Rates Of Invasive Pneumococcal Disease Research Articles

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.

Decline in Pneumococcal Disease Attenuated in Older Adults and Those With Comorbidities Following Universal Childhood PCV13 Immunization.

BackgroundFollowing introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the United States, epidemiology of pneumococcal disease shifted such that disease incidence in the elderly exceeded that in children. We evaluated the impact of replacing PCV7 with PCV13 on disease burden in adults and identified age/risk-specific subgroups with the highest remaining disease burden.MethodsA retrospective design and data from two US healthcare claims repositories were used. Study population included adults aged ≥18 years and was stratified by age (18–49, 50–64, 65–74, ≥75) and risk profile (healthy, at-risk, high-risk). Rate ratios comparing invasive pneumococcal disease (IPD), all-cause hospitalized pneumonia (ACHP), and pneumococcal pneumonia requiring hospitalization among at-risk and high-risk adults vs healthy counterparts were estimated for 2007–2010 (pre-PCV13), 2011–2012 (peri-PCV13), and 2013–2015 (post-PCV13).ResultsAcross study periods, IPD and ACHP rates increased with age (2–27 times higher in persons ≥75 vs 18–49) and comorbidity (4–20 times higher in high-risk vs healthy). From pre- to post-PCV13 period, IPD rates declined 5%–48% and ACHP rates declined 4%–19% across age and risk groups (ACHP did not decline in persons ≥75). Decline in IPD and ACHP was attenuated among older adults and those with comorbidities. Accordingly, rate ratios among at-risk and high-risk persons (vs healthy counterparts) increased during the peri- and post-PCV13 periods compared with the pre-PCV13 period.ConclusionsThe switch to PCV13 was associated with large declines in pneumococcal disease among US adults. However, the decline was attenuated with increasing age (and, for ACHP, was absent in persons ≥75) and in those with comorbidities.

Clinical and economic burden of pneumococcal disease in US adults aged 19\u201364\xa0years with chronic or immunocompromising diseases: an observational database study

BackgroundDespite the widespread availability of pneumococcal vaccines, rates of pneumococcal disease are disproportionately high in adults with chronic and immunocompromising conditions. This study investigated pneumococcal disease rates and associated resource utilization and costs in this group.MethodsA retrospective, observational study was conducted using the Truven Health MarketScan® Commercial Claims and Encounters database. The study population was adults aged 19–64 years with continuous health plan enrollment for at least one year before and at least one day after January 1st 2012, 2013 and/or 2014. Medical conditions were identified using ICD-9-CM diagnosis codes and grouped into at-risk (chronic) and high-risk (immunocompromising) conditions. Pneumococcal disease was stratified into all-cause pneumonia (ACP) and invasive pneumococcal disease (IPD).ResultsThirty-six million adults aged 19–64 years were included in the study. 17% had a condition that put them at increased risk for pneumococcal disease. Rates of ACP and IPD in adults with at-risk conditions were 3.6 and 4.6 times the rate in healthy adults, respectively, and 5.3 and 10.5 for adults with high-risk conditions. Risk was particularly high in adults with ≥2 medical conditions: rates of ACP and IPD were 8.1 and 10.6 times higher in adults with at-risk conditions than healthy adults and 6.3 and 13.4 times higher in adults with high-risk conditions, respectively. Resource use and costs were substantially higher per episode of ACP in at-risk and high-risk adults, with costs reaching $6,534 and $9,168, compared to $4,725 for healthy adults.ConclusionsPneumococcal disease rates in at-risk and high-risk adults are significantly higher than healthy adults leading to substantial economic burden.

Preterm Children Have Higher Risk Than Full-term Children of Invasive Pneumococcal Disease During the First 2 Years of Life.

