Effectiveness of the new serotypes in the 13-valent pneumococcal conjugate vaccine

Efficacy of the new serotypes in the 13-valent pneumococcal conjugate vaccine (PCV13) against invasive pneumococcal disease (IPD) was based on a putative correlate of protection. In England and Wales, PCV13 replaced PCV7 in the 2, 4, and 13 month schedule in April 2010. Using non-vaccine type IPD cases as controls, we estimated vaccine effectiveness (VE) for the new serotypes. Among 166 IPD cases in PCV13 eligible children reported by July 2011 with known serotype and vaccination status, VE for 2 doses under a year was 78% (95% confidence interval −18% to 96%) and 77% (38-91%) for one dose over a year. VE for 7F and 19A was 76% (21-93%) and 70% (10-90%) respectively for ≥one dose. VE for serotypes 1 and 3 was 62% and 66% respectively although confidence intervals spanned zero. IPD due to PCV13-only serotypes halved in children under 2 years in the study period.     

Impact of private use of the 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal carriage among Portuguese children living in urban and rural regions

In Portugal, the 13-valent pneumococcal conjugate vaccine (PCV13) was commercially available between 2010 and 2015, following a decade of private use of PCV7. We evaluated changes on serotype distribution and antimicrobial susceptibility of pneumococci carried by children living in two regions of Portugal (one urban and one rural). Three epidemiological periods were defined: pre-PCV13 (2009–2010), early-PCV13 (2011–2012), and late-PCV13 (2015–2016). Nasopharyngeal samples (n = 4,232) were obtained from children 0–6 years old attending day-care centers. Private use of PCVs was very high in both regions (>75%). Pneumococcal carriage remained stable and high over time (62.1%, 62.4% and 61.6% (p = 0.909) in the urban region; and 59.8%, 62.8%, 59.5% (p = 0.543) in the rural region). Carriage of PCV7 serotypes remained low (5.3%, 7.8% and 4.3% in the urban region; and 2.5%, 3.7% and 4.8% in the rural region). Carriage of PCV13 serotypes not targeted by PCV7 decreased in both the urban (16.4%, 7.3%, and 1.6%; p < 0.001) and rural regions (13.2%, 7.8%, and 1.9%; p < 0.001). This decline was mostly attributable to serotype 19A (14.1%, 4.4% and 1.3% in the urban region; and 11.1%, 3.6% and 0.8% in the rural region, both p < 0.001). Serotype 3 declined over time in the urban region (10.1%, 4.4%, 0.8%; p < 0.001) and had no obvious trend in the rural region (4.2%, 6.7%, 2.4%; p = 0.505). Serotype 6C decreased in both regions while serotypes 11D, 15A/B/C, 16F, 21, 22F, 23A/B, 24F, 35F, and NT were the most prevalent in the late-PCV13 period. Intermediate resistance to penicillin and non-susceptibility to erythromycin decreased significantly in both regions (19.5%, 13.3%, and 9.3%; and 25.4%, 25.9%, and 13.4%; both p < 0.001, respectively in the urban region; and 12.4%, 11.1%, and 2.8% (p < 0.001); and 15.3%, 14.7%, and 9.2% (p = 0.037), respectively, in the rural region). In conclusion, private use of PCV13 led to significant changes on the pneumococcal population carried by children in Portugal.     

Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study

BackgroundPneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010–11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet).MethodsWe compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012–2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose.ResultsThe PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0–88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8–96.1) < 12 months to 85.1% (72.0–92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7–94.7) against fatal PCV13 IPD, 64.5% (43.7–77.6), 83.2% (73.7–89.3) and 85.1% (67.6–93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3–94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4–92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2–96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and ?14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively.ConclusionsPCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.     

