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fractionation and analysis of mycobacterial proteins.the extraction and isolation of native bacterial proteins continue to be valuable technical pursuits in order to understand bacterial physiology, screen for virulence determinants, and describe antigens. in this chapter, methods for the manipulation of whole mycobacterial cells are described in detail. specifically, the concentration of spent culture filtrate media is described in order to permit separation of soluble, secreted proteins; several discrete separation techniques, including precipit ...201525779310
role of subunit exchange and electrostatic interactions on the chaperone activity of mycobacterium leprae hsp18.mycobacterium leprae hsp18, a major immunodominant antigen of m. leprae pathogen, is a small heat shock protein. previously, we reported that hsp18 is a molecular chaperone that prevents aggregation of different chemically and thermally stressed client proteins and assists refolding of denatured enzyme at normal temperature. we also demonstrated that it can efficiently prevent the thermal killing of e. coli at higher temperature. however, molecular mechanism behind the chaperone function of hsp1 ...201526098662
african histoplasmosis: the first report of an indigenous case in india.african histoplasmosis, caused by histoplasma capsulatum var. duboisii, is an invasive fungal infection endemic in central and west africa. cases seen outside africa are generally imported. we report a disseminated purely cutaneous form of this infection in an otherwise healthy person from kerala, in southern india.201525514986
association of tumor necrosis factor-alpha and interferon gamma gene polymorphisms and their plasma levels in leprosy, hiv and other peripheral neuropathies.mycobacterium leprae and human immunodeficiency virus (hiv) are causative agents known to be involved in nerve damage in leprosy and hiv-peripheral neuropathy (hiv-pn) respectively. among other peripheral neuropathies the most common is diabetic neuropathy, which is metabolically induced. the proinflammatory cytokines tnf-α and ifn-γ have been implicated in the pathogenesis of peripheral neuropathy. the association between the plasma levels of these cytokines and their single nucleotide polymorp ...201526431782
leprosy reactions in patients coinfected with hiv: clinical aspects and outcomes in two comparative cohorts in the amazon region, brazil.leprosy, caused by mycobacterium leprae, can lead to scarring and deformities. human immunodeficiency virus (hiv), a lymphotropic virus with high rates of replication, leads to cell death in various stages of infection. these diseases have major social and quality of life costs, and although the relevance of their comorbidity is recognized, several aspects are still not fully understood.201526029928
lupus and leprosy: beyond the coincidence.systemic lupus erythematous (sle) is an autoimmune disease that presents an increased susceptibility to infections which may trigger reactivation. disease flares have been mostly associated with parvovirus b19, cytomegalovirus, ebv and mycobacterium tuberculosis infections, but it is probable that many other agents may also induce innate and adaptive immune system stimulation including the production of autoantibodies as ana, anti ndna and anti-ß2-gpi mainly in lepromatous leprosy. mycobacterium ...201525412733
polymerase chain reaction detection of leishmania dna in skin biopsy samples in sri lanka where the causative agent of cutaneous leishmaniasis is leishmania donovani.leishmania donovani is the known causative agent of both cutaneous (cl) and visceral leishmaniasis in sri lanka. cl is considered to be under-reported partly due to relatively poor sensitivity and specificity of microscopic diagnosis. we compared robustness of three previously described polymerase chain reaction (pcr) based methods to detect leishmania dna in 38 punch biopsy samples from patients presented with suspected lesions in 2010. both, leishmania genus-specific jw11/jw12 kdna and litsr/l ...201526676321
mucocutaneous leishmaniasis caused by leishmania donovani infection in an indian man.leishmaniasis is a protozoal disease caused by species of leishmania. mucocutaneous leishmaniasis (mcl) involves the skin and mucosa. india is endemic for species such as leishmania donovani and leishmania major, which are responsible for visceral and cutaneous leishmaniasis, respectively. although mcl has been reported from india previously, the implicated pathogen was identified as l. donovani in only one case.201525557311
the draft genome of mycobacterium aurum, a potential model organism for investigating drugs against mycobacterium tuberculosis and mycobacterium leprae.mycobacterium aurum (m. aurum) is an environmental mycobacteria that has previously been used in studies of anti-mycobacterial drugs due to its fast growth rate and low pathogenicity. the m. aurum genome has been sequenced and assembled into 46 contigs, with a total length of 6.02mb containing 5684 annotated protein-coding genes. a phylogenetic analysis using whole genome alignments positioned m. aurum close to mycobacterium vaccae and mycobacterium vanbaalenii, within a clade related to fast-gr ...201527649868
comparison of four dna extraction methods for the detection of mycobacterium leprae from ziehl-neelsen-stained microscopic slides.the diagnosis of leprosy has been a challenge due to the low sensibility of the conventional methods and the impossibility of culturing the causative organism. in this study, four methods for mycobacterium leprae nucleic-acid extraction from ziehl-neelsen-stained slides (zns slides) were compared: phenol/chloroform, chelex 100 resin, and two commercial kits (wizard genomic dna purification kit and qiaamp dna mini kit).201526964809
presence of mycobacterium leprae dna and pgl-1 antigen in household contacts of leprosy patients from a hyperendemic area in brazil.leprosy is a highly infectious disease endemic to underdeveloped countries. in maranhão state, northeastern brazil, the hyperendemic rate of 56.11 cases/100,000 inhabitants increased the necessity of better understanding the epidemiological profile of this population, particularly regarding efficient methods for evaluating individuals residing with diagnosed patients to understand disease transmission and the risk of infection. in this study, we examined the percentage of contacts with positive ...201526600506
zoonotic leprosy in the southeastern united states.nine-banded armadillos (dasypus novemcinctus) are naturally infected with mycobacterium leprae and have been implicated in zoonotic transmission of leprosy. early studies found this disease mainly in texas and louisiana, but armadillos in the southeastern united states appeared to be free of infection. we screened 645 armadillos from 8 locations in the southeastern united states not known to harbor enzootic leprosy for m. leprae dna and antibodies. we found m. leprae-infected armadillos at each ...201526583204
