Level of Recall Bias Regarding Pneumococcal Vaccination History among Adults Hospitalized with Community-Acquired Pneumonia: Results from the University of Louisville Pneumonia Study

Background: Recall bias is likely to occur in vaccine effectiveness studies using self-reported vaccination history. The validity of patient-reported vaccination status for adults is not well defined. The objective of this study was to evaluate the validity of self-reported pneumococcal vaccination history among patients hospitalized with community-acquired pneumonia (CAP). Methods: Prospective ancillary study of a population-based observational study of hospitalized patients with CAP in the city of Louisville. To be included in the analysis, patients had to (i) be reached by phone 30-days after discharge from the hospital and (ii) report that they remembered whether or not they received a pneumococcal vaccine in the past five years. The vaccination history was classified as 1) Subjective: patient recollection, or 2) Objective: vaccination records from insurance companies or primary care physicians. Results: A total of 2,787 patients who recalled their vaccination history were included in the analysis. Subjective vaccination history was documented to be inaccurate in 1,023 (37%) patients. Conclusions: Our study indicates that in adult patients, self-reported data regarding pneumococcal vaccination is likely to be inaccurate in one out of three patients. This level of recall bias may incorporate a fatal flaw in vaccine effectiveness studies

The epidemiologic and biologic basis for classifying older age as a high-risk, immunocompromising condition for pneumococcal vaccine policy

Introduction: Immunosenescence is a normal biologic process involving deterioration of protective immune responses. Consequently, older adults experience increased risk of infectious diseases, particularly pneumonia, and its leading bacterial cause, Streptococcus pneumoniae. Pneumococcal vaccine recommendations are often limited to adults with specific medical conditions despite similar disease risks among older adults due to immunosenescence. Areas covered: This article reviews epidemiologic, biologic, and clinical evidence supporting the consideration of older age due to immunosenescence as an immunocompromising condition for the purpose of pneumococcal vaccine policy and the role vaccination can play in healthy aging. Expert opinion: Epidemiologic and biologic evidence suggest that pneumococcal disease risk increases with age and is comparable for healthy older adults and younger adults with immunocompromising conditions. Because immunocompromising conditions are already indicated for pneumococcal conjugate vaccines (PCVs), a comprehensive public health strategy would also recognize immunosenescence. Moreover, older persons should be vaccinated before reaching the highest risk ages, consistent with the approach for other immunocompromising conditions. To facilitate PCV use among older adults, vaccine technical committees (VTCs) could classify older age as an immunocompromising condition based on the process of immunosenescence. With global aging, VTCs will need to consider immunosenescence and vaccine use during healthy aging

Rationale and Methods of the Study Protocol: Streptococcus pneumoniae Serotypes in Adults 18 Years and Older with Radiographically-Confirmed Community-Acquired Pneumonia (CAP)

This study was an active, prospective surveillance study of adults 18 years and older hospitalized with community-acquired pneumonia (CAP) due to Streptococcus pneumoniae conducted at 21 hospitals in ten cities across the United States. This report describes the surveillance methodology applied between October 7, 2013 and September 30, 2016, including the identification and description of surveillance areas and populations at-risk for CAP hospitalization for estimation of incidence rates for selected study sites

Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia

BACKGROUND: Few studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults. METHODS: This observational, prospective surveillance study recruited hospitalized adults aged \u3e /=18years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13. RESULTS: Of 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1years and 52.7% were aged \u3e /=65years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged \u3e /=65years. Among patients aged 18-64years PCV13 serotypes were detected in 3.8-5.3% of patients depending on their risk status. CONCLUSIONS: After implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population

