Serotypes,antimicrobial susceptibility,and molecular epidemiology of invasive and non-invasive Streptococcus pneumoniae isolates in paediatric patients after the introduction of 13-valent conjugate vaccine in a nationwide surveillance study conducted in Japan in 2012–2014

Pneumococcal infection in children is a major public health problem worldwide, including in Japan. The pneumococcal conjugate vaccine 7 (PCV7) was licensed for use in Japan in 2010 followed by PCV13 in 2013. This report includes the results of a nationwide surveillance of invasive pneumococcal disease (IPD) and non-IPD in paediatric patients from January 2012 to December 2014. We collected 343 isolates from 337 IPD patients and 286 isolates from 278 non-IPD patients. Of the IPD isolates, the most identified serotypes included 19A, 24F, and 15A. The prevalence of non-PCV13 serotype isolates increased significantly from 2012 to 2014 (51.6–71.4%, p = 0.004). Serotypes 19A, 15A and 35B were highly non-susceptible to penicillin, and the rates of non-susceptible isolates from IPD patients to penicillin and cefotaxime significantly declined during the study period (p = 0.029 and p = 0.013, respectively). The non-susceptible rate to meropenem increased, particularly for serotype 15A. The IPD isolates comprised clonal complex (CC) 3111 (93.8% was serotype 19A) followed by CC2572 (81.5% was serotype 24F) and CC63 (97.1% was serotype 15A). CC3111, CC63 and CC156 (33.3% was serotype 23A, 28.6% was serotype 6B, and 14.3% was serotype 19A) were highly non-susceptible to penicillin. Of the non-IPD isolates, the most identified serotypes included 19A, 15A, and 3. In conclusion, the introduction of PCV7 and PCV13 resulted in increasing non-PCV13 serotypes and clones, including antimicrobial resistant serotypes 15A and CC63 (Sweden^15A-25 clone).     

Early Streptococcus pneumoniae serotype changes in Utah adults after the introduction of PCV13 in children

IntroductionPneumococcal conjugate vaccines (PCV) have indirect effects due to decreased Streptococcus pneumoniae colonization in vaccine recipients. We sought to determine whether the introduction of PCV13 in children led to changes in the epidemiology and clinical manifestations of invasive pneumococcal disease (IPD) in adults.MethodsWe described demographics, comorbidities, clinical manifestations, and serotypes of IPD in Utah adults before (November 2009−February 2010) and after (March 2010−March 2012) the introduction of PCV13 in children. We also compare serotypes causing IPD in Utah adults and children.ResultsAfter the introduction of PCV13 in the childhood vaccine program, the proportion of IPD due to PCV13 exclusive serotypes decreased significantly in Utah adults (64−40%, p = 0.009), primarily due to a decline in serotype 7F (36−15%, p = 0.008). There were non-significant increases in IPD due to Pneumococcal polysaccharide 23 (PPV23) unique serotypes and non-vaccine serotypes, most notably serotype 22F. Changes in the proportions of vaccine and non-vaccine serotypes were similar in adults and children. Meningitis was more commonly due to non-vaccine serotypes relative to non-meningitis cases (47% vs. 18%, p = 0.007). When stratified by sex, decreases in PCV13 serotype IPD were only noted in men (76−33%, p = 0.001).ConclusionsSerotype epidemiology of IPD in adults closely follows that of children in the PCV13 era. Continued surveillance is needed to confirm whether replacement serotypes will lead to increases in pneumococcal meningitis and whether there are sex differences in the indirect effects of PCV vaccination in children.     

