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tnf -308g>a single nucleotide polymorphism is associated with leprosy among brazilians: a genetic epidemiology assessment, meta-analysis, and functional study.leprosy is an infectious disease caused by mycobacterium leprae. tumor necrosis factor (tnf) plays a key role in the host response. some association studies have implicated the single nucleotide polymorphism tnf -308g>a in leprosy susceptibility, but these results are still controversial. we first conducted 4 association studies (2639 individuals) that showed a protective effect of the -308a allele (odds ratio [or] = 0.77; p = .005). next, results of a meta-analysis reinforced this association a ...201121917899
[our role in sentinel surveillance for drug resistance in leprosy by global leprosy programme].sentinel surveillance for drug resistance in leprosy by global leprosy programme has launched in 2006. possible contribution of japanese researchers to global leprosy control in the future were discussed on the base of circumstances of the project and our assignment in the sueveillance.201121941835
modulation of the cytokine response in human monocytes by mycobacterium leprae phenolic glycolipid-1.leprosy is a chronic but treatable infectious disease caused by the intracellular pathogen mycobacterium leprae. m. leprae cell wall is characterized by a unique phenolic glycolipid-1 (pgl-1) reported to have several immune functions. we have examined the role of pgl-1 in the modulation of monocyte cytokine/chemokine production in naive human monocytes. pgl-1 in its purified form or expressed in a recombinant mycobacterium bovis bacillus colmette-guérin (bcg) background (rbcg-pgl-1) was tested. ...201121981546
diagnosing leprosy: revisiting the role of the slit-skin smear with critical analysis of the applicability of polymerase chain reaction in diagnosis.diagnosing leprosy is challenging, especially in early-stage cases, and the need for a sensitive diagnostic tool is urgent. polymerase chain reaction (pcr) holds promise as a simple and sensitive diagnostic tool, but its usefulness in the indian context requires further evaluation. slit-skin smear (sss) remains the conventional method of leprosy detection. hence, this study was undertaken to evaluate and compare the diagnostic efficacy of pcr versus that of sss.201122097999
Peptides of Lsr2 of Mycobacterium leprae show hierarchical responses in lymphoproliferative assays with selective recognition by anergic lepromatous leprosy patients.Lsr2 protein of Mycobacterium leprae (ML) was shown earlier to elicit B and T cell responses in leprosy patients (20, 28). Lymphproliferation to ML and Lsr 2 antigens respectively was observed in > 70% of tuberculoid (T) and in 16 and 34 % of lepromatous (L) patients. We focused on the ML non responders in the lepromatous group using 22 synthetic Lsr 2 peptides (end to end: A to F, overlapping: p1 to p16) in in vitro T cell responses. A total of 125 leprosy, 13 tuberculosis patients and 17 healt ...201122144494
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
childhood leprosy in a tertiary-care hospital in delhi, india: a reappraisal in the post-elimination era.to assess the profile and describe the clinical presentations, clinico-histopathological profile, complications and treatment compliance of childhood leprosy at a tertiary care hospital in north-east district of delhi during 2000-2009.201122125934
Comparative analyses of transport proteins encoded within the genomes of Mycobacterium tuberculosis and Mycobacterium leprae.The co-emergence of multidrug resistant pathogenic bacterial strains and the HIV pandemic has made tuberculosis a leading public health threat. The causative agent is Mycobacterium tuberculosis (Mtu), a facultative intracellular parasite. Mycobacterium leprae (Mle), a related organism that causes leprosy, is an obligate intracellular parasite. Given that different transporters are required for bacterial growth and persistence under a variety of growth conditions, we conducted comparative analyse ...201122179038
comparison between microsatellites and ml mnth gene as targets to identify mycobacterium leprae by pcr in leprosy.the polymerase chain reaction (pcr) technique has been frequently used in the molecular diagnosis of leprosy.201121987128
study of the density and distribution of mycobacterium leprae in the epidermis and skin appendages in lepromatous patients. 201121860164
A network of regulatory pathways in lepromatous leprosy. 201121903479
thalidomide modulates mycobacterium leprae-induced nf-κb pathway and lower cytokine response.it is widely accepted that tumor necrosis factor alpha (tnf-α) plays a critical role in the development of tissue and nerve damage in leprosy and during the reactional episodes of acute inflammation. thalidomide (n-α-phthalimidoglutarimide), a drug used to treat leprosy reaction, modulates immune response, inhibits inflammation and nf-κb activity. here we investigated whether thalidomide inhibits nf-κb activation induced by mycobacterium leprae, p38 and erk1/2 mapk activation. emsa and supershif ...201121925494
