Invasive Pneumococcal Disease Surveillance Data Research Articles

Increase of invasive pneumococcal disease in children temporally associated with RSV outbreak in Quebec: a time-series analysis

Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections. We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021-2022 was estimated. A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in <5-year-old children in October 2021, exceeding the pre-NPI trend (+62%). This was temporally associated with an unusual surge in RSV cases (+53% versus pre-NPI trend). During this 2021-22 surge, the fraction of IPD attributable to RSV dynamics in children was 77% (95% CI [33-100]). By contrast, the IPD incidence in older age-groups remained low, and was temporally associated with influenza dynamics. These results provide new evidence on the role of respiratory viruses in driving IPD dynamics, with possible differences between children and adults. In the coming future, the potential benefit of interventions targeting RSV, such as vaccines, for IPD prevention should be considered. The study was supported by a grant from the Quebec Ministry of Health and Social Services ('ministère de la Santé et des Services sociaux du Québec'). Publication was supported by a grant from "Fondation de l'Assistance Publique - Hôpitaux de Paris et de l'Alliance«Tous Unis contre le Virus » (Fondation de France/Institut Pasteur/APHP)". N.O. was supported by the ESPID (European Society of Pediatric Infectious Diseases) 2021-2023 Fellowship Award and the 2022 ISPPD (International Symposium on Pneumococci and Pneumococcal Diseases) Robert Austrian Research award.

Reemergence of Invasive Pneumococcal Disease in Germany During the Spring and Summer of 2021.

BackgroundThe incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020 and the first quarter of 2021, concurrent with nonpharmaceutical interventions (NPIs) intended to stymie transmission of SARS-CoV-2. In 2021, the stringency of these NPI strategies has varied. We investigated age- and serotype-specific variations in IPD case counts in Germany in 2020–2021.MethodsIPD cases through 30 November 2021 were stratified by age group, serotype, or geographic location. IPD surveillance data in 2020–2021 were compared with (1) IPD surveillance data from 2015–2019, (2) mobility data during 2020 and 2021, and (3) NPI stringency data in 2020 and 2021.ResultsIPD incidence began to return toward baseline among children 0–4 years old in April 2021 and exceeded baseline by June 2021 (a 9% increase over the average monthly values for 2015–2019). Children aged 5–14 years and adults aged 15–34 or ≥80 years showed increases in IPD cases that exceeded baseline values starting in July 2021, with increases also starting in spring 2021. The age distribution and proportion of vaccine-serotype IPD remained comparable to those in previous years, despite lower overall case counts in 2020 and 2021. The percentage change in IPD incidence compared with the previous 5 years was correlated with changes in mobility and with NPI stringency.ConclusionsIPD levels began to return to and exceed seasonal levels in spring and summer 2021 in Germany, following sharp declines in 2020 that coincided with NPIs related to the coronavirus disease 2019 pandemic. Proportions of vaccine serotypes remained largely consistent throughout 2020–2021.

Invasive Pneumococcal Disease in Latvia in PCV10 Vaccination Era, 2012-2018.

