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computational genome analyses of metabolic enzymes in mycobacterium leprae for drug target identification.leprosy is an infectious disease caused by mycobacterium leprae. m. leprae has undergone a major reductive evolution leaving a minimal set of functional genes for survival. it remains non-cultivable. as m. leprae develops resistance against most of the drugs, novel drug targets are required in order to design new drugs. as most of the essential genes mediate several biosynthetic and metabolic pathways, the pathway predictions can predict essential genes. we used comparative genome analysis of me ...201020975887
mycobacterium leprae phenolglycolipid-1 expressed by engineered m. bovis bcg modulates early interaction with human phagocytes.the species-specific phenolic glycolipid 1 (pgl-1) is suspected to play a critical role in the pathogenesis of leprosy, a chronic disease of the skin and peripheral nerves caused by mycobacterium leprae. based on studies using the purified compound, pgl-1 was proposed to mediate the tropism of m. leprae for the nervous system and to modulate host immune responses. however, deciphering the biological function of this glycolipid has been hampered by the inability to grow m. leprae in vitro and to ...201020975946
the mycobrowser portal: a comprehensive and manually annotated resource for mycobacterial genomes.in this paper, we present the mycobrowser portal (http://mycobrowser.epfl.ch/), a resource that provides both in silico generated and manually reviewed information within databases dedicated to the complete genomes of mycobacterium tuberculosis, mycobacterium leprae, mycobacterium marinum and mycobacterium smegmatis. a central component of mycobrowser is tuberculist (http://tuberculist.epfl.ch), which has recently benefited from a new data management system and web interface. these improvements ...201020980200
isolation of mycobacterium leprae in culture. 194620984878
rhomboid homologs in mycobacteria: insights from phylogeny and genomic analysis.rhomboids are ubiquitous proteins with diverse functions in all life kingdoms, and are emerging as important factors in the biology of some pathogenic apicomplexa and providencia stuartii. although prokaryotic genomes contain one rhomboid, actinobacteria can have two or more copies whose sequences have not been analyzed for the presence putative rhomboid catalytic signatures. we report detailed phylogenetic and genomic analyses devoted to prokaryotic rhomboids of an important genus, mycobacteriu ...201021029479
atp synthase in slow- and fast-growing mycobacteria is active in atp synthesis and blocked in atp hydrolysis direction.atp synthase is a validated drug target for the treatment of tuberculosis, and atp synthase inhibitors are promising candidate drugs for the treatment of infections caused by other slow-growing mycobacteria, such as mycobacterium leprae and mycobacterium ulcerans. atp synthase is an essential enzyme in the energy metabolism of mycobacterium tuberculosis; however, no biochemical data are available to characterize the role of atp synthase in slow-growing mycobacterial strains. here, we show that i ...201021039782
the pseudogenes of mycobacterium leprae reveal the functional relevance of gene order within operons.almost 50 years following the discovery of the prokaryotic operon, the functional relevance of gene order within operons remains unclear. in this work, we take advantage of the eroded genome of mycobacterium leprae to add evidence supporting the notion that functionally less important genes have a tendency to be located at the end of its operons. m. leprae's genome includes 1133 pseudogenes and 1614 protein-coding genes and can be compared with the close genome of m. tuberculosis. assuming m. le ...201021051341
a potential role for complement in immune evasion by mycobacterium leprae.lepromatous leprosy is a model of immune evasion wherein pathogen-specific il-10-secreting t cells and concomitant failure of th-1 immunity permit uncontrolled proliferation of the intracellular pathogen, mycobacterium leprae (m. leprae). the mechanism of this immune escape is unknown. here, the authors report that phenolic glycolipid-1 (pgl-1), a major and distinguishing feature of the m. leprae cell wall, is expressed in the cell membrane of m. leprae-infected human dendritic cells, where it c ...201021061760
leprosy and hiv, where are we at?the impact of leprosy and hiv co-infection is an evolving picture. surprisingly the outcomes that were feared, of more lepromatous disease has not materialised. but with the roll-out of antiretroviral therapy, the emergence of leprosy as immune reconstitution inflammatory syndrome is re-focusing attention on the characteristics of this important co-infection.201021067057
a big challenge in case finding at low endemic situation: analysis on 1462 new leprosy patients detected in china in 2007.to understand the characteristics of newly detected leprosy patients at low endemic situation in china in order to provide information for better leprosy control.201021067058
hand atrophy in a leprosy patient--treatment with polymethylmethacrylate.leprosy, an infectious disease caused by mycobacterium leprae, affects mostly the skin and peripheral nerves. the polymethylmethacrylate has been used as bone cement, knee and intraocular implants as a bioexpansor, filling the area where it is applied. we describe the case of a brazilian male with tuberculoid leprosy who developed muscular wasting between the metacarpals of both hands. ten years after leprosy treatment, he was submitted to five applications of 10% polymethylmethacrylate. the tre ...201021067062
histoid leprosy in an hiv positive patient taking cart. 201021067063
amino acid sequence of b-cell epitope of n-terminal region of esat-6 mycobacterium leprae role as specific antigen for diagnosis of leprosy.the objective of this study was to find a specific b-cell epitope of n-terminal region of antigen l-esat-6 from leprosy patients, healthy individuals and healthy nurses working for more than 10 years in the leprosy ward of dr. a. rivai abdullah leprosy hospital, palembang, indonesia. fifty subjects were enrolled in this study, comprising 10 subjects with ll type leprosy, 10 subjects with bb type leprosy, 10 subjects with tt type leprosy, 10 healthy nurses from leprosy ward and 10 healthy individ ...201021073037
