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a study of the distribution of mycobacterium leprae strains among cases in a rural and urban population of maharashtra, india.the elimination of leprosy continues to be a challenge with several countries remaining endemic for the disease. india accounts for the highest number of cases and the identification of child cases indicates recent transmission. genetic markers like vntrs and snps have been identified to track transmission of the pathogen mycobacterium leprae. these were used to describe m. leprae strains detected in 48 skin biopsies of leprosy patients in the state of maharashtra in western india in a rural and ...201122205800
Changes in the size and number of skin lesions in PB leprosy on treatment and follow-up.The increase in size of existing skin lesions and appearance of new skin lesions are considered important signs of clinical activity both in untreated and treated leprosy. To confirm such activity, the number and size of lesions need to be recorded methodically prior to therapy and on follow-up, especially in PB leprosy where clinical signs alone define the reactivation of the disease. However, no systematic follow-up studies are available on changes in size and number of skin lesions in PB lepr ...201122125932
leprosy initially misdiagnosed as sarcoidosis, adult-onset still disease, or autoinflammatory disease.leprosy is a chronic granulomatous disease caused by mycobacterium leprae. we describe the case of a 20-year-old man from india living in italy since 2003, who presented with erythematous papules and nodules distributed on his arms, legs, and face in 2006. he also had episodes of high fever, polyarthritis, and episcleritis. sarcoidosis was suspected on the basis of elevated angiotensin-converting enzyme and bronchoalveolar lavage fluid, and the patient was treated with corticosteroids for about ...201122089994
an enlarged, adaptable active site in cyp164 family p450 enzymes, the sole p450 in mycobacterium leprae.cyp164 family p450 enzymes are found in only a subset of mycobacteria and include cyp164a1, which is the sole p450 found in mycobacterium leprae, the causative agent of leprosy. this has previously led to interest in this enzyme as a potential drug target. here we describe the first crystal structure of a cyp164 enzyme, cyp164a2 from mycobacterium smegmatis. cyp164a2 has a distinctive, enlarged hydrophobic active site that extends above the porphyrin ring toward the access channels. unusually, w ...201222037849
early diagnosis of relapse in borderline leprosy: two case reports.two cases of relapse in borderline leprosy were reported. despite the late-reversal, reaction-like feature, the suspicion of relapse in both was based on persistent and slow-developing skin lesions and an absence of acute neuritis or reaction during one year of follow-up. the authors have considered this possible occurrence in lepromatous borderline-treated patients after their immune cellular restoration and defend that not all type 1 reactions would be an inflammatory answer to persistent myco ...201122183459
Oral lesion in leprosy: borderline tuberculoid diagnosis based on detection of Mycobacterium leprae DNA by qPCR.Oral lesions are rarely reported in paucibacillary forms of leprosy. We report here a case with an erythematous hyposensitive lesion in the palate and no skin lesions. In addition to routine tests, biopsies of the lesion in the palate and of clinically normal surrounding areas were performed and subjected to real-time PCR for detection of Mycobacterium leprae DNA. The biopsy of the oral lesion was positive for bacilli DNA, followed by positive serum anti-PGL-1 and Mitsuda test, but with negative ...201121879249
Serum metabolomics reveals higher levels of polyunsaturated fatty acids in lepromatous leprosy: potential markers for susceptibility and pathogenesis.Leprosy is a disease of the skin and peripheral nervous system caused by the obligate intracellular bacterium Mycobacterium leprae. The clinical presentations of leprosy are spectral, with the severity of disease determined by the balance between the cellular and humoral immune response of the host. The exact mechanisms that facilitate disease susceptibility, onset and progression to certain clinical phenotypes are presently unclear. Various studies have examined lipid metabolism in leprosy, but ...201121909445
dynamics of mycobacterium leprae transmission in environmental context: deciphering the role of environment as a potential reservoir.leprosy is a disease caused by mycobacterium leprae. various modes of transmission have been suggested for this disease. transmission and risk of the infection is perhaps related to presence of the infectious cases and is controlled by environmental factors. evidence suggests that humidity may favor survival of m. leprae in the environment. several reports show that non-human sources like 'naturally' infected armadillos or monkeys could act as reservoir for m. leprae. inanimate objects or fomite ...201222101333
evaluation of cellular phenotypes implicated in immunopathogenesis and monitoring immune reconstitution inflammatory syndrome in hiv/leprosy cases.it is now evident that haart-associated immunological improvement often leads to a variety of new clinical manifestations, collectively termed immune reconstitution inflammatory syndrome, or iris. this phenomenon has already been described in cases of hiv coinfection with mycobacterium leprae, most of them belonging to the tuberculoid spectrum of leprosy disease, as observed in leprosy reversal reaction (rr). however, the events related to the pathogenesis of this association need to be clarifie ...201122205964
Nail Involvement in Leprosy.Leprosy, a disease caused by Mycobacterium leprae, primarily affects the skin and nerves, but the nails are also involved in as many as 3 out of 4 patients .The factors that trigger nail changes in leprosy are numerous and include repeated trauma, neuropathy, vascular impairment, infections, lepra reactions, and the drugs used to manage the disease. The changes most often reported include subungual hematomas, onycholysis, onychauxis, onychogryphosis, pterygium unguis, and onychoheterotopia, most ...201122056258
what is the evidence that the putative mycobacterium lepromatosis species causes diffuse lepromatous leprosy?han et al. have made a retrospective isolation of dna from two patients with fatal lucio's phenomenon. this dna does have some molecular differences to m. leprae and may constitute a variant of m. leprae. however the experiments and data needed to confirm that this is a new leprosy-causing species have not yet been done. we have outlined the work that does need to be done. for the moment the assertion that 'm. lepromatosis' is a new leprosy-causing species is not proven.201122125927
