Reduction In Invasive Pneumococcal Disease Research Articles

Non-pharmaceutical interventions for COVID-19 transiently reduced pneumococcal and Haemophilus influenzae carriage in a cross-sectional pediatric cohort in Southampton, UK.

The Southampton pneumococcal carriage study of children under 5 years old continued during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present data from October 2018 to March 2023 describing prevalence of pneumococci and other pathobionts during the winter seasons before, during, and after the introduction of non-pharmaceutical interventions (NPIs) to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nasopharyngeal swabs were collected from children attending outpatient clinics at a secondary care hospital and community healthcare sites. Pre-NPIs, in 2019/2020, the carriage prevalence of pneumococci at the hospital site was 32% (n = 161 positive/499 participants). During NPIs, this fell to 19% (n = 12/64), although based on fewer participants compared to previous years due to COVID-19 restrictions on health-care attendance. In 2021/2022, after NPIs had eased, prevalence rebounded to 33% (n = 15/46) [compared to NPIs period, χ2 (1, N = 110) =2.78, P = 0.09]. Carriage prevalence at community healthcare sites fell significantly from 27% (n = 127/470) in 2019/2020 to 19% during the NPI period (n = 44/228) in 2020/2021 [χ2 (1, N = 698) =4.95, P = 0.026]. No rebound was observed in 2021/2022 [19% (n = 56/288)]. However, in a multivariate logistic regression model, neither site had a significantly lower carriage prevalence during the NPI period compared to the post NPI period. A reduction in serotype diversity was observed in 2020/2021. Carriage of Haemophilus influenzae was particularly affected by NPIs with a significant reduction observed. In conclusion, among children under 5 years of age, transient, modest, and statistically non-significant alterations in carriage of both Streptococcus pneumoniae and H. influenzae were associated with SARS-CoV-2 NPIs.IMPORTANCEStreptococcus pneumoniae (the pneumococcus) continues to be a major contributor to global morbidity and mortality. Using our long-running pediatric study, we examined changes in pneumococcal carriage prevalence in nearly 3,000 children under the age of 5 years between the winters of 2018/2019 and 2022/2023. This period coincided with the severe acute respiratory syndrome coronavirus 2 pandemic and, in particular, the implementation of national strategies to limit disease transmission in the UK. We observed a transient reduction of both Streptococcus pneumoniae and Haemophilus influenzae in these populations during this period of non-pharmaceutical interventions. This aligned with the reduction in invasive pneumococcal disease seen in the UK and is therefore a likely contributor to this phenomenon.

The impact of introduction of the 10-valent pneumococcal conjugate vaccine on pneumococcal carriage in Nigeria

Pneumococcal conjugate vaccines (PCVs) protect against invasive pneumococcal disease (IPD) among vaccinees. However, at population level, this protection is driven by indirect effects. PCVs prevent nasopharyngeal acquisition of vaccine-serotype (VT) pneumococci, reducing onward transmission. Each disease episode is preceded by infection from a carrier, so vaccine impacts on carriage provide a minimum estimate of disease reduction in settings lacking expensive IPD surveillance. We documented carriage prevalence and vaccine coverage in two settings in Nigeria annually (2016–2020) following PCV10 introduction in 2016. Among 4,684 rural participants, VT carriage prevalence fell from 21 to 12% as childhood (<5 years) vaccine coverage rose from 7 to 84%. Among 2,135 urban participants, VT carriage prevalence fell from 16 to 9% as uptake rose from 15 to 94%. Within these ranges, carriage prevalence declined with uptake. Increasing PCV10 coverage reduced pneumococcal infection at all ages, implying at least a comparable reduction in IPD.

Impact of COVID-19 Nonpharmaceutical Interventions on Pneumococcal Carriage Prevalence and Density in Vietnam.

