Insight into the evolution and origin of leprosy bacilli from the genome sequence of
            <i>Mycobacterium lepromatosis</i>

Singh, Pushpendra; Benjak, Andrej; Schuenemann, Verena J.; Herbig, Alexander; Avanzi, Charlotte; Busso, Philippe; Nieselt, Kay; Krause, Johannes; Vera-Cabrera, Lucio; Cole, Stewart T.

doi:10.1073/pnas.1421504112

Cited by 142 publications

(155 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. 3 Thus, M. lepromatosis and M. leprae are closely related species distinguishable at the genomic level that cause similar clinical manifestations on infection of humans.…”

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%

mentioning

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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“…It also hints at the ancient divergence of the two bacilli, ϳ10 million years ago, from their last common ancestor (9, 13). Most recently, genomes of two M. lepromatosis strains were sequenced, revealing an ϳ13% genome-wide difference from M. leprae but with similar genome sizes and organizations between the species (14,15). Analysis of the one of the draft genomes also refined the divergence time to 13.9 million years (14).…”

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Diffuse Lepromatous Leprosy Due to Mycobacterium lepromatosis in Quintana Roo, Mexico

Han

Quintanilla

2015

J Clin Microbiol

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A 43-year-old woman of Mayan origin from Quintana Roo, Mexico, was diagnosed with diffuse lepromatous leprosy. The etiologic bacillus was determined to be Mycobacterium lepromatosis instead of Mycobacterium leprae. This case likely represents the first report of this leprosy form and its agent in the southeastern tip of Mexico. CASE REPORTA 43-year-old woman of Mayan ancestry sought dermatologic care in the town of Chetumal, Quintana Roo, Mexico. The patient complained of a 2-year history of burning skin sensation, loss of eyelashes and eyebrows, lower leg edema, and generalized weakness. She was a widowed housewife and had been previously healthy.Physical examination revealed generalized skin infiltration, including areas of prominent "peau d=orange" (erythematous and turgid appearance) and shining skin on the central face, cheeks, and chin. There was extensive loss of hair on arms, legs, and the pubic area. There were no eye lashes or eyebrows. The cornea reflex was diminished. The earlobes were enlarged and indurated. The body skin was dry and did not sweat. There was a generalized loss of sensation to needle pricks over the body. Laboratory examinations showed a normal hemoglobin level (140g/liter), normal counts of blood leukocytes (6.0 ϫ 10 9 / liter) and platelets, a negative VDRL test, a negative human immunodeficiency virus test, and a normal urine test. No thickened nerves were noted. Smears of the nasal mucosa and an earlobe showed acid-fast bacilli with intensities of ϩ and ϩϩ, respectively. These findings led to a working diagnosis of diffuse lepromatous leprosy (DLL) in view of the absence of skin nodules.A skin biopsy of the chin was performed. Histopathology showed extensive infiltration of histiocytes that involved skin appendages and a small nerve (Fig. 1). A Fite stain revealed moderate number of acid-fast bacilli in the skin tissue, with additional locations in the endothelia and a nerve (Fig. 2). These results rendered the diagnosis of DLL.The patient was treated with a multidrug regimen consisting of dapsone, rifampin, and clofazimine. In the third month of treatment, she developed weakness and red nodules on the face and arms, which was consistent with erythema nodosum leprosum. This mild reaction was controlled with 30 mg prednisone daily for 1 week with taper. Upon treatment for 12 months, nasal and earlobe smears remained positive for intact acid-fast bacilli, which led to continued treatment. The patient completed 18 months of treatment, resulting in negative smears and resolution of the skin infiltration and partial recovery of pain sensation, sweating, and hair (in the legs especially). At a 3-year follow-up, she showed nearly complete recovery of sensation and regrowth of hair on her eyelids and eyebrows. Thus, she was considered cured.The diagnosis of DLL prompted a quest to determine the identity of the acid-fast bacillus. Thus, differential PCRs were used to test the DNA extracted from the formalin-fixed paraffin-embedded biopsy tissue. The PCRs targeted the 16S rRNA genes of the...