evaluation of various cytokines elicited during antigen-specific recall as potential risk indicators for the differential development of leprosy.leprosy is a dermato-neurological disease caused by mycobacterium leprae infection that manifests across a wide range of clinical and immunological outcomes. diagnosis is still currently based on clinical manifestations and simple tests are needed. this study investigated whether biomarkers induced by defined m. leprae proteins in 24-h whole blood assays (wba) could discriminate active leprosy patients from at-risk contacts. newly diagnosed, untreated paucibacillary (pb; tuberculoid leprosy/bord ...201122076550
the activity of several newer antimicrobials against logarithmically multiplying m. leprae in mice.moxifloxacin, rifampicin, rifapentine, linezolid, and pa 824, alone and in combination, have been previously administered, as single doses and five times daily doses, to m. leprae infected mice during lag phase multiplication and were each found to have some bactericidal activity.201122125933
mycobacterium leprae reca is structurally analogous but functionally distinct from mycobacterium tuberculosis reca protein.mycobacterium leprae is closely related to mycobacterium tuberculosis, yet causes a very different illness. detailed genomic comparison between these two species of mycobacteria reveals that the decaying m. leprae genome contains less than half of the m. tuberculosis functional genes. the reduction of genome size and accumulation of pseudogenes in the m. leprae genome is thought to result from multiple recombination events between related repetitive sequences, which provided the impetus to inves ...201122001565
a mycobacterium leprae hsp65 mutant as a candidate for mitigating lupus aggravation in mice.hsp60 is an abundant and highly conserved family of intracellular molecules. increased levels of this family of proteins have been observed in the extracellular compartment in chronic inflammation. administration of m. leprae hsp65 [wt] in [nzbxnzw]f(1) mice accelerates the systemic lupus erythematosus [sle] progression whereas the point mutated k(409)a hsp65 protein delays the disease. here, the biological effects of m. leprae hsp65 leader pep and k(409)a pep synthetic peptides, which cover res ...201121961033
expression of the chemokine receptor cxcr4 on lymphocytes of leprosy patients.leprosy is caused by mycobacterium leprae, which induces chronic granulomatous infection of the skin and peripheral nerves. the disease ranges from the tuberculoid to the lepromatous forms, depending on the cellular immune response of the host. chemokines are thought to be involved in the immunopathogenesis of leprosy, but few studies have investigated the expression of chemokine receptors on leukocytes of leprosy patients. in the present study, we evaluated 21 leprosy patients (m/f: 16/5) with ...201122002092
a lipopeptide facilitate induction of mycobacterium leprae killing in host cells.little is known of the direct microbicidal activity of t cells in leprosy, so a lipopeptide consisting of the n-terminal 13 amino acids lipopeptide (lipok) of a 33-kd lipoprotein of mycobacterium leprae, was synthesized. lipok activated m. leprae infected human dendritic cells (dcs) to induce the production of il-12. these activated dcs stimulated autologous cd4(+) or cd8(+) t cells towards type 1 immune response by inducing interferon-gamma secretion. t cell proliferation was also evident from ...201122132248
i've tried rattlesnake, frog legs and other exotic foods. are there any i should avoid? 201122059261
elimination of leprosy as a public health problem by 2000 ad: an epidemiological perspective.leprosy is caused by mycobacterium leprae and manifests as damage to the skin and peripheral nerves. the disease is dreaded because it causes deformities, blindness and disfigurement. worldwide, 2 million people are estimated to be disabled by leprosy. multidrug therapy is highly effective in curing leprosy, but treating the nerve damage is much more difficult. the world health assembly targeted to eliminate leprosy as a public health problem from the world by 2000. the objective of the review w ...201122145052
real-time pcr and high resolution melt analysis for rapid detection of mycobacterium leprae drug resistance mutations and strain types.drug resistance surveillance and strain typing of mycobacterium leprae are necessary to investigate ongoing transmission of leprosy in endemic regions. to enable wider implementation of these molecular analyses, novel real time-pcr-high resolution melt (rt-pcr-hrm) assays without allele specific primers or probes and post pcr sample handling were developed. for the detection of mutations within drug resistance determining regions (drdrs) of folp1, rpob and gyra, targets for dapsone, rifampicin a ...201122170923
tnf -308g>a single nucleotide polymorphism is associated with leprosy among brazilians: a genetic epidemiology assessment, meta-analysis, and functional study.leprosy is an infectious disease caused by mycobacterium leprae. tumor necrosis factor (tnf) plays a key role in the host response. some association studies have implicated the single nucleotide polymorphism tnf -308g>a in leprosy susceptibility, but these results are still controversial. we first conducted 4 association studies (2639 individuals) that showed a protective effect of the -308a allele (odds ratio [or] = 0.77; p = .005). next, results of a meta-analysis reinforced this association a ...201121917899
[our role in sentinel surveillance for drug resistance in leprosy by global leprosy programme].sentinel surveillance for drug resistance in leprosy by global leprosy programme has launched in 2006. possible contribution of japanese researchers to global leprosy control in the future were discussed on the base of circumstances of the project and our assignment in the sueveillance.201121941835
modulation of the cytokine response in human monocytes by mycobacterium leprae phenolic glycolipid-1.leprosy is a chronic but treatable infectious disease caused by the intracellular pathogen mycobacterium leprae. m. leprae cell wall is characterized by a unique phenolic glycolipid-1 (pgl-1) reported to have several immune functions. we have examined the role of pgl-1 in the modulation of monocyte cytokine/chemokine production in naive human monocytes. pgl-1 in its purified form or expressed in a recombinant mycobacterium bovis bacillus colmette-guérin (bcg) background (rbcg-pgl-1) was tested. ...201121981546
diagnosing leprosy: revisiting the role of the slit-skin smear with critical analysis of the applicability of polymerase chain reaction in diagnosis.diagnosing leprosy is challenging, especially in early-stage cases, and the need for a sensitive diagnostic tool is urgent. polymerase chain reaction (pcr) holds promise as a simple and sensitive diagnostic tool, but its usefulness in the indian context requires further evaluation. slit-skin smear (sss) remains the conventional method of leprosy detection. hence, this study was undertaken to evaluate and compare the diagnostic efficacy of pcr versus that of sss.201122097999