In 2010 in Latvia, invasive pneumococcal disease (IPD) became a cause for concern and vaccination of infants with four doses of 7–valent pneumococcal conjugate vaccine (PCV7) commenced. In 2012, 10–valent pneumococcal conjugate vaccine (PCV10) (three doses at 2, 4, and 12–15 month of age) vaccination was introduced. We described incidence and serotype distribution of IPD in Latvia and investigated serotypes associated with death from IPD based on surveillance data. Adult vaccination against pneumococcal infection is not included in the national immunization program. Laboratory confirmed IPD cases are passively notified to the Center for Disease Prevention and Control of Latvia (CDPC) by laboratories and clinicians. We calculated incidence by age, sex, case fatality, and trend in serotypes by conducting a retrospective population-based cross-sectional study based on national IPD surveillance data. From 2012 to 2018 466 cases of IPD were reported. The highest notified incidence was in 2015 at 4.4/100,000, which fell to 3.9 in 2018. The highest mean annual IPD incidence was in infants (4.8) and in the elderly (6.0). PCV10 vaccine serotypes were the most prevalent in IPD cases up to 2015 with a decreasing trend from 50% (20/40) in 2012 to 19% (14/74) in 2018 (chi2 test for trend of odds = 0.000). PCV23nonPCV13 vaccine serotypes had an increasing trend and rose from 18% (7/40) to 34% (25/74) (chi2 test for trend of odds = 0.000). Non-Vaccine serotypes had an increasing trend and rose from 13% (5/40) to 27% (20/74) (chi2 test for trend of odds = 0.038). Reported total case fatality was 19% (87/466). The highest, at 36% (20/56), was reported in 2013. After adjusting for age, Streptococcus pneumoniae serotype 3 was associated with death from IPD (adjusted OR 2.3 95%CI 1.25–4.12 p 0.007). Surveillance data indicate evidence of serotype replacement with an increasing trend of serotype 19A and PPV23nonPCV13 and Non-Vaccine serotypes. Serotype 3 and age were associated with fatal IPD outcome. Further studies of S. pneumoniae carriage would be useful in providing more evidence to characterize serotypes' circulation.

The Impact of Pneumococcal Conjugate Vaccine (PCV) Coverage Heterogeneities on the Changing Epidemiology of Invasive Pneumococcal Disease in Switzerland, 2005-2019.

Pneumococcal conjugate vaccines (PCVs) have lowered the incidence of invasive pneumococcal disease (IPD) worldwide. However, the influence of regional vaccine uptake differences on the changing epidemiology of IPD remains unclear. We aimed to examine the overall impact of both seven- and 13-valent PCVs (PCV7 and PCV13) on IPD in Switzerland. Three-year periods from 2005–2010 and 2011–2019 were considered, respectively, as (early and late) PCV7 eras and (early, mid and late) PCV13 eras. Vaccine coverage was estimated from a nationwide survey according to east (German-speaking) and west (French/Italian-speaking) regions for each period. Reported incidence rate ratios (IRRs) were compared between successive periods and regions using nationwide IPD surveillance data. Overall IPD incidence across all ages was only 16% lower in the late PCV13 era compared to the early PCV7 era (IRR 0.83, 95% CI 0.79–0.88), due to increasing incidence of non-PCV-type IPD (2.59, 2.37–2.83) in all age groups, except children <5 years. PCV uptake rates in swiss children were slightly higher in the west than the east (p < 0.001), and were accompanied by lower IPD incidences across all age groups in the former region. Post-PCV13, non-PCV serotypes 8, 22F and 9N were the major cause of IPD in adults ≥65 years. Increased PCV coverage in both areas of Switzerland resulted in a decrease in vaccine-type and overall IPD incidence across all age groups, in a regionally dependent manner. However, the rising incidence of non-vaccine-type IPD, exclusive to older adults, may undermine indirect beneficial effects.

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

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

Changes in Invasive Pneumococcal Disease Caused by Streptococcus pneumoniae Serotype 1 Following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project.

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for <5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years, 0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3 + 0 schedule constrains generalizability and data from these settings are needed.

Application of the screening and indirect cohort methods to evaluate the effectiveness of pneumococcal vaccination program in adults 75\u2009years and older in Taiwan