human immunodeficiency virus and leprosy: an update.coinfection with human immunodeficiency virus (hiv) has a major effect on the natural history of many infectious diseases, particularly mycobacterial diseases. early in the hiv epidemic, it was predicted that hiv infection would worsen leprosy outcomes, with more patients developing lepromatous disease, an impaired response to multidrug therapy and fewer reactions. however, studies on the epidemiologic and clinical aspects of leprosy suggest that the course of leprosy in coinfected patients has ...201121095536
seyes - support system for preventing the development of ocular disabilities in leprosy.leprosy is an infectious disease caused by mycobacterium leprae, and generally compromises neural fibers, leading to the development of disabilities. these limit daily activities or social life. in leprosy, the study of disability considered functional (physical) and activity limitations; and social participation. these are measured respectively by ehf and salsa scales; by and participation scale: the objective of this work was to propose a support system, seyes, to eyes disabilities development ...201021097149
whole-genome expression analysis of mycobacterium leprae and its clinical application.the whole-genome sequence analysis of mycobacterium leprae, which was completed in 2001, revealed the characteristics of this microbe's genomic structure. half of the m. leprae genome consists of a limited number of protein-coding genes and the rest comprises non-coding regions and pseudogenes. we performed membrane array and tiling array analyses to analyze the gene-expression profile of the m. leprae genome and found that pseudogenes and non-coding regions were expressed similarly to coding re ...201021099087
possible mode of emergence for drug-resistant leprosy is revealed by an analysis of samples from mexico.mexico is a country with sporadic leprosy cases, and the reemergence of drug resistance is a concern. in this study, molecular analysis of mycobacterium leprae was employed to clarify the spread of drug-resistant leprosy. thus, drug resistance-determining regions in the folp1, rpob, and gyra genes, which are associated with resistance to dapsone, rifampicin, and ofloxacin, respectively, were analyzed by direct sequencing of the pcr product. no mutations in the folp1 gene were observed in any of ...201021099091
mutation analysis of the mycobacterium leprae folp1 gene and dapsone resistance.diaminodiphenylsulfone (dapsone) has long been used as a first-line drug worldwide for the treatment of leprosy. diagnosis for dapsone resistance of mycobacterium leprae by dna tests would be of great clinical value, but the relationship between the nucleotide substitutions and susceptibility to dapsone must be clarified before use. in this study, we constructed recombinant strains of cultivable mycobacterium smegmatis carrying the m. leprae folp1 gene with or without a point mutation, disruptin ...201021115799
leprosy and the human genome.despite the availability of effective treatment for several decades, leprosy remains an important medical problem in many regions of the world. infection with mycobacterium leprae can produce paucibacillary disease, characterized by well-formed granulomas and a th1 t-cell response, or multibacillary disease, characterized by poorly organized cellular infiltrates and th2 cytokines. these diametric immune responses confer states of relative resistance or susceptibility to leprosy, respectively, an ...201021119019
false-positive amplified mycobacterium tuberculosis direct tests in skin specimens of leprosy.the amplified mycobacterium tuberculosis (m tuberculosis) direct test (mtd) is reported to be a highly sensitive (92.6%) and specific (100%) test for the detection of m tuberculosis. we report two cases of human leprosy in which false-positive amplified mtd testing on skin biopsies led to initial misdiagnoses of cutaneous m tuberculosis.201121119554
armadillo meat intake was not associated with leprosy in a case control study, curitiba (brazil).leprosy's progression and its maintained endemic status, despite the availability of effective treatments, are not fully understood and recent studies have highlighted the possibility of involved mycobacterium leprae ambient reservoirs. wild armadillos can carry leprosy and, because their meat is eaten by humans, development of the disease among armadillo meat consumers has been investigated. this study evaluated the frequency of armadillo meat intake among leprosy patients as well as age and ge ...201021120353
transmission of leprosy in qiubei county, yunnan, china: insights from an 8-year molecular epidemiology investigation.leprosy continues to be endemic in parts of china. to track the occurrence of leprosy and determine at risk communities, molecular strain typing based on variable number of tandem repeats (vntrs) was applied in qiubei county, wenshan prefecture, yunnan province of the people's republic of china, a multiethnic region that is home to four predominant ethnic minorities. a previous study, conducted between 2002 and 2005, provided the first descriptions of mycobacterium leprae strains in the region. ...201021129505
a subunit vaccine based on biodegradable microspheres carrying rhsp65 protein and klk protects balb/c mice against tuberculosis infection.of the hundreds of new tuberculosis (tb) vaccine candidates, some have therapeutic value in addition to their prophylactic properties. this is the case for the dna vaccine encoding heat-shock protein 65 (dnahsp65) from mycobacterium leprae. however, there are concerns about the use of dna vaccines in certain populations such as newborns and pregnant women. thus, the optimization of vaccination strategies that circumvent this limitation is a priority. this study evaluated the efficacy of a single ...201021157178
immunostimulatory activity of major membrane protein ii from mycobacterium tuberculosis.previously, we observed that both major membrane protein ii of mycobacterium leprae (mmp-ml) and its fusion with m. bovis bcg (bcg)-derived heat shock protein 70 (hsp70) (fusion-ml) are immunogenic and that recombinant bcg secreting either of these proteins effectively inhibits the multiplication of m. leprae in mice. here, we purified m. tuberculosis-derived major membrane protein ii (mmp-mtb) and its fusion with hsp70 (fusion-mtb) in a lipopolysaccharide-free condition and evaluated their immu ...201021159924
mycobacterium leprae: genes, pseudogenes and genetic diversity.leprosy, which has afflicted human populations for millenia, results from infection with mycobacterium leprae, an unculturable pathogen with an exceptionally long generation time. considerable insight into the biology and drug resistance of the leprosy bacillus has been obtained from genomics. m. leprae has undergone reductive evolution and pseudogenes now occupy half of its genome. comparative genomics of four different strains revealed remarkable conservation of the genome (99.995% identity) y ...201121162636