Peptides of Lsr2 of Mycobacterium leprae show hierarchical responses in lymphoproliferative assays with selective recognition by anergic lepromatous leprosy patients.Lsr2 protein of Mycobacterium leprae (ML) was shown earlier to elicit B and T cell responses in leprosy patients (20, 28). Lymphproliferation to ML and Lsr 2 antigens respectively was observed in > 70% of tuberculoid (T) and in 16 and 34 % of lepromatous (L) patients. We focused on the ML non responders in the lepromatous group using 22 synthetic Lsr 2 peptides (end to end: A to F, overlapping: p1 to p16) in in vitro T cell responses. A total of 125 leprosy, 13 tuberculosis patients and 17 healt ...201122144494
transmission of dapsone-resistant leprosy detected by molecular epidemiological approaches.drug resistance surveillance identified six untreated leprosy patients in the philippines with mycobacterium leprae folp1 mutations which confer dapsone resistance. five patients share a village of residence; four who carried the mutation, thr53val, were also linked by m. leprae variable-number tandem repeat (vntr) strain types. in india, folp1 mutations were detected in two relapse patients with a history of dapsone treatment. mutations were not found in the rifampin target gene rpob. these fin ...201121859943
childhood leprosy in a tertiary-care hospital in delhi, india: a reappraisal in the post-elimination era.to assess the profile and describe the clinical presentations, clinico-histopathological profile, complications and treatment compliance of childhood leprosy at a tertiary care hospital in north-east district of delhi during 2000-2009.201122125934
Comparative analyses of transport proteins encoded within the genomes of Mycobacterium tuberculosis and Mycobacterium leprae.The co-emergence of multidrug resistant pathogenic bacterial strains and the HIV pandemic has made tuberculosis a leading public health threat. The causative agent is Mycobacterium tuberculosis (Mtu), a facultative intracellular parasite. Mycobacterium leprae (Mle), a related organism that causes leprosy, is an obligate intracellular parasite. Given that different transporters are required for bacterial growth and persistence under a variety of growth conditions, we conducted comparative analyse ...201122179038
comparison between microsatellites and ml mnth gene as targets to identify mycobacterium leprae by pcr in leprosy.the polymerase chain reaction (pcr) technique has been frequently used in the molecular diagnosis of leprosy.201121987128
study of the density and distribution of mycobacterium leprae in the epidermis and skin appendages in lepromatous patients. 201121860164
A network of regulatory pathways in lepromatous leprosy. 201121903479
thalidomide modulates mycobacterium leprae-induced nf-κb pathway and lower cytokine response.it is widely accepted that tumor necrosis factor alpha (tnf-α) plays a critical role in the development of tissue and nerve damage in leprosy and during the reactional episodes of acute inflammation. thalidomide (n-α-phthalimidoglutarimide), a drug used to treat leprosy reaction, modulates immune response, inhibits inflammation and nf-κb activity. here we investigated whether thalidomide inhibits nf-κb activation induced by mycobacterium leprae, p38 and erk1/2 mapk activation. emsa and supershif ...201121925494
Chimpanzees used for medical research shed light on the pathoetiology of leprosy.Leprosy is a chronic infectious disorder caused by Mycobacterium leprae, which mainly affects skin and peripheral nerves. It is classified as either paucibacillary or multibacillary based upon clinical manifestations and slit-skin smear results. It is speculated that leprosy develops after a long latency period following M. leprae infection. However, the actual time of infection and the duration of latency have never been proven in human patients. To date, four cases of spontaneous leprosy have ...201122004034
frequencies of mica alleles in patients from southern brazil with multibacillary and paucibacillary leprosy.leprosy is a chronic infectious disease caused by mycobacterium leprae, which mainly affects the skin and nervous system. the disease has several clinical forms. this study investigated the mica and hla-b genes in 223 samples from leprosy patients and 201 samples from healthy individuals matched for age, gender and ethnical background. of the patients, 153 had multibacillary, 45 paucibacillary and 25 indeterminate leprosy. the aim of this case-control study was to assess whether the mica alleles ...201122168250
current status of leprosy: epidemiology, basic science and clinical perspectives.leprosy has affected humans for millennia and remains an important health problem worldwide, as evidenced by nearly 250 000 new cases detected every year. it is a chronic infectious disorder, caused by mycobacterium leprae, that primarily affects the skin and peripheral nerves. recent advances in basic science have improved our knowledge of the disease. variation in the cellular immune response is the basis of a range of clinical manifestations. the introduction of multidrug therapy has signific ...201121973237
does clofazimine prevent erythema nodosum leprosum (enl) in leprosy? a retrospective study, comparing the experience of multibacillary patients receiving either 12 or 24 months who-mdt.to compare the occurrence, duration and severity of enl in leprosy patients treated with either 12 or 24 months of standard multi-drug therapy (mdt).201122125929
A study of knowledge, attitude and practices regarding leprosy among undergraduates and interns of a medical college and hospital from rural India.Leprosy is an Infectious disease caused by Mycobacterium leprae and acquired through droplet infection. India has been carrying the 2/3rd global leprosy burden. Inadequate or incorrect information and knowledge about the disease and its treatment are the root causes of many stigmas and inhibitions prevalent in the various sections of the community. The present study was undertaken to assess the knowledge, attitude and practices (KAP) regarding leprosy among undergraduates (final year medical stu ...201121972659
Homology modeling and docking analyses of M. leprae Mur ligases reveals the common binding residues for structure based drug designing to eradicate leprosy.Multi drug resistance capacity for Mycobacterium leprae (MDR-Mle) demands the profound need for developing new anti-leprosy drugs. Since most of the drugs target a single enzyme, mutation in the active site renders the antibiotic ineffective. However, structural and mechanistic information on essential bacterial enzymes in a pathway could lead to the development of antibiotics that targets multiple enzymes. Peptidoglycan is an important component of the cell wall of M. leprae. The biosynthesis o ...201122102165
