Publications

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 ...	2014	24661741
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 ...	2014	24657272
gerhard henrik armauer hansen (1841-1912)--100 years anniversary tribute.	2012 marks the 100th year of death of gerhard henrik armauer hansen (1841-1912), who discovered mycobacterium leprae, but also gave the first systematic scientific work on the leprosy of the eye. the article reviews his life and scientific achievements with special regard to eye and ophthalmology.	2014	23710612
an attempt to improve pure neural leprosy diagnosis using immunohistochemistry tests in peripheral nerve biopsy specimens.	the diagnosis of pure neural leprosy (pnl) is based on clinical and laboratory data, including the histopathology of nerve biopsy specimens and detection of mycobacterium leprae dna by polymerase chain reaction (pcr). given that histopathologic examination and pcr methods may not be sufficient to confirm the diagnosis, immunolabeling of lipoarabinomanan (lam) and/or phenolic glycolipid 1 (pgl-1) m. leprae wall components was utilized in the present investigation in an attempt to detect any vesti ...	2014	23702646
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 ...	2014	24033793
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- ...	2014	24022478
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.	2014	24065328
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 ...	2014	24168291
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 ...	2014	24214631
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 ...	2014	24264476
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 ...	2014	24328380
reactive perforating leprosy: pustular erythema nodosum leprosum with epidermal perforation and liberation of mycobacterium leprae.		2014	24319988
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 ...	2014	24279882
case of arthritis secondary to leprosy.	leprosy is a chronic granulomatous infectious disease, which is caused by mycobacterium leprae. high numbers of people are still affected by this disease in some of the developing countries however, it is rarely seen in non-endemic regions. cutaneous and neurological manifestations are the common and classical presentations of leprosy. musculoskeletal involvement is the third most common manifestation but is less frequently reported. joint involvement can present as acute symmetrical polyarthrit ...	2014	26034700
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 ...	2014	24370984
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.	2014	24361943
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.	2014	24907710
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 ...	2014	24907144
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 ...	2014	24880131
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 ...	2014	24874086
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 ...	2014	24861093
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 ...	2014	24810599
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 ...	2014	24495190
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 ...	2014	24493677
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 ...	2014	24483959
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 ...	2014	24480058
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 ...	2014	24478496
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 ...	2014	24469317
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 ...	2014	24469081
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 ...	2014	24464703
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 ...	2014	24460757
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.	2014	24454972
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 ...	2014	24619112
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 ...	2014	24615444
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 ...	2014	24612452
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 ...	2014	24607935
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 ...	2014	24563210
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 ...	2014	24552180
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 ...	2014	24551248
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 ...	2014	24527821
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 ...	2014	24520878
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.	2014	24512544
mycobacterium leprae is identified in the oral mucosa from paucibacillary and multibacillary leprosy patients.	in leprosy, the nasal mucosa is considered as the principal route of transmission for the bacillus mycobacterium leprae. the objective of this study was to identify m. leprae in the oral mucosa of 50 untreated leprosy patients, including 21 paucibacillary (pb) and 29 multibacillary (mb) patients, using immunohistochemistry (ihc), with antibodies against bacillus calmette-guérin (bcg) and phenolic glycolipid antigen-1 (pgl-1), and polymerase chain reaction (pcr), with mnth-specific primers for m. ...	2014	23473290
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.	2015	24177608
