title: Analysis of drug-resistant strains of Mycobacterium leprae in an endemic area of Vietnam.
abstract: BACKGROUND
  Multidrug therapy has effectively reduced the number of leprosy cases in the world. However, the rate of reduction has decelerated over the years, giving early detection of Mycobacterium leprae and epidemiological study of relapse renewed relevance in attempts to eliminate the disease.
  
  
  METHODS
  A molecular epidemiological survey for drug-resistant M. leprae was conducted in the central and highland regions of Vietnam. A total of 423 samples taken from patients, including 83 patients with new cases, 321 patients receiving treatment, and 19 patients with relapse, were studied for detection of M. leprae with mutations relating to drug resistance by sequencing the drug resistance determining region of the folP1, rpoB, and gyrA genes, which are responsible for dapsone, rifampicin, and ofloxacin resistance, respectively.
  
  
  RESULTS
  Nineteen mutations were found in the folP1 gene samples, and no mutations relating to drug resistance were found in either the rpoB or gyrA genes. Samples from patients with relapse showed folP1 mutation rates as high as 57%, and the mutation rates in samples from new and recent cases were <10%. Patients with relapse who had histories of treatment with dapsone monotherapy showed high mutation rates (78%), compared with patients with relapse who had previously only received multidrug therapy (33%).
  
  
  CONCLUSIONS
  Our study indicated high rates of dapsone resistance in patients with relapse, compared with patients with new and recent cases of leprosy. Moreover, it was observed that many of the patients with relapse who had dapsone-resistant mutations had histories of treatment with dapsone monotherapy.
authors.affiliation: Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo, Japan. mkai@nih.go.jp
authors.forename: Masanori
authors.initials: M
authors.lastname: Kai
authors.forename: Nhu Ha
authors.initials: NH
authors.lastname: Nguyen Phuc
authors.forename: Hoang An
authors.initials: HA
authors.lastname: Nguyen
authors.forename: Thi Hoang Bich Diu
authors.initials: TH
authors.lastname: Pham
authors.forename: Khanh Hoa
authors.initials: KH
authors.lastname: Nguyen
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yumi
authors.initials: Y
authors.lastname: Maeda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Fukutomi
authors.forename: Noboru
authors.initials: N
authors.lastname: Nakata
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Makino
authors.forename: Thanh Tan
authors.initials: TT
authors.lastname: Nguyen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D019353:Endemic Diseases; D005838:Genotype; D006801:Humans; D007917:Leprostatic Agents / Q000494:pharmacology*; D007918:Leprosy / Q000453:epidemiology* / Q000382:microbiology*; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D012008:Recurrence; D017422:Sequence Analysis, DNA; D014744:Vietnam / Q000453:epidemiology
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007917:Leprostatic Agents