Nonpharmaceutical interventions (NPIs) implemented to contain SARS-CoV-2 have decreased invasive pneumococcal disease. Previous studies have proposed the decline is due to reduced pneumococcal transmission or suppression of respiratory viruses, but the mechanism remains unclear. We undertook a secondary analysis of data collected from a clinical trial to evaluate the impact of NPIs on pneumococcal carriage and density, drivers of transmission and disease, during the COVID-19 pandemic in Ho Chi Minh City, Vietnam. Nasopharyngeal samples from children aged 24 months were assessed in three periods - one pre-COVID-19 period (n = 1,537) and two periods where NPIs were implemented with increasing stringency (NPI period 1 [NPI-1, n = 307], and NPI period 2 [NPI-2, n = 262]). Pneumococci were quantified using lytA quantitative PCR and serotyped by DNA microarray. Overall, capsular, and nonencapsulated pneumococcal carriage and density were assessed in each NPI period compared with the pre-COVID-19 period using unadjusted log-binomial and linear regression. Pneumococcal carriage was generally stable after the implementation of NPIs. In contrast, overall pneumococcal carriage density decreased by 0.44 log10 genome equivalents/mL (95% confidence interval [CI]: 0.19 to 0.69) in NPI-1 and by 0.84 log10 genome equivalents/mL (95% CI: 0.55 to 1.13) in NPI-2 compared with the pre-COVID-19 period. Reductions in overall pneumococcal density were driven by reductions in capsular pneumococci, with no corresponding reduction in nonencapsulated density. As higher pneumococcal density is a risk factor for disease, the decline in density provides a plausible explanation for the reductions in invasive pneumococcal disease that have been observed in many countries in the absence of a substantive reduction in pneumococcal carriage. IMPORTANCE The pneumococcus is a major cause of mortality globally. Implementation of NPIs during the COVID-19 pandemic led to reductions in invasive pneumococcal disease in many countries. However, no studies have conducted a fully quantitative assessment on the impact of NPIs on pneumococcal carriage density, which could explain this reduction. We evaluated the impact of COVID-19 NPIs on pneumococcal carriage prevalence and density in 2,106 children aged 24 months in Vietnam and found pneumococcal carriage density decreased up to 91.5% after NPI introduction compared with the pre-COVID-19 period, which was mainly attributed to capsular pneumococci. Only a minor effect on carriage prevalence was observed. As respiratory viruses are known to increase pneumococcal carriage density, transmission, and disease, this work suggests that interventions targeting respiratory viruses may have the added benefit of reducing invasive pneumococcal disease and explain the reductions observed following NPI implementation.

Invasive pneumococcal surveillance to assess the potential benefits of extended spectrum conjugate vaccines (PCV15/PCV20) in older adults.

The introduction of pneumococcal conjugate vaccines (PCV) into the childhood vaccination programme has reduced invasive pneumococcal disease (IPD). Although anticipated from data elsewhere, surveillance in Ireland has confirmed reductions in IPD amongst those ⩾65 years of age due to a decline of PCV serotypes in this age group. Currently, direct protection against IPD in the elderly is focused on immunisation with the 23-valent pneumococcal polysaccharide vaccine (PPV23). However, immunity may not be as effective as with PCV and, furthermore, PPV23 uptake is poor in Ireland. Hence, consideration should be given to providing a PCV to this age group.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

Global Epidemiology of Vaccine-preventable Bacterial Meningitis.

1299. Epidemiology of Invasive Pneumococcal Disease (IPD) in the United States 2011-2019

Abstract Background Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for U.S. children aged &amp;lt; 5 years in February 2010 and recommended in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥ 65 years in 2014. PCV13 has led to dramatic reductions in invasive pneumococcal disease (IPD) burden. New, higher valency PCVs (PCV15, PCV20) are expected to be licensed for adults in late 2021. We examined remaining PCV13-type IPD among children and adults and assessed IPD burden potentially preventable through PCV15 and PCV20 use. Methods IPD cases (isolation of pneumococcus from sterile sites) were identified through CDC’s Active Bacterial Core surveillance during 1998–2019. Isolates were serotyped by Quellung or whole genome sequencing. Incidence rates (cases/100,000) were calculated using U.S. Census Bureau population denominators. Results After introduction of PCV13 in children, by 2013–2014, PCV13-type IPD declined 89% (from 15 to 2 cases/100,000) in children age &amp;lt; 5 years and 67% (from 19 to 7 cases/100,000) in adults age ≥ 65 years. During 2014–2019, rates of PCV13-type IPD in children and adults remained stable. In 2018–2019, among children age &amp;lt; 5 years, serotypes 3, 19F, 19A, and 6C accounted for most of the remaining PCV13-type IPD (46%, 32%, 14% and 4% respectively) (Figure 1). Among adults age ≥ 65 years, serotypes 3, 6C, 19A, and 19F accounted for most of the remaining PCV13-type IPD (62%, 12%, 10%, and 9% respectively) (Figure 1). During 2015–2019, rates of PCV15 and PCV20-type IPD have remained stable. In 2018–2019, among adults age ≥ 65 years, PCV15 non-PCV13-type IPD rates were 3.6 cases per 100,000 and accounted for 15% of all IPD. PCV20 non-PCV13-type IPD rates were 6.8 cases per 100,000 and accounted for 29% of all IPD (Figure 2). Among children age &amp;lt; 5 years, PCV15 non-PCV13-type IPD rates were 1.6 cases per 100,000 and accounted for 17% of all IPD. PCV20 non-PCV13-type IPD rates were 2.8 cases per 100,000 and accounted for 39% of all IPD (Figure 2). Figure 1. Incidence rates of IPD among children &amp;lt; 5 years old, by pneumococcal conjugate vaccine type and individual PCV13 serotypes, 2011–2019 Figure 2. Incidence rates of IPD among adults ≥ 65 years old, by pneumococcal conjugate vaccine type and individual PCV13 serotypes, 2011–2019 Conclusion Following the dramatic reductions after PCV13 introduction, PCV13-type IPD has remained stable during the past five years. There are opportunities to prevent an additional 30% IPD burden among adults through new PCV use. Disclosures William Schaffner, MD, VBI Vaccines (Consultant) Lee Harrison, MD, GSK, Merck, Pfizer, Sanofi Pasteur (Consultant)