The role of neuregulin-1 in the response to nerve injury.Axons and Schwann cells exist in a highly interdependent relationship: damage to one cell type invariably leads to pathophysiological changes in the other. Greater understanding of communication between these cell types will not only give insight into peripheral nerve development, but also the reaction to and recovery from peripheral nerve injury. The type III isoform of neuregulin-1 (NRG1) has emerged as a key signaling factor that is expressed on axons and, through binding to erbB2/3 receptors ...201122121335
Report of three new leprosy cases in children under fifteen in the municipality of Itaguai, Rio de Janeiro: event alert for epidemiological investigation.Leprosy is an infectious disease with an average incubation period of two to five years. It is caused by Mycobacterium leprae, mainly affecting skin, mucous membranes and peripheral nerves. When it occurs in children under fifteen, it reflects an intense and long contact period, with a high bacillary load. Therefore, it is considered an important alert sign that points to the challenge of controlling the disease. The authors report three cases of leprosy in children under fifteen that occurred i ...201122147046
A history of leprosy in Iran during the 19th and 20th centuries.From ancient time leprosy has been regarded as a terrifying, stigmatized disease; nevertheless, its cause remained unidentified up to the late 19th century. For centuries numerous leprosy victims worldwide suffered from its morbidity and were socially isolated. The afflicted individuals were segregated because they were considered 'unclean' and had to live in leper colonies, generally under very poor conditions. Physicians believed that leprosy was an incurable, highly contagious, and hereditary ...201122039850
the long-term effect of current and new interventions on the new case detection of leprosy: a modeling study.although the number of newly detected leprosy cases has decreased globally, a quarter of a million new cases are detected annually and eradication remains far away. current options for leprosy prevention are contact tracing and bcg vaccination of infants. future options may include chemoprophylaxis and early diagnosis of subclinical infections. this study compared the predicted trends in leprosy case detection of future intervention strategies.201121949895
Circulating levels of Insulin-like Growth Factor-I (IGF-I) correlate with disease status in leprosy.ABSTRACT: BACKGROUND: Caused by Mycobacterium leprae (ML), leprosy presents a strong immune-inflammatory component, whose status dictates both the clinical form of the disease and the occurrence of reactional episodes. Evidence has shown that, during the immune-inflammatory response to infection, the growth hormone/insulin-like growth factor-I (GH/IGF-I) plays a prominent regulatory role. However, in leprosy, little, if anything, is known about the interaction between the immune and neuroendocr ...201122166091
association of variants in bat1-lta-tnf-btnl2 genes within 6p21.3 region show graded risk to leprosy in unrelated cohorts of indian population.host immune response against mycobacterium leprae plays an important role in providing resistance to infection and disease progression. genome-wide linkage and association studies suggest the possibility of multiple risk loci within hla (6p21.3) region. any systematic study of relevance within the histocompatibility complex of importance in host immune response would be pertinent because of non-replication of the known loci and unavailable information on some of the unexplored genes and regions. ...201122071774
Genetic variations and interactions in anti-inflammatory cytokine pathway genes in the outcome of leprosy: a study conducted on a MassARRAY platform.Mycobacterium leprae is the etiologic pathogen that causes leprosy. The outcome of disease is dependent on the host genetic background.201121917900
polymorphisms of nod2 and the risk of tuberculosis: a validation study in the chinese population.a genome-wide association study (gwas) of leprosy reported four specific genetic polymorphisms of nod2 that were associated with susceptibility to mycobacterium leprae in china. considering the role of nod2 in innate immune defence, we performed a study in a chinese population to determine whether the same snps of nod2 that were associated with disease caused by m. leprae were also associated with disease caused by mycobacterium tuberculosis. we performed a frequency-matched case-control study i ...201222212192
identification of the leprosy agent mycobacterium lepromatosis in singapore.background: a new leprosy-causing species, namely mycobacterium lepromatosis, was discovered recently to be the cause of diffuse lepromatous leprosy (dll) in mexico. it is unknown whether this organism exists beyond mexico. methods: we sought to determine the identity of the mycobacteria in the skin tissue of two patients from singapore who died of dll. dna was extracted from archived biopsy tissue, and conserved polymerase chain reaction primers were used to amplify and sequence two to three my ...201222270197
cojedes: a leprosy hyperendemic state.background  leprosy is a chronic infectious disease produced by mycobacterium leprae. in 1997 venezuela reached the goal of elimination of leprosy as a public health problem (according to the world health organization a prevalence rate of ≤1/10,000 inhabitants), but five states still had prevalence rates over that goal. for this study we selected cojedes state, where prevalence rates remain over the elimination goal. objective  evaluate the real leprosy situation in high-prevalence areas of coje ...201222250629
snp genotypes of mycobacterium leprae isolates in thailand and their combination with rpot and ttc genotyping for analysis of leprosy distribution and transmission.based on the discovery of three single nucleotide polymorphisms (snps) in mycobacterium leprae, it has been previously reported that there are four major snp types associated with different geographic regions around the world. another typing system for global differentiation of m. leprae is the analysis of the variable number of short tandem repeats within the rpot gene. to expand the analysis of geographic distribution of m. leprae, classified by snp and rpot gene polymorphisms, we studied ...201222274158
clinicohistopathological correlation in leprosy.leprosy is a chronic, infectious disease caused by mycobacterium leprae. it is classified into five groups based on clinical, histological, microbiological and immunological criteria (ridley and jopling classification) . however, a great variation has been observed in the interpretation of histopathological examination ok skin biopsies and clinical presentation of the disease.201122710532
