Implementation of genetic screening test to reduce the incidence of dapsone hypersensitivity syndrome among patients with leprosy in Papua, Indonesia: a study protocol.

INTRODUCTION: The mainstay of leprosy treatment is multidrug treatment (MDT), which contains rifampicin, dapsone and clofazimine. The occurrence of dapsone hypersensitivity syndrome (DHS), a sudden, potentially fatal and traumatic adverse reaction due to dapsone, may affect treatment adherence and may result in fatality if untreated. Before MDT administration, screening for HLA-B*13:01 in patients with leprosy can potentially reduce DHS risk. The study aims to assess the effectiveness of using a screening test for HLA-B*13:01 in reducing the incidence of DHS and to evaluate the feasibility of using the quantitative PCR-based screening tool as DHS predictors before dapsone administration using individual patient testing in a referral centralised-lab model. METHODS AND ANALYSIS: A total of 310 newly diagnosed patients with leprosy will be recruited from health centres in two highly endemic districts in Indonesia. Dried blood will be taken on filter paper as the specimen receptacle to collect DNA from the patients and transported at room temperature to the leprosy referral laboratory before MDT administration. Checking for HLA-B*13:01 from human DNA is performed using the Nala PGx 1301 V.1 kit. The results will be shared with the leprosy health workers on the site via phone call and courier. Patients with a positive test result will be treated with MDT without dapsone, and patients with a negative result will be treated with complete MDT. Physical examination (weight, height, skin, muscle and nerve function examination), complete blood tests (including renal function test) will be carried out at baseline. Follow-up will be performed at the fourth and eighth weeks to observe any development of adverse drug reactions. ETHICS AND DISSEMINATION: The ethical approval for the study was issued by the Ethical Committee of the National Institute of Health Research and Development, Ministry of Health, Indonesia. Written informed consent will be sought from all participants.

Validation study of HLA-B*13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia.

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.