Geographically distinct isolates of <i>Mycobacterium leprae</i> exhibit no genotypic diversity by restriction fragment‐length polymorphism analysis

Williams, Diana L.; Gillis, Thomas P.; Portaels, F

doi:10.1111/j.1365-2958.1990.tb00542.x

Cited by 43 publications

(30 citation statements)

References 19 publications

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“…Although many attempts have been made to subtype M. leprae isolates by genomic divergence (4,9,19), no useful methods for epidemiological analysis have been developed. Recently two genomic polymorphisms successfully discriminated isolates of M. leprae (12,17).…”

Section: Discussionmentioning

confidence: 99%

“…Restriction fragment length polymorphism analysis, which is the method most widely used for molecular epidemiology of tuberculosis, is not applicable for leprosy, since M. leprae cannot be grown in artificial medium, and almost no divergence was found by this fingerprinting assay (19). Shin et al discovered a genomic divergence of M. leprae by the variation of TTC repeats (17) and subdivided 34 isolates into 15 subtypes.…”

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confidence: 99%

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Genotyping of Mycobacterium leprae on the Basis of the Polymorphism of TTC Repeats for Analysis of Leprosy Transmission

Matsuoka

Zhang

Budiawan³

et al. 2004

J Clin Microbiol

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The polymorphism of TTC repeats in Mycobacterium leprae was examined using the bacilli obtained from residents in villages at North Maluku where M. leprae infections are highly endemic (as well as from patients at North Sulawesi of Indonesia) to elucidate the possible mode of leprosy transmission. TTC genotypes are stable for several generations of passages in nude mice footpads and, hence, are feasible for the genotyping of isolates and epidemiological analysis of leprosy transmission. It was found that bacilli with different TTC genotypes were distributed among residents at the same dwelling in villages in which leprosy is endemic and that some household contacts harbored bacilli with a different genotype from that harbored by the patient. Investigations of a father-and-son pair of patients indicated that infections of bacilli with 10 and 18 copies, respectively, had occurred. Genotypes of TTC repeats were found to differ between a son under treatment and two brothers. These results reveal the possibility that in addition to exposure via the presence of a leprosy patient with a multibacillary infection who was living with family members, there might have been some infectious sources to which the residents had been commonly exposed outside the dwellings. A limited discriminative capacity of the TTC polymorphism in the epidemiological analysis implies the need of searching other useful polymorphic loci for detailed subdivision of clinical isolates.Leprosy is a chronic infectious disease caused by Mycobacterium leprae infection. It has long being believed that the source of infection is untreated leprosy patients. It has also been predicted that multidrug therapy (MDT) with strong bactericidal antibiotics (such as rifampin) would reduce the source of infection and consequently interrupt further transmission to others. The number of new cases, however, has shown no substantial decline even though MDT with strong bactericidal drugs has been used in the past two decades. It is reported that about 600,000 to 700,000 new cases are continuously found in the world every year (20), which suggests that the transmission of leprosy bacilli still occurs, especially in countries of endemicity. Elucidation of the mode of transmission would be essential to help prevent new infection. The differentiation of strains of leprosy bacilli by genomic polymorphism might be of great value in efforts to understand the mode of transmission of the disease.The range of molecular techniques for epidemiological analysis has expanded in recent years, and there are now many genotypic methods that allow a high level of discrimination between bacterial strains. Restriction fragment length polymorphism analysis, which is the method most widely used for molecular epidemiology of tuberculosis, is not applicable for leprosy, since M. leprae cannot be grown in artificial medium, and almost no divergence was found by this fingerprinting assay (19). Shin et al. discovered a genomic divergence of M. leprae by the variation of TTC repeats (17) and subdivi...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Genotyping of Mycobacterium leprae on the Basis of the Polymorphism of TTC Repeats for Analysis of Leprosy Transmission

Matsuoka

Zhang

Budiawan³

et al. 2004

J Clin Microbiol

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“…However, M. leprae exhibits exceptionally high genetic homogeneity within different strains across the world (3,7,8,10,13); thus, M. leprae may not account for such a diverse range of clinical manifestations. Recently, Han et al (4,5) have established the existence of "Mycobacterium lepromatosis," a closely related but distinct species, as a causative agent of DLL in two patients of Mexican origin in Arizona, who succumbed to the disease.…”

Section: Case Reportmentioning

confidence: 99%

Case of Diffuse Lepromatous Leprosy Associated with “Mycobacterium lepromatosis”

