03468nas a2200385   4500000000100000008004100001260004600042653002100088653001700109653001000126653002500136653003100161653001700192653001400209653001200223100002100235700001100256700001200267700001500279700001100294700001500305700001500320700001200335700001300347700001200360700001700372700001300389700001500402245018900417856009900606300001100705490000700716520234500723022001403068       2026                            d  c08/2026bPublic Library of Science (PLoS)10aHypersensitivity10ametaanalysis10aNepal10aMedical risk factors10aNext generation sequencing10aEpidemiology10aallergies10aDapsone1 aDivya RSJB Rana 1 aShah M1 aBaral S1 aShrestha R1 aKoju K1 aShrestha K1 aMaharjan P1 aJoshi J1 aNapit IB1 aSingh P1 aKrismawati H1 aHagge DA1 aFastenau A00aEvaluating 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  uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0014568&type=printable  a1 - 230 v203 a<p><strong>Background</strong></p>

<p>Dapsone Hypersensitivity Syndrome (DHS) is a serious debilitating condition which can develop after 2–8 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.</p>

<p><strong>Methodology/Principal Finding</strong></p>

<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 = 0.0018). The positive predictive value of the HLA test in the Nepalese population was ~ 24.</p>

<p><strong>Conclusion</strong></p>

<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.</p>
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