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cd4+cd25+ t regs with acetylated foxp3 are associated with immune suppression in human leprosy.leprosy is a chronic human disease that results from infection of mycobacterium leprae. t reg cells have been shown to have important implications in various diseases. however, in leprosy, it is still unclear whether t regs can mediate immune suppression during progression of the disease. in the present study, we have proposed the putative mechanism leading to high proportion of t reg cells and investigated its significance in human leprosy. high levels of tgf-β followed by adaptation of foxp3(+ ...201323911408
the eradication of leprosy: molecular modeling techniques for novel drug discovery.leprosy is a slowly progressing bacterial infection caused by mycobacterium leprae. the world health organization recommended multidrug therapy (mdt) which is extremely effective and halts the progress of the disease. even though the objective of eliminating leprosy as a public health problem has been achieved successfully, leprosy is not yet eradicated. furthermore, the long-term use of mdt results in single- and multidrug resistance. therefore, there is still a need for new drug discovery for ...201323924296
leprous neuropathy.leprous neuropathy, which is due to infection of nerve cells by mycobacterium leprae, still affects millions of people in many developing countries. the clinical and pathological manifestations are determined by the natural resistance of the host to invasion of m. leprae. failure of early detection of leprosy often leads to severe disability in spite of eradication of mycobacterium at a later date. in the lepromatous type, bacilli are easily found in the skin and in nerve cells including schwann ...201323931798
insights into ancient leprosy and tuberculosis using metagenomics.leprosy and tuberculosis were widespread in the past and remain significant diseases today. comparison of ancient and modern genomes of mycobacterium leprae and mycobacterium tuberculosis gives insight into their evolution and a calibration of the timescale for observed changes. recently, whole genome sequencing has revealed genotypes and mixed-strain infections.201323932433
leprosy and hepatitis b coinfection in southern brazil.to investigate the association of leprosy with hepatitis b virus (hbv) infection, as yet unknown for south brazil, we assessed hepatitis b virus coinfection in 199 south brazilian leprosy patients (119 lepromatous, 15 tuberculoid, 30 borderline, 12 undetermined and 23 unspecified) and in 681 matched blood donors by screening for the hepatitis b virus markers hbsag and anti-hbc, using elisa. positive samples were retested and anti-hbc+ only samples were tested for the hepatitis b surface antibody ...201423933408
leprosy association with low masp-2 levels generated by masp2 haplotypes and polymorphisms flanking map19 exon 5.the gene masp2 (mannan-binding lectin (mbl)-associated serine protease 2) encodes two proteins, masp-2 and map19 (mbl-associated protein of 19 kda), bound in plasma to mbl and ficolins. the binding of mbl/masp-2 and ficolin/masp-2 complexes to microorganisms activates the lectin pathway of complement and may increase the ingestion of intracellular pathogens such as mycobacterium leprae.201323935922
haplotypes of the il10 gene as potential protection factors in leprosy patients.leprosy is an infectious disease caused by mycobacterium leprae characterized by dermatoneurological signs and symptoms that has a large number of new cases worldwide. several studies have associated interleukin 10 with susceptibility/resistance to several diseases. we investigated haplotypes formed by three single nucleotide polymorphisms (snps) located in the il10 gene (a-1082g, c-819t, and c-592a) in order to better understand the susceptibility to and severity of leprosy in an admixed northe ...201323966553
new findings in the pathogenesis of leprosy and implications for the management of leprosy.this review focuses on recent work in leprosy pathogenesis. new research of both innate and adaptive immune responses to mycobacterium leprae is described. the proposition that mycobacterium lepromatosis is a new species causing leprosy is discussed.201323982232
rifampicin-resistant mycobacterium leprae in an elderly leprosy patient in the people's republic of china.the reported number of registered leprosy patients worldwide declined with the introduction of multidrug therapy. however, the emergence of rifampicin resistance in leprosy patients engenders difficulties for an individual patient, and its dissemination could pose a threat to leprosy control. this study reports an elderly patient who was diagnosed with rifampicin-resistant lepromatous leprosy. this case indicates that inadequate treatment and poor compliance may eventually result in rifampicin r ...201323986632
the ubiquitin ligase parkin mediates resistance to intracellular pathogens.ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen mycobacterium tuberculosis. however, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. the parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (park2) lead to increased susceptibility ...201324005326
lrrk2 and ripk2 variants in the nod 2-mediated signaling pathway are associated with susceptibility to mycobacterium leprae in indian populations.in recent years, genome wide association studies have discovered a large number of gene loci that play a functional role in innate and adaptive immune pathways associated with leprosy susceptibility. the immunological control of intracellular bacteria m. leprae is modulated by nod2-mediated signaling of th1 responses. in this study, we investigated 211 clinically classified leprosy patients and 230 ethnically matched controls in indian population by genotyping four variants in nod2 (rs9302752a/g ...201324015287
[genotyping of mycobacterium leprae in guangdong province].to understand the genotypes of mycobacterium leprae collected from guangdong province, china and to analyze the routes of leprosy transmission both inside and outside of guangdong. the impact of emigrant leprosy patients to the endemic nature of the disease in guangdong was also studied.201324016427
profiling microrna expression in bovine alveolar macrophages using rna-seq.micrornas (mirnas) are important regulators of gene expression and are known to play a key role in regulating both adaptive and innate immunity. bovine alveolar macrophages (bams) help maintain lung homeostasis and constitute the front line of host defense against several infectious respiratory diseases, such as bovine tuberculosis. little is known, however, about the role mirnas play in these cells. in this study, we used a high-throughput sequencing approach, rna-seq, to determine the expressi ...201324021155