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 ...	2015	24346893
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 ...	2015	25007893
case for diagnosis.	hansen's disease is a chronic infecto-contagious disease caused by mycobacterium leprae. the bacillus prefers low-temperature areas and the nose is usually the initial site of lesions. transmission of the bacilli occurs by nasal and oropharyngeal secretions, and through solutions of continuity of the skin and/or mucosae. nasal manifestations are found in the later stages of the disease.	2015	25184933
a report of rifampin-resistant leprosy from northern and eastern india: identification and in silico analysis of molecular interactions.	presence of point mutations within the drug resistance determining regions of mycobacterium leprae (m. leprae) genome confers molecular basis of drug resistance to dapsone, rifampin and ofloxacin in leprosy. this study is focused on the identification of mutations within the rpob gene region of m. leprae that are specific for rifampin interaction, and further in silico analysis was carried out to determine the variations in the interactions. dna and rna were isolated from slit skin scrapings of ...	2015	25201810
benefits and limitations of fine needle aspiration cytology in the diagnosis and classification of leprosy in primary and secondary healthcare settings.	the goal of the world health organization (who) is to eliminate leprosy as a public health problem. this will only be possible when all patients are detected and cured using multidrug therapy, which requires accurate diagnosis prior to treatment. the objective of this study was to evaluate the possibility of the diagnosis of leprosy lesions by fine needle aspiration cytology according to a modification of the ridley-jopling scale, as it can be used in primary and secondary healthcare centres, es ...	2015	25196453
carbohydrate-dependent binding of langerin to sodc, a cell wall glycoprotein of mycobacterium leprae.	langerhans cells participate in the immune response in leprosy by their ability to activate t cells that recognize the pathogen, mycobacterium leprae, in a langerin-dependent manner. we hypothesized that langerin, the distinguishing c-type lectin of langerhans cells, would recognize the highly mannosylated structures in pathogenic mycobacterium spp. the coding region for the extracellular and neck domain of human langerin was cloned and expressed to produce a recombinant active trimeric form of ...	2015	25422308
association of the lrrk2 genetic polymorphisms with leprosy in han chinese from southwest china.	leprosy is a chronic infectious and neurological disease that is caused by infection of mycobacterium leprae (m. leprae). a recent genome-wide association study indicated a suggestive association of lrrk2 genetic variant rs1873613 with leprosy in chinese population. to validate this association and further identify potential causal variants of lrrk2 with leprosy, we genotyped 13 lrrk2 variants in 548 leprosy patients and 1078 healthy individuals from yunnan province and (re-)analyzed 3225 han ch ...	2015	25521227
cxcl10, mcp-1, and other immunologic markers involved in neural leprosy.	nerve damage in leprosy can be directly induced by mycobacterium leprae in the early stages of infection, however, immunomediated mechanisms add gravity to the impairment of neural function in symptomatic periods of the disease. this study investigated the immunohistochemical expression of immunomarkers involved in the pathogenic mechanisms of leprosy nerve damage. these markers selected were cxcl10, ccl2 chemokines and immunomarkers as cd3, cd4, cd8, cd45ra, cd45ro, cd68, hla-dr, and metallopro ...	2015	25221954
protecting people against leprosy: chemoprophylaxis and immunoprophylaxis.	elimination of leprosy cannot be achieved by multidrug therapy alone, and new tools are needed to prevent leprosy. a randomized controlled trial with chemoprophylaxis for contacts of leprosy patients using a single dose of rifampicin (sdr) has shown an overall protective effect of approximately 60%, effective in the first 2 years after the intervention. when a contact who previously received bacillus calmette-guérin (bcg) vaccination also receives sdr, the protective effect is additive, approxim ...	2015	25432807
immunology of leprosy and diagnostic challenges.	leprosy, caused by noncultivable mycobacterium leprae (ml), has varied manifestations, which are associated with the host immune responses. the dermal involvement is accompanied by peripheral nerve damage, which leads to sensory motor loss and deformities. both innate and acquired immune responses are involved. the main cell to be compromised is the cd4 + t helper cell, which shows antigen specific unresponsiveness to only ml and not to other common antigens in the bacilliferous generalized lepr ...	2015	25432814