BackgroundThe Taiwanese national 23-valent pneumococcal polysaccharide vaccine (PPV23) program in adults ≥75 years of age and the 13-valent pneumococcal conjugate vaccine (PCV13) program for children were implemented in 2008 and 2013, respectively. In this study we evaluated PPV23 vaccine effectiveness (PPV23VE) in the elderly, with regard to both direct protection from the vaccine itself and the indirect protection conferred by PCV13 immunization in children.MethodsThe incidence of invasive pneumococcal disease (IPD) in Taiwan from July 2008 to June 2016 was collected from IPD surveillance data. A comparison of IPD incidence with a nationwide vaccination registry allowed an estimation of PPV23VE by the screening and indirect cohort methods.ResultsThe incidence of IPD in adults ≥75 years of age ranged from 13.9 per 100,000 inhabitants during the period July 2008–June 2013 to 10.4 per 100,000 inhabitants between July 2013 and June 2016 (relative risk [RR]: 0.75; 95% confidence interval [95% CI]: 0.67–0.85). According to the screening method, PPV23VE against death within 30 days of IPD onset, all IPD, and PPV23-serotype IPD was 32.5% (95% CI: 17.5–44.7%), 33.9% (95% CI: 25.2–41.5%) and 43.4% (95% CI: 34.4–51.2%), respectively. PPV23VE with the indirect cohort method was 39.0% (95% CI: 15.5–55.9%) for all PPV23 serotypes and 71.5% (95% CI: 44.2–85.4%) for 11 serotypes included in PPV23 but not in PCV13. During the period July 2008–June 2012, PPV23VE against PPV23-serotype IPD was 55.1% (95% CI: 27.2–72.3%).ConclusionsPPV23 is able to prevent IPD and 30-day fatality in adults 75 years of age and older due to a combination of direct effects from PPV23 and indirect effects from PCV13. It might confer higher protection against PPV23-serotype IPD before the introduction of PCV13 program in children.

OP388 17-Year Disease Reduction Predicted By A Transmission Dynamic Model After Pneumococcal Conjugate Vaccine Introduction In The United States

IntroductionAfter the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in the United States (US) in the year 2000, the incidence of invasive pneumococcal disease (IPD) caused by the seven vaccine serotypes declined by 80 percent in vaccinated children and 30 percent in unvaccinated adults. A transmission dynamic equation model developed in 2009 captured the direct and indirect effects of vaccination in the early years after vaccination. Subsequently, the vaccine program switched to the 13-valent PCV and adult PCV13 vaccination. This work explores the accuracy of the mathematical model to predict long-term IPD due to changes in US immunization practices.MethodsThe model simulates the acquisition of asymptomatic carriage of pneumococci and the development of IPD among individuals aged &lt;2, 2–4, 5–17, 18–49, 50–64, and ≥65 years. Pneumococcal serotypes were stratified into three categories: PCV7-type (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV6-type (1, 3, 5, 6A, 7F, and 19A), and non-PCV-type (all others). Model parameters were calibrated using US IPD surveillance data from 1998–2006. Model results were compared to observed epidemiology.ResultsThe model was previously shown to predict observed IPD well through 2007. After adjusting model parameters for PCV13 efficacy and adult vaccine coverage, modeled IPD closely replicated observed IPD. Observed baseline pre-vaccine incidence for children &lt;2 years of age was 192 cases/100,000 and 13.5 cases in 2016, versus 18.5 cases estimated by the model. Similarly, observed versus modeled cases in the ≥65-year-old age group were 24 and 23.6 cases.ConclusionsThis epidemiologic model accurately simulates the observed US IPD surveillance data 17 years after initial introduction of PCV, highlighting the direct and indirect benefits of vaccination. Well-constructed mathematical models can accurately replicate real-world scenarios. Key input parameters of these models can then be modified to predict the impact of alternate scenarios, providing insights to inform public health policy-making.

An outbreak of serotype-1 sequence type 306 invasive pneumococcal disease in an Australian Indigenous population.

Between 2010 and 2013, an outbreak of serotype-1 sequence type 306 (ST306) invasive pneumococcal disease (IPD) occurred primarily in remote locations of Northern and Central Australia. This is a descriptive study of the epidemiology of the outbreak using nationwide IPD surveillance data, supplemented with more detailed data held by affected jurisdictions, and of the response to the outbreak, including vaccination strategies. In the year the outbreak peaked (2011), serotype-1 IPD incidence was over 30-fold higher in the affected regions than in the rest of Australia (incidence rate ratio: 30.7 [95% CI 20.1-48.9]). The study includes 245 cases of serotype-1 IPD from the outbreak regions, with 75.5% identified as Indigenous. No reported cases of serotype-1 IPD occurred in young children who had completed either a 10- or 13-valent pneumococcal conjugate vaccine schedule. However serotype-1 IPD did occur in older children who had previously received 23-valent pneumococcal polysaccharide vaccine. Development of public-health-focused national IPD management guidelines, including suitable vaccine strategies for consistent use nationwide, could potentially decrease the duration and intensity of similar outbreaks in the future.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease After Introduction Into Routine Pediatric Use.

