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unsolved matters in leprosy: a descriptive review and call for further research.leprosy, a chronic mycobacterial infection caused by mycobacterium leprae, is an infectious disease that has ravaged human societies throughout millennia. this ancestral pathogen causes disfiguring cutaneous lesions, peripheral nerve injury, ostearticular deformity, limb loss and dysfunction, blindness and stigma. despite ongoing efforts in interrupting leprosy transmission, large numbers of new cases are persistently identified in many endemic areas. moreover, at the time of diagnosis, most new ...201627209077
pauci- and multibacillary leprosy: two distinct, genetically neglected diseases.after sustained exposure to mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (pb) to the multibacillary (mb) form of the disease. this "polarization" of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. but while leprosy per se has been shown to be under tight human gen ...201627219008
increasing incidence of leprosy and transmission from armadillos in central florida: a case series. 201627222885
leprosy in children and adolescents under 15 years old in an urban centre in brazil.this original study describes the intra-urban distribution of cases of leprosy in residents under 15 years old in salvador, bahia, brazil; the study also identifies the environment in which mycobacterium leprae is being transmitted. the cases were distributed by operational classification, clinical forms, type of contact and the addresses were geo-referenced by neighborhood. between 2007 and 2011, were reported 145 cases of leprosy in target population living in salvador, corresponding to detect ...201627223655
[methods for determining the antimicrobial susceptibility of mycobacteria].mycobacteria are a large group of microorganisms, multiple species of which are major causes of morbidity and mortality, such as tuberculosis and leprosy. at present, the emergence and spread of multidrug-resistant strains of mycobacterium tuberculosis complex are one of the most serious health problems worldwide. furthermore, in contrast to m. tuberculosis and mycobacterium leprae, non-tuberculous mycobacteria (ntm) are more frequently isolated and, in many cases, treatment is based on drug sus ...201627236235
mycobacterium leprae specific genomic target in the promoter region of probable 4-alpha-glucanotransferase (ml1545) gene with potential sensitivity for polymerase chain reaction based diagnosis of leprosy.with the absence of an effective diagnostic tool for leprosy, cases with negative bacteriological index and limited clinical manifestations often pose diagnostic challenges. in this study, we investigated the utility of a novel mycobacterium leprae specific 112-bp dna sequence in the promoter region of probable 4-alpha-glucanotransferase (pseudogene, ml1545) for polymerase chain reaction (pcr) based diagnosis of leprosy in comparison to that of the rlep gene. dna was extracted from slit skin scr ...201627242223
expression profile of rab5, rab7, tryptophan aspartate-containing coat protein, leprae lipoarabinomannan, and phenolic glycolipid-1 on the failure of the phagolysosome process in macrophages of leprosy patients as a viability marker of mycobacterium leprae.phagolysosome process in macrophage of leprosy patients' is important in the early phase of eliminating mycobacterium leprae invasion. this study was to clarify the involvement of rab5, rab7, and trytophan aspartate-containing coat protein (taco) from host macrophage and leprae lipoarabinomannan (lep-lam) and phenolic glycolipid-1 (pgl-1) from m. leprae cell wall as the reflection of phagolysosome process in relation to 16 subunit ribosomal rna (16s rrna) m. leprae as a marker of viability of m. ...201627242226
[borderline leprosy as a rare differential diagnosis].history and clinical findings | a 42-year-old migrant from brazil presented with persistent sensory disturbances, skin discolorations and local alopecia in the upper limbs. decisive for the presentation in our tropical medicine clinic were new occurrences of severe pain and redness and swelling in the area of the lesions that had already been assessed by a number of medical specialists without a clear diagnosis could be made. investigations and diagnosis | the histological analysis of skin biops ...201627254633
association of viable mycobacterium leprae with type 1 reaction in leprosy.the working hypothesis is that, viable mycobacterium leprae (m. leprae) play a crucial role in the precipitation of type 1 reaction (t1r) in leprosy.201627255061
mutation at codon 442 in the rpob gene of mycobacterium leprae does not confer resistance to rifampicin.rifampicin is the major drug in the treatment of leprosy. the rifampicin resistance of mycobacterium leprae results from a mutation in the rpob gene, encoding the β subunit of rna polymerase. as m. leprae is a non-cultivable organism observation of its growth using mouse food-pad (mfp) is the only gold standard assay used for confirmation of "in-vivo" drug resistance.201627255062
autochthonous borderline tuberculoid leprosy in a man from florida.leprosy (hansen's disease) is a chronic contagious granulomatous disease principally affecting the skin and peripheral nervous system, caused by mycobacterium leprae. in this report, we present a case of autochthonous leprosy in a man from florida as the first human case reported from this region. authors believe dermatologists need to be aware of the possibility of autochthonous transmission of leprosy in the eastern-southern united states, and should consider leprosy in any patient with atypic ...201627255063
tuberculosis and leprosy infections in the marshallese population of arkansas, usa.the cross-immunity between tuberculosis and leprosy is unknown. the aim of this pilot study was to evaluate the occurrence of mycobacterium tuberculosis and m. leprae infection in marshallese adult volunteers in springdale, arkansas, u.s.a., a population that experiences high rates of leprosy and tuberculosis. we used immunodiagnostic testing for tuberculosis and leprosy infection and found significant prevalence of latent tuberculosis infection (19.0%), and asymptomatic mycobacterium leprae inf ...201627255065
soil-transmitted helminth infections and leprosy: a cross-sectional study of the association between two major neglected tropical diseases in indonesia.the clinical spectrum of leprosy is dependent on the host immune response against mycobacterium leprae or the newly discovered mycobacterium lepromatosis antigen. helminth infections have been shown to affect the development of several diseases through immune regulation and thus may play a role in the clinical manifestations of leprosy and leprosy reactions. the purpose of this study is to determine the proportion of helminth infections in leprosy and its association with the type of leprosy and ...201627278453
