{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:21:02Z","timestamp":1789957262070,"version":"4.0.1"},"reference-count":37,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Livestock and Dairy Development Project","award":["RP-C-01-10"],"award-info":[{"award-number":["RP-C-01-10"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In endemic dairy systems, the interpretation of serological tests for bovine brucellosis is compromised using fixed diagnostic cut-offs, which fail to account for continuous antibody distributions and population heterogeneity. This study aimed to apply a Bayesian hierarchical Gaussian mixture model (BHGMM) to resolve diagnostic uncertainty by deriving probabilistic, biologically informed thresholds for indirect ELISA (iELISA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A cross-sectional dataset comprising 2,696 milk samples from large-scale dairy herds was analysed. Log-transformed and standardised antibody values were modelled using a three-component hierarchical mixture representing healthy, latent, and diseased populations. Posterior class distributions, herd-specific cut-offs, and prevalence were estimated, and model performance was evaluated using convergence diagnostics, posterior predictive checks, and ROC analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three distinct serological populations were identified. Mean antibody levels (S\/P%) were 5.29 in healthy, 17.07 in latent, and 299.84 in diseased animals. Dual diagnostic thresholds were estimated at 10.7 S\/P% and 82.2 S\/P%. Estimated class proportions were 23.5% healthy, 43.6% latent, and 32.9% diseased. Substantial between-herd heterogeneity was observed, with confirmatory cut-offs ranging from approximately 68\u2013133 S\/P% and herd-level true prevalence varying from about 1% to 67%. The model demonstrated high diagnostic accuracy (AUC\u2009=\u200984.5%) and stability across prior specifications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Bayesian modelling captures intermediate serological \u201cgray zones\u201d and herd-level variability overlooked by standard binary interpretations. This probabilistic approach supports targeted control strategies in complex endemic environments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0347719","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:28:34Z","timestamp":1785432514000},"page":"e0347719","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bayesian hierarchical mixture modelling to derive probabilistic iELISA thresholds for bovine brucellosis in endemic dairy systems"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4701-0569","authenticated-orcid":true,"given":"Md. Shaffiul","family":"Alam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1752-9210","authenticated-orcid":true,"given":"Md. Nazmul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishwo Jyoti","family":"Adhikari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanta","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6139-5906","authenticated-orcid":true,"given":"RS","family":"Mahmud Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4919-9973","authenticated-orcid":true,"given":"Md. Siddiqur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6657-0300","authenticated-orcid":true,"given":"M. Ariful","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Aktaruzzaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lefteris","family":"Meletis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7051-1541","authenticated-orcid":true,"given":"Polychronis","family":"Kostoulas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9660-4949","authenticated-orcid":true,"given":"A K M Anisur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"issue":"9","key":"pone.0347719.ref001","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.3168\/jds.2023-24626","article-title":"Global losses due to dairy cattle diseases: a comorbidity-adjusted economic analysis","volume":"107","author":"P Rasmussen","year":"2024","journal-title":"J Dairy Sci"},{"key":"pone.0347719.ref002","doi-asserted-by":"crossref","first-page":"27","DOI":"10.12691\/ajeid-5-2-2","article-title":"Public health and economic importance of bovine brucellosis: an overview","volume":"5","author":"M Pal","year":"2017","journal-title":"AJEID"},{"issue":"2","key":"pone.0347719.ref003","doi-asserted-by":"crossref","first-page":"16","DOI":"10.47285\/hr.v1i2.62","article-title":"Review of bovine brucellosis and its public health significance","volume":"1","author":"W Mitiku","year":"2020","journal-title":"HR"},{"issue":"1","key":"pone.0347719.ref004","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/01652176.2020.1868616","article-title":"Bovine