BackgroundIn 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent PCV (PCV7) for protection against invasive pneumococcal disease (IPD). This study used laboratory surveillance data to examine the effect of PCV13 on IPD before and after PCV13 introduction among children aged 6 weeks to <6 years and those aged ≥6 weeks.MethodsObservational laboratory-based IPD surveillance data were compared for the periods May 2010–April 2018 and May 2008–April 2010 (the PCV7 period) using a database of Kaiser Permanente Northern California (KPNC) members with laboratory-confirmed IPD.ResultsAmong children aged 6 weeks to 6 years, overall IPD incidence decreased from 11.57 per 100 000 during the PCV7 period to 4.09 per 100 000 after PCV13 introduction; PCV13-type IPD incidence decreased from 5.12 to 0.84 per 100 000. Non-PCV13−serotype IPD did not change significantly in this age group (PCV7 period, 1.71 per 100 000 and after PCV13, 2.52 per 100 000). Of cases occurring in this group, bacteremia was the most common clinical diagnosis. Across all ages, IPD decreased from 9.49 to 6.23 per 100 000 and PCV13-type IPD decreased from 4.67 to 1.89 per 100 000, changes being mostly due to decreases in serotypes 19A and 7F. IPD caused by non-PCV13 serotypes did not change (3.34 and 3.35 per 100 000). Overall, pneumococci isolated after PCV13 introduction had increased susceptibility to penicillin, cefotaxime, and ceftriaxone.This prospective, laboratory-based surveillance study in Kaiser Permanente Northern California members examined annual IPD incidence before and after PCV13 introduction. In children aged 6 weeks to <6 years, IPD caused by PCV13 serotypes decreased significantly (84%) during the surveillance period.ConclusionsIPD incidence decreased further in every age group after PCV13 introduction, suggesting both direct vaccination effects in the infant population and indirect effects in adults. Clinical Trials RegistrationNCT01128439.

PIN59 17-YEAR DISEASE REDUCTION PREDICTED BY A TRANSMISSION DYNAMIC MODEL AFTER PNEUMOCOCCAL CONJUGATE VACCINE INTRODUCTION IN THE UNITED STATES

After the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in the year 2000, the incidence of invasive pneumococcal disease (IPD) in the US declined by 80 percent in vaccinated children and 30 percent in unvaccinated adults. Subsequently, US vaccine policy switched to the 13-valent PCV and added adult PCV13 vaccination. This work explores the accuracy of a transmission dynamic model developed in 2009 to predict long-term IPD due to changes in US immunization practices. The differential equation model simulates the transfer and acquisition of asymptomatic carriage of pneumococci and the development of IPD among individuals aged <2, 2–4, 5–17, 18-49, 50-64, and ≥65 years. Pneumococcal serotypes were stratified into 3 categories: PCV7-type (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV6-type (1, 3, 5, 6A, 7F, and 19A), and non-PCV-type (all others). Model parameters were calibrated using US IPD surveillance data from 1998-2006. Model results were compared to observed epidemiology to determine its long-term accuracy to predict the incidence of IMD. After adjusting model parameters for PCV13 efficacy and adult vaccine coverage, modeled IPD closely replicated observed IPD from 2000 through 2016. Observed baseline pre-vaccine incidence for children <2 years of age was 192 cases/100,000 and 13.5 cases in 2016, versus 18.5 cases estimated by the model. Similarly, observed versus modeled cases in the ≥65-year-old age group were 24 and 23.6 cases. This epidemiologic model accurately estimates the observed US IPD surveillance data 17 years after initial introduction of PCV, accounting for direct and indirect benefits of vaccination. The work demonstrates that well-constructed mathematical models can accurately replicate real-world scenarios where key input parameters can be varied to predict the impact of alternate scenarios, providing insights to inform public health policymaking.