Chimpanzees used for medical research shed light on the pathoetiology of leprosy.Leprosy is a chronic infectious disorder caused by Mycobacterium leprae, which mainly affects skin and peripheral nerves. It is classified as either paucibacillary or multibacillary based upon clinical manifestations and slit-skin smear results. It is speculated that leprosy develops after a long latency period following M. leprae infection. However, the actual time of infection and the duration of latency have never been proven in human patients. To date, four cases of spontaneous leprosy have ...201122004034
frequencies of mica alleles in patients from southern brazil with multibacillary and paucibacillary leprosy.leprosy is a chronic infectious disease caused by mycobacterium leprae, which mainly affects the skin and nervous system. the disease has several clinical forms. this study investigated the mica and hla-b genes in 223 samples from leprosy patients and 201 samples from healthy individuals matched for age, gender and ethnical background. of the patients, 153 had multibacillary, 45 paucibacillary and 25 indeterminate leprosy. the aim of this case-control study was to assess whether the mica alleles ...201122168250
current status of leprosy: epidemiology, basic science and clinical perspectives.leprosy has affected humans for millennia and remains an important health problem worldwide, as evidenced by nearly 250 000 new cases detected every year. it is a chronic infectious disorder, caused by mycobacterium leprae, that primarily affects the skin and peripheral nerves. recent advances in basic science have improved our knowledge of the disease. variation in the cellular immune response is the basis of a range of clinical manifestations. the introduction of multidrug therapy has signific ...201121973237
does clofazimine prevent erythema nodosum leprosum (enl) in leprosy? a retrospective study, comparing the experience of multibacillary patients receiving either 12 or 24 months who-mdt.to compare the occurrence, duration and severity of enl in leprosy patients treated with either 12 or 24 months of standard multi-drug therapy (mdt).201122125929
A study of knowledge, attitude and practices regarding leprosy among undergraduates and interns of a medical college and hospital from rural India.Leprosy is an Infectious disease caused by Mycobacterium leprae and acquired through droplet infection. India has been carrying the 2/3rd global leprosy burden. Inadequate or incorrect information and knowledge about the disease and its treatment are the root causes of many stigmas and inhibitions prevalent in the various sections of the community. The present study was undertaken to assess the knowledge, attitude and practices (KAP) regarding leprosy among undergraduates (final year medical stu ...201121972659
Homology modeling and docking analyses of M. leprae Mur ligases reveals the common binding residues for structure based drug designing to eradicate leprosy.Multi drug resistance capacity for Mycobacterium leprae (MDR-Mle) demands the profound need for developing new anti-leprosy drugs. Since most of the drugs target a single enzyme, mutation in the active site renders the antibiotic ineffective. However, structural and mechanistic information on essential bacterial enzymes in a pathway could lead to the development of antibiotics that targets multiple enzymes. Peptidoglycan is an important component of the cell wall of M. leprae. The biosynthesis o ...201122102165
The role of neuregulin-1 in the response to nerve injury.Axons and Schwann cells exist in a highly interdependent relationship: damage to one cell type invariably leads to pathophysiological changes in the other. Greater understanding of communication between these cell types will not only give insight into peripheral nerve development, but also the reaction to and recovery from peripheral nerve injury. The type III isoform of neuregulin-1 (NRG1) has emerged as a key signaling factor that is expressed on axons and, through binding to erbB2/3 receptors ...201122121335
Report of three new leprosy cases in children under fifteen in the municipality of Itaguai, Rio de Janeiro: event alert for epidemiological investigation.Leprosy is an infectious disease with an average incubation period of two to five years. It is caused by Mycobacterium leprae, mainly affecting skin, mucous membranes and peripheral nerves. When it occurs in children under fifteen, it reflects an intense and long contact period, with a high bacillary load. Therefore, it is considered an important alert sign that points to the challenge of controlling the disease. The authors report three cases of leprosy in children under fifteen that occurred i ...201122147046