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“…de se compliquer de manifestations vasculaires cliniques [9]. Ce variant génomique dériverait d'un ancêtre commun avec M. leprae, avec lequel il partage heureusement une sensibilité commune aux antibiotiques antilépreux [10].…”

Section: Des Progrès Majeurs Dans La Compréhension De La Structure Géunclassified

La lèpre n’est pas une maladie du passé

Mahé

2015

Med Sci (Paris)

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> Cette revue synthétique présente, à partir des données épidémiologiques et de recherche les plus récentes sur le sujet, les enjeux actuels de la lutte contre la lèpre. À côté des progrès importants réalisés dans l'étude génomique du bacille de la lèpre, ainsi que dans la compréhension des mécanismes fondamentaux de sensibilité individuelle à la maladie, la stagnation de l'incidence des nouveaux cas annuels observée depuis une dizaine d'années est source d'interrogations. Si l'efficacité des traitements recommandés est confirmée par un faible taux de rechute, le tarissement espéré des nouveaux cas par réduction de la contagiosité des cas traités tarde à se manifester. Des études récentes sont en faveur de l'efficacité d'une prophylaxie par prise unique de rifampicine et/ ou vaccination par le BCG des sujets contacts, ce qui pourrait permettre une accélération de la réduction de l'incidence de la maladie. Toutefois, aucune prise de position officielle sur ces travaux ne valide la mise en oeuvre de telles stratégies. Du fait d'une ambiguïté dans l'expression des objectifs opérationnels de prise en charge de la lèpre, « l'élimination en tant que problème de santé publique » de la maladie ne devant notamment pas être confondue avec une « éradication » qui n'est nullement d'actualité, une démobilisation dans la lutte contre la lèpre est à redouter. < le juste reflet des importants -et réels -succès obtenus dans la lutte organisée contre ce fléau, qui n'est indiscutablement plus ce qu'il a pu être. Mais, pour une maladie dont aucune donnée n'indique qu'elle est éradiquée, ou seulement en passe de l'être, il paraît licite de faire le point sur l'état des connaissances la concernant aujourd'hui, ne seraitce qu'au regard des plus de 200 000 nouveaux cas encore répertoriés de par le monde chaque année [1]. Nous souhaitons présenter ici un panorama des principales avancées récentes ainsi que des enjeux concernant la lutte contre la lèpre aujourd'hui. Données épidémiologiquesL'introduction au début des années 1980 de protocoles thérapeutiques « courts » (de 6 mois à 2 ans selon la forme clinique) comportant de la rifampicine et permettant de guérir bactériologiquement les malades avec un taux de rechute extrêmement faible, alors qu'il s'agissait volontiers autrefois de traitements « à vie », a bouleversé l'épidé-miologie mondiale de la maladie [2]. Dès lors qu'on passait, pour évaluer le nombre de malades, de files actives cumulatives à un reflet de l'incidence annuelle de nouveaux cas, le nombre de « malades de la lèpre » (c'est-à-dire, en pratique, de malades diagnostiqués et traités par antibacillaires) a considérablement chuté, passant de plus cinq millions en 1985 à moins de trois cent mille cas annuels depuis 2005 (Tableau I). Un espoir implicite de cette stratégie était que, puisque le risque d'exposition des sujets sains à des malades actifs disséminateurs de bacilles diminuait de façon drastique, l'incidence des nouveaux cas devait se tarir en quelque sorte d'elle-même du fait d'une réduction « mathématique » du r...

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Insight into the evolution and origin of leprosy bacilli from the genome sequence of Mycobacterium lepromatosis

Cited by 142 publications

References 43 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

Diffuse Lepromatous Leprosy Due to Mycobacterium lepromatosis in Quintana Roo, Mexico

La lèpre n’est pas une maladie du passé

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