{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:27:29Z","timestamp":1790908049989,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"8","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Resources and Services Administration and the National Institute of Allergy and Infectious Diseases","award":["AAI15006"],"award-info":[{"award-number":["AAI15006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mycobacterium leprae was thought to be the exclusive causative agent of leprosy until Mycobacterium lepromatosis was identified in a rare form of leprosy known as diffuse lepromatous leprosy (DLL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We isolated M. lepromatosis from a patient with DLL and propagated it in athymic nude mouse footpads. Genomic analysis of this strain (NHDP-385) identified a unique repetitive element, RLPM, on which a specific real-time quantitative polymerase chain reaction assay was developed. The RLPM assay, and a previously developed RLEP quantitative polymerase chain reaction assay for M. leprae, were validated as clinical diagnostic assays according to Clinical Laboratory Improvement Amendments guidelines. We tested DNA from archived histological sections, patient specimens from the United States, Philippines, and Mexico, and US wild armadillos.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The limit of detection for the RLEP and RLPM assays is 30 M. leprae per specimen (0.76 bacilli per reaction; coefficient of variation, 0.65%\u20132.44%) and 122 M. lepromatosis per specimen (3.05 bacilli per reaction; 0.84%\u20132.9%), respectively. In histological sections (n = 10), 1 lepromatous leprosy (LL), 1 DLL, and 3 Lucio reactions contained M. lepromatosis; 2 LL and 2 Lucio reactions contained M. leprae; and 1 LL reaction contained both species. M. lepromatosis was detected in 3 of 218 US biopsy specimens (1.38%). All Philippines specimens (n = 180) were M. lepromatosis negative and M. leprae positive. Conversely, 15 of 47 Mexican specimens (31.91%) were positive for M. lepromatosis, 19 of 47 (40.43%) were positive for M. leprae, and 2 of 47 (4.26%) contained both organisms. All armadillos were M. lepromatosis negative.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The RLPM and RLEP assays will aid healthcare providers in the clinical diagnosis and surveillance of leprosy.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciz1121","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T20:10:13Z","timestamp":1573589413000},"page":"e262-e269","source":"Crossref","is-referenced-by-count":70,"title":["Isolation of<i>Mycobacterium lepromatosis<\/i>and Development of Molecular Diagnostic Assays to Distinguish<i>Mycobacterium leprae<\/i>and<i>M. lepromatosis<\/i>"],"prefix":"10.1093","volume":"71","author":[{"given":"Rahul","family":"Sharma","sequence":"first","affiliation":[{"name":"US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, National Hansen\u2019s Disease Program, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushpendra","family":"Singh","sequence":"additional","affiliation":[{"name":"US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, National Hansen\u2019s Disease Program, Baton Rouge, Louisiana, USA"},{"name":"National Institute of Research in Tribal Health, Jabalpur, MP India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv C","family":"McCoy","sequence":"additional","affiliation":[{"name":"Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon M","family":"Lenz","sequence":"additional","affiliation":[{"name":"IHRC, Inc., Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Donovan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Southern California, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Estrada-Garcia","sequence":"additional","affiliation":[{"name":"Departamento Immunologia, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayra","family":"Silva-Miranda","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Ciencia y Tecnologia (National Council of Science and Technology)\u2013Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fermin","family":"Jurado-Santa Cruz","sequence":"additional","affiliation":[{"name":"Centro Dermatol\u00f3gico Dr. Ladislao de la Pascua, Secretaria de Salud de la Ciudad de M\u00e9xico, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marivic F","family":"Balagon","sequence":"additional","affiliation":[{"name":"Leonard Wood Memorial, Center for Leprosy Research, Cebu, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Stryjewska","sequence":"additional","affiliation":[{"name":"US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, National Hansen\u2019s Disease Program, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Scollard","sequence":"additional","affiliation":[{"name":"US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, National Hansen\u2019s Disease