A few previous studies have reported an increased risk of invasive pneumococcal disease (IPD) in children born preterm, but this has not been investigated in a cohort study. The impact of 7-valent pneumococcal conjugate vaccine (PCV7) on IPD incidence rates in preterm children is unknown. Data from the Medical Birth Registry of Norway (2002-2010) were linked to other national registries. In total, 628,138 children were included in our study and followed until 2 years of age. Incidence rate ratios (IRRs) and confidence intervals (CIs) were estimated with Poisson regression. We identified 411 cases of IPD. We observed higher rates of IPD in preterm than in full-term children for the intervals 0-23, 0-5 and 6-23 months of age, IRRs = 1.83 (95 % CI: 1.36-2.47), 2.95 (95% CI: 1.44-6.06) and 1.69 (95% CI: 1.22-2.34), respectively. The risk for IPD was reduced in the PCV7-period (2007-2010) compared with that of the pre PCV7-period (2002-2005) for children 6-23 months of age, IRRs = 0.20 (95% CI: 0.08-0.53) for preterm children and 0.28 (95% CI: 0.21-0.38) for full-term children, but not for those 0-5 months of age, IRRs = 1.94 (95% CI: 0.48-7.80) and 0.71 (95% CI: 0.38-1.33). Preterm children had an increased risk of IPD. After introduction of PCV7, the rate of IPD was reduced among preterm and full-term children from 6 months of age.

Incidence of invasive pneumococcal disease in immunocompromised patients: A systematic review and meta-analysis.

Invasive pneumococcal disease (IPD) is associated with high morbidity and mortality, with immunocompromised patients (ICPs) at particular risk. Therefore, guidelines recommend pneumococcal vaccination for these patients. However, guidelines are scarcely underpinned with references to incidence studies of IPD in this population. This, potentially results in unawareness of the importance of vaccination and low vaccination rates. The objective of this systematic review and meta-analysis was to assess the incidence of IPD in ICPs. We systematically searched PubMed and Embase to identify studies in English published before December 6th, 2017 that included terms related to 'incidence', 'rate', 'pneumococcal', 'pneumoniae', 'meningitis', 'septicemia', or 'bacteremia'. We focused on patients with HIV, transplantation and chronic inflammatory diseases. We included 45 studies in the systematic review reporting an incidence or rate of IPD, defined as isolation of Streptococcus pneumoniae from a normally sterile site. Random effects meta-analysis of 38 studies showed a pooled IPD incidence of 331/100,000 person years in patients with HIV in the late-antiretroviral treatment era in non-African countries, and 318/100,000 in African countries; 696 and 812/100,000 in patients who underwent an autologous or allogeneic stem cell transplantation, respectively; 465/100,000 in patients with a solid organ transplantation; and 65/100,000 in patients with chronic inflammatory diseases. In healthy control cohorts, the pooled incidence was 10/100,000. ICPs are at increased risk of contracting IPD, especially those with HIV, and those who underwent transplantation. Based on our findings, we recommend pneumococcal vaccination in immunocompromised patients. ID: CRD42016048438.

Invasive pneumococcal disease in Northern Alberta, not a Red Queen but a dark horse

BackgroundThe consequences of the introduction of various pneumococcal protein conjugate vaccines (PCV) for children and adults is poorly understood. ObjectiveWe undertook a population-based cohort study of invasive pneumococcal disease (IPD) in Northern Alberta (Canada) from 2000 to 2014, years spanning pre-and early PCV (2000–2004) vs PCV-7 (2005–2009) vs PCV-13 (2010–2014) time periods. DesignWe collected clinical, laboratory, and Streptococcus pneumoniae serotype information on all patients from 2000 to 2014. We determined changes in presentation, outcomes, serotypes, and incidence in children and adults across time periods. SettingThere were 509 cases of IPD in children, an 80% decrease over time. Rates of empyema (4.0–15.7%, p < 0.001), ICU admission (13.1–20%), and mortality (1.8–8.4%, p < 0.001) increased over time. There were 2417 cases of IPD in adults. Unlike children, incidence of IPD did not change nor did rates of empyema. ICU admissions increased (p = 0.004) and mortality decreased (18.7–16.5%, p = 0.002). The total number of serotypes causing IPD remained stable in children (22 vs 26 vs 20) while they decreased in adults (49 vs 47 vs 42). Conclusions and relevanceFor children, PCV vaccination strategies resulted in decreased overall rates of IPD and we observed increased rates of empyema and mortality; for adults, there was no change in IPD rates although disease severity increased while mortality decreased. On a population-wide basis, our results suggest that current PCV vaccination strategies are associated with an overall decrease in IPD but disease severity seems to be increasing in both children and adults.