validation of qpcr methods for the detection of mycobacterium in new world animal reservoirs.zoonotic pathogens that cause leprosy (mycobacterium leprae) and tuberculosis (mycobacterium tuberculosis complex, mtbc) continue to impact modern human populations. therefore, methods able to survey mycobacterial infection in potential animal hosts are necessary for proper evaluation of human exposure threats. here we tested for mycobacterial-specific single- and multi-copy loci using qpcr. in a trial study in which armadillos were artificially infected with m. leprae, these techniques were spe ...201526571269
rapid identification of mycobacterium leprae by polymerase chain reaction-restriction fragment length polymorphism analysis of the heat shock protein 65 gene from skin specimens. 201526521798
differential expression of solute carrier family 11a member 1 and inducible nitric oxide synthase 2 in skin biopsies from leprosy patients.leprosy is a chronic granulomatous infection caused by mycobacterium leprae, an intracellular parasite that resides within macrophages and cannot be eliminated effectively. solute carrier family 11a member 1 (slc11a1) and inducible nitric oxide synthase (inos), both expressed in macrophages, play major roles in host defense against several intracellular pathogens. however, the roles of these molecules in natural infection with m. leprae remain unknown.201526515838
longitudinal immune profiles in type 1 leprosy reactions in bangladesh, brazil, ethiopia and nepal.acute inflammatory reactions are a frequently occurring, tissue destructing phenomenon in infectious- as well as autoimmune diseases, providing clinical challenges for early diagnosis. in leprosy, an infectious disease initiated by mycobacterium leprae (m. leprae), these reactions represent the major cause of permanent neuropathy. however, laboratory tests for early diagnosis of reactional episodes which would significantly contribute to prevention of tissue damage are not yet available. althoug ...201526510990
current knowledge on mycobacterium leprae transmission: a systematic literature review.summary201526502685
leprosy mimicking psoriasis. 201526500993
could mycobacterium leprae infection be an occupational disease? a survey in healthcare workers from an endemic area in the amazonian region.a serologic survey was conducted to evaluate the prevalence of mycobacterium leprae infection among healthcare workers and associated factors. of 280 workers, 26 (9.3%) were positive using immunoglobulin m serology for pgl-i m. leprae antigen. exposure to leprosy patients in the workplace was significantly associated with seropositivity (p=.044).201526456726
genotyping of mycobacterium leprae strains from a region of high endemic leprosy prevalence in india.leprosy is still a major health problem in india which has the highest number of cases. multiple locus variable number of tandem repeat analysis (mlva) and single nucleotide polymorphism (snp) have been proposed as tools of strain typing for tracking the transmission of leprosy. however, empirical data for a defined population from scale and duration were lacking for studying the transmission chain of leprosy. seventy slit skin scrapings were collected from purulia (west bengal), miraj (maharash ...201526444583
new insights into the geographic distribution of mycobacterium leprae snp genotypes determined for isolates from leprosy cases diagnosed in metropolitan france and french territories.between 20 and 30 bacteriologically confirmed cases of leprosy are diagnosed each year at the french national reference center for mycobacteria. patients are mainly immigrants from various endemic countries or living in french overseas territories. we aimed at expanding data regarding the geographical distribution of the snp genotypes of the m. leprae isolates from these patients.201526441080
indigenous cases of leprosy (hansen's disease) in southern mississippi.hansen's disease or leprosy is a chronic infection of the skin and peripheral nerves caused by mycobacterium leprae. in the u.s., leprosy is mainly reported in immigrants, but indigenous leprosy cases have been also reported in this country, especially in semitropical southern states (i.e., texas, louisiana). the objective of this series of cases is to describe indigenous leprosy cases reported in southern mississippi (ms) during the period 2012-2014. information was collected from medical recor ...201526434167
performance of pcr-reverse blot hybridization assay for detection of rifampicin-resistant mycobacterium leprae.drug resistance in mycobacterium leprae is a significant problem in countries where leprosy is endemic. a sensitive, specific, and high-throughput reverse blot hybridization assay (reba) for the detection of genotypic resistance to rifampicin (rif) was designed and evaluated. it has been shown that resistance to rif in m. leprae involves mutations in the rpob gene encoding the -subunit of the rna polymerase. the pcr-reba simultaneously detects both 6 wild-type regions and 5 different mutations ( ...201526428919
update on the epidemiology, diagnosis, and treatment of leprosy.leprosy is an infectious disease that has now been reported for more than 2000 years. the leprosy elimination goal set by the world health organization (who), i.e. a global prevalence rate <1 patient per 10,000 population, was achieved in the year 2000, but more than 200,000 new case patients are still reported each year, particularly in india, brazil, and indonesia. leprosy is a specific infection: (i) it is a chronic infection primarily affecting the skin and peripheral nerves, (ii) mycobacter ...201526428602
a study of liver function tests in leprosy.leprosy is a chronic progressive granulomatous disease caused by mycobacterium leprae. hepatic involvement is seen in early stages of the disease. administration of the hepatotoxic drugs like rifampicin and dapsone may further deteriorate the liver function. the present study was undertaken to evaluate hepatic status by studying the various liver function tests in leprosy patients and compared to healthy controls. thirty untreated leprosy patients (18 multibacillary, 12 paucibacillary) with dura ...201526411248
b cells expressing il-10 mrna modulate memory t cells after dna-hsp65 immunization.in dna vaccines, the gene of interest is cloned into a bacterial plasmid that is engineered to induce protein production for long periods in eukaryotic cells. previous research has shown that the intramuscular immunization of balb/c mice with a naked plasmid dna fragment encoding the mycobacterium leprae 65-kda heat-shock protein (pcdna3-hsp65) induces protection against m. tuberculosis challenge. a key stage in the protective immune response after immunization is the generation of memory t cell ...201526397973
