Abstract

ABSTRACT Reports on antimicrobial resistance (AMR) of Mycobacterium leprae, relationship with bacteriological index (BI), and transmission in China are limited. We investigated the emergence of AMR mutations, the relationship between BI and AMR in complete, moderate and lack of BI decline cases, and molecular epidemiological features of AMR cases by enrolling 290 leprosy cases from four endemic provinces. Seven (2.41%), one (0.34%), five (1.72%), one (0.34%), and one (0.34%) strains had single mutations in folP1, rpoC, gyrA, gyrB, and 23S rRNA, respectively. Double mutations in folP1 and gyrA, rpoB and gyrA, and gyrA and 23S rRNA were observed in one (0.34%) strain each. Mutated strains occurred in three out of 81 (95% CI−0.005-0.079, p = 0.083) cases with complete BI decline, in seven out of 103 (95% CI 0.018-0.117, p = 0.008) cases with moderate BI decline, and in four out of 34 (95% CI 0.003-0.231, p = 0.044) cases with lack of BI decline. Most of these mutated strains were geographically separated and diverged genotypically. AMR mutations may not be the main cause of the lack of BI decline. The low transmission of AMR strains at the county level indicates an ongoing transmission at close contact levels.

Highlights

  • Leprosy is a chronic granulomatous disease that mainly affects the skin, peripheral nerves, and mucous membrane [1]

  • In the complete bacteriological index (BI) decline group, BI rapidly declined from the initial to the release from treatment (RFT) and remained stable towards the 1-year post-RFT

  • As very limited studies described the prevalence of gene mutations associated with antimicrobial resistance (AMR), the present study highlighted the characterization of the emergence of drug resistance by analysing DRDRs and some extended potential DRDR genes of M. leprae in China

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Summary

Introduction

Leprosy is a chronic granulomatous disease that mainly affects the skin, peripheral nerves, and mucous membrane [1]. The reduction in leprosy prevalence has been observed in recent years in China; a considerable number of new, relapse, and drug-resistant cases occurred representing a major public health concern [3]. Drug resistance detection of WHO-recommended DRDRs containing folP1, rpoB, and gyrA associated with dapsone, rifampicin, and ofloxacin resistance respectively is well established and has been incorporated in the WHO guidelines for AMR surveillance. There are several AMR reports available regarding dapsone [4], rifampicin [5], and ofloxacin [6] resistance in leprosy. In addition to mutations in WHO-recommended DRDRs, compensatory AMRassociated mutations, including nth (DNA repair), rpoA (rifampicin), rpoB, rpoC (rifampicin), gyrA, gyrB (ofloxacin), and 23S rRNA (clarithromycin) have been reported in Mycobacterium tuberculosis and Mycobacterium leprae. The roles of these mutations in M. leprae are yet to be confirmed [7,8,9]

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