{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T14:30:00Z","timestamp":1759847400679,"version":"3.40.5"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Gu\u00e9rin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3\u20133.9, <jats:italic>P<\/jats:italic> = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0303050","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T17:47:17Z","timestamp":1715276837000},"page":"e0303050","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5883-9472","authenticated-orcid":true,"given":"Yun","family":"Choi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In Kyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Jung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Sung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7783-5271","authenticated-orcid":true,"given":"Young Ae","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0050-8018","authenticated-orcid":true,"given":"Jin Su","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"volume-title":"Global tuberculosis report","year":"2022","author":"World Health Organization","key":"pone.0303050.ref001"},{"issue":"7","key":"pone.0303050.ref002","doi-asserted-by":"crossref","first-page":"567","DOI":"10.5588\/ijtld.21.0060","article-title":"Nosocomial TB in two neonatal intensive care units at a tertiary care centre: infection risk and outcomes","volume":"25","author":"B Yangthara","year":"2021","journal-title":"The International Journal of Tuberculosis and Lung Disease"},{"issue":"50","key":"pone.0303050.ref003","first-page":"1280","article-title":"Mycobacterium tuberculosis transmission in newborn nursery and maternity ward- New York City, 2003","volume":"54","author":"Centers for Disease Control and Prevention","year":"2005","journal-title":"Morbidity and Mortality Weekly Report"},{"issue":"40","key":"pone.0303050.ref004","doi-asserted-by":"crossref","DOI":"10.2807\/ese.16.40.19984-en","article-title":"Suspected transmission of tuberculosis in a maternity ward from a smear-positive nurse: preliminary results of clinical evaluations and testing of neonates potentially exposed, Rome, Italy, 1 January to 28 July 2011","volume":"16","author":"P Borgia","year":"2011","journal-title":"Eurosurveillance"},{"key":"pone.0303050.ref005","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1164\/rccm.200511-1809SO","article-title":"Childhood Pulmonary tuberculosis: old wisdom and new challenges","volume":"173","author":"BJ Marais","year":"2006","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"issue":"2","key":"pone.0303050.ref006","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/cid\/ciw778","article-title":"Official America Thoracic Society\/Infectious Diseases Society of America\/Centers for Disease Control and Prevention clinical practice guidelines: Diagnosis of tuberculosis in adults and children","volume":"64","author":"DM Lewinsohn","year":"2017","journal-title":"Clinical Infectious Disease"},{"key":"pone.0303050.ref007","unstructured":"Centers for Disease Control and Prevention. Tuberculin skin test factsheet. Available: https:\/\/www.cdc.gov\/tb\/publications\/factsheets\/testing\/skintesting.htm. Accessed August 31 2023."},{"issue":"2","key":"pone.0303050.ref008","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.chest.2017.01.001","article-title":"The long-term effect of Bacille Calmette-Gu\u00e9rin vaccination on tuberculin skin testing: A 55-year follow-up study","volume":"152","author":"JD Mancuso","year":"2017","journal-title":"Chest"},{"issue":"11","key":"pone.0303050.ref009","first-page":"1192","article-title":"False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria?","volume":"10","author":"M Farhat","year":"2006","journal-title":"The International Journal of Tuberculosis and Lung Disease"},{"issue":"3","key":"pone.0303050.ref010","doi-asserted-by":"crossref","first-page":"344","DOI":"10.5588\/ijtld.18.0201","article-title":"Effect of neonatal bacilli Calmette-Gu\u00e9rin on the tuberculin skin test reaction in the first 2 years of life","volume":"23","author":"T Kurtz","year":"2019","journal-title":"The International Journal of Tuberculosis and Lung Disease"},{"issue":"3","key":"pone.0303050.ref011","doi-asserted-by":"crossref","first-page":"384","DOI":"10.4103\/2249-4863.161327","article-title":"Scar formation and tuberculin conversion following BCG vaccination in infants: A prospective cohort study","volume":"4","author":"SS Dhanawade","year":"2015","journal-title":"Journal of Family Medicine and Primary Care"},{"issue":"6","key":"pone.0303050.ref012","doi-asserted-by":"crossref","first-page":"448","DOI":"10.24171\/j.phrp.2022.0235","article-title":"A low risk of nosocomial transmission of subclinical tuberculosis to neonates in a postpartum care center under COVID-19 control measures","volume":"13","author":"IK Kim","year":"2022","journal-title":"Osong Public Health and Research Perspectives"},{"issue":"6","key":"pone.0303050.ref013","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1086\/517975","article-title":"Exposure to pulmonary tuberculosis in a neonatal intensive care unit: unique aspects of contact investigation and management of hospitalized neonates","volume":"28","author":"JJ Nania","year":"2007","journal-title":"Infection Control and Hospital