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Genomic Study Points to Wild Armadillo Source for Leprosy Infections in Southern US

By Andrea Anderson

NEW YORK (GenomeWeb News) – A genetic study published in the New England Journal of Medicine today supports the notion that wild armadillos may be a source of some leprosy infections in the southern US.

Researchers from the US, Switzerland, and Paris sequenced the genomes of Mycobacterium leprae bacteria isolated from three leprosy patients and a single wild armadillo. Using SNP, indel, and variable-number tandem-repeat information from these and other M. leprae genomes sequenced previously, they then profiled genetic patterns in leprosy bugs from nearly 120 American and Venezuelan leprosy patients and dozens more wild armadillos from five states.

The findings offer microbiological and genomic evidence that many leprosy cases in the southern US and Gulf Coast area are caused by organisms that are essentially identical to those found in wild armadillos in the region, co-lead author Richard Truman, chief of microbiology for the US Health Resources and Services Administration's National Hansen's Disease Program (NHDP), told GenomeWeb Daily News.

"This provides a microbiological linkage," he added, "and suggests that armadillos can be a source of infection for some of our patients and that this is a probable zoonosis in the southern United States."

Nevertheless, James Krahenbuhl, who is director of the NHDP but was not directly involved in the new study, emphasized, "This knowledge about the probable connection between [leprosy in] armadillos and humans does not change the risk of acquiring leprosy from the armadillos."

"It's infinitesimally small to begin with," he told GWDN. "That hasn't changed. And this knowledge might actually reduce this risk even further by making people a little bit more wary of their contact with armadillos."

Roughly a quarter of a million cases of leprosy, also known as Hansen's disease, are reported around the world each year — including an estimated 150 to 250 cases in the US.

Many American cases appear to stem from travel to other parts of the world, researchers explained. But as many as a third of US cases involve individuals who have neither traveled to leprosy-endemic locales nor been exposed to individuals with the disease.

The source of these infections is unclear, though past work suggests as many as one fifth of wild nine-banded armadillos living in parts of the southern states are infected with the M. leprae pathogen.

"Humans and armadillos are the only animals that are natural hosts of this disease," Truman explained.

The animal's susceptibility to leprosy has made it a useful model system for studying the disease, researchers explained, particularly since the pathogen can't be grown in laboratory media. But such infections hint that the animals might also have the potential to act as a reservoir for the disease in parts of Mexico and in southern states such as Texas, Louisiana, Alabama, Arkansas, and Mississippi.

Past case-control studies support that theory, Truman noted, though there are still questions about how armadillo infections relate to those seen in humans.

"It's been speculated that the animals could contribute to human infection," he said. "But … it was not really clear whether this was an anecdotal occurrence or whether they were important in the ecology of the disease or exactly what was going on."

In the hopes of understanding this potential relationship, Truman and his colleagues used the Illumina Genome Analyzer II to sequence the genomes of four M. leprae isolates: one from a wild armadillo and three from individuals being treated for leprosy.

When they compared these with four previously sequenced M. leprae genomes from India, Brazil, the US, and Thailand, the team identified 51 SNPs found solely in southern US strains and 21 sites that varied amongst these strains — variants that they subsequently verified by Sanger sequencing.

Using such variants, the researchers then genotyped M. leprae isolates from 33 more wild armadillos in five states, along with samples from 50 individuals treated for leprosy at a Louisiana clinic and from 64 Venezuelan leprosy patients.

Overall, researchers reported, M. leprae strains from around the world remain very similar to one another genetically.

Even so, their analyses suggest wild armadillo populations in the southern US harbor a type of M. leprae — dubbed 3I-2-v1 based on genotype, indel, and VNTR patterns — that has not been found anywhere else in the world.

Just five of the wild armadillos tested were not infected with this M. leprae genotype. Of the 39 American patients living in areas where wild armadillos carry M. leprae 3I-2-v1, meanwhile, 25 individuals were infected pathogens sharing this genotype.

"This is the first time that we've had the technology to do transmission chains," Truman said. "So we can not only do it here in the United States, between humans and armadillos, but we can do it elsewhere in other human transmission chains.

"Using these techniques we can very rapidly determine whether there are other point sources or non-human reservoirs of infection that may be affecting the ecology of the disease in other areas," he added.

While the researchers emphasized that the risk of contracting leprosy from an armadillo remains very low, they said the current findings highlight the need for caution for those who may come in contact with the animals.

And, they say, the apparent link may make physicians in the southern US and Gulf Coast region more apt to consider leprosy infections when making diagnoses.

"We're hoping that this encourages physicians to consider leprosy in their differential diagnoses," Truman said, "because that has a tremendous impact on the long-term prognosis of patients — early diagnosis and treatment."