Indirect cohort analysis of 10-valent pneumococcal conjugate vaccine effectiveness against vaccine-type and vaccine-related invasive pneumococcal disease

We applied the indirect cohort method to estimate effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) among young children in Brazil. Cases of invasive pneumococcal disease (IPD), i.e., Streptococcus pneumoniae, detected in normally sterile fluid identified through laboratory-based surveillance and previously enrolled in a matched case-control effectiveness study are included. We estimated PCV10 effectiveness using multivariable logistic regression comparing PCV10 vaccination among children with vaccine-type or vaccine-related IPD vs. children with non-vaccine-type disease. The adjusted effectiveness of ≥1 doses against vaccine-type (72.8%, 95% confidence interval [CI] [44.1, 86.7]) and vaccine-related (61.3%, 95%CI [14.5, 82.5]) IPD were similar to the effectiveness observed in the original case-control study (which required enrollment >1200 controls). We also found significant protection of ≥1 dose against individual vaccine serotypes (14, 6B, 23F, 18C) and against vaccine-related serotype 19A. The indirect cohort methods leverages existing surveillance is a feasible approach for evaluating pneumococcal conjugate vaccines, particularly in resource-limited settings.     

Reduction in the incidence of invasive pneumococcal disease after general vaccination with 7-valent pneumococcal conjugate vaccine in Germany

General vaccination with the 7-valent pneumococcal conjugate vaccine was recommended in Germany in July 2006 for all children <2 years. The proportion of reported invasive pneumococcal disease (IPD) caused by vaccine serotypes before vaccine introduction was considerably lower than in the US.     

Long-term impact of 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease among children in Finland

BackgroundThe ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in September 2010. The impact of PCV10 vaccination against invasive pneumococcal disease (IPD) in vaccine-eligible children has been high. We evaluated the long-term impact of PCV10 vaccination against IPD in vaccine-eligible and older, unvaccinated children six years after PCV10 introduction with a special focus on cross-protection against PCV10-related serotypes (serotypes in the same serogroups as the PCV10 types).MethodsWe used data on IPD from the national, population-based surveillance. A target cohort of vaccine-eligible children (born June 2010 or later) was followed from 3 months of age until the end of 2016. For the indirect effect, another cohort of older PCV10-ineligible children was followed from 2012 through 2016. IPD rates were compared with those of season- and age-matched reference cohorts before NVP introduction.ResultsAmong vaccine-eligible children, the incidence of all IPD decreased by 79% (95% CI 74–83%). There was a statistically significant reduction in the incidence of 6A IPD, but for 19A, the reduction was non-significant and the incidence of 19A increased towards the end of the study period in the older vaccine-eligible children. The increase in non-PCV10 related serotypes was non-significant.In the unvaccinated older children, the incidence of all IPD decreased by 33% (95% CI 8–52%) compared to the reference cohort, and there was no impact on serotype 6A or 19A IPD.ConclusionOverall, the impact of PCV10 vaccination on IPD was high in vaccine-eligible children, with a major reduction in vaccine-type disease, and without notable replacement by other serotype groups. Our data suggest that PCV10 results in long-lasting direct cross-protection against 6A IPD. For 19A, no net reduction was observed six years after NVP introduction in the vaccine-eligible cohort. The indirect impact on IPD in unvaccinated children sustained.     

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.     

Vaccine effectiveness of the 7-valent and 13-valent pneumococcal conjugate vaccines in Canada: An IMPACT study

We used an indirect cohort analysis in children under 5 years-old from 2002 to 2018 to examine vaccine effectiveness (VE) of the 7-valent pneumococcal conjugate vaccine (PCV) (3 + 1 doses in most regions) and the 13-valent PCV (2 + 1 doses in all regions) against invasive pneumococcal disease (IPD) caused by vaccine serotypes in children in Canada. Cases were identified from the Canadian Immunization Monitoring Program ACTive (IMPACT), a national active surveillance network of 12 tertiary care pediatric hospitals that represent about 90% of tertiary care hospital beds in Canada. There were 1477 children evaluated for PCV7 VE and 489 for PCV13 VE. PCV7 VE in children with vaccination up to date for their age was 96% (95% CI: 67–99%) after a single dose and 95% (95% CI: 92–97%) after ≥2 doses. The VE was 91% (95% CI: 85–94%) in children who had received doses but were not up to date for their age. PCV13 VE in children with vaccinations up to date for their age was 55% (95% CI: 28–72%) after ≥2 doses. The PCV13-vaccine serotypes causing breakthrough IPD in children up to date for their age with 2+ doses of PCV13 were 3 (13/27, 48.2%),19A (11/27, 40.7%), and 19F (3/27, 11.1%). When serotype 3 and 19A were excluded, the VE of PCV13 against the remaining vaccine serotypes was 89% (95% CI: 64–97%) in children with ≥2 doses. The lower VE of PCV13 may be due to lower effectiveness against serotypes 3 and 19A, which could be influenced by the change in dosing schedule from 4 to 3 total doses with the introduction of PCV13, combined with vaccine uptake of 80%. However, PCV13 still provides the benefit of protection against more serotypes than PCV7, and good VE against all serotypes except 3 and 19A.     