Epidemiology"},{"issue":"7","key":"pone.0303050.ref014","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1086\/670995","article-title":"Nosocomial pulmonary tuberculosis contact investigation in a neonatal intensive care unit","volume":"34","author":"KE Fisher","year":"2013","journal-title":"Infection Control and Hospital Epidemiology"},{"volume-title":"Guidelines on tuberculosis management.","year":"2023","author":"Korea Disease Control and Prevention Agency","key":"pone.0303050.ref015"},{"issue":"14","key":"pone.0303050.ref016","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1002\/sim.7273","article-title":"Firth\u2019s logistic regression with rare events: accurate effect estimates and predictions?","volume":"36","author":"R Puhr","year":"2017","journal-title":"Statistics in Medicine"},{"issue":"4","key":"pone.0303050.ref017","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1183\/09031936.00201609","article-title":"Tuberculosis contact investigation in low prevalence countries: a European consensus","volume":"36","author":"CGM Erkens","year":"2010","journal-title":"European Respiratory Journal"},{"issue":"6491","key":"pone.0303050.ref018","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1126\/science.aaz9447","article-title":"Vaccination strategies to enhance immunity in neonates","volume":"368","author":"TR Kollmann","year":"2020","journal-title":"Science"},{"issue":"2","key":"pone.0303050.ref019","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/jpids\/piy142","article-title":"Maternal Priming: Bacillus Calmette-Gu\u00e9rin (BCG) vaccine scarring in mothers enhances the survival of their child with a BCG vaccine scar","volume":"9","author":"MLT Berendsen","year":"2020","journal-title":"Journal of the Pediatric Infectious Disease Society"},{"issue":"9","key":"pone.0303050.ref020","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1136\/thorax.57.9.804","article-title":"A meta-analysis of the effect of Bacille Calmette Gu\u00e9rin vaccination on tuberculin skin test measurements","volume":"57","author":"L Wang","year":"2002","journal-title":"Thorax"},{"issue":"10","key":"pone.0303050.ref021","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1136\/thoraxjnl-2015-207687","article-title":"The impact of BCG vaccination on tuberculin skin test responses in children is age dependent: evidence to be considered when screening children for tuberculosis infection","volume":"71","author":"JA Seddon","year":"2016","journal-title":"Thorax"},{"issue":"2","key":"pone.0303050.ref022","doi-asserted-by":"crossref","first-page":"208","DOI":"10.14776\/kjpid.2002.9.2.208","article-title":"Tuberculin reactivity in neonates vaccinated with BCG at primary care clinics\u2014two types of BCG vaccine and two strengths of PPD","volume":"9","author":"WJ Kim","year":"2002","journal-title":"Korean Journal of Pediatric Infectious Disease"},{"issue":"2","key":"pone.0303050.ref023","first-page":"201","article-title":"Observation of response to PPD skin test and local side reactions at multiple inoculation sites after percutaneous inoculation with BCG Tokyo 172 strain","volume":"79","author":"JS Lee","year":"2000","journal-title":"Korean Journal of Pediatric Infectious Disease"},{"issue":"11","key":"pone.0303050.ref024","first-page":"1502","article-title":"Tuberculin response in infants after BCG vaccination during neonatal stage","volume":"42","author":"JH Kim","year":"1999","journal-title":"Journal of the Korean Pediatric Society"},{"issue":"4","key":"pone.0303050.ref025","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1086\/499825","article-title":"The effect of Bacille Galmette-Gu\u00e9rin vaccine strain and route of administration on induced immune responses in vaccinated infants","volume":"193","author":"V Davids","year":"2006","journal-title":"Journal of Infectious Disease"},{"issue":"9","key":"pone.0303050.ref026","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1136\/thx.54.9.762","article-title":"Administration of the BCG vaccination using the multipuncture method in schoolchildren: a comparison with the intradermal method","volume":"54","author":"NA Jarad","year":"1999","journal-title":"Thorax"},{"issue":"1","key":"pone.0303050.ref027","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1136\/adc.69.1.155","article-title":"Tuberculin reactivity after neonatal percutaneous BCG immunisation","volume":"69","author":"LP Ormerod","year":"1993","journal-title":"Archives of Disease in Childhood"},{"key":"pone.0303050.ref028","unstructured":"Ministry of Government Legislation. Article 11(Tuberculosis Examination, etc.) of Tuberculosis Prevention Act in South Korea. Sejong, Republic of Korea: MOGL, 2023. Available: https:\/\/www.law.go.kr\/LSW\/eng\/engLsSc.do?menuId=2&section=lawNm&query=Tuberculosis+prevention&x=0&y=0#liBgcolor1. Accessed August 31 2023."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0303050","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T17:47:30Z","timestamp":1715276850000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0303050"}},"subtitle":[],"editor":[{"given":"Novel Njweipi","family":"Chegou","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":28,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0303050","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2024,5,9]]}}}