immunogenicity of mycobacterium leprae unique antigens in leprosy endemic populations in asia and africa.ongoing transmission of leprosy is evident from the stable disease incidence in high burden areas. tools for early detection of mycobacterium leprae (m. leprae) infection, particularly in sub-clinically infected individuals, are urgently required to reduce transmission. following the sequencing of the m. leprae genome, many m. leprae-unique candidate proteins have been identified, several of which have been tested for induction of m. leprae specific t cell responses in different leprosy endemic ...201122439283
cytokine responses to mycobacterium leprae unique proteins differentiate between mycobacterium leprae infected and naive armadillos.new diagnostic tools for early detection of leprosy are necessary to help reduce its transmission and severity. m. leprae unique proteins have been used to assess differences in human t-cell responses in leprosy patients, household contacts and endemic controls. in this study, we examined the response of m. leprae-infected armadillos to a variety of m. leprae recombinant antigen candidates currently being examined for diagnostic efficacy in humans. among recently m. leprae infected armadillos, i ...201122439281
postgenomic mycobacterium leprae antigens for cellular and serological diagnosis of m. leprae exposure, infection and leprosy disease.due to changes in leprosy control programs and the special expertise required for diagnosis, the need for simple rapid diagnostic tests that could be applied in non-expert settings may now be greater than ever before. since the sequencing of the m. leprae genome, many research groups have investigated the potential of m. leprae antigens in either serologic or cell mediated assays. here we provide an overview of the nearly 200 recombinant single proteins that were investigated during the last dec ...201122439280
serological detection of leprosy employing mycobacterium leprae derived serine-rich 45 kda, esat-6, cfp-10 and pgl-i: a compilation of data from studies in indian populations.this article is a compilation of our findings recorded in the recent past where we have investigated the serological performance of mycobacterium leprae antigens like-serine-rich 45 kda protein (45 kd), early secretary antigenic target-6 (esat-6), culture filtrate protein-10 (cfp-10) and phenolic glycolipid-i (pgl-i) for detection (employing antibody detecting elisa) of leprosy patients, particularly those belonging to the paucibacillary (pb) group. all of these antigens were capable of detectin ...201122439278
anti-pgl-i seroepidemiology in leprosy cases: household contacts and school children from a hyperendemic municipality of the brazilian amazon.we investigated the prevalence of antibodies against pgl-i in people affected by leprosy (pal) who were diagnosed and treated between 2004 and 2010, their household contacts (hc) and school children (sc) from a hyperendemic municipality in the brazilian amazon, and determined the prevalence of previously undiagnosed leprosy (ppul) among both the hc and sc.201122439276
the role of mycobacterium leprae phenolic glycolipid i (pgl-i) in serodiagnosis and in the pathogenesis of leprosy.pgl-i (phenolic glycolipid i) emerged in the early 1980s on the one hand as part of intensive efforts to define the typing antigens of a host of mycobacterium spp. and also from characterisation of the lipids of skin biopsies from highly bacillary positive lepromatous leprosy patients. pgl-i, despite its extreme lipophilicity due to its inherent phthiocerol dimycocerosyl component, is highly antigenic evoking high titre igm antibodies in lepromatous leprosy patients, attributable largely to the ...201122439275
[leprosy--today forgotten in croatia?].leprosy is an infectious skin disease caused by mycobacterium leprae, which predominantly affects the skin, peripheral nerves and mucous membrane of the upper respiratory tract and oral cavity. in spite of today's efficient treatment, leprosy represents a public health problem in some countries of the world. it is estimated that 12 to 15 million patients are currently affected in the world. leprosy ravaged across europe, including croatia, for centuries, so this paper provides a few historical f ...201122359893
the role of intracellular receptor nods for cytokine production by macrophages infected with mycobacterium leprae.the nucleotide-oligomerization domain (nod) proteins are members of the nod-like receptor (nlr) family, which are intracellular and cytoplasmic receptors. we analyzed the role of nods for cytokine production by macrophages infected with intracellular pathogen m. leprae, the causative agent of leprosy. production of pro-inflammatory cytokines such as il-1β and tnf-α was inhibited in the presence of cytochalasin d, an agent blocking phagocytosis, suggesting that intracellular signaling was, partia ...201122346786
infectious diseases of khmer immigrants in the united states: review of published reports.infectious diseases are influenced by where patients have lived or travelled in the past, e.g., infection with schistosoma mekongi can be acquired during freshwater contact in cambodia, but not in the united states. here the infectious diseases of khmer immigrants in the united states were studied by reviewing published reports. thirteen case series and 9 case reports of 5,222 patients were identified. most reports were of infections with gastrointestinal parasites (8, 36%), plasmnodium species ...201123272458
clinicohistopathological concordance in leprosy - a clinical, histopathological and bacteriological study of 100 cases.leprosy is a treatable chronic infectious disease, prevalent in south asian countries, especially india. before labeling a patient as a case of leprosy and starting multidrug treatment for particular type, the clinical findings should be correlated and confirmed with histopathological examination and bacteriological index of skin biopsy. skin biopsy is an important tool in diagnosing leprosy and determining the type of leprosy. in the present study, one hundred untreated clinically diagnosed cas ...201223484336
histological diagnosis of early and suspicious leprosy by in situ pcr.leprosy is a chronic mycobacterial disease whose diagnosis is primarily based on clinico-pathological examination and supported by slit skin smears for the presence of acid fast bacilli (afb). however, definitive diagnosis of early leprosy and those suspected to have the disease but not histologically confirmed pose major public health problems. the present study reports the utility of the in situ polymerase chain reaction amplification (pcr) directed at a 530bp fragment of dna encoding the 36kd ...201223484333
patient-related factors predicting the effectiveness of rifampicin chemoprophylaxis in contacts: 6 year follow up of the colep cohort in bangladesh.the colep trial in bangladesh showed a 57% reduction in leprosy incidence among contacts of newly diagnosed patients in the first 2 years after chemoprophylaxis with single dose rifampicin (sdr). we assessed the impact of this intervention after 6 years and identified characteristics of the leprosy index patients predicting the effectiveness of this intervention.201223356030