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.     

Effectiveness of thirteen-valent pneumococcal conjugate vaccine to prevent serotype 3 invasive pneumococcal disease in Quebec in children,Canada

In the province of Quebec, Canada, a 2 + 1 dose pneumococcal conjugate vaccine (PCV) program for children was implemented in 2004. PCV7 was replaced by PCV10 in 2009, by PCV13 in 2011 and by PCV10 in 2018, without catch-up in all instances. The objective was to estimate PCV13 effectiveness to prevent serotype 3 invasive pneumococcal disease in children aged less than 5 years, using 2010–2018 mandatory notification and laboratory surveillance data, an indirect cohort design and multivariate logistic regression models. A total of 29 cases of serotype 3 and 290 non-vaccine serotype cases as controls were analysed. Overall vaccine effectiveness (≥1 dose) was estimated at 59% [-39% to 88%]. During the first year after the last dose effectivness was 88% [47% to 97%] whereas no protection was observed thereafter. There was no trend towards increased effectiveness with the number of doses. PCV13 protection against serotype 3 IPD seems to be short-lived.     

Evaluation of the impact of 13-valent pneumococcal conjugate vaccine immunization in children by surveillance of culture-confirmed pneumococcal disease: A prospective clinical microbiological study

The study aimed to investigate the impact of 13-valent pneumococcal conjugate vaccine (PCV13) immunization on the overall pneumococcal disease in children in Taiwan by surveillance of culture-confirmed pneumococcal disease (CCPD). This study was conducted in a medical center from 2012 to 2016. Clinical isolates of Streptococcus pneumoniae were prospectively collected from pediatric patients. Serotyping, multi-locus sequence typing, and antimicrobial susceptibility testing were performed. A total of 473 patients with CCPD, including 58 with invasive pneumococcal disease (IPD), were identified. The incidence of CCPD per 10,000 admissions decreased from 71.7 in 2012 to 27.0 in 2016. The proportion of additional PCV13 serotypes significantly decreased from 52.0% in 2012 to 21.7% in 2015 but increased slightly to 26.7% because of serotype 19A in 2016 (P < 0.0001). The proportion of non-vaccine serotypes (NVTs) increased significantly from 18.4% in 2012 to 66.7% in 2016, but the increase of the incidence of CCPD caused by NVTs was not considered significant (P = 0.0885). Genotyping identified predominant clones, ST63^15A, ST83^15B, and ST166/338^23A, for major NVTs. The penicillin non-susceptibility of PCV13 serotypes was significantly higher than that of NVTs (P < 0.0001). Surveillance of CCPD appears superior to IPD alone for evaluation of the overall impact of pneumococcal immunization. Serotype replacement occurred quickly after the use of PCV13, while the incidence of NVT infection did not show a significant increase in children over the years. The gradual introduction of PCV13 into national immunization program is effective in reducing overall pneumococcal disease in children.     

Long-term population impact of infant 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in adults in Finland

