Serotype-specific Urinary Antigen Detection Research Articles

Multicountry Review of Streptococcus pneumoniae Serotype Distribution Among Adults With Community-Acquired Pneumonia.

Nonbacteremic community-acquired pneumonia (CAP) is a leading presentation of severe pneumococcal disease in adults. Serotype-specific urinary antigen detection (UAD) assay can detect serotypes causing pneumococcal CAP, including nonbacteremic cases, and guide recommendations for use of higher valency pneumococcal conjugate vaccines (PCVs). Adult CAP serotype distribution studies that used both Pfizer UADs (UAD1, detects PCV13 serotypes; UAD2, detects PCV20 non-PCV13 serotypes plus 2, 9N, 17F, and 20) were identified by review of an internal study database and included if results were published. The percentages of all-cause radiologically confirmed CAP (RAD + CAP) due to individual or grouped (PCV13, PCV15, and PCV20) serotypes as detected from culture or UAD were reported. Six studies (n = 2, United States; n = 1 each, Germany, Sweden, Spain, and Greece) were included. The percentage of RAD + CAP among adults ≥18 years with PCV13 serotypes equaled 4.6% to 12.9%, with PCV15 serotypes 5.9% to 14.5%, and with PCV20 serotypes 7.8% to 23.8%. The percentage of RAD + CAP due to PCV15 and PCV20 serotypes was 1.1-1.3 and 1.3-1.8 times higher than PCV13 serotypes, respectively. PCV13 serotypes remain a cause of RAD + CAP among adults even in settings with pediatric PCV use. Higher valency PCVs among adults could address an important proportion of RAD + CAP in this population.

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

Pneumococcal serotypes in adults hospitalized with community-acquired pneumonia in Greece using urinary antigen detection tests: the EGNATIA study, November 2017 – April 2019

ABSTRACT Greece introduced a 13-valent pneumococcal conjugate vaccine (PCV13) into the infant national immunization program in 2010 (3 + 1 schedule until June 2019). Since 2015, PCV13 has been recommended for adults aged 19–64 years with comorbidities and adults ≥65 years sequentially with 23-valent pneumococcal polysaccharide vaccine (PPSV23). We examined pneumococcal serotype distribution among Greek adults aged ≥19 years hospitalized with community-acquired pneumonia (CAP) during November 2017-April 2019. This was an interim analysis of EGNATIA, a prospective study of adult hospitalized CAP in the cities of Ioannina and Kavala. Pneumococcus was identified using cultures, BinaxNow®, serotype-specific urinary antigen detection assays (UAD-1/2). Our analysis included overall 482 hospitalized CAP patients (mean age: 70.5 years; 56.4% male). 53.53% of patients belonged to the highest pneumonia severity index (PSI) classes (IV-V). Pneumococcus was detected in 65 (13.5%) patients, with more than half (57%) of cases detected only by UAD. Approximately two-thirds of pneumococcal CAP occurred in those aged ≥65 years (n = 40, 8.3% of CAP). More than half of pneumococcal CAP (n = 35, 53.8%) was caused by PCV13 serotypes. Most frequently detected PCV13 serotypes were 3, 19A, 23F, collectively accounting for 83% of PCV13 vaccine-type (VT) CAP and 6% of all-cause CAP. Overall, 82.9% of PCV13 VT CAP occurred among persons with an indication (age/risk-based) for PCV13 vaccination. Even with a mature PCV13 childhood immunization program, a persistent burden of PCV13 VT CAP exists in Greek adults. Strategies to increase PCV13 (and higher-valency PCVs, when licensed) coverage in adults should be implemented to reduce the disease burden.

Incidence, aetiology and serotype coverage for pneumococcal vaccines of community-acquired pneumonia in adults: a population-based prospective active surveillance study in Brazil

ObjectivesTo determine the incidence, aetiology and pneumococcal serotype distribution of community-acquired pneumonia (CAP) in Brazilian adults during a 2-year period.DesignProspective population-based surveillance study.SettingPatients from two emergency hospitals in Brazil were...