Unusual Cause of Severe Jaundice in an HIV Infected Patient

Lobar pneumonia as a cause of jaundice with non-obstructive conjugated hyperbilirubinemia is an uncommon complication of pneumococcus. More commonly seen in immunocompromised and elderly patients, it is believed that the offending microbe produces a toxin that directly causes hepatocellular injury and impairment of bilirubin excretion. Biopsies of patients with pneumococcal pneumonia-associated jaundice commonly depict patchy areas of hepatic necrosis and dilated biliary canaliculi without metastatic foci of infection. In the pre-antibiotic era, the prevalence of jaundice in patients with lobar pneumonia was reported to be about 14% and carried significant mortality rates. Seen less commonly today, mortality rates of invasive pneumococcal disease remain as high as 5% to 35%. We present a case of a 29 year-old-male with no medical history presented with subjective fevers, productive cough, dark urine and myalgias for three days. He was profoundly jaundiced without stigmata of chronic liver disease. Computerized tomography (CT) of the chest revealed a right lower lobe pneumonia. The patient had leukocytosis, significant elevation of transaminases, hyperbilirubinemia and was found to be influenza positive. Antibody for human immunodeficiency virus (HIV) was also positive and later confirmed with polymerase chain reaction (PCR). An extensive workup for his jaundice and hyperbilirubinemia was unrevealing and it was deemed that his clinical signs were a result of invasive pneumococcal infection from his pneumonia. The patient was treated with antimicrobials and highly active antiretroviral therapy (HAART). He ultimately had complete resolution of his jaundice and laboratory abnormalities. Although seen infrequently today, unusual manifestations of pneumococcal infection still occur and may be unrecognized in practice.

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.

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.

Trends in Pediatric Complicated Pneumonia in an Ontario Local Health Integration Network.

Following the introduction of 7-valent pneumococcal vaccine (PCV7), while overall rates of invasive pneumococcal disease and pneumococcal pneumonia in children declined, rates of empyema increased. We examined changes in the incidence of hospitalization for pediatric complicated pneumonia (PCOMP) in Eastern Ontario, Canada, particularly since the introduction of the 13-valent vaccine (PCV13). A retrospective chart review was carried out evaluating previously healthy children admitted with PCOMP, which included empyema, parapneumonic effusion, necrotizing pneumonia, and lung abscess between 2002 and 2015. Three-hundred seventy-one children were included. Subjects had a median age of four years, and 188/370 (50.8%) required a chest tube. Admission rates changed markedly during this time period. The number of admissions per year rose most sharply between 2009 and 2012, corresponding to the period following introduction of PCV7 and then the occurrence of pandemic influenza A (H1N1). In children who likely received PCV13, the incidence of PCOMP returned to approximately pre-PCV7 levels. In contrast, rates of PCOMP in older children (who would not have received PCV13) remained elevated during the post-PCV13 time period. While rates of PCOMP, particularly in older children, remain elevated following the introduction of PCV13, this might be expected to resolve with more widespread vaccine coverage with PCV13 and herd immunity.

Emergence of Streptococcus pneumoniae Serotype 12F after Sequential Introduction of 7- and 13-Valent Vaccines, Israel.

Israel implemented use of 7- and 13-valent pneumococcal vaccine in 2009 and 2010, respectively. We describe results of prospective, population-based, nationwide active surveillance of Streptococcus pneumoniae serotype 12F (Sp12F) invasive pneumococcal disease (IPD) dynamics in the 7 years after vaccine introduction. Of 4,573 IPD episodes during July 2009–June 2016, a total of 434 (9.5%) were caused by Sp12F. Sp12F IPD rates (cases/100,000 population) increased in children <5 years of age, from 1.44 in 2009–2010 to >3.9 since 2011–2012, followed by an increase in all ages. During 2011–2016, Sp12F was the most prevalent IPD serotype. Sp12F isolates were mostly penicillin nonsusceptible (MIC >0.06 µg/mL; MIC50 = 0.12) and predominantly of sequence type 3774), a clone exclusively found in Israel (constituting ≈90% of isolates in 2000–2009). The sharp increase, long duration, and predominance of Sp12F IPD after vaccine implementation reflect a single clone expansion and may represent more than a transient outbreak.