BackgroundLimited data are available on long-term indirect effects of ten-valent pneumococcal conjugate vaccine (PCV10) programmes. We evaluated changes in invasive pneumococcal disease (IPD) incidence, mortality, and serotype distribution in adults up to 9 years after infant PCV10 introduction.MethodsCulture-confirmed IPD cases ≥18 years (n = 5610; 85% were pneumonia) were identified through national, population-based laboratory surveillance; data were linked with population registry to conduct nationwide follow-up study. In a time-series model, we compared serotype-specific IPD incidence and associated 30-day mortality rates before and after PCV10 by using negative binomial regression models.ResultsDuring pre-PCV10 period (7/2004–6/2010), overall IPD incidence in adults ≥18 years increased yearly by 4.8%. After adjusting for trend and seasonality, the observed PCV10 serotype IPD incidence in 7/2018–6/2019 was 90% (12/100,000 person-years) lower than the expected rate without PCV10 program. Non-PCV10 serotype incidence was 40% (4.4/100,000 person-years) higher than expected; serotypes 3, 19A, 22F, and 6C accounted for most of the rate increase. However, incidence of non-PCV10 IPD levelled off by end of follow-up. The observed-expected incidence rate-ratio (IRR) was 0·7 (95 %CI 0·5–0.8) for all IPD and 0·7 (95 %CI 0·3–1·3) for IPD-associated 30-day mortality. Case-fatality proportion decreased from 11·9% to 10.0% (p < 0.01). In persons ≥65 years, the IRR was 0·7 (95 %CI 0·5–0.95).ConclusionsSignificant indirect effects were seen for vaccine-serotype IPD and for overall IPD in all adult age groups. For non-vaccine IPD, the incidence stabilized 5 years after infant PVC10 program introduction, resulting in a steady state in which non-vaccine IPD accounted for nearly 90% of overall IPD. Substantial pneumococcal disease burden remains in older adults.     

Impact of national introduction of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in Bangladesh: Case-control and time-trend studies

BackgroundBangladesh introduced the ten-valent pneumococcal conjugate vaccine (PCV10) into its national immunization program in March 2015 creating an opportunity to assess the real-world impact of PCV on invasive pneumococcal disease (IPD).MethodsBetween January 2014 and June 2018, children aged 3–35 months in three rural sub-districts of Sylhet district of Bangladesh were visited every two months to collect morbidity and care-seeking data. Children attending sub-district hospitals with pneumonia, meningitis, or sepsis were assessed for IPD after obtaining informed consent. Blood and cerebrospinal fluid were collected from enrolled children to isolate pneumococcus using culture and molecular test. Children who were age-eligible to receive the PCV and had pneumococcus isolated were enrolled as cases. Four age and sex-matched clinic and community controls were selected for each case within one to two weeks of case identification. Data on immunization status and confounders were collected. PCV coverage was estimated using vaccine coverage surveys. Case-control and incidence trend analyses were conducted to assess the impact of PCV on IPD.ResultsThe community cohort yielded 217,605 child years of observations and 154,773 sick child-visits to study hospitals. Pneumococcus was isolated from 44 children who were age-eligible to receive PCV; these children were enrolled as cases. The cases were matched with 166 community- and 150 clinic-controls. The matched case-control analyses using community-controls showed 83% effectiveness (95% CI: 1.57–97.1%) and clinic controls showed 90% effectiveness (95% CI: −26.0% to 99.1%) of PCV in preventing IPD. Incidence trend analysis estimated vaccine effectiveness at 80.1% (95% CI: 38.4, 93.6).ConclusionPCV in this pediatric population in Bangladesh was highly effective in preventing IPD.     

Effectiveness of a 3 + 0 pneumococcal conjugate vaccine schedule against invasive pneumococcal disease among a birth cohort of 1.4 million children in Australia