The Evolution and Distribution of Pneumococcal Serotypes in Adults Hospitalized With Community-Acquired Pneumonia in Spain Using a Serotype-Specific Urinary Antigen Detection Test: The CAPA Study, 2011-2018.

BackgroundSpain introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in the childhood National Immunization Program in 2015–2016 with coverage of 3 doses of 94.8% in 2018. We assessed the evolution of all pneumococcal, PCV13 vaccine type (VT), and experimental PCV20-VT (PCV13 + serotypes 8, 10A, 11A, 12F, 15B, 22F, 33F) hospitalized community-acquired pneumonia (CAP) in adults in Spain from 2011–2018.MethodsA prospective observational study of immunocompetent adults (≥18 years) admitted to 4 Spanish hospitals with chest X-ray–confirmed CAP between November 2011 and November 2018. Microbiological confirmation was obtained using the Pfizer serotype-specific urinary antigen detection tests (UAD1/UAD2), BinaxNow test for urine, and conventional cultures of blood, pleural fluid, and high-quality sputum.ResultsOf 3107 adults hospitalized with CAP, 1943 were ≥65 years. Underlying conditions were present in 87% (n = 2704) of the participants. Among all patients, 895 (28.8%) had pneumococcal CAP and 439 (14.1%) had PCV13-VT CAP, decreasing from 17.9% (n = 77) to 13.2% (n = 68) from 2011–2012 to 2017–2018 (P = .049). PCV20-VT CAP occurred in 243 (23.8%) of those included in 2016–2018. The most identified serotypes were 3 and 8. Serotype 3 accounted for 6.9% (n = 215) of CAP cases, remaining stable during the study period, and was associated with disease severity.ConclusionsPCV13-VT caused a substantial proportion of CAP in Spanish immunocompetent adults 8 years after introduction of childhood PCV13 immunization. Improving direct PCV13 coverage of targeted adult populations could further reduce PCV13-VT burden, a benefit that could be increased further if PCV20 is licensed and implemented.

Application of a Pneumococcal Serotype-specific Urinary Antigen Detection Test for Identification of Pediatric Pneumonia in Burkina Faso.

Serotype-specific diagnosis of pneumococcal community-acquired pneumonia in children under age 5 years would mark a major advancement for understanding pneumococcal epidemiology and supporting vaccine decision-making. A Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and subsequently validated in adults, but its applicability to children is unknown. This study aimed to set appropriate cutoffs for use of the UAD in a healthy pediatric population and apply these cutoffs in children with pneumonia in sub-Saharan Africa. The cutoffs were determined by assessing 379 urines obtained from healthy children under age 5 years from the Bobo-Dioulasso area for serotypes included in 13-valent pneumococcal conjugate vaccine (UAD-1) and the 11 other serotypes unique to 23-valent pneumococcal polysaccharide vaccine (UAD-2). Based on the assigned cutoff values, among 108 children who met the World Health Organization consolidation endpoint criteria, UAD-1 and UAD-2 were positive in 23.3% and 8.3%, respectively; among 364 children with clinically suspected pneumonia who did not meet the World Health Organization criteria, UAD-1 and UAD-2 were positive for 6.6% and 3.6%, respectively. Pneumococcal carriage prevalence was similar among pneumonia cases (30%) versus controls (35%) as was semiquantitative carriage density. UAD-1 and UAD-2 were able to distinguish community controls from children with pneumonia, particularly pneumonia with consolidation. Future studies are needed to confirm these results and more fully assess the contribution of pneumococcal carriage and concurrent viral infection.

