases of necrotizing pneumonia and 86% of cases of parapneumonic empyema identified from January 2001 through March 2006 were due to nonvaccine serotypes. These reports represent the latest part of the changing ecology of pneumococcal disease in association with the universal vaccination of infants with PCV-7. PCV-7 was introduced in 2000 for universal vaccination of infants 85% of cases of invasive pneumococcal disease (IPD) in children in North America. Following the introduction of PCV-7, a rapid decrease in the incidence of IPD occurred as a result of the direct effect of vaccination. A decrease in the incidence of IPD in children <5

Epidemiology of Invasive Pneumococcal Disease in BC during the Introduction of Conjugated Pneumococcal Vaccine

Antimicrobial resistance in Streptococcus pneumoniae has increased in recent decades. We linked two surveillance programs to evaluate trends in incidence, serotype distribution, and antimicrobial resistance in invasive pneumococcal disease (IPD) since the heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in BC in 2003. IPD case reports for BC from 2002-2005 from the BC Centre for Disease Control were linked to serotype and antimicrobial susceptibility results from the National Centre for Streptococcus (NCS). There was a significant decrease in IPD incidence in children <5 from 54/100,000 in 2002 to 16/100,000 population in 2005 (70% decrease, p < 0.001). The most dramatic decline was in children aged 1 year, where the rate fell from 135/100,000 to 15/100,000 (89% decrease, p for trend <0.001). Overall, 728/1288 (56.5%) reported cases of IPD were referred to NCS. For all matched cases, the proportion of isolates of PCV7 preventable serotypes decreased from 68.9% to 43.8% (p for trend <0.001) between 2002 and 2005. In children <2 years, this proportion decreased from 83.0% (39/47 cases) to 16.7% (1/6 cases) (p = 0.006). The prevalence of non-susceptible isolates was highest for trimethoprim-sulfamethoxazole (15.3%, 111/725 tested), penicillin (9.1%, 66/728), and erythromycin (9.1%, 66/727). 10.3% (75/728) were non-susceptible to > or =2 classes of antimicrobials. Children <15 years of age had the highest proportion of non-susceptible isolates. The incidence of IPD in children has decreased significantly since the introduction of PCV7. Comprehensive serotype and antimicrobial susceptibility can aid in evaluating the impact of immunization programs.

Invasive pneumococcal disease in Portugal prior to and after the introduction of pneumococcal heptavalent conjugate vaccine

The rates of invasive pneumococcal disease (IPD), serotype distribution and antimicrobial susceptibility prior to and after the introduction of the heptavalent pneumococcal conjugate vaccine in Portuguese children were evaluated. The changes in incidence of IPD in children under 1 year old between the two periods of the study was not significant (P=0.53), despite the 21% decline. In children under 18 years old there was a 27.7% decrease in vaccine serotypes. All nonvaccine serotypes increased 71.4%. The decrease in vaccine serotypes was more impressive during the first year of life (-54.8%) than for children between 1 and 5 years of age (-19.1%). Among children under 1 year old, penicillin nonsusceptible isolates declined between the two periods of the study (47.2% vs. 25.0%) (P=0.03), as did those of cefotaxime and ceftriaxone nonsusceptible isolates. No changes were observed for isolates nonsusceptible to tetracycline and macrolides. The serotypes of these nonsusceptible isolates differed after the introduction of vaccine (P=0.01). Multiresistance increased 57.1% after the introduction of vaccine. Multiresistant isolates with vaccine serotype declined 42.9% (P<0.001), and nonvaccine serotypes appeared during the vaccination period (P<0.001). These findings suggest a replacement of vaccine serotypes by nonvaccine serotypes, mainly among nonsusceptible isolates.