a case of hansen disease presenting as tinea versicolor.hansen disease (leprosy) is an infectious disease that targets macrophages and schwann cells, caused by the acid fast intracellular organism, mycobacterium leprae. clinically, it presents with a spectrum of findings that may include hypopigmented macules, erythematous plaques and nodules, and thickened or tender peripheral nerves. the most feared complication is mutilating damage to facial structures or digits resulting from loss of sensation in affected skin. in non-endemic areas, the diagnosis ...201324021367
assessment of serum level of interleukin-1b and interleukin-12 in leprosy: impact of previous bacillus calmitte guerin vaccination.macrophages play an important role in attempt to eliminate mycobacteria, via production of cytokines, including interleukin-1, and interleukin-12. bacillus calmitte guerin (bcg) vaccination, known to induce interleukin-1β in tuberculosis, was originally aimed at tuberculosis control, but it showed efficacy against leprosy. our aim was to estimate serum levels of interleukin-1β and interleukin-12, in leprosy, and to assess the impact of previous bcg vaccination on their levels. serum interleukin- ...201424022478
a s52p mutation in the 'α-crystallin domain' of mycobacterium leprae hsp18 reduces its oligomeric size and chaperone function.mycobacterium leprae hsp18 is a small heat shock protein (shsp). it is a major immunodominant antigen of m. leprae pathogen. previously, we have reported the existence of two m. leprae hsp18 variants in various leprotic patients. one of the variants has serine at position 52, whereas the other one has proline at the same position. we have also reported that hsp18 having proline at position 52 (hsp18p(52)) is a nonameric protein and exhibits chaperone function. however, the structural and functio ...201324024660
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
mycobacterium leprae dna in peripheral blood may indicate a bacilli migration route and high-risk for leprosy onset.leprosy epidemiological studies have been restricted to mycobacterium leprae dna detection in nasal and oral mucosa samples with scarce literature on peripheral blood. we present the largest study applying quantitative real-time pcr (qpcr) for the detection of m. leprae dna in peripheral blood samples of 200 untreated leprosy patients and 826 household contacts, with results associated with clinical and laboratory parameters. to detect m. leprae dna a taqman qpcr assay targeting the m. leprae ml ...201424033793
leprosy in pregnant woman, united states. 201324050493
haemoglobins of mycobacteria: structural features and biological functions.the genus mycobacterium is comprised of gram-positive bacteria occupying a wide range of natural habitats and includes species that range from severe intracellular pathogens to economically useful and harmless microbes. the recent upsurge in the availability of microbial genome data has shown that genes encoding haemoglobin-like proteins are ubiquitous among mycobacteria and that multiple haemoglobins (hbs) of different classes may be present in pathogenic and non-pathogenic species. the occurre ...201324054797
drug resistance in patients with leprosy in the united states.molecular drug susceptibility testing was performed on 39 us patients with leprosy. of these, 2 had dapsone-resistant mycobacterium leprae and 1 of these patients also had rifampin-resistant m. leprae. even though antileprosy drug resistance occurs in this leprosy population, resistance does not appear to be a major problem.201424065328
mycobacterial phenolic glycolipids with a simplified lipid aglycone modulate cytokine levels through toll-like receptor 2.phenolic glycolipids (pgls) are virulence factors present in the cell walls of many pathogenic mycobacteria. pgls have been implicated in various aspects of mycobacterial disease, but there are limited structure-activity data available for these molecules. we report here the preparation of seven synthetic pgl analogues, differing from the native compounds in the replacement of the complex phenolic lipid moiety with a p-methoxyphenyl group. the ability of these compounds to stimulate or inhibit t ...201324115598
leprosy neuropathy: clinical presentations.leprosy is a chronic infectious peripheral neuropathy caused by mycobacterium leprae. the different clinical presentations of the disease are determined by the quality of the host immune response. early detection of leprosy and treatment by multidrug therapy are the most important steps in preventing deformity and disability. thus the early recognition of the clinical leprosy presentation is essential. mononeuritis, mononeuritis multiplex (mm), polyneuritis (mm summation) are the most frequent. ...201324141500
development of a quantitative rapid diagnostic test for multibacillary leprosy using smart phone technology.despite efforts to eliminate leprosy as public health problem, delayed diagnosis and disabilities still occur in many countries. leprosy diagnosis remains based on clinical manifestations and the number of clinicians with expertise in leprosy diagnosis is in decline. we have developed a new immunochromatographic test with the goal of producing a simple and rapid system that can be used, with a minimal amount of training, to provide an objective and consistent diagnosis of multibacillary leprosy.201324152601
sensory improvement of leprosy peripheral neuropathy in patients treated with perineural injection of platelet-rich plasma.leprosy (hansen's disease) is a chronic granulomatous infection caused by mycobacterium leprae with peripheral neuropathy as cutaneous and neurological manifestations. peripheral nerve regeneration may be stimulated by vascular endothelial growth factor and other growth factors (gfs) that have important roles in extracellular matrix regeneration. all of those gfs can be found in platelet-rich plasma (prp) preparation. the effect of prp injection in leprosy peripheral neuropathy has never been re ...201424168291
genetic association of g896a polymorphism of tlr4 gene in leprosy through family-based and case-control study designs.polymorphisms in tlr4 may change the function of the protein and alter the efficiency of immune response of host to infection. the high relevance of host gene polymorphisms with outcome of mycobacterium leprae infection led us to study the genetic association of tlr4 g896a polymorphism in order to identify its risk among contacts of affected leprosy patients.201324169261
pancytopenia due to lepromatous involvement of the bone marrow: successful treatment with multidrug therapy.leprosy is a chronic infectious disease with a wide spectrum of signs and symptoms depending on the ability of the host's immune system to resist the infection. the disease is frequently associated with sensory loss in skin lesions and damage in peripheral nerve trunks leading to nerve function impairment. in lepromatous leprosy, the immune system offers no protection against the multiplying bacilli and this results in heavy infiltration of the internal organs. we report a case of florid leproma ...201324171241