Non-Invasive Pneumococcal Pneumonia Due to Vaccine Serotypes: A Systematic Review and Meta-Analysis

Background: Non-invasive pneumococcal pneumonia causes significant morbidity and mortality in older adults globally. Understanding pneumococcal sero-epidemiology in adults ≥50 years is necessary to inform pneumococcal vaccination policies and direct the updating of pneumococcal vaccines. Methods: We conducted a systematic review and random-effects meta-analysis to determine the proportion of community-acquired pneumonia (CAP) in people ≥50 years due to pneumococcus and the proportion caused by current pneumococcal vaccine serotypes. Heterogeneity was explored by subgroup analysis according to a) patient group (stratified versus age) and depth of testing, b) detection/serotyping method, and c) continent. The protocol is registered with PROSPERO (CRN42020192002).Findings There were 28 included studies (34,216 patients). The estimated proportion of pneumococcal CAP was highest in studies that mainly used 24-valent serotype-specific urinary antigen detection (ss-UAD)(30% [95%CI 28-31%]), followed by serology (29% [26-32%]), PCR (21% [20-23%]), ss-UAD13 (17% [13-22%]), and culture alone (14% [10-19%]). Inter-continental heterogeneity was observed, with a higher pooled estimate in Europe (26% [21-30%, I2 =92%] than North America (11% [9-12%, I2 =87·2%](p<0·001). PCV13-serotype estimates were also influenced by serotyping methods. Interpretation: Non-invasive pneumococcal CAP, including disease due to current pneumococcal vaccine serotypes, remains a burden in adults aged ≥50 years, despite the introduction of pneumococcal infant immunisation in most countries. Studies heavily reliant on ss-UADs restricted to vaccine-type serotypes may overestimate the proportion of potentially vaccine-preventable pneumococcal pneumonia. Sero-epidemiological data from low-income countries are lacking. Funding LL is funded by the National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, UK. Declaration of Interest: Professor Lim reports grants from National Institute for Health Research (NIHR), grants from Pfizer, outside the submitted work. All other authors declare no competing interests.

Epidemiology of community-acquired pneumonia in the era of extended serotype-covering multivalent pneumococcal conjugate vaccines

BackgroundSouth Korea has been providing 10-valent pneumococcal conjugate vaccine/(PCV10)/13-valent pneumococcal conjugate vaccine (PCV13) to children and 23-valent pneumococcal polysaccharide vaccine (PPSV23) to older adults as part of a national immunization program. MethodsFrom September 2015 to August 2017, a prospective cohort study was conducted for adults aged ≥19 years with community-acquired pneumonia (CAP) at four university hospitals. All-cause and pneumococcal CAP incidence and mortality rates were evaluated on the basis of hospital catchment population. Serotype distribution of pneumococcal CAP was also evaluated. ResultsAmong 2669 patients with CAP, 252 cases (9.4%) were pneumococcal CAP cases. The annual incidences of all-cause and pneumococcal CAP were 194.3 cases and 18.3 cases respectively, per 100,000 persons. Serotyped Streptococcus pneumoniae was identified in 107 cases (42.5%) through culture or a serotype-specific urinary antigen detection assay. Pneumococcal CAP caused by the PCV13 and PPSV23 serotypes were 50 cases (46.7% of serotyped pneumococcal CAP and 19.8% of pneumococcal CAP), and 83 cases (77.6% of serotyped pneumococcal CAP and 32.9% of pneumococcal CAP), respectively. The most prevalent serotype was 3 (n = 21, 19.6% of serotyped pneumococcal CAP), followed by 19A (n = 10, 9.3% of serotyped pneumococcal CAP) and 11A (n = 10, 9.3% of serotyped pneumococcal CAP). Compared with non-pneumococcal CAP patients, pneumococcal CAP patients were more likely to have a higher CURB-65 scores (P = 0.002). The overall 30-day mortality rate of pneumococcal CAP was higher than that of non-pneumococcal CAP (6.3% versus 5.6%; odds ratio [OR], 1.15; 95% confidence interval [CI], 0.67–1.96), but this trend was reversed in patients aged 65–74 years (4.2% versus 8.6%; OR, 0.47; 95% CI, 0.14–1.54). ConclusionsThe disease burden of PCV13-serotype pneumococcal CAP remains significantly high in Korean adults, particularly among elderly people, even after a high uptake of pediatric PCVs.

