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cd163 favors mycobacterium leprae survival and persistence by promoting anti-inflammatory pathways in lepromatous macrophages.lepromatous macrophages possess a regulatory phenotype that contributes to the immunosuppression observed in leprosy. cd163, a scavenger receptor that recognizes hemoglobin-haptoglobin complexes, is expressed at higher levels in lepromatous cells, although its functional role in leprosy is not yet established. we herein demonstrate that human lepromatous lesions are microenvironments rich in ido⁺cd163⁺. cells isolated from these lesions were cd68⁺ido⁺cd163⁺ while higher levels of scd163 in lepro ...201222851198
limited susceptibility of cynomolgus monkeys (macaca fascicularis) to leprosy after experimental administration of mycobacterium leprae.cynomolgus monkeys are a useful model for human tuberculosis, but susceptibility to m. leprae is unknown. a cynomolgus model of leprosy could increase understanding of pathogenesis-importantly, neuritis and nerve-damaging reactions. we administered viable mycobacterium leprae to 24 cynomolgus monkeys by three routes, with a median follow-up period of 6 years (range = 1-19 years) involving biopsies, nasal smears, antiphenolic glycolipid-1 (pgl-1) antibody serology, and lepromin skin testing. most ...201222855766
mycobacterium tuberculosis complex lipid virulence factors preserved in the 17,000-year-old skeleton of an extinct bison, bison antiquus.tracing the evolution of ancient diseases depends on the availability and accessibility of suitable biomarkers in archaeological specimens. dna is potentially information-rich but it depends on a favourable environment for preservation. in the case of the major mycobacterial pathogens, mycobacterium tuberculosis and mycobacterium leprae, robust lipid biomarkers are established as alternatives or complements to dna analyses. a dna report, a decade ago, suggested that a 17,000-year-old skeleton of ...201222860031
detection of antibiotic resistance in leprosy using genotype lepraedr, a novel ready-to-use molecular test.although leprosy is efficiently treated by multidrug therapy, resistance to first-line (dapsone, rifampin) and to second-line drugs (fluoroquinolones) was described worldwide. since mycobacterium leprae is not growing in vitro, phenotypic susceptibility testing requires a one year experiment in the mouse model and this is rarely performed. genetics on antibiotic resistance provide the basis for molecular tests able to detect for antibiotic resistance in leprosy.201222860144
leprosy and rheumatoid arthritis: consequence or association?leprosy or hansen's disease is a chronic granulomatous infectious disease caused by mycobacterium leprae with a high prevalence in some developing countries however, it is rarely seen in non-endemic regions. arthritis has been described in all types of hansen's disease. chronic arthritis is known to exist even in paucibacillary forms, resolved or treated disease and in patients without reaction, suggesting a perpetuated inflammatory process. in these cases leprosy can mimic some autoimmune disea ...201222891014
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
microbial heat shock protein 65 attenuates airway hyperresponsiveness and inflammation by modulating the function of dendritic cells.heat shock proteins (hsps), produced in response to stress, are suppressive in disease models. we previously showed that mycobacterium leprae hsp65 prevented development of airway hyperresponsiveness and inflammation in mice. our goal in this study was to define the mechanism responsible for the suppressive effects of hsp. in one in vivo approach, balb/c mice were sensitized to ova, followed by primary ova challenges. several weeks later, hsp65 was administered prior to a single, provocative sec ...201222933632
peroneus longus transfer for drop foot in hansen disease.leprosy or hansen's disease is a chronic infectious disease caused by the mycobacterium leprae. nerve injury is a central feature of the pathogenesis of leprosy that results in autonomic, sensory and motor neuropathy. one of the most common secondary disabilities caused by hansen's disease is the drop foot and it is found in 2% to 5% of newly-diagnosed leprosy patients. unlike the clinical picture of traumatic injury of the common peroneal nerve where both of its branches (the deep peroneal nerv ...201222938641
susceptibility to leprosy is associated with m-ficolin polymorphisms.mycobacterium leprae exploits complement activation and opsonophagocytosis to infect phagocytes. m-ficolin is encoded by the fcn1 gene and initiates the lectin pathway on monocyte surfaces. we investigated fcn1 promoter polymorphisms that could be responsible for the high interindividual variability of m-ficolin levels and for modulating leprosy susceptibility.201322941510
knowledge of the patients regarding leprosy and adherence to treatment.leprosy is a chronic infectious disease caused by mycobacterium leprae. it is known for its great disfiguring capacity and is considered an extremely serious disease to public health worldwide. the state of ceará ranks 13th in number of cases of leprosy in brazil, and fourth in northeastern region, with an average of 2,149 new cases diagnosed every year. this study aimed to evaluate the knowledge of leprosy patients regarding treatment, and to assess the level of treatment adherence and its poss ...201222980586
leprosy: an overview of pathophysiology.leprosy, also known as hansen's disease, is a chronic infectious disease caused by mycobacterium leprae, a microorganism that has a predilection for the skin and nerves. the disease is clinically characterized by one or more of the three cardinal signs: hypopigmented or erythematous skin patches with definite loss of sensation, thickened peripheral nerves, and acid-fast bacilli detected on skin smears or biopsy material. m. leprae primarily infects schwann cells in the peripheral nerves leading ...201222988457