analysis of antibody responses to mycobacterium leprae phenolic glycolipid i, lipoarabinomannan, and recombinant proteins to define disease subtype-specific antigenic profiles in leprosy.a simple serodiagnostic test based on the mycobacterium leprae-specific phenolic glycolipid i(pgl-i), for individuals with leprosy is nearly universally positive in leprosy patients with high bacillary loads but cannot be used as a stand-alone diagnostic test for the entire spectrum of the disease process. for patients with early infection with no detectable acid-fast bacilli in lesions or with low or no antibody titer to pgl-i, as in those at the tuberculoid end of the disease spectrum, this di ...201021177913
insight toward early diagnosis of leprosy through analysis of the developing antibody responses of mycobacterium leprae-infected armadillos.leprosy is a debilitating chronic disease caused by infection with mycobacterium leprae. a world health organization-directed control strategy based upon the identification and treatment of patients has resulted in a marked reduction in the number of registered worldwide leprosy cases over the last 20 years. despite these efforts, the number of new leprosy cases detected each year now remains relatively stable, and m. leprae infection continues to pose a health problem. it is suggested that earl ...201021177914
oral mucosa as a source of mycobacterium leprae infection and transmission, and implications of bacterial dna detection and the immunological status.clin microbiol infect abstract: leprosy is an important health problem in brazil despite extensive use of multidrug therapy. the nasal mucosa is the preferential site of entry and exit of mycobacterium leprae, and although lesions have been found in the oral mucosa, its potential involvement in the transmission of leprosy bacilli has never been investigated. we investigated the presence of the m. leprae dna in buccal swabs of leprosy patients (334) and household contacts (1288) through polymeras ...201021199152
granulomatous reactivation during the course of a leprosy infection: reaction or relapse.leprosy is a chronic granulomatous infectious disease and is still endemic in many parts of the world. it causes disabilities which are the consequence of nerve damage. this damage is in most cases the result of immunological reactions.201021200422
vaccine for tuberculosis: up-regulation of il-15 by ag85a and not by esat-6.ifn-γ is the most commonly measured cytokine released by the cells to define the cellular immune responses induced by the vaccine candidates for tuberculosis. il-15 acts as a co-stimulator in ifn-γ production by nk cells and may therefore be important in the control of mycobacterium tuberculosis that requires ifn-γ for clearance. the aim of the study is to determine whether ag85a can also stimulate the innate immune response through the expression of il-15, a cytokine that bridges the innate and ...201121212022
transepidermal elimination of mycobacterium leprae in histoid leprosy: a case report suggesting possible participation of skin in leprosy transmission.an indian patient of histoid leprosy presenting de novo, having numerous solid staining bacilli inside the intact epidermis and eliminating bacilli from the intact and the eroded epidermis, is reported. the diagnosis, suggested by the clinical features, was confirmed histopathologically. this unusual report indicates possible participation of skin in leprosy transmission.201121220882
study of cytokine response against panel of purified mycobacterium leprae antigens by using whole blood assay in subjects residing in a resettlement village of cured leprosy patients.mycobacterium leprae being an intracellular pathogen, cell mediated immunity is very important in the clinical outcome of leprosy. manifestation of the disease is correlated with the level and type of cell mediated immune response. the main objective of this study was to analyse tnf-alpha and ifn-gamma production by t-cells when challenged with different m. leprae purified antigens in subjects with known exposure. 50 subjects residing in resettlement village of cured leprosy patients were includ ...201021229844
immunologically reactive m. leprae antigens with relevance to diagnosis and vaccine development.leprosy is a chronic infectious disease caused by mycobacterium leprae that can manifest a wide variety of immunological and clinical outcomes ranging from potent humoral responses among borderline lepromatous (bl) and lepromatous (ll) patients to strong cellular responses among tuberculoid (tt) and borderline tuberculoid (bt) patients. until recently, relatively little has been known about the immune responses to individual proteins of m. leprae recognized during leprosy.201121269435
a quantitative view on mycobacterium leprae antigens by proteomics.leprosy is an ancient disease and the focus of the researchers' scrutiny for more than a century. however, many of the molecular aspects related to transmission, virulence, antigens and immune responses are far from known. initially, the implementation of recombinant dna library screens raised interesting antigen candidates. finally, the availability of mycobacterium leprae genomic information showed an intriguing genome reduction which is now largely used in comparative genomics. while predicti ...201121278007
analysis of drug-resistant strains of mycobacterium leprae in an endemic area of vietnam.multidrug therapy has effectively reduced the number of leprosy cases in the world. however, the rate of reduction has decelerated over the years, giving early detection of mycobacterium leprae and epidemiological study of relapse renewed relevance in attempts to eliminate the disease.201121292655
[leprosy--a stigma in the 21st century].for the initiation of the french journalist raoul follereau in 1954 the uno inaugurated the leprosy day (martyr's day) that is celebrated on the last sunday of january every year. although the bacterium that causes leprosy was isolated by the norwegian scientist gerhard henrik armauer hansen in 1873 and from 1982 this disease can be cured with a special pharmaceutical complex, still 219.826 new leprous are detected on earth every year, according to the data published in august, 2010 by who-exper ...201121296733
[serological and cellular reactivity to mycobacterial proteins in hansen's disease].the study was designed for evaluating immunological reactivity to various mycobacterial protein preparations using serological and cell-mediated immunological tests in patients with clinical leprosy signs, predominantly, with the multibacillary forms. all patients were adults with ages between 20 and 30 years. fifty eight (n = 81) percent corresponded to lepromatous leprosy (ll), 29% (n = 41) to borderline lepromatous leprosy (bl) and 10% (n = 41) to borderline borderline leprosy (bb); only 3% w ...201021305770
