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Peer reviewedOpen accessLeprosy

Evaluating the risk of dapsone hypersensitivity syndrome in Nepalese Leprosy Patients via HLA-B* 13:01 screening using real-time PCR and comparative meta-analysis of international data

PLOS Neglected Tropical Diseases·

Divya RSJB Rana, Mahesh Shah, Suwash Baral, Reejana Shrestha, Kishor Koju, Kanchha Shrestha, Preeti Maharjan, Jarina Joshi, Indra Bahadur Napit, Pushpendra Singh, Hana Krismawati, Deanna A. Hagge

DOI
10.1371/journal.pntd.0014568
PMID
42594150
PMCID
OpenAlex
W7202363485
Study type
Meta-analysis
Publisher
Public Library of Science (PLoS)
Article type
journal-article
Integrity
current

Why this research matters now

Routine pre-therapy genetic assessment might lower the burden of severe medication-related complications in endemic regions with limited laboratory infrastructure.

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Structured evidence summary

Research question

Does the HLA-B*13:01 allele correlate with dapsone-induced hypersensitivity reactions in a Nepalese leprosy cohort, and can a rapid polymerase chain reaction assay reliably substitute for more complex sequencing methods?

Study design

The authors conducted a combined case-control evaluation utilizing both historical and newly identified patient samples, supplemented by a comprehensive meta-analysis of previously published international datasets.

Population and setting

The primary cohort comprised multi-ethnic leprosy patients undergoing standard multidrug therapy in Nepal, while the secondary analysis incorporated aggregated results from global investigations focusing on the same pharmacogenetic interaction.

Main findings

Statistical modeling revealed a pronounced correlation between the genetic variant and the adverse drug event within the local sample. The rapid molecular screening technique achieved near-perfect alignment with established sequencing protocols. Aggregated global metrics strengthened this association, and demographic breakdowns showed that genetically positive individuals experienced symptom onset considerably earlier than their counterparts.

Public-health relevance

Routine pre-therapy genetic assessment might lower the burden of severe medication-related complications in endemic regions with limited laboratory infrastructure.

Important limitations

Nearly a quarter of diagnosed reaction cases tested negative for the target allele, highlighting incomplete sensitivity. Furthermore, the screening tool demonstrated a modest positive predictive value, meaning many positive results would not correspond to actual clinical events.

GIDS interpretation

The article establishes a quantifiable biological marker linked to a documented treatment complication, offering a reference point for tracking diagnostic advancements and regional pharmacovigilance frameworks.

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Related GIDS surveillance

Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.

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Evidence relationships

This article has 9 auditable classifier relationships to diseases, places, topics, and study design.

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