Changing Epidemiology of Community-Acquired Pneumonia in the Era of Extended Serotype-Covering Multivalent Pneumococcal Conjugate Vaccines

Background: With high pneumococcal vaccine uptake rates in South Korea, the burden of community-acquired pneumonia (CAP) and serotype distribution of pneumococcal CAP may change. Methods: From September 2015 to August 2017, a prospective cohort study was conducted for Korean adults aged ≥ 19 years who were hospitalized with CAP at four university hospitals. All-cause and pneumococcal CAP incidence and mortality rates were evaluated based on the hospital catchment population. Pneumococcal CAP was identified by culture and BinaxNOW urinary antigen test. A newly developed 24 serotype-specific urinary antigen detection (UAD) assay was also used. Findings: Among 2,669 patients with medically attended CAP, 252 cases (9.4%) were pneumococcal CAP. Pneumococcal serotypes were determined in 107 cases. Annual incidence of all-cause and pneumococcal CAP were 194.3 cases and 18.3 cases per 100,000 persons, respectively. Pneumococcal CAP caused by PCV13 and PPSV23 serotypes comprised 46.7% and 77.6% of all serotypable S. pneumonia, respectively. The most prevalent serotype was 3 (19.6%), followed by 19A (9.3%) and 11A (9.3%). The overall 30-day mortality rate of pneumococcal CAP was higher than that of all-cause CAP (6.3% versus 5.7%), but the opposite was found in patients aged 65–74 years (4.2% versus 8.1%) Interpretation: Indirect herd effect from pediatric vaccination might be insufficient. To better control adult CAP, age- and risk-targeted individual PCV13 vaccination should be considered. PPSV23 might decrease the severity of pneumococcal pneumonia, thereby lowering the mortality rate in elderly patients aged 65–74 years. Funding Statement: This work was supported by a Korea University Guro Hospital grant (no. K1719481) that was underwritten by Pfizer. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was conducted after approval by Institutional Review Boards at each participating study hospital.

A post-hoc analysis of serotype-specific vaccine efficacy of 13-valent pneumococcal conjugate vaccine against clinical community acquired pneumonia from a randomized clinical trial in the Netherlands

BackgroundSerotype-specific vaccine efficacy (VE) against adult community acquired pneumonia (CAP) remains poorly defined, yet such data are important for assessing the utility of adult pneumococcal conjugate vaccine (PCV) programs. MethodsWe evaluated the Community Acquired Pneumonia Immunization Trial in Adults to assess serotype-specific VE for CAP. This parallel-arm randomized clinical trial assessed 13-valent PCV (PCV13) VE among community dwelling persons aged ≥65 years in The Netherlands. In the original analysis, PCV13 VE against first episodes of vaccine-type (VT) chest radiology confirmed CAP was 45.6% (95% confidence interval [CI] 21.8–62.5%). Unlike the original analysis, we included any subject that met a clinical definition of CAP regardless of radiographic findings. VT-CAP was identified by culture (sterile or non-sterile) or serotype-specific urinary antigen detection (SSUAD) test. Only the five serotypes with at least 10 episodes in the control arm, based on the original analysis, were included for VE assessment. ResultsOf 272 clinical CAP visits with VT serotypes identified, 253 (93%) were identified by SSUAD including 210 (77%) by SSUAD alone. VE was determined for serotypes 1, 3, 6A, 7F, and 19A, with total first episodes of, respectively, 27, 36, 25, 38, and 48. VE (95%CI) for the five evaluated serotypes against first clinical CAP episodes were: serotype 1, 20.0% (−83.1% to 65.8%); serotype 3, 61.5% (17.6–83.4%); serotype 6A, 33.3% (−58.6% to 73.2%); serotype 7F, 73.3% (40.5–89.4%); and serotype 19A, 45.2% (−2.2% to 71.5%). DiscussionStatistically significant VE was observed for serotypes 3 and 7F for clinical CAP among elderly community dwelling adults. The VE point estimates and CIs for serotypes 1, 6A, and 19A were lower but consistent with the overall VT-CAP VE of 45.6% previously reported. These findings may be relevant in models to accurately account for the potential impact of adult PCV13 immunization.