mycobacterium leprae-induced insulin-like growth factor i attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages.mycobacterium leprae (ml), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. in the present study, the participation of hormone insulin-like growth factor i (igf-i) in this phenomenum was investigated. macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (ll) of leprosy expressed higher levels of igf-i than those from the self-limited paucibacillary tuberculoid form (bt). higher le ...201627282338
human nod2 recognizes structurally unique muramyl dipeptides from mycobacterium leprae.the innate immune system recognizes microbial pathogens via pattern recognition receptors. one such receptor, nod2, via recognition of muramyl dipeptide (mdp), triggers a distinct network of innate immune responses, including the production of interleukin-32 (il-32), which leads to the differentiation of monocytes into dendritic cells (dc). nod2 has been implicated in the pathogenesis of human leprosy, yet it is not clear whether mycobacterium leprae, which has a distinct mdp structure, can acti ...201627297389
mechanisms of defense against intracellular pathogens mediated by human macrophages.the key question our work has sought to address has been, "what are the necessary and sufficient conditions that engender protection from intracellular pathogens in the human host?" the origins of this work derive from a long-standing interest in the mechanisms of protection against two such paradigmatic intracellular pathogens, mycobacterium tuberculosis and mycobacterium leprae, that have brilliantly adapted to the human host. it was obvious that these pathogens, which cause chronic diseases a ...201627337485
mutations in the drug resistance-determining region of mycobacterium lepromatosis isolated from leprosy patients in mexico.mycobacterium lepromatosis, an independent species from mycobacterium leprae, has been found to be a causative agent for diffuse lepromatous leprosy (dll) in mexico, but remains poorly studied. here, the drug resistance-determining regions (drdr) of folp1, rpob and gyra (conferring resistance to dapsone, rifampicin and quinolone, respectively) in m. lepromatosis from leprosy patients in mexico were characterized. no mutations or silent mutations were found at previously characterized major sites ...201627345334
s100a12 is part of the antimicrobial network against mycobacterium leprae in human macrophages.triggering antimicrobial mechanisms in macrophages infected with intracellular pathogens, such as mycobacteria, is critical to host defense against the infection. to uncover the unique and shared antimicrobial networks induced by the innate and adaptive immune systems, gene expression profiles generated by rna sequencing (rnaseq) from human monocyte-derived macrophages (mdms) activated with tlr2/1 ligand (tlr2/1l) or ifn-γ were analyzed. weighed gene correlation network analysis identified modul ...201627355424
regional anaesthesia management in a patient with leprosy: rare case with rare application.leprosy is a chronic infectious disease that is caused by mycobacterium leprae and affects the skin and nerves. patients with leprosy having related peripheral neuropathy and involvement of other organs may have cardiac, respiratory dysautonomia and autonomic dysfunctions. there are very few studies regarding anaesthetic management of patients suffering from leprosy. moreover, very few studies concerning regional anaesthesia in patients with lepromatous leprosy have been reported. in this study, ...201627366553
imported and autochthonous leprosy presenting in madrid (1989-2015): a case series and review of the literature.leprosy remains infrequent in non-endemic areas. the objective of this study was to describe the cases of leprosy reviewed at a referral unit for imported diseases in europe and to compare these findings with published data on imported leprosy.201727393660
association between str -794 catt5-8 and snp -173 g/c polymorphisms in the mif gene and lepromatous leprosy in mestizo patients of western mexico.lepromatous leprosy (ll) is the most common presentation of leprosy in mexico. ll patients are unable to activate an effective inflammatory response against mycobacterium leprae probably due to the genetics of the host. macrophage migration inhibitory factor (mif) is important to trigger inflammation processes. two polymorphisms have been reported for human mif: str -794 catt5-8 and snp -173 g/c. 7-8 catt repeats at -794 and the c allele at -173 increase the expression of mif. we aim to determin ...201627426952
immunohistochemical assessment of cell populations in leprosy-spectrum lesions and reactional forms.in situ immunophenotyping of leprosy lesions can improve our understanding of the biology of inflammatory cells during the immune response to mycobacterium leprae antigens. in the present study, biopsies from 10 healthy controls and 70 leprosy patients were selected, 10 for each of the following conditions: clinical tuberculoid (tt), borderline tuberculoid (bt), borderline borderline (bb), borderline lepromatous (bl), lepromatous (ll), reversal reaction (r1), and erythema nodosum leprosum (r2). ...201727444702
diguanylate cyclase activity of the mycobacterium leprae t cell antigen ml1419c.the second messenger, bis-(3',5')-cyclic dimeric guanosine monophosphate (cyclic di-gmp), is involved in the control of multiple bacterial phenotypes, including those that impact host-pathogen interactions. bioinformatics analyses predicted that mycobacterium leprae, an obligate intracellular bacterium and the causative agent of leprosy, encodes three active diguanylate cyclases. in contrast, the related pathogen mycobacterium tuberculosis encodes only a single diguanylate cyclase. one of the m. ...201627450520
leprae reaction resembling rheumatologic disease as presenting feature of leprosy.leprosy is a chronic granulomatous infection caused by mycobacterium leprae with predominant involvement of skin and nerves. we present a 70-year-old man with leprosy whose initial presentation resembled rheumatologic disease, due to leprae reaction. he presented with an 8-week history of worsening neuropathic pain in the right forearm, associated with necrotic skin lesions on his fingers that had ulcerated. physical examination revealed two tender necrotic ulcers at the tip of the right middle ...201627456320