health care utilisation in indian leprosy patients in the era of elimination.the health care utilisation pattern among indian leprosy patients accessing a tertiary care centre over an 18 month period was studied.201021313975
leprosy reactions: the effect of gender and household contacts.various host-related factors have been reported as relevant risk factors for leprosy reactions. to support a new hypothesis that an antigenic load in local tissues that is sufficient to trigger the immune response may come from an external supply of mycobacterium leprae organisms, the prevalence of reactional leprosy was assessed against the number of household contacts. the number of contacts was ascertained at diagnosis in leprosy patients coming from an endemic area of brazil. the prevalence ...201121340362
electronic access to mycobacterium tuberculosis sequence data.the complete genome sequence of the well studied laboratory strain of mycobacterium tuberculosis (h37rv) has been published by the sanger centre (1), and this information will soon be complemented by the completion of a recent clinical isolate of m. tuberculosis (cdc1551/csu93) by the institute for genomic research (2). in addition to these sequences, projects for the genomic sequencing of mycobacterium bovis (3), mycobacterium leprae (4), and mycobacterium avium (5) are underway. a vast wealth ...200121341084
decaprenylphosphoryl-ß-d-ribose 2'-epimerase, the target of benzothiazinones and dinitrobenzamides, is an essential enzyme in mycobacterium smegmatis.the unique cell wall of bacteria of the suborder corynebacterineae is essential for the growth and survival of significant human pathogens including mycobacterium tuberculosis and mycobacterium leprae. drug resistance in mycobacteria is an increasingly common development, making identification of new antimicrobials a priority. recent studies have revealed potent anti-mycobacterial compounds, the benzothiazinones and dinitrobenzamides, active against dpre1, a subunit of decaprenylphosphoribose 2' ...201121346818
function-specific accelerations in rates of sequence evolution suggest predictable epistatic responses to reduced effective population size.changes in effective population size impinge on patterns of molecular evolution. notably, slightly deleterious mutations are more likely to drift to fixation in smaller populations, which should typically also lead to an overall acceleration in the rates of evolution. this prediction has been validated empirically for several endosymbiont and island taxa. here, we first show that rate accelerations are also evident in bacterial pathogens whose recent shifts in virulence make them prime candidate ...201121349981
mycobacterium leprae-host-cell interactions and genetic determinants in leprosy: an overview.leprosy, also known as hansen's disease, is a chronic infectious disease caused by mycobacterium leprae in which susceptibility to the mycobacteria and its clinical manifestations are attributed to the host immune response. even though leprosy prevalence has decreased dramatically, the high number of new cases indicates active transmission. owing to its singular features, m. leprae infection is an attractive model for investigating the regulation of human immune responses to pathogen-induced dis ...201121366421
in vitro thalidomide does not interfere with the activation of complement by m. leprae.erythema nodosum leprosum (enl) is an inflammatory reaction that may occur in multibacillary leprosy patients, and thalidomide is the treatment of choice. its cause and the mechanism by which thalidomide suppresses enl are not known. in the skin lesions, im- mune complexes and split products of complement are found. the activation of complement could precipitate enl, and thalidomide could suppress the inflammation by inhibiting the activation of complement. to determine if thalidomide could supp ...201121369644
a nine-year clinico-epidemiological study of histoid hansen in india.histoid hansen is rare but a well-defined entity with specific clinical, histopathological, and bacteriological features. the incidence has been reported to vary from 1-2% amongst total leprosy patients.201121389593
mycobacterium leprae in ocular tissues: histopathological findings in experimental leprosy. 201121393973
[molecular mechanism of the acquisition of new-quinolone resistance in mycobacterium leprae and m. tuberculosis and rapid differentiation methods for resistant bacilli].drugs included in new-quinolone are used for the treatment of leprosy with single lesion. these drugs are also known to be effective drugs for the treatment of multi-drug resistant m. tuberculosis. recent emergence of new-quinolone resistant m. leprae and m. tuberculosis enforced the urgent elucidation of the mode of emergence of new-quinolone resistant strains. in this review, new-quinolone drugs, their mode of action and mechanism of acquisition of resistance by m. leprae and m. tuberculosis w ...201121404592
[leprosy in a chimpanzee].leprosy is suspected to develop after a long period of latency following infection with mycobacterium leprae (m. leprae) during infancy, but definitive proof has been lacking. we found a rare case of leprosy in a chimpanzee (pan troglodytes) born in west africa (sierra leone) and brought to japan around 2 years of age. at 31, the ape started exhibiting pathognomic signs of leprosy. pathological diagnosis, skin smear, serum anti-phenolic glycolipid-i (pgl-i) antibody, and by pcr analysis demonstr ...201121404593
[review of sentinel surveillance for drug resistance in leprosy conducted by who global leprosy programme]. 201121404598
leprosy.the world health organization field leprosy classification is based on the number of skin lesions: paucibacillary leprosy (1-5 skin lesions), and multibacillary leprosy (more than 5 skin lesions). worldwide, about 250,000 new cases of leprosy are reported each year, and about 2 million people have leprosy-related disabilities. methods and outcomes: we conducted a systematic review and aimed to answer the following clinical questions: what are the effects of interventions to prevent leprosy? what ...201021418690
persistent skin lesions in a 75-year-old man--quiz case. lepromatous leprosy (ll). 201121422347
leprosy among patient contacts: a multilevel study of risk factors.this study aimed to evaluate the risk factors associated with developing leprosy among the contacts of newly-diagnosed leprosy patients.201121423643