Pneumococcal epidemiology among us adults hospitalized for community-acquired pneumonia

BackgroundFew 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. MethodsThis observational, prospective surveillance study recruited hospitalized adults aged ≥18 years 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 30 days 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. ResultsOf 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1 years and 52.7% were aged ≥65 years. 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 ≥65 years. Among patients aged 18–64 years PCV13 serotypes were detected in 3.8–5.3% of patients depending on their risk status. ConclusionsAfter 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.

Post hoc analysis of the efficacy of the 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia in at-risk older adults

BackgroundIndividuals with certain chronic medical conditions are at higher risk of developing pneumonia and pneumococcal disease than those without. Using data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), this post hoc analysis assessed the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥65 years with at-risk conditions. MethodsThe Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) was a double-blind, parallel-group, randomized, placebo-controlled study in the Netherlands in which adults aged ≥65 years received either PCV13 or placebo. Outcomes of interest were identified using prespecified clinical criteria, radiographic confirmation, routine microbiologic testing, and a serotype-specific urinary antigen detection assay.In this post hoc analysis, participants were classified by at-risk status based on self-reporting of any of the following chronic medical conditions: heart disease, lung disease, asthma, diabetes, liver disease, and smoking. The objective of this analysis was to assess PCV13 vaccine efficacy (VE) against a first episode of vaccine-serotype community-acquired pneumonia (VT-CAP) in at-risk participants. ResultsOf the 84,496 adults enrolled in the study, 41,385 (49.2%) were considered at risk owing to chronic medical conditions. Of the 139 VT-CAP cases, 115 (82.7%) occurred in these participants. VE of PCV13 against a first episode of VT-CAP among participants with at-risk conditions was 40.3% (95.2% CI: 11.4%, 60.2%). Average duration of follow-up since vaccination was 3.95 years for at-risk participants; protection did not wane over the study period. ConclusionsThis post hoc analysis of the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) showed significant and persistent efficacy of PCV13 against VT-CAP in at-risk older adults.ClinicalTrials.gov identifier: NCT00744263.

Pneumococcal Community-Acquired Pneumonia Detected by Serotype-Specific Urinary Antigen Detection Assays.

Streptococcus pneumoniae is considered the leading bacterial cause of pneumonia in adults. Yet, it was not commonly detected by traditional culture-based and conventional urinary testing in a recent multicenter etiology study of adults hospitalized with community-acquired pneumonia (CAP). We used novel serotype-specific urinary antigen detection (SSUAD) assays to determine whether pneumococcal cases were missed by traditional testing. We studied adult patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010-2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study. Traditional diagnostic testing included blood and sputum cultures and conventional urine antigen detection (ie, BinaxNOW). We applied SSUAD assays that target serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13) to stored residual urine specimens. Among 1736 patients with SSUAD and ≥1 traditional pneumococcal test performed, we identified 169 (9.7%) cases of pneumococcal CAP. Traditional tests identified 93 (5.4%) and SSUAD identified 76 (4.4%) additional cases. Among 14 PCV13-serotype cases identified by culture, SSUAD correctly identified the same serotype in all of them. Cases identified by SSUAD vs traditional tests were similar in most demographic and clinical characteristics, although disease severity and procalcitonin concentration were highest among those with positive blood cultures. The proportion of pneumonia cases caused by serotypes exclusively covered by PCV13 was not significantly different between the first and second July-June study periods (6.4% vs 4.0%). Although restricted to the detection of only 13 serotypes, SSUAD testing substantially increased the detection of pneumococcal pneumonia among adults hospitalized with CAP.