Program, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T","family":"Pena","sequence":"additional","affiliation":[{"name":"US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, National Hansen\u2019s Disease Program, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramanuj","family":"Lahiri","sequence":"additional","affiliation":[{"name":"US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, National Hansen\u2019s Disease Program, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana L","family":"Williams","sequence":"additional","affiliation":[{"name":"US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, National Hansen\u2019s Disease Program, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W","family":"Truman","sequence":"additional","affiliation":[{"name":"US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, National Hansen\u2019s Disease Program, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6265-3531","authenticated-orcid":false,"given":"Linda B","family":"Adams","sequence":"additional","affiliation":[{"name":"US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, National Hansen\u2019s Disease Program, Baton Rouge, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,16]]},"reference":[{"key":"2021060919582787700_CIT0001"},{"key":"2021060919582787700_CIT0002","first-page":"110","article-title":"The Lucio-Alvarado form of leprosy: a case observed in Brazil","volume":"27","author":"Furtado","year":"1959","journal-title":"Int J Lepr"},{"key":"2021060919582787700_CIT0003","first-page":"169","article-title":"Clinical and histologic variations among thirty patients with Lucio\u2019s phenomenon and pure and primitive diffuse lepromatosis (Latapi\u2019s lepromatosis)","volume":"73","author":"Rea","year":"2005","journal-title":"Int J Lepr Other Mycobact Dis"},{"key":"2021060919582787700_CIT0004","doi-asserted-by":"crossref","DOI":"10.1489\/itl.2.4","article-title":"Pathogenesis and pathology of leprosy","volume-title":"International textbook of leprosy","author":"Scollard","year":"2016"},{"key":"2021060919582787700_CIT0005","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1309\/AJCPP72FJZZRRVMM","article-title":"A new Mycobacterium species causing diffuse lepromatous leprosy","volume":"130","author":"Han","year":"2008","journal-title":"Am J Clin Pathol"},{"key":"2021060919582787700_CIT0006","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1099\/13500872-140-8-1983","article-title":"Mycobacterium leprae isolates from different sources have identical sequences of the spacer region between the 16S and 23S ribosomal RNA genes","volume":"140","author":"de Wit","year":"1994","journal-title":"Microbiol"},{"key":"2021060919582787700_CIT0007","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1128\/JB.00762-09","article-title":"Comparative sequence analysis of Mycobacterium leprae and the new leprosy-causing Mycobacterium lepromatosis","volume":"191","author":"Han","year":"2009","journal-title":"J Bacteriol"},{"key":"2021060919582787700_CIT0008","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1111\/j.1365-4632.2011.05414.x","article-title":"The leprosy agents Mycobacterium lepromatosis and Mycobacterium leprae in Mexico","volume":"51","author":"Han","year":"2012","journal-title":"Int J Dermatol"},{"key":"2021060919582787700_CIT0009","doi-asserted-by":"crossref","first-page":"e328","DOI":"10.1371\/journal.pntd.0000328","article-title":"Enumeration of Mycobacterium leprae using real-time PCR","volume":"2","author":"Truman","year":"2008","journal-title":"PLoS Negl Trop Dis"},{"key":"2021060919582787700_CIT0010","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1128\/CMR.00074-09","article-title":"Validation of laboratory-developed molecular assays for infectious diseases","volume":"23","author":"Burd","year":"2010","journal-title":"Clin Microbiol Rev"},{"key":"2021060919582787700_CIT0011","first-page":"1","article-title":"Viable M. leprae as a research reagent","volume":"69","author":"Truman","year":"2001","journal-title":"Int J Lepr Other Mycobact Dis"},{"key":"2021060919582787700_CIT0012","first-page":"209","article-title":"Investigations into the cultivation of Mycobacterium leprae: a multifactorial approach","volume":"57","author":"Kato","year":"1986","journal-title":"Lepr Rev"},{"key":"2021060919582787700_CIT0013","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1099\/jmm.0.45700-0","article-title":"Application of a viability-staining method for Mycobacterium leprae derived from the athymic (nu\/nu) mouse foot pad","volume":"54","author":"Lahiri","year":"2005","journal-title":"J Med Microbiol"},{"key":"2021060919582787700_CIT0014","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1093\/bioinformatics\/btm091","article-title":"Enhancements and modifications of primer design program Primer3","volume":"23","author":"Koressaar","year":"2007","journal-title":"Bioinformatics"},{"key":"2021060919582787700_CIT0015","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.3201\/eid2112.150501","article-title":"Zoonotic