type 1 reaction in leprosy: a model for a better understanding of tissue immunity under an immunopathological condition.	type 1 reaction (t1r) or reversal reaction is the leading cause of physical disabilities and deformities in leprosy. leprosy patients, even after being considered cured and released from treatment, may suffer from reactional episodes for long periods of time. early diagnosis is a great challenge for effectively treating and managing t1r. there is an urgent need to identify the most significant biomarkers to prevent recurrent t1r and to differentiate late t1r from relapse. t1r continues to be tre ...	2015	25666357
association of tnf -1031 c/c as a potential protection marker for leprosy development in amazonas state patients, brazil.	polymorphisms present in the tnf promoter region has shown to influence the gene transcription. leprosy displays different clinical manifestations according to the immune responses of the individual infected with mycobacterium leprae. in this study, we evaluated the single nucleotide polymorphisms (snps) -238 g/a (rs361525), -308 g/a (rs1800629), -857 c/t (rs1799724), -863 a/c (rs1800630) and -1031 t/c (rs1799964) in the promoter region of the tnf to see whether these snps influence host-suscept ...	2015	25636570
the role of erbb2 gene polymorphisms in leprosy susceptibility.	mycobacterium leprae infects skin and peripheral nerves causing deformities and disability. the m. leprae bacterium binds to erbb2 on the schwann cell surface causing demyelination and favoring spread of the bacilli and causing nerve injury. polymorphisms at the erbb2 gene were previously investigated as genetic risk factors for leprosy in two brazilian populations but with inconsistent results. herein we extend the analysis of erbb2 variants to a third geographically distinct population in braz ...	2015	25636184
evaluation of a low-density hydrogel microarray technique for mycobacterial species identification.	in addition to the obligatory pathogenic species of the mycobacterium tuberculosis complex and mycobacterium leprae, the genus mycobacterium also includes conditionally pathogenic species that in rare cases can lead to the development of nontuberculous mycobacterial diseases. because tuberculosis and mycobacteriosis have similar clinical signs, the accurate identification of the causative agent in a clinical microbiology laboratory is important for diagnostic verification and appropriate treatme ...	2015	25609722
human leukocyte antigen class i and class ii alleles are associated with susceptibility and resistance in borderline leprosy patients from southeast brazil.	evidence suggests that human leukocyte antigen (hla) alleles influence the host immune response against mycobacterium leprae. however, the association between hla alleles and borderline (b) leprosy has not been studied. the aim of this study was to determine whether hla class i and ii molecules are associated with susceptibility or resistance to b leprosy including borderline-tuberculoid (bt), borderline-borderline (bb), and borderline-lepromatous (bl).	2015	25605482
molecular mimicry between mycobacterium leprae proteins (50s ribosomal protein l2 and lysyl-trna synthetase) and myelin basic protein: a possible mechanism of nerve damage in leprosy.	autoantibodies against various components of host are known to occur in leprosy. nerve damage is the primary cause of disability associated with leprosy. the aim of this study was to detect the level of autoantibodies and lympho-proliferative response against myelin basic protein (mbp) in leprosy patients (lps) and their correlation with clinical phenotypes of lps. further, probable role of molecular mimicry in nerve damage of lps was investigated. we observed significantly high level of anti-mb ...	2015	25576930
biosynthesis of cell envelope-associated phenolic glycolipids in mycobacterium marinum.	phenolic glycolipids (pgls) are polyketide synthase-derived glycolipids unique to pathogenic mycobacteria. pgls are found in several clinically relevant species, including various mycobacterium tuberculosis strains, mycobacterium leprae, and several nontuberculous mycobacterial pathogens, such as m. marinum. multiple lines of investigation implicate pgls in virulence, thus underscoring the relevance of a deep understanding of pgl biosynthesis. we report mutational and biochemical studies that in ...	2015	25561717
bacterial-induced cell reprogramming to stem cell-like cells: new premise in host-pathogen interactions.	bacterial pathogens employ a myriad of strategies to alter host tissue cell functions for bacterial advantage during infection. recent advances revealed a fusion of infection biology with stem cell biology by demonstrating developmental reprogramming of lineage committed host glial cells to progenitor/stem cell-like cells by an intracellular bacterial pathogen mycobacterium leprae. acquisition of migratory and immunomodulatory properties of such reprogrammed cells provides an added advantage for ...	2015	25541240
interaction of atp with a small heat shock protein from mycobacterium leprae: effect on its structure and function.	adenosine-5'-triphosphate (atp) is an important phosphate metabolite abundantly found in mycobacterium leprae bacilli. this pathogen does not derive atp from its host but has its own mechanism for the generation of atp. interestingly, this molecule as well as several antigenic proteins act as bio-markers for the detection of leprosy. one such bio-marker is the 18 kda antigen. this 18 kda antigen is a small heat shock protein (hsp18) whose molecular chaperone function is believed to help in the g ...	2015	25811190