ofloxacin multicentre trial in mb leprosy fuam-manaus and ilsl-bauru, brazil.recently antimicrobials of the fluoroquinolone class (pefloxacin and ofloxacin) were found far more effective against mycobacterium leprae in studies with both mice and patients than dapsone and clofazimine. as multicentre trial participants, we evaluated the therapeutic efficacy, in terms of rate of relapse, of two new multidrug regimens containing ofloxacin, comparing them to 1 year and 2 years of standard who-mdt regimen in multibacillary (mb) leprosy patients. a total of 198mb patients were ...201223356027
cohort study of the seasonal effect on nasal carriage and the presence of mycobacterium leprae in an endemic area in the general population.leprosy continues to be a significant health problem in certain pockets in developing countries. better understanding of the transmission and source of the infection would help to decipher the transmission link, leading to control of the spread of the disease. the nose is considered to be a portal of entry, suggesting an aerial route for transmission through droplet infection. the evidence suggests that many individuals from endemic countries carry mycobacterium leprae in their nasal cavities wi ...201223331372
hansen's disease with mccune-albright syndrome.mccune-albright syndrome (mas) comprises a triad of fibrous dysplasia of bone, café-au-lait macule, and endocrinopathy. the disease is due to activating mutation of g protein-coupled receptor leading to hyperfunction of glands. hansen's disease is caused by infection with mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals. we recently encountered a patient with hansen's disease along with underlying mas and report the same in this ...201223326081
mycobacterium leprae in six-banded (euphractus sexcinctus) and nine-banded armadillos (dasypus novemcinctus) in northeast brazil.human beings are the main reservoir of the causative agent of leprosy, mycobacterium leprae. in the americas, nine-banded armadillos (dasypus novemcinctus) also act as a reservoir for the bacillus. in the state of ceará (ce), which is located in northeast brazil and is an endemic area of leprosy, there are several species of armadillos, including d. novemcinctus and euphractus sexcinctus (six-banded armadillo). contact between humans and armadillos occur mainly through hunting, cleaning, prepari ...201223283473
insights from animal models on the immunogenetics of leprosy: a review.a variety of host immunogenetic factors appear to influence both an individual's susceptibility to infection with mycobacterium leprae and the pathologic course of the disease. animal models can contribute to a better understanding of the role of immunogenetics in leprosy through comparative studies helping to confirm the significance of various identified traits and in deciphering the underlying mechanisms that may be involved in expression of different disease related phenotypes. genetically e ...201223283472
mycobacterial laminin-binding histone-like protein mediates collagen-dependent cytoadherence.when grown in the presence of exogenous collagen i, mycobacterium bovis bcg was shown to form clumps. scanning electron microscopy examination of these clumps revealed the presence of collagen fibres cross-linking the bacilli. since collagen is a major constituent of the eukaryotic extracellular matrices, we assayed bcg cytoadherence in the presence of exogenous collagen i. collagen increased the interaction of the bacilli with a549 type ii pneumocytes or u937 macrophages, suggesting that bcg is ...201223283469
differential expression of the costimulatory molecules cd86, cd28, cd152 and pd-1 correlates with the host-parasite outcome in leprosy.leprosy is a spectral disease exhibiting two polar sides, namely, lepromatous leprosy (ll) characterised by impaired t-cell responses and tuberculoid leprosy in which t-cell responses are strong. proper t-cell activation requires signalling through costimulatory molecules expressed by antigen presenting cells and their ligands on t-cells. we studied the influence of costimulatory molecules on the immune responses of subjects along the leprosy spectrum. the expression of the costimulatory molecul ...201223283468
deciphering the contribution of lipid droplets in leprosy: multifunctional organelles with roles in mycobacterium leprae pathogenesis.leprosy is an infectious disease caused by mycobacterium leprae that affects the skin and nerves, presenting a singular clinical picture. across the leprosy spectrum, lepromatous leprosy (ll) exhibits a classical hallmark: the presence of a collection of m. leprae-infected foamy macrophages/schwann cells characterised by their high lipid content. the significance of this foamy aspect in mycobacterial infections has garnered renewed attention in leprosy due to the recent observation that the foam ...201223283467
association analysis of human leukocyte antigen class ii (drb1) alleles with leprosy in individuals from são luís, state of maranhão, brazil.epidemiological studies have demonstrated that the variability of the clinical response to infection caused by mycobacterium leprae is associated with host genetic factors. the present study investigated the frequency of human leukocyte antigen (hla) class ii (drb1) alleles in patients with leprosy from são luís, maranhão, brazil. a case-control study was performed in 85 individuals with leprosy and 85 healthy subjects. all samples were analysed via polymerase chain reaction-sequence specific ol ...201223283466
genotyping of mycobacterium leprae present on ziehl-neelsen-stained microscopic slides and in skin biopsy samples from leprosy patients in different geographic regions of brazil.we analysed 16 variable number tandem repeats (vntr) and three single-nucleotide polymorphisms (snp) in mycobacterium leprae present on 115 ziehl-neelsen (z-n)-stained slides and in 51 skin biopsy samples derived from leprosy patients from ceará (n = 23), pernambuco (n = 41), rio de janeiro (n = 22) and rondônia (ro) (n = 78). all skin biopsies yielded snp-based genotypes, while 48 of the samples (94.1%) yielded complete vntr genotypes. we evaluated two procedures for extracting m. leprae dna fr ...201223283465
mycobacterium leprae virulence-associated peptides are indicators of exposure to m. leprae in brazil, ethiopia and nepal.silent transmission of mycobacterium leprae, as evidenced by stable leprosy incidence rates in various countries, remains a health challenge despite the implementation of multidrug therapy worldwide. therefore, the development of tools for the early diagnosis of m. leprae infection should be emphasised in leprosy research. as part of the continuing effort to identify antigens that have diagnostic potential, unique m. leprae peptides derived from predicted virulence-associated proteins (group iv. ...201223283462