BackgroundMost studies use indirect cohort or case-control methods to estimate vaccine effectiveness (VE) of 7- and 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) against invasive pneumococcal disease (IPD). Neither method can measure the benefit vaccination programs afford the unvaccinated and many studies were unable to estimate dose-specific VE. We linked Australia’s national immunisation register with health data from two states to calculate IPD incidence by vaccination status and VE for a 3 + 0 PCV schedule (doses at 2, 4, 6 months, no booster) among a cohort of 1.4 million births.MethodsBirths records for 2001–2012 were probabilistically linked to IPD notifications, hospitalisations, deaths, and vaccination history (available until December 2013). IPD rates in vaccinated and unvaccinated children <2 years old were compared using Cox proportional hazards models (adjusting for potential confounders), with VE = (1 − adjusted hazard ratio) × 100. Separate models were performed for all-cause, PCV7, PCV13 and PCV13-non-PCV7 serotype-specific IPD, and for Aboriginal and non-Aboriginal children.ResultsFollowing introduction of universal PCV7 in 2005, rates of PCV7 serotype and all-cause IPD in unvaccinated children declined 89.5% and 61.4%, respectively, to be similar to rates in vaccinated children. Among non-Aboriginal children, VEs for 3 doses were 94.2% (95%CI: 81.9–98.1) for PCV7 serotype-specific IPD, 85.6% (95%CI: 60.5–94.8) for PCV13-non-PCV7 serotype-specific IPD and 80.1% (95%CI: 59.4–90.3) for all-cause IPD. There were no statistically significant differences between the VEs for 3 doses and for 1 or 2 doses against PCV13 and PCV13-non-PCV7 serotype-specific IPD, or between Aboriginal and non-Aboriginal children.ConclusionOur population-based cohort study demonstrates that >90% coverage in the first year of a universal 3 + 0 PCV program provided high population-level protection, predominantly attributable to strong herd effects. The size of the cohort enabled calculation of robust dose-specific VE estimates for important population sub-groups relevant to vaccination policies internationally.     

接种13价肺炎球菌结合疫苗对就诊儿童肺炎链球菌血清型和耐药性的影响

目的  了解就诊儿童肺炎链球菌(Streptococcus pneumoniae, Spn)血清型分布和耐药特征,探索接种13价肺炎球菌结合疫苗(13-valent pneumococcal conjugate vaccine, PCV13)对Spn的影响。方法  收集2017—2019年苏州大学附属儿童医院疫苗接种信息明确的就诊儿童的Spn菌株,根据疫苗接种情况进行分组,并采用荚膜肿胀法进行血清分型,E-test法检测菌株抗生素的耐药性,比较是否接种PCV13对Spn血清型和耐药性的差别。结果  共收集692株Spn,其中20株分离自接种PCV13儿童。接种组中常见的血清型为19F、6B、19A、23F,对照组中常见的血清型为19F、6B、23F、19A、14,两组血清型分布差别无统计学意义(P=0.868),PCV13血清型覆盖率分别为70.0% 和72.4%(P=0.491)。所有菌株对红霉素、四环素、克林霉素高度耐药,且多重耐药率达98.5%。接种组和对照组的Spn菌株对青霉素的不敏感率分别为5.0%和9.1%(P=0.804)。结论  苏州大学附属儿童医院监测就诊儿童Spn血清型以PCV13覆盖的血清型为主,菌株对β-内酰胺类抗生素的耐药性有所下降,但对红霉素等其他常用抗菌药物的耐药性依旧严峻,并存在大量的多重耐药情况。尚未观察到接种PCV13对菌株血清型分布及降低抗生素耐药性的明显效果。     

Four years of universal pneumococcal conjugate infant vaccination in Germany: Impact on incidence of invasive pneumococcal disease and serotype distribution in children

Introduction

Vaccination with pneumococcal conjugate vaccine (PCV) for all children <2 years was recommended in Germany in July 2006. Initially PCV7 was exclusively used; PCV10 became available from April 2009 and PCV7 was replaced by PCV13 in December 2009.

Objective

To compare the incidence and serotype distribution of invasive pneumococcal disease (IPD) for pneumococcal meningitis and non-meningitis IPD in children from 2007 to 2010 with reference to the pre-vaccination period from 1997 to 2001.

Methods

Nationwide surveillance of IPD for children <16 years in Germany was based on two independent reporting sources: active surveillance in paediatric hospitals and passive web-based surveillance through microbiological laboratories. Serotyping was performed using the Neufeld Quellung reaction. Case definition: isolation of Streptococcus pneumoniae from a normally sterile body site. IPD incidence was estimated by capture–recapture analysis. Rate ratios comparing post- to pre-vaccination incidence were calculated as well as PCV7 and non-PCV7 serotype specific incidences.

Results

While PCV7 incidence decreased by 88% (95%CI: 83 to 91) in children <16 years both in pneumococcal meningitis and non-meningitis IPD, an increase in Non-PCV7 serotypes was observed which was more pronounced in non-meningitis cases (168%; 95%CI: 140–257) than in pneumoccocal meningitis (65%; 95%CI: 23–123). The changes in incidence after four years were: <16 years: −35% (95%CI: −49 to −19), <2 years: −46% (95%CI: −61 to −27) for pneumococcal meningitis and + 11% (95%CI: −4 to  + 29) and −26% (95%CI: −41 to −7) for non-meningitis IPD respectively.