mycobacterium leprae activates toll-like receptor-4 signaling and expression on macrophages depending on previous bacillus calmette-guerin vaccination.toll-like receptor (tlr)-1 and tlr2 have been shown to be receptors for mycobacterium leprae (m. leprae), yet it is unclear whether m. leprae can signal through alternative tlrs. other mycobacterial species possess ligands for tlr4 and genetic association studies in human populations suggest that people with tlr4 polymorphisms may be protected against leprosy. using human embryonic kidney (hek)-293 cells co-transfected with tlr4, we demonstrate that m. leprae activates tlr4. we used human macrop ...201627458573
spatial and temporal epidemiology of mycobacterium leprae infection among leprosy patients and household contacts of an endemic region in southeast brazil.leprosy is a chronic infectious disease that remains a public health problem in low- and middle-income countries. household contacts of leprosy patients (hhcs) have increased risk of developing disease and are important links in the chain of transmission of mycobacterium leprae. based on epidemiological and operational factors, the global elimination strategy depends on the geographic stratification of endemic areas to intensify control activities. the purpose of the study was to integrate epide ...201627469619
dna sensing via tlr-9 constitutes a major innate immunity pathway activated during erythema nodosum leprosum.the chronic course of lepromatous leprosy may be interrupted by acute inflammatory episodes known as erythema nodosum leprosum (enl). despite its being a major cause of peripheral nerve damage in leprosy patients, the immunopathogenesis of enl remains ill-defined. recognized by distinct families of germline-encoded pattern recognition receptors, endogenous and pathogen-derived nucleic acids are highly immunostimulatory molecules that play a major role in the host defense against infections, auto ...201627474073
profiling of intracellular metabolites: an approach to understanding the characteristic physiology of mycobacterium leprae.mycobacterium leprae is the causative agent of leprosy and also known to possess unique features such as inability to proliferate in vitro. among the cellular components of m. leprae, various glycolipids present on the cell envelope are well characterized and some of them are identified to be pathogenic factors responsible for intracellular survival in host cells, while other intracellular metabolites, assumed to be associated with basic physiological feature, remain largely unknown. in the pres ...201627479467
renal amyloidosis in leprosy, an infrequent cause of nephrotic syndrome in europe.leprosy is a chronic infectious disease caused by mycobacterium leprae the main clinical manifestations involve the skin and the peripheral nervous system. several types of nephropathy have been described in leprosy. one frequent form of renal involvement is amyloidosis, especially in patients with lepromatous leprosy. in these patients, end-stage renal disease is an important contributor to morbidity and mortality. here, we present the case of a patient with nephrotic syndrome caused by seconda ...201627489069
bone changes in an italian ancient human skeleton--possibly caused by leprosy.leprosy is an infectious disease caused by mycobacterium leprae and mycobacterium lepromatosis. in the last stage it can afflict the skeleton with a series of specific and non-specific bone changes. the possibility of studyingthe skeleton of an individual who lived in the pre-antibiotic era (roman period) with skeletal changes in the rhino-maxillary region and hand and foot bones, permitted skeletal lesions to be analyzed directly. in addition, the localization and the complexity of the bony les ...201627506007
application of mycobacterium leprae-specific cellular and serological tests for the differential diagnosis of leprosy from confounding dermatoses.mycobacterium leprae-specific serological and cell-mediated-immunity/cmi test were evaluated for the differential diagnosis of multibacillary/mb, and paucibacillary/pb leprosy from other dermatoses. whole-blood assay/wba/ifnγ stimulated with lid-1 antigen and elisa tests for igg to lid-1 and igm to pgl-i were performed. wba/lid-1/ifnγ production was observed in 72% pb, 11% mb leprosy, 38% dermatoses, 40% healthy endemic controls/ec. the receiver operating curve/roc for wba/lid-1 in pb versus oth ...201627506457
presence of viable mycobacterium leprae in environmental specimens around houses of leprosy patients.leprosy is a chronic systemic infectious disease caused by mycobacterium leprae, one of the first organisms to be established as the cause for disease in humans. because of high prevalence pockets of leprosy in the endemic regions, it is necessary to identify the possible sources of m. leprae in the environment and its mode of transmission.201727514953
gene-family extension measures and correlations.the existence of multiple copies of genes is a well-known phenomenon. a gene family is a set of sufficiently similar genes, formed by gene duplication. in earlier works conducted on a limited number of completely sequenced and annotated genomes it was found that size of gene family and size of genome are positively correlated. additionally, it was found that several atypical microbes deviated from the observed general trend. in this study, we reexamined these associations on a larger dataset con ...201627527218
the role of primary infection of schwann cells in the aetiology of infective inflammatory neuropathies.numerous different pathogens are responsible for infective peripheral neuropathies and this is generally the result of the indirect effects of pathogen infection, namely anti pathogen antibodies cross reacting with epitopes on peripheral nerve, auto reactive t cells attacking myelin, circulating immune complexes and complement fixation. primary infection of schwann cells (sc) associated with peripheral nerve inflammation is rare requiring pathogens to cross the blood peripheral nerve barrier (bp ...201627546064
trisaccharides of phenolic glycolipids confer advantages to pathogenic mycobacteria through manipulation of host-cell pattern-recognition receptors.despite mycobacterial pathogens continue to be a threat to public health, the mechanisms that allow them to persist by modulating the host immune response are poorly understood. among the factors suspected to play a role are phenolic glycolipids (pgls), produced notably by the major pathogenic species such as mycobacterium tuberculosis and mycobacterium leprae. here, we report an original strategy combining genetic reprogramming of the pgl pathway in mycobacterium bovis bcg and chemical synthesi ...201627548027