ackerman's tumour of buccal mucosa in a leprosy patient.leprosy (hansen's disease) is a chronic granulomatous disease caused by mycobacterium leprae (hansen's bacillus). oral manifestations occur in 20-60% of cases, usually in lepromatous leprosy, and are well documented. they may involve both the oral hard and soft tissues. incidence of verrucous carcinoma/ackerman's tumour developing in anogenital region and plantar surfaces of feet in lepromatous leprosy has been sufficiently documented in the literature. however, association of oral verrucous car ...201324171242
estimation of serum level of interleukin-17 and interleukin-4 in leprosy, towards more understanding of leprosy immunopathogenesis.combating mycobacterium leprae is known to be via t-helper1 response. however, other t-helper effector cells; t-helper17 and t-helper2; play a role, particularly in the context of disease type.201524177608
molecular assays for determining mycobacterium leprae viability in tissues of experimentally infected mice.the inability of mycobacterium leprae to grow on axenic media has necessitated specialized techniques in order to determine viability of this organism. the purpose of this study was to develop a simple and sensitive molecular assay for determining m. leprae viability directly from infected tissues.201324179562
gerhard henrik armauer hansen (1841-1912)--the 100th anniversary of the death of the discoverer of mycobacterium leprae.the year 2012 marked the 100th anniversary of the death of gerhard henrik armauer hansen (1841-1912), a norwegian physician known for his identification of mycobacterium leprae as the causative agent of leprosy. in the second half of the 19th century, the medical community believed leprosy had a noninfectious etiology, and it was not until hansen uncovered the relationship between m leprae and the clinical manifestations of this disease did that belief begin to change. strengthening of the late ...201324205518
foxp3 provides competitive fitness to cd4⁺cd25⁺ t cells in leprosy patients via transcriptional regulation.leprosy is a chronic infectious disease caused by mycobacterium leprae. foxp3 have been shown to have important implications in various diseases. the present study describes the mechanism of action of foxp3 in cd4⁺cd25⁺ t cells derived from leprosy patients. increased molecular interactions of foxp3 with histone deacetylases 7/9 in the nucleus of cd4⁺cd25⁺ t cells derived from borderline lepromatous leprosy/lepromatous leprosy (bl/ll) patients were found to be responsible for foxp3-driven immune ...201424214631
ulcerating type 1 lepra reaction mimicking lazarine leprosy: an unusual presentation of immune reconstitution inflammatory syndrome in an hiv-infected patient.leprosy maybe "unmasked" in the context of immune reconstitution inflammatory syndrome and treating dermatologists, particularly in highly endemic areas for hansen's disease, need to be cognizant to this possibility. it may also reflect emergence of a previously clinically silent infection in the course of immunologic restoration.201324216029
non pitting edema, arthritis and ichthyosis; presenting manifestation of leprosy.leprosy is a chronic granulomatous infection caused by mycobacterium leprae. predominantly involving skin and nerves and having classic clinical description, the diagnosis may be clear-cut in majority of patients but may be challenging in others. non-pitting edema, ichthyosis and arthritis are uncommon in leprosy and very rare in tuberculoid type where the diagnosis may be challenging unlike relatively clear-cut clinical picture in lepromatous type. musculoskeletal manifestation is seen in 1-5% ...201324236367
increased frequency of cd4 and cd8 regulatory t cells in individuals under 15 years with multibacillary leprosy.leprosy is a chronic disease, caused by mycobacterium leprae, which poses a serious public health problem worldwide. its high incidence in people under 15 years old in ceará state, brazil, reflects the difficulty of its control. the spectrum of clinical manifestations is associated with the immune response developed, with the th1 and th2 responses being related to the paucibacillary and multibacillary forms, respectively. regulatory t cells (treg), which can suppress th1 and th2 response, have r ...201324244424
resistance of m. leprae to quinolones: a question of relativity?multidrug resistant leprosy, defined as resistance to rifampin, dapsone and fluoroquinolones (fq), has been described in mycobacterium leprae. however, the in vivo impact of fluoroquinolone resistance, mainly mediated by mutations in dna gyrase (gyra2gyrb2), has not been precisely assessed. our objective was to measure the impact of a dna gyrase mutation whose implication in fluoroquinolone resistance has been previously demonstrated through biochemical studies, on the in vivo activity of 3 fluo ...201324244784
autophagy gene polymorphism is associated with susceptibility to leprosy by affecting inflammatory cytokines.autophagy and inflammation closely interact with each other, and together, they play critical roles in bacterial infection. leprosy is caused by the infection of mycobacterium leprae (m. leprae). the objective of the study was to investigate the association between polymorphisms in irgm, an autophagy gene, and susceptibility to leprosy, and identify possible functions of the polymorphism in the infection of m. leprae. two polymorphisms in irgm, rs4958842 and rs13361189, were tested in 412 lepros ...201424264476
antioxidant factors, nitric oxide levels, and cellular damage in leprosy patients.the immune response caused by mycobacterium leprae is a risk factor for the development of oxidative stress (os) in leprosy patients. this study aimed to assess os in leprosy patients before the use of a multidrug therapy.201324270257
innate immune response precedes mycobacterium leprae-induced reprogramming of adult schwann cells.recently, we showed a natural reprogramming process during infection with mycobacterium leprae (ml), the causative organism of human leprosy. ml hijacks the notable plasticity of adult schwann cells in the peripheral nervous system (pns), bacteria's preferred nonimmune niche, to reprogram infected cells to progenitor/stem cell-like cells (pslcs). whereas ml appear to use this reprogramming process as a sophisticated bacterial strategy to spread infection to other tissues, understanding the mecha ...201424279882
reactive perforating leprosy: pustular erythema nodosum leprosum with epidermal perforation and liberation of mycobacterium leprae. 201424319988