[phagocytosis of mycobacterium leprae down-regulates anti-microbial activity of murine macrophages against mycobacterium intracellulare].patients with highly bacillated lepromatous leprosy (ll) essentially lack t cell-mediated immune responses specific to mycobacterium leprae (ml) antigens, resulting in severely impaired host resistance to leprosy bacilli. such type of immune unresponsiveness characteristic of ll patients is mainly attributable to markedly depressed t cell ability to activate/expand in response to ml antigens. in this study, we examined profiles of antimycobacterial activity of macrophages, which phagocytized lep ...201223012845
genotyping of mycobacterium leprae in myanmar and possible transmission modes.the polymorphism of ttc repeats in mycobacterium leprae was examined using bacilli from slit skin samples of leprosy patients attending at central special skin clinic, yangon general hospital and nasal swabs of their contacts to elucidate the possible mode of leprosy transmission. it was found that bacilli with different ttc genotypes were distributed among same household contacts and also harbored bacilli in patients were different ttc genotype from that harbored on the nasal mucus of the healt ...201223012847
[enhanced activation of t lymphocytes by urease-deficient recombinant bacillus calmette-guérin producing heat shock protein 70-major membrane protein-ii fusion protein].to activate naïve t cells convincingly using mycobacterium bovis bcg (bcg), rbcg (bcg-d70m) that was deficient in urease, expressed with gene encoding the fusion of bcg-derived heat shock protein (hsp) 70 and mycobacterium leprae-derived major membrane protein (mmp)-ii, one of the immunodominant ags of m. leprae, was newly constructed. bcg-d70m was more potent in activation of both cd4+ and cd8+ subsets of naïve t cells than rbcgs including urease-deficient bcg and bcg-70m secreting hsp70-mmp-ii ...201223012848
[collaboration between korea and japan for basic research on leprosy].new case detection in japan has been markedly decreased and same trends have been also shown in korea. despite of unfavorable circumstances, research activities are still continuing and we have the accumulation of knowledge on leprosy both in japan and korea. following basic studies for leprosy on going in japan were reviewed. 1. analysis of drug resistance mechanism and its application for clinical samples. 2. establishment of early diagnostic technique. 3. clarification of mechanisms of neurop ...201223012849
development and characterization of a new oral dapsone nanoemulsion system: permeability and in silico bioavailability studies.dapsone is described as being active against mycobacterium leprae, hence its role in the treatment of leprosy and related pathologies. despite its therapeutic potential, the low solubility of dapsone in water results in low bioavailability and high microbial resistance. nanoemulsions are pharmaceutical delivery systems derived from micellar solutions with a good capacity for improving absorption. the aim of this work was to develop and compare the permeability of a series of dapsone nanoemulsion ...201223055729
albinism and disease causing pathogens in tanzania: are alleles that are associated with oca2 being maintained by balancing selection?oculocutaneous albinism type 2 (oca2) is present at significantly higher frequencies in sub-saharan african populations compared to populations in other regions of the world. in tanzania and other sub-saharan countries, most oca2 is associated with a common 2.7kb deletion allele. leprosy is also in high prevalence in sub-saharan african populations. the infectious agent of leprosy, mycobacterium leprae, contains a gene, 38l, that is similar to oca2. hypopigmented patches of skin are early sympto ...201223063908
impact of amino acid substitutions in b subunit of dna gyrase in mycobacterium leprae on fluoroquinolone resistance.ofloxacin is a fluoroquinolone (fq) used for the treatment of leprosy. fqs are known to interact with both a and b subunits of dna gyrase and inhibit supercoiling activity of this enzyme. mutations conferring fq resistance have been reported to be found only in the gene encoding a subunit of this enzyme (gyra) of m. leprae, although there are many reports on the fq resistance-associated mutation in gyrb in other bacteria, including m. tuberculosis, a bacterial species in the same genus as m. lep ...201223071850
severe leprosy reactions due to mycobacterium lepromatosis.leprosy is caused by the well-known mycobacterium leprae and the newly discovered m lepromatosis. here, the authors describe 2 cases of leprosy with unusual clinical presentation caused by m lepromatosis. the patients, a 32-year-old man and a 50-year-old woman, both of mexican origin, manifested high fever, lymphadenopathy and florid skin lesions in the form of erythema nodosum and lucio's phenomenon as the first clinical presentation. heavy infiltration of acid-fast bacilli was identified in th ...201323111393
molecular mimicry between hsp 65 of mycobacterium leprae and cytokeratin 10 of the host keratin; role in pathogenesis of leprosy.mycobacteria are known to induce autoimmune response in the host. anti-host keratrin antibodies (akabs) might be responsible for the autoimmune phenomena in leprosy patients as majority of leprosy lesions are manifested in the skin and occurrence of keratosis is not an uncommon feature. the aim of this study was to find out the level of akabs in leprosy patients across the spectrum and to explore its correlation with the clinical manifestation of the disease. further, mimicking epitopes of kerat ...201223121977