A history of leprosy in Iran during the 19th and 20th centuries.From ancient time leprosy has been regarded as a terrifying, stigmatized disease; nevertheless, its cause remained unidentified up to the late 19th century. For centuries numerous leprosy victims worldwide suffered from its morbidity and were socially isolated. The afflicted individuals were segregated because they were considered 'unclean' and had to live in leper colonies, generally under very poor conditions. Physicians believed that leprosy was an incurable, highly contagious, and hereditary ...201122039850
the long-term effect of current and new interventions on the new case detection of leprosy: a modeling study.although the number of newly detected leprosy cases has decreased globally, a quarter of a million new cases are detected annually and eradication remains far away. current options for leprosy prevention are contact tracing and bcg vaccination of infants. future options may include chemoprophylaxis and early diagnosis of subclinical infections. this study compared the predicted trends in leprosy case detection of future intervention strategies.201121949895
Circulating levels of Insulin-like Growth Factor-I (IGF-I) correlate with disease status in leprosy.ABSTRACT: BACKGROUND: Caused by Mycobacterium leprae (ML), leprosy presents a strong immune-inflammatory component, whose status dictates both the clinical form of the disease and the occurrence of reactional episodes. Evidence has shown that, during the immune-inflammatory response to infection, the growth hormone/insulin-like growth factor-I (GH/IGF-I) plays a prominent regulatory role. However, in leprosy, little, if anything, is known about the interaction between the immune and neuroendocr ...201122166091
association of variants in bat1-lta-tnf-btnl2 genes within 6p21.3 region show graded risk to leprosy in unrelated cohorts of indian population.host immune response against mycobacterium leprae plays an important role in providing resistance to infection and disease progression. genome-wide linkage and association studies suggest the possibility of multiple risk loci within hla (6p21.3) region. any systematic study of relevance within the histocompatibility complex of importance in host immune response would be pertinent because of non-replication of the known loci and unavailable information on some of the unexplored genes and regions. ...201122071774
Genetic variations and interactions in anti-inflammatory cytokine pathway genes in the outcome of leprosy: a study conducted on a MassARRAY platform.Mycobacterium leprae is the etiologic pathogen that causes leprosy. The outcome of disease is dependent on the host genetic background.201121917900
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
teaching neuroimages: neuropathy caused by mycobacterium leprae. 201121825271
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
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
amino acid substitutions at position 95 in gyra can add fluoroquinolone resistance to mycobacterium leprae.amino acid substitutions at position 89 or 91 in gyra of fluoroquinolone-resistant mycobacterium leprae clinical isolates have been reported. in contrast, those at position 94 in m. tuberculosis, equivalent to position 95 in m. leprae, have been identified most frequently. to verify the possible contribution of amino acid substitutions at position 95 in m. leprae to fluoroquinolone resistance, we conducted an in vitro assay using wild-type and mutant recombinant dna gyrases. fluoroquinolone-medi ...201122106221
a study of the distribution of mycobacterium leprae strains among cases in a rural and urban population of maharashtra, india.the elimination of leprosy continues to be a challenge with several countries remaining endemic for the disease. india accounts for the highest number of cases and the identification of child cases indicates recent transmission. genetic markers like vntrs and snps have been identified to track transmission of the pathogen mycobacterium leprae. these were used to describe m. leprae strains detected in 48 skin biopsies of leprosy patients in the state of maharashtra in western india in a rural and ...201122205800
Changes in the size and number of skin lesions in PB leprosy on treatment and follow-up.The increase in size of existing skin lesions and appearance of new skin lesions are considered important signs of clinical activity both in untreated and treated leprosy. To confirm such activity, the number and size of lesions need to be recorded methodically prior to therapy and on follow-up, especially in PB leprosy where clinical signs alone define the reactivation of the disease. However, no systematic follow-up studies are available on changes in size and number of skin lesions in PB lepr ...201122125932