leprosy as a model of immunity.leprosy displays a spectrum of clinical manifestations, such as lepromatous and tuberculoid leprosy, and type i and ii lepra reactions, which are thought to be a reflection of the host's immunological response against mycobacterium leprae. therefore, differential recognition of m. leprae, as well as its degraded components, and subsequent activation of cellular immunity will be an important factor for the clinical manifestation of leprosy. although m. leprae mainly parasitizes tissue macrophages ...201424328380
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
reprogramming diminishes retention of mycobacterium leprae in schwann cells and elevates bacterial transfer property to fibroblasts.bacterial pathogens can manipulate or subvert host tissue cells to their advantage at different stages during infection, from initial colonization in primary host niches to dissemination. recently, we have shown that mycobacterium leprae (ml), the causative agent of human leprosy, reprogrammed its preferred host niche de-differentiated adult schwann cells to progenitor/stem cell-like cells (pslc) which appear to facilitate bacterial spread. here, we studied how this cell fate change influences b ...201324358891
epidemiological and clinical patterns of 92 patients co-infected with hiv and mycobacterium leprae from rio de janeiro state, brazil.many articles have shown that hiv infection can modify the clinical course of leprosy, but very scant epidemiological and clinical data about this co-infection are available in the peer-reviewed literature.201424361943
mycobacterium haemophilum masquerading as leprosy in a renal transplant patient.opportunistic infections following immunosuppression in solid organ transplant (sot) patients are common complications with the skin being a common sight of infection. nontuberculous mycobacteria (ntm) are rare but potential causes of skin infection in sot patients. we present a case of an adult male immunosuppressed following renal transplantation who presented with an asymptomatic rash for several months. the patient's skin eruption consisted of erythematous papules and plaques coalescing into ...201324369511
longitudinal immune responses and gene expression profiles in type 1 leprosy reactions.leprosy, a chronic disease initiated by mycobacterium leprae, is often complicated by acute inflammatory reactions. although such episodes occur in at least 50% of all leprosy patients and may cause irreversible nerve damage, no laboratory tests are available for early diagnosis or prediction of reactions. since immune- and genetic host factors are critical in leprosy reactions, we hypothesize that identification of host-derived biomarkers correlated to leprosy reactions can provide the basis fo ...201424370984
serial measurement of the circulating levels of tumour necrosis factor and its soluble receptors 1 and 2 for monitoring leprosy patients during multidrug treatment.leprosy is an infectious and contagious spectral disease accompanied by a series of immunological events triggered by the host response to the aetiologic agent, mycobacterium leprae . the induction and maintenance of the immune/inflammatory response in leprosy are linked to multiple cell interactions and soluble factors, primarily through the action of cytokines. the purpose of the present study was to evaluate the serum levels of tumour necrosis factor (tnf)-α and its soluble receptors (stnf-r1 ...201324402158
mycobacterium leprae and mycobacterium haemophilum co-infection in an iatrogenically immunosuppressed patient.we present the case of a native texan who was diagnosed with tuberculoid leprosy and later developed a cutaneous infection with m. haemophilum following iatrogenic immunosuppression. to our knowledge, there are no such reports of m. haemophilum and m. leprae infection occurring simultaneously in the same host.201424439137
increase in tgf-β secreting cd4⁺cd25⁺ foxp3⁺ t regulatory cells in anergic lepromatous leprosy patients.lepromatous leprosy caused by mycobacterium leprae is associated with antigen specific t cell unresponsiveness/anergy whose underlying mechanisms are not fully defined. we investigated the role of cd25(+)foxp3(+) regulatory t cells in both skin lesions and m.leprae stimulated pbmc cultures of 28 each of freshly diagnosed patients with borderline tuberculoid (bt) and lepromatous leprosy (ll) as well as 7 healthy household contacts of leprosy patients and 4 normal skin samples.201424454972
high resolution structural changes of schwann cell and endothelial cells in peripheral nerves across leprosy spectrum.a systematic ultrastructure of peripheral nerves across the spectrum of leprosy was studied with an aim to better understanding the pathogenesis of nerve involvement in leprosy using light and electron microscope. the pathogenesis of nerve destruction varies in leprosy considerably along the spectrum. the study has begun to shed new light on some aspects of the infection of mycobacterium leprae (m. lepare) and phenomenon has opened new avenue of research and possible mechanism of pathogenesis in ...201424460757
combination of site directed mutagenesis and secondary structure analysis predicts the amino acids essential for stability of m. leprae mure.the life-threatening infections caused by mycobacterium leprae (mle) remain a major challenge in developing countries as well as globe and there is a need to design potent anti-leprosy drugs. in our previous studies, atp-dependent mle-mure ligase involved in biosynthesis of peptidoglycan was identified as one of the common drug targets, homology modeled and reported. in this work in silico site directed mutagenesis study was carried out on the homology modeled mle-mure ligase. this predicted the ...201424464703
mycobacterium leprae upregulates irgm expression in monocytes and monocyte-derived macrophages.leprosy is caused by the infection of mycobacterium leprae, which evokes a strong inflammatory response and leads to nerve damage. immunity-related gtpase family m protein (irgm) plays critical roles in controlling inflammation. the objective of the study was to investigate whether irgm is involved in the infection of m. leprae. levels of irgm were assessed in m. leprae-infected cd4(+) t cells, monocytes, and monocyte-derived macrophages. data revealed that both protein and mrna levels of irgm w ...201424469081
exploring the molecular basis for selective binding of homoserine dehydrogenase from mycobacterium leprae tn toward inhibitors: a virtual screening study.homoserine dehydrogenase (hsd) from mycobacterium leprae tn is an antifungal target for antifungal properties including efficacy against the human pathogen. the 3d structure of hsd has been firmly established by homology modeling methods. using the template, homoserine dehydrogenase from thiobacillus denitrificans (pdb id 3mtj), a sequence identity of 40% was found and molecular dynamics simulation was used to optimize a reliable structure. the substrate and co-factor-binding regions in hsd were ...201424469317