the essential role of cholesterol metabolism in the intracellular survival of mycobacterium leprae is not coupled to central carbon metabolism and energy production.mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and schwann cells. cholesterol is among the lipids with increased abundance in m. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. the present study investigated the capacity of m. leprae to acquire and metabolize cholesterol. in silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), th ...201526391209
influence of genetic ancestry on indel markers of nfkβ1, casp8, par1, il4 and cyp19a1 genes in leprosy patients.leprosy is an insidious infectious disease caused by the obligate intracellular bacteria mycobacterium leprae, and host genetic factors can modulate the immune response and generate distinct categories of leprosy susceptibility that are also influenced by genetic ancestry.201526367014
downregulation of phex in multibacillary leprosy patients: observational cross-sectional study.peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. the phosphate-regulating gene with homologies to endopeptidase on the x chromosome (phex) encodes a homonymous protein (phex) implicated in bone metabolism. phex/phex alterations may result in bone and cartilage lesions. phex expression is downregulated by intracellular mycobacterium leprae (m. leprae) in cultures of human schwann cells and osteoblasts. m. leprae in vivo effect on ph ...201526362198
human genetic ancestral composition correlates with the origin of mycobacterium leprae strains in a leprosy endemic population.recent reports have suggested that leprosy originated in africa, extended to asia and europe, and arrived in the americas during european colonization and the african slave trade. due to colonization, the contemporary colombian population is an admixture of native-american, european and african ancestries. because microorganisms are known to accompany humans during migrations, patterns of human migration can be traced by examining genomic changes in associated microbes. the current study analyze ...201526360617
common variants of opa1 conferring genetic susceptibility to leprosy in han chinese from southwest china.leprosy is an ancient chronic infection caused by mycobacterium leprae. onset of leprosy was highly affected by host nutritional condition and energy production, (partially) due to genomic loss and parasitic life style of m. leprae. the optic atrophy 1 (opa1) gene plays an essential role in mitochondria, which function in cellular energy supply and innate immunity.201526360011
inflammatory mediators of leprosy reactional episodes and dental infections: a systematic review.reactional episodes in leprosy are a result of complex interactions between the immune system, mycobacterium leprae, and predisposing factors, including dental infections. to determine the main inflammatory mediators in the immunopathological process of dental infections and leprosy reactions, we conducted a systematic review of primary literature published between 1996 and 2013. a three-stage literature search was performed (stage i, "leprosy reactions" and "inflammatory mediators"; stage ii, " ...201526339136
new players in the same old game: disturbance of group 2 innate lymphoid cells in hiv-1 and mycobacterium leprae co-infected patients.leprosy control is achieved through a fine-tuning of th1 and th2 immune response pattern balance. given the increasing epidemiological overlay of hiv and m. leprae infections, immune response in co-infected patients consists in an important contemporary issue. here we describe for the first time the innate lymphoid cells compartment in peripheral blood of leprosy and hiv/m. leprae co-infected patients, and show that co-infection increases group 2 innate lymphoid whilst decreasing group 1 innate ...201526335023
laryngeal involvement causing dysphonia in a 29 year old nursing mother with lepromatous leprosy.leprosy is a granulomatous disease that mainly affects the skin and peripheral nerves. it is caused by infection with mycobacterium leprae or mycobacterium lepromatosus. in most instances, diagnosis of leprosy can easily be made based on the clinical signs and symptoms. however, when patients present with atypical features, clinical diagnosis can be a challenge. we report a case of a nursing mother with lepromatous leprosy who presented with dysphonia and skin lesions initially thought to be a d ...201526327983
emergence of primary drug resistance to rifampicin in mycobacterium leprae strains from leprosy patients in india. 201526314915
diffuse lepromatous leprosy due to mycobacterium lepromatosis in quintana roo, mexico.a 43-year-old woman of mayan origin from quintana roo, mexico, was diagnosed with diffuse lepromatous leprosy. the etiologic bacillus was determined to be mycobacterium lepromatosis instead of mycobacterium leprae. this case likely represents the first report of this leprosy form and its agent in the southeastern tip of mexico.201526311856
gene association with leprosy: a review of published data.leprosy is a chronic infectious disease caused by an obligate intracellular bacterium known as mycobacterium leprae. exposure to the bacillus is necessary, but this alone does not mean an individual will develop clinical symptoms of the disease. in recent years, several genes have been associated with leprosy and the innate immune response pathways converge on the main hypothesis that genes are involved in the susceptibility for the disease in two distinct steps: for leprosy per se and in the de ...201526793196
expression of nucleotide-oligomerization domain (nod) and related genes in mouse tissues infected with mycobacterium leprae.the nucleotide-oligomerization domain (nod) is an important molecule involved in host defense against bacterial infection. to study the role of nods in the host response to mycobacterium leprae, we measured the mrna levels of nods and related genes in infected mouse tissues. the mrna expression of nod1, nod2, caspase-1 and asc was increased in mouse footpads. whereas nod2 expression in macrophages was increased at 2 and 24 h post-infection with m. leprae, there was no expression of nod1 at these ...201526770186
draft genome sequence of new leprosy agent mycobacterium lepromatosis.mycobacterium lepromatosis is a newly discovered cause of leprosy. here, we present a near-complete genome of m. lepromatosis from strain fj924 obtained from a patient who died of leprosy. the genome contained 3,215,823 nucleotides and matched ~87% with the mycobacterium leprae genome. this genome is likely the smallest of all mycobacterial genomes known to date.201525999555
surgical treatment of type i neuritis in a teenage boy with borderline tuberculoid leprosy.exacerbation of the immune response against mycobacterium leprae can lead to neuritis, which is commonly treated via immunosuppression with corticosteroids. early neurolysis may be performed concurrently, especially in young patients with a risk of functional sequelae. we report the case of a young patient experienced intense pain in the left elbow one year after the treatment of tuberculoid-tuberculoid leprosy. the pain was associated with paresthesias in the ulnar edge and left ulnar claw. aft ...201525992943
