Bayesian accuracy estimates and fit for purpose thresholds of cytology and culture of endometrial swab samples for detecting endometritis in mares

Abstract

The overall aim of this work was to identify the potential impact of misclassification errors associated with routine screening and diagnostic testing for endometritis in mares. Using Bayesian latent class models (BLCM), specific objectives were to: 1) estimate the diagnostic accuracy of cytology and culture of endometrial swab samples to detect endometritis in mares; 2) assess the impact of different cytology thresholds on test accuracy and misclassification costs; and 3) assess the sensitivity (Se) and specificity (Sp) of a diagnostic strategy including both tests interpreted in series and parallel. Diagnostic and pre-breeding endometrial swab samples collected from 3448 mares based at breeding premises located in the South East of England between 2014 and 2020 were retrospectively analysed. Culture results were classified as positive according to three different case definitions: (A) > 90% of the growth colonies were a monoculture; (B) pathogenic or pathogenic and non-pathogenic bacteria were identified; and (C) any growth was observed. Endometrial smears were graded based on the percent of polymorphonuclear cells (PMN) per high power field (HPF). A hierarchical BLCM was fitted using the cross-tabulated results of the three culture case definitions with a cytology threshold fixed at > 0.5% PMN. Fit for purpose cytology thresholds were proposed using a misclassification cost analysis in the context of good antimicrobial stewardship and for varying endometritis prevalence estimates. Median [95% Bayesian credible intervals (BCI)] cytology Se estimates were 6.5% (2.2–11.6), 6.4% (2.2–10.8) and 6.3% (2.2–10.8) for scenario A, B and C, respectively. Median (95% BCI) cytology Sp estimates were 88.8% (83.1–94.8), 88.9% (83.9–93.8) and 88.8% (84.0–93.8) for scenarios A, B and C, respectively. Median (95% BCI) culture Se estimates were 37.5% (29.9–46.0), 42.3% (33.8–51.1) and 46.4% (35.7–55.9) for scenarios A, B and C, respectively. Median (95% BCI) culture Sp estimates were 92.8% (84.3–99.0), 91.5% (82.5–98.0) and 90.8% (80.1–97.4) for scenarios A, B and C, respectively. Regardless of the culture case definition, Se and Sp of cytology (> 0.5% PMN) was lower than previously reported for swab samples in studies using histology as the reference standard test. The misclassification cost term decreased as the cytology threshold increased for all scenarios and all prevalence contexts, suggesting that, regardless of the endometritis prevalence in the population, increasing the cytology threshold would reduce the misclassification costs associated with false positive mares contributing to good antimicrobial stewardship.