How nasopharyngeal pneumococcal carriage evolved during and after a PCV13-to-PCV10 vaccination programme switch in Belgium, 2016 to 2018.

BackgroundThe current carriage study was set up to reinforce surveillance during/after the PCV13-to-PCVC10 switch in Belgium.AimThis observational study monitored carriage of Streptococcus pneumoniae (Sp) serotypes, particularly those no longer covered (3, 6A, 19A), as well as Haemophilus influenzae (Hi), because PCV10 contains the non-typeable Hi protein D.MethodsA total of 2,615 nasopharyngeal swabs from children (6–30 months old) attending day care were collected in three periods over 2016–2018. Children’s demographic and clinical characteristics and vaccination status were obtained through a questionnaire. Sp and Hi were identified by culture and PCR. Pneumococcal strains were tested for antimicrobial (non-)susceptibility by disc diffusion and serotyped by Quellung-reaction (Quellung-reaction and PCR for serotypes 3, 6A, 19A).ResultsThe carriage prevalence of Sp (> 75%) remained stable over the successive periods but that of Hi increased (87.4%, 664 Hi-carriers/760 in 2016 vs 93.9%, 895/953 in 2017–2018). The proportion of non-PCV13 vaccine serotypes decreased (94.6%, 438 isolates/463 in 2016 vs 89.7%, 599/668 in 2017–2018) while that of PCV13-non-PCV10 vaccine serotypes (3 + 6A + 19A) increased (0.9%, 4 isolates/463 in 2016 vs 7.8%, 52/668 in 2017–2018), with serotype 19A most frequently identified (87.9%, 58/66 isolates). Non-susceptibility of pneumococci against any of the tested antibiotics was stable over the study period (> 44%).ConclusionsDuring and after the PCV13-to-PCV10 vaccine switch, the proportion of non-PCV13 serotypes decreased, mainly due to a serotype 19A carriage prevalence increase. These results complement invasive pneumococcal disease surveillance data, providing further basis for pneumococcal vaccination programme policy making.

Invasive pneumococcal diseases in children and adults before and after introduction of the 10-valent pneumococcal conjugate vaccine into the Austrian national immunization program.

BackgroundIn February 2012 the ten-valent pneumococcal conjugate vaccine (PCV10) with a 2+1 doses schedule (3, 5, 12 or 14 months of age) without catch-up vaccination was introduced in Austria. We assessed direct and indirect vaccine effects on invasive pneumococcal disease (IPD) by a population-based intervention study.MethodsThe study period was divided into pre- (2009–2011) and post-period (2013–2017, February), regarding 2012 as transition year. Outcomes were defined as PCV10 ST-IPD, the PCV10-related ST 6A and 19A IPD and non-PCV10 excluding ST 6A-/19A-IPD (NVT-IPD). We used national surveillance data and compared average monthly incidence rate (IR) between pre- and post-period among <5, 5–49 and ≥50 years old. Additionally, for the 5–49 and ≥50 years old, and the 50–59 and ≥60 years old, we analyzed monthly incidence data of the pre-, post-period, and estimated trend and level changes by using a segmented time-series regression.ResultsThe PCV-10 IPD was reduced by 58% (95% CI: 30%; 74%) and 67% (95% CI: 32%; 84%) among <5 and ≥50 years old; the reduction in ≥60 years was 71% (95% CI: 36%; 88%). There were no significant changes in the pre-post-rate or incidence trend of NVT-IPD in the <5 and ≥50 years old. ST-specific analyses revealed no ST 6A- and ST 19A IPD decline in any age-group, and a ST 8 IPD increase among ≥50 years old (IR ratio: 3.5; 95% CI: 1.7; 7.2). We found no vaccine effects among 5–49 years old.ConclusionsOur study adds to the evidence on direct and indirect protection of a childhood PCV10 vaccine program. Elderlies seem to benefit the most. Findings did not support PCV 10 cross-protection, but indicate replacement at least for ST 8 among the ≥50 years old. Follow-up analyses of IPD surveillance data are needed to fully characterize the magnitude of serotype replacement and further vaccine-attributable IPD reduction with time.

