BACKGROUND In the southern region of the United States, such as in Louisiana and Texas, there are autochthonous cases of leprosy among native-born Americans with no history of foreign exposure. In the same region, as well as in Mexico, wild armadillos are infected with Mycobacterium leprae. METHODS Whole-genome resequencing of M. leprae from one wild armadillo and three U.S. patients with leprosy revealed that the infective strains were essentially identical. Comparative genomic analysis of these strains and M. leprae strains from Asia and Brazil identified 51 single-nucleotide polymorphisms and an 11-bp insertion–deletion. We genotyped these polymorphic sites, in combination with 10 variable-number tandem repeats, in M. leprae strains obtained from 33 wild armadillos from five southern states, 50 U.S. outpatients seen at a clinic in Louisiana, and 64 Venezuelan patients, as well as in four foreign reference strains. RESULTS The M. leprae genotype of patients with foreign exposure generally reflected their country of origin or travel history. However, a unique M. leprae genotype (3I-2-v1) was found in 28 of the 33 wild armadillos and 25 of the 39 U.S. patients who resided in areas where exposure to armadillo-borne M. leprae was possible. This genotype has not been reported elsewhere in the world. CONCLUSIONS Wild armadillos and many patients with leprosy in the southern United States are infected with the same strain of M. leprae. Armadillos are a large natural reservoir for M. leprae, and leprosy may be a zoonosis in the region. (Funded by the National Institute of Allergy and Infectious Diseases and others.)

The emergence of rifampin-resistant strains of pathogenic mycobacteria has threatened the usefulness of this drug in treating mycobacterial diseases. Critical to the treatment of individuals infected with resistant strains is the rapid identification of these strains directly from clinical specimens. It Rifampin is an important component of effective multidrug therapies for tuberculosis and leprosy; however, widespread use has led to the emergence of rifampin-resistant (Rif) strains, threatening its usefulness in treating mycobacterial diseases (4-6, 8, 26, 27). Rapid information about drug susceptibility patterns is critical to the treatment of individuals with mycobacterial disease for which rifampin is indicated. Since conventional drug susceptibility testing can require 2 to 4 weeks after growth detection (Mycobacterium tuberculosis) or up to a year (Mycobacterium leprae) in mouse footpads, improvements are needed to yield accurate analysis in a shorter time. DNA diagnostic assays have the potential to provide rapid analysis of rifampin resistance in mycobacteria because of their high degree of sensitivity and specificity and the fact that they do not rely on in vitro growth for results. Shortening the time between diagnosis and the onset of effective therapy should improve patients' survival (tuberculosis) or decrease physical deformities and ocular manifestations resulting in disabilities and blindness (leprosy).Developing such assays requires knowledge of the molecular basis of Rif' in pathogenic mycobacteria. Mutations resulting in the Rif' phenotype in prokaryotes have been mapped to the gene encoding the 1-subunit of the DNA-dependent RNA polymerase (rpoB gene) (10, 11). Recently, the entire rpoB genes of M. leprae (7) resistance have been identified in both species (8,12,28,29). To further characterize mutations associated with the Rif phenotype in M. tuberculosis, M. leprae, and other pathogenic mycobacteria, we developed a rapid PCR-based, DNA sequencing protocol targeted to a 305-bp region of rpoB. By direct DNA sequencing of PCR products, the nucleic acid sequence within this region was determined in 4 rifampinsusceptible (Rifs) and 4 Rif' strains of M. leprae and in 12 Rif' and 110 Rif' strains of M. tuberculosis. In addition, mutations were identified in this region of Rif' strains of Mycobacterium africanum and Mycobacterium avium, the latter causing frequent opportunistic infections in immunocompromised hosts. On the basis of these results we have established conditions for a PCR-heteroduplex formation assay (PCR-HDF) for the rapid detection of the Rif' phenotype in pathogenic mycobacteria. MATERUILS AND METHODSMycobacterial strains. Rifampin-susceptible and -resistant strains of M. leprae were isolated initially from homogenates of skin biopsy samples from lepromatous leprosy patients not responding to antileprosy therapy, which included rifampin, and were subsequently defined as resistant to rifampin by the standard mouse footpad drug susceptibility assay (23). These strains were amplifie...

This 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.