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Background <p>Accurate interpretation of <i>Candida</i> detection in women with vulvovaginal symptoms remains difficult, because organism recovery may reflect either clinically relevant infection or nonpathogenic colonization. We have recently demonstrated that the secreted fungal zinc-binding protein, Pra1 is responsible for driving the inflammatory immunopathology of VVC. We therefore reasoned that <i>PRA1</i> expression by <i>Candida albicans</i> in the vagina may act as a diagnostic tool to discriminate between commensal colonisation and active disease.</p> Methods <p>We conducted a 12-week prospective, single-center exploratory biomarker analysis nested within a registered parent clinical trial. Nine women with vulvovaginal symptoms provided cervicovaginal lavage samples and clinical data at baseline and at weeks 4, 8, and 12. This report does not present the primary efficacy analysis of the randomized trial. At each visit, <i>Candida</i> culture status and clinical severity score (CSS) were recorded. Symptomatic <i>Candida</i> vaginitis was defined as <i>Candida</i> culture positivity with CSS ≥ 3 at the same visit. Species identification of fungal isolates was performed by MALDI-TOF mass spectrometry, and vaginal <i>PRA1</i> was quantified by SYBR Green real-time qPCR. Vaginal <i>PRA1</i> concentrations were assessed as a time-varying same-visit biomarker using repeated-measures approaches, non-parametric comparisons, correlation analyses, and receiver operating characteristic (ROC) curves.</p> Results <p><i>PRA1</i> concentrations were substantially higher in <i>Candida</i> culture-positive than in culture-negative samples (median 4,011 vs. 21.5 pg/µL, <i>p</i> = 3.99 × 10⁻⁵). <i>PRA1</i> was also higher in samples meeting criteria for symptomatic <i>Candida</i> vaginitis than in asymptomatic culture-negative samples (median 11,762 vs. 21.5 pg/µL, <i>p</i> = 8.15 × 10⁻⁵). Among culture-positive observations, <i>PRA1</i> was associated with symptom severity (Spearman rho = 0.67; Pearson <i>r</i> = 0.56 after log10 transformation). Same-visit discrimination was high in this cohort for both <i>Candida</i> culture positivity and symptomatic <i>Candida</i> vaginitis (AUC approximately 0.95 for each outcome). In this small exploratory cohort, lower <i>PRA1</i> thresholds achieved 100% sensitivity and negative predictive value for clinically significant <i>Candida</i> vaginitis. These estimates require validation in larger studies.</p> Conclusions <p>These preliminary findings suggest that vaginal <i>PRA1</i> may help distinguish symptomatic <i>Candida</i>-associated disease from clinically insignificant <i>Candida</i> detection and may be particularly useful as a rule-out biomarker. Given the small sample size and exploratory design, these results should be regarded as hypothesis-generating and require validation in larger, independent cohorts. The study protocol was approved by the Hungarian National Institutional Review Medical Research Council (approval No. 3282-7/2023/EUIG).</p> <p>The parent trial is registered at ClinicalTrials.gov (NCT05895162; 2023-06-08).</p>

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Vaginal PRA1 identifies clinically relevant Candida albicans vaginitis and excludes asymptomatic colonization: an exploratory study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月17日

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  • Elena Roselletti,
  • Barbara Kozma,
  • David Ratonyi,
  • Alexandra Kunkli,
  • Bence Kozma,
  • Peter Takacs,
  • Duncan Wilson

摘要

Background

Accurate interpretation of Candida detection in women with vulvovaginal symptoms remains difficult, because organism recovery may reflect either clinically relevant infection or nonpathogenic colonization. We have recently demonstrated that the secreted fungal zinc-binding protein, Pra1 is responsible for driving the inflammatory immunopathology of VVC. We therefore reasoned that PRA1 expression by Candida albicans in the vagina may act as a diagnostic tool to discriminate between commensal colonisation and active disease.

Methods

We conducted a 12-week prospective, single-center exploratory biomarker analysis nested within a registered parent clinical trial. Nine women with vulvovaginal symptoms provided cervicovaginal lavage samples and clinical data at baseline and at weeks 4, 8, and 12. This report does not present the primary efficacy analysis of the randomized trial. At each visit, Candida culture status and clinical severity score (CSS) were recorded. Symptomatic Candida vaginitis was defined as Candida culture positivity with CSS ≥ 3 at the same visit. Species identification of fungal isolates was performed by MALDI-TOF mass spectrometry, and vaginal PRA1 was quantified by SYBR Green real-time qPCR. Vaginal PRA1 concentrations were assessed as a time-varying same-visit biomarker using repeated-measures approaches, non-parametric comparisons, correlation analyses, and receiver operating characteristic (ROC) curves.

Results

PRA1 concentrations were substantially higher in Candida culture-positive than in culture-negative samples (median 4,011 vs. 21.5 pg/µL, p = 3.99 × 10⁻⁵). PRA1 was also higher in samples meeting criteria for symptomatic Candida vaginitis than in asymptomatic culture-negative samples (median 11,762 vs. 21.5 pg/µL, p = 8.15 × 10⁻⁵). Among culture-positive observations, PRA1 was associated with symptom severity (Spearman rho = 0.67; Pearson r = 0.56 after log10 transformation). Same-visit discrimination was high in this cohort for both Candida culture positivity and symptomatic Candida vaginitis (AUC approximately 0.95 for each outcome). In this small exploratory cohort, lower PRA1 thresholds achieved 100% sensitivity and negative predictive value for clinically significant Candida vaginitis. These estimates require validation in larger studies.

Conclusions

These preliminary findings suggest that vaginal PRA1 may help distinguish symptomatic Candida-associated disease from clinically insignificant Candida detection and may be particularly useful as a rule-out biomarker. Given the small sample size and exploratory design, these results should be regarded as hypothesis-generating and require validation in larger, independent cohorts. The study protocol was approved by the Hungarian National Institutional Review Medical Research Council (approval No. 3282-7/2023/EUIG).

The parent trial is registered at ClinicalTrials.gov (NCT05895162; 2023-06-08).