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. 2011 Apr 28;364(17):1626-33.
doi: 10.1056/NEJMoa1010536.

Probable zoonotic leprosy in the southern United States

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Probable zoonotic leprosy in the southern United States

Richard W Truman et al. N Engl J Med. .

Abstract

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.).

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Figures

Figure 1
Figure 1. Distribution of Leprosy in the United States
Counties in which leprosy cases have been reported are shown, with darker color indicating a greater total numbers of cases since 1894, according to the National Hansen’s Disease Registry. The currently estimated range of armadillos is outlined in red. Yellow circles indicate approximate locations of wild armadillos infected with Mycobacterium leprae — in Arkansas, Alabama, Louisiana, Mississippi, and Texas — suggesting that the central Gulf Coast is an area of endemic transmission to people. Leprosy cases in counties outside the armadillos’ range are due to familial contact, foreign exposure, or unknown sources.
Figure 2
Figure 2. Genotyping of Mycobacterium leprae Strains
SNP7614 and indel_17915 allowed for rapid and unambiguous identification of M. leprae strains containing SNP type 3I. Type 3I SNPs can be further subdivided into types 3I-1 and 3I-2 on the basis of SNP1527056 and four other SNPs (not shown). Samples with two copies of indel_17915 are classified into major SNP types 1, 2, 3, and 4 (as previously described) and then further subtyped as a single letter from A though P, as shown, on the basis of the listed SNPs (which are representative of a panel of 84 SNPs). Further high-resolution classification was then based on analysis of 10 variable-number tandem repeats (VNTRs).
Figure 3
Figure 3. Minimum-Spanning Phylogenetic Tree of Mycobacterium leprae Genotypes Based on Analysis of Single-Nucleotide Polymorphisms (SNPs) and Variable-Number Tandem Repeats (VNTRs)
Minimum-spanning-tree analysis was performed with the use of combined VNTR and SNP data from human and armadillo M. leprae strains. Each circle represents a genotype (human unless marked as armadillo) based on the combined data, with the circle size directly proportional to the number of strains with the corresponding genotype. Numbers along the links between circles indicate the number of loci that differ between the genotypes on either side of the link. Three fully sequenced reference M. leprae strains (TN, Thai53, and Br4923,) are labeled, as are two other reference strains (LWM26 and 43926) of foreign origin. Samples from patients with a history of foreign residence are indicated with an asterisk (with three asterisks indicating three patients). The 114 polymorphisms investigated include 84 SNPs described previously and 30 identified during our study; 10 VNTRs were also analyzed. The large circle illustrates the predominance of the 3I-2-v1 M. leprae genotype in our study, with 25 patients and 28 armadillos having this identical genotype.

References

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