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new biomarkers with relevance to leprosy diagnosis applicable in areas hyperendemic for leprosy.leprosy is not eradicable with currently available diagnostics or interventions, as evidenced by its stable incidence. early diagnosis of mycobacterium leprae infection should therefore be emphasized in leprosy research. it remains challenging to develop tests based on immunological biomarkers that distinguish individuals controlling bacterial replication from those developing disease. to identify biomarkers for field-applicable diagnostics, we determined cytokines/chemokines induced by m. lepra ...201222504648
drug and multidrug resistance among mycobacterium leprae isolates from brazilian relapsed leprosy patients.skin biopsy samples from 145 relapse leprosy cases and from five different regions in brazil were submitted for sequence analysis of part of the genes associated with mycobacterium leprae drug resistance. single nucleotide polymorphisms (snps) in these genes were observed in m. leprae from 4 out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpob only, another sample with snps in both folp1 and rpob, and two cases showing mutations in folp1, rpob, and gyra, ...201222495562
multibacillary leprosy: erythema as the only clinical presentation.leprosy is a chronic granulomatous infection caused by mycobacterium leprae, which primarily affects the skin and peripheral nerves. in this article, we present a 45-year-old man and a 39-year-old women who suffered from asymptomatic irregular erythemas on their trunk and extremities. since both patients denied the history of exposure to leprosy patients and were absent clinical signs of superficial sensation dysfunction and enlarged peripheral nerves, they were diagnosed of mycosis fungoides an ...201222490424
[lucio's phenomenon in a patient with leprosy on aruba].lucio's phenomenon is a rare leprosy reaction characterised by bizarrely-shaped, purpuric skin lesions and ulceration. it occurs in diffuse lepromatous leprosy and it is mainly reported in patients from mexico and the caribbean.201222475236
transforming growth factor β and apoptosis in leprosy skin lesions: possible relationship with the control of the tissue immune response in the mycobacterium leprae infection.the course of leprosy depends of the host immune response which ranges from the lepromatous pole (ll) to the tuberculoid pole (tt). a comparative study was conducted in 60 patients with the ll and tt. the results showed a mean expression of tgf-β of 339 ± 99.4 cells/field for tt and of 519.2 ± 68.2 cells/field for ll. frequency of apoptosis was 6.3 ± 1.8 in tt and 14.0 ± 6.1 in ll. a correlation (p = 0.0251) between tgf-β and caspase-3 in the ll was found. this finding indicates a role of tgf-β ...201222429842
histopathological examination of nerve samples from pure neural leprosy patients: obtaining maximum information to improve diagnostic efficiency.nerve biopsy examination is an important auxiliary procedure for diagnosing pure neural leprosy (pnl). when acid-fast bacilli (afb) are not detected in the nerve sample, the value of other nonspecific histological alterations should be considered along with pertinent clinical, electroneuromyographical and laboratory data (the detection of mycobacterium leprae dna with polymerase chain reaction and the detection of serum anti-phenolic glycolipid 1 antibodies) to support a possible or probable pnl ...201222415265
potential selective inhibitors against rv0183 of mycobacterium tuberculosis targeting host lipid metabolism.tuberculosis is the second leading infectious killer with 9 million new cases in 2009. extensive use of pathogen's lipid metabolism especially in utilizing the host lipids and virulence highlights the importance of exported lipid-catabolizing enzymes. current study aims to emphasize the importance of rv0183, an exported monoacylglycerol lipase, involved in metabolizing the host cell membrane lipids. sequence analysis and homology modeling shows rv0183 is highly conserved throughout mycobacterial ...201222405030
hansen's disease (leprosy): current and future pharmacotherapy and treatment of disease-related immunologic reactions.hansen's disease, also known as leprosy, remains an important public health problem throughout the world, including north america. the causative microbe in hansen's disease is mycobacterium leprae, an acid-fast organism that is difficult to grow in vitro. the nine-banded armadillo is the major animal reservoir in the united states. manifestations of disease vary based on host immune response and can range from tuberculoid to lepromatous leprosy (paucibacillary to multibacillary disease). hansen' ...201222392826
epidemiological, clinical, and operational aspects of leprosy patients assisted at a referral service in the state of maranhão, brazil.leprosy is an infectious disease caused by mycobacterium leprae. the aim of this study was to describe the epidemiological, clinical, and operational aspects of leprosy carriers.201222370835