Structural, Genetic, and Serological Elucidation of Streptococcus pneumoniae Serogroup 24 Serotypes: Discovery of a New Serotype, 24C, with a Variable Capsule Structure.

Pneumococcal capsules are important in pneumococcal pathogenesis and vaccine development. Although conjugate vaccines have brought about a significant reduction in invasive pneumococcal disease (IPD) caused by vaccine serotypes, the relative serotype prevalence has shifted with the dramatic emergence of serotype 24F in some countries. Here, we describe 14 isolates (13 IPD and 1 non-IPD) expressing a new capsule type, 24C, which resembles 24F but has a novel serological profile. We also describe the antigenic, biochemical, and genetic basis of 24F and 24C and the related serotypes 24A and 24B. Structural studies show that 24B, 24C, and 24F have identical polysaccharide backbones [β-Ribf-(1→4)-α-Rhap-(1→3)-β-GlcpNAc-(1→4)-β-Rhap-(1→4)-β-Glcp] but with different side chains, as follows: 24F has arabinitol-phosphate and 24B has ribitol-phosphate. 24C has a mixture of 24F and 24B repeating units, with the ratio of ribitol to arabinitol being strain dependent. In contrast, the 24A capsule has a backbone without β-Ribf but with arabinitol-phosphate and phosphocholine side chains. These structures indicate that factor-sera 24d and 24e recognize arabinitol and ribitol, respectively, which explains the serology of serogroup 24, including those of 24C. The structures can be genetically described by the bispecificity of wcxG, which is capable of transferring arabinitol or ribitol when arabinitol is limiting. Arabinitol is likely not produced in 24B but is produced in reduced amounts in 24C due to various mutations in abpA or abpB genes. Our findings demonstrate how pneumococci modulate their capsule structure and immunologic properties with small genetic changes, thereby evading host immune responses. Our findings also suggest a potential for new capsule types within serogroup 24.

1475. Impact of a Routine Infant PCV Program on the Serotype Distribution of Episodes of Invasive Pneumococcal Disease (IPD) and Non-bacteremic Pneumococcal Pneumonia in Adults

BackgroundHerd immunity from pediatric pneumococcal conjugate vaccine (PCV) programs has resulted in substantial reductions in IPD due to PCV serotypes (ST). We assessed whether similar changes in ST distribution occur in non-bacteremic pneumococcal pneumonia (NBPP).MethodsThe Toronto Invasive Bacterial Diseases Network performs population-based surveillance for IPD and hospitalized, culture-confirmed NBPP in Toronto/Peel Region, Canada (Pop 4.5M). Patient data are collected by interview/chart review; illness associated with respiratory isolates is categorized using Musher criteria.ResultsSince 2002, 6627 episodes of IPD, and 7323 non-bacteremic episodes with a respiratory isolate of S. pneumoniae (2180 meeting modified Musher criteria for NBPP) have occurred in adults. Distributions of vaccine-type serotypes in IPD and NBPP pre-PCV7 (2002-2004), post-PCV7 (2006-2009) and late post-PCV13 (2014-2019) are shown in the Figure. There were no significant changes in distribution of vaccine serotype groups from 2014-2019 in IPD or NBPP. From 2014-2019, serotypes included in PCV13 and PCV20 were associated with 33% and 59% of IPD cases, and 29% and 49% of NBPP cases in adults..Figure. distribution of serotype groups included in different pneumococcal vaccines in cases of IPD and non-bacteremic pneumonia ConclusionEight years post routine infant PCV13 implementation, PCV13 type IPD and NBPP persists in adults. The distribution of vaccine-type strains is similar in IPD and NBPP; although non-vaccine-type strains are more common in NBPP.Disclosures Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)

Impact of PCV-13 vaccine on invasive pneumococcal disease in hospitalised children: A multi-institutional analysis.