rapid quantitative serological test for detection of infection with mycobacterium leprae, the causative agent of leprosy.leprosy remains an important health problem in a number of regions. early detection of infection, followed by effective treatment, is critical to reduce disease progression. new sensitive and specific tools for early detection of infection will be a critical component of an effective leprosy elimination campaign. diagnosis is made by recognizing clinical signs and symptoms, but few clinicians are able to confidently identify these. simple tests to facilitate referral to leprosy experts are not w ...201424478496
case of lepromatous leprosy misdiagnosed as systemic sclerosis.hansen's disease (hd) is a chronic granulomatous infectious disease caused by mycobacterium leprae. the worldwide prevalence rate of hd has decreased gradually over the years. the clinical manifestations of hd are extensive, with involvement of the skin and various organs, and these can resemble those of many rheumatic diseases. our patient initially presented with gradual sclerotic skin change and slight sclerodactyly with raynaud's phenomenon, which is frequently observed in systemic sclerosis ...201424480058
micronutrients influencing the immune response in leprosy.leprosy is a chronic infectious disease caused by mycobacterium leprae, an intracellular bacillus of airborne transmission. the disease affects the skin and peripheral nerves and can cause neurological sequelae. the bacillus multiplies slowly in the host and the disease probably occurs due to malfunctioning in host immune response. this review addresses the role of some specific micronutrients in the immune response, such as vitamins a, d, e, c, zinc and selenium, detailing their mechanisms of a ...201424483959
application of rlep real-time pcr for detection of m. leprae dna in paraffin-embedded skin biopsy specimens for diagnosis of paucibacillary leprosy.the taqman real-time polymerase chain reaction (pcr) assay was evaluated systematically with respect to the standard curve, linear range, and used for detecting mycobacterium leprae dna in paraffin-embedded skin biopsy specimens from 60 confirmed leprosy patients and three healthy individuals and 29 other dermatoses and bacterial dna from 21 different species. the test was further evaluated with 51 paucibacillary (pb) patients. the results showed that the test had good sensitivity (8 fg) and goo ...201424493677
analysis of polymorphic sites in the promoter of the nitric oxide synthase 2 gene in brazilian patients with leprosy.leprosy is one of the most neglected infectious tropical diseases of the skin and the nerves caused by the intracellular pathogen mycobacterium leprae. the inducible nos isoform encoded by nos2a plays a vital role in host defence against bacterial infections. the functional promoter polymorphisms in nos2a are associated with various autoimmune and infectious diseases. we investigated the association of nos2a variants with progression of leprosy in a brazilian cohort including 221 clinically clas ...201424495190
protein tyrosine phosphatase non-receptor type 22 gene polymorphism c1858t is not associated with leprosy in azerbaijan, northwest iran.leprosy (hansen's disease) is a human chronic granulomatous infectious disease caused by mycobacterium leprae. several types of study support a role for host genetics in susceptibility to leprosy. the protein tyrosine phosphatase non-receptor type 22 (ptpn22) gene encodes an intracellular lymphoid protein tyrosine phosphatase that has been shown to play a negative regulatory role in t-cell activation.201324497703
an exploration of health, family and economic experiences of leprosy patients, iran.this study aims to explore the life experiences of iranian leprosy patients in health, family and economic dimensions. mycobacterium leprae is responsible for leprosy, a type of chronic inflammatory disease that existed from ancient times, still hearing the name of leprosy creates an awful imagination of cutting the organ, blindness and isolation and it has still remained as a serious social problem. the patients are confronted with particular problems physically and mentally. the phenomenologic ...201324502149
immune reconstitution inflammatory syndrome associated with bacterial infections.immune reconstitution inflammatory syndrome (iris) is defined by various clinical manifestations following the initiation of antiretroviral treatment (art) in hiv patients primarily infected with mycobacteria. iris has clinical similarities with lepromatous reactions in patients with leprosy following antibiotic initiation.201424512544
paleopathological evidence and detection of mycobacterium leprae dna from archaeological skeletal remains of nabe-kaburi (head-covered with iron pots) burials in japan.the nabe-kaburi is a unique burial method, the purpose of which is shrouded in mystery. the burials were performed during the 15(th) to 18(th) centuries in eastern japan, and involved covering the heads of the deceased with iron pots or mortars. the identification of leprosy-specific osteological lesions among some of the excavated remains has led to the suggestion that nabe-kaburi burials were a reflection of the social stigma against certain infectious diseases, such as leprosy, tuberculosis o ...201424516638
single nucleotide polymorphism-based molecular typing of m. leprae from multicase families of leprosy patients and their surroundings to understand the transmission of leprosy.the exact mode of transmission of leprosy is not clearly understood; however, many studies have demonstrated active transmission of leprosy around a source case. families of five active leprosy cases and their household contacts were chosen from a high endemic area in purulia. fifty-two soil samples were also collected from different areas of their houses. dna was extracted from slit-skin smears (sss) and soil samples and the mycobacterium leprae-specific rlep (129 bp) region was amplified using ...201424520878
brain involvement by leprosy presenting as a frontal cystic lesion.leprosy has a predilection for peripheral nerves and is not considered to involve the cns. the idea that the cns is exempt from mycobacterium leprae bacilli has been suspected from a clinical perspective or csf study in leprosy patients. however, there has been no direct evidence for cns involvement by leprosy in a living patient. to the best of the authors' knowledge, the present case is the first report providing histopathological and molecular evidence for cns involvement by leprosy in a livi ...201424527821