The choice of analytical methodology can alter conclusions regarding herd effects of paediatric pneumococcal vaccination programmes

BackgroundEstimation of the magnitude of the herd effect on invasive pneumococcal disease (IPD) is important when evaluating health benefits and cost-effectiveness of paediatric pneumococcal conjugate vaccine (PCV) programmes and may influence policy makers’ decisions on PCV use. Several epidemiological, programmatic, and immunological factors can affect the magnitude of the PCV herd effect. We investigated to what extent the choice of analytical methodology may also influence herd effect estimates. MethodsTo estimate the magnitude of the herd effect from paediatric PCV programmes, we examined overall IPD incidence rates in ≥65-year-olds from Finland, Australia, England/Wales, and the United States under different analytical scenarios. We used two different statistical methods: before/after comparison of average IPD incidence rates and interrupted time series (ITS) analysis accounting for underlying time trends. We also investigated how varying the length of the pre- and post-PCV analysis periods influenced the outcomes. ResultsThe estimated impact of paediatric PCV programmes on IPD incidence rates in adults ≥65 years varied substantially across the different scenarios within each country. The choice of statistical method and analysis periods contributed to this variation, and their influence varied by setting. For the datasets from England/Wales and the United States, the different scenarios produced relatively minor variation in estimated impact. For the Australian and Finnish datasets, differences were more prominent. In particular, for Finland, opposite conclusions could be drawn depending on the methodology: while no estimated herd effect was seen with the before/after method, a herd effect was evident with the ITS method. ConclusionsThe choice of statistical method and analysis periods can substantially influence the magnitude of estimated herd effects from paediatric PCV programmes. It is important to consider the reliability and presence of pre-PCV patterns in the IPD surveillance data used for analysis, the methodology and associated assumptions used to estimate herd effects.

Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000–17: a prospective national observational cohort study

Pneumococcal conjugate vaccines (PCVs) have substantially reduced the incidence of invasive pneumococcal disease caused by vaccine serotypes; however, replacement disease with non-PCV serotypes remains a concern. We describe the population effect of the seven-valent and 13-valent PCVs (PCV7 and PCV13) on invasive pneumococcal disease in England and Wales. Using national invasive pneumococcal disease surveillance data for 2016/17, we compared incidence rate ratios (IRRs) against pre-PCV13 (2008/09-2009/10) and pre-PCV7 (2000/01-2005/06) baselines. We also estimated the number of invasive pneumococcal disease cases prevented since the introduction of PCVs. In 2016/17, overall invasive pneumococcal disease incidence (9·87 cases per 100 000; 5450 cases) across all age groups was 37% lower (IRR 0·63, 95% CI 0·60-0·65) than pre-PCV7 incidence (14·79 per 100 000; 8167 cases) and 7% lower (0·93; 0·89-0·97) than pre-PCV13 incidence (10·13 per 100 000; 5595 cases). By 2016/17, PCV7-type invasive pneumococcal disease incidence across all age groups had decreased by 97% (0·24 per 100 000; 0·03, 0·02-0·04) compared with the pre-PCV7 period, whereas additional PCV13-type invasive pneumococcal disease decreased by 64% (1·66 per 100 000; 0·36, 0·32-0·40) since the introduction of PCV13. Invasive pneumococcal disease incidence due to non-PCV13 serotypes doubled (7·97 per 100 000; 1·97, 1·86-2·09) since the introduction of PCV7, and accelerated since 2013/14-especially serotypes 8, 12F, and 9N, which were responsible for more than 40% of invasive pneumococcal disease cases by 2016/17. Invasive pneumococcal disease incidence in children younger than 5 years remained stable since 2013/14, with nearly all replacement disease occurring in adults. We estimated 38 366 invasive pneumococcal disease cases were prevented in the 11 years since the introduction of PCV7. Both PCV7 and PCV13 have had a major effect in reducing the burden of invasive pneumococcal disease in England and Wales; however, rapid increases in some non-PCV13 serotypes are compromising the benefits of the programme. Public Health England.