leprosy in the southeastern United States","volume":"21","author":"Sharma","year":"2015","journal-title":"Emerg Infect Dis"},{"key":"2021060919582787700_CIT0016","doi-asserted-by":"crossref","first-page":"4459","DOI":"10.1073\/pnas.1421504112","article-title":"Insight into the evolution and origin of leprosy bacilli from the genome sequence of Mycobacterium lepromatosis","volume":"112","author":"Singh","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2021060919582787700_CIT0017","doi-asserted-by":"crossref","first-page":"e01924","DOI":"10.1128\/JCM.01924-17","article-title":"The repetitive element RLEP is a highly specific target for detection of Mycobacterium leprae","volume":"56","author":"Braet","year":"2018","journal-title":"J Clin Microbiol"},{"key":"2021060919582787700_CIT0018","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3389\/fpubh.2017.00109","article-title":"Development and validation of a novel real-time assay for the detection and quantification of Vibrio cholerae","volume":"5","author":"Rashid","year":"2017","journal-title":"Front Pub Health"},{"key":"2021060919582787700_CIT0019","volume-title":"Basic QC practices: training in statistical quality control for medical laboratories","author":"Westgard","year":"2016","edition":"4th ed."},{"key":"2021060919582787700_CIT0020","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1056\/NEJMoa1010536","article-title":"Probable zoonotic leprosy in the southern United States","volume":"364","author":"Truman","year":"2011","journal-title":"N Engl J Med"},{"key":"2021060919582787700_CIT0021","first-page":"229","article-title":"Leprosy-like illness in a patient with Mycobacterium lepromatosis from Ontario, Canada","volume":"11","author":"Jessamine","year":"2012","journal-title":"J Drugs Dermatol"},{"key":"2021060919582787700_CIT0022","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1309\/AJCP1GLCBE5CDZRM","article-title":"Analysis of the leprosy agents Mycobacterium leprae and Mycobacterium lepromatosis in four countries","volume":"142","author":"Han","year":"2014","journal-title":"Am J Clin Pathol"},{"key":"2021060919582787700_CIT0023","first-page":"168","article-title":"Identification of the leprosy agent Mycobacterium lepromatosis in Singapore","volume":"11","author":"Han","year":"2012","journal-title":"J Drugs Dermatol"},{"key":"2021060919582787700_CIT0024","doi-asserted-by":"crossref","first-page":"260","DOI":"10.4269\/ajtmh.16-0713","article-title":"Detection of the leprosy agent Mycobacterium lepromatosis in South America and Europe","volume":"96","author":"Han","year":"2017","journal-title":"Am J Trop Med Hyg"},{"key":"2021060919582787700_CIT0025","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.cmi.2019.05.020","article-title":"Diagnostic accuracy of tests for leprosy: a systematic review and meta-analysis","volume":"25","author":"Gurung","year":"2019","journal-title":"Clin Microbiol Infect"},{"key":"2021060919582787700_CIT0026","doi-asserted-by":"crossref","first-page":"e0007284","DOI":"10.1371\/journal.pntd.0007284","article-title":"Development and evaluation of a droplet digital PCR assay for the diagnosis of paucibacillary leprosy in skin biopsy specimens","volume":"13","author":"Cheng","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"2021060919582787700_CIT0027","doi-asserted-by":"crossref","first-page":"e1354","DOI":"10.1371\/journal.pntd.0001354","article-title":"Evaluation of qPCR-based assays for leprosy diagnosis directly in clinical specimens","volume":"5","author":"Martinez","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"2021060919582787700_CIT0028","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.mayocp.2018.11.022","article-title":"Leprosy in a Midwestern dermatology clinic: report of 9 patients","volume":"94","author":"Bezalel","year":"2019","journal-title":"Mayo Clin Proc"},{"key":"2021060919582787700_CIT0029","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.3201\/eid2311.171104","article-title":"Mycobacterium lepromatosis lepromatous leprosy in US citizen who traveled to disease-endemic areas","volume":"23","author":"Virk","year":"2017","journal-title":"Emerg Infect Dis"},{"key":"2021060919582787700_CIT0030","author":"Yan"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciz1121\/32990310\/ciz1121.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/71\/8\/e262\/38575686\/ciz1121.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/71\/8\/e262\/38575686\/ciz1121.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T21:24:51Z","timestamp":1695417891000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/71\/8\/e262\/5626481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,16]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,11,16]]},"published-print":{"date-parts":[[2020,11,5]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciz1121","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,10,15]]},"published":{"date-parts":[[2019,11,16]]}}}