on the age of leprosy.leprosy is a chronic infection of the skin and nerves caused by mycobacterium leprae and the newly discovered mycobacterium lepromatosis. human leprosy has been documented for millennia in ancient cultures. recent genomic studies of worldwide m. leprae strains have further traced it along global human dispersals during the past ∼ 100,000 years. because leprosy bacilli are strictly intracellular, we wonder how long humans have been affected by this disease-causing parasite. based on recently publ ...201424551248
mycobacterium leprae intracellular survival relies on cholesterol accumulation in infected macrophages: a potential target for new drugs for leprosy treatment.we recently showed that mycobacterium leprae (ml) is able to induce lipid droplet formation in infected macrophages. we herein confirm that cholesterol (cho) is one of the host lipid molecules that accumulate in ml-infected macrophages and investigate the effects of ml on cellular cho metabolism responsible for its accumulation. the expression levels of ldl receptors (ldl-r, cd36, sra-1, sr-b1, and lrp-1) and enzymes involved in cho biosynthesis were investigated by qrt-pcr and/or western blot a ...201424552180
cubn and nebl common variants in the chromosome 10p13 linkage region are associated with multibacillary leprosy in vietnam.leprosy is caused by infection with mycobacterium leprae and is classified clinically into paucibacillary (pb) or multibacillary (mb) subtypes based on the number of skin lesions and the bacillary index detected in skin smears. we previously identified a major pb susceptibility locus on chromosome region 10p13 in vietnamese families by linkage analysis. in the current study, we conducted high-density association mapping of the 9.5 mb linkage peak on chromosome region 10p13 covering 39 genes. usi ...201424563210
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
immunotherapy of tuberculosis with mycobacterium leprae hsp65 as a dna vaccine triggers cross-reactive antibodies against mammalian hsp60 but not pathological autoimmunity.despite substantial efforts in recent years toward the development of new vaccines and drugs against tuberculosis (tb), success has remained elusive. immunotherapy of tb with mycobacterial hsp65 as a dna vaccine (dna-hsp65) results in a reduction of systemic bacterial loads and lung tissue damage, but the high homology of hsp65 with the mammalian protein raises concern that pathological autoimmune responses may also be triggered. we searched for autoimmune responses elicited by dna-hsp65 immunot ...201424607935
genome-wide re-sequencing of multidrug-resistant mycobacterium leprae airaku-3.genotyping and molecular characterization of drug resistance mechanisms in mycobacterium leprae enables disease transmission and drug resistance trends to be monitored. in the present study, we performed genome-wide analysis of airaku-3, a multidrug-resistant strain with an unknown mechanism of resistance to rifampicin. we identified 12 unique non-synonymous single-nucleotide polymorphisms (snps) including two in the transporter-encoding ctpc and ctpi genes. in addition, two snps were found that ...201424612452
the armadillo as a model for peripheral neuropathy in leprosy.leprosy (also known as hansen's disease) is a chronic infectious disease caused by mycobacterium leprae that primarily targets the peripheral nervous system; skin, muscle, and other tissues are also affected. other than humans, nine-banded armadillos (dasypus novemcinctus) are the only natural hosts of m. leprae, and they are the only laboratory animals that develop extensive neurological involvement with this bacterium. infection in the armadillo closely recapitulates many of the structural, ph ...201424615444
synergistic antigen combinations for the development of interferon gamma release assays for paucibacillary leprosy.the development of immunodiagnostic tests for paucibacillary leprosy (pb) is based on mycobacterium leprae specific-cell mediated immunity (cmi)/ifn-γ production. recently, novel m. leprae protein antigens that stimulate cmi have been described. this study evaluated different m. leprae antigen combinations in whole blood assay (wba). five study groups were tested (20 per group): newly diagnosed, untreated pb patients and multibacillary leprosy patients (mb); household contacts of mb patients (hh ...201424619112
epidemiological situation of leprosy in salvador from 2001 to 2009.mycobacterium leprae was first described as the bacillus that causes leprosy, a chronic granulomatous infectious disease, in 1873 by amauer hansen. leprosy is part of a group of 10 neglected diseases and bahia has endemic levels of this illness, varying between high and very high. the detection of 52 new cases of leprosy in children under 15 years old in salvador in 2006 is alarming, and suggests an early contact with the disease. the aim of this review is to analyze the epidemiological situatio ...201724626655
association of genetic polymorphism of hla-drb1 antigens with the susceptibility to lepromatous leprosy.despite the introduction of multidrug therapy and the overall reduction of leprosy prevalence in mexico, the disease remains endemic in certain regions of the country. a genetic basis for the immune susceptibility to mycobacterium leprae has already been established in different populations worldwide. in this study, we investigated the possible association of the hla-drb1 alleles with leprosy in a mexican mestizo population. the results demonstrated that the hla-drb1*01 allele is associated with ...201324649058
chronic pain in leprosy: new aspects to be considered.leprosy is still considered to be endemic in several developing countries, such as india and brazil. infection with mycobacterium leprae leads to chronic granulomatous inflammation in skin and peripheral nerves that can lead to sensory, motor and autonomic impairments. since the disease causes severe sensory loss, little attention has been given to pain in leprosy. however, chronic pain in leprosy is being increasingly recognized as an important late complication of leprosy. this article discuss ...201324654763
a case of lepromatous leprosy complicated by hemophagocytosis misdiagnosed as hemophagocytic lymphohistiocytosis.leprosy is an infectious chronic granulomatous disease caused by mycobacterium leprae. the disease mainly affects the skin, peripheral nerves, mucosa, and viscera. the world health organization has reported that most countries with high endemicity have reached the goal of eliminating leprosy (defined as reaching a prevalence of <1 leprosy case per 10 000 population) at the national level, after years of proactive control campaigns. the incidence of leprosy has been decreasing across the globe ye ...201424657272