The burden of PCV13 serotypes in hospitalized pneumococcal pneumonia in Spain using a novel urinary antigen detection test. CAPA study

Streptococcus pneumoniae serotypes distribution in community-acquired pneumonia (CAP) requiring hospitalization in adults after introduction of PCV13 in children is not well known. Our aim was to evaluate the distribution of serotypes in pneumococcal pneumonia according to risk factors and comorbidity conditions after the introduction of PCV13 in children in 2010. A prospective study from 2011 to 2014 was performed in immunocompetent adults hospitalized with CAP in 3 Spanish hospitals. Microbiological confirmation was obtained using a serotype specific urinary antigen detection test (UAD test), Binax Now and conventional cultures. 1258 adults were enrolled and pneumococcal pneumonia (invasive disease in 17.7%) was confirmed in 368 (29.3%) and 17.6% of the any-cause CAP were caused by PVC13 serotypes (3.5% PCV7 serotypes). Around 60% of pneumococcal CAP were caused by PCV13 serotypes (74.6% in invasive episodes vs 57.4% in non-invasive ones). The most prevalent serotypes in invasive disease were 1, 3, 7F, 19A and 14. No significant differences were observed in the distribution of PCV13 serotypes across the study periods. Regarding comorbidity, the rate of PCV13 serotypes was similar among them, and it was slightly higher in those with no underlying conditions. Serotypes included in PCV13 caused a significant proportion of CAP in adults with underlying conditions and in healthy adults, with no significant changes in cases due to PCV7 or PCV13 from 2011 to 2014, suggesting an insufficient indirect protection from childhood vaccination. Strategies for implementing pneumococcal vaccination of adults are encouraged to reduce the incidence of pneumococcal episodes.

Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly

BackgroundHerd protection from infant pneumococcal conjugate vaccination is well established for invasive pneumococcal disease (IPD) but not for non-IPD pneumococcal community-acquired pneumonia (PCAP). We assessed the contribution of vaccine-serotypes in non-IPD PCAP in adults 65 years and older in the period 2008–2013. MethodsThis is a post hoc analysis of two prospective studies from the Netherlands. Serotype specific urinary antigen detection and routine microbiological testing were used to categorize episodes as IPD or non-IPD PCAP caused by 7-valent pneumococcal conjugate vaccine (PCV7), PCV10-7 (three additional PCV10 serotypes), PCV13-10 (three additional PCV13 serotypes), and non-PCV13 serotypes. Proportions per vaccine-serotype group were assessed per year from June 1st to May 31st. Time trends were compared to national IPD data. ResultsOf 270 non-IPD PCAP episodes with known serotype, PCV7 serotypes decreased from 28% in 2008/2009 to 7% in 2012/2013 (p-value for trend <0.001). No change in PCV10-7 (19% overall) and PCV13-10 (29% overall) serotypes was observed. Non-PCV13 serotypes increased from 30% in 2008/2009 to 37% in 2012/2013 (p-value for trend 0.048). Trends corresponded with national IPD data. ConclusionPCV7 serotypes declined in non-IPD PCAP among elderly between 2008 and 2013, comparable to IPD data. No reduction in the additional PCV10 serotypes could be demonstrated within the first two years after PCV10 introduction.

New Pneumococcal Diagnostics---further ahead or more confused?