correlation between central memory t cell expression and proinflammatory cytokine production with clinical presentation of multibacillary leprosy relapse.despite the efficacy of multidrug therapy, surviving mycobacterium leprae causes relapse in some leprosy patients, and these patients present signs and symptoms of disease after healing. this study focused on the cellular immune response in relapsed multibacillary patients but also included non-relapsed multibacillary cured individuals, newly diagnosed and untreated multibacillary patients, paucibacillary patients just before the beginning of treatment, and voluntary healthy individuals for comp ...201525992795
drug resistance in mycobacterium leprae from patients with leprosy in china.previous studies of drug resistance have shown that mutations in the drug resistance-determining region (drdr) in the folp1, rpob and gyra genes of mycobacterium leprae are responsible for resistance to dapsone, rifampin and ofloxacin, respectively.201525991507
multibacillary leprosy in an active duty military member. 201525989473
identification of functional candidates amongst hypothetical proteins of mycobacterium leprae br4923, a causative agent of leprosy.mycobacterium leprae is an intracellular obligate parasite that causes leprosy in humans, and it leads to the destruction of peripheral nerves and skin deformation. here, we report an extensive analysis of the hypothetical proteins (hps) from m. leprae strain br4923, assigning their functions to better understand the mechanism of pathogenesis and to search for potential therapeutic interventions. the genome of m. leprae encodes 1604 proteins, of which the functions of 632 are not known (hps). in ...201525985983
osteological, biomolecular and geochemical examination of an early anglo-saxon case of lepromatous leprosy.we have examined a 5th to 6th century inhumation from great chesterford, essex, uk. the incomplete remains are those of a young male, aged around 21-35 years at death. the remains show osteological evidence of lepromatous leprosy (ll) and this was confirmed by lipid biomarker analysis and ancient dna (adna) analysis, which provided evidence for both multi-copy and single copy loci from the mycobacterium leprae genome. genotyping showed the strain belonged to the 3i lineage, but the great chester ...201525970602
attenuation of experimental asthma by mycobacterial protein combined with cpg requires a tlr9-dependent ifn-γ-ccr2 signalling circuit.allergic asthma is a chronic pulmonary disease characterized by a th2 inflammatory response. the modulation of a th2 immune response based on immune deviation to a th1 pattern or induction and migration of regulatory t cells to the lungs constitutes one of the major therapeutic approaches that is being investigated for the treatment of allergic asthma. the potentials of mycobacterium leprae 65-kd heat-shock protein or toll-like receptor 9 ligand (cpg oligodeoxynucleotides) as immune modulators f ...201525944185
diagnosis and treatment of leprosy type 1 (reversal) reaction.leprosy is a chronic granulomatous infection caused by the organism mycobacterium leprae that primarily affects the skin and peripheral nerves. leprosy has several distinct clinical presentations ranging from moderate to severe, with the extent of disease generally depending on the host's immune response to the infection. treatment typically involves antimicrobials (eg, clofazimine, dapsone, rifampin). once treatment is started, an important aspect of patient care is the recognition of possible ...201525942024
vasculitis and infectious diseases.vasculitis usually presents without a well-known underline cause (idiopathic vasculitis), nevertheless, it is sometimes possible to find out one or more causative agents (secondary vasculitis). nowadays, thanks to the increasing amount of precise diagnostic tools, a piece of idiopathic vasculitis is reclassified as associated with probable etiology, which can be set off by several factors, such as infections. infections are considered to be the most common cause of secondary vasculitis. virtuall ...201525876145
leprosy: a 'common' and curable cause of peripheral neuropathy with skin lesions.leprosy (or hansen's disease) is a curable chronic infectious disease caused by the acid-fast bacillus mycobacterium leprae. while leprosy remains one of the most common causes of neuropathy worldwide, its rarity in the uk means that many doctors are unfamiliar with the typical clinical features. this is problematic because early recognition and treatment is vital in order to minimise disease-related complications such as nerve injury. we describe a 75-year-old man who presented with multiple mo ...201525874829
computational modelling of dapsone interaction with dihydropteroate synthase in mycobacterium leprae; insights into molecular basis of dapsone resistance in leprosy.the molecular basis for determination of resistance to anti-leprosy drugs is the presence of point mutations within the genes of mycobacterium leprae (m. leprae) that encode active drug targets. the downstream structural and functional implications of these point mutations on drug targets were scarcely studied. in this study, we utilized computational tools to develop native and mutant protein models for 5 point mutations at codon positions 53 and 55 in 6-hydroxymethyl-7, 8-dihydropteroate synth ...201525833404
insight into the evolution and origin of leprosy bacilli from the genome sequence of mycobacterium lepromatosis.mycobacterium lepromatosis is an uncultured human pathogen associated with diffuse lepromatous leprosy and a reactional state known as lucio's phenomenon. by using deep sequencing with and without dna enrichment, we obtained the near-complete genome sequence of m. lepromatosis present in a skin biopsy from a mexican patient, and compared it with that of mycobacterium leprae, which has undergone extensive reductive evolution. the genomes display extensive synteny and are similar in size (∼3.27 mb ...201525831531
interaction of mycobacterium leprae with the hacat human keratinocyte cell line: new frontiers in the cellular immunology of leprosy.leprosy is a chronic granulomatous disease caused by mycobacterium leprae affecting the skin and peripheral nerves. despite m. leprae invasion of the skin and keratinocytes importance in innate immunity, the interaction of these cells in vitro during m. leprae infection is poorly understood. conventional and fluorescence optical microscopy, transmission electronic microscopy, flow cytometry and elisa were used to study the in vitro interaction of m. leprae with the hacat human keratinocyte cell ...201525828729