comparative genomics for mycobacterial peptidoglycan remodelling enzymes reveals extensive genetic multiplicity.mycobacteria comprise diverse species including non-pathogenic, environmental organisms, animal disease agents and human pathogens, notably mycobacterium tuberculosis. considering that the mycobacterial cell wall constitutes a significant barrier to drug penetration, the aim of this study was to conduct a comparative genomics analysis of the repertoire of enzymes involved in peptidoglycan (pg) remodelling to determine the potential of exploiting this area of bacterial metabolism for the discover ...201424661741
a rapid elisa for the diagnosis of mb leprosy based on complementary detection of antibodies against a novel protein-glycolipid conjugate.despite the widespread use of multidrug therapy for treatment, delays in clinical recognition and under-reporting of leprosy indicate that mycobacterium leprae transmission is continuing. thus, leprosy is likely to persist as a significant burden on health systems in many regions. in this study, we combined 2 previously characterized leprosy antigens, leprosy idri diagnostic-1 (lid-1) and nd-o, into the single fusion complex (nd-o-lid) and determined the serum antibody responses of leprosy patie ...201424666703
mycobacterium leprae hsp65 administration reduces the lifespan of aged high antibody producer mice.aging process may result in immune modifications that lead to disruption of innate and acquired immunity mechanisms that may induce chronic-degenerative events. the heat shock proteins (hsp), phylogeneticaly conserved among organisms, present as main function the ability of folding and refolding proteins, but they also are associated with chronic-degenerative disorders. here were evaluated the role of m. leprae native hsp65 (wt) and its point-mutated (k409a) on survival and anti-dna and anti-hsp ...201424669842
examining erbb2 as a candidate gene for susceptibility to leprosy (hansen's disease) in brazil.leprosy remains prevalent in brazil. erbb2 is a receptor for leprosy bacilli entering schwann cells, which mediates mycobacterium leprae-induced demyelination and the erbb2 gene lies within a leprosy susceptibility locus on chromosome 17q11-q21. to determine whether polymorphisms at the erbb2 locus contribute to this linkage peak, three haplotype tagging single nucleotide polymorphisms (tag-snps) (rs2517956, rs2952156, rs1058808) were genotyped in 72 families (208 cases; 372 individuals) from th ...201424676663
optimized protocols for mycobacterium leprae strain management: frozen stock preservation and maintenance in athymic nude mice.leprosy, caused by mycobacterium leprae, is an important infectious disease that is still endemic in many countries around the world, including brazil. there are currently no known methods for growing m. leprae in vitro, presenting a major obstacle in the study of this pathogen in the laboratory. therefore, the maintenance and growth of m. leprae strains are preferably performed in athymic nude mice (nu-foxn1(nu)). the laboratory conditions for using mice are readily available, easy to perform, ...201424686247
protides of n-(3-(5-(2'-deoxyuridine))prop-2-ynyl)octanamide as potential anti-tubercular and anti-viral agents.the flavin-dependent thymidylate synthase x (thyx), rare in eukaryotes and completely absent in humans, is crucial in the metabolism of thymidine (a dna precursor) in many microorganisms including several human pathogens. conserved in mycobacteria, including mycobacterium leprae, and mycobacterium tuberculosis, it represents a prospective anti-mycobacterial therapeutic target. in a m. tuberculosis thyx-enzyme inhibition assay, n-(3-(5-(2'-deoxyuridine-5'-phosphate))prop-2-ynyl)octanamide was rep ...201424690527
mycobacterium leprae genomes from a british medieval leprosy hospital: towards understanding an ancient epidemic.leprosy has afflicted humankind throughout history leaving evidence in both early texts and the archaeological record. in britain, leprosy was widespread throughout the middle ages until its gradual and unexplained decline between the 14th and 16th centuries. the nature of this ancient endemic leprosy and its relationship to modern strains is only partly understood. modern leprosy strains are currently divided into 5 phylogenetic groups, types 0 to 4, each with strong geographical links. until r ...201424708363
pcr-based techniques for leprosy diagnosis: from the laboratory to the clinic.in leprosy, classic diagnostic tools based on bacillary counts and histopathology have been facing hurdles, especially in distinguishing latent infection from active disease and diagnosing paucibacillary clinical forms. serological tests and ifn-gamma releasing assays (igra) that employ humoral and cellular immune parameters, respectively, are also being used, but recent results indicate that quantitative pcr (qpcr) is a key technique due to its higher sensitivity and specificity. in fact, advan ...201424722358
t-cell regulation in lepromatous leprosy.regulatory t (treg) cells are known for their role in maintaining self-tolerance and balancing immune reactions in autoimmune diseases and chronic infections. however, regulatory mechanisms can also lead to prolonged survival of pathogens in chronic infections like leprosy and tuberculosis (tb). despite high humoral responses against mycobacterium leprae (m. leprae), lepromatous leprosy (ll) patients have the characteristic inability to generate t helper 1 (th1) responses against the bacterium. ...201424722473
leprosy: review of the epidemiological, clinical, and etiopathogenic aspects - part 1.leprosy is caused by mycobacterium leprae and has been known since biblical times. it is still endemic in many regions of the world and a public health problem in brazil. the prevalence rate in 2011 reached 1.54 cases per 10,000 inhabitants in brazil. the mechanism of transmission of leprosy consists of prolonged close contact between susceptible and genetically predisposed individuals and untreated multibacillary patients. transmission occurs through inhalation of bacilli present in upper airwa ...201724770495
field-evaluation of a new lateral flow assay for detection of cellular and humoral immunity against mycobacterium leprae.field-applicable tests detecting asymptomatic mycobacterium leprae (m. leprae) infection or predicting progression to leprosy, are urgently required. since the outcome of m. leprae infection is determined by cellular- and humoral immunity, we aim to develop diagnostic tests detecting pro-/anti-inflammatory and regulatory cytokines as well as antibodies against m. leprae. previously, we developed lateral flow assays (lfa) for detection of cytokines and anti-pgl-i antibodies. here we evaluate prog ...201424810599
