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.
Importance: Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy (MDT) which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, leprosy is still a problem. Furthermore, there had been reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. HLA-B*13:01 has been found to be associated with DHS and prospective screening has proven its ability to prevent DHS in the Chinese population, but has not been validated in Indonesians.
Objective: To validate HLA-B*13:01 as a biomarker for DHS in the Indonesian population.
Design: This is a case-control study.
Setting: Population-based, multi-district recruitment from primary care centers in two of the top 3 most prevalent provinces in Indonesia, Papua and West Papua.
Participants: Leprosy patients who presented themselves with DHS were recruited as case subjects (34 cases) and leprosy patients without DHS were recruited as control subjects (52 controls).
Exposure: Leprosy patients who had undergone multi-drug treatment for leprosy under the standard WHO guideline, consisting of rifampicin, dapsone and clofazamine.
Main Outcome and Measures: The association of HLA-B*13:01 to DHS based on difference in allele frequencies between cases and controls. HLA-B alleles were typed using the gold-standard Sequence Based Typing method. Results were analyzed using logistic regression and risk assessment was carried out.
Results: The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio=247.6 and P-value=4.81E-9, confirming the strong association of HLA-B*13:01 to DHS in the Indonesian population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95.
Conclusions and Relevance: HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.
Keywords: HLA-B*13:01, dapsone hypersensitivity syndrome, leprosy, dapsone, adverse drug reaction, Papua, Indonesia
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