borderline tuberculoid leprosy in childhood onset systemic lupus erythematosus patient.leprosy is a contagious and chronic systemic granulomatous disease caused by the bacillus mycobacterium leprae. to our knowledge, no case of leprosy in a childhood-onset systemic lupus erythematosus (c-sle) patient has been reported. for a period of 31 years, 312 c-sle patients were followed at the pediatric rheumatology unit of our university hospital. one of them (0.3%) had tuberculoid leprosy skin lesions during the disease course and is here reported. a 10-year-old boy from northwest of braz ...201526113359
use of approximate bayesian computation to assess and fit models of mycobacterium leprae to predict outcomes of the brazilian control program.hansen's disease (leprosy) elimination has proven difficult in several countries, including brazil, and there is a need for a mathematical model that can predict control program efficacy. this study applied the approximate bayesian computation algorithm to fit 6 different proposed models to each of the 5 regions of brazil, then fitted hierarchical models based on the best-fit regional models to the entire country. the best model proposed for most regions was a simple model. posterior checks foun ...201526107951
it is time to review concepts on renal involvement in leprosy: pre- and post-treatment evaluation of 189 patients.functional and morphological renal lesions have been widely described in leprosy for decades. nevertheless few studies have assessed renal function pre- and during treatment after the advent of multidrug therapy (mdt).201526099294
histoid leprosy: review of the literature.leprosy is a chronic granulomatous inflammation primarily of the peripheral nervous system, skin, and reticuloendothelial system caused by mycobacterium leprae. it presents clinically as an erythematous or hypopigmented anesthetic patch and a thickened and/or tender cutaneous nerve trunk. leprosy is also called hansen disease. leprosy is a great imitator of other skin diseases, and it can present with different morphological lesions, which is why an expert eye is needed to diagnose it. one of th ...201526094829
the immunology and inflammatory responses of human melanocytes in infectious diseases.melanin is a canonical and major defense molecule in invertebrates but its role in mammalian immunity remains unexplored. in contrast, several recent studies have highlighted the emerging innate immune activities of human melanin-producing cells which can sense and respond to bacterial and viral infections. indeed, the skin is a major portal of entry for pathogens such as arboviruses (chikungunya, dengue) and bacteria (mycobacterium leprae, leptospira spirochetes). melanocytes of the epidermis c ...201526092350
a historical overview of leprosy epidemiology and control activities in amazonas, brazil.leprosy is an ancient infectious disease caused by mycobacterium leprae. according to comparative genomics studies, this disease originated in eastern africa or the near east and spread with successive human migrations. the europeans and north africans introduced leprosy into west africa and the americas within the past 500 years. in brazil, this disease arrived with the colonizers who disembarked at the first colonies, rio de janeiro, salvador and recife, at the end of the sixteenth century, af ...201526061371
pure neuritic leprosy presenting as ulnar nerve neuropathy: a case report of electrodiagnostic, radiographic, and histopathological findings.hansen's disease, or leprosy, is a chronic infectious disease with many manifestations. though still a major health concern and leading cause of peripheral neuropathy in the developing world, it is rare in the united states, with only about 150 cases reported each year. nevertheless, it is imperative that neurosurgeons consider it in the differential diagnosis of neuropathy. the causative organism is mycobacterium leprae, which infects and damages schwann cells in the peripheral nervous system, ...201526047418
il-27 suppresses antimicrobial activity in human leprosy.the mechanisms by which intracellular pathogens trigger immunosuppressive pathways are critical for understanding the pathogenesis of microbial infection. one pathway that inhibits host defense responses involves the induction of type i interferons and subsequently il-10, yet the mechanism by which type i ifn induces il-10 remains unclear. our studies of gene expression profiles derived from leprosy skin lesions suggested a link between il-27 and the ifn-β induced il-10 pathway. here, we demonst ...201526030183
alterations to antigen-specific immune responses before and after multidrug therapy of leprosy.this study evaluated the impact of leprosy multidrug therapy (mdt) on cell-mediated immunity (cmi) and antibody responses at diagnosis in untreated paucibacillary (pb) (n=15) and multibacillary (mb) patients (n=15) using a panel of mycobacterium leprae recombinant antigens (rmls) (cmi: 46f, ml0276, ml2055, leprosy idri diagnostic 1 [lid-1], and ml2629, as negative control; serology: lid-1, 46f, 92f, and 33f, as negative control, and phenolic glycolipid i [pgl-i]) and at 2 time points after mdt ( ...201526233487
human-armadillo interaction in ceará, brazil: potential for transmission of mycobacterium leprae.several factors suggest that armadillos present an important risk for human leprosy infection. this study uses semi-structured interviews to better illustrate how human interaction with armadillos may increase the risk of leprosy transmission. the participants were all residents of the state of ceará, in northeastern brazil, all acknowledged contact with armadillos either through hunting, through cooking, or through consumption of its meat. this study raises important issues about contact betwee ...201526232656
leprosy agents mycobacterium lepromatosis and mycobacterium leprae in mexico: a clarification. 201526224842
activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated mycobacterium leprae induces decreased level of il-12p70 in lepromatous leprosy.dendritic cells (dcs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. studies on the interaction of monocyte-derived dcs (mo-dcs) using mycobacterium leprae in leprosy patients are rare. the present study demonstrated that the differentiation of mos to dcs was similar in all forms of leprosy compared to normal healthy individuals. in vitro stimulation of immature mo-dcs with sonicated m. leprae induced variable degrees of dc maturation a ...201526222022
quantiferon-gold tuberculosis test cannot detect latent tuberculosis in patients with leprosy.five of 10 paucibacillary leprosy patients were quantiferon gold (q-g) positive with negative chest x-rays. forty multibacillary leprosy patients were negative. reports have shown 100% cross-reactivity of esat6 and cfp10 between mycobacterium leprae and mycobacterium tuberculosis. the q-g test cannot detect latent tuberculosis in patients with leprosy.201526209684
