Multiplex Urinary Antigen Detection for 13 Streptococcus pneumoniae Serotypes Improves Diagnosis of Pneumococcal Pneumonia in South African HIV-Infected Adults

Author:

Albrich Werner C.12,Pride Michael W.3,Madhi Shabir A.14,Callahan Jan5,Adrian Peter V.14,French Roger6,van Niekerk Nadia1,Sebastian Shite3,Souza Victor3,Telles Jean-Noel7,Paranhos-Baccalà Glaucia7,Jansen Kathrin U.3,Klugman Keith P.148

Affiliation:

1. Respiratory and Meningeal Pathogens Research Unit/Medical Research Council, Johannesburg, South Africa

2. Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

3. Pfizer Vaccine Research and Development, Pfizer Inc., Pearl River, New York, USA

4. National Institute for Communicable Diseases, Johannesburg, South Africa

5. Callahan Associates Inc., La Jolla, California, USA

6. Biotechnology Clinical Development Statistics, Pfizer Inc., Pearl River, New York, USA

7. Emerging Pathogens Laboratory, Fondation Mérieux, Lyon, France

8. Hubert Department of Global Health and Division of Infectious Diseases, Emory University, Atlanta, Georgia, USA

Abstract

ABSTRACT A serotype-specific urinary antigen detection (UAD) assay for 13 serotypes included in the pneumococcal conjugate vaccine (PCV13) was recently reported as a useful diagnostic tool for pneumococcal pneumonia. We aimed to assess the diagnostic accuracy of the UAD in HIV-infected South African adults. Urine specimens from a well-defined cohort of HIV-infected South African adults with pneumonia were evaluated retrospectively in the UAD assay. Pneumonia was considered pneumococcal if either sputum Gram stain, sputum culture, blood culture, or the immunochromatographic (ICT) BinaxNow S. pneumoniae test (composite diagnostic) was positive. Among 235 enrolled pneumonia patients, the UAD assay was more frequently positive (104 [44.3%]) than the composite diagnostic (71 [30.2%]; P < 0.001) and increased the pneumococcal etiology from 30.2% by an additional 22.6% to 52.8%. The UAD assay detected more pneumococcal etiologies (45.0%) than the serotype-independent ICT (23.4%, P < 0.001). UAD identified 6/7 patients with PCV13 serotype bacteremia without misclassification of bacteremia episodes due to non-PCV13 serotypes. UAD was positive for 5.1% of asymptomatic HIV-infected persons, with higher rates among those with nasopharyngeal carriage. Concordance between serotypes identified by UAD and by Quellung reaction and PCR serotyping was 70/86 (81.4%). UAD identified the dominant serotype in multiple serotype carriage. This study confirms the utility of the UAD assay for HIV-infected adults comparing favorably with other diagnostic tests. A highly valent UAD may become a new standard for detection of pneumococcal pneumonia in adults. Prior to PCV introduction, at least 53% of pneumonia cases were due to pneumococci in HIV-infected South African adults.

Funder

Center for AIDS Research, Emory University

Publisher

American Society for Microbiology

Subject

Microbiology (medical)

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