human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions.leprosy, a chronic granulomatous disease affecting the skin and nerves, is caused by mycobacterium leprae (m. leprae). the type of leprosy developed depends upon the host immune response. type 1 reactions (t1rs), that complicate borderline and lepromatous leprosy, are due to an increase in cell-mediated immunity and manifest as nerve damage and skin inflammation. owing to the increase in inflammation in the skin of patients with t1rs, we sought to investigate the activation of the innate immune ...201223133681
minocycline-induced hyperpigmentation in multibacillary leprosy.minocycline has been used in the treatment of leprosy since the demonstration of its efficacy in inhibiting mycobacterium leprae growth in 1987. hyperpigmentation, a well-documented adverse effect, classically shows 3 clinical and histological patterns: type i consists of blue-black pigmentation in areas of current or previous inflammation, type ii consists of blue-gray pigmentation of normal skin, often seen on the legs, and type iii consists of diffuse muddy-brown pigmentation accentuated on s ...201223169418
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
lipid droplets and mycobacterium leprae infection.leprosy is a chronic infectious disease and is a major source of morbidity in developing countries. leprosy is caused by the obligate intracellular bacterium mycobacterium leprae, which infects as primary target schwann cells. lepromatous leprosy exhibits multiple lesions of the skin, eyes, nerves, and lymph nodes. the sites of infection are characterized by the presence of foamy macrophages, fully packed with lipid droplets (lds), which are induced by m. leprae. in the last years, it has become ...201223209912
the immunological skin tests in leprosy. part i. the isolation of a protein antigen of mycobacterium leprae. 1942. 201223210149
clinically unsuspected neuritic leprosy with caseation necrosis.leprosy is a devastating disease caused by mycobacterium leprae. it includes a spectrum of clinicopathological lesions. neuritic leprosy with caseation necrosis (abscess) manifesting as a soft tissue mass is a relatively rare presentation of leprosy. here, the authors report their experience with three patients with neuritic leprosy. the patients presented with swellings in the right ulnar nerve, the right great auricular nerve, and the temporal branch of the right sixth cranial nerve. the clini ...201223216235
the armadillo: a model for the neuropathy of leprosy and potentially other neurodegenerative diseases.leprosy (also known as hansen's disease) is an infectious peripheral neurological disorder caused by mycobacterium leprae that even today leaves millions of individuals worldwide with life-long disabilities. the specific mechanisms by which this bacterium induces nerve injury remain largely unknown, mainly owing to ethical and practical limitations in obtaining affected human nerve samples. in addition to humans, nine-banded armadillos (dasypus novemcinctus) are the only other natural host of m. ...201323223615
development and pre-clinical assessment of a 73 kd chimeric fusion protein as a defined sub-unit vaccine for leprosy.despite the advances toward the elimination of leprosy through widespread provision of multi-drug therapy to registered patients over the last 2 decades, new case detection rates have stabilized and leprosy remains endemic in a number of localized regions. a vaccine could overcome the inherent limitations of the drug treatment program by providing protection in individuals who are not already harboring the mycobacterium leprae bacilli at the time of administration and effectively interrupt the t ...201323228811
clofazimine modulates the expression of lipid metabolism proteins in mycobacterium leprae-infected macrophages.mycobacterium leprae (m. leprae) lives and replicates within macrophages in a foamy, lipid-laden phagosome. the lipids provide essential nutrition for the mycobacteria, and m. leprae infection modulates expression of important host proteins related to lipid metabolism. thus, m. leprae infection increases the expression of adipophilin/adipose differentiation-related protein (adrp) and decreases hormone-sensitive lipase (hsl), facilitating the accumulation and maintenance of lipid-rich environment ...201223236531
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
il12b snps and copy number variation in il23r gene associated with susceptibility to leprosy.genome-wide studies have identified both human leucocyte antigen (hla) and non-hla regions in association with leprosy. involvement of novel functional loci within these regions has been proposed by us earlier.201323240095
galectin-3 regulates the innate immune response of human monocytes.galectin-3 is a β-galactoside-binding lectin widely expressed on epithelial and hematopoietic cells, and its expression is frequently associated with a poor prognosis in cancer. because it has not been well-studied in human infectious disease, we examined galectin-3 expression in mycobacterial infection by studying leprosy, an intracellular infection caused by mycobacterium leprae. galectin-3 was highly expressed on macrophages in lesions of patients with the clinically progressive lepromatous f ...201323255567
infectious diseases of khmer immigrants in the united states: review of published reports.infectious diseases are influenced by where patients have lived or travelled in the past, e.g., infection with schistosoma mekongi can be acquired during freshwater contact in cambodia, but not in the united states. here the infectious diseases of khmer immigrants in the united states were studied by reviewing published reports. thirteen case series and 9 case reports of 5,222 patients were identified. most reports were of infections with gastrointestinal parasites (8, 36%), plasmnodium species ...201123272458