Early impact of sequential introduction of 7-valent and 13-valent pneumococcal conjugate vaccine on IPD in Israeli children <5 years: An active prospective nationwide surveillance

BackgroundThe 7-valent pneumococcal conjugated vaccine (PCV7) was introduced to the Israeli national immunization plan (NIP) in July 2009 (administered at age 2, 4 and 12 months), with a fast reduction of invasive pneumococcal disease (IPD) caused by PCV7 serotypes. Starting in November 2010, PCV13 gradually replaced PCV7.AimTo report the impact of PCV7/PCV13 sequential introduction on IPD in Israeli children <5 years.MethodsAn ongoing nationwide, prospective, population-based, active surveillance. All IPD episodes (Streptococcus pneumoniae isolated from blood and/or cerebrospinal fluid) from July 2004 through June 2013 were included.ResultsOverall, 2670 IPD episodes were recorded. Incidence of IPD caused by PCV7 + 6A serotypes during the PCV13 period vs. pre-PCV period decreased by 95% (Incidence Rate Ratio [IRR] = 0.05; 95% CI = 0.03–0.09). This reduction was observed in a two-step manner: 90% in the PCV7-period and further 5% in the PCV13-period. The rates of IPD caused by the 5 additional PCV13-serotypes (1, 3, 5, 7F, 19A; 5VT) increased initially by 47%, but subsequently decreased by 79%, resulting in an overall 70% reduction during the entire study period (IRR = 0.30; 0.21–0.44). A two-fold increase in non-PCV13 serotypes IPD was observed (IRR = 2.43; 1.73–3.66). In total, a 63% reduction of all-serotype IPD episodes was observed in children <5 years (69% and 48% in children <2 and 2–4 years old, respectively).ConclusionsAfter initiation of PCV NIP, a rapid and substantial 2-step IPD reduction was observed in children <5 years. The serotype-specific rate reduction reflected the sequential introduction of PCV7/PCV13.     

Effectiveness of three pneumococcal conjugate vaccines to prevent invasive pneumococcal disease in Quebec,Canada

BackgroundIn Quebec, a pneumococcal conjugate vaccine (PCV) program was implemented in December 2004. The recommended schedule is 2 + 1 doses for low-risk infants. PCV-7 was first used (including catch-up for children <5 years of age), replaced by PCV10 in June 2009, and by PCV13 in January 2011 (no catch-up in both instances). From the beginning, >90% of children received the recommended number of doses.ObjectiveTo assess the effectiveness of the three PCVs sequentially used to prevent invasive infectious disease (IPD).MethodsIPD cases in children 2–59 months during the years 2005–2013 were eligible. Controls were randomly identified in the provincial health insurance registry. Parents were interviewed and immunization records reviewed. Vaccine effectiveness (VE) was computed using multivariate logistic regression models.ResultsOut of 889 IPD cases reported, full participation was obtained for 516 cases (58%) and for 1767 controls. Against vaccine-type IPD, VE (≥1 dose) was 90% (82–95%) for PCV7, 97% (84–99%) for PCV10 and 86% (62–95%) for PCV13. Against 19A IPD, VE was, respectively, 42% (−9% to 69%), 71% (24–89%), and 74% (11–92%). VE (≥2 doses) against PCV13-type IPD was 85% for PCV10 (66–94%), 85% for PCV13 (55–94%), and 89% (58–97%) for a mixed PCV10 + PCV13 schedule.ConclusionsAll three PCV vaccines showed high level of protection against IPD caused by serotypes included in their formulation and there was a high level of cross-protection against 19A for PCV10. No substantial difference was seen between PCV10, PCV13, or a mixed PCV10 + PCV13 schedule.     

Indirect (herd) protection,following pneumococcal conjugated vaccines introduction: A systematic review of the literature