leprosy treatment during pregnancy and breastfeeding: a case report and brief review of literature.leprosy is a chronic disease which primarily affects the skin, mucous membranes and peripheral nerves due to mycobacterium leprae. it is now infrequent in europe and is rarely reported during pregnancy. leprosy can be exacerbated during pregnancy, and without treatment it can permanently damage the skin, nerves, limbs and eyes. therefore, it is important to treat leprosy during pregnancy. this article describes a patient with multibacillary lepromatous leprosy who was treated with multidrug ther ...201727549245
genetic variants of the mavs, mita and mfn2 genes are not associated with leprosy in han chinese from southwest china.leprosy is a chronic infectious disease caused by mycobacterium leprae (m. leprae), which has massive genomic decay and dependence on host metabolism. accumulating evidence showed a crucial role of mitochondria in metabolism and innate immunity. we hypothesized that the mitochondrial-related antimicrobial/antiviral immune genes mavs (mitochondrial antiviral signaling protein), mita (mediator of irf3 activation) and mfn2 (mitofusin 2) would confer a risk to leprosy. in this study, we performed a ...201627553710
subversion of schwann cell glucose metabolism by mycobacterium leprae.mycobacterium leprae, the intracellular etiological agent of leprosy, infects schwann promoting irreversible physical disabilities and deformities. these cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. in the present work, we observed that infected schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (g6pdh) activity, the key enzyme of the oxidative pen ...201627555322
molecular evidence for the aerial route of infection of mycobacterium leprae and the role of asymptomatic carriers in the persistence of leprosy.leprosy persists as a public health problem. the chain of transmission and mechanism of infection are not completely understood. in the current study, we investigated the route of infection and of disease onset, from airway exposure, colonization, and bloodstream dissemination.201627558564
editorial commentary: evidences of aerial route of mycobacterium leprae infection and doubts about transmission and natural protection in leprosy. 201627558566
transmission of drug-resistant leprosy in guinea-conakry detected using molecular epidemiological approaches.molecular drug susceptibility testing was performed on skin biopsies from 24 leprosy patients from guinea-conakry for the first time. we identified primary drug resistance in 4 cases and a dapsone-resistant cluster caused by the same strain. primary transmission of drug-resistant mycobacterium leprae, including a rifampicin-resistant strain, is reported.201627558568
a case of fluoroquinolone-resistant leprosy discovered after 9 years of misdiagnosis.we report a case of misdiagnosed leprosy in a 21-year-old malagasy male, who, improperly treated, developed secondary mycobacterial resistance to fluoroquinolone. the patient contracted the infection 9 years prior to the current consultation, displaying on the right thigh a single papulonodular lesion, which progressively spread to the lower leg, back, and face. initial administration of ciprofloxacin and prednisolone led to temporary and fluctuating improvement. subsequent long-term self-medica ...201627579195
[pure neural leprosy. diagnostic aspects of a clinical case].leprosy is an infectious disease caused by the bacteria mycobacterium leprae. it is particularly prone to affect the skin and the nerve trunks and, in fact, both are compromised in most infected patients. it is transmitted by exposure to those with the disease and sometimes by reactivation. one uncommon possibility is pure neural leprosy, which is characterised by neuropathy, but without skin lesions. we report the case of a patient with pure neural leprosy and review the diagnostic aspects.201627600740
prevalence and correlates of leprosy in a high-risk community setting in sri lanka.leprosy is caused by the mycobacterium leprae bacillus. pockets of high endemicity remain in a number of countries including sri lanka, in spite of the fact that elimination has been achieved at the national level. in 2012, in a village in the puttlam district, dermatologists reported an increase in individuals with leprosy. this village had been established in the 1990s for people displaced from northern sri lanka during a civil war. a comprehensive household survey was conducted by district he ...201627605468
the oral cavity in leprosy: what clinicians need to know.leprosy is a chronic infectious disease caused by mycobacterium leprae, a bacillus that has a tropism for skin and peripheral nerves. leprosy treatment is based on a multidrug therapy established by the world health organization in 1982 and, despite its widespread use, brazil ranks second worldwide in numbers of cases. oral involvement in leprosy has been poorly described in the literature, and few studies have shown that although the bacillus is found in mucosa, specific leprosy lesions are rar ...201627606832
investigating potential exogenous tumor initiating and promoting factors for cutaneous t-cell lymphomas (ctcl), a rare skin malignancy.most skin malignancies are caused by external and often preventable environmental agents. multiple reports demonstrated that cutaneous t-cell lymphomas (ctcl) can occur in married couples and cluster in families. furthermore, recent studies document geographic clustering of this malignancy in texas as well as in other areas of the united states. multiple infectious, occupational, and medication causes have been proposed as triggers or promoters of this malignancy including hydrochlorothiazide di ...201627622024
genomic diversity in mycobacterium leprae isolates from leprosy cases in south india.the objective of this study was to identify the strain diversity of mycobacterium leprae in terms of snp types and subtypes stratified as per genomic single nucleotide polymorphisms, in clinical isolates of leprosy patients from a tertiary care leprosy center in south india. further, the associations of snp types with clinical outcomes in leprosy were also investigated.201627642139
rab32 restriction of intracellular bacterial pathogens.our immune system is engaged in a continuous battle against invading pathogens, many of which have evolved to survive in intracellular niches of mammalian hosts. a variety of cellular processes are involved in preventing bacterial invasion or in killing bacteria that successfully invade host cells. recently, the rab gtpase rab32 emerged as critical regulator of a host defense pathway that can eliminate bacterial pathogens. salmonella enterica is an intracellular bacterium and a major cause of in ...201627645564
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