hansen's disease: a vanishing disease?the introduction, implementation, successes and failures of multidrug therapy (mdt) in all hansen's disease endemic countries are discussed in this paper. the high efficacy of leprosy treatment with mdt and the global reduction of prevalence led the world health organization, in 1991, to establish the goal of elimination of hansen's disease (less than 1 patient per 10,000 inhabitants) to be accomplished by the year 2000. brazil, nepal and east timor are among the few countries that didn't reach ...201223283447
the role of human t cell lymphotrophic virus type 1, hepatitis b virus and hepatitis c virus coinfections in leprosy.leprosy spectrum and outcome is associated with the host immune response against mycobacterium leprae. the role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. leprosy remains endemic in several regions where human t cell lymphotrophic virus type 1 (htlv-1), hepatitis b virus (hbv) or hepatitis c virus (hcv) are also endemic. we have evaluated the evidence for the possible role of these viruses in the clinical ma ...201223283452
unveiling healthy carriers and subclinical infections among household contacts of leprosy patients who play potential roles in the disease chain of transmission.leprosy transmission still occurs despite the availability of highly effective treatment. the next step towards successfully eliminating leprosy is interrupting the chain of transmission of the aetiological agent, mycobacterium leprae. in this investigation, we provide evidence that household contacts (hhcs) of leprosy patients might not only have subclinical infections, but may also be actively involved in bacilli transmission. we studied 444 patients and 1,352 contacts using anti-phenolic glyc ...201223283454
identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy.although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. in this study, we examined the reactivity of sera from lepromatous and tuberculoid lepro ...201223283458
serologic follow-up of igg responses against recombinant mycobacterial proteins ml0405, ml2331 and lid-1 in a leprosy hyperendemic area in venezuela.leprosy is a slowly evolving disease that occurs mainly in adults. in this study, the mamaría village, state of portuguesa was selected because it had one of the highest prevalence rates (13.25%) of leprosy cases in 1997. between 1998-2004, 20.2% of the 89 cases registered in this village were less than 15 years old and 61.8% were males. paucibacillary (pb) lesions were the predominant clinical forms identified, although also multibacillary (mb) forms were found. additionally, 76% of the patient ...201223283459
seroreactivity to new mycobacterium leprae protein antigens in different leprosy-endemic regions in brazil.new mycobacterium leprae protein antigens can contribute to improved serologic tests for leprosy diagnosis/classification and multidrug therapy (mdt) monitoring. this study describes seroreactivity to m. leprae proteins among participants from three highly endemic leprosy areas in brazil: central-western goiânia/goiás (go) (n = 225), rondonópolis/mato grosso (mt) (n = 764) and northern prata village/pará (pa) (n = 93). elisa was performed to detect igg to proteins (92f, 46f, leprosy idri diagnos ...201223283461
mycobacterium leprae virulence-associated peptides are indicators of exposure to m. leprae in brazil, ethiopia and nepal.silent transmission of mycobacterium leprae, as evidenced by stable leprosy incidence rates in various countries, remains a health challenge despite the implementation of multidrug therapy worldwide. therefore, the development of tools for the early diagnosis of m. leprae infection should be emphasised in leprosy research. as part of the continuing effort to identify antigens that have diagnostic potential, unique m. leprae peptides derived from predicted virulence-associated proteins (group iv. ...201223283462
genotyping of mycobacterium leprae present on ziehl-neelsen-stained microscopic slides and in skin biopsy samples from leprosy patients in different geographic regions of brazil.we analysed 16 variable number tandem repeats (vntr) and three single-nucleotide polymorphisms (snp) in mycobacterium leprae present on 115 ziehl-neelsen (z-n)-stained slides and in 51 skin biopsy samples derived from leprosy patients from ceará (n = 23), pernambuco (n = 41), rio de janeiro (n = 22) and rondônia (ro) (n = 78). all skin biopsies yielded snp-based genotypes, while 48 of the samples (94.1%) yielded complete vntr genotypes. we evaluated two procedures for extracting m. leprae dna fr ...201223283465
association analysis of human leukocyte antigen class ii (drb1) alleles with leprosy in individuals from são luís, state of maranhão, brazil.epidemiological studies have demonstrated that the variability of the clinical response to infection caused by mycobacterium leprae is associated with host genetic factors. the present study investigated the frequency of human leukocyte antigen (hla) class ii (drb1) alleles in patients with leprosy from são luís, maranhão, brazil. a case-control study was performed in 85 individuals with leprosy and 85 healthy subjects. all samples were analysed via polymerase chain reaction-sequence specific ol ...201223283466
deciphering the contribution of lipid droplets in leprosy: multifunctional organelles with roles in mycobacterium leprae pathogenesis.leprosy is an infectious disease caused by mycobacterium leprae that affects the skin and nerves, presenting a singular clinical picture. across the leprosy spectrum, lepromatous leprosy (ll) exhibits a classical hallmark: the presence of a collection of m. leprae-infected foamy macrophages/schwann cells characterised by their high lipid content. the significance of this foamy aspect in mycobacterial infections has garnered renewed attention in leprosy due to the recent observation that the foam ...201223283467
