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

Abstract

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