BackgroundPneumococcal diseases are major causes of morbidity among adults, especially those over 50 years of age. While pneumococcal conjugated vaccines (PCV’s) impact on pneumococcal disease rates among children is well established, the extent of its impact on adult pneumococcal related illness remains unclear. The aim of this systematic literature review was to describe the impact of PCV introduction to childhood national immunization programs worldwide on PCV-naive adult population.MethodsA systematic literature search was performed using the PubMed database. The search was limited to articles written in English and published between January 2000 and February 2016. Studies evaluating pneumococcal disease rates in individuals over 5 years of age were included. Independent extraction of articles was performed by the two authors. Search terms included: Pneumococcal conjugated vaccine, herd, indirect, adults, and pneumonia.ResultsForty-nine articles meeting the selection criteria were identified, 39 regarding invasive pneumococcal disease (IPD, one on meningitis only), 8 regarding pneumonia, and 2 on both IPD and pneumonia. The majority of reports were from the US, UK and Canada. Considerable variability in the data sources, quality and completeness was observed. While most studies reported either statistically significant reduction or insignificant changes in IPD and pneumonia disease rates in adults following PCV nationwide implementation, few studies reported statistically significant increase in pneumococcal disease rates, these were mainly from countries with low PCV coverage rates and/or inadequate surveillance.ConclusionInvasive pneumococcal diseases and pneumonia rates among the adult population decreased in most countries following PCV introduction into the NIP. This indirect effect on older population seems to be dependent on PCV coverage rates and time from PCV nationwide implementation. Adults >65 years old seem to benefit the most from PCV introduction.     

Nationwide population-based surveillance of invasive pneumococcal disease in Japanese children: Effects of the seven-valent pneumococcal conjugate vaccine

BackgroundIn Japan, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2010. PCV13 has replaced PCV7 since November 2013.MethodsThe effectiveness of PCV7 in protecting against invasive pneumococcal disease (IPD) in children aged <5 years was evaluated in a nationwide active population-based surveillance of IPD in 2008–2013 in 10 prefectures in Japan.Results1181 cases were identified; 711 pneumococcal strains were analyzed for serotyping and antimicrobial resistance. Compared with the baseline IPD incidence (25.0 per 100,000), a 98% decline in IPD caused by PCV7 serotypes was found after the introduction of PCV7. This was partially offset by an increased incidence of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes, resulting in a 57% decline in overall IPD incidence. Absolute increases in the incidence rates of IPD caused by PCV13 minus PCV7 and non-PCV13 serotypes were 2.1 and 2.8 per 100,000 during the study period, respectively. The proportion of meropenem-nonsusceptible strains, especially with serotypes 19A and 15A, increased significantly after PCV7 introduction.ConclusionsOur data confirmed a 98% decline in IPD incidence caused by PCV7 serotypes in children aged <5 years and serotype replacement after PCV7 introduction. This shows the importance of continuing surveillance of serotypes responsible for IPD and their antimicrobial resistance in Japan.     

The rise and fall of pneumococcal serotypes carried in the PCV era

Streptococcus pneumoniae is a major cause of meningitis, sepsis and pneumonia worldwide. Vaccination using pneumococcal conjugate vaccines (PCV) has therefore been part of the UK’s childhood immunisation programme since 2006. Here we describe pneumococcal carriage rates in children under five years of age attending the paediatric department of a large UK hospital in response to vaccine implementation over seven winter seasons from 2006 to 2013. S. pneumoniae (n = 696) were isolated from nasopharyngeal swabs (n = 2267) collected during seven consecutive winters, October to March, 2006/7 to 2012/13. This includes the period immediately following the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in 2006 in addition to pre- and post-PCV13 introduction in 2010. We show a decrease in PCV13 vaccine serotypes (VT) in the three years following PCV13 vaccine implementation (2010/11 to 2012/13). Serotype 6A represented the only observed VT following PCV13 implementation with all others (including PCV7 serotypes) absent from carriage. Overall pneumococcal carriage, attributable to non-VT (NVT), was consistent across all sampling years with a mean of 31·1%. The ten most frequently isolated NVTs were 6C, 11A, 15B, 23B, 15A, 21, 22F, 35F, 23A and 15C. Fluctuations in the prevalence of each were however noted. Comparing prevalence at 2006/07 with 2012/13 only 15A was shown to have increased significantly (p value of 0·003) during the course of PCV implementation. These data support the increasing evidence that the primary effect of PCVs is due to population immunity by reducing or eliminating the carriage of invasive VT serotypes. With IPD being increasingly attributed to non-vaccine serotypes, surveillance of carriage data continues to act as an early warning system for vaccine design and public health policy that require continual data of both carried pneumococcal serotypes and IPD attributed serotype data.     