differential expression of the costimulatory molecules cd86, cd28, cd152 and pd-1 correlates with the host-parasite outcome in leprosy.leprosy is a spectral disease exhibiting two polar sides, namely, lepromatous leprosy (ll) characterised by impaired t-cell responses and tuberculoid leprosy in which t-cell responses are strong. proper t-cell activation requires signalling through costimulatory molecules expressed by antigen presenting cells and their ligands on t-cells. we studied the influence of costimulatory molecules on the immune responses of subjects along the leprosy spectrum. the expression of the costimulatory molecul ...201223283468
mycobacterial laminin-binding histone-like protein mediates collagen-dependent cytoadherence.when grown in the presence of exogenous collagen i, mycobacterium bovis bcg was shown to form clumps. scanning electron microscopy examination of these clumps revealed the presence of collagen fibres cross-linking the bacilli. since collagen is a major constituent of the eukaryotic extracellular matrices, we assayed bcg cytoadherence in the presence of exogenous collagen i. collagen increased the interaction of the bacilli with a549 type ii pneumocytes or u937 macrophages, suggesting that bcg is ...201223283469
insights from animal models on the immunogenetics of leprosy: a review.a variety of host immunogenetic factors appear to influence both an individual's susceptibility to infection with mycobacterium leprae and the pathologic course of the disease. animal models can contribute to a better understanding of the role of immunogenetics in leprosy through comparative studies helping to confirm the significance of various identified traits and in deciphering the underlying mechanisms that may be involved in expression of different disease related phenotypes. genetically e ...201223283472
mycobacterium leprae in six-banded (euphractus sexcinctus) and nine-banded armadillos (dasypus novemcinctus) in northeast brazil.human beings are the main reservoir of the causative agent of leprosy, mycobacterium leprae. in the americas, nine-banded armadillos (dasypus novemcinctus) also act as a reservoir for the bacillus. in the state of ceará (ce), which is located in northeast brazil and is an endemic area of leprosy, there are several species of armadillos, including d. novemcinctus and euphractus sexcinctus (six-banded armadillo). contact between humans and armadillos occur mainly through hunting, cleaning, prepari ...201223283473
molecular, ethno-spatial epidemiology of leprosy in china: novel insights for tracing leprosy in endemic and non endemic provinces.leprosy continues to be detected at near stable rates in china even with established control programs, necessitating new knowledge and alternative methods to interrupt transmission. a molecular epidemiology investigation of 190 patients was undertaken to define mycobacterium leprae strain types and discern genetic relationships and clusters in endemic and non-endemic regions spanning seventeen provinces and two autonomous regions. the findings support multiple locus variable number of tandem rep ...201323291419
mycobacterium leprae in colombia described by snp7614 in gyra, two minisatellites and geography.new cases of leprosy are still being detected in colombia after the country declared achievement of the who defined 'elimination' status. to study the ecology of leprosy in endemic regions, a combination of geographic and molecular tools were applied for a group of 201 multibacillary patients including six multi-case families from eleven departments. the location (latitude and longitude) of patient residences were mapped. slit skin smears and/or skin biopsies were collected and dna was extracted ...201323291420
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
synthesis of gatifloxacin derivatives and their biological activities against mycobacterium leprae and mycobacterium tuberculosis.novel 3'-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4-quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by (1)h, (13)c and (19)f nmr, and hrms. the activity of these derivatives against pathogenic mycobacteria (m. leprae and m. tuberculosis), wild-type (wt) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (mic) and/or dna supercoi ...201223294829
an unusual cause of mononeuritis multiplex.a middle-aged man of south asian decent presented with a 4-month history of bilateral sensory disturbance affecting the median nerve distribution and dorsum of both feet. neurological examination was otherwise normal. a patchy absence of sensory responses was noted on nerve conduction studies and electromyogram (ncs/emg). over the next 3 months sensory symptoms progressed to involve median, radial, ulnar, sural and peroneal nerves bilaterally. repeat ncs/emg confirmed a mononeuritis multiplex pr ...201323315459
hansen's disease with mccune-albright syndrome.mccune-albright syndrome (mas) comprises a triad of fibrous dysplasia of bone, café-au-lait macule, and endocrinopathy. the disease is due to activating mutation of g protein-coupled receptor leading to hyperfunction of glands. hansen's disease is caused by infection with mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals. we recently encountered a patient with hansen's disease along with underlying mas and report the same in this ...201223326081
cohort study of the seasonal effect on nasal carriage and the presence of mycobacterium leprae in an endemic area in the general population.leprosy continues to be a significant health problem in certain pockets in developing countries. better understanding of the transmission and source of the infection would help to decipher the transmission link, leading to control of the spread of the disease. the nose is considered to be a portal of entry, suggesting an aerial route for transmission through droplet infection. the evidence suggests that many individuals from endemic countries carry mycobacterium leprae in their nasal cavities wi ...201223331372