Conclusion

Infant PCV7 vaccination in Germany prompted a decrease in the incidence of pneumococcal meningitis similar to that observed in England/Wales. In non-meningitis IPD the decrease was smaller and confined to the age group <2 years with no change or an increase in incidence in other age groups pointing to potential ascertainment bias due to increased blood-culturing.     

Pneumococcal carriage in vaccine-eligible children and unvaccinated infants in Lao PDR two years following the introduction of the 13-valent pneumococcal conjugate vaccine

Pneumococcal carriage is a prerequisite for disease, and underpins herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few data on the impact of PCVs in lower income settings, particularly in Asia. In 2013, the Lao People's Democratic Republic (Lao PDR) introduced 13-valent PCV (PCV13) as a 3?+?0 schedule (doses at 6, 10 and 14?weeks of age) with limited catch-up vaccination. We conducted two cross-sectional carriage surveys (pre- and two years post-PCV) to assess the impact of PCV13 on nasopharyngeal pneumococcal carriage in 5–8?week old infants (n?=?1000) and 12–23?month old children (n?=?1010). Pneumococci were detected by quantitative real-time PCR, and molecular serotyping was performed using DNA microarray. Post PCV13, there was a 23% relative reduction in PCV13-type carriage in children aged 12–23?months (adjusted prevalence ratio [aPR] 0.77 [0.61–0.96]), and no significant change in non-PCV13 serotype carriage (aPR 1.11 [0.89–1.38]). In infants too young to be vaccinated, there was no significant change in carriage of PCV13 serotypes (aPR 0.74 [0.43–1.27]) or non-PCV13 serotypes (aPR 1.29 [0.85–1.96]), although trends were suggestive of indirect effects. Over 70% of pneumococcal-positive samples contained at least one antimicrobial resistance gene, which were more common in PCV13 serotypes (p?<?0.001). In 12–23?month old children, pneumococcal density of both PCV13 serotypes and non-PCV13 serotypes was higher in PCV13-vaccinated compared with undervaccinated children (p?=?0.004 and p?<?0.001, respectively). This study provides evidence of PCV13 impact on carriage in a population without prior PCV7 utilisation, and provides important data from a lower-middle income setting in Asia. The reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Lao PDR.     

Effectiveness of 10-valent pneumococcal conjugate vaccine estimated with three parallel study designs among vaccine-eligible children in Finland

BackgroundTen-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Finnish National Vaccination Programme (NVP) in 9/2010. We estimated the individual-level effectiveness (VE) of PCV10 in children during eight years of vaccine implementation.MethodsData on invasive pneumococcal disease (IPD) were collected from national, population-based surveillance, and vaccination status from the vaccination register. Vaccine-eligible children were followed from six months of age until end of 2018 (born 6/2010 or later, ages 6–102 months). VE was estimated with three parallel approaches: full cohort, nested case-control and indirect cohort designs adjusting with age-group, sex and calendar year.ResultsVE against PCV10 serotype IPD was estimated at 93% (95% credible interval 87–97%), 98% (90–100%) and 100% (98–100%), and against PCV10-related serotypes at 46% (−13–72%), 51% (−24–79%), and 78% (−7–97%), with the full cohort, nested case-control, and indirect cohort designs, respectively.The estimated VE against non-PCV10-related (neither PCV10 nor PCV10-related) serotypes was negative but included zero effectiveness (full cohort VE −67%, −711–52%; nested case-control VE −77%, −929–59%). VE against all IPD was estimated with these two methods at 54% (24–71%) and 61% (26–79%). Over time, VE against PCV10 IPD remained stable but VE against all IPD decreased.DiscussionAll designs provided estimates that were concordant with each other, but those with the full cohort design were usually the most precise. PCV10 offered sustained high VE against PCV10-serotype IPD on vaccinated children during the first decade after introduction into the programme.     

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.