We aimed to describe changes in invasive pneumococcal disease (IPD) hospitalisations after introduction of the pneumococcal conjugate vaccine (PCV13). This was a retrospective analysis of the Pediatric Health Information System (PHIS) database, including children with IPD pre-PCV13 (2004-2009) and post-PCV13 (2012-2017). Healthy children and those with chronic conditions were analysed separately. The primary outcome was IPD incidence. Secondary outcomes included length of stay, intensive care unit (ICU) admission, mechanical ventilation and mortality. 9160 hospitalisations for IPD were included. The IPD rate per 100000 discharges was 180 pre-PVC13 and 150 post-PCV13 [17% decrease (P=0.085)]. The observed IPD rate in 2017 was 45.5% lower than the rate predicted by the pre-PCV13 trend (95% CI: 44%-46%). While a significant decrease in IPD (32%, P=0.026) was observed among healthy children, there was no change in those with chronic conditions (9%, P=0.24). In the post-PCV13 period, more IPD patients had chronic conditions, ICU admissions and longer ICU stays. Although there was no overall reduction in IPD after PCV13, we observed a significant decrease in IPD among healthy patients. Further research is needed to elucidate microbiology or other factors contributing to persistent IPD hospitalisations.

Incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate pneumococcal vaccine in British Columbia: A retrospective cohort study.

A significant reduction in invasive pneumococcal disease (IPD) has been reported, across all ages, following the implementation of 7-valent conjugate pneumococcal vaccine (PCV7) globally, as part of infant immunization programs. We explored the additional impact of PCV13 on IPD over a 14-year period. Using provincial laboratory surveillance and hospitalization data (N = 5791), we calculated the annual incidence of IPD following the implementation of PCV13 vaccine. Poisson regression was used to evaluate changes in the overall incidence of IPD, and serotype-specific IPD between PCV7 (2004-10) and PCV13 (2011-2015) eras. Overall, IPD rates have seen a modest decline in the PCV13 compared to the PCV7 era (IRR 0.84; 95% CI: 0.79-0.89); this was seen in children ≤2 years of age, and the majority of the adult cohort. Rates of vaccine-type IPD (PCV7 and PCV13) also decreased in the PCV13 era. In contrast, IPD incidence related to non-PCV13 (IRR: 1.56; 95%CI:1.43-1.72) and non-vaccine serotypes (IRR: 2.12; 95%CI:1.84-2.45) increased in the PCV13 era compared to the PCV7 era. A modest reduction in IPD from the PCV13 vaccine was observed, with gains limited to the immunized cohort and adults. However, a significant increase in non-vaccine serotypes emphasizes the need for continued surveillance.

Impact and Effectiveness of 13-Valent Pneumococcal Conjugate Vaccine on Population Incidence of Vaccine and Non-Vaccine Serotype Invasive Pneumococcal Disease in Blantyre, Malawi, 2006-2018: Prospective Observational Time-Series and Case-Control Studies

Background: Population impact of pneumococcal conjugate vaccines (PCV) depend on direct and indirect protection. Following Malawi’s 2011 introduction of the 13-valent PCV (PCV13), we examined impact on vaccine serotype (VT) and non-VT (NVT) invasive pneumococcal disease (IPD) among vaccine-age-eligible and vaccine-age-ineligible children and adults. Methods: Laboratory-based surveillance at a government hospital in Malawi included 6 years before and 7 years after PCV13 introduction. Using negative-binomial regression, we evaluated secular trend-adjusted Incidence Rate Ratio (IRR) in VT- and NVT-IPD prior to and post PCV introduction. We compared predicted counterfactual incidence in hypothetical absence of vaccine with empirically observed incidence following vaccine introduction. A case-control study assessed vaccine effectiveness compared PCV uptake among vaccine-age-eligible IPD cases versus matched community controls. Findings: Surveillance covered 10 281 476 person-years observation, with 140 498 blood and 63 291 cerebrospinal fluid cultures. IPD decline preceded PCV introduction. Compared to the counterfactually predicted incidence, post-vaccine VT-IPD incidence was 38% (95%CI: 37, 40) lower among infants, 74% (70, 78) among young children, 79% (76, 83) among older children and 47% (44, 51) among adolescents and adults. Though NVT-IPD has increased since 2015 , absolute rates remain low. The case-control study, (19 cases and 76 controls), showed vaccine effectiveness against VT-IPD of 80·7% (-73·7, 97·9). Interpretation: Even with pre-existing declines, infant PCV13 introduction has led to substantial IPD reduction among vaccine-age-eligible children. However, seven years after PCV introduction, indirect effects benefitting unvaccinated infants and adults were more modest. Policy decisions should consider alternative strategies, including targeted vaccination outside infant EP to benefit vulnerable populations. Funding Statement: This work was funded by Bill & Melinda Gates Foundation, USA (OPP117653) to RSH and a Wellcome Trust Programme Grant (WT091909/B/10/Z) to NF, NAC, RSH; National Institute for Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens using UK aid from the UK Government (Project number 16/136/46) to RSH. The MLW Clinical Research Programme is supported by a Strategic Award from the Wellcome Trust, UK (206545/Z/17/Z) to SG. Declaration of Interests: NBZ, NAC & NF have received investigator-initiated research grants from GlaxoSmithKline Biologicals. NBZ & NAC received investigator-initiated research grants from Takeda Pharmaceuticals. NAC has received research grant support and honoraria for participation in rotavirus vaccine advisory board meetings from GlaxoSmithKline Biologicals. All other authors declare no competing interests. Ethics Approval Statement: The study protocol was approved by Malawi’s National Health Sciences Research Committee (NHSRC; protocol 867), by the University of Malawi College of Medicine Research and Ethics Committee (COMREC; P.01/08/609 and P.09/09/826) and the University of Liverpool Research Ethics Committee (UoLREC; RETH490). The Centers for Disease Control and Prevention relied on the UoLREC for ethical approval. For the case-control component, the parent/guardian of all child participants provided written informed consent and, in addition, children 8 years or older provided written informed assent. This included consent for publication.

