Comparative Sequence Analysis of<i>Mycobacterium leprae</i>and the New Leprosy-Causing<i>Mycobacterium lepromatosis</i>

Han, Xiang-Yang; Sizer, Kurt C.; Thompson, Erika J.; Kabanja, Juma; Li, Jun; Hu, Peter; Gómez-Valero, Laura; Silva, Francisco J.

doi:10.1128/jb.00762-09

Cited by 112 publications

(75 citation statements)

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“…2 Most recently, genomes of two M. lepromatosis strains were sequenced, revealing an ∼13% genome-wide difference. 3,4 Analysis of one of the draft genomes refined the divergence time to 13.9 million years and showed similar genomic organization of the two bacilli.…”

Section: Discussion and Literature Reviewmentioning

confidence: 99%

“…Also of note, the brother's positive syphilis tests and high ANA titer can be attributed to cross-reactive antibodies in lepromatous leprosy. 2,3,9 Therefore, based on the above literature review and discussion, we summarize M. lepromatosis leprosy as the following: 1) M. lepromatosis causes a range of clinical manifestations comparable to typical M. leprae infection in patients in Mexico and elsewhere; 2) the clinical manifestations of patients vary remarkably as seen with M. leprae infections, and it remains to be determined whether differences between infections with M. leprae and M. lepromatosis can be recognized clinically; 3) the pathologic diagnosis is identical for both Mycobacterium species (species distinction requires DNA analysis); 4) the treatment with a multidrug regimen should be effective although more experience is needed. At this time, the identification of M. lepromatosis is primarily of epidemiologic value.…”

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confidence: 99%

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Two Cases of Leprosy in Siblings Caused by Mycobacterium lepromatosis and Review of the Literature

Sotiriou¹,

Stryjewska²,

Hill³

2016

The American Society of Tropical Medicine and Hygiene

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Abstract. We describe two leprosy cases in Mexican siblings caused by a new species Mycobacterium lepromatosis. This is likely the first report of family clustering of this infection. The patients showed severe prolonged leprosy reactions after antimicrobial treatment, raising a challenge for clinical management. The current status of M. lepromatosis infection is reviewed. REPORT OF CASESA 25-year-old male, living in Minneapolis but originally from Guerrero, Mexico, presented with a one-and-half year history of pruritus, swelling, and pain involving the distal extremities and the ears in January 2007. Physical examinations at the time and shortly after revealed madarosis (Figure 1), nonpitting edema of the ears, bilateral loss of eyelashes, and ill-defined, somewhat dusky, hyperpigmented patches scattered diffusely and symmetrically on his extremities with sparing of the trunk and neck. His hands and feet showed nonpitting edema and induration. No neurologic deficits were noted. Extensive laboratory workup revealed the following abnormal results: elevated erythrocyte sedimentation rate (ESR) of 54 mm/hour, reactive rapid plasma reagin, borderline fluorescent treponemal antibody absorption test, and an antinuclear antibody (ANA) titer of 1:320 with a speckled pattern. An anti-dsDNA antibody was negative. A skin biopsy from the left thigh was performed, and the patient was treated empirically with intramuscular benzathione penicillin in view of the borderline positive syphilis tests.Histopathology of the skin biopsy demonstrated granulomatous infiltrates, with perineural and perivascular involvement, and a large number of acid-fast bacilli on Fite stain ( Figure 2). These findings, together with clinical presentation and laboratory results, rendered the diagnosis of borderline lepromatous leprosy. The patient was treated with minocycline 100 mg daily, rifampin 600 mg monthly, and dapsone 50 mg daily.Approximately 11 months into the multidrug therapy for leprosy, the patient developed signs and symptoms suggestive of both reversal reaction and erythema nodosum leprosum (ENL), including worsened skin lesions and swelling of hands and feet and new onset of fevers, recurrent crops of tender erythematous nodules on all extremities, and joint pains. He also reported a yellowish exudate from a preexisting lesion on the right leg. On examination, nonpitting edema and induration were noted on all distal extremities and a new dusky violaceous hue was observed on his hands and feet. The sore on his right leg appeared as a healing ulceration with an overlying hemorrhagic crust. Neurologic examination at this time revealed palpable and slightly tender ulnar nerves bilaterally and mild (scale 4 of 5) weakness of all distal extremities. Decreased sensation to pain and light touch was noted over most of his dorsal left hand and the lower legs, from the mid-calves to dorsal feet. Reflexes were symmetric and intact. A bluish discoloration on his nose and ears was also observed, which was thought to be the effect of minocycline, lea...

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Section: Discussion and Literature Reviewmentioning

confidence: 99%

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confidence: 99%

Two Cases of Leprosy in Siblings Caused by Mycobacterium lepromatosis and Review of the Literature

Sotiriou¹,

Stryjewska²,

Hill³

2016

The American Society of Tropical Medicine and Hygiene

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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. Those authors have further investigated the existence of M. lepromatosis in leprosy patients in Mexico and have claimed that M. lepromatosis, particularly the DLL form, is the predominant cause of leprosy there (5).…”

Section: Case Reportmentioning

confidence: 99%

“…Like M. leprae, M. lepromatosis cannot be cultured on artificial media; it also shares other features such as an unusually low GϩC content for a mycobacterium (57.8%), the presence of pseudogenes, unique AT-rich insertions in the 16S rRNA gene, and identical six-base tandem repeats in sigA (4,5). Cases of M. lepromatosis infection have exhibited much higher morbidity and even mortality rates than cases of M. leprae infection (4).…”

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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“…Among these, M. leprae is a known obligate intracellular parasite. Most other species are facultative with the exception of the recently discovered M. lepromatosis that also causes leprosy (Han et al 2009;Han and Silva 2014). Obligate intracellular bacteria are typically characterized by smaller genome sizes compared to facultative intracellular or free-living bacteria (Bordenstein and Reznikoff 2005).…”

Section: Figurementioning

confidence: 99%

Estimation of Gene Insertion/Deletion Rates with Missing Data

et al. 2016

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Lateral gene transfer is an important mechanism for evolution among bacteria. Here, genome-wide gene insertion and deletion rates are modeled in a maximum-likelihood framework with the additional flexibility of modeling potential missing data. The performance of the models is illustrated using simulations and a data set on gene family phyletic patterns from Gardnerella vaginalis that includes an ancient taxon. A novel application involving pseudogenization/genome reduction magnitudes is also illustrated, using gene family data from Mycobacterium spp. Finally, an R package called indelmiss is available from the Comprehensive R Archive Network at https://cran.r-project.org/package=indelmiss, with support documentation and examples.

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Comparative Sequence Analysis ofMycobacterium lepraeand the New Leprosy-CausingMycobacterium lepromatosis

Cited by 112 publications

References 28 publications

Two Cases of Leprosy in Siblings Caused by Mycobacterium lepromatosis and Review of the Literature

Two Cases of Leprosy in Siblings Caused by Mycobacterium lepromatosis and Review of the Literature

Case of Diffuse Lepromatous Leprosy Associated with “Mycobacterium lepromatosis”

Estimation of Gene Insertion/Deletion Rates with Missing Data

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