identifying leprosy and those at risk of developing leprosy by detection of antibodies against lid-1 and lid-ndo.leprosy is caused by mycobacterium leprae infection and remains a major public health problem in many areas of the world. challenges to its timely diagnosis result in delay in treatment, which is usually associated with severe disability. although phenolic glycolipid (pgl)-i has been reported as auxiliary diagnostic tool, currently there is no serological assay routinely used in leprosy diagnosis. the aim of this study was to evaluate the effectiveness of two related reagents, lid-1 and lid-ndo, ...201627658042
consensus numbering system for the rifampicin resistance-associated rpob gene mutations in pathogenic mycobacteria.the rpob gene codes for the rna polymerase β subunit, which is the target of rifampicin, an essential drug in the treatment of tuberculosis and other mycobacterial infections. this gene is present in all bacteria, but its length and nucleotide sequence vary between bacterial species, including mycobacteria. mutations in the rpob gene alter the structure of this protein and cause drug resistance. to describe the resistance-associated mutations, the scientific and medical communities have been usi ...201727664776
dc-159a shows inhibitory activity against dna gyrases of mycobacterium leprae.fluoroquinolones are a class of antibacterial agents used for leprosy treatment. some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. for example, dc-159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. nonetheless, the efficacy of dc-159a against mycobacterium leprae is yet ...201627681932
quantitative lateral flow strip assays as user-friendly tools to detect biomarker profiles for leprosy.leprosy is a debilitating, infectious disease caused by mycobacterium leprae. despite the availability of multidrug therapy, transmission is unremitting. thus, early identification of m. leprae infection is essential to reduce transmission. the immune response to m. leprae is determined by host genetics, resulting in paucibacillary (pb) and multibacillary (mb) leprosy associated with dominant cellular or humoral immunity, respectively. this spectral pathology of leprosy compels detection of immu ...201627682181
mycobacteriophages as incubators for intein dissemination and evolution.inteins are self-splicing protein elements that are mobile at the dna level and are sporadically distributed across microbial genomes. inteins appear to be horizontally transferred, and it has been speculated that phages may play a role in intein distribution. our attention turns to mycobacteriophages, which infect mycobacteria, where both phage and host harbor inteins. using bioinformatics, mycobacteriophage genomes were mined for inteins. this study reveals that these mobile elements are prese ...201627703073
sequential formation of two branched intermediates during protein splicing of class three inteins.inteins are the protein equivalent of introns. they are seamlessly removed during post-translational maturation of their host protein (extein). inteins from extremophiles played a key role in understanding intein-mediated protein splicing. there are currently three classes of inteins defined by catalytic mechanism and sequence signatures. this study demonstrates splicing of three class 3 mini-inteins: burkholderia vietnamiensis g4 bvi icmo intein, mycobacterium smegmatis mc2 155 msm dnab-1 intei ...201727704298
leprosy drug resistance surveillance in colombia: the experience of a sentinel country.an active search for mycobacterium leprae drug resistance was carried out, 243 multibacillary patients from endemic regions of colombia were included from 2004 to 2013 in a surveillance program. this program was a world health organization initiative for drug resistance surveillance in leprosy, where colombia is a sentinel country. m. leprae dna from slit skin smear and/or skin biopsy samples was amplified and sequenced to identify mutations in the drug resistance determining region (drdr) in rp ...201627706165
paleomicrobiology of leprosy.the use of paleomicrobiological techniques in leprosy has the potential to assist paleopathologists in many important aspects of their studies on the bones of victims, solving at times diagnostic problems. with mycobacterium leprae, because of the unique nature of the organism, these techniques can help solve problems of differential diagnosis. in cases of co-infection with mycobacterium tuberculosis, they can also suggest a cause of death and possibly even trace the migratory patterns of people ...201627726813
role of teffector/memory cells, tbx21 gene expression and t-cell homing receptor on type 1 reaction in borderline lepromatous leprosy patients.in spite of hyporesponsivity to mycobacterium leprae, borderline lepromatous (bl) patients show clinical and immunological instability, and undergo frequent acute inflammatory episodes such as type 1 reaction (t1r), which may cause nerve damages. this work focused on the participation of t cell subsets from blood and skin at t1r onset. we observed a significantly increased ex vivo frequency of both effector and memory cd4+ and cd8+ t cells in t1r group. besides, ex vivo frequency of t cell homin ...201627764137
[immunological evaluation during treatment of a case of borderline lepromatous leprosy].leprosy is a chronic granulomatous infection that affects skin and peripheral nerves. its prevalence has declined, but is still observed mainly in poor rural areas.201727795222
a unique case of concomitant intra and extracranial hansen's disease.leprosy is a debilitating disease that usually involves the peripheral branches of the cranial nerves leading to anesthetic/hypoesthetic skin lesions and thickened peripheral nerves. however, the involvement of the central nervous system (cns) is extremely rare. to the best of the author's knowledge, the involvement of the cranial nerve nuclei by leprosy has not been reported in the literature and the present case is the first report of involvement of the facial nerve nuclei by leprosy.201727830326
red squirrels in the british isles are infected with leprosy bacilli.leprosy, caused by infection with mycobacterium leprae or the recently discovered mycobacterium lepromatosis, was once endemic in humans in the british isles. red squirrels in great britain (sciurus vulgaris) have increasingly been observed with leprosy-like lesions on the head and limbs. using genomics, histopathology, and serology, we found m. lepromatosis in squirrels from england, ireland, and scotland, and m. leprae in squirrels from brownsea island, england. infection was detected in overt ...201627846605
a negative feedback loop between autophagy and immune responses in mycobacterium leprae infection.the obligate intracellular bacterium mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. so far, the underlying reasons allowing m. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in m. leprae infection. we found that ...201727854511