micropathological changes in the sub-epidermal zone of normal appearing skin in leprosy.leprosy is a chronic inflammatory disease caused by mycobacterium leprae, which affects not only the peripheral nerves and skin but also various internal viscera through the hematogenous spread, especially in lepromatous cases. the micropathological changes in epidermis, nerves and skin appendages from lesioned skin reported by various authors but reports of involvement of apparently normal sites are few. we investigated skin biopsy material taken from 130 patients with clinically diagnosed lepr ...201121424049
evaluation of diagnostic role of in situ pcr on slit-skin smears in pediatric leprosy.a large proportion of early cases of leprosy in children remain afb negative in skin smears. such cases required additional techniques to confirm the diagnosis. in situ pcr on slit- skin smears is minimally invasive and less cumbersome as compared to skin biopsies. this study was initiated in our institute with the objective to evaluate the diagnostic value of in situ pcr on slit- skin smears in pediatric leprosy. a total of 25 cases of leprosy below 16 years of age were included in the study. a ...201021434596
use of the ml-flow test as a tool in classifying and treating leprosy.the treatment of leprosy is defined by the classification of patients as paucibacillary (pb) or multibacillary (mb). the who (world health organization) classifies patients according to the number of lesions, but ridley-jopling (r & j) also uses complementary exams, which are difficult to use outside reference services. in 2003, a test called ml-flow, an alternative to elisa serology, was developed to help classify patients as pb or mb and decide about their treatment.201121437528
molecular drug susceptibility testing and genotyping of mycobacterium leprae strains from south america.possible drug resistance in mycobacterium leprae strains from venezuela and three other south american countries was surveyed by molecular methods. none of the 230 strains from new leprosy cases exhibited drug resistance-associated mutations. however, two of the three strains from relapsed cases contained dapsone resistance mutations, and one strain also harbored a rifampin resistance mutation. single nucleotide polymorphism analysis of these strains revealed five subtypes: 3i (73.8%), 4p (11.6% ...201121444694
nitric oxide metabolites in sera of patients across the spectrum of leprosy.leprosy, a chronic infectious disease, caused by mycobacterium leprae infection, manifests itself as a clinical spectrum depending on the patients' immunological response, finally leading to peripheral nerve damage and deformities in the patients. nitric oxide (no) which is known to contribute to pathogenesis of several neurological diseases has been detected in tissues and urine of leprosy patients. this is the first study assessing no as its stable end products, nitrites and nitrates, in sera ...201021449223
disruption of hla-dr raft, deregulations of lck-zap-70-cbl-b cross-talk and mir181a towards t cell hyporesponsiveness in leprosy.leprosy, a chronic human disease, results from infection of mycobacterium leprae. defective cmi and t cell hyporesponsiveness are the major hallmark of m. leprae pathogenesis. the present study demonstrates immunological-deregulations that eventually lead to t cell anergy/hyporesponsiveness in m. lepare infection. we firstly, evaluated the membrane fluidity and antigen-presenting-lipid-raft (hla-dr) on macrophages of leprosy patients using fluorescence anisotropy and confocal microscopy, respect ...201121453975
interferon-gamma receptor-1 gene promoter polymorphisms and susceptibility to leprosy in children of a single family.the autosomal recessive disorder, because of a single mutation in interferon-? receptor-1(ifngr1) at position -56, was found to be associated with susceptibility to leprosy in children of the same family. the existence of such heterozygous carriers might explain the crucial role of ifngr1 in the host defense against intracellular pathogens such as mycobacterium leprae. the single nucleotide polymorphisms (snps) in major candidate genes, i.e., natural resistance-associated macrophage protein 1 (n ...201121460021
hansen's disease mimicking a systemic vasculitis.hansen's disease, caused by mycobacterium leprae, classically presents with cutaneous and neurological manifestations. rheumatologic manifestations present in 1 to 5% of the patients, and include arthritis, arthralgias, charcot arthropathy, erythema nodosum and vasculitis. we report a case of a 86 year old woman with polyarthritis, subcutaneous nodules and leg ulcers whose differential diagnosis included primary vasculitis and diffuse connective tissue diseases and ended to be leprosy in a non e ...201121483282
comparative modeling of udp-n-acetylmuramoyl-glycyl-d-glutamate-2, 6-diaminopimelate ligase from mycobacterium leprae and analysis of its binding features through molecular docking studies.leprosy is an infectious disease caused by mycobacterium leprae. the increasing drug and multi-drug resistance of m. leprae enforce the importance of finding new drug targets. mycobacterium has unusually impermeable cell wall that contributes to considerable resistance to many drugs. peptidoglycan is an important component of the cell wall of m. leprae. udp-n-acetylmuramoyl-glycyl-d-glutamate-2, 6-diaminopimelate ligase (mure) plays a crucial role in the peptidoglycan biosynthesis and hence it c ...201121491188
leprosy in the philippines: a review.leprosy is a skin disease that accounts for serious deformities and disabilities, leading to stigmatization and psychosocial suffering. it is included in "the neglected tropical diseases". not surprisingly, its management is increasingly reported as a function of dermatology departments, with a strong community-orientated bias. prompt and accurate diagnosis of leprosy is crucial in the control of leprosy. its management requires a multidisciplinary team of skilled physicians, laboratory staff, a ...201121506975
probable zoonotic leprosy in the southern united states.in the southern region of the united states, such as in louisiana and texas, there are autochthonous cases of leprosy among native-born americans with no history of foreign exposure. in the same region, as well as in mexico, wild armadillos are infected with mycobacterium leprae.201121524213
images in clinical medicine. tuberculoid leprosy. 201121524216