leprosy initially misdiagnosed as sarcoidosis, adult-onset still disease, or autoinflammatory disease.leprosy is a chronic granulomatous disease caused by mycobacterium leprae. we describe the case of a 20-year-old man from india living in italy since 2003, who presented with erythematous papules and nodules distributed on his arms, legs, and face in 2006. he also had episodes of high fever, polyarthritis, and episcleritis. sarcoidosis was suspected on the basis of elevated angiotensin-converting enzyme and bronchoalveolar lavage fluid, and the patient was treated with corticosteroids for about ...201122089994
expression of mycobacterium leprae hsp65 in tobacco and its effectiveness as an oral treatment in adjuvant-induced arthritis.transgenic plants are able to express molecules with antigenic properties. in recent years, this has led the pharmaceutical industry to use plants as alternative systems for the production of recombinant proteins. plant-produced recombinant proteins can have important applications in therapeutics, such as in the treatment of rheumatoid arthritis (ra). in this study, the mycobacterial hsp65 protein expressed in tobacco plants was found to be effective as a treatment for adjuvant-induced arthritis ...201120526808
hansen's disease (leprosy) complicated by secondary mycobacterial infection.a patient with hansen's disease received corticosteroids for a type 1 leprosy reaction and subsequently developed a new cutaneous lesion at the original biopsy site from which mycobacterium fortuitum was cultured. a review of the literature found only two other cases of coinfection with atypical mycobacteria and mycobacterium leprae, although there are many reports of pulmonary tuberculosis in patients with leprosy. this case highlights the diagnostic difficulties encountered when a patient has ...201120494478
leprosy in transplant recipients: report of a case after liver transplantation and review of the literature.leprosy still is an important public health problem in several parts of the world including brazil. unlike the diseases caused by other mycobacteria, the incidence and clinical presentation of leprosy seems little affected in immunosuppressed patients. we report the first case, to our knowledge, of a liver transplant patient who developed multi-bacillary leprosy. the patient presented with papules and infiltrated plaques with loss of sensation suggestive of leprosy 3.5 years after living-related ...201120678090
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
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
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
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
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
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
early diagnosis of relapse in borderline leprosy: two case reports.two cases of relapse in borderline leprosy were reported. despite the late-reversal, reaction-like feature, the suspicion of relapse in both was based on persistent and slow-developing skin lesions and an absence of acute neuritis or reaction during one year of follow-up. the authors have considered this possible occurrence in lepromatous borderline-treated patients after their immune cellular restoration and defend that not all type 1 reactions would be an inflammatory answer to persistent myco ...201122183459
Oral lesion in leprosy: borderline tuberculoid diagnosis based on detection of Mycobacterium leprae DNA by qPCR.Oral lesions are rarely reported in paucibacillary forms of leprosy. We report here a case with an erythematous hyposensitive lesion in the palate and no skin lesions. In addition to routine tests, biopsies of the lesion in the palate and of clinically normal surrounding areas were performed and subjected to real-time PCR for detection of Mycobacterium leprae DNA. The biopsy of the oral lesion was positive for bacilli DNA, followed by positive serum anti-PGL-1 and Mitsuda test, but with negative ...201121879249
Serum metabolomics reveals higher levels of polyunsaturated fatty acids in lepromatous leprosy: potential markers for susceptibility and pathogenesis.Leprosy is a disease of the skin and peripheral nervous system caused by the obligate intracellular bacterium Mycobacterium leprae. The clinical presentations of leprosy are spectral, with the severity of disease determined by the balance between the cellular and humoral immune response of the host. The exact mechanisms that facilitate disease susceptibility, onset and progression to certain clinical phenotypes are presently unclear. Various studies have examined lipid metabolism in leprosy, but ...201121909445
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
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
clinicohistopathological correlation in leprosy.leprosy is a chronic, infectious disease caused by mycobacterium leprae. it is classified into five groups based on clinical, histological, microbiological and immunological criteria (ridley and jopling classification) . however, a great variation has been observed in the interpretation of histopathological examination ok skin biopsies and clinical presentation of the disease.201122710532
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