skin imprinting in silica plates: a potential diagnostic methodology for leprosy using high-resolution mass spectrometry.	leprosy is a chronic infectious disease caused by mycobacterium leprae, which primarily infects macrophages and schwann cells, affecting skin and peripheral nerves. clinically, the most common form of identification is through the observation of anesthetic lesions on skin; however, up to 30% of infected patients may not present this clinical manifestation. currently, the gold standard diagnostic test for leprosy is based on skin lesion biopsy, which is invasive and presents low sensibility for s ...	2015	25785304
ancient dna analysis - an established technique in charting the evolution of tuberculosis and leprosy.	many tuberculosis and leprosy infections are latent or paucibacillary, suggesting a long time-scale for host and pathogen co-existence. palaeopathology enables recognition of archaeological cases and pcr detects pathogen ancient dna (adna). mycobacterium tuberculosis and mycobacterium leprae cell wall lipids are more stable than adna and restrict permeability, thereby possibly aiding long-term persistence of pathogen adna. amplification of adna, using specific pcr primers designed for short frag ...	2015	25773651
m. leprae components induce nerve damage by complement activation: identification of lipoarabinomannan as the dominant complement activator.	peripheral nerve damage is the hallmark of leprosy pathology but its etiology is unclear. we previously identified the membrane attack complex (mac) of the complement system as a key determinant of post-traumatic nerve damage and demonstrated that its inhibition is neuroprotective. here, we determined the contribution of the mac to nerve damage caused by mycobacterium leprae and its components in mouse. furthermore, we studied the association between mac and the key m. leprae component lipoarabi ...	2015	25772973
immunohistochemical analysis of the expression of cellular transcription nfκb (p65), ap-1 (c-fos and c-jun), and jak/stat in leprosy.	leprosy is a disease whose clinical spectrum depends on the cytokine patterns produced during the early stages of the immune response. the main objective of this study was to describe the activation pattern of cellular transcription factors and to correlate these factors with the clinical forms of leprosy. skin samples were obtained from 16 patients with the tuberculoid (tt) form and 14 with the lepromatous (ll) form. the histologic sections were immunostained with anti-c-fos and anti-c-jun mono ...	2015	25771902
mathematical modelling of leprosy and its control.	leprosy or hansen's disease is an infectious disease caused by the bacterium mycobacterium leprae. the annual number of new leprosy cases registered worldwide has remained stable over the past years at over 200,000. early case finding and multidrug therapy have not been able interrupt transmission completely. elimination requires innovation in control and sustained commitment. mathematical models can be used to predict the course of leprosy incidence and the effect of intervention strategies. tw ...	2015	25765193
report of rpob mutation in clinically suspected cases of drug resistant leprosy: a study from eastern india.	the current strategy for leprosy control depends mainly on early case detection and providing the recommended multidrug therapy (mdt) dosage. understanding the molecular mechanisms of drug resistance to each of these drugs is essential in providing effective treatment and preventing the spread of resistant strains in the community. the progress of molecular biology research provides a very efficient opportunity for the diagnosis of drug resistance by in vitro method.	2015	25751332
clinical manifestations of leprosy after bcg vaccination: an observational study in bangladesh.	although bcg is used as a vaccine against tuberculosis, it also protects against leprosy. previous evaluation over 18 years of an intervention of two doses bcg for 3536 household contacts of leprosy patients showed that 28 (23%) out of 122 contacts diagnosed with leprosy, developed symptoms 2-10 months after vaccination. this study describes contacts of leprosy patients in bangladesh who developed leprosy within 12 weeks after receiving a single bcg dose.	2015	25701674
a migration-driven model for the historical spread of leprosy in medieval eastern and central europe.	leprosy was rare in europe during the roman period, yet its prevalence increased dramatically in medieval times. we examined human remains, with paleopathological lesions indicative of leprosy, dated to the 6th-11th century ad, from central and eastern europe and byzantine anatolia. analysis of ancient dna and bacterial cell wall lipid biomarkers revealed mycobacterium leprae in skeletal remains from 6th-8th century northern italy, 7th-11th century hungary, 8th-9th century austria, the slavic gr ...	2015	25680828