orbital apex syndrome due to trigeminal perineural spread of sinonasal leprosy: a case report.leprosy is a granulomatous disease primarily affecting the skin and peripheral nerves caused by mycobacterium leprae, but also significantly involving sinonasal cavities and cranial nerves. it continues to be a significant public health problem, and despite multidrug therapy, it can still cause significant morbidity. the awareness of cranial nerve, intracranial and orbital apex involvement as in our case is important for appropriate treatment measures.201222370135
peptides derived from mycobacterium leprae ml1601c discriminate between leprosy patients and healthy endemic controls.the stable incidence of new leprosy cases suggests that transmission of infection continues despite worldwide implementation of mdt. thus, specific tools are needed to diagnose early stage mycobacterium leprae infection, the likely sources of transmission. m. leprae antigens that induce t-cell responses in m. leprae exposed and/or infected individuals thus are major targets for new diagnostic tools. previously, we showed that ml1601c was immunogenic in patients and healthy household contacts (hh ...201222363349
ninjurin1 single nucleotide polymorphism and nerve damage in leprosy.leprosy, a chronic infectious disease caused by mycobacterium leprae, can damage the peripheral nervous system and represents one of the leading causes of nontraumatic neuropathy in some developing countries. the ninjurin1 is a cell adhesion molecule that provides suitable substrates for repair of schwann cells after peripheral nerve injury. the single nucleotide polymorphism ninj1, is the result of a transversion of an adenine to a nucleotide polymorphic cytokine (a→c), responsible for an amino ...201222326538
relative entropy differences in bacterial chromosomes, plasmids, phages and genomic islands.we sought to assess whether the concept of relative entropy (information capacity), could aid our understanding of the process of horizontal gene transfer in microbes. we analyzed the differences in information capacity between prokaryotic chromosomes, genomic islands (gi), phages, and plasmids. relative entropy was estimated using the kullback-leibler measure.201222325062
recurrent disseminated intravascular coagulation caused by intermittent dosing of rifampin.daily rifampin therapy is associated with minimal adverse effects, but administration on an intermittent or interrupted basis has been associated with severe immunoallergic reactions such as hemolytic anemia, acute renal failure, and disseminated intravascular coagulation. we describe a patient with mycobacterium leprae infection who experienced recurrent episodes of disseminated intravascular coagulation after intermittent exposures to rifampin, and review eight previously reported cases of rif ...201222302861
use of the polymerase chain reaction to detect mycobacterium leprae in urine.leprosy is an infectious disease caused by mycobacterium leprae. the polymerase chain reaction (pcr) has been applied to detect m. leprae in different clinical samples and urine seems to be attractive for this purpose. pcr was used to improve the sensitivity for diagnosing leprosy by amplifying a 151-bp pcr fragment of the m. leprae pra gene (pcr-pra) in urine samples. seventy-three leprosy patients (39 males and 34 females, 14 to 78 years old) were selected for leprosy diagnosis at a reference ...201222286535
lower numbers of natural killer t cells in hiv-1 and mycobacterium leprae co-infected patients.natural killer t (nkt) cells are a heterogeneous population of lymphocytes that recognize antigens presented by cd1d and have attracted attention because of their potential role linking innate and adaptive immune responses. peripheral nkt cells display a memory-activated phenotype and can rapidly secrete large amounts of pro-inflammatory cytokines upon antigenic activation. in this study, we evaluated nkt cells in the context of patients co-infected with hiv-1 and mycobacterium leprae. the volun ...201222269018
mutation analysis of mycobacterial rpob genes and rifampin resistance using recombinant mycobacterium smegmatis.rifampin is a major drug used to treat leprosy and tuberculosis. the rifampin resistance of mycobacterium leprae and mycobacterium tuberculosis results from a mutation in the rpob gene, encoding the β subunit of rna polymerase. a method for the molecular determination of rifampin resistance in these two mycobacteria would be clinically valuable, but the relationship between the mutations and susceptibility to rifampin must be clarified before its use. analyses of mutations responsible for rifamp ...201222252831
advances in proteomics of mycobacterium leprae.although mycobacterium leprae was the first bacterial pathogen identified causing human disease, it remains one of the few that is non-cultivable. understanding the biology of m. leprae is one of the primary challenges in current leprosy research. genomics has been extremely valuable, nonetheless, functional proteins are ultimately responsible for controlling most aspects of cellular functions, which in turn could facilitate parasitizing the host. furthermore, bacterial proteins provide targets ...201222229831
mycobacterium leprae: pathogenic agent in leprosy. discovery of new species mycobacterium lepromatosis. perspectives in research and diagnosis of leprosy.m. leprae was presumed as an aetiologic agent in dll, without specific microbiologic studios in the past. the sequencing of the genome through genetic testing led to the discovery of a new species m. lepromatosis by han et al. in 2008.201224595978
