Abstract
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.
Highlights
In the era of leprosy elimination, many efforts have been done by the government to combat leprosy[1]
This review showed that 72.5% of the global Dapsone Hypersensitivity Syndrome (DHS) incidence originated in Asia and 71.8% of these DHS cases happened in leprosy patients
Two other controls were not able to be sequenced successfully as only 25% of the reads were able to be mapped on the AccuTypeTM Software, and it failed to distinguish which HLA-B alleles these sample carry
Summary
In the era of leprosy elimination, many efforts have been done by the government to combat leprosy[1]. Dapsone is an antibiotic and anti-inflammatory agent used for the prevention and treatment of infectious and chronic inflammatory diseases. Dapsone is used to treat leprosy, malaria, actinomycetoma as well as Pneumocystis jirovecii pneumonia in persons with human immunodeficiency virus (HIV), whereas as an anti-inflammatory agent, it’s used to treat dermatitis herpetiformis, linear IgA dermatosis, subcorneal pustular dermatosis and erythema elevatum dilutinum[5,6]. Among all these diseases, leprosy is currently the one that most prevalently uses dapsone for treatment
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