The incidence of invasive pneumococcal serotype 3 disease in the Danish population is not reduced by PCV-13 vaccination.

Since 2010, Denmark has included the 13-valent pneumococcal conjugated vaccine (PCV-13) in the childhood immunization programme. However, serotype 3 remains as an important cause of invasive pneumococcal disease (IPD) in Denmark. IPD surveillance data (1999–2016) was used to calculate the incidence and age-distribution of serotype 3 IPD, and the effect of PCV-13 on serotype 3 IPD incidence was examined. The incidence of serotype 3 IPD in the age group below 65 years was 0.51/100,000 pre PCV-13, and 0.45/100,000 post PCV-13. In the group 0–4 years, serotype 3 IPD incidence was 0.28/100,000 pre PCV-13, and 0.16/100,000 post PCV-13. Serotype 3 IPD incidence in the elderly showed a mean of 4.27/100,000 pre PCV-13, and 4.32/100,000 post PCV-13. PCV-13 childhood immunization in Denmark has not lead to a reduction of the incidence of IPD caused by serotype 3. The reason behind this missing effect needs to be investigated further.

Persistent Sex Disparities in Invasive Pneumococcal Diseases in the Conjugate Vaccine Era.

Few studies have characterized the role of sex on the incidence of invasive pneumococcal disease (IPD). We examined sex differences in rates of IPD, and trends after the introduction of pneumococcal conjugate vaccines (PCVs). We used active population and laboratory-based IPD surveillance data from the Centers for Disease Control and Prevention Active Bacterial Core surveillance program (1998-2013) in Tennessee. Population-based rates of IPD by sex, race, age group, and PCV era were calculated. Rates were compared using incidence rate ratios. Throughout the study years, rates of IPD were higher in male than in female subjects, particularly in children <2 years and adults 40-64 years of age, with male subjects having IPD rates 1.5-2 times higher than female subjects. The proportions of comorbid conditions were similar in male and female subjects . Sex rate differences persisted after stratification by race. Although the introductions of 7-valent PCV (PCV7) and 13-valent PCV (PCV13) were associated with declines in IPD rates in both sexes, rates of IPD after PCV13 were still significantly higher in male than in female subjects among children and adults 40-64 and >74 years of age. Rates of IPD were generally higher in male than in female subjects. These sex differences were observed in different race groups and persisted after introduction of both PCVs.

Invasive Pneumococcal Disease Following the Introduction of 13-Valent Conjugate Vaccine in Children in New York City From 2007 to 2012.

Invasive pneumococcal disease (IPD) is a leading cause of pneumonia, meningitis, and bacteremia in children. In March 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) was introduced to the routine childhood immunization schedule. The PCV13 contains 6 serotypes not included in the previously recommended 7-valent pneumococcal conjugate vaccine, including serotype 19A, the predominant cause of IPD prior to the introduction of PCV13. To describe changes in the epidemiology and incidence of IPD in children younger than 5 years in New York City (NYC) after the introduction of PCV13 and assess PCV13 coverage in NYC. Retrospective analysis of population-based IPD surveillance data of the general population residing in NYC between January 1, 2007, and December 31, 2012. Invasive pneumococcal disease cases were identified by laboratory reporting of positive pneumococcal cultures from a normally sterile body site in NYC residents younger than 5 years. Isolates were serotyped. Participants included 468 cases younger than 5 years with IPD reported through routine surveillance to the NYC Department of Health and Mental Hygiene. Absolute differences and percentage changes in IPD incidence before and after the introduction of PCV13 by serotype grouping, age, and race/ethnicity. The number of PCV13 doses administered to children younger than 5 years was calculated using the NYC immunization information system. There were 468 IPD cases from 2007 to 2012. The incidence of IPD decreased by 69.6% (95% CI, -79.3% to -55.5%) from 21.0 cases per 100 000 (2007-2009 mean) pre-PCV13 to 6.4 cases per 100 000 (2011-2012 mean) post-PCV13. Estimates of disease caused by serotypes included in the PCV13 decreased by 82.5% (95% CI, -90.0% to -69.3%), including a 79.7% reduction in serotype 19A (95% CI, -89.0% to -62.4%). Reductions in IPD incidence were seen in all age groups, with the largest reduction in children younger than 12 months (80.4%; P = .005). Incidence decreased significantly in all racial/ethnic groups. The percentage of children younger than 5 years in NYC with 1 or more doses of PCV13 increased from 47.8% in 2010 to 89.8% in 2012. The incidence of IPD in NYC children younger than 5 years and, particularly, the incidence of IPD caused by serotype 19A decreased dramatically following the introduction of PCV13, with reductions among all age and racial/ethnic groups. This represents a significant achievement for public health immunization programs and underscores the importance of achieving high immunization coverage.

