Vaccine-serotype Invasive Pneumococcal Disease Research Articles

Effectiveness of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease among children

The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in March 2015 in Bangladesh. In this study, we aimed to estimate the impact of PCV10 on invasive pneumococcal disease (IPD) identified by blood cultures and severe pneumonia identified clinically and its effectiveness on invasive disease caused by vaccine serotypes.We conducted population-based surveillance among children aged 2- <24 months between April 2012 through March 2019 in Mirzapur, a rural sub-district of Bangladesh. We compared incidence of IPD and severe pneumonia before (April 2012 to March 2015) and after (April 2015 to March 2019) the introduction of PCV10. Vaccine effectiveness was measured using an indirect cohort analysis of data from four sentinel sites in which PCV10 vaccination status was compared between children with IPD caused by vaccine serotype vs. non-vaccine serotypes.We identified 24 IPD cases by blood culture and 1,704 severe pneumonia hospitalizations during the surveillance period. IPD incidence in under-2-year-old children fell 25 % (95 % CI: −1.2 % to 76 %; p-value = 0.59) from 106 cases per 100,000 child-years at baseline to 79.3 in April 2018- March 2019. Vaccine serotype-IPD incidence was lower (77 % reduction, 95 % CI: −0.45 % to 96 %; p-value = 0.068) in April 2018 - March 2019 than in the pre-vaccine period (85.7 cases to 19.8/100,000 child-years). A significant decline of 54.0 % (95 % CI: 47.0 % to 59.0 %; p-value < 0.001) was observed in hospitalizations due to severe pneumonia. From indirect cohort analysis, the effectiveness of PCV10 against vaccine serotype IPD was 37 % (95 % CI: −141.0 % to 83.5 %; p = 0.5) after the 1st dose and 63.1 % (95 % CI: −3.3 % to 85.9 %, p = 0.0411) after the 2nd or the 3rd dose.This study demonstrates that PCV10 introduction prevented hospitalizations with severe pneumonia and provided individual protection against vaccine serotypes.

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

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

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

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

Waning of antibody levels induced by a 13-valent pneumococcal conjugate vaccine, using a 3 + 0 schedule, within the first year of life among children younger than 5 years in Blantyre, Malawi: an observational, population-level, serosurveillance study

Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine-serotype carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty surrrounding correlate of protection (CoP) estimates and with persistent vaccine-serotype carriage and vaccine-serotype IPD after PCV13 introduction, we aimed to profile population-level immunogenicity among children younger than 5 years in Blantyre, Malawi. For this serosurveillance study, we used a random subset of samples from a prospective population-based serosurvey in Blantyre, Malawi, done between Dec 16, 2016, and June 27, 2018. Sample selection was based on age category optimisation among children younger than 5 years, adequate sample volume, and available budget. We measured serotype-specific IgGs against the 13 vaccine serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and two non-vaccine serotypes (12F and 33F), as well as IgGs against three pneumococcal proteins (PsaA, NanA, and Ply), using ELISA and a direct-binding electrochemiluminescence-based multiplex assay. We estimated population-level, serotype-specific immunogenicity profiles using a linear spline regression model. Analyses included samples stratified to 20 3-month age strata (eg, age <3 months to 57-59 months). We evaluated 638 plasma samples: 556 primary samples and 82 unique secondary samples (each linked to one primary sample). Immunogenicity profiles revealed a consistent pattern among vaccine serotypes except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3, we observed no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination nadir (from 11·2 months [19A] to 27·3 months [7F]). The age at peak IgG titre ranged from 2·69 months (5) to 6·64 months (14). Titres dropped below CoPs against IPD among nine vaccine serotypes (1, 3, 4, 5, 6B, 7F, 9V, 18C, and 23F) and below CoPs against carriage for ten vaccine serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F). Increasing antibody concentrations among older children and seroincident events were consistent with ongoing vaccine-serotype exposure. A 3 + 0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several vaccine serotypes, potentially contributing to persistent vaccine-serotype carriage and residual vaccine-serotype IPD in Malawi and other similar settings. Policy decisions should consider alternative vaccine strategies, including a booster dose, to achieve sustained vaccine-induced antibody titres, and thus control. Bill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health and Care Research.

Changing Incidence of Invasive Pneumococcal Disease in Infants Less Than 90 Days of Age Before and After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Blantyre, Malawi: A 14-Year Hospital Based Surveillance Study.