primary motor cortex representation of handgrip muscles in patients with leprosy.leprosy is an endemic infectious disease caused by mycobacterium leprae that predominantly attacks the skin and peripheral nerves, leading to progressive impairment of motor, sensory and autonomic function. little is known about how this peripheral neuropathy affects corticospinal excitability of handgrip muscles. our purpose was to explore the motor cortex organization after progressive peripheral nerve injury and upper-limb dysfunction induced by leprosy using noninvasive transcranial magnetic ...201526203653
asymptomatic leprosy infection among blood donors may predict disease development and suggests a potential mode of transmission.blood donor samples (1,007) were assessed for anti-phenolic glycolipid 1 (pgl-1) igm antibodies and mycobacterium leprae dna presence, which had 3.8% and 0.3% positivity, respectively. after a 5-year follow-up period, six individuals with positive markers developed leprosy, raising the hypothesis that asymptomatic infection among blood donors may be an undisclosed mode of leprosy transmission via transfusion.201526202111
characterization of mycobacterium leprae genotypes in china--identification of a new polymorphism c251t in the 16s rrna gene.leprosy continues to be prevalent in some mountainous regions of china, and genotypes of leprosy strains endemic to the country are not known. mycobacterium lepromatosis is a new species that was discovered in mexico in 2008, and it remains unclear whether this species exists in china. here, we conducted pcr- restriction fragment length polymorphism (rflp) analysis to classify genotypes of 85 dna samples collected from patients from 18 different provinces. all 171 dna samples from skin biopsies ...201526196543
the curse of the nine-banded armadillo: case report and review.hansen's disease (leprosy) is an ancient condition characterized by hypopigmented patches that progress to become plaques with hypoesthesia. several case reports suggest that armadillos may be a source of mycobacterium leprae for clinical cases, and contact with armadillos has been shown to be a significant risk factor in several case-control studies. early diagnosis and treatment result in an excellent prognosis and provide an effective means to prevent complications of peripheral nerve injury, ...201526126264
interaction of atp with a small heat shock protein from mycobacterium leprae: effect on its structure and function.adenosine-5'-triphosphate (atp) is an important phosphate metabolite abundantly found in mycobacterium leprae bacilli. this pathogen does not derive atp from its host but has its own mechanism for the generation of atp. interestingly, this molecule as well as several antigenic proteins act as bio-markers for the detection of leprosy. one such bio-marker is the 18 kda antigen. this 18 kda antigen is a small heat shock protein (hsp18) whose molecular chaperone function is believed to help in the g ...201525811190
skin imprinting in silica plates: a potential diagnostic methodology for leprosy using high-resolution mass spectrometry.leprosy is a chronic infectious disease caused by mycobacterium leprae, which primarily infects macrophages and schwann cells, affecting skin and peripheral nerves. clinically, the most common form of identification is through the observation of anesthetic lesions on skin; however, up to 30% of infected patients may not present this clinical manifestation. currently, the gold standard diagnostic test for leprosy is based on skin lesion biopsy, which is invasive and presents low sensibility for s ...201525785304
ancient dna analysis - an established technique in charting the evolution of tuberculosis and leprosy.many tuberculosis and leprosy infections are latent or paucibacillary, suggesting a long time-scale for host and pathogen co-existence. palaeopathology enables recognition of archaeological cases and pcr detects pathogen ancient dna (adna). mycobacterium tuberculosis and mycobacterium leprae cell wall lipids are more stable than adna and restrict permeability, thereby possibly aiding long-term persistence of pathogen adna. amplification of adna, using specific pcr primers designed for short frag ...201525773651
m. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. we previously identified the membrane attack complex (mac) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. here, we determined the contribution of the mac to nerve damage caused by mycobacterium leprae and its components in mouse. furthermore, we studied the association between mac and the key m. leprae component lipoarabi ...201525772973
immunohistochemical analysis of the expression of cellular transcription nfκb (p65), ap-1 (c-fos and c-jun), and jak/stat in leprosy.leprosy is a disease whose clinical spectrum depends on the cytokine patterns produced during the early stages of the immune response. the main objective of this study was to describe the activation pattern of cellular transcription factors and to correlate these factors with the clinical forms of leprosy. skin samples were obtained from 16 patients with the tuberculoid (tt) form and 14 with the lepromatous (ll) form. the histologic sections were immunostained with anti-c-fos and anti-c-jun mono ...201525771902
mathematical modelling of leprosy and its control.leprosy or hansen's disease is an infectious disease caused by the bacterium mycobacterium leprae. the annual number of new leprosy cases registered worldwide has remained stable over the past years at over 200,000. early case finding and multidrug therapy have not been able interrupt transmission completely. elimination requires innovation in control and sustained commitment. mathematical models can be used to predict the course of leprosy incidence and the effect of intervention strategies. tw ...201525765193
report of rpob mutation in clinically suspected cases of drug resistant leprosy: a study from eastern india.the current strategy for leprosy control depends mainly on early case detection and providing the recommended multidrug therapy (mdt) dosage. understanding the molecular mechanisms of drug resistance to each of these drugs is essential in providing effective treatment and preventing the spread of resistant strains in the community. the progress of molecular biology research provides a very efficient opportunity for the diagnosis of drug resistance by in vitro method.201525751332
clinical manifestations of leprosy after bcg vaccination: an observational study in bangladesh.although bcg is used as a vaccine against tuberculosis, it also protects against leprosy. previous evaluation over 18 years of an intervention of two doses bcg for 3536 household contacts of leprosy patients showed that 28 (23%) out of 122 contacts diagnosed with leprosy, developed symptoms 2-10 months after vaccination. this study describes contacts of leprosy patients in bangladesh who developed leprosy within 12 weeks after receiving a single bcg dose.201525701674
