{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:27:51Z","timestamp":1788143271890,"version":"build-2803163510"},"reference-count":95,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021734","name":"Leprosy Research Initiative","doi-asserted-by":"publisher","award":["707.19.20"],"award-info":[{"award-number":["707.19.20"]}],"id":[{"id":"10.13039\/501100021734","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dapsone Hypersensitivity Syndrome (DHS) is a serious debilitating condition which can develop after 2\u20138 weeks of dapsone treatment in varying proportions between genetically diverse populations. Approximately 10% of the affected individuals die, and DHS patients often spend weeks to months in the hospital, which impacts health and psychological morbidity and household financial burden. In recent years, a human leukocyte antigen, HLA-B*13:01, has been consistently associated with up to 85% of DHS cases across international population studies; however, the necessity of next generation sequencing (NGS) severely limits clinical applications in low resource contexts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/Principal Finding<\/jats:title>\n                    <jats:p>To investigate HLA-B*13:01 associations with DHS among Nepalese leprosy cases, retrospective and active DHS cases and dapsone-tolerant controls treated at least for 3 months with multi-drug therapy (MDT) were sampled and screened by HLA-B*13:01 qPCR. In the present study we enrolled 34 DHS cases and 82 dapsone tolerant controls and found that the association is maintained in a multi-ethnic Nepali population with an Odds Ratio of 50.1 (95% CI: 15.0-166.6). A previously validated qPCR-based commercial kit was used in the study, and we revalidated the methodology (23 negative and 35 positives by commercial qPCR) using Next Generation sequencing (NGS) method and found a concordance rate of 98.3%. We meta-analyzed all eligible HLA-B*13:01 and DHS association studies and found a summary Odds Ratio of 61.86 (95% CI 32.60 - 117.4). As 23.5% of the DHS cases were HLA-B*13:01 negative in our study, further analyses of the HLA-B*13:01 positive and negative study participants revealed that HLA-B*13:01 positive DHS cases were significantly younger than HLA-B*13:01 negative DHS cases (35.5 years vs. 66 years, p\u2009=\u20090.0018). The positive predictive value of the HLA test in the Nepalese population was\u2009~\u200924.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study validates the association between HLA-B*13:01 and DHS in Nepalese leprosy population. Inclusion of a genetic screening test before starting MDT could potentially prevent significant proportion of DHS occurring in leprosy cases, especially in South Asian and Southeast countries.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0014568","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T17:44:07Z","timestamp":1786643047000},"page":"e0014568","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the risk of dapsone hypersensitivity syndrome in Nepalese Leprosy Patients via HLA-B* 13:01 screening using real-time PCR and comparative meta-analysis of international data"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5709-5958","authenticated-orcid":true,"given":"Divya","family":"RSJB Rana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suwash","family":"Baral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reejana","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishor","family":"Koju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanchha","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeti","family":"Maharjan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarina","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indra Bahadur","family":"Napit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pushpendra","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Krismawati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna A.","family":"Hagge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"issue":"4","key":"pntd.0014568.ref001","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1093\/jhmas\/jrq068","article-title":"A short history of dapsone, or an alternative model of drug development","volume":"66","author":"J Barr","year":"2011","journal-title":"J Hist Med Allied Sci"},{"key":"pntd.0014568.ref002","unstructured":"WHO. 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