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Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13:01, a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10−9, confirming the strong association of HLA-B*13:01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future. Author summary: Leprosy as a chronic infectious disease that affects the skin and nervous system is treated with a treatment cocktail, including rifampicin, clofazimine and dapsone. Unfortunately, one of these drugs, namely dapsone, may cause the patient to exhibit adverse symptoms that appear as skin hypersensitivity and may potentially lead to death up to 9.9% of the time. In a previous study, it has been established that this adverse drug reaction, which is called dapsone hypersensitivity syndrome (DHS), is associated with an allele in the human leukocyte antigen, HLA-B*13:01. In the light of validating the association of HLA-B*13:01 with DHS in a leprosy endemic area like Indonesia, we conducted a study involving leprosy patients who had DHS during the course of their multi-drug treatment as well as leprosy patients who managed to complete their course of treatment without exhibiting DHS. The results of this study validated the association of HLA-B*13:01 and DHS at a very significant level of evidence and the odds of people carrying at least one allele is 233.3-times the risk of non-carriers. This allele was also able to predict a person at risk of DHS 95% of the time. Thus, screening of HLA-B*13:01 to prevent DHS is warranted. [ABSTRACT FROM AUTHOR]