Defining the True Sensitivity of Culture for the Diagnosis of Melioidosis Using Bayesian Latent Class Models

BACKGROUND: Culture remains the diagnostic gold standard for many bacterial infections, and the method against which other tests are often evaluated. Specificity of culture is 100% if the pathogenic organism is not found in healthy subjects, but the sensitivity of culture is more difficult to determine and may be low. Here, we apply Bayesian latent class models (LCMs) to data from patients with a single Gram-negative bacterial infection and define the true sensitivity of culture together with the impact of misclassification by culture on the reported accuracy of alternative diagnostic tests. METHODS/PRINCIPAL FINDINGS: Data from published studies describing the application of five diagnostic tests (culture and four serological tests) to a patient cohort with suspected melioidosis were re-analysed using several Bayesian LCMs. Sensitivities, specificities, and positive and negative predictive values (PPVs and NPVs) were calculated. Of 320 patients with suspected melioidosis, 119 (37%) had culture confirmed melioidosis. Using the final model (Bayesian LCM with conditional dependence between serological tests), the sensitivity of culture was estimated to be 60.2%. Prediction accuracy of the final model was assessed using a classification tool to grade patients according to the likelihood of melioidosis, which indicated that an estimated disease prevalence of 61.6% was credible. Estimates of sensitivities, specificities, PPVs and NPVs of four serological tests were significantly different from previously published values in which culture was used as the gold standard. CONCLUSIONS/SIGNIFICANCE: Culture has low sensitivity and low NPV for the diagnosis of melioidosis and is an imperfect gold standard against which to evaluate alternative tests. Models should be used to support the evaluation of diagnostic tests with an imperfect gold standard. It is likely that the poor sensitivity/specificity of culture is not specific for melioidosis, but rather a generic problem for many bacterial and fungal infections

Pseudomonas pseudomallei liver abscesses: a clinical, laboratory, and ultrasonographic study.

Ultrasonography revealed evidence of liver abscess in 126 patients who were admitted to one hospital in northeastern Thailand over a 3-year period. There were 50 cases for which a pyogenic bacterial etiology was confirmed; 34 cases (group 1) were caused by Pseudomonas pseudomallei (nine patients died) and 16 cases (group 2) were caused by other bacteria (two patients died). Melioidosis was associated with anemia and underlying diabetes or renal disease; right-upper-quadrant pain and jaundice were more common in group 2 (P less than .05). Blood cultures were positive for bacteria in 68% of group 1 and 50% of group 2. Chest radiographs revealed abnormalities in 17 of 30 group 1 patients and 6 of 12 group 2 patients. The radiographic appearances of a blood-borne pneumonia suggested melioidosis. The serum indirect hemagglutination assay for antibodies to P. pseudomallei was of limited value in differentiating the two types of abscesses. Multiple hypoechoic areas on ultrasonography were significantly associated with melioidosis (P less than .01); associated splenic abscess occurred in 19 group 1 patients but only one group 2 patient (2-107, 95% confidence interval; odds ratio, 19). In an area where P. pseudomallei is endemic, these characteristic ultrasonographic findings should prompt immediate treatment for melioidosis

Prospective observational study of the frequency and features of intra-abdominal abscesses in patients with melioidosis in northeast Thailand.

Retrospective case series from Thailand have reported the presence of intra-abdominal abscesses in around half of patients with melioidosis, a much higher rate than our clinical experience would suggest. We performed a prospective, observational study of 230 adult patients with culture-confirmed melioidosis in which all patients underwent abdominal ultrasound. One or more abscesses were detected in the liver and/or spleen in 77 (33%) cases. These were often multiple (70%, 31/44 in hepatic abscesses and 88%, 50/57 in splenic abscesses) and clinically silent (27% of cases with abscesses presenting with abdominal pain). The mortality rate at 4 weeks post-discharge was lower in patients who were abscess-positive vs abscess-negative (10%, 8/77 vs 20%, 31/153)