seroreactivity to new mycobacterium leprae protein antigens in different leprosy-endemic regions in brazil.new mycobacterium leprae protein antigens can contribute to improved serologic tests for leprosy diagnosis/classification and multidrug therapy (mdt) monitoring. this study describes seroreactivity to m. leprae proteins among participants from three highly endemic leprosy areas in brazil: central-western goiânia/goiás (go) (n = 225), rondonópolis/mato grosso (mt) (n = 764) and northern prata village/pará (pa) (n = 93). elisa was performed to detect igg to proteins (92f, 46f, leprosy idri diagnos ...201223283461
serologic follow-up of igg responses against recombinant mycobacterial proteins ml0405, ml2331 and lid-1 in a leprosy hyperendemic area in venezuela.leprosy is a slowly evolving disease that occurs mainly in adults. in this study, the mamaría village, state of portuguesa was selected because it had one of the highest prevalence rates (13.25%) of leprosy cases in 1997. between 1998-2004, 20.2% of the 89 cases registered in this village were less than 15 years old and 61.8% were males. paucibacillary (pb) lesions were the predominant clinical forms identified, although also multibacillary (mb) forms were found. additionally, 76% of the patient ...201223283459
identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy.although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. in this study, we examined the reactivity of sera from lepromatous and tuberculoid lepro ...201223283458
unveiling healthy carriers and subclinical infections among household contacts of leprosy patients who play potential roles in the disease chain of transmission.leprosy transmission still occurs despite the availability of highly effective treatment. the next step towards successfully eliminating leprosy is interrupting the chain of transmission of the aetiological agent, mycobacterium leprae. in this investigation, we provide evidence that household contacts (hhcs) of leprosy patients might not only have subclinical infections, but may also be actively involved in bacilli transmission. we studied 444 patients and 1,352 contacts using anti-phenolic glyc ...201223283454
the role of human t cell lymphotrophic virus type 1, hepatitis b virus and hepatitis c virus coinfections in leprosy.leprosy spectrum and outcome is associated with the host immune response against mycobacterium leprae. the role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. leprosy remains endemic in several regions where human t cell lymphotrophic virus type 1 (htlv-1), hepatitis b virus (hbv) or hepatitis c virus (hcv) are also endemic. we have evaluated the evidence for the possible role of these viruses in the clinical ma ...201223283452
hansen's disease: a vanishing disease?the introduction, implementation, successes and failures of multidrug therapy (mdt) in all hansen's disease endemic countries are discussed in this paper. the high efficacy of leprosy treatment with mdt and the global reduction of prevalence led the world health organization, in 1991, to establish the goal of elimination of hansen's disease (less than 1 patient per 10,000 inhabitants) to be accomplished by the year 2000. brazil, nepal and east timor are among the few countries that didn't reach ...201223283447
synthesis of gatifloxacin derivatives and their biological activities against mycobacterium leprae and mycobacterium tuberculosis.novel 3'-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4-quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by (1)h, (13)c and (19)f nmr, and hrms. the activity of these derivatives against pathogenic mycobacteria (m. leprae and m. tuberculosis), wild-type (wt) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (mic) and/or dna supercoi ...201223294829
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
genetic diversity of toll-like receptors and immunity to m. leprae infection.genetic association studies of leprosy cohorts across the world have identified numerous polymorphisms which alter susceptibility and outcome to infection with mycobacterium leprae. as expected, many of the polymorphisms reside within genes that encode components of the innate and adaptive immune system. despite the preponderance of these studies, our understanding of the mechanisms that underlie these genetic associations remains sparse. toll-like receptors (tlrs) have emerged as an essential f ...201222529866
current and past strategies for bacterial culture in clinical microbiology.a pure bacterial culture remains essential for the study of its virulence, its antibiotic susceptibility, and its genome sequence in order to facilitate the understanding and treatment of caused diseases. the first culture conditions empirically varied incubation time, nutrients, atmosphere, and temperature; culture was then gradually abandoned in favor of molecular methods. the rebirth of culture in clinical microbiology was prompted by microbiologists specializing in intracellular bacteria. th ...201525567228
paleopathological evidence and detection of mycobacterium leprae dna from archaeological skeletal remains of nabe-kaburi (head-covered with iron pots) burials in japan.the nabe-kaburi is a unique burial method, the purpose of which is shrouded in mystery. the burials were performed during the 15(th) to 18(th) centuries in eastern japan, and involved covering the heads of the deceased with iron pots or mortars. the identification of leprosy-specific osteological lesions among some of the excavated remains has led to the suggestion that nabe-kaburi burials were a reflection of the social stigma against certain infectious diseases, such as leprosy, tuberculosis o ...201424516638
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
microrna-21 targets the vitamin d-dependent antimicrobial pathway in leprosy.leprosy provides a model to investigate mechanisms of immune regulation in humans, given that the disease forms a spectrum of clinical presentations that correlate with host immune responses. here we identified 13 mirnas that were differentially expressed in the lesions of subjects with progressive lepromatous (l-lep) versus the self-limited tuberculoid (t-lep) disease. bioinformatic analysis revealed a significant enrichment of l-lep-specific mirnas that preferentially target key immune genes d ...201222286305
rbcg30-induced immunity and cross-protection against mycobacterium leprae challenge are enhanced by boosting with the mycobacterium tuberculosis 30-kilodalton antigen 85b.leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. vaccines are needed that protect against both infections and do so better than the suboptimal mycobacterium bovis bcg vaccine. here, we evaluated rbcg30, a vaccine previously demonstrated to induce protection superior to that of bcg against mycobacterium tuberculosis and mycobacterium bovis challenge in animal models, for efficacy against mycobacterium leprae challenge in a murine mode ...201425001602
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