Background:Invasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants <90 days old in Blantyre, Malawi over a 14-year period and evaluated the indirect impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on vaccine-serotype IPD (VT-IPD) in this population.Methods:We conducted laboratory-based prospective IPD surveillance in infants <90 days of age admitted to Queen Elizabeth Central Hospital in Blantyre between 2005 and 2018, including 7 years pre-PCV13 and 7 years post-PCV13 introduction. IPD was defined as Streptococcus pneumoniae identified by culture from blood or cerebrospinal fluid. Serotypes were determined by multiplex polymerase chain reaction and latex agglutination testing.Results:We identified 130 cases of culture-confirmed IPD in infants <90 days old between 2005 and 2018. Total IPD incidence was declining before PCV13 introduction. The mean incidence of IPD was significantly lower in the post-PCV13 era. Serotypes 5 (27.8%) and 1 (15.6%) were most prevalent. Even after PCV13 introduction, VTs remained the primary cause of IPD, with serotype 5 accounting for 17.4% and serotype 1 for 13.0% of cases in young infants.Conclusion:Vaccine serotypes 1 and 5 were the main cause of IPD in neonates and young infants, both before and after PCV13 introduction. This suggests incomplete indirect protection with persisting VT carriage across the population despite vaccination in this setting. Alternative vaccine schedules and other vaccine introduction approaches need to be considered to protect this vulnerable population.

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.

PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA).

The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) evaluated older adult pneumococcal vaccination and was one of the largest vaccine clinical trials ever conducted. Among older adults aged ≥65 years, the trial established 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing first episodes of bacteremic and nonbacteremic pneumococcal vaccine serotype (VT) community acquired pneumonia (CAP), and of vaccine serotype invasive pneumococcal disease (VT-IPD). Since the publication of the original trial results, 15 additional publications have extended the analyses. In this review, we summarize and integrate the full body of evidence generated by these studies, contextualize the results in light of their public health relevance, and discuss their implications for the assessment of current and future adult pneumococcal vaccination. This accumulating evidence has helped to better understand PCV13 efficacy, serotype-specific efficacy, efficacy in subgroups, the interpretation of immunogenicity data, and the public health value of adult PCV vaccination.

Impact and effectiveness of 13-valent pneumococcal conjugate vaccine on population incidence of vaccine and non-vaccine serotype invasive pneumococcal disease in Blantyre, Malawi, 2006–18: prospective observational time-series and case-control studies

SummaryBackgroundThe population impact of pneumococcal conjugate vaccines (PCVs) depends on direct and indirect protection. Following Malawi's introduction of the 13-valent PCV (PCV13) in 2011, we examined its impact on vaccine and non-vaccine serotype invasive pneumococcal disease among vaccine-eligible-age and vaccine-ineligible-age children and adults.MethodsWe did a prospective observational time-series analysis and a case-control study. We used data from between Jan 1, 2006, and Dec 31, 2018, from laboratory-based surveillance at a government hospital in Malawi. This period included 6 years before and 7 years after introduction of PCV13. By use of negative-binomial regression, we evaluated secular trend-adjusted incidence rate ratio (IRR) in vaccine serotype and non-vaccine serotype invasive pneumococcal disease before and after introduction of PCV. We compared predicted counterfactual incidence in hypothetical absence of vaccine with empirically observed incidence following vaccine introduction. The case-control study assessed vaccine effectiveness, comparing PCV uptake among cases of vaccine-eligible-age invasive pneumococcal disease versus matched community controls.FindingsSurveillance covered 10 281 476 person-years of observation, with 140 498 blood and 63 291 cerebrospinal fluid cultures. A reduction in total (vaccine serotype plus non-vaccine serotype) invasive pneumococcal disease incidence preceded introduction of PCV: 19% (IRR 0·81, 95% CI 0·74 to 0·88, p<0·0001) among infants (<1 year old), 14% (0·86, 0·80 to 0·93, p<0·0001) among children aged 1–4 years, and 8% (0·92, 0·83 to 1·01, p=0·084) among adolescents and adults (≥15 years old). Among children aged 5–14 years there was a 2% increase in total invasive pneumococcal disease (1·02, 0·93 to 1·11, p=0·72). Compared with the counterfactually predicted incidence, incidence of post-PCV13 vaccine serotype invasive pneumococcal disease was 74% (95% CI 70 to 78) lower among children aged 1–4 years and 79% (76 to 83) lower among children aged 5–14 years, but only 38% (37 to 40) lower among infants and 47% (44 to 51) lower among adolescents and adults. Although non-vaccine serotype invasive pneumococcal disease has increased in incidence since 2015, observed incidence remains low. The case-control study (19 cases and 76 controls) showed vaccine effectiveness against vaccine serotype invasive pneumococcal disease of 80·7% (–73·7 to 97·9).InterpretationIn a high-mortality, high-HIV-prevalence setting in Africa, there were significant pre-vaccine reductions in the incidence of invasive pneumococcal disease. 7 years after PCV introduction, although vaccine-attributable impact among vaccine-eligible-age children was significant, indirect effects benefitting unvaccinated infants and adults were not. Policy decisions should consider multiple alternative strategies for reducing disease burden, including targeted vaccination outside infant Expanded Programme of Immunization to benefit vulnerable populations.FundingBill & Melinda Gates Foundation, Wellcome Trust, and National Institute for Health Research.