Impact of PCV7/PCV13 introduction on invasive pneumococcal disease (IPD) in young children: Comparison between meningitis and non-meningitis IPD

BackgroundThe worldwide introduction of pneumococcal conjugate vaccines (PCV) into National Immunization Programs resulted in rapid and substantial reduction of invasive pneumococcal disease (IPD) rates in children. However, the reduction of meningitis vs. non-meningitis IPD (nm-IPD) was not yet fully elucidated. We compared 7-valent and 13-valent PCV (PCV7 and PCV13) impact on pneumococcal-meningitis vs. nm-IPD in Israeli children <5 years.MethodsWe conducted an ongoing nationwide, prospective, population-based, active surveillance. PCV7 and PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All pneumococcal isolates (blood and/or CSF) from IPD episodes in children <5 years from July 2000 through June 2015 were included. Extrapolation for missing serotypes (34.7% of all isolates) was conducted.Results4163 IPD cases were identified; 3739 nm-IPD (89.8%) and 424 meningitis (10.2%). During the pre-PCV period (2000–2008), children <12 months constituted 52.1% and 33.7% of meningitis and nm-IPD, respectively (p < 0.001). The respective proportions of non-PCV13 serotypes (non-VT) were 18.2% vs. 10.1%, (p < 0.001).Comparing the last study year (2014–2015) to the mean of pre-PCV period, meningitis incidence in children <5 years decreased non-significantly by 27%, while nm-IPD decreased significantly by 69%. Dynamic rates of meningitis and nm-IPD caused by PCV13 serotypes were similar, with 93% and 95% overall reductions, respectively. However, non-VT increased in meningitis relatively to nm-IPD, mainly in children <24 months. Serotype 12F rose sharply and significantly since 2009–2010 through 2014–2015 (28.6% of all non-VT meningitis in children <24 m).ConclusionsThe overall impact of PCV7/PCV13 in children <5 years in Israel was less prominent in meningitis than in nm-IPD. This could be attributed to the younger age of children with meningitis and differences in causative serotypes between the two groups, as the decline of the incidence of meningitis and nm-IPD caused by vaccine-serotypes is similar. Continuous monitoring of meningitis and nm-IPD is warranted.     

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

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

Invasive pneumococcal disease among hospitalized children in Brazil before and after the introduction of a pneumococcal conjugate vaccine

BackgroundMost of the available data on invasive pneumococcal disease in Latin America are derived from laboratory-based surveillance systems. There is a lack of epidemiological data on the disease severity and mortality from hospitalized patients with pneumococcal infection.MethodsIn this hospital-based retrospective historical series of hospitalized children with laboratory-confirmed IPD, we evaluated changes in disease episodes, in-hospital fatality rates, and need for intensive care unit admission after the inclusion of PCV10 in the Brazilian vaccination schedule. Invasive pneumococcal strains isolated by culture were serotyped. Changes over time were assessed, and pre-vaccination (2005–2009) to post-vaccination (2011–2015) disease rates and serotypes were compared.Results260 patients with IPD and positive pneumococcal isolates were identified (198 during the pre-PCV10 period). When comparing both periods, hospitalizations were reduced from 20 cases to 5 cases per 10,000 pediatric admissions (p < 0.0001). Likewise, fatalities reduced from 6.6 to 2.0 cases per 10,000 pediatric admissions (p < 0.0001). Pneumonia was the most frequent clinical diagnosis (58%) – of which 49.6% had pleural effusion – followed by meningitis (22%) and bacteremia (15.9%). Overall 30% of cases were sent to ICU, with no percentual changes after PCV10. Additional PCV13 serotypes increased from 7% before vaccine introduction to 21% after PCV10 use. Similarly, serotypes not included in PCV13 increased from 11% to 29%.ConclusionsThere was a significant reduction in the hospitalizations rates, ICU admissions, and fatalities due to IPD after PCV10 introduction in Brazil. Cases due to PCV10 serotypes were reduced, while infections rates caused by non-PCV10 serotypes increased.     

Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly

BackgroundHerd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older in the period 2008–2013.MethodsThis is a post hoc analysis of two prospective studies from the Netherlands. Serotype specific urinary antigen detection and routine microbiological testing were used to categorize episodes as IPD or non-IPD PCAP caused by 7-valent pneumococcal conjugate vaccine (PCV7), PCV10-7 (three additional PCV10 serotypes), PCV13-10 (three additional PCV13 serotypes), and non-PCV13 serotypes. Proportions per vaccine-serotype group were assessed per year from June 1st to May 31st. Time trends were compared to national IPD data.ResultsOf 270 non-IPD PCAP episodes with known serotype, PCV7 serotypes decreased from 28% in 2008/2009 to 7% in 2012/2013 (p-value for trend <0.001). No change in PCV10-7 (19% overall) and PCV13-10 (29% overall) serotypes was observed. Non-PCV13 serotypes increased from 30% in 2008/2009 to 37% in 2012/2013 (p-value for trend 0.048). Trends corresponded with national IPD data.ConclusionPCV7 serotypes declined in non-IPD PCAP among elderly between 2008 and 2013, comparable to IPD data. No reduction in the additional PCV10 serotypes could be demonstrated within the first two years after PCV10 introduction.     

Impact of the 13-valent pneumococcal conjugate vaccine (pcv13) on invasive pneumococcal disease and carriage in Alaska

BackgroundAlaska Native (AN) children have experienced high rates of invasive pneumococcal disease (IPD). In March 2010, PCV13 was introduced statewide in Alaska. We evaluated the impact of PCV13 on IPD in children and adults, 45 months after introduction.MethodsPneumococcal sterile site isolates, reported through state-wide surveillance, were serotyped using standard methods. We defined a pre-PCV13 time period 2005–2008 and post-PCV13 time period April 2010–December 2013; excluding Jan 2009–March 2010 because PCV13 was introduced pre-licensure in one high-risk region in 2009.ResultsAmong Alaska children <5 years, PCV13 serotypes comprised 65% of IPD in the pre-PCV13 period and 26% in the PCV13 period. Among all Alaska children <5 years, IPD rates decreased from 60.9 (pre) to 25.4 (post) per 100,000/year (P<0.001); PCV13 serotype IPD decreased from 37.7 to 6.4 (P<0.001). Among AN children <5 years, IPD rates decreased from 149.2 to 60.8 (P<0.001); PCV13 serotype IPD decreased from 87.0 to 17.4 (P<0.001); non-PCV13 serotype IPD did not change significantly. Among persons 5–17 and ≥45 years, the post-vaccine IPD rate was similar to the baseline period, but declined in persons 18–44 years (39%, P < 0.001); this decline was similar in AN and non-AN persons (38%, P = 0.016, 43%, P = 0.014, respectively).ConclusionsForty-five months after PCV13 introduction, overall IPD and PCV13-serotype IPD rates had decreased 58% and 83%, respectively, in Alaska children <5 years of age when compared with 2005–2008. We observed evidence of indirect effect among adults with a 39% reduction in IPD among persons 18–44 years.     

Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies

BackgroundNeither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines.MethodsWe collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated.ResultsAmong 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes.ConclusionsVaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.     

The changing epidemiology of invasive pneumococcal disease after PCV13 vaccination in a country with intermediate vaccination coverage

