Transmission of dapsone-resistant leprosy detected by molecular epidemiological approaches

Wei Li1, Rama M Sakamuri, Danielle E Lyons

  • 1Department of Microbiology, Colorado State University, Fort Collins, Colorado 80523, USA.

Insights

Drug resistance surveillance found Mycobacterium leprae folP1 mutations conferring dapsone resistance in untreated and relapse leprosy patients. These mutations, particularly Thr53Val, suggest dapsone-resistant leprosy strains are actively transmitted.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Genetics

Background:

  • Leprosy, a neglected tropical disease, requires effective multidrug treatment.
  • Emergence of drug resistance is a significant threat to leprosy control efforts.
  • Surveillance for drug resistance mutations is crucial for guiding treatment strategies.

Purpose of the Study:

  • To investigate the prevalence and transmission of dapsone resistance in Mycobacterium leprae.
  • To identify specific mutations in the folP1 gene associated with dapsone resistance.
  • To assess the genetic relatedness of resistant strains.

Main Methods:

  • Drug resistance surveillance of leprosy patients.
  • Genomic analysis of Mycobacterium leprae, focusing on the folP1 gene.
  • Variable-number tandem repeat (VNTR) typing to assess strain relatedness.

Main Results:

  • Six untreated leprosy patients in the Philippines harbored Mycobacterium leprae with folP1 mutations conferring dapsone resistance.
  • Four of these patients shared a village and a specific Thr53Val mutation, linked by M. leprae VNTR strain types.
  • Two relapse patients in India also showed folP1 mutations after dapsone treatment.
  • No mutations were detected in the rifampin resistance-associated rpoB gene.

Conclusions:

  • The findings indicate the active transmission of dapsone-resistant leprosy strains.
  • The Thr53Val mutation in folP1 is a key marker for dapsone resistance.
  • Community-based surveillance and molecular typing are essential for monitoring and controlling drug resistance in leprosy.

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