a migration-driven model for the historical spread of leprosy in medieval eastern and central europe.leprosy was rare in europe during the roman period, yet its prevalence increased dramatically in medieval times. we examined human remains, with paleopathological lesions indicative of leprosy, dated to the 6th-11th century ad, from central and eastern europe and byzantine anatolia. analysis of ancient dna and bacterial cell wall lipid biomarkers revealed mycobacterium leprae in skeletal remains from 6th-8th century northern italy, 7th-11th century hungary, 8th-9th century austria, the slavic gr ...201525680828
computational simulation techniques to understand rifampicin resistance mutation (s425l) of rpob in m. leprae.mycobacterium leprae, the etiologic agent of leprosy, is non-cultivable in vitro. consequently, the assessment of antibiotic activity against m. leprae hinge mainly upon the time consuming mouse footpad system. as m. leprae develops resistance against most of the drugs, the evolution of new long acting antimycobacterial compounds stand in need for leprosy control. the rpob of m. leprae is the target of antimycobacterial drug, rifampicin. recently, cases were reported that rpob mutation (s425l) b ...201525676141
association of tnf -1031 c/c as a potential protection marker for leprosy development in amazonas state patients, brazil.polymorphisms present in the tnf promoter region has shown to influence the gene transcription. leprosy displays different clinical manifestations according to the immune responses of the individual infected with mycobacterium leprae. in this study, we evaluated the single nucleotide polymorphisms (snps) -238 g/a (rs361525), -308 g/a (rs1800629), -857 c/t (rs1799724), -863 a/c (rs1800630) and -1031 t/c (rs1799964) in the promoter region of the tnf to see whether these snps influence host-suscept ...201525636570
the role of erbb2 gene polymorphisms in leprosy susceptibility.mycobacterium leprae infects skin and peripheral nerves causing deformities and disability. the m. leprae bacterium binds to erbb2 on the schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. polymorphisms at the erbb2 gene were previously investigated as genetic risk factors for leprosy in two brazilian populations but with inconsistent results. herein we extend the analysis of erbb2 variants to a third geographically distinct population in braz ...201525636184
evaluation of a low-density hydrogel microarray technique for mycobacterial species identification.in addition to the obligatory pathogenic species of the mycobacterium tuberculosis complex and mycobacterium leprae, the genus mycobacterium also includes conditionally pathogenic species that in rare cases can lead to the development of nontuberculous mycobacterial diseases. because tuberculosis and mycobacteriosis have similar clinical signs, the accurate identification of the causative agent in a clinical microbiology laboratory is important for diagnostic verification and appropriate treatme ...201525609722
human leukocyte antigen class i and class ii alleles are associated with susceptibility and resistance in borderline leprosy patients from southeast brazil.evidence suggests that human leukocyte antigen (hla) alleles influence the host immune response against mycobacterium leprae. however, the association between hla alleles and borderline (b) leprosy has not been studied. the aim of this study was to determine whether hla class i and ii molecules are associated with susceptibility or resistance to b leprosy including borderline-tuberculoid (bt), borderline-borderline (bb), and borderline-lepromatous (bl).201525605482
molecular mimicry between mycobacterium leprae proteins (50s ribosomal protein l2 and lysyl-trna synthetase) and myelin basic protein: a possible mechanism of nerve damage in leprosy.autoantibodies against various components of host are known to occur in leprosy. nerve damage is the primary cause of disability associated with leprosy. the aim of this study was to detect the level of autoantibodies and lympho-proliferative response against myelin basic protein (mbp) in leprosy patients (lps) and their correlation with clinical phenotypes of lps. further, probable role of molecular mimicry in nerve damage of lps was investigated. we observed significantly high level of anti-mb ...201525576930
biosynthesis of cell envelope-associated phenolic glycolipids in mycobacterium marinum.phenolic glycolipids (pgls) are polyketide synthase-derived glycolipids unique to pathogenic mycobacteria. pgls are found in several clinically relevant species, including various mycobacterium tuberculosis strains, mycobacterium leprae, and several nontuberculous mycobacterial pathogens, such as m. marinum. multiple lines of investigation implicate pgls in virulence, thus underscoring the relevance of a deep understanding of pgl biosynthesis. we report mutational and biochemical studies that in ...201525561717
bacterial-induced cell reprogramming to stem cell-like cells: new premise in host-pathogen interactions.bacterial pathogens employ a myriad of strategies to alter host tissue cell functions for bacterial advantage during infection. recent advances revealed a fusion of infection biology with stem cell biology by demonstrating developmental reprogramming of lineage committed host glial cells to progenitor/stem cell-like cells by an intracellular bacterial pathogen mycobacterium leprae. acquisition of migratory and immunomodulatory properties of such reprogrammed cells provides an added advantage for ...201525541240
genome-wide screening of mrna expression in leprosy patients.leprosy, an infectious disease caused by mycobacterium leprae, affects millions of people worldwide. however, little is known regarding its molecular pathophysiological mechanisms. in this study, a comprehensive assessment of human mrna was performed on leprosy skin lesions by using dna chip microarrays, which included the entire spectrum of the disease along with its reactional states. sixty-six samples from leprotic lesions (10tt, 10bt, 10bb, 10bl, 4ll, 14r1, and 10r2) and nine skin biopsies f ...201526635870
maldi imaging reveals lipid changes in the skin of leprosy patients before and after multidrug therapy (mdt).leprosy still represents a health problem in several countries. affecting skin and peripheral nerves, it may lead to permanent disabilities. disturbances on skin lipid metabolism in leprosy were already observed; however, the localization and distribution of lipids could not be accessed. the role of lipids on infectious disease has been fully addressed only recently, as they directly influence immune response. matrix-assisted laser desorption/ionization imaging mass spectrometry provides a power ...201526634971
