title: The frequency of drug resistance mutations in Mycobacterium leprae isolates in untreated and relapsed leprosy patients from Myanmar, Indonesia and the Philippines.
abstract: BACKGROUND
  The magnitude of drug resistance in Mycobacterium leprae to dapsone, rifampicin, and ofloxacin was studied in three Southeast Asian countries with a high prevalence of leprosy.
  
  
  METHODS
  M. leprae from the skin of leprosy patients was collected in North Maluku and North Sulawesi in Indonesia, Yangon in Myanmar, and Cebu in the Philippines. Mutations in the drug resistance determining regions in the folP1, rpoB, and gyrA genes, which have been proven to confer resistance, were analysed. In addition, samples from 51 newly diagnosed cases and 13 patients with leprosy relapse in Cebu were submitted for susceptibility testing in the mouse footpad.
  
  
  RESULTS
  Of 252 isolates obtained from new cases, 3% were dapsone resistant and 2% were rifampicin resistant. In samples taken from patients with relapsed leprosy (n = 53), significantly more resistance mutations were detected: 15% had dapsone resistance mutations, and 8% had rifampicin resistance mutations. Two patients with relapsed leprosy had mutations for both dapsone and rifampicin resistance. No mutations conferring quinolone resistance were detected. No mutations were detected in the folP1 gene of M. leprae isolates with a low degree of resistance to dapsone.
  
  
  CONCLUSIONS
  Detection of drug-resistant cases by mutation detection in the drug resistance determining region of the genome is a practical method for monitoring resistance. A comparison of the results obtained in this study with previous data obtained prior to the use of multidrug therapy (MDT), does not indicate clearly whether the magnitude of drug resistance has changed. Larger studies of resistance mutations in M. leprae isolated from patients with relapsed leprosy are needed to confirm our results.
  
  
  CONCLUSIONS
  We recommend monitoring the magnitude of drug resistance globally, by testing M. leprae DNA from relapse cases and a representative sample of new cases.
authors.affiliation: Leprosy Research Centre, National Institute of Infectious Diseases, Tokyo, Japan. matsuoka@nih.go.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Teky
authors.initials: T
authors.lastname: Budiawan
authors.forename: Khin Saw
authors.initials: KS
authors.lastname: Aye
authors.forename: Kyaw
authors.initials: K
authors.lastname: Kyaw
authors.forename: Esterlina Virtudes
authors.initials: EV
authors.lastname: Tan
authors.forename: Eduardo Dela
authors.initials: ED
authors.lastname: Cruz
authors.forename: Robert
authors.initials: R
authors.lastname: Gelber
authors.forename: Paul
authors.initials: P
authors.lastname: Saunderson
authors.forename: Victoria
authors.initials: V
authors.lastname: Balagon
authors.forename: Vijaykumar
authors.initials: V
authors.lastname: Pannikar
mesh_terms: D017931:DNA Primers; D004269:DNA, Bacterial / Q000032:analysis; D024881:Drug Resistance, Bacterial; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D007917:Leprostatic Agents / Q000494:pharmacology; D007918:Leprosy / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology; D009154:Mutation; D009166:Mycobacterium leprae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D010679:Philippines / Q000453:epidemiology; D016133:Polymerase Chain Reaction; D012008:Recurrence
chemical_list: D017931:DNA Primers; D004269:DNA, Bacterial; D007917:Leprostatic Agents