detailed structural and quantitative analysis reveals the spatial organization of the cell walls of in vivo grown mycobacterium leprae and in vitro grown m. tuberculosis.the cell wall of mycobacteria consists of an outer membrane, analogous to that of gram-negative bacteria, attached to peptidoglycan (pg) via a connecting polysaccharide arabinogalactan (ag). although the primary structure of these components is fairly well deciphered, issues such as the coverage of the pg layer by covalently attached mycolates in the outer membrane and the spatial details of the mycolic acid attachment to the arabinan have remained unknown. it is also not understood how these co ...201121555513
recent food shortage is associated with leprosy disease in bangladesh: a case-control study.leprosy is remaining prevalent in the poorest areas of the world. intensive control programmes with multidrug therapy (mdt) reduced the number of registered cases in these areas, but transmission of mycobacterium leprae continues in most endemic countries. socio-economic circumstances are considered to be a major determinant, but uncertainty exists regarding the association between leprosy and poverty. we assessed the association between different socio-economic factors and the risk of acquiring ...201121572979
immunophenotype of skin lymphocytic infiltrate in m.leprae and hiv co-infected patients: a scenario dependent of cd8(+) and/or cd20(+) cells.background.  leprosy occurs rarely in human immunodeficiency virus (hiv) positive patients. as opposed to tuberculosis, neither an increase in hiv prevalence among leprosy patients nor differences in leprosy's clinical spectrum has been reported so far. while several studies describe the systemic immune response profile in hiv-leprosy co-infected patients, local immune skin response has been only evaluated in a small number of case reports and limited series of patients. patients and methods.  w ...201121574977
leprosy susceptibility: genetic variations regulate innate and adaptive immunity, and disease outcome.the past few years have been very productive concerning the identification of genes associated with leprosy. candidate gene strategies using both case-control and family-based designs, as well as large-scale approaches such as linkage and gene-expression genomic scans and, more recently, genome-wide association studies, have refined and enriched the list of genes highlighting the most important innate and adaptive immune pathways associated with leprosy susceptibility or resistance. during the e ...201121585261
gene expression analysis of leprosy by using a multiplex branched dna assay.leprosy is caused by mycobacterium leprae, and the global registered prevalence of leprosy at the beginning of 2009 stood at 213 036 cases. it has long been thought that leprosy has a strong genetic risk. recently, we have identified significant associations (p < 1.00 × 10(-10) ) between snps in the genes ccdc122, c13orf31, nod2, tnfsf15, hla-dr and ripk2 and a trend towards an association (p = 5.10 × 10(-5) ) with a snp in lrrk2. here, we investigated the expression of these seven genes in form ...201121585556
the role of indoleamine 2, 3-dioxygenase in lepromatous leprosy immunosuppression.to elucidate further the possible role of the tryptophan, rate-limiting enzyme indoleamine 2, 3-dioxygenase (ido) in leprosy, the distribution of ido-positive cells and ido activity in the skin biopsies and sera of these patients representing the entire spectrum of the disease were studied. an increased number of macrophages/dendritic cells (dc-lineage ido(+) cells were found in lepromatous (ll) compared to tuberculoid (bt) and reversal reaction (rr) patients. ido-positive cells showing cd68 and ...201121592112
inactivation of tesa reduces cell-wall lipid production and increases drug susceptibility in mycobacteria.phthiocerol dimycocerosates (pdims) and phenolic glycolipids (pgls) are structurally-related lipids noncovalently bound to the outer cell wall layer of mycobacterium tuberculosis, mycobacterium leprae and several opportunistic mycobacterial human pathogens. pdims and pgls are important effectors of virulence. elucidation of the biosynthesis of these complex lipids will not only expand our understanding of mycobacterial cell wall biosynthesis, but it may also illuminate potential routes to novel ...201121592957
genotyping of mycobacterium leprae from brazilian leprosy patients suggest the occurrence of re-infection or of bacterial population shift during disease relapse.we performed genotyping of mycobacterium leprae, present in skin biopsy samples that were collected during the initial and the relapse stage from eight leprosy patients, suffering from disease relapse. sequence analysis of part of the m. leprae genes rpob, folp1, gyrb and gyra did not show genetic change that supported the presence of drug resistant bacilli. however, we observed a synonymous nucleotide change at position 297 of gyra among five of these patients, one being cgyrat and four present ...201121596907
enoyl-coa hydratase and ag85b of mycobacterium habana are specifically recognized by antibodies in sera from leprosy patients.leprosy is an infectious disease caused by mycobacterium leprae which is a non-cultivable bacterium. one of the principal goals of leprosy research is to develop serological tests that will allow identification and early treatment of leprosy patients. m. habana is a cultivable non-pathogenic mycobacterium and candidate vaccine for leprosy, and several antigens that cross-react between m. leprae and m. habana have been discovered. the aim of the present study was to extend the identification of c ...201121613461
leprosy now: epidemiology, progress, challenges, and research gaps.leprosy continues to be a challenge to health worldwide, with about 250 000 new cases being detected every year. despite widespread implementation of effective multidrug therapy, leprosy has not been eliminated. a third of newly diagnosed patients have nerve damage and might develop disabilities, although the proportion varies according to several factors, including level of self-care. women who develop leprosy continue to be especially disadvantaged, with rates of late diagnosis and disability ...201121616456
fta card utility for pcr detection of mycobacterium leprae.the suitability of the fta® elute card for the collection of slit skin smear (sss) samples for pcr detection of mycobacterium leprae was evaluated. a total of 192 sss leprosy samples, of bacillary index (bi) 1 to 5, were collected from patients attending two skin clinics in myanmar and preserved using both fta® elute cards and 70% ethanol tubes. to compare the efficacy of pcr detection of dna from each bi class, pcr was performed to amplify an m. leprae-specific repetitive element. of the 192 sa ...201121617312