characterization of the msmeg_2631 gene (mmp) encoding a multidrug and toxic compound extrusion (mate) family protein in mycobacterium smegmatis and exploration of its polyspecific nature using biolog phenotype microarray.in mycobacterium, multidrug efflux pumps can be associated with intrinsic drug resistance. comparison of putative mycobacterial transport genes revealed a single annotated open reading frame (orf) for a multidrug and toxic compound extrusion (mate) family efflux pump in all sequenced mycobacteria except mycobacterium leprae. since mate efflux pumps function as multidrug efflux pumps by conferring resistance to structurally diverse antibiotics and dna-damaging chemicals, we studied this gene (msm ...201323292779
phylogenetic analysis of vitamin b12-related metabolism in mycobacterium tuberculosis.comparison of genome sequences from clinical isolates of mycobacterium tuberculosis with phylogenetically-related pathogens mycobacterium marinum, mycobacterium kansasii, and mycobacterium leprae reveals diversity amongst genes associated with vitamin b12-related metabolism. diversity is generated by gene deletion events, differential acquisition of genes by horizontal transfer, and single nucleotide polymorphisms (snps) with predicted impact on protein function and transcriptional regulation. d ...201525988174
parallel detection of ancient pathogens via array-based dna capture.dna capture coupled with next generation sequencing is highly suitable for the study of ancient pathogens. screening for pathogens can, however, be meticulous when assays are restricted to the enrichment of single organisms, which is common practice. here, we report on an array-based dna capture screening technique for the parallel detection of nearly 100 pathogens that could have potentially left behind molecular signatures in preserved ancient tissues. we demonstrate the sensitivity of our met ...201525487327
production of recombinant proteins in mycobacterium smegmatis for structural and functional studies.protein production using recombinant dna technology has a fundamental impact on our understanding of biology through providing proteins for structural and functional studies. escherichia coli (e. coli) has been traditionally used as the default expression host to over-express and purify proteins from many different organisms. e. coli does, however, have known shortcomings for obtaining soluble, properly folded proteins suitable for downstream studies. these shortcomings are even more pronounced ...201425303009
long-term survival and virulence of mycobacterium leprae in amoebal cysts.leprosy is a curable neglected disease of humans caused by mycobacterium leprae that affects the skin and peripheral nerves and manifests clinically in various forms ranging from self-resolving, tuberculoid leprosy to lepromatous leprosy having significant pathology with ensuing disfiguration disability and social stigma. despite the global success of multi-drug therapy (mdt), incidences of clinical leprosy have been observed in individuals with no apparent exposure to other cases, suggestive of ...201425521850
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
the antibiotic resistance arrow of time: efflux pump induction is a general first step in the evolution of mycobacterial drug resistance.we hypothesize that low-level efflux pump expression is the first step in the development of high-level drug resistance in mycobacteria. we performed 28-day azithromycin dose-effect and dose-scheduling studies in our hollow-fiber model of disseminated mycobacterium avium-m. intracellulare complex. both microbial kill and resistance emergence were most closely linked to the within-macrophage area under the concentration-time curve (auc)/mic ratio. quantitative pcr revealed that subtherapeutic azi ...201222751536
regulatory t-cells at the interface between human host and pathogens in infectious diseases and vaccination.regulatory t-cells (tregs) act at the interface of host and pathogen interactions in human infectious diseases. tregs are induced by a wide range of pathogens, but distinct effects of tregs have been demonstrated for different pathogens and in different stages of infection. moreover, tregs that are induced by a specific pathogen may non-specifically suppress immunity against other microbes and parasites. thus, treg effects need to be assessed not only in homologous but also in heterologous infec ...201526029205
mycobacterium leprae hsp65 administration reduces the lifespan of aged high antibody producer mice.aging process may result in immune modifications that lead to disruption of innate and acquired immunity mechanisms that may induce chronic-degenerative events. the heat shock proteins (hsp), phylogeneticaly conserved among organisms, present as main function the ability of folding and refolding proteins, but they also are associated with chronic-degenerative disorders. here were evaluated the role of m. leprae native hsp65 (wt) and its point-mutated (k409a) on survival and anti-dna and anti-hsp ...201424669842
spatial heterogeneity in projected leprosy trends in india.leprosy is caused by infection with mycobacterium leprae and is characterized by peripheral nerve damage and skin lesions. the disease is classified into paucibacillary (pb) and multibacillary (mb) leprosy. the 2012 london declaration formulated the following targets for leprosy control: (1) global interruption of transmission or elimination by 2020, and (2) reduction of grade-2 disabilities in newly detected cases to below 1 per million population at a global level by 2020. leprosy is treatable ...201526490137
characteristics of a dengue outbreak in a remote pacific island chain--republic of the marshall islands, 2011-2012.dengue is a potentially fatal acute febrile illness caused by four mosquito-transmitted dengue viruses (denv-1-4). although dengue outbreaks regularly occur in many regions of the pacific, little is known about dengue in the republic of the marshall islands (rmi). to better understand dengue in rmi, we investigated an explosive outbreak that began in october 2011. suspected cases were reported to the ministry of health, serum specimens were tested with a dengue rapid diagnostic test (rdt), and c ...201425268134
experimental infection of rhodnius prolixus (hemiptera, triatominae) with mycobacterium leprae indicates potential for leprosy transmission.leprosy is a chronic dermato-neurological disease caused by infection with mycobacterium leprae. in 2013 almost 200,000 new cases of leprosy were detected around the world. since the first symptoms take from years to decades to appear, the total number of asymptomatic patients is impossible to predict. although leprosy is one of the oldest records of human disease, the mechanisms involved with its transmission and epidemiology are still not completely understood. in the present work, we experime ...201627203082
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