2701. The Impact of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Children in British Columbia, Canada

BackgroundA significant reduction in invasive pneumococcal disease (IPD) has been reported following implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) infant immunization program, but not much has been reported after introduction of the 13-valent vaccine (PCV13). This study represents the effect of PCV13 on IPD in British Columbia, Canada over a 14 year period (2002–2015).MethodsUsing provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in children less than 17 years of age. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression.ResultsA total of 697 cases were reported over the 14 year period. The overall annual incidence decreased from 10.9 cases per 100,000 population in 2002 to 4.64 cases per 100,000 population in 2015. While overall decline of IPD was 59% (IRR 0.41; 95% CI: 0.35–0.51) compared with baseline, this reduction was greatest after introduction of PCV7 (IRR 0.44; 95% CI: 0.37–0.53); the incremental change after introduction of PCV13 was non-significant (IRR 0.94; 95% CI: 0.78–1.13). The greatest reduction in IPD was in children <2 years of age (PCV13 vs baseline: IRR 0.19; 95% CI: 0.14–0.25), followed by children 3–5 years of age (PCV13 vs baseline: IRR 0.34; 95% CI: 0.21–0.56); no significant change was observed in 6–17 year olds.ConclusionWhile IPD rates have been significantly reduced since the introduction of the PCV vaccines, the impact of the additional 6 serotypes in the PCV13 vaccine is non-significant.Disclosures All authors: No reported disclosures.

2706. Indirect Effects of Infant 13-valent Conjugate Pneumococcal Vaccination Program on Invasive Pneumococcal Disease in Adults in British Columbia, Canada

BackgroundMany jurisdictions report a significant reduction in invasive pneumococcal disease (IPD) in adults following implementation of the pneumococcal conjugate vaccines, 7-valent (PCV7) and 13-valent (PCV13) in childhood immunization programs. This study evaluates the indirect effect of conjugate vaccines on IPD in British Columbia, Canada over a 14 year period (2002–2015).MethodsUsing provincial IPD laboratory surveillance data, we calculated the annual incidence following implementation of PCV7 (September 2004), and PCV13 (September 2010) in adults 18 years of age and older. We also compared incidence rate ratios (IRR) against pre-PCV13 (2004–2010) and pre-PCV7 (2002–2003) baselines for overall and age-specific IPD rates using Poisson regression.ResultsA total of 3793 cases were reported over the 14 year period. The overall annual incidence increased from 4.32 cases per 100,000 population in 2002 to 8.61 cases per 100,000 population in 2015. Overall, IPD has increased by 80% (IRR: 1.80; 95% CI: 1.59–2.04) compared with baseline, especially in adults ≥ 85 years of age (PCV13 vs baseline: IRR: 1.90; 95% CI: 1.25–03.05). This increase was the highest after introduction of PCV7 (IRR: 1.87; 95% CI: 1.65–2.11); the incremental change after introduction of PCV13 was non-significant (IRR 0.96; 95% CI: 0.90–1.03). While PCV7 type IPD plummeted by 76% (IRR 0.24; 95% CI: 0.18–0.31) since introduction of PCV7 compared with baseline, a modest decline in PCV13 type IPD of 20% was seen (IRR 0.80; 95% CI: 0.71–0.89) since introduction of PCV13.ConclusionAlthough PCV7-type IPD has decreased substantially, only a modest reduction in IPD from the additional 6 serotypes in the PCV13 vaccine was observed.Disclosures All authors: No reported disclosures.