Invited Lecture AbstractsISPPD-0205 New Pneumococcal Diagnostics---further ahead or more confused?: USEFULNESS OF SEROTYPE SPECIFIC URINARY ANTIGEN DETECTION (UAD) ASSAY TO DETECT PNEUMOCOCCAL PNEUMONIA IN ADULTSW. Albrich1, M.W. Pride2, S.A. Madhi3, J. Callahan4, P.V. Adrian3, R. French5, N. van Niekerk6, S. Sebastian2, V. Souza2, K.U. Jansen2, K.P. Klugman31Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland; 2Pfizer Vaccine Research and Early Development, Pfizer Inc., Pearl River, USA; 3Respiratory and Meningeal Pathogens Research Unit/Medical Research Council, National Institute for Communicable Diseases, Johannesburg, South Africa; 4Callahan Associates Inc, Callahan Associates Inc, La Jolla, USA; 5Biotechnology Clinical Development Statistics, Pfizer Inc., Pearl River, USA; 6Respiratory and Meningeal Pathogens Research Unit/Medical Research Council, Respiratory and Meningeal Pathogens Research Unit/Medical Research Council, Johannesburg, South AfricaBackground and Aims: A urinary antigen detection assay (UAD) for 13 pneumococcal serotypes was recently reported as a useful diagnostic tool for pneumococcal pneumonia. We tested this assay in a well-defined cohort of HIV-infected South African adults with X-ray confirmed pneumonia.Methods: A Luminex xMAP bead-based multiplex UAD detecting the PCV13 serotypes was tested retrospectively in HIV-infected South African adults with pneumonia. UAD positivity cut-offs were established in HIV-infected South Africans without respiratory disease. Pneumonia was considered pneumococcal if a composite diagnostic including any of sputum Gram stain, sputum culture, blood culture or urinary Binax was positive.Results: The UAD identified 6/7 (85.7%) patients with bacteremia due to a PCV13 serotype and did not misclassify any of 3 patients with bacteremia due to a non-PCV13 serotype. Even though the UAD detects only 13 serotypes, it detected more cases of presumed pneumococcal pneumonia among X — ray confirmed cases than the serotype-independent urine Binax (106/235 (45.1%) vs. 52/235 (22.1%); p < 0.001). The UAD was positive in 52/71 (73.2%) patients with a positive composite diagnostic suggesting that 73% of disease was due to PCV13 vaccine types and overall detected significantly more cases than the composite (106/235 (45.1%) vs 71/235 (30.2%); p < 0.001). No correlation was detected between nasopharyngeal colonization density measured by lytA rtPCR and quantitative UAD values.Conclusions: The UAD compared more favourably with other diagnostic tests for pneumococcal pneumonia in adults and may become a new standard for detection of pneumococcal pneumonia in adults.Conflict of interestISPPD-0569 New Pneumococcal Diagnostics---further ahead or more confused?: DISSECTING THE COMPLEXITY OF CARRIAGE: MOLECULAR MINING BY MICROARRAYJ. Hinds11Bacterial Microarray Group, St George’s University of London, London, United KingdomNasopharyngeal carriage represents the natural host reservoir from which Streptococcus pneumoniae may achieve transmission to a new host or cause invasive disease. The biology of the pneumococcus has evolved for successful colonization of this complex niche, including strategies to avoid host defences and co-exist with other microbes. The dynamic microbial community of the nasopharynx is in constant flux and presents opportunities for genetic exchange, both impacting on the effectiveness of pneumococcal vaccines and antimicrobial resistance. Diagnostic methods have revealed key insights into carriage of co-colonizing species and pneumococcal serotypes. As nasopharyngeal carriage is a precursor to invasive pneumococcal disease and has a role in herd immunity, monitoring the effect of vaccines on carriage is especially important. In the era of polysaccharide conjugate vaccines, serotyping has been a key technique to study the impact upon circulating vaccine and non-vaccine serotypes. The microarray-based molecular serotyping method has shown high specificity and sensitivity for detection of multiple pneumococcal serotypes in carriage samples. Enhanced detection of additional serotypes at low abundance may affect metrics used in assessing vaccine efficacy, such as acquisition and duration of carriage, and also case:carrier ratios. Furthermore, the ability to detect serotype variants and non-typeables along with closely related species, antimicrobial resistance determinants and pneumococcal genotype provide valuable supplementary information. This combines to help dissect the complex nasopharyngeal niche and also contextualise an individual sample within other local or global studies.Conflict of interest

Next generation vaccines

Next generation vaccines

Predicting pneumococcal community-acquired pneumonia in the emergency department: Evaluation of clinical parameters