computational simulation techniques to understand rifampicin resistance mutation (s425l) of rpob in m. leprae.	mycobacterium leprae, the etiologic agent of leprosy, is non-cultivable in vitro. consequently, the assessment of antibiotic activity against m. leprae hinge mainly upon the time consuming mouse footpad system. as m. leprae develops resistance against most of the drugs, the evolution of new long acting antimycobacterial compounds stand in need for leprosy control. the rpob of m. leprae is the target of antimycobacterial drug, rifampicin. recently, cases were reported that rpob mutation (s425l) b ...	2015	25676141
comparative evaluation of pcr amplification of rlep, 16s rrna, rpot and sod a gene targets for detection of m. leprae dna from clinical and environmental samples.	pcr assay is a highly sensitive, specific and reliable diagnostic tool for the identification of pathogens in many infectious diseases. genome sequencing mycobacterium leprae revealed several gene targets that could be used for the detection of dna from clinical and environmental samples. the pcr sensitivity of particular gene targets for specific clinical and environmental isolates has not yet been established. the present study was conducted to compare the sensitivity of rlep, rpot, sod a and ...	2015	26655199
gene association with leprosy: a review of published data.	leprosy is a chronic infectious disease caused by an obligate intracellular bacterium known as mycobacterium leprae. exposure to the bacillus is necessary, but this alone does not mean an individual will develop clinical symptoms of the disease. in recent years, several genes have been associated with leprosy and the innate immune response pathways converge on the main hypothesis that genes are involved in the susceptibility for the disease in two distinct steps: for leprosy per se and in the de ...	2015	26793196
expression of nucleotide-oligomerization domain (nod) and related genes in mouse tissues infected with mycobacterium leprae.	the nucleotide-oligomerization domain (nod) is an important molecule involved in host defense against bacterial infection. to study the role of nods in the host response to mycobacterium leprae, we measured the mrna levels of nods and related genes in infected mouse tissues. the mrna expression of nod1, nod2, caspase-1 and asc was increased in mouse footpads. whereas nod2 expression in macrophages was increased at 2 and 24 h post-infection with m. leprae, there was no expression of nod1 at these ...	2015	26770186
presence of mycobacterium leprae dna and pgl-1 antigen in household contacts of leprosy patients from a hyperendemic area in brazil.	leprosy is a highly infectious disease endemic to underdeveloped countries. in maranhão state, northeastern brazil, the hyperendemic rate of 56.11 cases/100,000 inhabitants increased the necessity of better understanding the epidemiological profile of this population, particularly regarding efficient methods for evaluating individuals residing with diagnosed patients to understand disease transmission and the risk of infection. in this study, we examined the percentage of contacts with positive ...	2015	26600506
zoonotic leprosy in the southeastern united states.	nine-banded armadillos (dasypus novemcinctus) are naturally infected with mycobacterium leprae and have been implicated in zoonotic transmission of leprosy. early studies found this disease mainly in texas and louisiana, but armadillos in the southeastern united states appeared to be free of infection. we screened 645 armadillos from 8 locations in the southeastern united states not known to harbor enzootic leprosy for m. leprae dna and antibodies. we found m. leprae-infected armadillos at each ...	2015	26583204
validation of qpcr methods for the detection of mycobacterium in new world animal reservoirs.	zoonotic pathogens that cause leprosy (mycobacterium leprae) and tuberculosis (mycobacterium tuberculosis complex, mtbc) continue to impact modern human populations. therefore, methods able to survey mycobacterial infection in potential animal hosts are necessary for proper evaluation of human exposure threats. here we tested for mycobacterial-specific single- and multi-copy loci using qpcr. in a trial study in which armadillos were artificially infected with m. leprae, these techniques were spe ...	2015	26571269
rapid identification of mycobacterium leprae by polymerase chain reaction-restriction fragment length polymorphism analysis of the heat shock protein 65 gene from skin specimens.		2015	26521798
differential expression of solute carrier family 11a member 1 and inducible nitric oxide synthase 2 in skin biopsies from leprosy patients.	leprosy is a chronic granulomatous infection caused by mycobacterium leprae, an intracellular parasite that resides within macrophages and cannot be eliminated effectively. solute carrier family 11a member 1 (slc11a1) and inducible nitric oxide synthase (inos), both expressed in macrophages, play major roles in host defense against several intracellular pathogens. however, the roles of these molecules in natural infection with m. leprae remain unknown.	2015	26515838