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
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
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
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
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
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
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
increased serum circulatory levels of interleukin 17f in type 1 reactions of leprosy.leprosy is a chronic infectious disease caused by mycobacterium leprae affecting mainly skin and peripheral nerves. acute inflammatory episodes in the borderline immunological spectrum of the disease cause severe nerve and tissue damage leading to deformities. finding of any serological marker for leprosy reactions will help in prediction of reactions and in early treatment intervention. the objective of this study was to measure the serum circulatory levels of interleukin 17f (il 17f) and to co ...201222847545
[current status of leprosy].leprosy, known since antiquity, is a world infectious disease due to mycobacterium leprae. the transmission is probably via nasal droplets. the clinical range, from tuberculoid to lepromatous leprosy is a result of variation in the cell-mediated immune response, with a chronic inflammation in skin and peripheral nerves. diagnosis of leprosy is clinical with anesthetic skin lesion and skin smears detect acid fast bacilli. besides the classification of patients due to the ridley scale which is cli ...201222838263
the leprosy agents mycobacterium lepromatosis and mycobacterium leprae in mexico.mycobacterium leprae was the only known cause of leprosy until 2008, when a new species, named mycobacterium lepromatosis, was found to cause diffuse lepromatous leprosy (dll), a unique form of leprosy endemic in mexico.201222788812
complex regional pain syndrome secondary to leprosy.leprosy is a chronic infectious disease caused by mycobacterium leprae affecting the skin and the nerves. complex regional pain syndrome (crps/sudeck's dystrophy) is a painful and disabling condition--a triad of autonomic, sensory, and motor symptoms disproportionate to the inciting event (inflammatory, infective, or traumatic nerve damage).201222757620
lshgd: a database for human leprosy susceptible genes.studies aiming to explore the involvement of host genetic factors to determine susceptibility to develop disease and individual's response to the infection with mycobacterium leprae have increased in recent years. to address this issue, we have developed a leprosy susceptible human gene database (lshgd) to integrate leprosy and human associated 45 genes by profound literature search. this will serve as a user-friendly and interactive platform to understand the involvement of human polymorphisms ...201222750101
[childhood memories…].leprosy is still a largely worldwide spread disease but rarely encountered in metropolitan france. its identification implies a multidisciplinary clinical, pathological and bacteriological diagnosis which is necessary to an efficient antibiotic treatment against a crippling disease which remains curable. here we report the case of a 24-year-old man who was showing an original both cutaneous and pulmonary presence of acido-alcooloresistant bacillus which have been identified as mycobacterium lepr ...201222748342
impact of pgl-i seropositivity on the protective effect of bcg vaccination among leprosy contacts: a cohort study.contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. seropositivity to the phenolic glycolipid i (pgl-i) antigen of mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. in the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by bacille calmette guerin (bcg) vaccination after index case diagnosis.201222724040
mitochondrial dna copy number, but not haplogroup, confers a genetic susceptibility to leprosy in han chinese from southwest china.leprosy is a chronic infectious disease caused by mycobacterium leprae, an unculturable pathogen with an exceptionally eroded genome. the high level of inactivation of gene function in m. leprae, including many genes in its metabolic pathways, has led to a dependence on host energy production and nutritional products. we hypothesized that host cellular powerhouse--the mitochondria--may affect host susceptibility to m. leprae and the onset of clinical leprosy, and this may be reflected by mitocho ...201222719964
quality of life of patients with paucibacillary leprosy.leprosy, an infectious disease caused by mycobacterium leprae, can affect the skin and the peripheral nervous system and, depending on the level of involvement, it can lead to severe deformities. leprosy is classified into two major groups: paucibacillary (up to five lesions) and multibacillary (more than five lesions). the deformities that appear during the progress of the disease can affect the quality of life.201222714756
epidemiological profile of leprosy in the brazilian state of piauí between 2003 and 2008.leprosy is a chronic infectious disease caused by mycobacterium leprae. it is considered a major public health issue in developing countries.201222714753