mannose-binding lectin serum levels in patients with leprosy are influenced by age and mbl2 genotypes.background: mannose-binding lectin (mbl) activates the complement system promoting opsonophagocytosis, which could represent an advantage for mycobacterium leprae, an intracellular pathogen. therefore, a single nucleotide polymorphism (snp) in the mbl2 gene associated with low levels of mbl could confer protection against the development of leprosy disease. methods: in this study, we investigated snps of the mbl2 gene and mbl levels in 228 brazilian leprosy patients and 232 controls. results: th ...201121640628
detection of mutations in folp1, rpob and gyra genes of m. leprae by pcr- direct sequencing--a rapid tool for screening drug resistance in leprosy.conventional mouse foot-pad (mfp) assay for screening drug resistance in m. leprae is cumbersome and time-consuming (approximately 6 to 12 months). molecular targets for different anti-leprosy drugs have been well defined. molecular tools for rapid detection of drug resistance in m. leprae have been standardised. a study to compare molecular methods with mfp assay in determining the drug susceptibility of m. leprae was carried out.201121644470
report on the sixth meeting of the ideal (initiative for diagnostic and epidemiological assays for leprosy) consortium held in beijing, china on 23-25 august 2010. 201121644477
lepromatous leprosy in a kidney transplant recipient: a case report.leprosy is a chronic granulomatous disease of the skin and peripheral nerves caused by mycobacterium leprae. among mycobacterial infections, leprosy is rare in renal transplant recipients. here, we report the manifestations of lepromatous leprosy in a 41-year-old renal transplant recipient. before the renal transplant, the patient had recurrent bullous lesions on his extremities with no systemic complaints. he was on an immunosuppressive regimen that included prednisolone (1 mg/kg/d), cyclospori ...201121649570
multiple loci variable number tandem repeat (vntr) analysis (mlva) of mycobacterium leprae isolates amplified from european archaeological human remains with lepromatous leprosy.molecular typing methods based on polymorphisms in single nucleotides and short tandem repeat motifs have been developed as epidemiological typing tools for mycobacterium leprae. we have used a variable number tandem repeat method based on three variable loci to identify strain variation in archaeological cases of lepromatous leprosy. the panel of polymorphic loci used revealed unique profiles in five cases of leprosy, including those with identical snp type and subtype. these were also differen ...201121658464
surveillance of drug resistance in leprosy: 2010. 201121661275
palaeogenomics of mycobacterium tuberculosis: epidemic bursts with a degrading genome.genome-scale analysis suggests that the last common ancestor of the mycobacterium tuberculosis complex and mycobacterium leprae diverged 36 million years ago, and members of the mycobacterium tuberculosis complex differentiated 40ôçê000 years ago. analysis of palaeomicrobiological data from a 17ôçê000-year-old sample from a bison and a 9000-year-old sample from a human being suggested that m tuberculosis preceded mycobacterium bovis and related species. whole-genome comparisons show that members ...201121672667
leprosy and hiv coinfection: a critical approach.an increase in leprosy among hiv patients, similar to that observed in patients with tb, was expected approximately 20 years ago. studies conducted in the 1990s together with those reported recently seemed to indicate that a coinfection with hiv did not alter the incidence and the clinical spectrum of leprosy and that each disease progressed as a single infection. by contrast, in countries with a high seroprevalence of hiv, tb was noted to increase. explanations may be provided by the difference ...201121692674
a histone-like protein of mycobacteria possesses ferritin superfamily protein-like activity and protects against dna damage by fenton reaction.iron is an essential metal for living organisms but its level must be strictly controlled in cells, because ferrous ion induces toxicity by generating highly active reactive oxygen, hydroxyl radicals, through the fenton reaction. in addition, ferric ion shows low solubility under physiological conditions. to overcome these obstacles living organisms possess ferritin superfamily proteins that are distributed in all three domains of life: bacteria, archaea, and eukaryotes. these proteins minimize ...201121698192
Autolytic Mycobacterium leprae Hsp65 fragments may act as biological markers for autoimmune diseases.Investigating the proteolytic activity of the recombinant Mycobacterium leprae Heat Shock Protein of 65-ákDa (rHsp65), chaperonin 2 (cpn2), we observed that it displays high instability. The fragmentation process starts at the C-terminus followed by progressive degradation of the N-terminus, which leads to a stable fragment comprising the middle region of the molecule. Urea was able to prevent autolysis, probably due to its denaturing action, while EDTA increased degradation levels indicating th ...201121699972
ml1419c peptide immunization induces mycobacterium leprae-specific hla-a*0201-restricted ctl in vivo with potential to kill live mycobacteria.mhc class i-restricted cd8(+) t cells play an important role in protective immunity against mycobacteria. previously, we showed that p113-121, derived from mycobacterium leprae protein ml1419c, induced significant ifn-+¦ production by cd8(+) t cells in 90% of paucibacillary leprosy patients and in 80% of multibacillary patients' contacts, demonstrating induction of m. leprae-specific cd8(+) t cell immunity. in this work, we studied the in vivo role and functional profile of ml1419c p113-121-indu ...201121705623
towards the molecular epidemiology of mycobacterium leprae: strategies, successes, and shortcomings.mycobacterium leprae, the causative agent of leprosy, is an unusual organism that presents unique challenges to those studying the disease through molecular epidemiology. as a consequence, many basic aspects of disease transmission and biology remain unilluminated. in this review, we explore the general principles of molecular epidemiology, and the special difficulties surrounding the application of molecular epidemiology to m. leprae. we briefly discuss the computational tools commonly employed ...201121708290
molecular typing of mycobacterium leprae strains from northern india using short tandem repeats.due to the inability to cultivate mycobacterium leprae in vitro and most cases being paucibacillary, it has been difficult to apply classical genotyping methods to this organism. the objective of this study was therefore, to analyze the diversity among m. leprae strains from uttar pradesh, north india, by targeting ten short tandem repeats (strs) as molecular markers.201121727660