Invasive Pneumococcal Disease in Children below 14 Years before and after the Introduction of Pneumococcal Conjugated Vaccine

Background: Invasive Pneumococcal Disease (IPD) is a life-threatening disease, which could be prevented by vaccination using Pneumococcal Conjugated Vaccine (PCV). Therefore, the aim of this study was compare the incidence before and after the introduction of the vaccine among children in King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia, and to determine the extent of the disease prevention by the vaccine. Methodology: A retrospective cohort study including all children who are ≤ 14 years of age and microbiologically confirmed as infected (cases) with Streptococcus pneumonia (SP) from a sterile body fluid (blood or cerebrospinal fluid) before the introduction of the pneumococcal conjugated vaccine between the years of 2004-2008 and after the introduction of the pneumococcal conjugated vaccine (2009-2015) in KAMC, Riyadh, Saudi Arabia. Results: Out of 171 retrieved cases, 131/171(76.6%) were not vaccinated and 40/171(23.4%) were vaccinated. Streptococcus Pneumonia was isolated from blood in 163/171(95%) of the cases, and from cerebrospinal fluid in 23/171(13.5%) of the cases. Conclusion: The introduction of PCV7 has significantly decreased the incidence rates of IPD in children. The conjugate vaccines have shown a significant efficacy in reducing IPD among our population.

Incidence of invasive pneumococcal disease before and during an era of use of three different pneumococcal conjugate vaccines in Quebec

BackgroundIn Quebec, 7-valent (PCV7), 10-valent (PCV10) and 13-valent (PCV13) pneumococcal conjugate vaccines were successively used for the immunization of children according to a 2+1 doses schedule. ObjectiveOur aim was to assess the impact of this program on the epidemiology of invasive pneumococcal disease (IPD) in children and adults. MethodsNotification and laboratory surveillance data were analyzed and the immunization status of IPD cases in children was checked. ResultsIn children < 5 years, the IPD rate decreased from 69/100,000 in 2003 to 12/100,000 in 2016 (83% reduction). Following PCV7 introduction in 2004, there has been a rapid decline in PCV7-type IPD cases and 6A. 7F and 19A serotypes emerged but their incidence decreased following PCV10 introduction in 2009 and PCV13 in 2011, whereas decrease in serotype 3 IPD was modest. Non-PCV13 types increased and represented 79% of cases in 2016. The same pattern was seen in adults but replacement was complete and there was no decrease in overall IPD rate. In those 65 years and over, PCV13 serotypes represented 28% of cases in 2016 and 62% were serotypes included in the 23-valent polysaccharide vaccine. Out of 10 IPD cases caused by serotype 3 in children vaccinated with PCV13 in 2011–2016, 6 occurred more than one year following the booster dose, which suggests short-term protection. Out of 31 breakthrough 19A cases, 19 occurred in children aged between 8 and 14 months who had received the 2 primary PCV13 doses but not the toddler booster dose, which suggests a window of susceptibility in a 2+1 schedule. ConclusionPCVs had a major impact on the IPD rate in children but not in adults. Among elderly adults, the proportion of cases caused by serotypes included in PCV13 is diminishing year after year but a majority of cases remains covered by the 23-valent polysaccharide vaccine.

Immunization, Antibiotic Use, and Pneumococcal Colonization Over a 15-Year Period.

Rates of invasive pneumococcal disease have declined since widespread introduction of pneumococcal conjugate vaccines (PCVs) in the United States. We evaluated the impact of immunization status and recent antibiotic use on an individual child's risk of colonization. This study extends previously reported data from children <7 years of age seen for well child or acute care visits in Massachusetts communities. Nasopharyngeal swabs were collected during 6 surveillance seasons from 2000 to 2014. Parent surveys and medical record reviews confirmed immunization status and recent antibiotic use. We estimated the proportions of children colonized with PCV7-included, additional PCV13-included, and non-PCV13 serotypes. Risk factors for colonization with additional PCV13-included and non-PCV13 serotypes were assessed by using generalized linear mixed models adjusted for clustering by community. Among 6537 children, 19A emerged as the predominant serotype in 2004, with substantial reductions in 2014. Among non-PCV serotypes, 15B/C, 35B, 23B, 11A, and 23A were most common in 2014. We observed greater odds for both additional PCV13 and non-PCV13 colonization in younger children, those with more child care exposure, and those with a concomitant respiratory tract infection. Adjusted odds for additional PCV13 colonization was lower (odds ratio 0.48 [95% confidence interval 0.31-0.75]) among children up-to-date for PCV13 vaccines. Recent antibiotic use was associated with higher odds of additional PCV13 colonization but substantially lower odds of non-PCV13 colonization. Despite the success of pneumococcal vaccines in reducing colonization and disease due to targeted serotypes, ongoing community-based surveillance will be critical to evaluate the impact of interventions on pneumococcal colonization and disease.