Effectiveness of Pneumococcal Conjugate Vaccines Against Community-acquired Alveolar Pneumonia Attributable to Vaccine-serotype Streptococcus pneumoniae Among Children

Abstract Introduction Streptococcus pneumoniae is a leading cause of pneumonia among children. However, owing to diagnostic limitations, the protection conferred by pneumococcal conjugate vaccines (PCVs) against pediatric pneumonia attributable to vaccine-serotype pneumococci remains unknown. Methods We analyzed data on vaccination and nasopharyngeal pneumococcal detection among children &amp;lt;5 years old with community-acquired alveolar pneumonia (CAAP; “cases”) and those without respiratory symptoms (“controls”), who were enrolled in population-based prospective surveillance studies in southern Israel between 2009 and 2018. We measured PCV-conferred protection against carriage of vaccine-serotype pneumococci via the relative risk of detecting these serotypes among vaccinated versus unvaccinated controls. We measured protection against progression of vaccine serotypes from carriage to CAAP via the relative association of vaccine-serotype detection in the nasopharynx with CAAP case status, among vaccinated and unvaccinated children. We measured PCV-conferred protection against CAAP attributable to vaccine-serotype pneumococci via the joint reduction in risks of carriage and disease progression. Results Our analyses included 1032 CAAP cases and 7743 controls. At ages 12–35 months, a PCV13 schedule containing 2 primary doses and 1 booster dose provided 87.2% (95% confidence interval: 8.1–100.0%) protection against CAAP attributable to PCV13-serotype pneumococci, and 92.3% (–0.9%, 100.0%) protection against CAAP attributable to PCV7-serotype pneumococci. Protection against PCV13-serotype and PCV7-serotype CAAP was 67.0% (–424.3%, 100.0%) and 67.7% (–1962.9%, 100.0%), respectively, at ages 36–59 months. At ages 4–11 months, 2 PCV13 doses provided 98.9% (–309.8%, 100.0%) and 91.4% (–191.4%, 100.0%) against PCV13-serotype and PCV7-serotype CAAP. Conclusions Among children, PCV-conferred protection against CAAP attributable to vaccine-targeted pneumococcal serotypes resembles protection against vaccine-serotype invasive pneumococcal disease.

Characteristics of Serotype 3 Invasive Pneumococcal Disease before and after Universal Childhood Immunization with PCV13 in Massachusetts.

Background: Although a substantial decline in vaccine-serotype invasive pneumococcal disease (IPD) incidence was observed following the introduction of pneumococcal conjugate vaccines (PCV), the estimated range of thirteen-valent conjugate vaccine (PCV13) effectiveness for serotype 3 disease is wide and includes zero. We assessed the impact of PCV13 on serotype 3 IPD incidence and disease characteristics in Massachusetts’ children. Methods: Serotype 3 IPD cases in children <18 years old were identified via enhanced passive surveillance system in Massachusetts. We compared incidence rates and characteristics of IPD cases before and after PCV13. Results: A total of 47 serotype 3 IPD cases were identified from 2002 to 2017; incidence of serotype 3 IPD in the years following PCV13 was 0.19 per 100,000 children compared to 0.21 before PCV 13, incidence rate ratio (IRR) = 0.86 (95% CI 0.47–1.57). The majority (78%) of post-PCV13 serotype 3 IPD cases occurred among fully vaccinated children. Age distribution, clinical syndrome and presence of comorbidities among serotype 3 IPD cases were similar before and after PCV13 introduction. There was no association between the date of the last PCV13 dose and time to IPD to suggest waning of immunity. Conclusions: seven years following PCV 13 we found no significant changes in serotype 3 IPD incidence or disease characteristics in children in Massachusetts.