solution structure of the mycobacterium tuberculosis esxg{middle dot}esxh complex: functional implications and comparisons with other m. tuberculosis esx family complexes.mycobacterium tuberculosis encodes five type vii secretion systems that are responsible for exporting a number of proteins, including members of the esx family, which have been linked to tuberculosis pathogenesis and survival within host cells. the gene cluster encoding esx-3 is regulated by the availability of iron and zinc, and secreted protein products such as the esxg-àesxh complex have been associated with metal ion acquisition. esxg and esxh have previously been shown to form a stable 1:1 ...201121730061
interleukin 4-590t/c polymorphism and susceptibility to leprosy.background: leprosy is a chronic infectious disease caused by mycobacterium leprae. cell-mediated (th1) immune response and humoral (th2) immune response play different roles in leprosy infection. interleukin 4 (il-4) is a typical th2 cytokine. it is a critical mediator of the th1/th2 balance.objective: the objective of this study is to investigate the association between il-4 gene -590t/c polymorphism and the susceptibility to leprosy in a chinese population. methods: the il-4 variant -590t/c w ...201121749213
hansen disease among micronesian and marshallese persons living in the united states.an increasing proportion of hansen disease cases in the united states occurs among migrants from the micronesian region, where leprosy prevalence is high. we abstracted surveillance and clinical records of the national hansen's disease program to determine geographic, demographic, and clinical patterns. since 2004, 13% of us cases have occurred in this migrant population. although hawaii reported the most cases, reports have increased in the central and southern states. multibacillary disease in ...201121762573
dna fingerprinting of <em>mycobacterium leprae</em> strains using variable number tandem repeat (vntr) - fragment length analysis (fla).the study of the transmission of leprosy is particularly difficult since the causative agent, mycobacterium leprae, cannot be cultured in the laboratory. the only sources of the bacteria are leprosy patients, and experimentally infected armadillos and nude mice. thus, many of the methods used in modern epidemiology are not available for the study of leprosy. despite an extensive global drug treatment program for leprosy implemented by the who(1), leprosy remains endemic in many countries with ap ...201121775969
secondary leprosy infection in a patient with psoriasis during treatment with infliximab.tumor necrosis factor a antagonists are proven to be effective for the treatment of chronic inflammatory conditions, such as psoriasis. a major concern for patients is the risk of acquiring granulomatous infectious diseases caused by the immunosuppressive effects of the drugs. we report a 60-year-old man with psoriasis who underwent infliximab treatment for 2 years and developed secondary leprosy, presenting extensive erythematous and infiltrated plaques on the trunk and limbs with loss of sensi ...201121778902
[study on the factors influencing steady transmission of leprosy in qiubei county, china].to explore the factors influencing the steady transmission of leprosy as indicated by new case detection rate in qiubei county, yunnan province, china despite the implementation of mdt for the last 25 years.201121781471
prokaryotic expression, identification and bioinformatics analysis of fbpb-esxa fusing gene from mycobacterium tuberculosis.to obtain fbpb-esxa fusing gene of mycobacterium tuberculosis (mtb), express the encoded fusing protein in escherichia coli (e. coli), identify protein acquired, and predict the structure and function of the protein utilizing methods of bioinformatics.201121803303
th3 immune responses in the progression of leprosy via molecular cross-talks of tgf-ß, ctla-4 and cbl-b.leprosy is a chronic human disease; primarily affecting skin, peripheral nerves, eyes, testis etc. comprehensive-expressional-profiling of th1-th2-th3 associated markers (84 genes) using qrt-pcr array, negated the previously prevailing notion, th2 bias towards multibacillary stage of leprosy. high production tgf-ß further supported the dearth of any immune response(s) in leprosy progression. over expression of cbl-b, could emerge as plausible reason for contributing t cell hyporesponsiveness, po ...201121807564
tlr6-driven lipid droplets in mycobacterium leprae-infected schwann cells: immunoinflammatory platforms associated with bacterial persistence.the mechanisms responsible for nerve injury in leprosy need further elucidation. we recently demonstrated that the foamy phenotype of mycobacterium leprae-infected schwann cells (scs) observed in nerves of multibacillary patients results from the capacity of m. leprae to induce and recruit lipid droplets (lds; also known as lipid bodies) to bacterial-containing phagosomes. in this study, we analyzed the parameters that govern ld biogenesis by m. leprae in scs and how this contributes to the inna ...201121813774
teaching neuroimages: neuropathy caused by mycobacterium leprae. 201121825271
incorporation of immunostimulatory motifs in the transcribed region of a plasmid dna vaccine enhances th1 immune responses and therapeutic effect against mycobacterium tuberculosis in mice.t-helper type 1 (th1) immune response is involved in the development of protective immunity against mycobacterium tuberculosis. thus, an increase in th1 and cellular immune responses should lead to enhanced anti-mycobacterial activity. in this study, we aimed to improve th1 immune responses to a dna vaccine by adding potentially immunostimulatory nucleotide sequences into the transcribed region downstream of the antigen. the mycobacterium leprae gene for hsp65, codon-optimized for expression in ...201121856352
transmission of dapsone-resistant leprosy detected by molecular epidemiological approaches.drug resistance surveillance identified six untreated leprosy patients in the philippines with mycobacterium leprae folp1 mutations which confer dapsone resistance. five patients share a village of residence; four who carried the mutation, thr53val, were also linked by m. leprae variable-number tandem repeat (vntr) strain types. in india, folp1 mutations were detected in two relapse patients with a history of dapsone treatment. mutations were not found in the rifampin target gene rpob. these fin ...201121859943
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