{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:37:43Z","timestamp":1792787863397,"version":"4.5.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":87,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Debrecen","id":[{"id":"https:\/\/ror.org\/02xf66n48","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Accurate interpretation of\n                      <jats:italic>Candida<\/jats:italic>\n                      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\n                      <jats:italic>PRA1<\/jats:italic>\n                      expression by\n                      <jats:italic>Candida albicans<\/jats:italic>\n                      in the vagina may act as a diagnostic tool to discriminate between commensal colonisation and active disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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,\n                      <jats:italic>Candida<\/jats:italic>\n                      culture status and clinical severity score (CSS) were recorded. Symptomatic\n                      <jats:italic>Candida<\/jats:italic>\n                      vaginitis was defined as\n                      <jats:italic>Candida<\/jats:italic>\n                      culture positivity with CSS\u2009\u2265\u20093 at the same visit. Species identification of fungal isolates was performed by MALDI-TOF mass spectrometry, and vaginal\n                      <jats:italic>PRA1<\/jats:italic>\n                      was quantified by SYBR Green real-time qPCR. Vaginal\n                      <jats:italic>PRA1<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>PRA1<\/jats:italic>\n                      concentrations were substantially higher in\n                      <jats:italic>Candida<\/jats:italic>\n                      culture-positive than in culture-negative samples (median 4,011 vs. 21.5 pg\/\u00b5L,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20093.99\u2009\u00d7\u200910\u207b\u2075).\n                      <jats:italic>PRA1<\/jats:italic>\n                      was also higher in samples meeting criteria for symptomatic\n                      <jats:italic>Candida<\/jats:italic>\n                      vaginitis than in asymptomatic culture-negative samples (median 11,762 vs. 21.5 pg\/\u00b5L,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20098.15\u2009\u00d7\u200910\u207b\u2075). Among culture-positive observations,\n                      <jats:italic>PRA1<\/jats:italic>\n                      was associated with symptom severity (Spearman rho\u2009=\u20090.67; Pearson\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.56 after log10 transformation). Same-visit discrimination was high in this cohort for both\n                      <jats:italic>Candida<\/jats:italic>\n                      culture positivity and symptomatic\n                      <jats:italic>Candida<\/jats:italic>\n                      vaginitis (AUC approximately 0.95 for each outcome). In this small exploratory cohort, lower\n                      <jats:italic>PRA1<\/jats:italic>\n                      thresholds achieved 100% sensitivity and negative predictive value for clinically significant\n                      <jats:italic>Candida<\/jats:italic>\n                      vaginitis. These estimates require validation in larger studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These preliminary findings suggest that vaginal\n                      <jats:italic>PRA1<\/jats:italic>\n                      may help distinguish symptomatic\n                      <jats:italic>Candida<\/jats:italic>\n                      -associated disease from clinically insignificant\n                      <jats:italic>Candida<\/jats:italic>\n                      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).\n                    <\/jats:p>\n                    <jats:p>The parent trial is registered at ClinicalTrials.gov (NCT05895162; 2023-06-08).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-026-05405-w","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:05:45Z","timestamp":1784246745000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vaginal PRA1 identifies clinically relevant Candida albicans vaginitis and excludes asymptomatic colonization: an exploratory study"],"prefix":"10.1186","volume":"26","author":[{"given":"Elena","family":"Roselletti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Kozma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ratonyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kunkli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bence","family":"Kozma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Takacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duncan","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"5405_CR1","doi-asserted-by":"crossref","unstructured":"Parambath S, Dao A, Kim HY, Zawahir S, Izquierdo A, Tacconelli E, et al. 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Virulence. 2013;4(2):119.","DOI":"10.4161\/viru.22913"}],"container-title":["BMC Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12866-026-05405-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-026-05405-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12866-026-05405-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:03:25Z","timestamp":1791817405000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12866-026-05405-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5405"],"URL":"https:\/\/doi.org\/10.1186\/s12866-026-05405-w","relation":{},"ISSN":["1471-2180"],"issn-type":[{"value":"1471-2180","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"assertion":[{"value":"4 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"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). Each participant signed a written informed consent form. All procedures performed in studies involving human participants were under the ethical standards of the Hungarian National Institutional Review Medical Research Council and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"879"}}