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A cost-effective conventional endpoint PCR assay for HLA-B*13:01 genotyping to guide personalized dapsone therapy in leprosy in low-resource settings.

Divya Rsjb Rana·Kishor Koju·Jivan Shakya·Sarita Manandhar·Anjana Singh·Mahesh Shah·Deanna A Hagge·Jarina Joshi
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Abstract

BACKGROUND: Dapsone is a drug used to treat leprosy. Dapsone causes a highly morbid and potentially fatal severe drug hypersensitivity reaction (DHS) in 1-3% of leprosy cases. The allele HLA-B*13:01 is a known genetic risk factor for DHS. However, resource-intensive genotyping methods preclude its testing in resource-limited settings. This study aimed to develop an endpoint PCR assay to detect the presence of HLA-B*13:01. RESEARCH DESIGN AND METHODS: DNA was extracted from blood samples of leprosy patients at Anandaban Hospital, Nepal (2022-24). A duplex endpoint PCR was optimized and validated against a previously validated commercial qPCR method and NGS (next‑generation sequencing). RESULTS: In 113 samples, duplex PCR showed 100% (95% CI: 79.4-100%) sensitivity and 100% specificity (95% CI: 96.2-100%) compared to the validated qPCR method. The same accuracy was confirmed in 58 NGS-typed samples (concordance 98.3%, 95% CI: 90.7-99.9%). The assay reliably differentiated HLA-B*13:01 from closely related allele. Analytical sensitivity reached a lower detection limit of 100 genome equivalents (0.67 ng DNA/reaction). CONCLUSION: The developed duplex endpoint PCR offers a simple and affordable method for detecting HLA-B*13:01, suitable in low-resource settings. Its use may significantly reduce the risk of DHS by guiding safer drug choices prior to MDT initiation.

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HumansDapsoneLeprosyPolymerase Chain ReactionGenotypeAllelesDrug HypersensitivityCost-Benefit AnalysisFemaleHLA-B13 AntigenGenotyping TechniquesMaleSensitivity and SpecificityLeprostatic AgentsHLA-B AntigensAdultPolymerase chain reactiondapsonedrug hypersensitivityhuman leukocyte antigenleprosyJournal Article

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Divya Rsjb Rana, Kishor Koju, Jivan Shakya, Sarita Manandhar, Anjana Singh, Mahesh Shah, Deanna A Hagge, Jarina Joshi. 2026-08-30. A cost-effective conventional endpoint PCR assay for HLA-B*13:01 genotyping to guide personalized dapsone therapy in leprosy in low-resource settings.. https://doi.org/10.1080/17410541.2026.2724106

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