Effectiveness of the seven-valent and thirteen-valent pneumococcal conjugate vaccines in England: The indirect cohort design, 2006–2018

BackgroundThe 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the UK childhood immunisation programme in 2006 and replaced with a 13-valent vaccine (PCV13) in 2010. Both vaccines led to rapid declines in vaccine-serotype invasive pneumococcal disease (IPD). Here, we assessed the long-term vaccine-effectiveness (VE) of both vaccines in England. MethodsPublic Health England conducts enhanced national surveillance of IPD in England. VE against IPD was estimated using vaccine-serotype IPD cases and non-vaccine serotype IPD controls among vaccine-eligible children from September 2006 to June 2018 (the Broome method). ResultsVaccine history was available for 3421 IPD cases, including 1299 due to the additional PCV13 serotypes and the PCV13-related serotype 6C, 274 PCV7 serotypes and 1848 non-PCV13 serotypes. For the complete 2 + 1 schedule, both PCV7 and PCV13 showed high effectiveness against PCV7 serotypes with a combined VE of 92.0% (95%CI, 81.7–96.7). For the 2 + 1 schedule, PCV13 VE against the additional PCV13 serotypes plus 6C was 73.7% (31.1–89.9) compared to 90.0% (75.3 – 96.0) for PCV7 against PCV7 serotypes, although PCV13 VE increased to 84.8% (58.7–94.4) if serotype 3 was excluded; all 36 eligible serotype 3 IPD cases were fully-vaccinated with PCV13. Case numbers were low in older ages but there was evidence of waning, which was significant for serotype 19A for which there were sufficient numbers of cases for analysis. ConclusionsPCVs are highly effective in preventing vaccine-serotype IPD except for serotype 3 which has been increasing in incidence. Serotype 19A IPD has also persisted, likely due to a slightly lower VE and/or more rapid waning of protection.

Impact of 13-Valent Pneumococcal Conjugate Vaccine on Colonization and Invasive Disease in Cambodian Children.

BackgroundCambodia introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in January 2015 using a 3 + 0 dosing schedule and no catch-up campaign. We investigated the effects of this introduction on pneumococcal colonization and invasive disease in children aged <5 years.MethodsThere were 6 colonization surveys done between January 2014 and January 2018 in children attending the outpatient department of a nongovernmental pediatric hospital in Siem Reap. Nasopharyngeal swabs were analyzed by phenotypic and genotypic methods to detect pneumococcal serotypes and antimicrobial resistance. Invasive pneumococcal disease (IPD) data for January 2012–December 2018 were retrieved from hospital databases. Pre-PCV IPD data and pre-/post-PCV colonization data were modelled to estimate vaccine effectiveness (VE).ResultsComparing 2014 with 2016–2018, and using adjusted prevalence ratios, VE estimates for colonization were 16.6% (95% confidence interval [CI] 10.6–21.8) for all pneumococci and 39.2% (95% CI 26.7–46.1) for vaccine serotype (VT) pneumococci. There was a 26.0% (95% CI 17.7–33.0) decrease in multidrug-resistant pneumococcal colonization. The IPD incidence was estimated to have declined by 26.4% (95% CI 14.4–35.8) by 2018, with a decrease of 36.3% (95% CI 23.8–46.9) for VT IPD and an increase of 101.4% (95% CI 62.0–145.4) for non-VT IPD.ConclusionsFollowing PCV13 introduction into the Cambodian immunization schedule, there have been declines in VT pneumococcal colonization and disease in children aged <5 years. Modelling of dominant serotype colonization data produced plausible VE estimates.

