Abstract
ObjectivesAntimicrobial resistance (AMR) is a priority for surveillance in bacterial infections. For leprosy, AMR has not been assessed because Mycobacterium leprae does not grow in vitro. We aim to obtain AMR data using molecular detection of resistance genes and to conduct a prospective open survey of resistance to antileprosy drugs in countries where leprosy is endemic through a WHO surveillance network. MethodsFrom 2009 to 2015, multi-bacillary leprosy cases at sentinel sites of 19 countries were studied for resistance to rifampicin, dapsone and ofloxacin by PCR sequencing of the drug-resistance-determining regions of the genes rpoB, folP1 and gyrA. ResultsAmong 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and 21 for ofloxacin). Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin. Rifampicin resistance was observed among relapse (58/1143, 5.1%) and new (16/789, 2.0%) cases in 12 countries. India, Brazil and Colombia reported more than five rifampicin-resistant cases. ConclusionsThis is the first study reporting global data on AMR in leprosy. Rifampicin resistance emerged, stressing the need for expansion of surveillance. This is also a call for vigilance on the global use of antimicrobial agents, because ofloxacin resistance probably developed in relation to the general intake of antibiotics for other infections as it is not part of the multidrug combination used to treat leprosy.
Highlights
As treatment of leprosy and tuberculosis, the two main mycobacterial diseases, progressed during the 1950s and 1960s, the development of drug resistance was recognized as an obstacle to case management and control [1e3]
Among 1932 (1143 relapse and 789 new) cases studied, 154 (8.0%) M. leprae strains were found with mutations conferring resistance showing 182 resistance traits (74 for rifampicin, 87 for dapsone and for ofloxacin)
Twenty cases showed rifampicin and dapsone resistance, four showed ofloxacin and dapsone resistance, but no cases were resistant to rifampicin and ofloxacin
Summary
As treatment of leprosy and tuberculosis, the two main mycobacterial diseases, progressed during the 1950s and 1960s, the development of drug resistance was recognized as an obstacle to case management and control [1e3]. To prevent further drug-resistance development, the treatment of both diseases was standardized with a combination of antibiotics. We know that this policy was only partially successful because multidrug resistance is common and represents a major constraint on the control of tuberculosis [4]. To date, there have been no structured data available on resistance. Dapsone resistance was evident as clinical failure on long-term monotherapy, but it was detected through laboratory tests only with the development of the mouse foot-pad model, because
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