excavating the surface-associated and secretory proteome of mycobacterium leprae for identifying vaccines and diagnostic markers relevant immunodominant epitopes.for centuries, mycobacterium leprae, etiological agent of leprosy, has been afflicting mankind regardless of extensive use of live-attenuated vaccines and antibiotics. surface-associated and secretory proteins (sasps) are attractive targets against bacteria. we have integrated biological knowledge with computational approaches and present a proteome-wide identification of sasps. we also performed computational assignment of immunodominant epitopes as coordinates of prospective antigenic candidat ...201627856491
subversion of schwann cell glucose metabolism by mycobacterium leprae. 201627864529
common variants in the parl and pink1 genes increase the risk to leprosy in han chinese from south china.leprosy is a chronic infectious and neurological disease caused by mycobacterium leprae, an unculturable pathogen with massive genomic decay and dependence on host metabolism. we hypothesized that mitochondrial genes parl and pink1 would confer risk to leprosy. thirteen tag snps of parl and pink1 were analyzed in 3620 individuals with or without leprosy from china. we also sequenced the entire exons of parl, pink1 and park2 in 80 patients with a family history of leprosy by using the next genera ...201627876828
qpcr detection of mycobacterium leprae in biopsies and slit skin smear of different leprosy clinical forms.leprosy, whose etiological agent is mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. the diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. quantitative pcr (qpcr), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including mycobacterium leprae. the validation of this technique in a robust ...201727888674
evaluation of fluorescent staining for diagnosis of leprosy and its impact on grading of the disease: comparison with conventional staining.leprosy is a chronic infectious disease caused by mycobacterium leprae (m. leprae). histopathological examination of skin lesion is the gold standard for diagnosis. we evaluated the possible role of fluorescent microscopy in this direction which is increasingly used for rapid screening.201627891346
can baseline ml flow test results predict leprosy reactions? an investigation in a cohort of patients enrolled in the uniform multidrug therapy clinical trial for leprosy patients in brazil.the predictive value of the serology to detection of igm against the mycobacterium leprae-derived phenolic glycolipid-i/pgl-i to identify leprosy patients who are at higher risk of developing reactions remains controversial. whether baseline results of the ml flow test can predict leprosy reactions was investigated among a cohort of patients enrolled in the clinical trial for uniform multidrug therapy for leprosy patients in brazil (u-mdt/ct-br).201627919284
non-exponential growth of mycobacterium leprae thai-53 strain cultured in vitro.in this study, attempts were made to culture this bacterium in media supplemented with a variety of biological materials to determine why cultivation of mycobacterium leprae in vitro has not this far been successful. a slight increase in the number of cells in medium supplemented with human blood plasma and an extract of nude mouse tissue as observed after more than 3 months of cultivation at 30 °c. to ascertain whether this increase was real growth, the growth was analyzed by droplet digital pc ...201627925336
th9 cytokines response and its possible implications in the immunopathogenesis of leprosy.leprosy is an infectious-contagious disease whose clinical evolution depends on the interaction of the infectious agent with the immune response of the host, leading to a clinical spectrum that ranges from lepromatous leprosy (susceptibility, ll) to tuberculoid leprosy (resistance, tt). the immune response profile will depend on the pattern of cytokine production and on the activity of macrophages during infection. classically, the clinical evolution of leprosy has been associated with th1/th2 c ...201627927694
a large-scale genome-wide association and meta-analysis identified four novel susceptibility loci for leprosy.leprosy, a chronic infectious disease, results from the uncultivable pathogen mycobacterium leprae (m. leprae), and usually progresses to peripheral neuropathy and permanent progressive deformity if not treated. previously published genetic studies have identified 18 gene/loci significantly associated with leprosy at the genome-wide significant level. however as a complex disease, only a small proportion of leprosy risk could be explained by those gene/loci. to further identify more susceptibili ...201627976721
number of leprosy reactions during treatment: clinical correlations and laboratory diagnosis.the occurrence of leprosy reactions, a common event during treatment, may be mostly related to the action of multidrug therapy on mycobacterium leprae. the clinical and laboratory monitoring of patients with reactions is important, since collecting data that assists in predicting the risk of reactions may help to prevent disability.201728001221
evaluation of polymerase chain reaction (pcr) with slit skin smear examination (sss) to confirm clinical diagnosis of leprosy in eastern nepal.detection of mycobacterium leprae in slit skin smear (sss) is a gold standard technique for the leprosy diagnosis. over recent years, molecular diagnosis by using pcr has been increasingly used as an alternative for its diagnosis due to its higher sensitivity. this study was carried out for comparative evaluation of pcr and sss microscopy in a cohort of new leprosy cases diagnosed in b. p. koirala institute of health sciences, dharan, nepal.201628027305
autophagy is an innate mechanism associated with leprosy polarization.leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. levels of ifn-γ are significantly raised in paucibacillary tuberculoid (t-lep) when compared with multibacillary lepromatous (l-lep) patients. ifn-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. the involvement of autophagy in the immune response against mycobacterium leprae remains unexplored. here, we demonstrated by ...201728056107
mycobacterial hsp65 antigen upregulates the cellular immune response of healthy individuals compared with tuberculosis patients.previously we showed that 65-kda mycobacterium leprae heat shock protein (hsp65) is a target for the development of a tuberculosis vaccine. here we evaluated peripheral blood mononuclear cells (pbmc) from healthy individuals or tuberculosis patients stimulated with two forms of hsp65 antigen, recombinant dna that encodes hsp65 (dna-hsp65) or recombinant hsp65 protein (rhsp65) in attempting to mimic a prophylactic or therapeutic study in vitro, respectively. proliferation and cytokine-producing c ...201728059670