The aim of this study was to quantify the value of clinical predictors available in the emergency department (ED) in predicting Streptococcus pneumoniae as the cause of community-acquired pneumonia (CAP). A prospective, observational, cohort study of patients with CAP presenting in the ED was performed. Pneumococcal aetiology of CAP was based on either bacteraemia, or S. pneumoniae being cultured from sputum, or urinary immunochromatographic assay positivity, or positivity of a novel serotype-specific urinary antigen detection test. Multivariate logistic regression was used to identify independent predictors and various cut-off values of probability scores were used to evaluate the usefulness of the model. Three hundred and twenty-eight (31.0%) of 1057 patients with CAP had pneumococcal CAP. Nine independent predictors for pneumococcal pneumonia were identified, but the clinical utility of this prediction model was disappointing, because of low positive predictive values or a small yield. Clinical criteria have insufficient diagnostic capacity to predict pneumococcal CAP. Rapid antigen detection tests are needed to diagnose S. pneumoniae at the time of hospital admission.

Diagnostic accuracy of a serotype-specific antigen test in community-acquired pneumonia

Our aim was to evaluate the diagnostic accuracy and clinical utility of a serotype-specific urinary antigen detection multiplex assay for identification of 13 pneumococcal serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) in urine of patients with community-acquired pneumonia. Adult patients with clinical suspicion of community-acquired pneumonia were included. In addition to standard diagnostic procedures, a urine sample was collected to perform the urinary antigen detection test. Demographic, clinical, radiological and microbiological data were collected. Among 1095 community-acquired pneumonia patients Streptococcus pneumoniae was identified as causative pathogen in 257 (23%), when using conventional diagnostic methods and in 357 (33%) when urinary antigen detection was added. Of the 49 bacteraemic episodes caused by one of the 13 serotypes covered by the urinary antigen detection, 48 were detected by the urinary antigen detection, indicating a sensitivity of 98%. Of the 77 community-acquired pneumonia episodes with a "non-urinary antigen detection" causative pathogen, none had a positive urinary antigen detection result, indicating a specificity of 100%. Addition of the urinary antigen detection test to conventional diagnostic methods increased the prevalence of S. pneumoniae community-acquired pneumonia by 39%. Using bacteraemic episodes as reference sensitivity and specificity of the urinary antigen detection was 98% and 100%, respectively.

Diagnosis of Invasive Pneumococcal Infection by Serotype-Specific Urinary Antigen Detection

Widespread use of conjugate pneumococcal polysaccharide-protein vaccines may alter the spectrum of pneumococci producing invasive disease. Novel sensitive diagnostic methods would be valuable for monitoring the epidemiology of pneumococcal disease within populations and vaccine recipients. Ideally, these methods should allow determination of the serotype of the infecting clone. Serotype-specific enzyme-linked immunosorbent assays (ELISA) for 13 capsular polysaccharides (types 1, 3, 4, 5, 6A, 6B, 7A, 9 V, 14, 18C, 19 A, 19F, and 23 F) were developed. Experiments with pure capsular polysaccharide demonstrated that the assays were sensitive (0.01 to 1.0 ng/ml) and specific. These assays were used to detect capsular polysaccharide in urine from 263 adult patients with proven (blood culture-positive) invasive pneumococcal disease and pneumonia of unknown etiology and from patients with positive blood cultures yielding bacteria other than pneumococci (control group). Among 76 patients with invasive pneumococcal disease from whom blood culture isolates had been serotyped, 62 (82%) had infections with pneumococci of serotypes represented in the ELISA panel. Capsular antigen matching the serotype of the blood culture isolate was detected in the urine of 52 of these patients, giving a sensitivity of 83.9% for the target serotypes. The tests were significantly more sensitive for urine from patients with pneumococcal pneumonia (89.8%) than for urine from patients with non-pneumonic invasive infection (61.5%; P<0.05). Data from the control group indicated a specificity of 98.8%. These assays should prove valuable in epidemiological investigation of invasive pneumococcal infection in adults, particularly if combined with a sensitive C-polysaccharide detection assay to screen for positive samples.