single nucleotide polymorphisms typing of mycobacterium leprae reveals focal transmission of leprosy in high endemic regions of india.earlier studies indicate that genotyping of mycobaterium leprae based on single-nucleotide polymorphisms (snps) is useful for analysis of the global spread of leprosy. in the present study, we investigated the diversity of m. leprae at eight snp loci using 180 clinical isolates obtained from patients with leprosy residing mainly in delhi and purulia (west bengal) regions. it was observed that the frequency of snp type 1 and subtype d was most predominant in the indian population. further, the sn ...201323331718
park2 mediates interleukin 6 and monocyte chemoattractant protein 1 production by human macrophages.leprosy is a persistent infectious disease caused by mycobacterium leprae that still affects over 200,000 new patients annually. the host genetic background is an important risk factor for leprosy susceptibility and the park2 gene is a replicated leprosy susceptibility candidate gene. the protein product of park2, parkin, is an e3 ubiquitin ligase that is involved in the development of various forms of parkinsonism. the human macrophage is both a natural host cell of m. leprae as well as a prima ...201323350010
identification of mimotopes of mycobacterium leprae as potential diagnostic reagents.an early diagnostic test for detecting infection in leprosy is fundamental for reducing patients' sequelae. the currently used lepromin is not adequate for disease diagnosis and, so far, no antigen to be used in intradermoreaction has proved to be sensitive and specific for that purpose. aiming at identifying new reagents to be used in skin tests, candidate antigens were investigated.201323351151
ofloxacin multicentre trial in mb leprosy fuam-manaus and ilsl-bauru, brazil.recently antimicrobials of the fluoroquinolone class (pefloxacin and ofloxacin) were found far more effective against mycobacterium leprae in studies with both mice and patients than dapsone and clofazimine. as multicentre trial participants, we evaluated the therapeutic efficacy, in terms of rate of relapse, of two new multidrug regimens containing ofloxacin, comparing them to 1 year and 2 years of standard who-mdt regimen in multibacillary (mb) leprosy patients. a total of 198mb patients were ...201223356027
patient-related factors predicting the effectiveness of rifampicin chemoprophylaxis in contacts: 6 year follow up of the colep cohort in bangladesh.the colep trial in bangladesh showed a 57% reduction in leprosy incidence among contacts of newly diagnosed patients in the first 2 years after chemoprophylaxis with single dose rifampicin (sdr). we assessed the impact of this intervention after 6 years and identified characteristics of the leprosy index patients predicting the effectiveness of this intervention.201223356030
cellular microbiology: mycobacterium leprae turns back the clock. 201323377499
cellular microbiology: mycobacterium leprae turns back the clock. 201323385722
early revelation of leprosy in china by sequential antibody analyses with lid-1 and pgl-i.leprosy is a disabling chronic infection, with insidious onset that often evades early detection. in order to detect new leprosy cases in a timely manner, we conducted surveillance visits in some difficult-to-reach mountain areas in south west china where the disease is still prevalent. our data confirm that chinese multibacillary (mb) leprosy patients have strong antibody responses against mycobacterium leprae antigens nd-o-bsa and lid-1. contacts of clinically diagnosed patients were then moni ...201323431316
lsr2 of mycobacterium leprae and its synthetic peptides elicit restitution of t cell responses in erythema nodosum leprosum and reversal reactions in patients with lepromatous leprosy.the lsr2 protein of mycobacterium leprae and its synthetic peptides have been shown to elicit lymphoproliferation and gamma interferon (ifn-γ) release by peripheral blood mononuclear cells (pbmcs) of patients with lepromatous leprosy (m. chaduvula, a. murtaza, n. misra, n. p. narayan, v. ramesh, h. k. prasad, r. rani, r. k. chinnadurai, i. nath, infect. immun. 80:742-752, 2012). pbmcs from 16 patients with lepromatous leprosy who were undergoing erythema nodosum leprosum (enl) (type 2) and 5 pat ...201323446220
type i interferon suppresses type ii interferon-triggered human anti-mycobacterial responses.type i interferons (ifn-α and ifn-β) are important for protection against many viral infections, whereas type ii interferon (ifn-γ) is essential for host defense against some bacterial and parasitic pathogens. study of ifn responses in human leprosy revealed an inverse correlation between ifn-β and ifn-γ gene expression programs. ifn-γ and its downstream vitamin d-dependent antimicrobial genes were preferentially expressed in self-healing tuberculoid lesions and mediated antimicrobial activity a ...201323449998
a comparison of stigma among patients with leprosy in rural tanzania and urban united states: a role for public health in dermatology.leprosy is a chronic infection of the skin and peripheral nerves caused by the bacterium mycobacterium leprae, which causes peripheral insensitivity and disfigurements of the skin, limbs, and digits. social stigma is a common consequence of leprosy and may differ according to level of physical disfigurement and geographic location. the objective of this study was to assess social stigma encountered by patients with leprosy in clinical settings located in rural tanzania and urban usa and to compa ...201323451850
mycobacterium leprae is identified in the oral mucosa from paucibacillary and multibacillary leprosy patients.in leprosy, the nasal mucosa is considered as the principal route of transmission for the bacillus mycobacterium leprae. the objective of this study was to identify m. leprae in the oral mucosa of 50 untreated leprosy patients, including 21 paucibacillary (pb) and 29 multibacillary (mb) patients, using immunohistochemistry (ihc), with antibodies against bacillus calmette-guérin (bcg) and phenolic glycolipid antigen-1 (pgl-1), and polymerase chain reaction (pcr), with mnth-specific primers for m. ...201423473290