s100a12: friend or foe in pulmonary tuberculosis?in humans, s100a12 (also named calgranulin c and en-rage) is mainly expressed and secreted by neutrophil granulocytes. extracellular s100a12 is involved in innate immune responses against microorganisms and parasites. s100a12 is a ligand for the receptor for advanced glycation end products (rage), which is a cell surface receptor on macrophages, endothelium, and lymphocytes. in a recent study, realegeno et al. showed that s100a12 exerts antimicrobial activity against mycobacterium leprae in infe ...201728110121
evaluation and monitoring of mycobacterium leprae transmission in household contacts of patients with hansen's disease in colombia.leprosy in colombia is in a stage of post elimination-since 1997, prevalence of the disease is less than 1/10000. however, the incidence of leprosy has remained stable, with 400-500 new cases reported annually, with mb leprosy representing 70% of these case and 10% having grade 2 disability. thus, leprosy transmission is still occurring, and household contacts (hhcs) of leprosy patients are a population at high risk of contracting and suffering from the effects of the disease during their lifeti ...201728114411
investigation of a medieval pilgrim burial excavated from the leprosarium of st mary magdalen winchester, uk.we have examined the remains of a pilgrim burial from st mary magdalen, winchester. the individual was a young adult male, aged around 18-25 years at the time of death. radiocarbon dating showed the remains dated to the late 11th-early 12th centuries, a time when pilgrimages were at their height in europe. several lines of evidence in connection with the burial suggested this was an individual of some means and prestige. although buried within the leprosarium cemetery, the skeleton showed only m ...201728125649
antigen-specific secretion of ifnγ and cxcl10 in whole blood assay detects mycobacterium leprae infection but does not discriminate asymptomatic infection from symptomatic leprosy.to advance toward a whole blood assay (wba)-based test capable of facilitating the diagnosis of paucibacillary (pb) leprosy, we evaluated a prototype in-tube wba using combinations of mycobacterium leprae antigens. blood was collected from newly diagnosed untreated pb (n=38), multibacillary (mb) (n=30), healthy household contacts (hhc) of mb (n=27), and endemic controls (n=61) residing in goiânia and fortaleza, brazil. blood was incubated with m. leprae cell sonicate, recombinant proteins (46f+l ...201728126361
pathogenic mechanisms of intracellular bacteria.we wished to overview recent data on a subset of epigenetic changes elicited by intracellular bacteria in human cells. reprogramming the gene expression pattern of various host cells may facilitate bacterial growth, survival, and spread.201728134679
nasal pcr assay for the detection of mycobacterium leprae pra gene to study subclinical infection in a community.leprosy is a chronic infectious disease caused by mycobacterium leprae. identification of mycobacterium leprae is difficult in part due to the inability of the leprosy bacillus to grow in vitro. a number of diagnostic methods for leprosy diagnosis have been proposed. both serological tests and molecular probes have shown certain potential for detection and identification of mycobacterium leprae in patients. in this study, we have investigated whether mycobacterium leprae dna from the nasal secre ...201728137508
rifz (amed_0655) is a pathway-specific regulator for rifamycin biosynthesis in amycolatopsis mediterranei.rifamycin and its derivatives are particularly effective against the pathogenic mycobacteria mycobacterium tuberculosis and mycobacterium leprae although the biosynthetic pathway of rifamycin has been extensively studied in amycolatopsis mediterranei, little is known about the regulation in rifamycin biosynthesis. here, an in vivo transposon system was employed to identify genes involved in the regulation of rifamycin production in a. mediterranei u32. in total, nine rifamycin-deficient mutants ...201728159794
the influence of innate and adaptative immune responses on the differential clinical outcomes of leprosy.leprosy is a chronic infectious disease caused by mycobacterium leprae. according to official reports from 121 countries across five who regions, there were 213 899 newly diagnosed cases in 2014. although leprosy affects the skin and peripheral nerves, it can present across a spectrum of clinical and histopathological forms that are strongly influenced by the immune response of the infected individuals. these forms comprise the extremes of tuberculoid leprosy (tt), with a m. leprae-specific th1, ...201728162092
a review on dapsone hypersensitivity syndrome among chinese patients with an emphasis on preventing adverse drug reactions with genetic testing.dapsone is a bactericidal and bacteriostatic against mycobacterium leprae, a causative agent of leprosy. dapsone is also applied in a range of medical fields because of its anti-inflammatory and immunomodulatory effects. dapsone hypersensitivity syndrome (dhs) is a rare yet serious adverse drug reaction (adr) caused by dapsone involving multiple organs. we performed a systematic review of published articles describing dapsone-induced hypersensitivity syndrome, including all chinese articles and ...201728167593
histoid leprosy in varanasi.seventeen cases of histoid leprosy were found in skin out patients department of institute of medical sciences in one year out of a total of 1394 cases of leprosy registered. the histoid leprosy rate is thus 1.2 %. the total lepromitous leprosy cases were 194 with which lepromatous index works out to be 13.9% about half of the histoid leprosy cases had no antileprosy treatment. bacteriological index was high (4 to 6 + ) and morphological index renged from 20 to 70%. in this study there does not ...201728176731
multibacillary leprosy by population groups in brazil: lessons from an observational study.leprosy remains an important public health problem in brazil where 28,761 new cases were diagnosed in 2015, the second highest number of new cases detected globally. the disease is caused by mycobacterium leprae, a pathogen spread by patients with multibacillary (mb) leprosy. this study was designed to identify population groups most at risk for mb disease in brazil, contributing to new ideas for early diagnosis and leprosy control.201728192426
leprosy reactions: the predictive value of mycobacterium leprae-specific serology evaluated in a brazilian cohort of leprosy patients (u-mdt/ct-br).leprosy reactions, reversal reactions/rr and erythema nodosum leprosum/enl, can cause irreversible nerve damage, handicaps and deformities. the study of mycobacterium leprae-specific serologic responses at diagnosis in the cohort of patients enrolled at the clinical trial for uniform multidrug therapy regimen for leprosy patients in brazil/u-mdt/ct-br is suitable to evaluate its prognostic value for the development of reactions.201728222139