Upper Respiratory Tract Colonization With Streptococcus pneumoniae in Adults

Introduction: Most of the current evidence regarding pneumococcal upper respiratory colonization in adults suggests that despite high disease burden, carriage prevalence is low. Contemporary studies on adult pneumococcal colonization have largely followed the pediatric approach by which samples are obtained mostly from the nasopharynx and bacterial detection is evaluated by routine culture alone. Recent evidence suggests that the ‘pediatric approach’ may be insufficient in adults and pneumococcal detection in this population may be improved by longitudinal studies that include samples from additional respiratory sites combined with more extensive laboratory testing. Areas covered: In this article, relevant literature published in peer review journals on adult pneumococcal colonization, epidemiology, detection methods, and recommendations were reviewed. Expert opinion: Respiratory carriage of Streptococcus pneumoniae has been underestimated in adults. Contemporary pneumococcal carriage studies in adults that collect samples from alternative respiratory sites such as the oropharynx, saliva, or nasal wash; are culture-enriched for pneumococcus; and use molecular diagnostic methods designed to target two pneumococcal DNA sequences should enhance pneumococcal detection in the adult respiratory tract. This finding may have implications for the interpretation of dynamics of pneumococcal transmission and vaccination

Expanded Analysis of 20 Pneumococcal Serotypes Associated With Radiographically Confirmed Community-Acquired Pneumonia in Hospitalized US Adults

BACKGROUND: Streptococcus pneumoniae is a causative agent of community-acquired pneumonia (CAP). The 13-valent pneumococcal conjugate vaccine (PCV13) has significantly decreased the burden of PCV13-serotype pneumococcal disease; however, disease due to nonvaccine serotypes remains substantial. A recent study documented the persistence of PCV13 serotypes among US adults hospitalized with radiographically confirmed CAP. The current analysis used a recently developed urinary antigen detection (UAD) assay (UAD2) to extend these results to additional serotypes included in an investigational PCV20 vaccine. METHODS: This prospective study enrolled adults aged \u3e /=18 years hospitalized with radiographically confirmed CAP between October 2013-September 2016. Presence of S pneumoniae was determined by blood and respiratory sample culture, BinaxNOW(R) urine testing, and UAD. In addition to Quellung on cultured isolates when available, serotypes were identified from urine specimens using UAD1 for PCV13 serotypes and UAD2 for 7 PCV20-unique serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) and 4 additional serotypes (2, 9N, 17F, and 20). RESULTS: Among 12,055 subjects with radiographically confirmed CAP, 1482 were positive for S pneumoniae. PCV13 and PCV20-unique serotypes were associated with 37.7% (n=559) and 27.0% (n=400) of cases, respectively; 288 subjects were exclusively diagnosed as positive for S pneumoniae by UAD2. Demographic and clinical disease characteristics were similar between subjects with CAP caused by PCV13 and PCV20-unique serotypes. CONCLUSIONS: The current analysis using UAD2 identified a sizeable proportion of hospitalized adult CAP associated with PCV20-unique serotypes. PCV20 may therefore address the burden of CAP caused by the additional serotypes present in the vaccine

Decision-making for PCV in adults

Thirteen-valent pneumococcal conjugate vaccine (PCV13) was licensed in adults to address the unmet medical need of vaccine-type community acquired pneumonia (CAP) and the limitations of previous plain-polysaccharide vaccines. Since then, some have questioned the utility of adult PCV13 use, arguing that: i) high PCV13 uptake in young children would provide indirect effects that, by themselves, would sufficiently protect unvaccinated adults and ii) no data describing the real-world effectiveness of PCV13 use in adults, especially with immunocompromising conditions, exist. Even in countries like the United States where PCV13 has been routinely recommended for all adults aged ≥ 65 years, the recommendation is contingent on a re-evaluation to determine if continued use is needed in the context of a mature PCV13 pediatric immunization program. Emerging evidence, however, suggests that i) a meaningful burden of PCV13-type pneumococcal pneumonia still persists in adults at increased risk for pneumococcal disease, despite indirect effects from long-standing pediatric PCV13 use, ii) adult PCV13 use is effective and has reduced pneumococcal CAP, even in the elderly and those with chronic medical or immunocompromising conditions – and disease could come back if PCV13 were removed, and iii) ethical and pragmatic vaccine policy considerations support continued adult PCV13 use in countries that have already introduced the vaccine (eg, disparities in adult PCV13 uptake, confusion stemming from removing a previously-recommended vaccine for a non-safety-related concern, and the reality that next-generation PCVs are only a few years away). Together, these findings suggest that continued PCV13 vaccination in adults is needed to control vaccine-type CAP