Identification of the Leprosy Agent Mycobacterium lepromatosis in Singapore

February 2012 | Volume 11 | Issue 2 | Original Article | 168 | Copyright © 2012

Xiang Yang Han MD PhD,a Kurt Clement Sizer MD,a Hiok-Hee Tan MDb

aClinical Microbiology Laboratory, The University of Texas M. D. Anderson Cancer Center, Houston, TX bNational Skin Center, Singapore

Abstract

Background: A new leprosy-causing species, namely Mycobacterium lepromatosis, was discovered recently to be the cause of diffuse lepromatous leprosy (DLL) in Mexico. It is unknown whether this organism exists beyond Mexico.
Methods: We sought to determine the identity of the mycobacteria in the skin tissue of two patients from Singapore who died of DLL. DNA was extracted from archived biopsy tissue, and conserved polymerase chain reaction primers were used to amplify and sequence two to three mycobacterial genes in each skin sample.
Results: Both M. lepromatosis and the well-known leprosy agent Mycobacterium leprae were identified in each DLL skin sample. The M. lepromatosis gene sequences from the Singapore cases matched 99.9% with the known Mexican M. lepromatosis strain, but they only matched the corresponding M. leprae sequences by 89.2%.
Conclusions: The new species M. lepromatosis exists beyond Mexico and is the cause of DLL in Singapore. It may cause dual infections along with M. leprae in endemic areas. Archived skin biopsy can be used to differentiate the leprosy agents.

J Drugs Dermatol. 2012;11(2):168-172.

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INTRODUCTION

Diffuse lepromatous leprosy (DLL) is a unique, severe form of leprosy that is endemic in Mexico and the Caribbean.1 Initially recognized by Lucio and Alvarado in 18522 and further described by Latapi and Chevez-Zamora in 1948,3 DLL is also called diffuse leprosy of Lucio and Latapi,4,5 leprosy with Lucio's phenomenon,6,7 or merely Lucio's leprosy. This form of leprosy manifests a diffuse cutaneous infiltrate, with no nodule or plaque formation. DLL can be misdiagnosed, particularly in non-endemic areas.

The etiologic agent of DLL was presumed to be Mycobacterium leprae without specific microbiologic studies. In 2008, we performed multi-gene analyses of a mycobacterium from two patients of Mexico origin who died of DLL with typical clinical and pathologic features.8 The analyses revealed a remarkable genetic difference between M. leprae and the new mycobacterium, which led us to propose new species Mycobacterium lepromatosis for differentiation. Subsequent sequence analysis of 20 genes and pseudogenes (22814 nucleotides) from this organism substantiated species-level divergence from M. leprae by demonstrating a 9.1% difference.9 Additional analyses of phylogeny and nucleotide substitutions also indicated that the two species diverged from a common ancestor around 10 million years ago, which was much earlier than the well-known divergence between M. tuberculosis and M. bovis (113,000 years ago). Thus, M. lepromatosis is an ancient, previously unrecognized species.

The discovery of M. lepromatosis led us to dissect the etiologic agent(s) of 120 leprosy cases from Mexico.10 The study showed that M. lepromatosis was the specific cause of all cases of DLL. More important, M. lepromatosis caused even more cases of lepromatous leprosy (LL) than DLL, and the total number of leprosy cases caused by this species exceeded those caused by M. leprae by a ratio of three to one. This unexpected finding thus indicated M. lepromatosis as the dominant cause of leprosy in Mexico. Dual infections were also found, and they accounted for 16% of all species-confirmed cases. Therefore, in endemic areas, the two species may co-exist.

DLL has been reported rarely elsewhere, including Asia (India, Iran, Malaysia, and Singapore),11-15 Europe (France),16 North America (United States),17 South America (Brazil),18,19 and

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