title: Drug and multidrug resistance among Mycobacterium leprae isolates from Brazilian relapsed leprosy patients.
abstract: Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil were submitted for sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms (SNPs) in these genes were observed in M. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB, and two cases showing mutations in folP1, rpoB, and gyrA, suggesting the existence of multidrug resistance (MDR). The nature of the mutations was as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, with two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe), and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 years; P = 0.0038). More than 70% of the relapses were multibacillary, including three of the mutation-carrying cases; one MDR relapse patient was paucibacillary.
authors.affiliation: Laboratory of Molecular Biology Applied to Mycobacteria, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Adalgiza
authors.initials: A
authors.lastname: da Silva Rocha
authors.forename: Maria das Graças
authors.initials: Md
authors.lastname: Cunha
authors.forename: Lucia Martins
authors.initials: LM
authors.lastname: Diniz
authors.forename: Claudio
authors.initials: C
authors.lastname: Salgado
authors.forename: Maria Araci P
authors.initials: MA
authors.lastname: Aires
authors.forename: José Augusto
authors.initials: JA
authors.lastname: Nery
authors.forename: Eugênia Novisck
authors.initials: EN
authors.lastname: Gallo
authors.forename: Alice
authors.initials: A
authors.lastname: Miranda
authors.forename: Monica M F
authors.initials: MM
authors.lastname: Magnanini
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsuoka
authors.forename: Euzenir Nunes
authors.initials: EN
authors.lastname: Sarno
authors.forename: Philip Noel
authors.initials: PN
authors.lastname: Suffys
authors.forename: Maria Leide W
authors.initials: ML
authors.lastname: de Oliveira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001706:Biopsy; D001938:Brazil / Q000453:epidemiology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005260:Female; D005798:Genes, Bacterial; D006801:Humans; D007918:Leprosy / Q000453:epidemiology* / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009166:Mycobacterium leprae / Q000187:drug effects* / Q000302:isolation & purification*; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011446:Prospective Studies; D012008:Recurrence; D017422:Sequence Analysis, DNA; D012867:Skin / Q000382:microbiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial