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haemoglobins of mycobacteria: structural features and biological functions.the genus mycobacterium is comprised of gram-positive bacteria occupying a wide range of natural habitats and includes species that range from severe intracellular pathogens to economically useful and harmless microbes. the recent upsurge in the availability of microbial genome data has shown that genes encoding haemoglobin-like proteins are ubiquitous among mycobacteria and that multiple haemoglobins (hbs) of different classes may be present in pathogenic and non-pathogenic species. the occurre ...201324054797
leprosy in pregnant woman, united states. 201324050493
a case of hansen disease presenting as tinea versicolor.hansen disease (leprosy) is an infectious disease that targets macrophages and schwann cells, caused by the acid fast intracellular organism, mycobacterium leprae. clinically, it presents with a spectrum of findings that may include hypopigmented macules, erythematous plaques and nodules, and thickened or tender peripheral nerves. the most feared complication is mutilating damage to facial structures or digits resulting from loss of sensation in affected skin. in non-endemic areas, the diagnosis ...201324021367
profiling microrna expression in bovine alveolar macrophages using rna-seq.micrornas (mirnas) are important regulators of gene expression and are known to play a key role in regulating both adaptive and innate immunity. bovine alveolar macrophages (bams) help maintain lung homeostasis and constitute the front line of host defense against several infectious respiratory diseases, such as bovine tuberculosis. little is known, however, about the role mirnas play in these cells. in this study, we used a high-throughput sequencing approach, rna-seq, to determine the expressi ...201324021155
[genotyping of mycobacterium leprae in guangdong province].to understand the genotypes of mycobacterium leprae collected from guangdong province, china and to analyze the routes of leprosy transmission both inside and outside of guangdong. the impact of emigrant leprosy patients to the endemic nature of the disease in guangdong was also studied.201324016427
lrrk2 and ripk2 variants in the nod 2-mediated signaling pathway are associated with susceptibility to mycobacterium leprae in indian populations.in recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. the immunological control of intracellular bacteria m. leprae is modulated by nod2-mediated signaling of th1 responses. in this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in indian population by genotyping four variants in nod2 (rs9302752a/g ...201324015287
the ubiquitin ligase parkin mediates resistance to intracellular pathogens.ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen mycobacterium tuberculosis. however, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. the parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (park2) lead to increased susceptibility ...201324005326
rifampicin-resistant mycobacterium leprae in an elderly leprosy patient in the people's republic of china.the reported number of registered leprosy patients worldwide declined with the introduction of multidrug therapy. however, the emergence of rifampicin resistance in leprosy patients engenders difficulties for an individual patient, and its dissemination could pose a threat to leprosy control. this study reports an elderly patient who was diagnosed with rifampicin-resistant lepromatous leprosy. this case indicates that inadequate treatment and poor compliance may eventually result in rifampicin r ...201323986632
new findings in the pathogenesis of leprosy and implications for the management of leprosy.this review focuses on recent work in leprosy pathogenesis. new research of both innate and adaptive immune responses to mycobacterium leprae is described. the proposition that mycobacterium lepromatosis is a new species causing leprosy is discussed.201323982232
haplotypes of the il10 gene as potential protection factors in leprosy patients.leprosy is an infectious disease caused by mycobacterium leprae characterized by dermatoneurological signs and symptoms that has a large number of new cases worldwide. several studies have associated interleukin 10 with susceptibility/resistance to several diseases. we investigated haplotypes formed by three single nucleotide polymorphisms (snps) located in the il10 gene (a-1082g, c-819t, and c-592a) in order to better understand the susceptibility to and severity of leprosy in an admixed northe ...201323966553
leprosy association with low masp-2 levels generated by masp2 haplotypes and polymorphisms flanking map19 exon 5.the gene masp2 (mannan-binding lectin (mbl)-associated serine protease 2) encodes two proteins, masp-2 and map19 (mbl-associated protein of 19 kda), bound in plasma to mbl and ficolins. the binding of mbl/masp-2 and ficolin/masp-2 complexes to microorganisms activates the lectin pathway of complement and may increase the ingestion of intracellular pathogens such as mycobacterium leprae.201323935922
insights into ancient leprosy and tuberculosis using metagenomics.leprosy and tuberculosis were widespread in the past and remain significant diseases today. comparison of ancient and modern genomes of mycobacterium leprae and mycobacterium tuberculosis gives insight into their evolution and a calibration of the timescale for observed changes. recently, whole genome sequencing has revealed genotypes and mixed-strain infections.201323932433
leprous neuropathy.leprous neuropathy, which is due to infection of nerve cells by mycobacterium leprae, still affects millions of people in many developing countries. the clinical and pathological manifestations are determined by the natural resistance of the host to invasion of m. leprae. failure of early detection of leprosy often leads to severe disability in spite of eradication of mycobacterium at a later date. in the lepromatous type, bacilli are easily found in the skin and in nerve cells including schwann ...201323931798
the eradication of leprosy: molecular modeling techniques for novel drug discovery.leprosy is a slowly progressing bacterial infection caused by mycobacterium leprae. the world health organization recommended multidrug therapy (mdt) which is extremely effective and halts the progress of the disease. even though the objective of eliminating leprosy as a public health problem has been achieved successfully, leprosy is not yet eradicated. furthermore, the long-term use of mdt results in single- and multidrug resistance. therefore, there is still a need for new drug discovery for ...201323924296
cd4+cd25+ t regs with acetylated foxp3 are associated with immune suppression in human leprosy.leprosy is a chronic human disease that results from infection of mycobacterium leprae. t reg cells have been shown to have important implications in various diseases. however, in leprosy, it is still unclear whether t regs can mediate immune suppression during progression of the disease. in the present study, we have proposed the putative mechanism leading to high proportion of t reg cells and investigated its significance in human leprosy. high levels of tgf-β followed by adaptation of foxp3(+ ...201323911408
detection of mycobacterium leprae in saliva and the evaluation of oral sensitivity in patients with leprosy.the aim of this study was to investigate sensitivity disorders in the oral cavity related to the presence of mycobacterium leprae in the saliva of treatment-naïve patients with leprosy in the state of amazonas, brazil. a cross-sectional study was conducted involving 45 subjects with leprosy. the subjects were interviewed to evaluate the sensitivity of the oral cavity. for the detection of m. leprae, saliva and slit-skin smear samples were collected. the samples were analysed using a bacteriologi ...201323903971
characteristic mutations found in the ml0411 gene of mycobacterium leprae isolated in northeast asian countries.genome analysis of mycobacterium leprae strain kyoto-2 in this study revealed characteristic nucleotide substitutions in gene ml0411, compared to the reference genome m. leprae strain tn. the ml0411 gene of kyoto-2 had six snps compared to that of tn. all snps in ml0411 were non-synonymous mutations that result in amino acid replacements. in addition, a seventh snp was found 41 bp upstream of the start codon in the regulatory region. the seven snp sites in the ml0411 region were investigated by ...201323892035
gene set signature of reversal reaction type i in leprosy patients.leprosy reversal reactions type 1 (t1r) are acute immune episodes that affect a subset of leprosy patients and remain a major cause of nerve damage. little is known about the relative importance of innate versus environmental factors in the pathogenesis of t1r. in a retrospective design, we evaluated innate differences in response to mycobacterium leprae between healthy individuals and former leprosy patients affected or free of t1r by analyzing the transcriptome response of whole blood to m. le ...201323874223
anti-pgl1 salivary iga/igm, serum igg/igm, and nasal mycobacterium leprae dna in individuals with household contact with leprosy.leprosy household contacts represent a group at high risk of developing the disease. the aim of this study was to detect mycobacterium leprae subclinical infection in this group through serological and molecular parameters.201323871279
leprosy. an update: definition, pathogenesis, classification, diagnosis, and treatment.leprosy is a chronic granulomatous disease caused by the bacillus mycobacterium leprae. it primarily affects the skin and peripheral nerves and is still endemic in various regions of the world. clinical presentation depends on the patient's immune status at the time of infection and during the course of the disease. leprosy is associated with disability and marginalization. diagnosis is clinical and is made when the patient has at least 1 of the following cardinal signs specified by the world he ...201323870850
mapping of park2 and pacrg overlapping regulatory region reveals ld structure and functional variants in association with leprosy in unrelated indian population groups.leprosy is a chronic infectious disease caused by mycobacterium leprae, where the host genetic background plays an important role toward the disease pathogenesis. various studies have identified a number of human genes in association with leprosy or its clinical forms. however, non-replication of results has hinted at the heterogeneity among associations between different population groups, which could be due to differently evolved ld structures and differential frequencies of snps within the st ...201323861666
il-10 production from dendritic cells is associated with dc sign in human leprosy.the defective antigen presenting ability of antigen presenting cells (apcs) modulates host cytokines and co-stimulatory signals that may lead to severity of leprosy. in the present study, we sought to evaluate the phenotypic features of apcs along with whether dc sign (dc-specific intercellular adhesion molecule-grabbing nonintegrin) influences il-10 production while moving from tuberculoid (bt/tt) to lepromatous (bl/ll) pole in leprosy pathogenesis. the study revealed an increased expression of ...201323816300
gene expression profiling specifies chemokine, mitochondrial and lipid metabolism signatures in leprosy.herein, we performed microarray experiments in schwann cells infected with live m. leprae and identified novel differentially expressed genes (deg) in m. leprae infected cells. also, we selected candidate genes associated or implicated with leprosy in genetic studies and biological experiments. forty-seven genes were selected for validation in two independent types of samples by multiplex qpcr. first, an in vitro model using thp-1 cells was infected with live mycobacterium leprae and m. bovis ba ...201323798993
an in vitro model of mycobacterium leprae induced granuloma formation.leprosy is a contagious and chronic systemic granulomatous disease caused by mycobacterium leprae. in the pathogenesis of leprosy, granulomas play a key role, however, the mechanisms of the formation and maintenance of m. leprae granulomas are still not clearly understood.201323782413
nlrp1 haplotypes associated with leprosy in brazilian patients.polymorphisms in innate immunity genes are known to be involved in the multifactorial susceptibility to mycobacterium leprae infection. m. leprae can downregulate il-1β secretion escaping monocyte digestion. the intracellular receptors nlrps (nacht, lrr and pyd domains-containing proteins) sense pathogen associated molecular patterns (pamps) activating caspase-1 and il-1β secretion in the context of inflammasome. considering the possible role of inflammasome in the immune response against m. lep ...201323770116
genome-wide comparison of medieval and modern mycobacterium leprae.leprosy was endemic in europe until the middle ages. using dna array capture, we have obtained genome sequences of mycobacterium leprae from skeletons of five medieval leprosy cases from the united kingdom, sweden, and denmark. in one case, the dna was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. the ancient m. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geog ...201323765279
primary dapsone resistant mycobacterium leprae in a non endemic country. 201323760326
biomarkers for leprosy: would you prefer t (cells)?the need for rapid diagnostic tests that can be applied in non-expert settings may now be greater than ever before, due to changes in leprosy control programmes and the decrease in special expertise required for (early) diagnosis of leprosy. however, there is no test available that can detect asymptomatic mycobacterium leprae infection or predict progression of infection to clinical disease. the characteristics of the leprosy disease spectrum, in which both cellular and humoral immunity against ...201323741878
active search for leprosy cases in midwestern brazil: a serological evaluation of asymptomatic household contacts before and after prophylaxis with bacillus calmette-guérin.leprosy is a disease caused by mycobacterium leprae that carries a high risk of disability, making early diagnosis mandatory. this study aimed to determine the applicability of anti-pgl-1 igm antibody detection, using the ml flow technique, as an assistant tool for the detection of leprosy infection in asymptomatic household contacts (ahhc) of multibacillary leprosy index cases from midwest brazil. serological changes induced by the prophylaxis of these household contacts with bacillus calmette- ...201323740009
[leprosy, a pillar of human genetics of infectious diseases].despite a natural reservoir of mycobacterium leprae limited to humans and free availability of an effective antibiotic treatment, more than 200,000 people develop leprosy each year. this disease remains a major cause of disability and social stigma worldwide. the cause of this constant incidence is currently unknown and indicates that important aspects of the complex relationship between the pathogen and its human host remain to be discovered. an important contribution of host genetics to suscep ...201323711949
mycobacterium haemophilum masquerading as leprosy in a renal transplant patient.opportunistic infections following immunosuppression in solid organ transplant (sot) patients are common complications with the skin being a common sight of infection. nontuberculous mycobacteria (ntm) are rare but potential causes of skin infection in sot patients. we present a case of an adult male immunosuppressed following renal transplantation who presented with an asymptomatic rash for several months. the patient's skin eruption consisted of erythematous papules and plaques coalescing into ...201324369511
tender cutaneous nodules of the legs: diagnosis and clinical clues to diagnosis."tender cutaneous nodules of the legs" is a common manifestation in dermatology. histopathological investigation is usually required for this condition, because clinical data are frequently insufficient to make a definite diagnosis.201322928517
axenic culture of fastidious and intracellular bacteria.the culture of microorganisms has been the basis of microbiology. however, revolutionary tools such as metagenomics have made it possible to describe uncultivated bacteria, but several breakthroughs have occurred in culture leading to a revival of these techniques. in this review we focus on new applications that have successfully cultivated previously uncultivated bacteria. we also review the axenic cultivation of intracellular bacteria such as tropheryma whipplei and coxiella burnetii. these s ...201323182864
a s52p mutation in the 'α-crystallin domain' of mycobacterium leprae hsp18 reduces its oligomeric size and chaperone function.mycobacterium leprae hsp18 is a small heat shock protein (shsp). it is a major immunodominant antigen of m. leprae pathogen. previously, we have reported the existence of two m. leprae hsp18 variants in various leprotic patients. one of the variants has serine at position 52, whereas the other one has proline at the same position. we have also reported that hsp18 having proline at position 52 (hsp18p(52)) is a nonameric protein and exhibits chaperone function. however, the structural and functio ...201324024660
protective role of mycobacterium leprae small heat-shock protein in heterologous hosts, escherichia coli and mycobacterium smegmatis, grown under stress.the aim of this study is to examine the in vivo role of a small heat-shock protein (shsp18) from mycobacterium leprae in the survival of heterologous recombinant hosts carrying the gene encoding this protein under different environmental conditions that are normally encountered by m. leprae during its infection of the human host. using an escherichia coli system where shsp18 expression is controlled by its native promoter, we show that expression of shsp18 is induced under low oxygen tension, nu ...201323579398
gene expression profile and immunological evaluation of unique hypothetical unknown proteins of mycobacterium leprae by using quantitative real-time pcr.the cell-mediated immunity (cmi)-based in vitro gamma interferon release assay (igra) of mycobacterium leprae-specific antigens has potential as a promising diagnostic means to detect those individuals in the early stages of m. leprae infection. diagnosis of leprosy is a major obstacle toward ultimate disease control and has been compromised in the past by the lack of specific markers. comparative bioinformatic analysis among mycobacterial genomes identified potential m. leprae-specific proteins ...201323239802
ulcerating type 1 lepra reaction mimicking lazarine leprosy: an unusual presentation of immune reconstitution inflammatory syndrome in an hiv-infected patient.leprosy maybe "unmasked" in the context of immune reconstitution inflammatory syndrome and treating dermatologists, particularly in highly endemic areas for hansen's disease, need to be cognizant to this possibility. it may also reflect emergence of a previously clinically silent infection in the course of immunologic restoration.201324216029
characterization of the msmeg_2631 gene (mmp) encoding a multidrug and toxic compound extrusion (mate) family protein in mycobacterium smegmatis and exploration of its polyspecific nature using biolog phenotype microarray.in mycobacterium, multidrug efflux pumps can be associated with intrinsic drug resistance. comparison of putative mycobacterial transport genes revealed a single annotated open reading frame (orf) for a multidrug and toxic compound extrusion (mate) family efflux pump in all sequenced mycobacteria except mycobacterium leprae. since mate efflux pumps function as multidrug efflux pumps by conferring resistance to structurally diverse antibiotics and dna-damaging chemicals, we studied this gene (msm ...201323292779
rbcg30-induced immunity and cross-protection against mycobacterium leprae challenge are enhanced by boosting with the mycobacterium tuberculosis 30-kilodalton antigen 85b.leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. vaccines are needed that protect against both infections and do so better than the suboptimal mycobacterium bovis bcg vaccine. here, we evaluated rbcg30, a vaccine previously demonstrated to induce protection superior to that of bcg against mycobacterium tuberculosis and mycobacterium bovis challenge in animal models, for efficacy against mycobacterium leprae challenge in a murine mode ...201425001602
paleopathological evidence and detection of mycobacterium leprae dna from archaeological skeletal remains of nabe-kaburi (head-covered with iron pots) burials in japan.the nabe-kaburi is a unique burial method, the purpose of which is shrouded in mystery. the burials were performed during the 15(th) to 18(th) centuries in eastern japan, and involved covering the heads of the deceased with iron pots or mortars. the identification of leprosy-specific osteological lesions among some of the excavated remains has led to the suggestion that nabe-kaburi burials were a reflection of the social stigma against certain infectious diseases, such as leprosy, tuberculosis o ...201424516638
production of recombinant proteins in mycobacterium smegmatis for structural and functional studies.protein production using recombinant dna technology has a fundamental impact on our understanding of biology through providing proteins for structural and functional studies. escherichia coli (e. coli) has been traditionally used as the default expression host to over-express and purify proteins from many different organisms. e. coli does, however, have known shortcomings for obtaining soluble, properly folded proteins suitable for downstream studies. these shortcomings are even more pronounced ...201425303009
long-term survival and virulence of mycobacterium leprae in amoebal cysts.leprosy is a curable neglected disease of humans caused by mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. despite the global success of multi-drug therapy (mdt), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of ...201425521850
mycobacterium leprae hsp65 administration reduces the lifespan of aged high antibody producer mice.aging process may result in immune modifications that lead to disruption of innate and acquired immunity mechanisms that may induce chronic-degenerative events. the heat shock proteins (hsp), phylogeneticaly conserved among organisms, present as main function the ability of folding and refolding proteins, but they also are associated with chronic-degenerative disorders. here were evaluated the role of m. leprae native hsp65 (wt) and its point-mutated (k409a) on survival and anti-dna and anti-hsp ...201424669842
characteristics of a dengue outbreak in a remote pacific island chain--republic of the marshall islands, 2011-2012.dengue is a potentially fatal acute febrile illness caused by four mosquito-transmitted dengue viruses (denv-1-4). although dengue outbreaks regularly occur in many regions of the pacific, little is known about dengue in the republic of the marshall islands (rmi). to better understand dengue in rmi, we investigated an explosive outbreak that began in october 2011. suspected cases were reported to the ministry of health, serum specimens were tested with a dengue rapid diagnostic test (rdt), and c ...201425268134
leprosy and hepatitis b coinfection in southern brazil.to investigate the association of leprosy with hepatitis b virus (hbv) infection, as yet unknown for south brazil, we assessed hepatitis b virus coinfection in 199 south brazilian leprosy patients (119 lepromatous, 15 tuberculoid, 30 borderline, 12 undetermined and 23 unspecified) and in 681 matched blood donors by screening for the hepatitis b virus markers hbsag and anti-hbc, using elisa. positive samples were retested and anti-hbc+ only samples were tested for the hepatitis b surface antibody ...201423933408
noncanonical smc protein in mycobacterium smegmatis restricts maintenance of mycobacterium fortuitum plasmids.research on tuberculosis and leprosy was revolutionized by the development of a plasmid transformation system in the fast-growing surrogate, mycobacterium smegmatis. this transformation system was made possible by the successful isolation of a m. smegmatis mutant strain mc(2)155, whose efficient plasmid transformation (ept) phenotype supported the replication of mycobacterium fortuitum pal5000 plasmids. in this report, we identified the eptc gene, the loss of which confers the ept phenotype. ept ...201425197070
looking in amoebae as a source of mycobacteria.mycobacteria exhibit various relationships with amoebae, ranging from the killing of one partner by the other one, to amoebae hosting mycobacteria in trophozoites and cysts. this observation indicates that poorly described biological factors affect the relationships, including mycobacterial cell-wall glycolipids and the size of the mycobacteria. experimental observations indicate that a majority of environmental, opportunistic mycobacteria but also obligate pathogens including mycobacterium tube ...201425017516
mycobacterial pathogenomics and evolution.most mycobacterial species are harmless saprophytes, often found in aquatic environments. a few species seem to have evolved from this pool of environmental mycobacteria into major human pathogens, such as mycobacterium tuberculosis, the agent of tuberculosis, mycobacterium leprae, the leprosy bacillus, and mycobacterium ulcerans, the agent of buruli ulcer. while the pathogenicity of m. ulcerans relates to the acquisition of a large plasmid encoding a polyketide-derived toxin, the molecular mech ...201426082120
three-dimensional in vitro models of granuloma to study bacteria-host interactions, drug-susceptibility, and resuscitation of dormant mycobacteria.mycobacterium tuberculosis, mycobacterium leprae, mycobacterium bovis, and mycobacterium avium subsp. paratuberculosis can survive within host macrophages in a dormant state, encased within an organized aggregate of immune host cells called granuloma. granulomas consist of uninfected macrophages, foamy macrophages, epithelioid cells, and t lymphocytes accumulated around infected macrophages. within granulomas, activated macrophages can fuse to form multinucleated giant cells, also called giant l ...201424967387
statins increase rifampin mycobactericidal effect.mycobacterium leprae and mycobacterium tuberculosis antimicrobial resistance has been followed with great concern during the last years, while the need for new drugs able to control leprosy and tuberculosis, mainly due to extensively drug-resistant tuberculosis (xdr-tb), is pressing. our group recently showed that m. leprae is able to induce lipid body biogenesis and cholesterol accumulation in macrophages and schwann cells, facilitating its viability and replication. considering these previous ...201425049257
mycobacterium leprae and mycobacterium haemophilum co-infection in an iatrogenically immunosuppressed patient.we present the case of a native texan who was diagnosed with tuberculoid leprosy and later developed a cutaneous infection with m. haemophilum following iatrogenic immunosuppression. to our knowledge, there are no such reports of m. haemophilum and m. leprae infection occurring simultaneously in the same host.201424439137
[what hansen's disease research learned from tuberculosis research: from molecular biological aspect].as for the mycobacterium leprae which is a causative agent of hansen's disease, many studies had been done since it was identified in 1873. however, those studies, at the same time, experienced many struggles because of the difficulty of culture of m. leprae on the artificial growth media. hence, the study of hansen's disease progressed by taking the knowledge from the study of tuberculosis caused by the bacteria belonging to the same genus, genus mycobacterium. for instance, the knowledge of mu ...201425826852
drug resistance patterns in mycobacterium leprae isolates from relapsed leprosy patients attending the leprosy mission (tlm) hospitals in india.implementation of multidrug therapy (mdt) in leprosy control programmes has significantly reduced the global prevalence of the disease in the last two decades. after many years of use of mdt, it is expected that drug resistance in mycobacterium leprae may emerge. this is a major concern, especially during the stage of elimination. in the present study, slit-skin smears were collected from 140 leprosy relapse cases from different leprosy mission hospitals across india. dna extracted from 111 (79% ...201425509718
relationship between growth factors and its implication in the pathogenesis of leprosy.leprosy is a chronic infectious disease caused by mycobacterium leprae which affects the skin and peripheral nervous system. the immune response of the host determines the clinical course of the disease. the tuberculoid form is the result of high cell-mediated immunity characterized by a th1 response, whereas the lepromatous form is characterized by low cell-mediated immunity and a th2 humoral response. the neural damage established produces marked changes in the expression of growth factors suc ...201425457797
the armadillo as an animal model and reservoir host for mycobacterium leprae.apart from humans, armadillos are the only known natural hosts of mycobacterium leprae. they are well developed as hosts for in vivo propagation of m leprae and are advancing as models for studying the pathogenesis of leprosy and translational research. armadillos are immunologically intact. they exhibit the full ridley-jopling spectrum of histopathologic responses to m leprae and uniquely manifest extensive neurological involvement that closely recapitulates human leprosy. in addition, free-ran ...201425432816
ocular leprosy.ocular involvement in leprosy is estimated to be 70-75%, about 10-50% of leprosy patients suffer from severe ocular symptoms, and blindness occurs in about 5% of patients. the disease leads to many ophthalmologic symptoms and signs in the range of the eyeball itself, as well as of the bulb adnexa, ie, eyebrows, eyelids with eyelashes, and lacrimal drainage system. especially dangerous are complications of lagophthalmos and corneal hypoanesthesia, neurotrophic or infectious keratitis, and iridocy ...201425432813
treatment of leprosy.leprosy is a curable disease, having been eliminated from many countries, including india. this has been possible due to the wide availability of effective and safe drugs. treatment of leprosy has undergone considerable changes over decades, from chaulmoogra oil in 1915 to dapsone monotherapy in 1946, then eventually to multidrug therapy (mdt) in 1982. in the last two decades, reports of resistance to all first-line drugs have appeared in the literature, with the need to conduct clinical trials ...201425432811
mechanisms of nerve injury in leprosy.all patients with leprosy have some degree of nerve involvement. perineural inflammation is the histopathologic hallmark of leprosy, and this localization may reflect a vascular route of entry of mycobacterium leprae into nerves. once inside nerves, m. leprae are ingested by schwann cells, with a wide array of consequences. axonal atrophy may occur early in this process; ultimately, affected nerves undergo segmental demyelination. knowledge of the mechanisms of nerve injury in leprosy has been g ...201425432810
histopathology of the lepromatous skin biopsy.the histopathology of lepromatous skin varies according to the cell-mediated immunity of the host against mycobacterium leprae. in tuberculoid and borderline tuberculoid leprosy, epithelioid noncaseating granulomas predominate, and acid-fast bacilli (afb) are absent or only rarely present. in borderline lepromatous and lepromatous leprosy, the infiltrate is composed of macrophages with a vacuolar cytoplasm, lymphocytes, and plasma cells. afb are numerous. edema inside and outside the epithelioid ...201425432809
clinical aspects of leprosy.leprosy is a chronic, infectious disease caused by mycobacterium leprae. it mainly affects the peripheral nervous system, skin, and certain other tissues such as the reticulo-endothelial system, bones and joints, mucous membranes, eyes, testes, muscles, and adrenals. leprosy clinical presentation varies from few to widespread lesions. in most patients, early leprosy presents as macular and hypopigmented lesions. this initial clinical presentation is known as indeterminate leprosy and occurs in i ...201425432808
diagnostic challenges of single plaque-like lesion paucibacillary leprosy.the diagnosis of single-lesion paucibacillary leprosy remains a challenge. reviews by expert dermatopathologists and quantitative polymerase chain reaction (qpcr) results obtained from 66 single-plaque biopsy samples were compared. histological findings were graded as high (hp), medium (mp) or low (lp) probability of leprosy or other dermatopathy (od). mycobacterium leprae-specific genes were detected using qpcr. the biopsies of 47 out of 57 clinically diagnosed patients who received multidrug t ...201425411000
neural complications and physical disabilities in leprosy in a capital of northeastern brazil with high endemicity.leprosy is an infectious disease whose etiologic agent is mycobacterium leprae, manifested by dermatological and neurological signs and symptoms.201425388490
incidence of hansen's disease--united states, 1994-2011.hansen's disease (hd), or leprosy, is caused by the bacterium mycobacterium leprae and is reportable in many states. it is a chronic disease affecting the skin and nerves, commonly presenting as pale or reddish skin patches with diminished sensation. without treatment, it can progress to a severely debilitating disease with nerve damage, tissue destruction, and functional loss. an important factor in limiting hd morbidity is early diagnosis and prompt initiation of therapy. because hd is rare, c ...201425356604
diagnostic challenges of single plaque-like lesion paucibacillary leprosy.the diagnosis of single-lesion paucibacillary leprosy remains a challenge. reviews by expert dermatopathologists and quantitative polymerase chain reaction (qpcr) results obtained from 66 single-plaque biopsy samples were compared. histological findings were graded as high (hp), medium (mp) or low (lp) probability of leprosy or other dermatopathy (od). mycobacterium leprae-specific genes were detected using qpcr. the biopsies of 47 out of 57 clinically diagnosed patients who received multidrug t ...201425338157
periodontal findings in patients with hansen's disease.to find out whether there are any relationship between leprosy and periodontitis as evidenced by clinical parameters.201425312102
identification of primary drug resistance to rifampin in mycobacterium leprae strains from leprosy patients in amazonas state, brazil.the aim of this study was to identify polymorphisms in the folp1, gyra, and rpob genes in leprosy patients treated in amazonas state, brazil. among 197 slit-skin smear samples from untreated or relapsed patients, we found three cases of primary resistance to rifampin and one confirmed case of multidrug resistance.201425274993
structural studies suggest a peptidoglycan hydrolase function for the mycobacterium tuberculosis tat-secreted protein rv2525c.among the few proteins shown to be secreted by the tat system in mycobacterium tuberculosis, rv2525c is of particular interest, since its gene is conserved in the minimal genome of mycobacterium leprae. previous evidence linked this protein to cell wall metabolism and sensitivity to β-lactams. we describe here the crystal structure of rv2525c that shows a tim barrel-like fold characteristic of glycoside hydrolases of the gh25 family, which includes prokaryotic and phage-encoded peptidoglycan hyd ...201425260828
nfκb activation in cutaneous lesions of leprosy is associated with development of multibacillary infection.nuclear factor kappa b (nfκb) transcription factors play a central role in controlling the expression of genes involved in inflammatory reactions, proliferation, and survival of human cells. however, the in situ evaluation of nfκb activity in leprosy has not been completed previously. the aim of this study was to determine whether nfκb activity correlates with susceptibility or resistance to mycobacterium leprae infection in biopsies from skin lesions of 38 patients with the clinical and laborat ...201425258550
analysis of the leprosy agents mycobacterium leprae and mycobacterium lepromatosis in four countries.to differentiate the leprosy agents mycobacterium leprae and mycobacterium lepromatosis and correlate them with geographic distribution and clinicopathologic features.201425239420
factors associated with neural alterations and physical disabilities in patients with leprosy in são luis, state of maranhão, brazil.leprosy is a chronic infectious disease that is caused by mycobacterium leprae. the objective of this study was to evaluate the risk factors that are associated with neural alterations and physical disabilities in leprosy patients at the time of diagnosis.201425229291
leprosy elimination: a myth busted.leprosy is mainly a chronic infectious disease caused by mycobacterium leprae. the disease mainly affects the skin, the peripheral nerves, mucosa of the upper respiratory tract and eyes. though the target of leprosy elimination was achieved at national level in 2006 even then a large proportion of leprosy cases reported globally still constitute from india.201425540534
lepra: various etiologies from miasma to bacteriology and genetics.leprosy is a chronic infectious disease caused by a close relative of mycobacterium tuberculosis: mycobacterium leprae. there have been various beliefs in its etiology with two main concepts emerging: anticontagion and contagion. from ancient times through the early middle ages, the miasmatic theory of leprosy was the main anticontagion view. the development of histopathologic and cytologic studies in the second half of the 19th century provided a starting point to explain the etiology of lepros ...201425432805
lack of association of the polymorphisms il-17a (-197g/a) and il-17f (+7488a/g) with multibacillary leprosy in mexican patients.background. leprosy is a chronic infectious disease caused by the intracellular acid-fast bacilli mycobacterium leprae; it has been determined that genetic factors of the host play an important role in the disease susceptibility. thus, in this case-control study, we evaluated the possible association between the il-17a g-197a (rs227593) and il-17f a7488g (his161arg, rs763780) gene snps and susceptibility to leprosy disease in mexican population. methods. seventy-five leprosy patients and sixty-n ...201425431761
il-10 and nos2 modulate antigen-specific reactivity and nerve infiltration by t cells in experimental leprosy.although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. in the tuberculoid region of the spectrum, mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. the evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. il-10 has immunosuppressive properties and il-10 genetic variants have bee ...201425210773
pre-mir-146a (rs2910164 g>c) single nucleotide polymorphism is genetically and functionally associated with leprosy.mycobacterium leprae infects macrophages and schwann cells inducing a gene expression program to facilitate its replication and progression to disease. micrornas (mirnas) are key regulators of gene expression and could be involved during the infection. to address the genetic influence of mirnas in leprosy, we enrolled 1,098 individuals and conducted a case-control analysis in order to study four mirnas genes containing single nucleotide polymorphism (mirsnp). we tested mirsnp-125a (rs12975333 g> ...201425187983
evaluation of novel tools to facilitate the detection and characterization of leprosy patients in china.leprosy is the disabling outcome of chronic infection with mycobacterium leprae. the disease often evades early detection, particularly now that fewer clinicians are able to confidently diagnose the disease following the integration of leprosy control measures within general health services in many countries. although leprosy is officially eliminated in china, endemic regions remain in some difficult-to-reach, underdeveloped areas in southwest china. in order to better understand the extent of m ...201425184137
lepromatous leprosy and perianal tuberculosis: a case report and literature review.leprosy is a chronic infectious disease caused by mycobacterium leprae, a microorganism that usually affects skin and nerves. although it is usually well-controlled by multidrug therapy (mdt), the disease may be aggravated by acute inflammatory reaction episodes that cause permanent tissue damage particularly to peripheral nerves. tuberculosis is predominantly a disease of the lungs; however, it may spread to other organs and cause an extrapulmonary infection. both mycobacterial infections are e ...201425180030
tinea barbae: in released from treatment (rft) hansen's disease patient.hansen disease (leprosy) is a chronic inflammatory infectious disease that primarily targets skin, nerves and other internal organs (testis, liver etc.) caused by the acid fast intracellular bacilli, mycobacterium leprae. clinical presentation occurs with a wide spectrum including hypo pigmented anaesthetic patches, raised erythematous plaques and nodules and thickened peripheral nerves showing tenderness. the most important complication is the disability and deformity. the diagnosis of leprosy ...201425177622
phage display and synthetic peptides as promising biotechnological tools for the serological diagnosis of leprosy.the diagnosis of leprosy is primarily based on clinical manifestations, and there is no widely available laboratory test for the early detection of this disease, which is caused by mycobacterium leprae. in fact, early detection and treatment are the key elements to the successful control of leprosy.201425170947
apoptotic activity and treg cells in tissue lesions of patients with leprosy.in order to understand the apoptotic response and the participation of treg cells in the spectral clinical evolution of leprosy, this study evaluated the immunohistochemical expression of caspase-3 and foxp3 in skin lesions of leprosy patients with the polar forms of the disease. forty-nine patients with a confirmed diagnosis of the disease were selected, including 27 with the tt form and 22 with the ll form. quantitative analysis of caspase-3 immunostaining showed a higher expression of this me ...201425128092
serum th1/th2 and macrophage lineage cytokines in leprosy; correlation with circulating cd4(+) cd25(high) foxp3(+) t-regs cells.not only macrophages, t-helper (th)1 and th2, but also cd4(+) cd25(high) foxp3(+) regulatory t cells (t-regs) are involved in immune response to mycobacterium leprae. we aimed to evaluate serum interleukin (il)-1β and il-12p70 (macrophage cytokines), interferon-γ (ifn-γ) (th1 cytokine), il-4 (th2 cytokine) and circulating cd4(+) cd25(high) foxp3(+) t-regs, in untreated leprosy patients. forty three patients and 40 controls were assessed for the mentioned cytokines using elisa. patients were asse ...201425109693
analysis of antigens of mycobacterium leprae by interaction to sera igg, igm, and iga response to improve diagnosis of leprosy.till 2010, several countries have declared less than one leprosy patient among population of 10,000 and themselves feeling as eliminated from leprosy cases. however, new leprosy cases are still appearing from all these countries. in this situation one has to be confident to diagnose leprosy. this review paper highlighted already explored antigens for diagnosis purposes and finally suggested better combinations of protein antigens of m. leprae versus immunoglobulin as detector antibody to be usef ...201425101267
[rapid detection of mutations related to mycobacterium leprae drug resistance by using hp-rpcr (hairpin primer- real time pcr) method].rapid and simple detection method of drug resistance bacteria is required. in the present study, hp-rpcr (hairpin primer-real time pcr) was applied to mycobacterium leprae genes to detect mutations. target sites of the method were as follows: first base and second base on 53rd codon and second base on 55th codon infolp1 gene for dapsone resistance, first base on 441st codon and 451st codon and second base on 456th and 458th codon in rpob gene for rifampicin resistance, and first base on 89th cod ...201425076760
detection of mycobacterium leprae by pcr testing of sputa from a patient with pulmonary cryptococcus coinfection in northern australia.a case of fever, sepsis, and chest lesions evident on a computed tomography scan of an indigenous man in northern australia following burns to the feet is described. sputum pcr testing revealed mycobacterium leprae, and a fine-needle aspirate of the chest lesions demonstrated cryptococcus coinfection.201425056325
evaluation of major membrane protein-i as a serodiagnostic tool of pauci-bacillary leprosy.we have previously shown that the serodiagnosis using major membrane protein-ii (mmp-ii) is quite efficient in diagnosing leprosy. however, the detection rate of pauci-bacillary (pb) leprosy patients is still low. in this study, we examined the usefulness of major membrane protein-i (mmp-i) from mycobacterium leprae. the mmp-i-based serodiagnosis did not show significantly high detection rate. however, when the mixture of mmp-i and mmp-ii antigens was used, we detected 94.4% of multi-bacillary l ...201425041703
lichen scrofulosorum caused by mycobacterium leprae: first report.tuberculides are skin lesions caused by the hematogeneous dissemination of mycobacterium tuberculosis. bacilli are rapidly destroyed in the skin and are thus neither visible histologically nor identifiable by culture. diagnosis depends on previous knowledge of systemic and/or cutaneous tuberculosis. lichen scrofulosorum (ls), the most uncommon variant of tuberculid, is usually associated with m. tuberculosis infection of lymph nodes or bone but was also reported in association with other mycobac ...201425041689
mapping genetic variants in the cfh gene for association with leprosy in han chinese.complement factor h (cfh) is an essential regulator in the homeostasis of the complement system that plays multiple roles in leprosy. we previously reported a preliminary association of cfh with leprosy, but potentially causal variants remain to be identified. in this study, we performed a fine-mapping association analysis in 1110 individuals (527 leprosy patients and 583 controls) followed by bioinformatic analyses. we identified no association of typical missense cfh variants with leprosy and ...201425030427
protection against mycobacterium leprae infection by the id83/gla-se and id93/gla-se vaccines developed for tuberculosis.despite the dramatic reduction in the number of leprosy cases worldwide in the 1990s, transmission of the causative agent, mycobacterium leprae, is still occurring, and new cases continue to appear. new strategies are required in the pursuit of leprosy elimination. the cross-application of vaccines in development for tuberculosis may lead to tools applicable to elimination of leprosy. in this report, we demonstrate that the chimeric fusion proteins id83 and id93, developed as antigens for tuberc ...201425024362
effect of apoptotic cell recognition on macrophage polarization and mycobacterial persistence.intracellular mycobacterium leprae infection modifies host macrophage programming, creating a protective niche for bacterial survival. the milieu regulating cellular apoptosis in the tissue plays an important role in defining susceptible and/or resistant phenotypes. a higher density of apoptotic cells has been demonstrated in paucibacillary leprosy lesions than in multibacillary ones. however, the effect of apoptotic cell removal on m. leprae-stimulated cells has yet to be fully elucidated. in t ...201425024361
semi-automated protocol for purification of mycobacterium leprae from tissues using the gentlemacs™ octo dissociator.mycobacterium leprae, etiologic agent of leprosy, is propagated in athymic nude mouse footpads (fps). the current purification protocol is tedious and physically demanding. a simpler, semi-automated protocol was developed using gentlemacs™ octo dissociator. the gentlemacs protocol provided a very effective means for purification of highly viable m. leprae from tissue.201425019518
the role of micrornas in the control and mechanism of action of il-10.recent studies have shown an important interplay between interleukin 10 (il-10) and micrornas. il-10 can be directly post-transcriptionally regulated by several microrna, including mir-106a, mir-4661, mir-98, mir-27, let7 and mir-1423p/5p. mirna targeting of il-10 has been suggested to play a role in autoimmune and inflammatory diseases such as sle, reperfusion injury and asthma. another mirna, mir-21, has been shown to indirectly regulate il-10 via downregulation of the il-10 inhibitor pdcd4. t ...201425004817
evaluation of a rapid serological test for leprosy classification using human serum albumin as the antigen carrier.the presence of anti-bsa antibodies may interfere in serological tests, as elisa or immunochromatographic assays. bsa is frequently used as a blocking agent or as "inert" carrier of antigens, such as the nt-p-bsa, the semi-synthetic trisaccharide analogue of the pgl-i (phenolic glycolipid-i) antigen from the cell wall of the mycobacterium leprae. pgl-i was prepared and linked to human serum albumin based in the hypothesis that replacing bsa by a human protein carrier would enhance the performanc ...201424983877
is drug-resistant mycobacterium leprae a real cause for concern?: first approach to molecular monitoring of multibacillary colombian patients with and without previous leprosy treatment.there is no information in colombia on mycobacterium leprae primary and secondary drug resistance in regards to the who-multidrug therapy regime. on the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods.201424968045
t-cell regulation in lepromatous leprosy.regulatory t (treg) cells are known for their role in maintaining self-tolerance and balancing immune reactions in autoimmune diseases and chronic infections. however, regulatory mechanisms can also lead to prolonged survival of pathogens in chronic infections like leprosy and tuberculosis (tb). despite high humoral responses against mycobacterium leprae (m. leprae), lepromatous leprosy (ll) patients have the characteristic inability to generate t helper 1 (th1) responses against the bacterium. ...201424722473
pcr-based techniques for leprosy diagnosis: from the laboratory to the clinic.in leprosy, classic diagnostic tools based on bacillary counts and histopathology have been facing hurdles, especially in distinguishing latent infection from active disease and diagnosing paucibacillary clinical forms. serological tests and ifn-gamma releasing assays (igra) that employ humoral and cellular immune parameters, respectively, are also being used, but recent results indicate that quantitative pcr (qpcr) is a key technique due to its higher sensitivity and specificity. in fact, advan ...201424722358
mycobacterium leprae genomes from a british medieval leprosy hospital: towards understanding an ancient epidemic.leprosy has afflicted humankind throughout history leaving evidence in both early texts and the archaeological record. in britain, leprosy was widespread throughout the middle ages until its gradual and unexplained decline between the 14th and 16th centuries. the nature of this ancient endemic leprosy and its relationship to modern strains is only partly understood. modern leprosy strains are currently divided into 5 phylogenetic groups, types 0 to 4, each with strong geographical links. until r ...201424708363
protides of n-(3-(5-(2'-deoxyuridine))prop-2-ynyl)octanamide as potential anti-tubercular and anti-viral agents.the flavin-dependent thymidylate synthase x (thyx), rare in eukaryotes and completely absent in humans, is crucial in the metabolism of thymidine (a dna precursor) in many microorganisms including several human pathogens. conserved in mycobacteria, including mycobacterium leprae, and mycobacterium tuberculosis, it represents a prospective anti-mycobacterial therapeutic target. in a m. tuberculosis thyx-enzyme inhibition assay, n-(3-(5-(2'-deoxyuridine-5'-phosphate))prop-2-ynyl)octanamide was rep ...201424690527
optimized protocols for mycobacterium leprae strain management: frozen stock preservation and maintenance in athymic nude mice.leprosy, caused by mycobacterium leprae, is an important infectious disease that is still endemic in many countries around the world, including brazil. there are currently no known methods for growing m. leprae in vitro, presenting a major obstacle in the study of this pathogen in the laboratory. therefore, the maintenance and growth of m. leprae strains are preferably performed in athymic nude mice (nu-foxn1(nu)). the laboratory conditions for using mice are readily available, easy to perform, ...201424686247
examining erbb2 as a candidate gene for susceptibility to leprosy (hansen's disease) in brazil.leprosy remains prevalent in brazil. erbb2 is a receptor for leprosy bacilli entering schwann cells, which mediates mycobacterium leprae-induced demyelination and the erbb2 gene lies within a leprosy susceptibility locus on chromosome 17q11-q21. to determine whether polymorphisms at the erbb2 locus contribute to this linkage peak, three haplotype tagging single nucleotide polymorphisms (tag-snps) (rs2517956, rs2952156, rs1058808) were genotyped in 72 families (208 cases; 372 individuals) from th ...201424676663
a rapid elisa for the diagnosis of mb leprosy based on complementary detection of antibodies against a novel protein-glycolipid conjugate.despite the widespread use of multidrug therapy for treatment, delays in clinical recognition and under-reporting of leprosy indicate that mycobacterium leprae transmission is continuing. thus, leprosy is likely to persist as a significant burden on health systems in many regions. in this study, we combined 2 previously characterized leprosy antigens, leprosy idri diagnostic-1 (lid-1) and nd-o, into the single fusion complex (nd-o-lid) and determined the serum antibody responses of leprosy patie ...201424666703
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