leprosy late-onset neuropathy: an uncommon presentation of leprosy.clinical and pathological findings in leprosy are determined by the natural host immune response to mycobacterium leprae. we previously described cases of painful neuropathy (pn) with no concurrent cause apart from a past history of leprosy successfully treated. four leprosy previously treated patients who developed a pn years after multidrug therapy (mdt) are reported. the mean patient age was 52.75 years (47-64). the mean time interval of the recent neuropathy from the previous mdt was 19 year ...201222699535
nerve damage in leprosy: a continuing challenge to scientists, clinicians and service providers.this review focuses on nerve damage in leprosy. we present evidence to support the argument that leprosy is best seen as a chronic neurological condition rather than a simple skin disease. nerve damage affects small dermal nerves and peripheral nerve trunks. perineural inflammation is a characteristic and hallmark of early leprosy. t cell-mediated inflammation is the main pathological process in leprosy nerve damage. the level of nerve damage in leprosy is high with up to 60% of multibacillary p ...201224029146
atypical hansen's disease presenting as florid verrucous plaques on the lower extremities: a case report.verrucous leprosy is rare, with only 18 cases reported in the literature. visceral involvement is frequent but often overlooked, causing significant morbidity and mortality.201222607288
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
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
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
[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
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
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
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
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 immunological skin tests in leprosy. part i. the isolation of a protein antigen of mycobacterium leprae. 1942. 201223210149
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
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
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
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
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
cytoplasmic and extracellular expression of pharmaceutical-grade mycobacterial 65-kda heat shock protein in lactococcus lactis.lactic acid bacteria (lab) are an attractive and safe alternative for the expression of heterologous proteins, as they are nonpathogenic and endotoxin-free organisms. lactococcus lactis, the lab model organism, has been extensively employed in the biotechnology field for large-scale production of heterologous proteins, and its use as a "cell factory" has been widely studied. we have been particularly interested in the use of l. lactis for production of heat shock proteins (hsps), which reportedl ...201222614283
[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
[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
esx-1-mediated translocation to the cytosol controls virulence of mycobacteria.mycobacterium species, including mycobacterium tuberculosis and mycobacterium leprae, are among the most potent human bacterial pathogens. the discovery of cytosolic mycobacteria challenged the paradigm that these pathogens exclusively localize within the phagosome of host cells. as yet the biological relevance of mycobacterial translocation to the cytosol remained unclear. in this current study we used electron microscopy techniques to establish a clear link between translocation and mycobacter ...201222524898
the antibiotic resistance arrow of time: efflux pump induction is a general first step in the evolution of mycobacterial drug resistance.we hypothesize that low-level efflux pump expression is the first step in the development of high-level drug resistance in mycobacteria. we performed 28-day azithromycin dose-effect and dose-scheduling studies in our hollow-fiber model of disseminated mycobacterium avium-m. intracellulare complex. both microbial kill and resistance emergence were most closely linked to the within-macrophage area under the concentration-time curve (auc)/mic ratio. quantitative pcr revealed that subtherapeutic azi ...201222751536
gerhard hansen: discoverer of the organism of leprosy.this year marks the hundredth anniversary of the death, on 12 february 1912, of the norwegian leprologist, gerhard hansen, who was the first to describe the mycobacterium leprae (hansen's bacillus). it was, in fact, only the second specific disease-causing organism to be discovered, the first being the bacillus of anthrax.201222504759
microrna-21 targets the vitamin d-dependent antimicrobial pathway in leprosy.leprosy provides a model to investigate mechanisms of immune regulation in humans, given that the disease forms a spectrum of clinical presentations that correlate with host immune responses. here we identified 13 mirnas that were differentially expressed in the lesions of subjects with progressive lepromatous (l-lep) versus the self-limited tuberculoid (t-lep) disease. bioinformatic analysis revealed a significant enrichment of l-lep-specific mirnas that preferentially target key immune genes d ...201222286305