Molecular characterization of Streptococcus pneumoniae serotype 12F isolates associated with rural community outbreaks in Alaska.

Outbreaks of invasive pneumococcal disease (IPD) caused by Streptococcus pneumoniae serotype 12F were observed in two neighboring regions of rural Alaska in 2003 to 2006 and 2006 to 2008. IPD surveillance data from 1986 to 2009 and carriage survey data from 1998 to 2004 and 2008 to 2009 were reviewed to identify patterns of serotype 12F transmission. Pulsed-field gel electrophoresis was performed on all available isolates, and selected isolates were characterized by additional genetic subtyping methods. Serotype 12F IPD occurred in two waves in Alaska between 1986 and 2008. While cases of disease occurred nearly every year in Anchorage, in rural regions, 12F IPD occurred with rates 10- to 20-fold higher than those in Anchorage, often with many years between disease peaks and generally caused by a single predominant genetic clone. Carriage occurred predominantly in adults, except early in the rural outbreaks, when most carriage was in persons <18 years old. In rural regions, carriage of 12F disappeared completely after outbreaks. Different 12F clones appear to have been introduced episodically into rural populations, spread widely in young, immunologically naïve populations (leading to outbreaks of IPD lasting 1 to 3 years), and then disappeared rapidly from the population. Larger population centers might have been the reservoir for these clones. This epidemiologic pattern is consistent with a highly virulent, but immunogenic, form of pneumococcus.

Use of surveillance data to estimate the effectiveness of the 7-valent conjugate pneumococcal vaccine in children less than 5 years of age over a 9 year period

BackgroundCase–control studies evaluating post-licensure effectiveness of conjugate vaccines can be laborious and costly. We applied an indirect cohort method to evaluate the effectiveness of seven-valent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) and compared the results to the effectiveness measured using a standard case–control study conducted during the same time period. MethodsIPD cases among children 2–59 months old were identified through the Active Bacterial Core surveillance system during 2001–2009. We used logistic regression to calculate the odds ratio of vaccination (versus no vaccination) among cases (PCV7-type IPD cases) and non-cases (non-PCV7-type IPD cases), controlling for the presence of underlying conditions. Vaccine effectiveness (VE) was calculated as one minus the adjusted odds ratio. ResultsAmong 4225 IPD cases reported during 2001–2009, 2680 (63%) had serotype information and vaccine history. Effectiveness of ≥1 dose of PCV7 against PCV7-types was 88% (95% confidence interval (CI) 78–94%) among children with comorbid conditions and 97% (95% CI 92–98%) among healthy children. Among healthy children, VE was higher in 2001–2003 (97%, 95% CI 95–98%) compared to 2004–2009 (81%, 95% CI 64–90%). The annual estimates of VE in 2004–2009 showed great variability and wide confidence intervals due to the small number of PCV7-type cases. ConclusionsAn indirect cohort design using IPD surveillance data confirms the findings of the case–control study and, therefore, appears suitable for estimating PCV7effectiveness. This method would be most useful shortly after vaccine introduction, and less useful in a setting of very high vaccine coverage and fewer vaccine-type cases.