Effect of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease and nasopharyngeal carriage in Kenya: a longitudinal surveillance study

SummaryBackgroundTen-valent pneumococcal conjugate vaccine (PCV10), delivered at 6, 10, and 14 weeks of age was introduced in Kenya in January, 2011, accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years. Coverage with at least two PCV10 doses in children aged 2–11 months was 80% in 2011 and 84% in 2016; coverage with at least one dose in children aged 12–59 months was 66% in 2011 and 87% in 2016. We aimed to assess PCV10 effect against nasopharyngeal carriage and invasive pneumococcal disease (IPD) in children and adults in Kilifi County.MethodsThis study was done at the KEMRI-Wellcome Trust Research Programme among residents of the Kilifi Health and Demographic Surveillance System, a rural community on the Kenyan coast covering an area of 891 km2. We linked clinical and microbiological surveillance for IPD among admissions of all ages at Kilifi County Hospital, Kenya, which serves the community, to the Kilifi Health and Demographic Surveillance System from 1999 to 2016. We calculated the incidence rate ratio (IRR) comparing the prevaccine (Jan 1, 1999–Dec 31, 2010) and postvaccine (Jan 1, 2012–Dec 31, 2016) eras, adjusted for confounding, and reported percentage reduction in IPD as 1 minus IRR. Annual cross-sectional surveys of nasopharyngeal carriage were done from 2009 to 2016.FindingsSurveillance identified 667 cases of IPD in 3 211 403 person-years of observation. Yearly IPD incidence in children younger than 5 years reduced sharply in 2011 following vaccine introduction and remained low (PCV10-type IPD: 60·8 cases per 100 000 in the prevaccine era vs 3·2 per 100 000 in the postvaccine era [adjusted IRR 0·08, 95% CI 0·03–0·22]; IPD caused by any serotype: 81·6 per 100 000 vs 15·3 per 100 000 [0·32, 0·17–0·60]). PCV10-type IPD also declined in the post-vaccination era in unvaccinated age groups (<2 months [no cases in the postvaccine era], 5–14 years [adjusted IRR 0·26, 95% CI 0·11–0·59], and ≥15 years [0·19, 0·07–0·51]). Incidence of non-PCV10-type IPD did not differ between eras. In children younger than 5 years, PCV10-type carriage declined between eras (age-standardised adjusted prevalence ratio 0·26, 95% CI 0·19–0·35) and non-PCV10-type carriage increased (1·71, 1·47–1·99).InterpretationIntroduction of PCV10 in Kenya, accompanied by a catch-up campaign, resulted in a substantial reduction in PCV10-type IPD in children and adults without significant replacement disease. Although the catch-up campaign is likely to have brought forward the benefits by several years, the study suggests that routine infant PCV10 immunisation programmes will provide substantial direct and indirect protection in low-income settings in tropical Africa.FundingGavi, The Vaccine Alliance and The Wellcome Trust of Great Britain.

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.

Impact of the 10-valent pneumococcal conjugate vaccine on the southern area of Santiago (Chile), 2009-2015Efeito da vacina pneumocócica 10-valente conjugada na região sul de Santiago, Chile, 2009-2015

RESUMENObjetivoEl objetivo de este estudio fue evaluar el efecto de la incorporación de la vacuna antineumococica 10-valente (PCV 10) en la incidencia de la enfermedad neumocócica invasora (ENI) y en la neumonía adquirida en la comunidad (NAC) en niños hospitalizados menores de 5 años en el área sur de Santiago de Chile.MétodosSe realizó un estudio ecológico de la incidencia de ENI y NAC en menores de 5 años del área sur de Santiago de Chile de 2009 a 2015. Las fuentes de información utilizadas fueron las de los laboratorios de bacteriología de cuatro hospitales, del Instituto de Salud Pública de Chile (ISP) y los registros de egresos hospitalarios.ResultadosUn total de 6 461 casos de NAC y 173 casos de ENI fueron confirmados por el ISP, de los cuales 169 casos fueron diagnosticados en los laboratorios de bacteriología de los hospitales incluidos en el estudio. Al comparar la incidencia de casos de 2010 frente a 2011-2015, la razón de incidencias (RI) de ENI se redujo 10% anualmente (p = 0,026) y la de NAC, 8% en el mismo período (p <0,001). El total de días cama ocupados en el período 2009-2015 fue de 39 565 con una mediana de días cama ocupados entre 4 y 5. Hasta 2012 fallecieron 7 niños y desde entonces no ha habido fallecimientos por estas enfermedades.ConclusionesLa incorporación de la vacuna PCV-10 en el Programa Nacional de Inmunizaciones tuvo un efecto positivo, con una reducción significativa de las ENI y NAC y de la ocupación de camas por ENI y evitó casos y muertes.