genetic diversity of toll-like receptors and immunity to m. leprae infection.genetic association studies of leprosy cohorts across the world have identified numerous polymorphisms which alter susceptibility and outcome to infection with mycobacterium leprae. as expected, many of the polymorphisms reside within genes that encode components of the innate and adaptive immune system. despite the preponderance of these studies, our understanding of the mechanisms that underlie these genetic associations remains sparse. toll-like receptors (tlrs) have emerged as an essential f ...201222529866
polymorphisms of nod2 and the risk of tuberculosis: a validation study in the chinese population.a genome-wide association study (gwas) of leprosy reported four specific genetic polymorphisms of nod2 that were associated with susceptibility to mycobacterium leprae in china. considering the role of nod2 in innate immune defence, we performed a study in a chinese population to determine whether the same snps of nod2 that were associated with disease caused by m. leprae were also associated with disease caused by mycobacterium tuberculosis. we performed a frequency-matched case-control study i ...201222212192
identification of the leprosy agent mycobacterium lepromatosis in singapore.background: a new leprosy-causing species, namely mycobacterium lepromatosis, was discovered recently to be the cause of diffuse lepromatous leprosy (dll) in mexico. it is unknown whether this organism exists beyond mexico. methods: we sought to determine the identity of the mycobacteria in the skin tissue of two patients from singapore who died of dll. dna was extracted from archived biopsy tissue, and conserved polymerase chain reaction primers were used to amplify and sequence two to three my ...201222270197
cojedes: a leprosy hyperendemic state.background  leprosy is a chronic infectious disease produced by mycobacterium leprae. in 1997 venezuela reached the goal of elimination of leprosy as a public health problem (according to the world health organization a prevalence rate of ≤1/10,000 inhabitants), but five states still had prevalence rates over that goal. for this study we selected cojedes state, where prevalence rates remain over the elimination goal. objective  evaluate the real leprosy situation in high-prevalence areas of coje ...201222250629
snp genotypes of mycobacterium leprae isolates in thailand and their combination with rpot and ttc genotyping for analysis of leprosy distribution and transmission.based on the discovery of three single nucleotide polymorphisms (snps) in mycobacterium leprae, it has been previously reported that there are four major snp types associated with different geographic regions around the world. another typing system for global differentiation of m. leprae is the analysis of the variable number of short tandem repeats within the rpot gene. to expand the analysis of geographic distribution of m. leprae, classified by snp and rpot gene polymorphisms, we studied ...201222274158
an enlarged, adaptable active site in cyp164 family p450 enzymes, the sole p450 in mycobacterium leprae.cyp164 family p450 enzymes are found in only a subset of mycobacteria and include cyp164a1, which is the sole p450 found in mycobacterium leprae, the causative agent of leprosy. this has previously led to interest in this enzyme as a potential drug target. here we describe the first crystal structure of a cyp164 enzyme, cyp164a2 from mycobacterium smegmatis. cyp164a2 has a distinctive, enlarged hydrophobic active site that extends above the porphyrin ring toward the access channels. unusually, w ...201222037849
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
dynamics of mycobacterium leprae transmission in environmental context: deciphering the role of environment as a potential reservoir.leprosy is a disease caused by mycobacterium leprae. various modes of transmission have been suggested for this disease. transmission and risk of the infection is perhaps related to presence of the infectious cases and is controlled by environmental factors. evidence suggests that humidity may favor survival of m. leprae in the environment. several reports show that non-human sources like 'naturally' infected armadillos or monkeys could act as reservoir for m. leprae. inanimate objects or fomite ...201222101333
evaluation of cellular phenotypes implicated in immunopathogenesis and monitoring immune reconstitution inflammatory syndrome in hiv/leprosy cases.it is now evident that haart-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or iris. this phenomenon has already been described in cases of hiv coinfection with mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (rr). however, the events related to the pathogenesis of this association need to be clarifie ...201122205964
Nail Involvement in Leprosy.Leprosy, a disease caused by Mycobacterium leprae, primarily affects the skin and nerves, but the nails are also involved in as many as 3 out of 4 patients .The factors that trigger nail changes in leprosy are numerous and include repeated trauma, neuropathy, vascular impairment, infections, lepra reactions, and the drugs used to manage the disease. The changes most often reported include subungual hematomas, onycholysis, onychauxis, onychogryphosis, pterygium unguis, and onychoheterotopia, most ...201122056258