BackgroundWe studied the impact of 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of invasive pneumococcal disease (IPD) and serotype distribution in a region with intermediate levels of vaccination (around 64% in children aged <2 years).MethodsSurveillance data on IPD cases reported by microbiologists participating in the Microbiological Reporting System of Catalonia during 2006–2014 were analysed. We compared estimated incidence rate (IR) ratios for serotypes included in PCV7, PCV10non7, PCV13non10 and non-PCV13 between the PCV7 (2006–2009) and PCV13 periods (2010–2014). IR were corrected for missing serotypes according to year and age groups: <2 years, 2–4 years, 5–64 years and ≥65 years.ResultsA total of 9338 IPD cases were reported. Overall IPD incidence declined by 26.2% (from 16.4 to 12.1) in the PCV13 period. The largest decrease was observed in children aged 2–4 years (44.5%, from 37.4 to 20.8). Pneumonia fell in all age groups with the largest reduction in children aged 2–4 years (49.3%) and <2 years (42%). PCV13 serotypes decreased significantly in all age groups, from 52% (31.6 to 15.1) in children aged 2–4 years to 35% (22.8 to 14.8) in adults aged ≥65 years. Non-PCV13 serotypes rose by 13% (14.8 to 16.8) in people aged ≥65 years.ConclusionsIn a region with intermediate vaccination coverage, the introduction of PCV13 has reduced the overall incidence of IPD, mainly due to the decrease in PCV13 serotypes in all age groups, suggesting herd immunity. Non-PCV13 serotypes have increased in adults aged ≥65 years, suggesting serotype replacement. Higher PCV13 vaccination coverage in children will further reduce IPD incidence in all age groups.     

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.     

Early impact of PCV7/PCV13 sequential introduction to the national pediatric immunization plan,on adult invasive pneumococcal disease: A nationwide surveillance study

BackgroundPCV7 was introduced as a universal childhood vaccination in Israel on July 2009 and was gradually replaced by PCV13 from November 2010. We report data on adult invasive pneumococcal disease (IPD), two years post PCV13 implementation.MethodsAn ongoing nationwide active surveillance (all 27 laboratories performing blood/CSF cultures nationwide), initiated in 2009, providing all blood/CSF Streptococcus pneumoniae isolated from persons ≥18 years. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. Medical history and outcomes were recorded in ∼90%.ResultsOf 1809 IPD episodes, S. pneumoniae was isolated from the blood in 95% and most cases had pneumonia. Predisposing comorbidities were present in >70%. During the four study years, overall IPD incidence decreased from 9.2 to 7.2/100,000, incidence of pneumonia and particularly severe pneumonia cases decreased significantly from 6.6 to 4.7/100,000, (p = 0.029). Vaccine type (VT7/VT13) serotypes decreased by 70%/57% within 4 years. This was accompanied by a 52% increase in non-VT13 strains. These changes were most apparent in winter. PCV impact was most pronounced in younger adults (39% decrease in overall IPD with only a non-significant increase in non-VT13 cases) while in those >65 years a non-significant decrease in overall IPD was observed with a 64% increase in non-VT13 cases. Non-VT13 serotypes that increased significantly were 12F, 15A 10A and 6 C. A continuous reduction in isolates with penicillin MIC > 0.06 μg/ml was observed (26% to 11%, p < 0.001).ConclusionsFour years after PCV7 and 2.5 years after PCV13 universal implementation in children, incidence of adult IPD caused by VT7 and VT13 decreased in all ages, mainly in younger adults. Despite increase in non-VT13 IPD, overall IPD decreased. Additional follow-up is needed to determine the long-term impact of PCV13.     

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

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

The potential role of 13-valent pneumococcal conjugate vaccine in preventing respiratory complications in bacteraemic pneumococcal community-acquired pneumonia

IntroductionPneumococcal 13-valent vaccine (PCV-13) has a potential role in preventing bacteraemic pneumococcal pneumonia and its complications, but little is known about its ability to specifically prevent respiratory complications. Our aim were to analyse the pneumococcal serotypes associated with the development of respiratory complications and the potential role of PCV-13 in preventing respiratory complications in bacteraemic pneumococcal pneumonia.Material and methodsWe analysed demographic characteristics, comorbidities, antibiotic resistances and the outcomes of a cohort of 65 vaccine-naïve bacteraemic pneumococcal pneumonias, stratified by the pneumococcal serotypes included in PCV13 vs. those not included. Complications were clustered as follows: respiratory complications (hypoxemic respiratory failure; mechanical ventilation), systemic complications (septic shock; multiorgan failure), suppurative complications (empyema; pleural effusion; lung abscess).ResultsFrom a population of 65 CAP-SP, 47.7% of the isolates belonged to PCV-13 serotypes group. No differences in comorbidities or clinical manifestations were found between groups. With regard to biochemical parameters, we found more profound hypoxemia levels in PCV-13 serotypes group comparing to non-vaccine group [PaO₂/FiO₂ 209 (63) vs. 268 (57); p = 0.007]. Global complications were identified in 69.2% (45 patients), and the most frequent were respiratory complications, found in 47.7%. Respiratory complications were detected more frequently in PCV-13 groups compared to non-vaccine groups (61.3% vs. 35.3%; p = 0.036). Overall 30-day mortality was 30.8%. Mortality was similar between both groups (25.8% vs. 35.3%; p = 0.408).ConclusionsPneumococcal 13-valent conjugate vaccine includes the serotypes which cause more respiratory complications in our series; these serotypes were not associated with higher mortality in our series. PCV-13 may have a potential role in preventing respiratory complications due to bacteraemic pneumonoccal pneumonia.     