whole-blood nested-pcr amplification of m. leprae-specific dna for early diagnosis of leprosy.we evaluated the sensitivity and specificity of a nested-polymerase chain reaction (pcr) method for detection of mycobacterium leprae dna from whole blood. whole-blood specimens were subjected to nested-pcr amplification of m. leprae repeat dna sequences in 49 multibacillary (mb) and 30 paucibacillary (pb) leprosy patients, 96 household contacts (hhcs), 18 tuberculosis (tb) patients, and 35 normal healthy individuals. m. leprae dna was detected in 95.92% (47/49) of mb, 70% (21/30) of pb, and 6.2 ...201323478578
leprosy--evolution of the path to eradication.leprosy is among the world's oldest and most dreaded diseases and it has been synonymous with stigma and discrimination due to the hideous deformities it produced, mystery around its aetiology and transmission and lack of any effective remedy till recently. leprosy control started with the use of chaulmoogra oil and for the last three decades, multi drug therapy (mdt) has been our main tool against leprosy. in the last two decades, the reported global prevalence of active leprosy infection has d ...201323481049
transforming growth factor-β1 may be a key mediator of the fibrogenic properties of neural cells in leprosy.fibrosis is the main cause of irreversible nerve damage in leprosy. phenotypic changes in mycobacterium leprae (ml)-infected schwann cells (scs) have been suggested to mediate this process. we found that sc line cultures stimulated with ml upregulated transforming growth factor-β1 (tgf-β1), and that tgf-β1 or ml induced increased numbers of α-smooth muscle actin (α-sma)-positive cells with characteristic stress fibers. mycobacterium leprae and tgf-β1 also induced increased type i collagen and fi ...201323481710
histological diagnosis of early and suspicious leprosy by in situ pcr.leprosy is a chronic mycobacterial disease whose diagnosis is primarily based on clinico-pathological examination and supported by slit skin smears for the presence of acid fast bacilli (afb). however, definitive diagnosis of early leprosy and those suspected to have the disease but not histologically confirmed pose major public health problems. the present study reports the utility of the in situ polymerase chain reaction amplification (pcr) directed at a 530bp fragment of dna encoding the 36kd ...201223484333
clinicohistopathological concordance in leprosy - a clinical, histopathological and bacteriological study of 100 cases.leprosy is a treatable chronic infectious disease, prevalent in south asian countries, especially india. before labeling a patient as a case of leprosy and starting multidrug treatment for particular type, the clinical findings should be correlated and confirmed with histopathological examination and bacteriological index of skin biopsy. skin biopsy is an important tool in diagnosing leprosy and determining the type of leprosy. in the present study, one hundred untreated clinically diagnosed cas ...201223484336
active surveillance of hansen's disease (leprosy): importance for case finding among extra-domiciliary contacts.hansen's disease (leprosy) remains an important health problem in brazil, where 34,894 new cases were diagnosed in 2010, corresponding to 15.3% of the world's new cases detected in that year. the purpose of this study was to use home visits as a tool for surveillance of hansen's disease in a hyperendemic area in brazil. a total of 258 residences were visited with 719 individuals examined. of these, 82 individuals had had a previous history of hansen's disease, 209 were their household contacts a ...201323516645
challenges in immunodiagnostic tests for leprosy.despite the effectiveness of multidrug therapy, leprosy still represents a significant global health problem: transmission of mycobacterium leprae (m. leprae) is not sufficiently reduced as witnessed by unwavering new case rates in leprosy-endemic countries. early detection of m. leprae infection (before clinical manifestations occur) is vital to reduction of transmission. current diagnosis relies on detection of clinical signs since there are no tests available to detect asymptomatic m. leprae ...201323537134
toll-like receptor 1 n248s single-nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection.conflicting findings about the association between leprosy and tlr1 variants n248s and i602s have been reported. here, we performed case-control and family based studies, followed by replication in 2 case-control populations from brazil, involving 3162 individuals. results indicated an association between tlr1 248s and leprosy in the case-control study (ss genotype odds ratio [or], 1.81; p = .004) and the family based study (z = 2.02; p = .05). this association was consistently replicated in oth ...201323547143
leprosy and its dental management guidelines.leprosy is a chronic, non-fatal disease caused by mycobacterium leprae. it can cause cutaneous lesions, peripheral nerve lesions and orofacial manifestations, including destruction of the alveolar premaxillary process associated with loss of the maxillary incisors. the aims of this study were to assess orofacial manifestations of disease in patients attending the bombay leprosy project clinics and develop clinical guidelines for dentists.201323550518
role of cd8(+) t cells in triggering reversal reaction in hiv/leprosy patients.it has been reported that the initiation of highly active anti-retroviral therapy (haart) is associated with the development of reversal reaction (rr) in co-infected hiv/leprosy patients. nevertheless, the impact of hiv and haart on the cellular immune response to mycobacterium leprae (ml) remains unknown. in the present study, we observed that ex vivo peripheral blood mononuclear cells (pbmcs) of both rr and rr/hiv patients presented increased percentages of activated cd4(+) t cells when compar ...201323566249