brucellosis - a comprehensive review","volume":"41","author":"SK Khurana","year":"2021","journal-title":"Vet Q"},{"key":"pone.0347719.ref005","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1590\/S0100-736X2013000600012","article-title":"Economic losses due to bovine brucellosis in Brazil","volume":"33","author":"RL Santos","year":"2013","journal-title":"Pesq Vet Bras"},{"key":"pone.0347719.ref006","article-title":"A six-decade review: Research on cattle production, management and dairy products in Bangladesh","volume":"2","author":"MA Samad","year":"2020","journal-title":"JVMOHR"},{"key":"pone.0347719.ref007","doi-asserted-by":"crossref","first-page":"105596","DOI":"10.1016\/j.prevetmed.2022.105596","article-title":"Keeping continuous diagnostic data continuous: application of Bayesian latent class models in veterinary research","volume":"201","author":"DA Yang","year":"2022","journal-title":"Prev Vet Med"},{"key":"pone.0347719.ref008","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1146\/annurev-statistics-031017-100325","article-title":"Finite mixture models","volume":"6","author":"GJ McLachlan","year":"2019","journal-title":"Annu Rev Stat Appl"},{"issue":"1","key":"pone.0347719.ref009","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12917-017-1145-x","article-title":"Estimation of the sensitivity and specificity of two serum ELISAs and one fecal qPCR for diagnosis of paratuberculosis in sub-clinically infected young-adult French sheep using latent class Bayesian modeling","volume":"13","author":"Y Mathevon","year":"2017","journal-title":"BMC Vet Res"},{"key":"pone.0347719.ref010","doi-asserted-by":"crossref","DOI":"10.1201\/b16018","volume-title":"Bayesian data analysis","author":"A Gelman","year":"2013","edition":"3"},{"key":"pone.0347719.ref011","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.prevetmed.2004.09.009","article-title":"Bayesian modeling of animal- and herd-level prevalences","volume":"66","author":"AJ Branscum","year":"2004","journal-title":"Prev Vet Med"},{"key":"pone.0347719.ref012","unstructured":"Stevenson M, Nunes T, Heuer C, Marshall J, Sanchez J, Thornton R. epiR: tools for the analysis of epidemiological data. R package version. Vol 2. 2018. pp. 26."},{"key":"pone.0347719.ref013","volume-title":"R: A language and environment for statistical computing","author":"Team R Core","year":"2025"},{"key":"pone.0347719.ref014","article-title":"Bayesian evaluation of three serological tests for the diagnosis of bovine brucellosis in Bangladesh","volume":"147","author":"AKMA Rahman","year":"2019","journal-title":"Epidemiol Infect"},{"key":"pone.0347719.ref015","first-page":"147","article-title":"Intra-cluster","volume":"3","author":"M Otte","year":"1997","journal-title":"Prev Vet Med"},{"issue":"3","key":"pone.0347719.ref016","doi-asserted-by":"crossref","first-page":"989","DOI":"10.20506\/rst.23.3.1545","article-title":"Serological diagnosis of bovine brucellosis: a review of test performance and cost comparison","volume":"23","author":"D Gall","year":"2004","journal-title":"Rev Sci Tech"},{"key":"pone.0347719.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v076.i01","article-title":"Stan: a probabilistic programming language","volume":"76","author":"B Carpenter","year":"2017","journal-title":"J Stat Softw"},{"key":"pone.0347719.ref018","volume-title":"cmdstanr: R Interface to\u2019CmdStan\u2019","author":"J Gabry","year":"2021"},{"issue":"2","key":"pone.0347719.ref019","doi-asserted-by":"crossref","DOI":"10.1214\/20-BA1221","article-title":"Rank-normalization, folding, and localization: an improved R\u02c6 for assessing convergence of MCMC (with discussion)","volume":"16","author":"A Vehtari","year":"2021","journal-title":"Bayesian Anal"},{"key":"pone.0347719.ref020","volume-title":"Package \u2018pROC\u2019","author":"X Robin","year":"2021"},{"key":"pone.0347719.ref021","author":"World Organisation for Animal Health","year":"2024"},{"issue":"2","key":"pone.0347719.ref022","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1097\/01.ede.0000198422.64801.8d","article-title":"Estimating disease prevalence in a Bayesian framework using probabilistic constraints","volume":"17","author":"D Berkvens","year":"2006","journal-title":"Epidemiology"},{"issue":"2","key":"pone.0347719.ref023","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.prevetmed.2011.04.007","article-title":"Brucellosis at the animal\/ecosystem\/human interface at the beginning of the 21st century","volume":"102","author":"J Godfroid","year":"2011","journal-title":"Prev