Changes in invasive pneumococcal disease among adults living with HIV following introduction of 13-valent pneumococcal conjugate vaccine, 2008–2014

BackgroundPeople living with HIV (PLHIV) are at increased risk of invasive pneumococcal disease (IPD). Introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in children in 2010 reduced adult IPD burden (indirect effects). In 2012, PCV13 was recommended in series with 23-valent polysaccharide vaccine (PPSV23) for adults with immunocompromising conditions, including PLHIV. We evaluated changes in IPD incidence in adults ≥19 years old with and without HIV after PCV13 introduction for children in 2010 and for immunocompromised adults in 2012. PCV13 coverage for adults 19–64 years old with indications was 6% in 2014.MethodsIPD cases, defined as pneumococcal isolation from sterile sites, were identified through CDC’s Active Bacterial Core surveillance, with counts projected nationally. HIV status was obtained from medical records. Isolates were serotyped by Quellung reaction or PCR and grouped into PCV13-types, PPV11-types (unique to PPSV23), or non-vaccine types. We estimated IPD incidence (cases per 100,000 people) using national case-based HIV surveillance (for PLHIV) or US Census data (for non-PLHIV) as denominators. We compared IPD incidence in 2011–12 and 2013–14 to the pre-PCV13 baseline (2008–09) by serotype groups.ResultsOverall IPD incidence at baseline was 354.0 for PLHIV and 15.5 for non-PLHIV. From baseline to 2013–14, IPD rates declined in both PLHIV (-36.3%; 95% CI: -38.8, -33.7%) and non-PLHIV (-27.3%; 95% CI: -28.2, -26.5%). The largest reductions were noted in PCV13-type IPD in both PLHIV (Figure 1) and non-PLHIV (Figure 2) for both periods (-46.8% for PLHIV and -45.9% for non-PLHIV in 2011–12; -60.3% for PLHIV and -65.8% for non-PLHIV in 2013–14). Overall IPD rates were 22.8 (95% CI: 22.2, 23.4) times as high in PLHIV compared with non-PLHIV at baseline, and 19.4 (95% CI: 18.8, 20.0) times as high in 2013–2014.ConclusionIPD rates declined significantly in both PLHIV and non-PLHIV during the study period due to reductions in PCV13-type IPD; however, IPD rates remained 20-fold in PLHIV compared with non-PLHIV. Similar magnitude reductions in PCV13-type IPD in both groups and low PCV13 coverage in immunocompromised adults suggest that most of the observed decline is due to PCV13 indirect effects from childhood immunization.Disclosures L. Harrison, GSK: Scientific Advisor, Consulting fee; W. Schaffner, Pfizer: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Novavax: Consultant, Consulting fee; Dynavax: Consultant, Consulting fee; Sanofi-pasteur: Consultant, Consulting fee; GSK: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee

Direct and Indirect Impact of 13-valent Pneumococcal Conjugate Vaccine (PCV13) on Invasive Pneumococcal Disease (IPD) Among Children and Adults in the U.S.