Colonization with 19F and other pneumococcal conjugate vaccine serotypes in children in St. Louis,Missouri, USA

BackgroundThe epidemiology of nasopharyngeal (NP) pneumococcal carriage varies with geography and has changed in response to pneumococcal conjugate vaccine (PCV): a low prevalence (3% or less of colonizing isolates) of colonization by vaccine-type (VT) pneumococcal serotypes after PCV introduction has been reported. The primary goal of this study was to determine the VT serotype prevalence of NP pneumococcal colonization of children residing in the St. Louis, MO, USA metropolitan area following introduction of the 13-valent PCV in 2010. The secondary goal of this study was to identify characteristics associated with NP pneumococcal carriage of any serotype.MethodsBetween July 2013 and April 2016, we enrolled 397 healthy children, aged 0–17 years, who required sedation for procedures or minor surgeries at St. Louis Children’s Hospital. NP swabs were collected after sedation or anesthesia and cultured for pneumococcus. Vaccine records were obtained from primary care providers or from state immunization databases. Parents/guardians completed a questionnaire to provide demographics, past medical history and household characteristics.ResultsOf the 88 pneumococcal isolates recovered from 84 colonized subjects (21.2% of all enrolled subjects; 95% CI 17.2–25.2%), 16 were VT. Eleven isolates were serotype 19F (12.5%), four (4.5%) were 6A and one (1.1%) was 19A. Prevalence of VT among colonizing isolates was thus 18.2% (CI 10.1–26.1%) in our cohort, despite complete PCV vaccination in 87% of colonized children. Factors associated with pneumococcal colonization by any serotype included younger age and daycare attendance.ConclusionChildren in St. Louis exhibit a higher prevalence of VT serotypes among pneumococcal carriage isolates than has been reported in other areas in the US, demonstrating the necessity of ongoing surveillance of local epidemiology and providing evidence that serotype 19F can remain prevalent in a pediatric population despite high vaccine uptake.     

Five winters of pneumococcal serotype replacement in UK carriage following PCV introduction

The seven-valent pneumococcal conjugate vaccine (PCV7) was added to the UK national immunisation programme in September 2006. PCV13 replaced PCV7 in April 2010. As carriage precedes disease cases this study collected carried pneumococci from children each winter from 2006/7 to 2010/11 over PCV introduction. Conventional microbiology and whole genome sequencing were utilised to characterise pneumococcal strains.Overall prevalence of pneumococcal carriage remained stable. Vaccine serotypes (VT) decreased (p < 0.0001) with concomitant increases in non-vaccine serotypes (NVT). In winter 2010/11 only one isolate of PCV7 VT was observed (6B). PCV13 unique VTs decreased between winters immediately preceding and following PCV13 introduction (p = 0.04). Significant decreases for VTs 6B, 19F, 23F (PCV7) and 6A (PCV13) and increases for NVT 21, 23B, 33F and 35F were detected. The serotype replacement was accompanied by parallel changes in genotype prevalence for associated sequence types with clonal expansion contributing to replacement. By winter 2010/11, serotype coverage of PCV7 and PCV13 was 1% and 11% respectively.VT replacement was observed for PCV7 and PCV13 serotypes. Conjugate vaccine design and use requires continuous monitoring and revision.