comparative evaluation of pcr amplification of rlep, 16s rrna, rpot and sod a gene targets for detection of m. leprae dna from clinical and environmental samples.pcr assay is a highly sensitive, specific and reliable diagnostic tool for the identification of pathogens in many infectious diseases. genome sequencing mycobacterium leprae revealed several gene targets that could be used for the detection of dna from clinical and environmental samples. the pcr sensitivity of particular gene targets for specific clinical and environmental isolates has not yet been established. the present study was conducted to compare the sensitivity of rlep, rpot, sod a and ...201526655199
association of the lrrk2 genetic polymorphisms with leprosy in han chinese from southwest china.leprosy is a chronic infectious and neurological disease that is caused by infection of mycobacterium leprae (m. leprae). a recent genome-wide association study indicated a suggestive association of lrrk2 genetic variant rs1873613 with leprosy in chinese population. to validate this association and further identify potential causal variants of lrrk2 with leprosy, we genotyped 13 lrrk2 variants in 548 leprosy patients and 1078 healthy individuals from yunnan province and (re-)analyzed 3225 han ch ...201525521227
type 1 reaction in leprosy: a model for a better understanding of tissue immunity under an immunopathological condition.type 1 reaction (t1r) or reversal reaction is the leading cause of physical disabilities and deformities in leprosy. leprosy patients, even after being considered cured and released from treatment, may suffer from reactional episodes for long periods of time. early diagnosis is a great challenge for effectively treating and managing t1r. there is an urgent need to identify the most significant biomarkers to prevent recurrent t1r and to differentiate late t1r from relapse. t1r continues to be tre ...201525666357
protecting people against leprosy: chemoprophylaxis and immunoprophylaxis.elimination of leprosy cannot be achieved by multidrug therapy alone, and new tools are needed to prevent leprosy. a randomized controlled trial with chemoprophylaxis for contacts of leprosy patients using a single dose of rifampicin (sdr) has shown an overall protective effect of approximately 60%, effective in the first 2 years after the intervention. when a contact who previously received bacillus calmette-guérin (bcg) vaccination also receives sdr, the protective effect is additive, approxim ...201525432807
immunology of leprosy and diagnostic challenges.leprosy, caused by noncultivable mycobacterium leprae (ml), has varied manifestations, which are associated with the host immune responses. the dermal involvement is accompanied by peripheral nerve damage, which leads to sensory motor loss and deformities. both innate and acquired immune responses are involved. the main cell to be compromised is the cd4 + t helper cell, which shows antigen specific unresponsiveness to only ml and not to other common antigens in the bacilliferous generalized lepr ...201525432814
indeterminate leprosy and lepromatous index case: four cases in the same family.leprosy is a chronic infectious disease caused by mycobacterium leprae, which primarily affects the skin and peripheral nerves. brazil remains as the country with the second largest number of cases in the world. we report the case of three patients diagnosed with indeterminate leprosy in the same family. two patients were hiv positive. an active search led to the discovery of the index case. it was crucial to persist in the search of the index case. this report shows how important it is to teach ...201524346893
first genetic evidence of leprosy in early medieval austria.leprosy used to be a widespread, dreaded disease in europe during the middle ages, and it still remains an important health problem in some parts of the world today. herein, we present data on the earliest 'austrian' (an adult female from the early medieval period) proven to have suffered from leprosy. manifestations of the disease were first identified during a systematic screening of pathological changes in skeletons recovered from an archaeological site in pottenbrunn (lower austria). in the ...201525007893
cxcl10, mcp-1, and other immunologic markers involved in neural leprosy.nerve damage in leprosy can be directly induced by mycobacterium leprae in the early stages of infection, however, immunomediated mechanisms add gravity to the impairment of neural function in symptomatic periods of the disease. this study investigated the immunohistochemical expression of immunomarkers involved in the pathogenic mechanisms of leprosy nerve damage. these markers selected were cxcl10, ccl2 chemokines and immunomarkers as cd3, cd4, cd8, cd45ra, cd45ro, cd68, hla-dr, and metallopro ...201525221954
a report of rifampin-resistant leprosy from northern and eastern india: identification and in silico analysis of molecular interactions.presence of point mutations within the drug resistance determining regions of mycobacterium leprae (m. leprae) genome confers molecular basis of drug resistance to dapsone, rifampin and ofloxacin in leprosy. this study is focused on the identification of mutations within the rpob gene region of m. leprae that are specific for rifampin interaction, and further in silico analysis was carried out to determine the variations in the interactions. dna and rna were isolated from slit skin scrapings of ...201525201810
benefits and limitations of fine needle aspiration cytology in the diagnosis and classification of leprosy in primary and secondary healthcare settings.the goal of the world health organization (who) is to eliminate leprosy as a public health problem. this will only be possible when all patients are detected and cured using multidrug therapy, which requires accurate diagnosis prior to treatment. the objective of this study was to evaluate the possibility of the diagnosis of leprosy lesions by fine needle aspiration cytology according to a modification of the ridley-jopling scale, as it can be used in primary and secondary healthcare centres, es ...201525196453
carbohydrate-dependent binding of langerin to sodc, a cell wall glycoprotein of mycobacterium leprae.langerhans cells participate in the immune response in leprosy by their ability to activate t cells that recognize the pathogen, mycobacterium leprae, in a langerin-dependent manner. we hypothesized that langerin, the distinguishing c-type lectin of langerhans cells, would recognize the highly mannosylated structures in pathogenic mycobacterium spp. the coding region for the extracellular and neck domain of human langerin was cloned and expressed to produce a recombinant active trimeric form of ...201525422308
case for diagnosis.hansen's disease is a chronic infecto-contagious disease caused by mycobacterium leprae. the bacillus prefers low-temperature areas and the nose is usually the initial site of lesions. transmission of the bacilli occurs by nasal and oropharyngeal secretions, and through solutions of continuity of the skin and/or mucosae. nasal manifestations are found in the later stages of the disease.201525184933
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