Vet Med"},{"key":"pone.0347719.ref024","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0378-1135(02)00229-8","article-title":"Diagnosis of brucellosis by serology","volume":"90","author":"K Nielsen","year":"2002","journal-title":"Vet Microbiol"},{"issue":"1","key":"pone.0347719.ref025","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0022-1759(95)00121-P","article-title":"A modified ROC analysis for the selection of cut-off values and the definition of intermediate results of serodiagnostic tests","volume":"185","author":"M Greiner","year":"1995","journal-title":"J Immunol Methods"},{"issue":"9264","key":"pone.0347719.ref026","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/S0140-6736(00)04410-X","article-title":"Endemic stability--a veterinary idea applied to human public health","volume":"357","author":"PG Coleman","year":"2001","journal-title":"Lancet"},{"key":"pone.0347719.ref027","doi-asserted-by":"crossref","first-page":"9378976","DOI":"10.1155\/2018\/9378976","article-title":"Molecular detection of Brucella spp. from milk of seronegative cows from some selected area in Bangladesh","volume":"2018","author":"MS Islam","year":"2018","journal-title":"J Pathog"},{"key":"pone.0347719.ref028","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13620-016-0062-9","article-title":"Use of serology and real time PCR to control an outbreak of bovine brucellosis at a dairy cattle farm in the Nile Delta region, Egypt","volume":"69","author":"M Gwida","year":"2016","journal-title":"Ir Vet J"},{"key":"pone.0347719.ref029","doi-asserted-by":"crossref","first-page":"565324","DOI":"10.3389\/fvets.2020.565324","article-title":"The impact of paratuberculosis on milk production, fertility, and culling in large commercial hungarian dairy herds","volume":"7","author":"L Ozsvari","year":"2020","journal-title":"Front Vet Sci"},{"key":"pone.0347719.ref030","unstructured":"Bonfini B, Chiarenza G, Paci V, Sacchini F, Salini R, Vesco G, et al. Cross-reactivity in serological tests for brucellosis: a comparison of immune response of Escherichia coli O157: H7 and Yersinia enterocolitica O: 9 vs Brucella spp. 2018."},{"issue":"2","key":"pone.0347719.ref031","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1093\/ije\/dyt043","article-title":"Markov chain Monte Carlo: an introduction for epidemiologists","volume":"42","author":"G Hamra","year":"2013","journal-title":"Int J Epidemiol"},{"issue":"1","key":"pone.0347719.ref032","first-page":"1","article-title":"Concepts for risk-based surveillance in the field of veterinary medicine and veterinary public health: Review of current approaches","volume":"38","author":"KD St\u00e4rk","year":"2007","journal-title":"Vet Res"},{"key":"pone.0347719.ref033","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s41182-020-00272-1","article-title":"One health approach to tackle brucellosis: a systematic review","volume":"48","author":"MK Ghanbari","year":"2020","journal-title":"Trop Med Health"},{"issue":"1","key":"pone.0347719.ref034","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/s42522-025-00168-2","article-title":"A scoping review of the national strategy for brucellosis control in Egypt: logic framework, challenges, and prospects","volume":"7","author":"EW Abd El-Wahab","year":"2025","journal-title":"One Health Outlook"},{"issue":"8","key":"pone.0347719.ref035","doi-asserted-by":"crossref","first-page":"878","DOI":"10.3390\/vaccines9080878","article-title":"Cost-benefit analysis of a mass vaccination strategy to control brucellosis in sheep and goats in Northern Iraq","volume":"9","author":"A Al Hamada","year":"2021","journal-title":"Vaccines (Basel)"},{"issue":"1","key":"pone.0347719.ref036","doi-asserted-by":"crossref","first-page":"249","DOI":"10.20506\/rst.32.1.2197","article-title":"Economics of brucellosis impact and control in low-income countries","volume":"32","author":"J McDermott","year":"2013","journal-title":"Rev Sci Tech"},{"key":"pone.0347719.ref037","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3389\/fvets.2020.00521","article-title":"ONE health approach to address zoonotic brucellosis: a spatiotemporal associations study between animals and humans","volume":"7","author":"K Zhou","year":"2020","journal-title":"Front Vet Sci"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347719","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:28:43Z","timestamp":1785432523000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347719"}},"subtitle":[],"editor":[{"given":"Saurabh","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0347719","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]}}}