longitudinal immune profiles in type 1 leprosy reactions in bangladesh, brazil, ethiopia and nepal.	acute inflammatory reactions are a frequently occurring, tissue destructing phenomenon in infectious- as well as autoimmune diseases, providing clinical challenges for early diagnosis. in leprosy, an infectious disease initiated by mycobacterium leprae (m. leprae), these reactions represent the major cause of permanent neuropathy. however, laboratory tests for early diagnosis of reactional episodes which would significantly contribute to prevention of tissue damage are not yet available. althoug ...	2015	26510990
current knowledge on mycobacterium leprae transmission: a systematic literature review.	summary	2015	26502685
leprosy mimicking psoriasis.		2015	26500993
could mycobacterium leprae infection be an occupational disease? a survey in healthcare workers from an endemic area in the amazonian region.	a serologic survey was conducted to evaluate the prevalence of mycobacterium leprae infection among healthcare workers and associated factors. of 280 workers, 26 (9.3%) were positive using immunoglobulin m serology for pgl-i m. leprae antigen. exposure to leprosy patients in the workplace was significantly associated with seropositivity (p=.044).	2015	26456726
genotyping of mycobacterium leprae strains from a region of high endemic leprosy prevalence in india.	leprosy is still a major health problem in india which has the highest number of cases. multiple locus variable number of tandem repeat analysis (mlva) and single nucleotide polymorphism (snp) have been proposed as tools of strain typing for tracking the transmission of leprosy. however, empirical data for a defined population from scale and duration were lacking for studying the transmission chain of leprosy. seventy slit skin scrapings were collected from purulia (west bengal), miraj (maharash ...	2015	26444583
new insights into the geographic distribution of mycobacterium leprae snp genotypes determined for isolates from leprosy cases diagnosed in metropolitan france and french territories.	between 20 and 30 bacteriologically confirmed cases of leprosy are diagnosed each year at the french national reference center for mycobacteria. patients are mainly immigrants from various endemic countries or living in french overseas territories. we aimed at expanding data regarding the geographical distribution of the snp genotypes of the m. leprae isolates from these patients.	2015	26441080
indigenous cases of leprosy (hansen's disease) in southern mississippi.	hansen's disease or leprosy is a chronic infection of the skin and peripheral nerves caused by mycobacterium leprae. in the u.s., leprosy is mainly reported in immigrants, but indigenous leprosy cases have been also reported in this country, especially in semitropical southern states (i.e., texas, louisiana). the objective of this series of cases is to describe indigenous leprosy cases reported in southern mississippi (ms) during the period 2012-2014. information was collected from medical recor ...	2015	26434167
performance of pcr-reverse blot hybridization assay for detection of rifampicin-resistant mycobacterium leprae.	drug resistance in mycobacterium leprae is a significant problem in countries where leprosy is endemic. a sensitive, specific, and high-throughput reverse blot hybridization assay (reba) for the detection of genotypic resistance to rifampicin (rif) was designed and evaluated. it has been shown that resistance to rif in m. leprae involves mutations in the rpob gene encoding the -subunit of the rna polymerase. the pcr-reba simultaneously detects both 6 wild-type regions and 5 different mutations ( ...	2015	26428919
update on the epidemiology, diagnosis, and treatment of leprosy.	leprosy is an infectious disease that has now been reported for more than 2000 years. the leprosy elimination goal set by the world health organization (who), i.e. a global prevalence rate <1 patient per 10,000 population, was achieved in the year 2000, but more than 200,000 new case patients are still reported each year, particularly in india, brazil, and indonesia. leprosy is a specific infection: (i) it is a chronic infection primarily affecting the skin and peripheral nerves, (ii) mycobacter ...	2015	26428602
a study of liver function tests in leprosy.	leprosy is a chronic progressive granulomatous disease caused by mycobacterium leprae. hepatic involvement is seen in early stages of the disease. administration of the hepatotoxic drugs like rifampicin and dapsone may further deteriorate the liver function. the present study was undertaken to evaluate hepatic status by studying the various liver function tests in leprosy patients and compared to healthy controls. thirty untreated leprosy patients (18 multibacillary, 12 paucibacillary) with dura ...	2015	26411248