what is the evidence that the putative mycobacterium lepromatosis species causes diffuse lepromatous leprosy?han et al. have made a retrospective isolation of dna from two patients with fatal lucio's phenomenon. this dna does have some molecular differences to m. leprae and may constitute a variant of m. leprae. however the experiments and data needed to confirm that this is a new leprosy-causing species have not yet been done. we have outlined the work that does need to be done. for the moment the assertion that 'm. lepromatosis' is a new leprosy-causing species is not proven.201122125927
evaluation of various cytokines elicited during antigen-specific recall as potential risk indicators for the differential development of leprosy.leprosy is a dermato-neurological disease caused by mycobacterium leprae infection that manifests across a wide range of clinical and immunological outcomes. diagnosis is still currently based on clinical manifestations and simple tests are needed. this study investigated whether biomarkers induced by defined m. leprae proteins in 24-h whole blood assays (wba) could discriminate active leprosy patients from at-risk contacts. newly diagnosed, untreated paucibacillary (pb; tuberculoid leprosy/bord ...201122076550
the activity of several newer antimicrobials against logarithmically multiplying m. leprae in mice.moxifloxacin, rifampicin, rifapentine, linezolid, and pa 824, alone and in combination, have been previously administered, as single doses and five times daily doses, to m. leprae infected mice during lag phase multiplication and were each found to have some bactericidal activity.201122125933
mycobacterium leprae reca is structurally analogous but functionally distinct from mycobacterium tuberculosis reca protein.mycobacterium leprae is closely related to mycobacterium tuberculosis, yet causes a very different illness. detailed genomic comparison between these two species of mycobacteria reveals that the decaying m. leprae genome contains less than half of the m. tuberculosis functional genes. the reduction of genome size and accumulation of pseudogenes in the m. leprae genome is thought to result from multiple recombination events between related repetitive sequences, which provided the impetus to inves ...201122001565
a mycobacterium leprae hsp65 mutant as a candidate for mitigating lupus aggravation in mice.hsp60 is an abundant and highly conserved family of intracellular molecules. increased levels of this family of proteins have been observed in the extracellular compartment in chronic inflammation. administration of m. leprae hsp65 [wt] in [nzbxnzw]f(1) mice accelerates the systemic lupus erythematosus [sle] progression whereas the point mutated k(409)a hsp65 protein delays the disease. here, the biological effects of m. leprae hsp65 leader pep and k(409)a pep synthetic peptides, which cover res ...201121961033
expression of the chemokine receptor cxcr4 on lymphocytes of leprosy patients.leprosy is caused by mycobacterium leprae, which induces chronic granulomatous infection of the skin and peripheral nerves. the disease ranges from the tuberculoid to the lepromatous forms, depending on the cellular immune response of the host. chemokines are thought to be involved in the immunopathogenesis of leprosy, but few studies have investigated the expression of chemokine receptors on leukocytes of leprosy patients. in the present study, we evaluated 21 leprosy patients (m/f: 16/5) with ...201122002092
a lipopeptide facilitate induction of mycobacterium leprae killing in host cells.little is known of the direct microbicidal activity of t cells in leprosy, so a lipopeptide consisting of the n-terminal 13 amino acids lipopeptide (lipok) of a 33-kd lipoprotein of mycobacterium leprae, was synthesized. lipok activated m. leprae infected human dendritic cells (dcs) to induce the production of il-12. these activated dcs stimulated autologous cd4(+) or cd8(+) t cells towards type 1 immune response by inducing interferon-gamma secretion. t cell proliferation was also evident from ...201122132248
i've tried rattlesnake, frog legs and other exotic foods. are there any i should avoid? 201122059261
elimination of leprosy as a public health problem by 2000 ad: an epidemiological perspective.leprosy is caused by mycobacterium leprae and manifests as damage to the skin and peripheral nerves. the disease is dreaded because it causes deformities, blindness and disfigurement. worldwide, 2 million people are estimated to be disabled by leprosy. multidrug therapy is highly effective in curing leprosy, but treating the nerve damage is much more difficult. the world health assembly targeted to eliminate leprosy as a public health problem from the world by 2000. the objective of the review w ...201122145052
real-time pcr and high resolution melt analysis for rapid detection of mycobacterium leprae drug resistance mutations and strain types.drug resistance surveillance and strain typing of mycobacterium leprae are necessary to investigate ongoing transmission of leprosy in endemic regions. to enable wider implementation of these molecular analyses, novel real time-pcr-high resolution melt (rt-pcr-hrm) assays without allele specific primers or probes and post pcr sample handling were developed. for the detection of mutations within drug resistance determining regions (drdrs) of folp1, rpob and gyra, targets for dapsone, rifampicin a ...201122170923
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