BackgroundIn February 2010, PCV13 was introduced for routine use among children aged < 5 years. In June 2012, PCV13 was recommended for use in series with 23-valent polysaccharide vaccine (PPSV23) for adults ≥19 years with select medical conditions, and in August 2014, for all adults ≥65 years. We evaluated the direct and indirect effects of PCV13 6 years post-introduction on invasive pneumococcal disease (IPD).MethodsIPD cases (isolation of pneumococcus from sterile sites) were identified among residents of Active Bacterial Core surveillance (ABCs) sites during July 2007–June 2016. Isolates were serotyped by Quellung, PCR, or whole genome sequencing and classified as PCV13 or non-vaccine type (NVT). Incidence changes were estimated as percent changes (one minus rate ratio) and 95% confidence intervals (95% CI) between pre-PCV13 (2007–2009) and two post-PCV13 periods (July 2014–June 2015 and July 2015–June 2016).ResultsABCs identified 31,190 IPD cases between 2007 and 2015, with 2,750 cases among children <5 years and 10,930 among those ≥65 years. During the two post-PCV13 periods, overall IPD rates were 33%-62% lower relative to 2007–2009 among all age groups, including <5 years and ≥65 years (Figure). Significant reductions in PCV13-type IPD incidence were observed for all age groups during both post-PCV13 periods, with incidence 84% (q95% CI 78, 88%) and 68% (95% CI 63, 73%) lower in 2015–2016 among children < 5 years and adults ≥65 years, respectively. PCV13-type IPD reductions were driven by serotypes 19A and 7F. IPD due to non-vaccine types also declined significantly among children < 5 years (−27%, 95% CI –42, –9%) and adults ≥65 years (-24%, 95% CI –34, –14%). PCV13-type IPD incidence did not differ significantly between the two post-PCV13 periods.ConclusionIPD incidence declined among children and adults in the U.S. following PCV13 introduction among children. The lack of difference in PCV13 rates between 2014–2015 and 2015–2016 suggests no measurable early impact of PCV13 introduction among adults ≥65 years. To date, we found no evidence of significant replacement disease with non-PCV13 types. Further work is needed to explain reductions in non-vaccine type disease observed in the post-PCV13 era.Disclosures W. Schaffner, Pfizer: Scientific Advisor, Consulting fee; Merck: Scientific Advisor, Consulting fee; Novavax: Consultant, Consulting fee; Dynavax: Consultant, Consulting fee; Sanofi-pasteur: Consultant, Consulting fee; GSK: Consultant, Consulting fee; Seqirus: Consultant, Consulting fee; L. Harrison, GSK: Scientific Advisor, Consulting fee

Predictors of pneumococcal carriage and the effect of the 13-valent pneumococcal conjugate vaccination in the Western Australian Aboriginal population

BackgroundThe 7-valent pneumococcal conjugate vaccine (PCV7) was introduced to prevent invasive pneumococcal disease (IPD) in Western Australian (WA) Aboriginal people in 2001. PCV13 replaced PCV7 in July 2011, covering six additional pneumococcal serotypes; however, IPD rates remained high in Aboriginal people in WA. Upper respiratory tract pneumococcal carriage can precede IPD, and PCVs alter serotype distribution.MethodsTo assess the impact of PCV13 introduction, identify emerging serotypes, and assess risk factors for carriage, nasopharyngeal swabs and information on demographic characteristics, health, medication and living conditions from Aboriginal children and adults across WA from August 2008 to November 2014 were collected. Bacteria were cultured using selective media and pneumococcal isolates were serotyped by Quellung reaction. Risk factors were analysed by multivariable logistic regression.ResultsOne thousand five hundred swabs pre- and 1385 swabs post-PCV13 introduction were collected. Pneumococcal carriage was detected in 66.8% of children <5 years old and 53.2% of 5–14 year-olds post-PCV13, compared with pre-PCV13 prevalence of 72.2% and 49.4%, respectively. The prevalence of PCV13-non-PCV7 serotypes decreased in children <5 years old from 13.5% pre-PCV13 to 5.8% post-PCV13 (p < 0.01), and from 8.4% to 6.1% in children 5–14 years old (p > 0.05). The most common serotypes post-PCV13 were 11A (prevalence 4.0%), 15B (3.5%), 16F (3.5%), and 19F (3.2%).Risk of detection of pneumococcal carriage increased until age 12 months (odds ratio [OR] 4.19, 95% confidence interval [CI] 2.39–7.33), with nasal discharge (OR 2.49 [95% CI 2.00–3.09]), residence in a remote community (OR 2.21 [95% CI 1.67–2.92]) and household crowding (OR 1.36 [95% CI 1.11–1.67]). Recent antibiotic use was negatively associated with pneumococcal carriage (OR 0.48 [95% CI 0.33–0.69]). Complete resistance to penicillin was present among isolates of serotypes 19A (6.0%), 19F (2.3%) and non-serotypeable isolates (1.9%). Serotype 23F and newly emerged serotype 7B isolates showed high rates of resistance to cotrimoxazole, erythromycin and tetracycline (86.9%, 86.9%, 82.0%, respectively for 23F, 100.0%, 100.0% and 93.3% for 7B).ConclusionSince PCV13 replaced PCV7, carriage of PCV13-non-PCV7 serotypes decreased significantly among children <5 years old, those most likely to have received PCV13, and to a lesser extent in older people. Known risk factors for carriage including crowding and young age remain in the Aboriginal population.