deformities due to leprosy in children under fifteen years old as an indicator of quality of the leprosy control programme in brazilian municipalities.the present study aims at analysing the degree of deformity in leprosy cases diagnosed in children under 15 years old and its relationship with operational and epidemiological factors. this epidemiological cross-sectional study was carried out at municipalities of three microregions in a brazilian hyperendemic area. data between 1998 and 2010 was collected from the information system for notifiable diseases database. the average coefficient of detection was 32.96/100.000 inhabitants; 7.61% of ne ...201323577038
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
influence of intron ii microsatellite polymorphism in human toll-like receptor 2 gene in leprosy.leprosy is a chronic granulomatous infection caused by the obligate intracellular organism mycobacterium leprae. tlr2 plays a key role when activated by m. leprae lipoproteins initiating protective responses which induce bacterial killing and therefore control of disease spread. microsatellite polymorphisms in intron2 of tlr2 gene have been reported to be associated with development of clinical features of several infectious diseases. the study aims to evaluate the influence of gt microsatellite ...201323619473
nanobiotechnological approaches to delivery of dna vaccine against fungal infection.vaccines play an essential role in keeping humans healthy. innovative approaches to their use include the utilization of plasmid dna encoding sequences to express foreign antigens. dnahsp65 from mycobacterium leprae is suitable for this purpose due to its ability to elicit a powerful immune response. controlled release systems represent a promising approach to delivering vaccines. in this work, we used liposomes or plga systems to deliver dnahsp65 to treat the pulmonary fungal infection paracocc ...201323627048
detection and strain typing of ancient mycobacterium leprae from a medieval leprosy hospital.nine burials excavated from the magdalen hill archaeological research project (mharp) in winchester, uk, showing skeletal signs of lepromatous leprosy (ll) have been studied using a multidisciplinary approach including osteological, geochemical and biomolecular techniques. dna from mycobacterium leprae was amplified from all nine skeletons but not from control skeletons devoid of indicative pathology. in several specimens we corroborated the identification of m. leprae with detection of mycolic ...201323638071
interaction of mycobacterium leprae with human airway epithelial cells: adherence, entry, survival, and identification of potential adhesins by surface proteome analysis.this study examined the in vitro interaction between mycobacterium leprae, the causative agent of leprosy, and human alveolar and nasal epithelial cells, demonstrating that m. leprae can enter both cell types and that both are capable of sustaining bacterial survival. moreover, delivery of m. leprae to the nasal septum of mice resulted in macrophage and epithelial cell infection in the lung tissue, sustaining the idea that the airways constitute an important m. leprae entry route into the human ...201323670556
lepromatous leprosy: a rare presentation in australia.leprosy (hansen's disease) is caused by the obligate intracellular organism mycobacterium leprae. it is an infectious, chronic granulomatous disease transmitted through close contact. the latest current data shows that in 2010, eleven new cases of leprosy were reported to the national notifiable diseases surveillance system in australia. we report the case of a patient with untreated chronic lepromatous leprosy diagnosed in queensland, 2012. delay in diagnosis may have been due to the rarity of ...201323671461
an attempt to improve pure neural leprosy diagnosis using immunohistochemistry tests in peripheral nerve biopsy specimens.the diagnosis of pure neural leprosy (pnl) is based on clinical and laboratory data, including the histopathology of nerve biopsy specimens and detection of mycobacterium leprae dna by polymerase chain reaction (pcr). given that histopathologic examination and pcr methods may not be sufficient to confirm the diagnosis, immunolabeling of lipoarabinomanan (lam) and/or phenolic glycolipid 1 (pgl-1) m. leprae wall components was utilized in the present investigation in an attempt to detect any vesti ...201423702646
gerhard henrik armauer hansen (1841-1912)--100 years anniversary tribute.2012 marks the 100th year of death of gerhard henrik armauer hansen (1841-1912), who discovered mycobacterium leprae, but also gave the first systematic scientific work on the leprosy of the eye. the article reviews his life and scientific achievements with special regard to eye and ophthalmology.201423710612
[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
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
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
primary dapsone resistant mycobacterium leprae in a non endemic country. 201323760326
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
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
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
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
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
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
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
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
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
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
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
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