historical overview of leprosy control in cuba.introduction leprosy, an infectious disease caused by mycobacterium leprae, affects the nervous system, skin, internal organs, extremities and mucous membranes. biological, social and environmental factors influence its occurrence and transmission. the first effective treatments appeared in 1930 with the development of dapsone, a sulfone. the main components of a control and elimination strategy are early case detection and timely administration of multidrug therapy. objectives review the histor ...201728225542
unexpectedly high leprosy seroprevalence detected using a random surveillance strategy in midwestern brazil: a comparison of elisa and a rapid diagnostic test.leprosy diagnosis is mainly based on clinical evaluation, although this approach is difficult, especially for untrained physicians. we conducted a temporary campaign to detect previously unknown leprosy cases in midwestern brazil and to compare the performance of different serological tests.201728231244
leprosy in puerto rico: insight into the new millennia.leprosy, or hansen's disease, is a chronic infectious disease caused by the bacillus mycobacterium leprae. in 2000, the world health organization (who) defined the elimination of the disease as a global prevalence of less than one case per 10,000 population. however, disease transmission is an ongoing worldwide public health concern, as evidenced by the more than 220,000 new cases diagnosed each year.201728233305
t helper cells in leprosy: an update.leprosy is an ancient disease caused by gram positive, rod shaped bacilli called mycobacterium leprae. patients present with varied clinico-pathological disease depending on the host immune response to mycobacterium leprae. thus tuberculoid (tt) and lepromatous (ll) patients represent two ends of a spectrum where the former shows limited disease, high t cell mediate immune (cmi) response and low antibody (hi) levels in serum. in contrast the latter has low t cell and high humoral immune response ...201728235552
association of a new fcn3 haplotype with high ficolin-3 levels in leprosy.leprosy is a chronic inflammatory disease caused by mycobacterium leprae that mainly affects the skin and peripheral nervous system, leading to a high disability rate and social stigma. previous studies have shown a contribution of genes encoding products of the lectin pathway of complement in the modulation of the susceptibility to leprosy; however, the ficolin-3/fcn3 gene impact on leprosy is currently unknown. the aim of the present study was to investigate if fcn3 polymorphisms (rs532781899: ...201728241035
leprosy - one of the many forgotten tropical diseases.leprosy or hansen disease is caused by an infection of mycobacterium leprae. the large number of undetected cases (2000-2012 years 4 mln people) remains a threat to the elimination of leprosy. leprosy is an unheard in poland and generally is considered a condition so "exotic" that it is not worth to spend more attention to it. forgotten disease in developed countries still thrives in an environment of poor and uneducated. regardless of the conclusion that in the 21st century none infectious dise ...201728258667
leprosy: trophic skin ulcers.leprosy is a chronic infectious disease caused by mycobacterium leprae. approximately 30% of patients with leprosy develop nerve damage. trophic, or neuropathic, ulcer is a common complication of an anesthetic foot. the term plantar, trophic, or perforating ulcer was introduced in 1959. it was defined as a chronic ulceration of the anesthetic foot, situated in well-defined areas overlying bony prominences, resistant to local and/or systemic therapy, and characterized by a marked tendency to recu ...201728270310
editorial-mycobacterium leprae captured? 201728276399
multifaceted role of lipids in mycobacterium leprae.mycobacterium leprae must adopt a metabolic strategy and undergo various metabolic alterations upon infection to survive inside the human body for years in a dormant state. a change in lipid homeostasis upon infection is highly pronounced in mycobacterium leprae. lipids play an essential role in the survival and pathogenesis of mycobacteria. lipids are present in several forms and serve multiple roles from being a source of nutrition, providing rigidity, evading the host immune response to servi ...201728287297
leprosy on the scalp.leprosy is a chronic infectious disease caused by mycobacterium leprae. this bacillus has a high predilection for skin and peripheral nerves. the scalp's anatomical properties do not favor the development of such mycobacterium. we report a case of leprosy with scalp involvement, a rare occurrence in our literature.201728300899
association of nitric oxide synthase2 gene polymorphisms with leprosy reactions in northern indian population.the pathogen mycobacterium leprae causes leprosy that affects mainly skin and nerves. polymorphisms of certain genes are substantiated to be associated with the susceptibility/resistance to leprosy. the present investigation addressed the association of nitric oxide synthase2 gene polymorphisms and leprosy in a population from northern part of india. a total of 323 leprosy cases and 288 healthy controls were genotyped for four nos2 promoter variants (rs1800482, rs2779249, rs8078340 and rs2301369 ...201728315742
analysis of a novel multiplex polymerase chain reaction assay as a sensitive tool for the diagnosis of indeterminate and tuberculoid forms of leprosy.clinical diagnosis of indeterminate and tuberculoid leprosy is often difficult due to limited and confounding signs and symptoms. in the current study, we evaluated the utility of new multiplex polymerase chain reaction (pcr) using mycobacterium leprae-specific dna sequences in the pseudogene regions of ml1545, ml2180, and ml2179 for pcr-based diagnosis of indeterminate leprosy (ind) and leprosy cases across the immunological spectrum. the sensitivity was compared with that of rlep pcr.201728317797
mycobacterium lepraemurium uses tlr-6 and mr, but not lipid rafts or dc-sign, to gain access into mouse macrophages.mycobacterium lepraemurium (mlm), the etiologic agent of murine leprosy, is an intracellular parasite of macrophages; the mechanism used by this bacterium to enter macrophages is not known. the fate of the mlm phagosome inside macrophages is also unknown. this study was conducted to investigate how mlm enters macrophages and to define the maturation process of mlm phagosome inside macrophages.201728317806
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