1572. Conjugate Pneumococcal Vaccination Reduces Invasive Pneumococcal Disease Post Haemotopoietic Stem Cell Transplant

BackgroundImmunosuppressed patients, especially haematopoietic stem cell transplant (HSCT) recipients, are particularly vulnerable to invasive pneumococcal disease (IPD). However, uptake of pneumococcal vaccination tends to be lower in the immunosuppressed, partly due to concerns of vaccine effectiveness. Our institution introduced protocolised 10- or 13-valent conjugate pneumococcal vaccination (PCV) to all allogeneic and autologous HSCT recipients in 2010 to replace routine 23-valent polysaccharide vaccine (PPV23).MethodsWe conducted a retrospective single-centre observational study of all HSCT recipients from 2004 to 2015 to assess the impact of PCV introduction on IPD incidence. All HSCT recipients were reviewed for microbiological evidence of IPD following HSCT. The pre-2010 group of HSCT recipients who did not receive PCV, were compared with the post-2010 group of HSCT recipients who did receive PCV. Enrolment and compliance with the post-HSCT vaccination protocol was assessed.ResultsOf the 917 HSCT screened for IPD, 14 episodes of IPD occurred in 12 patients between 2004 and 2016. Twelve episodes occurred in the pre-2010 group, 40% of serotyped isolates would have been covered by PCV. Two episodes occurred in the post-2010 group, neither isolate serotype was covered by PCV. There was >90% enrolment and vaccination protocol completion for surviving HSCT recipients. Overall IPD rate reduced significantly from 31.9/1,000 transplants pre-2010, to 3.7/1,000 transplants post-2010 group (P < 0.05). Specific reductions occurred in the autologous transplant group from 26.2 to 2.8/1,000 transplants (P < 0.05) and the allogeneic transplant group from 45.5 to 5.3/1,000 transplants (P < 0.05).ConclusionIntroduction of PCV resulted in a significant reduction in IPD among our high-risk cohort, demonstrating clinical effectiveness of PCV in HSCT recipients and confirming immunogenicity data. To our knowledge, this is the first study to demonstrate the clinical effectiveness of PCV in this group, highlighting the importance of this vaccination to prevent infectious complications following allogeneic and autologous HSCT. The clinical effectiveness of PCV vaccine is enhanced by the high quality of our post-HSCT vaccination program.Disclosures All authors: No reported disclosures.

1427. A Dynamic Modeling Study of the Effect of Introducing a New Higher Valent Pneumococcal Conjugate Vaccine in a Paediatric Population in the United States

BackgroundRoutine use of pneumococcal conjugate vaccines (PCVs) in young children has substantially reduced vaccine-type invasive pneumococcal disease (IPD) in the United States and Europe. However, increases in disease and colonization caused by nonvaccine serotypes have been observed, suggesting the need for new PCVs with broader serotype coverage. The aim of this study was to estimate the population-level impact of new PCVs to replace the existing 13-valent vaccine (PCV13) in infants.MethodsAn age-structured dynamic transmission model of Streptococcus pneumoniae before and after PCVs introduction was developed. The model was fit to longitudinal Active Bacterial Core surveillance (ABCs) data (1997–2015) in the United States on distribution and cases of IPD, as well as population level prevalence and serotype distribution data. It was assumed that total S. pneumoniae carriage remains constant over time, with full carriage replacement within four years of introduction of any PCV. Two alternative new PCVs with differing IPD coverage are tested with an introduction date of 2024.ResultsWhen compared with continuing vaccination of infants with PCV13, 10 years after a new PCV is introduced (2,034) cases of IPD are substantially reduced (shown in the table below). Broader serotype coverage leads to greater reductions in IPD. The greatest IPD reduction occurs in the directly vaccinated infant groups, however similar reductions are also observed in the unvaccinated elderly population due to herd protection.Additional Vaccine Coverage Over PCV13 (2016/2024)aIPD Incidence Rate Reduction [%] (2,024 vs. 2,034)<2 Years2–5 Years50–64 Years≥65 YearsAll Ages11–21%/32–35%363533313115–30%/42–45%4242413940 aDefined as the proportion of IPD cases that are caused by serotypes covered by the new PCV in 2016/2024 (a range of values is given because of differences by age group; values differ between 2016 and 2024 as serotype prevalence has not reached steady state as of 2016).ConclusionA new, higher valent PCV given to infants in the United States has the potential to reduce future cases of IPD. Vaccination of infants may also have a substantial indirect benefit on IPD cases in adults and the elderly.Disclosures M. Madin-Warburton, Sanofi Pasteur: Consultant, IQVIA received consultancy fee. A. B. Pitcher, Sanofi Pasteur: Consultant, IQVIA received consultancy fee. M. H. Kyaw, Sanofi Pasteur: Employee, Salary. A. Kieffer, Sanofi Pasteur: Employee, Salary.