b cells expressing il-10 mrna modulate memory t cells after dna-hsp65 immunization.	in dna vaccines, the gene of interest is cloned into a bacterial plasmid that is engineered to induce protein production for long periods in eukaryotic cells. previous research has shown that the intramuscular immunization of balb/c mice with a naked plasmid dna fragment encoding the mycobacterium leprae 65-kda heat-shock protein (pcdna3-hsp65) induces protection against m. tuberculosis challenge. a key stage in the protective immune response after immunization is the generation of memory t cell ...	2015	26397973
the essential role of cholesterol metabolism in the intracellular survival of mycobacterium leprae is not coupled to central carbon metabolism and energy production.	mycobacterium leprae induces the formation of lipid droplets, which are recruited to pathogen-containing phagosomes in infected macrophages and schwann cells. cholesterol is among the lipids with increased abundance in m. leprae-infected cells, and intracellular survival relies on cholesterol accumulation. the present study investigated the capacity of m. leprae to acquire and metabolize cholesterol. in silico analyses showed that oxidation of cholesterol to cholest-4-en-3-one (cholestenone), th ...	2015	26391209
influence of genetic ancestry on indel markers of nfkβ1, casp8, par1, il4 and cyp19a1 genes in leprosy patients.	leprosy is an insidious infectious disease caused by the obligate intracellular bacteria mycobacterium leprae, and host genetic factors can modulate the immune response and generate distinct categories of leprosy susceptibility that are also influenced by genetic ancestry.	2015	26367014
downregulation of phex in multibacillary leprosy patients: observational cross-sectional study.	peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. the phosphate-regulating gene with homologies to endopeptidase on the x chromosome (phex) encodes a homonymous protein (phex) implicated in bone metabolism. phex/phex alterations may result in bone and cartilage lesions. phex expression is downregulated by intracellular mycobacterium leprae (m. leprae) in cultures of human schwann cells and osteoblasts. m. leprae in vivo effect on ph ...	2015	26362198
human genetic ancestral composition correlates with the origin of mycobacterium leprae strains in a leprosy endemic population.	recent reports have suggested that leprosy originated in africa, extended to asia and europe, and arrived in the americas during european colonization and the african slave trade. due to colonization, the contemporary colombian population is an admixture of native-american, european and african ancestries. because microorganisms are known to accompany humans during migrations, patterns of human migration can be traced by examining genomic changes in associated microbes. the current study analyze ...	2015	26360617
common variants of opa1 conferring genetic susceptibility to leprosy in han chinese from southwest china.	leprosy is an ancient chronic infection caused by mycobacterium leprae. onset of leprosy was highly affected by host nutritional condition and energy production, (partially) due to genomic loss and parasitic life style of m. leprae. the optic atrophy 1 (opa1) gene plays an essential role in mitochondria, which function in cellular energy supply and innate immunity.	2015	26360011
inflammatory mediators of leprosy reactional episodes and dental infections: a systematic review.	reactional episodes in leprosy are a result of complex interactions between the immune system, mycobacterium leprae, and predisposing factors, including dental infections. to determine the main inflammatory mediators in the immunopathological process of dental infections and leprosy reactions, we conducted a systematic review of primary literature published between 1996 and 2013. a three-stage literature search was performed (stage i, "leprosy reactions" and "inflammatory mediators"; stage ii, " ...	2015	26339136
new players in the same old game: disturbance of group 2 innate lymphoid cells in hiv-1 and mycobacterium leprae co-infected patients.	leprosy control is achieved through a fine-tuning of th1 and th2 immune response pattern balance. given the increasing epidemiological overlay of hiv and m. leprae infections, immune response in co-infected patients consists in an important contemporary issue. here we describe for the first time the innate lymphoid cells compartment in peripheral blood of leprosy and hiv/m. leprae co-infected patients, and show that co-infection increases group 2 innate lymphoid whilst decreasing group 1 innate ...	2015	26335023
laryngeal involvement causing dysphonia in a 29 year old nursing mother with lepromatous leprosy.	leprosy is a granulomatous disease that mainly affects the skin and peripheral nerves. it is caused by infection with mycobacterium leprae or mycobacterium lepromatosus. in most instances, diagnosis of leprosy can easily be made based on the clinical signs and symptoms. however, when patients present with atypical features, clinical diagnosis can be a challenge. we report a case of a nursing mother with lepromatous leprosy who presented with dysphonia and skin lesions initially thought to be a d ...	2015	26327983
emergence of primary drug resistance to rifampicin in mycobacterium leprae strains from leprosy patients in india.		2015	26314915