urticaria and bacterial infections.the association between urticaria and infectious diseases has been discussed for >100 years. however, a causal relationship with underlying or precipitating infection is difficult to establish. the purpose of this work was to perform a systematic analysis of the published cases of urticaria associated with bacterial infections. we give an umbrella breakdown of up-to-date systematic reviews and other important publications on the complex association of urticaria and bacterial infections. we did a ...201624857191
baropodometric evaluations and sensitivity alterations in plantar ulcer formation in leprosy.leprosy is a chronically evolving granulomatous disease caused by the bacillus mycobacterium leprae, which exhibits tropism for peripheral and motor nerves and slow-growing inflammation that affects the peripheral nervous system, especially the sensory fibers. the aim of this study was to observe the relationship between peak pressure and abnormal sensitivity for the formation of plantar ulcers in patients with multibacillary (mb) and paucibacillary (pb) leprosy. a total of 51 individuals with l ...201424861093
the challenge of producing skin test antigens with minimal resources suitable for human application against a neglected tropical disease; leprosy.true incidence of leprosy and its impact on transmission will not be understood until a tool is available to measure pre-symptomatic infection. diagnosis of leprosy disease is currently based on clinical symptoms, which on average take 3-10 years to manifest. the fact that incidence, as defined by new case detection, equates with prevalence, i.e., registered cases, suggests that the cycle of transmission has not been fully intercepted by implementation of multiple drug therapy. this is supported ...201424874086
detection of stealthy small amphiphilic biomarkers.pathogen-specific biomarkers are secreted in the host during infection. many important biomarkers are not proteins but rather small molecules that cannot be directly detected by conventional methods. however, these small molecule biomarkers, such as phenolic glycolipid-i (pgl-i) of mycobacterium leprae and mycobactin t (mbt) of mycobacterium tuberculosis, are critical to the pathophysiology of infection, and may be important in the development of diagnostics, vaccines, and novel therapeutic stra ...201424880131
synthesis and evaluation of novel dapsone-thalidomide hybrids for the treatment of type 2 leprosy reactions.we synthesized a series of novel dapsone-thalidomide hybrids (3a-i) by molecular hybridization and evaluated their potential for the treatment of type 2 leprosy reactions. all of the compounds had analgesic properties. compounds 3c and 3h were the most active antinociceptive compounds and reduced acetic acid-induced abdominal constrictions by 49.8% and 39.1%, respectively. the hybrid compounds also reduced tumor necrosis factor-α levels in lipopolysaccharide-stimulated l929 cells. compound 3i wa ...201424907144
utility of recombinant proteins lid-1 and padl in screening for mycobacterium leprae infection and leprosy.despite the widespread use of multidrug therapy, leprosy remains an important public health concern in many regions. detection is generally limited to clinical exam.201424907710
leprosy: a review of laboratory and therapeutic aspects--part 2.leprosy is a chronic infectious condition caused by mycobacterium leprae(m. leprae). it is endemic in many regions of the world and a public health problem in brazil. additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between m. leprae and host, and are related to the degree of immunity to the bacillus. the diagnosis of this disease is a clinical one. however, in some situations laboratory exams are necessary to confirm the diagnosis of l ...201724937811
three-dimensional in vitro models of granuloma to study bacteria-host interactions, drug-susceptibility, and resuscitation of dormant mycobacteria.mycobacterium tuberculosis, mycobacterium leprae, mycobacterium bovis, and mycobacterium avium subsp. paratuberculosis can survive within host macrophages in a dormant state, encased within an organized aggregate of immune host cells called granuloma. granulomas consist of uninfected macrophages, foamy macrophages, epithelioid cells, and t lymphocytes accumulated around infected macrophages. within granulomas, activated macrophages can fuse to form multinucleated giant cells, also called giant l ...201424967387
is drug-resistant mycobacterium leprae a real cause for concern?: first approach to molecular monitoring of multibacillary colombian patients with and without previous leprosy treatment.there is no information in colombia on mycobacterium leprae primary and secondary drug resistance in regards to the who-multidrug therapy regime. on the other hand, public health authorities around the world have issued various recommendations, one of which prompts for the immediate organization of resistance surveillance through simple molecular methods.201424968045
evaluation of a rapid serological test for leprosy classification using human serum albumin as the antigen carrier.the presence of anti-bsa antibodies may interfere in serological tests, as elisa or immunochromatographic assays. bsa is frequently used as a blocking agent or as "inert" carrier of antigens, such as the nt-p-bsa, the semi-synthetic trisaccharide analogue of the pgl-i (phenolic glycolipid-i) antigen from the cell wall of the mycobacterium leprae. pgl-i was prepared and linked to human serum albumin based in the hypothesis that replacing bsa by a human protein carrier would enhance the performanc ...201424983877
rbcg30-induced immunity and cross-protection against mycobacterium leprae challenge are enhanced by boosting with the mycobacterium tuberculosis 30-kilodalton antigen 85b.leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. vaccines are needed that protect against both infections and do so better than the suboptimal mycobacterium bovis bcg vaccine. here, we evaluated rbcg30, a vaccine previously demonstrated to induce protection superior to that of bcg against mycobacterium tuberculosis and mycobacterium bovis challenge in animal models, for efficacy against mycobacterium leprae challenge in a murine mode ...201425001602
the role of micrornas in the control and mechanism of action of il-10.recent studies have shown an important interplay between interleukin 10 (il-10) and micrornas. il-10 can be directly post-transcriptionally regulated by several microrna, including mir-106a, mir-4661, mir-98, mir-27, let7 and mir-1423p/5p. mirna targeting of il-10 has been suggested to play a role in autoimmune and inflammatory diseases such as sle, reperfusion injury and asthma. another mirna, mir-21, has been shown to indirectly regulate il-10 via downregulation of the il-10 inhibitor pdcd4. t ...201425004817
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
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