Prospective study on antimicrobial resistance in leprosy cases diagnosed in France from 2001 to 2015.

OBJECTIVES: Antimicrobial resistance (AMR) in leprosy is mostly unknown since Mycobacterium leprae does not grow in vitro and bacteriological investigations were abandoned. However, molecular detection of resistance can be applied to multibacillary (MB) cases.

METHODS: Patients living in France mainland or in French territories and diagnosed for leprosy from 2001 to 2015 were prospectively studied for AMR by detecting mutations in rpoB for rifampicin resistance, in folP1 for dapsone and in gyrA for ofloxacin. SNP 1-4 genotypes were determined for resistant strains.

RESULTS: Out of 334 skin biopsies received for suspicion of leprosy, 184 (55.1%) were positive for M. leprae (acid-fast bacilli and RLEP PCR) corresponding to 160 MB cases. AMR was detected in 18 cases (11.3%): 13 (8.1%) cases for dapsone resistance, 3 (1.9%) for rifampicin and 2 (1.3%) for ofloxacin. There were no strains with multidrug resistance. The mutations (numbering system of M. leprae TN strain genome) found were P55L (n=7), T53I (5), T53A (1) in folP1; S456L (2), S456F (1) in rpoB; and A91V (2) in gyrA. Resistance proportion differ significantly between new and relapse cases (7.0 % [9/127] vs 25.7 % [9/33], P = 0.003). The frequency distribution of SNP 1-4 types of resistant strains was 2, 1, 12 and 3 with 5 SNP3 cases from New Caledonia harboring the same T53I FolP1 substitution.

CONCLUSIONS: this is the first report of AMR surveillance for new and relapse cases of leprosy in Europe. Detection of resistance helped in individual treatment as well as in epidemiological investigations.