Vaccination among HIV-infected, HIV-exposed uninfected and HIV-uninfected children: a systematic review and meta-analysis of evidence related to vaccine efficacy and effectiveness

ABSTRACTEvidence-based approaches were used in making recommendations for vaccination against vaccine-preventable diseases for HIV-infected and HIV-exposed individuals but with limited substantiation. We conducted a systematic review and meta-analysis with randomized-controlled trials (RCTs), cohort and case–control studies that have efficacy and effectiveness of vaccines in HIV-infected and HIV-exposed children as outcomes. Web of Science, Cochrane Library, PubMed and Scopus databases were searched for articles. Efficacy of 9-valent pneumococcal conjugate vaccine (PCV9) against total vaccine serotype invasive pneumococcal disease was 32% in HIV-infected children and 78% among HIV-uninfected children. Vaccine effectiveness of Bacillus Calmette–Guérin vaccine in preventing tuberculosis in HIV-infected children was zero compared to 59% protection in HIV-unexposed children. Likewise, HIV-uninfected children have better protection against invasive Haemophilus influenzae type b disease than the HIV-infected children. Effectiveness studies of rotavirus vaccines show that HIV-exposed uninfected children have similar protection against rotavirus gastroenteritis compared to the non-exposed children. Children who are severely immunosuppressed are poorly protected against invasive pneumococcal diseases. HIV-infected children tend to have lesser vaccine protection against vaccine-preventable diseases when compared to unexposed children. HIV-infected children who are immunocompetent are more likely to have better vaccine protection against vaccine-preventable diseases than those who are immunosuppressed. The overall quality of the observational studies was very low with very little confidence in the effect estimate. The overall quality of evidence for the RCT outcomes was mainly high. This study reveals a dearth of efficacy and effectiveness studies among HIV-infected and exposed children.

The duopoly of ten-valent and 13-valent pneumococcal conjugate vaccines: do they differ?

The duopoly of ten-valent and 13-valent pneumococcal conjugate vaccines: do they differ?

Imputing the Direct and Indirect Effectiveness of Childhood Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease by Surveying Temporal Changes in Nasopharyngeal Pneumococcal Colonization.

The limited capability in most low- to middle-income countries to study the benefit of pneumococcal conjugate vaccine (PCV) in protecting against invasive pneumococcal disease (IPD) calls for alternate strategies to assess this. We used a mathematical model to predict the direct and indirect effectiveness of PCV by analyzing serotype-specific colonization prevalence and IPD incidence prior to and following childhood PCV immunization in South Africa. We analyzed IPD incidence from 2005 to 2012 and colonization studies undertaken in human immunodeficiency virus (HIV)-uninfected and HIV-infected child-mother dyads from 2007 to 2009 (pre-PCV era), in 2010 (7-valent PCV era), and in 2012 (13-valent PCV era). We compared the model-predicted changes in IPD incidence with observed changes in IPD incidence, according to HIV status, in children aged 3 months-5 years and in women aged 18-45 years. We observed reductions in vaccine-serotype colonization and IPD due to vaccine serotypes among children and women after PCV introduction. Using the changes in vaccine-serotype colonization data, the model-predicted changes in vaccine-serotype IPD incidence rates were similar to the observed changes in PCV-unvaccinated children and adults, but not among children under age 24 months. Surveillance of colonization prior to and following PCV use can be used to impute the indirect protection afforded by PCV in unvaccinated age groups, including those in high-HIV-prevalence settings.

Impact of PCV13 on Serotype 3 Invasive Pneumococcal Disease and Nasopharyngeal Carriage in Massachusetts’ Children

BackgroundAlthough a substantial decline in overall vaccine serotype invasive pneumococcal disease (IPD) incidence has been observed following immunization with PCV7 and subsequently PCV13, the reported effectiveness for individual vaccine serotypes has varied. Reported effectiveness of PCV13 for serotype 3 (ST3) disease has differed by study design and geography, with a wide range of estimates including zero. We assessed the impact of PCV13 on ST3 IPD cases and nasopharyngeal (NP) carriage in Massachusetts’ children.MethodsCases of ST3 IPD in children <18 years were identified via enhanced passive surveillance in conjunction with the Massachusetts Department of Public Health from 2002 to 2016. NP Carriage of ST3 in children aged 3 months to <7 years was identified via an active surveillance network of pediatric practices in Massachusetts from 2007 to 2014. Annual incidence rates of ST3 IPD were calculated using US Census estimates as population denominators. Annual prevalence rates of carriage were calculated using the surveillance population. We compared age distribution, clinical syndromes, presence of comorbidities and vaccination status for IPD cases and age distribution of children with ST3 carriage before and after PCV13 implementation.ResultsOverall 47 cases of ST3 IPD were identified from 2002 to 2016; the incidence of ST3 IPD before and after PCV13 was 0.23 and 0.20 per 100,000 children respectively (incidence rate ratio [IRR] = 1.13, 95% CI 0.62–2.05). There were no differences in age distribution, clinical syndrome or presence of comorbidities among ST3 IPD cases before and after PCV13. The majority (9/13) of post PCV13 ST3 IPD cases occurred among children who were fully vaccinated. No association was seen between date of last PCV13 dose and time of IPD to suggest waning immunity. Prevalence of ST3 carriage among children aged 3 months to <7 years before and after PCV13 implementation was 0.19 and 0.64 respectively (Prevalence ratio [PR] = 0.3, 95% CI 0.11–0.83).ConclusionSix years after PCV13 implementation, no significant changes in ST3 IPD incidence, age distribution, clinical syndrome or presence of comorbidity among cases in children <18 years of age were observed. An increase in NP carriage in children <7 years of age was observed.Disclosures K. M. Shea, Pfizer, Inc: Consultant and Grant Investigator, Consulting fee and Grant recipient; S. I. Pelton, Pfizer: Board Member and Grant Investigator, Consulting fee, Research grant and Speaker honorarium; Merck vaccines: Board Member, Consulting fee and Speaker honorarium; GSK: Board Member, Consulting fee and Speaker honorarium; Sequiris: Board Member, Consulting fee and Speaker honorarium

Influence of Childhood Pneumococcal Conjugate Vaccines on Invasive Pneumococcal Disease in Adults With Underlying Comorbidities in Calgary, Alberta (2000-2013).

Pneumococcal conjugate vaccine (PCV) was introduced into Alberta, Canada's routine childhood immunization programs in 2002 (7-valent [PCV7]) and 2010 (13-valent [PCV13]). We assessed the effect of these programs on the epidemiology of invasive pneumococcal disease (IPD) to determine if PCV-associated indirect protection was relatively reduced in adults with underlying comorbidities. Demographic and clinical data were collected by a prospective, population-based surveillance system in Calgary, Alberta, Canada, from January 2000 to December 2013. An indirect cohort study design was used to assess for changes in the proportion of IPD cases with underlying comorbidities. There were 1598 overall and 1346 adult IPD cases from 1 January 2000 to 31 December 2013. Overall IPD incidence decreased 33% (age 0-5 months), 86% (6-23 months), 67% (2-4 years), 26% (5-17 years), 22% (18-64 years), 36% (65-84 years), and 42% (≥85 years) from the prevaccine (January 2000-July 2002) to the post-PCV13 (July 2010-December 2013) period. Over the same timeframe, PCV7 serotype disease incidence declined to ≤1 case per 100 000 persons in all age groups. Neither the proportion of adult cases with immunocompetent comorbidities (relative risk ratio [RRR], 0.93; 95% confidence interval [CI], .62-1.40) nor immunocompromising comorbidities (RRR, 0.99; 95% CI, .61-1.61) differed between the pre-PCV period and post-PCV era. Childhood PCV programs have provided considerable benefit, with substantial declines in overall and vaccine-serotype IPD in vaccinated children and in unvaccinated persons. Conjugate vaccine-associated indirect protection for adults with comorbidities was similar to that for healthy adults.

Direct, indirect and total effects of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children in Navarra, Spain, 2001 to 2014: cohort and case-control study.

We estimated the direct, indirect and total effects of the 13-valent pneumococcal conjugate vaccine (PCV13) on invasive pneumococcal disease (IPD) in children. A population-based cohort study followed children aged between 2.5 and 59 months between 2001 and 2014 in Navarra, Spain. IPD incidence was compared by PCV status and period. All cases diagnosed from July 2010 to December 2014 and eight matched controls per case were analysed to estimate the adjusted direct effect of PCV13. A total of 120,980 children were followed and 206 IPD cases were detected. Compared with unvaccinated children in the baseline period (2001-2004), overall IPD incidence in 2011-2014 (76% average PCV coverage) declined equally in vaccinated (total effect: 76%; hazard ratio (HR): 0.24; 95% confidence interval (CI): 0.14-0.40) and unvaccinated children (indirect effect: 78%; HR: 0.22; 95% CI: 0.09-0.55). IPD incidence from non-PCV13 serotypes increased among vaccinated children (HR: 2.84; 95% CI: 1.02-7.88). The direct effect of one or more doses of PCV13 against vaccine serotypes was 95% (odds ratio: 0.05; 95% CI: 0.01-0.55). PCV13 was highly effective in preventing vaccine-serotype IPD. The results suggest substantial and similar population-level vaccine benefits in vaccinated and unvaccinated children through strong total and indirect effects.

