Determining Pneumocystis jirovecii Colonisation from Infection Using PCR-Based Diagnostics in HIV-Negative Individuals

Author:

Watson Anna Louise12,Woodford John3ORCID,Britton Sumudu1,Gupta Rita4,Whiley David45,McCarthy Kate1

Affiliation:

1. Infectious Diseases, Royal Brisbane & Women’s Hospital, Metro North Health, Herston, QLD 4006, Australia

2. Herston Infectious Diseases Institute, Herston, QLD 4006, Australia

3. Infectious Diseases, Ipswich Hospital, Ipswich, QLD 4305, Australia

4. Pathology Queensland, Herston, QLD 4006, Australia

5. The University of Queensland, Herston, QLD 4006, Australia

Abstract

Background: Pneumocystis jirovecii pneumonia is increasingly diagnosed with highly sensitive PCR diagnostics in immunocompromised, HIV-negative individuals. We assessed the performance of our in-house quantitative PCR with the aim to optimise interpretation. Methods: Retrospective audit of all positive P. jirovecii qPCRs on induced sputum or BAL fluid at a single centre from 2012 to 2023. Medical and laboratory records were analysed and people with HIV were excluded. Cases were categorised as colonisation, high-probability PCP or uncertain PCP infection against a clinical gold standard incorporating clinico-radiological data. Quantitative PCR assay targeting the 5s gene was utilised throughout the time period. Results: Of the 82 positive qPCRs, 28 were categorised as high-probability PCP infection, 30 as uncertain PCP and 24 as colonisation. There was a significant difference in qPCR values stratified by clinical category but not respiratory sample type. Current assay performance with a cutoff of 2.5 × 105 copies/mL had a sensitivity of 50% (95% CI, 30.65–69.35%) and specificity of 83.33% (95% CI, 62.62–95.26%). Youden Index calculated at 6.5 × 104 copies/mL had a sensitivity of 75% (56.64–87.32%, 95% CI) and specificity of 66.67% (46.71–82.03%, 95% CI). High and low cutoffs were explored. Significant variables associated with infection were age > 70 years old, the presence of fever, hypoxia or ground glass changes. Conclusions: A single qPCR cutoff cannot reliably determine P. jirovecii infection from colonisation. Low and high cutoffs are useful, however, a large “possible infection” cohort will remain where interpretation of clinic-radiological factors remains essential. Standardisation of assays with prospective validation in specific immunocompromised groups will allow greater generalisability and allow large-scale prospective assay validation to be performed.

Publisher

MDPI AG

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