New Guidance Clarifies Use of Pneumococcal, Influenza Vaccines in Older Adults

New Guidance Clarifies Use of Pneumococcal, Influenza Vaccines in Older Adults

Trends in Invasive Pneumococcal Disease in Cancer Patients After the Introduction of 7-valent Pneumococcal Conjugate Vaccine: A 20-year Longitudinal Study at a Major Urban Cancer Center.

Rates of invasive pneumococcal disease (IPD) declined since routine childhood immunization with the 7-valent pneumococcal conjugate vaccine (PCV7) in 2000. We studied the impact of PCV7 on the incidence of IPD in cancer patients. This was a retrospective analysis of adult and pediatric patients treated at Memorial Sloan Kettering Cancer Center from 1992 to 2012. Recovery of Streptococcus pneumoniae from a sterile site defined IPD. IPD incidence was calculated as cases per 1,000 unique patient-visits per year (UPV). IPD incidence was calculated for the periods: "before PCV7" (1992-2000), "after PCV7" (2001-2010) and "after PCV13" (2011-2012). Of 343 IPD cases, 165, 155, and 23 cases occurred "before PCV7," "after PCV7" and "after PCV13" respectively. The IPD incidence declined from 0.43 "before PCV7" to 0.17 "after PCV7" (95% confidence interval [CI]: 0.33-0.46, P < .001) and 0.11 "after PCV13" (95% CI: 0.42-0.96, P = .004). Adults with hematologic malignancies and children had the highest incidence. In patients 1-4 years old, the incidence declined from 11.2 "before PCV7" to 2.38 "after PCV7" (79% decrease, 95% CI: 0.1-0.4, P < .001). In patients with hematologic malignancies, the incidence declined from 2.55 "before PCV7" to 0.92 "after PCV7" (64% decrease, 95% CI: 0.27-0.47, P < .001). The incidence of IPD among cancer patients sharply declined after introduction of PCV7; especially in high risk groups. The decline in adults suggests an indirect effect from PCV7 childhood vaccination.

Effect of Age on the Manifestations and Outcomes of Invasive Pneumococcal Disease in Adults

BackgroundAlthough a considerable amount is known about the effect of age on the manifestations and outcomes of pneumonia, the same is not true for invasive pneumococcal disease. MethodsThis was a prospective observational study of all cases (2435) of invasive pneumococcal disease in adults in Northern Alberta from 2000 to 2014. Rates of invasive pneumococcal disease per 100,000, sociodemographic variables, clinical characteristics, and invasive pneumococcal disease–related outcomes were compared for the following age groups: 17-54, 55-64, 65-74, and ≥75 years. ResultsThe rate of invasive pneumococcal disease per 100,000 increased with increasing age. Although only 27.3% of the cases were in those aged ≥65 years, they accounted for 48% of the deaths. The case fatality rate increased with increasing age, from 9.6% for those aged 17-54 years to 31.7% for those aged ≥75 years. The rate of meningitis decreased with increasing age, as did admission to intensive care and use of mechanical ventilation. There was a marked reduction in the rate of invasive pneumococcal disease due to protein conjugate vaccine 7 and protein conjugate vaccine 13 serotypes in those aged ≥55 years but a much smaller decline in rates for those aged 17-54 years. Replacement with non-vaccine serotypes constituted approximately 50% of the cases. ConclusionsThe rate of invasive pneumococcal disease is highest in the very elderly, and manifestations of invasive pneumococcal disease are influenced by age.