The serotype distribution among healthy carriers before vaccination is essential for predicting the impact of pneumococcal conjugate vaccine on invasive disease.

Pneumococcal conjugate vaccines (PCVs) have substantially reduced morbidity and mortality of pneumococcal disease. The impact of the 7-valent PCV on all-serotype invasive pneumococcal disease (IPD) among children was reported to vary between high-income countries. We investigate the ability to predict this heterogeneity from pre-vaccination data. We propose a parsimonious model that predicts the impact of PCVs from the odds of vaccine serotype (VT) among carriers and IPD cases in the pre-PCV period, assuming that VT are eliminated in a mature PCV programme, that full serotype replacement occurs in carriage and that invasiveness of the NVT group is unchanged. We test model performance against the reported impact of PCV7 on childhood IPD in high-income countries from a recent meta-analysis. The odds of pre-PCV7 VT IPD, PCV schedule, PCV coverage and whether a catch up campaign was used for introduction was gathered from the same analysis. We conducted a literature review and meta-analysis to obtain the odds of pre-PCV7 VT carriage in the respective settings. The model predicted the reported impact on childhood IPD of mature PCV programmes; the ratio of predicted and observed incidence risk ratios was close to 1 in all settings. In the high income settings studied differences in schedule, coverage, and catch up campaigns were not associated with the observed heterogeneity in impact of PCV7 on childhood all-serotype IPD. The pre-PCV7 proportion of VT IPD alone also had limited predictive value. The pre-PCV7 proportion of VT carriage and IPD are the main determinants for the impact of PCV7 on childhood IPD and can be combined in a simple model to provide predictions of the vaccine preventable burden of IPD.

Controlling Pneumococcal Disease around the Globe

Invited Lecture AbstractsISPPD-0535 Controlling Pneumococcal Disease Around the Globe: UPDATE FROM AFRICAA. Von Gottberg11South AfricaSouth Africa introduced the seven-valent pneumococcal protein-polysaccharide conjugate vaccine (PCV-7) in 2009 using a novel 3-dose infant schedule (6, 14 and 36 weeks). We assessed PCV-7 impact using national disease surveillance data, accounting for HIV prevention effects. We conducted active, national, laboratory-based surveillance for invasive pneumococcal disease (IPD) from 2005 through 2012, including serotyping and susceptibility testing. We calculated the percentage change in IPD incidence, focusing on individuals aged <2 and 25–44 years, between post-vaccine (2011 and 2012) and pre-vaccine years (average of 2005 through 2008). From 2005 through 2012, 35,192 IPD cases were identified. Rates of PCV-7 vaccine-serotype IPD among children <2 years declined by 89% in 2012, from 32.1 cases per 100,000 person-years to 3.4/100,000 (95% confidence interval [CI], −92% to −86%) while nonvaccine-serotype IPD increased non-significantly from 8.9/100,000 to 9.5/100,000 (+6%; 95% CI, −16% to +23%). Among adults age 25 to 44 years, vaccine serotype IPD declined by 57% (95% CI, −63% to−50% [3.7/100,000 to 1.6/100,000]), compared with smaller nonvaccine serotype IPD declines (3.9/100,000 to 3.5/100,000; −11%, 95% CI, −21% to +4%). Among children <2 years, penicillin-nonsusceptible IPD rates decreased (34.1/100,000 to 6.1/100,000 [−82%; 95% CI, −85% to−78%]). The large reduction in disease caused by vaccine serotypes among both children and adults likely reflects substantial direct and indirect benefits from PCV-7 introduction. The smaller reduction in nonvaccine-serotype IPD suggests HIV prevention efforts are also playing a role in prevention of serious pneumococcal disease.Conflict of interest