Dynamics of Severe and Non-severe Invasive Pneumococcal Disease in Young Children in Israel Following PCV7/PCV13 Introduction.

The introduction of the pneumococcal conjugated vaccines (PCVs) resulted in a substantial reduction of invasive pneumococcal disease (IPD) rates. However, impact on nonsevere IPD (mostly occult bacteremia) has not yet been fully elucidated. We assessed severe and nonsevere IPD (SIPD and NSIPD, respectively) rate dynamics in children < 5 years in Israel before and after PCV7/PCV13 implementation. A prospective, population-based, nationwide surveillance. All IPD episodes recorded from 1999 through 2015 were included. NSIPD was defined as IPD episodes without meningitis, pneumonia or mastoiditis in a child with a favorable outcome (not hospitalized or hospitalized in a nonintensive care unit < 5 days, without mortality). Three subperiods were defined: pre-PCV (1999-2008), PCV7 (2010-2011) and PCV13 (2013-2015). Incidence rate ratios (IRRs) were calculated. Overall, 4,457 IPD episodes were identified; 3,398 (76.2%) SIPD, 1,022 (22.9%) NSIPD and 37 (0.8%) unknown. In 90% of NSIPD episodes, no focus was identified. In the PCV7 period, NSIPD rates significantly declined by 52%, while SIPD rates declined less prominently by 24%. Following PCV13 introduction, compared with the PCV7 period, NSIPD rates declined nonsignificantly by 17% while SIPD rates declined significantly further by an additional 53%. These trends resulted in overall reductions (comparing PCV13 and pre-PCV periods) of NSIPD and SIPD of 60% (IRR = 0.4; 0.32-0.51) and 64% (IRR = 0.36; 0.32-0.42), respectively. Following PCV7/PCV13 introduction, SIPD and NSIPD rates substantially declined, with differences in rate-dynamics, alluding to differences in serotype distribution between the 2 groups. Future surveillance is warranted when considering modification in treatment protocols for suspected occult bacteremia/NSIPD cases.

Elucidating the impact of the pneumococcal conjugate vaccine programme on pneumonia, sepsis and otitis media hospital admissions in England using a composite control

BackgroundThe seven-valent pneumococcal conjugate vaccine (PCV) was introduced in England in September 2006, changing to the 13-valent vaccine in April 2010. PCV impact on invasive pneumococcal disease (IPD) has been extensively reported, but less described is its impact on the burden of pneumonia, sepsis and otitis media in the hospital.MethodsUsing details on all admissions to hospitals in England, we compared the incidence of pneumococcal-specific and syndromic disease endpoints in a 24-month pre-PCV period beginning April 2004 to the 24-month period ending March 2015 to derive incidence rate ratios (IRRs). To adjust for possible secular trends in admission practice, IRRs were compared to the IRRs for five control conditions over the same period and the relative change assessed using the geometric mean of the five control IRRs as a composite, and individually for each control condition to give the min-max range. Relative changes were also compared with IRRs for IPD from the national laboratory database. The effect of stratifying cases into those with and without clinical risk factors for pneumococcal infection was explored.ResultsRelative reductions in pneumococcal pneumonia were seen in all age groups and in those with and without risk factors; in children under 15 years old reductions were similar in magnitude to reductions in IPD. For pneumonia of unspecified cause, relative reductions were seen in those under 15 years old (maximum reduction in children under 2 years of 34%, min-max: 11–49%) with a relative increase in 65+ year olds most marked in those with underlying risk conditions (41%, min-max: 0–82%). Reductions in pneumococcal sepsis were seen in all age groups, with the largest reduction in children younger than 2 years (67%, min-max 56–75%). Reductions in empyema and lung abscess were also seen in under 15 year olds. Results for other disease endpoints were varied. For disease endpoints showing an increase in raw IRR, the increase was generally reduced when expressed as a relative change.ConclusionsUse of a composite control and stratification by risk group status can help elucidate the impact of PCV on non-IPD disease endpoints and in vulnerable population groups. We estimate a substantial reduction in the hospitalised burden of pneumococcal pneumonia in all age groups and pneumonia of unspecified cause, empyema and lung abscess in children under 15 years of age since PCV introduction. The increase in unspecified pneumonia in high-risk 65+ year olds may in part reflect their greater susceptibility to develop pneumonia from less pathogenic serotypes that are replacing vaccine types in the nasopharynx.