et al. 2011

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An 86-year-old female patient from northeast Mexico presented with diffuse lepromatous leprosy (DLL). Sequence analysis of four genes (rrs, rpoB, sigA, and hsp65) from the skin biopsy specimen identified "Mycobacterium lepromatosis." This is the first independent confirmation of a case of DLL due to M. lepromatosis. CASE REPORTIn 2005, an 86-year-old female with no prior medical history of leprosy was admitted to our hospital due to a 10-day bout of distal cyanosis of the extremities (Fig. 1). Physical examination also showed generalized dermatosis characterized by diffuse infiltration of the skin, predominantly in the face, with thickening of the superciliary region and ears plus an accompanying absence of eyebrows and eyelashes. In the rest of the body, the skin had an atrophic "cigarette paper"-like appearance and diminished or absent body hair. The neurological examination revealed extensive areas of dysesthesia. The areas of diffuse lepromatous leprosy (DLL) associated with Lucio's phenomenon were characterized by a purpuric appearance, with necrosis and ulceration in some of the areas, leading to sloughing in acral sites such as fingers and toes. A presumptive diagnosis of cryoglobulinemia versus other vasculitis disorders was considered, and laboratory examination showed microcytic hypochromic anemia, thrombocytosis, leukocytosis, and a rheumatoid factor of 80. A skin biopsy was performed and treatment with pentoxifylline initiated. During the first week, the rheumatologist prescribed cyclophosphamide, but the patient did not improve and developed necrosis in areas that were previously cyanotic (Fig. 1). The skin biopsy specimen showed vasculitis with thrombosis and perivascular and periadnexial lymphocytic infiltrates (Fig. 2) as well as numerous acid-fast bacilli, leading to diagnosis of diffuse lepromatous leprosy (DLL) and Lucio's phenomenon. Treatment with prednisone and multidrug therapy for multibacillary leprosy was initiated. The patient improved after 10 days of treatment, was discharged after 2 weeks in stable condition, but died at home 3 months later of unknown cause.Leprosy is one of the oldest recorded human afflictions. Depending upon the immune response mounted against the bacilli, the disease presents with a broad clinical spectrum. At one pole are the tuberculoid (TT) patients, with effective T cell-mediated immunity resulting in very low bacterial numbers, while at the other, the lepromatous (LL) patients mount an ineffective humoral response and exhibit a high bacillary load. Other unstable forms, with characteristics between these poles, can also be observed. A particular variation of lepromatous leprosy involving diffuse nonnodular lesions is more frequent in Mexico and the Caribbean than in any other part of the world (2). This variation has been referred to as diffuse lepromatous leprosy (DLL) or Lucio's phenomenon (6, 11).All these forms of leprosy have been attributed to various host responses to the causative pathogen, Mycobacterium leprae. However, M. leprae exhibits exception...

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“…Approaches to uncovering polymorphisms attributed to single nucleotide mutations, insertion elements, and variablenumber tandem repeats (VNTRs) in the mycobacterial interspersed repetitive unit loci in a panel of M. leprae strains have not identified any molecular typing markers (8,35). However, it has been possible to recognize other potential polymorphic sites from the genome sequence of M. leprae (8).…”

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Multiple Polymorphic Loci for Molecular Typing of Strains of Mycobacterium leprae

Groathouse

Rivoire

Kim³

et al. 2004

J Clin Microbiol

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The need for molecular tools for the differentiation of isolates of Mycobacterium leprae, the organism that causes leprosy, is urgent in view of the continuing high levels of new case detection, despite years of aggressive chemotherapy and the consequent reduction in the prevalence of leprosy. The slow onset of leprosy and the reliance on physical examination for detection of disease have restricted the epidemiological tracking necessary to understand and control transmission. Two genetic loci in several isolates of M. leprae have previously been demonstrated to contain variable-number tandem repeats (VNTRs). On the basis of these reports and the availability of the full genome sequence, multiple-locus VNTR analysis for strain typing has been undertaken. A panel of 11 short tandem repeat (STR) loci with repeat units of 1, 2, 3, 6, 12, 18, 21, and 27 bp from four clinical isolates of M. leprae propagated in armadillo hosts were screened by PCR. Fragment length polymorphisms were detected at 9 of the 11 loci by agarose gel electrophoresis. Sequencing of representative DNA products confirmed the presence of VNTRs between isolates. The application of nine new polymorphic STRs in conjunction with automated methods for electrophoresis and size determination allows greater discrimination between isolates of M. leprae and enhances the potential of this technique to track the transmission of leprosy.The World Health Organization and its partners created the Global Alliance for Leprosy Elimination in 1999 with the aim of achieving the elimination of leprosy by the end of the year 2005, a goal originally set for the year 2000 (http://www.who .int/inf-pr-1999/en/pr99-70.html). Leprosy is effectively controlled by a multidrug therapy (MDT) regimen composed of dapsone, rifampin, and clofazimine. However, continuing large numbers of new cases are being detected in areas of the world where the disease is highly endemic, despite the application of the MDT program since 1982 (36). In order to comprehend this rising incidence of leprosy, it is necessary to identify the natural reservoir of Mycobacterium leprae, the route of infection, and the mode of its transmission. It is commonly believed that the human is the host and reservoir of M. leprae and that successful MDT will eliminate leprosy. However, other modes of transmission involving nonhuman reservoirs, such as soil (6, 15), water (20), vegetation (16), animals (including armadillos and sooty mangabeys) (22, 33), and arthropods (fleas, ticks, mosquitoes, and flies), have been suggested, as reviewed by Blake et al. (3). The route of infection is also unknown, although the entry and the exit of the bacteria via the nasal passages have been proposed (9). Methods that specifically detect M. leprae DNA in nasal swabs are being developed with the aim of early detection in populations at the community and village levels and for the monitoring of leprosy transmission (13,23). Typing methods for distinguishing cases of relapse from new infections are also required. Molecular typing wi...

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Geographically distinct isolates of Mycobacterium leprae exhibit no genotypic diversity by restriction fragment‐length polymorphism analysis

Cited by 43 publications

References 19 publications

Genotyping of Mycobacterium leprae on the Basis of the Polymorphism of TTC Repeats for Analysis of Leprosy Transmission

Genotyping of Mycobacterium leprae on the Basis of the Polymorphism of TTC Repeats for Analysis of Leprosy Transmission

Case of Diffuse Lepromatous Leprosy Associated with “Mycobacterium lepromatosis”

Multiple Polymorphic Loci for Molecular Typing of Strains of Mycobacterium leprae

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