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murine splenic natural killer cells do not develop immunological memory after re-encounter with mycobacterium bovis bcg.several lines of evidence have recently suggested that natural killer (nk) cells develop immunological memory against viral infections. however, there is no apparent evidence that nk cells acquire specific memory against mycobacterium bovis bacillus calmette-guérin (bcg), the only currently licensed vaccine for preventing tuberculosis. in the present study, we investigated whether murine splenic nk cells can be activated by bcg in a dendritic cell (dc)-independent or -dependent manner, and furth ...201626999357
persistent mycobacterium bovis-bcg is resistant to glutathione induced reductive stress killing.this study focuses on the redox stress response in mycobacteria elicited by a host-derived, thiol-based detoxification molecule, glutathione (gsh). although the growth and viability of mycobacterium bovis-bcg (bcg) was hampered by exposure to 8 mm gsh, oxygen depleted, persistent bcg (nrp bcg) resisted gsh-mediated killing. fast growing mycobacteria also resisted gsh-mediated killing. to determine the mechanisms behind these observations, we evaluated the levels of intracellular atp in both bcg ...201626997649
tuberculosis in rhinoceros: an underrecognized threat?historical evidence of tuberculosis (tb) affecting primarily captive rhinoceroses dates back almost two centuries. although the causative mycobacterium tuberculosis complex (mtc) species has not been determined in many cases, especially for those that occurred before bacterial culture techniques were available, the spectrum of documented reports illustrates the importance of tb as cause of morbidity and mortality in different rhinoceros species across continents. in more recent years, sporadic s ...201626996520
construction of eukaryotic expression vectors encoding cfp-10 and esat-6 genes and their potential in lymphocyte proliferation.mycobacterium (m.) bovis is the agent of bovine tuberculosis (tb) in a range of animal species, including humans. recent advances in immunology and the molecular biology of mycobacterium have allowed identification of a large number of antigens with the potential for the development of a new tb vaccine. the esat-6 and cfp-10 proteins of m. bovis are important structural and functional proteins known to be important immunogens.201326989718
investigation of 4-amino-5-alkynylpyrimidine-2(1h)-ones as anti-mycobacterial agents.in vitro anti-mycobacterial activities of novel 4-amino-5-alkynylpyrimidine-2(1h)-ones were investigated. 4-amino-5-heptynylpyrimidine-2(1h)-one (3) and 4-amino-5-(2-phenylethynyl)pyrimidine-2(1h)-one (7) displayed potent in vitro activity against mycobacterium bovis and mycobacterium tuberculosis. compounds 3 and 7 were also assessed for their in vivo activity in balb/c mice infected with m. tuberculosis (h37ra). both compounds showed promising in vivo efficacy at a dose of 25 mg/kg for 2 weeks ...201626988804
use of bacterial whole-genome sequencing to investigate local persistence and spread in bovine tuberculosis.mycobacterium bovis is the causal agent of bovine tuberculosis, one of the most important diseases currently facing the uk cattle industry. here, we use high-density whole genome sequencing (wgs) in a defined sub-population of m. bovis in 145 cattle across 66 herd breakdowns to gain insights into local spread and persistence. we show that despite low divergence among isolates, wgs can in principle expose contributions of under-sampled host populations to m. bovis transmission. however, we demons ...201626972511
mycobacterium bovis-infected macrophages from resistant and susceptible cattle exhibited a differential pro-inflammatory gene expression profile depending on strain virulence.mycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular bacterium that normally persists inside host macrophages. however, the influence of bacterial virulence and host resistance on the final outcome in this interaction is not well known. in this study, we infected macrophages isolated from natural disease resistant (r) and susceptible (s) cattle donors with m. bovis strains characterized as attenuated and virulent to assess pro-inflammatory cytokine (tnfα, il-12, i ...201626970816
experience with sequential intravesical gemcitabine and docetaxel as salvage therapy for non-muscle invasive bladder cancer.patients with high-grade muscle invasive bladder cancer (nmibc) receive intravesical therapy with bacillus calmette-guérin (bcg) as the well-established standard-of-care. however, even with prompt induction of intravesical therapy, approximately 40 % of patients will recur within 2 years. for patients who fail bcg, options include radical cystectomy, repeat bcg therapy, or alternative intravesical salvage therapy. in this review, we will discuss the most recent published evidence on salvage intr ...201626968418
mycobacterium bovis cerebellar abscess following treatment with bacillus calmette-guérin.bacillus calmette-guérin (bcg) is a live, attenuated strain of mycobacterium bovis that is used to treat superficial bladder cancer. although its use is typically associated with only mild, localized side effects, rare systemic complications can occur. disseminated mycobacterium infections after bcg therapy have been reported in over 30 cases; however, central nervous system (cns) infections do not commonly occur. we report a 74-year-old male who developed a m. bovis cerebellar abscess after rec ...201626966140
diagnosis of lymph node tuberculosis using the genexpert mtb/rif in tunisia.genexpert mtb/rif is a fully-automated diagnostic molecular test which simultaneously detects tuberculosis (tb) and rifampicin (rif) drug resistance. the purpose of this study is to evaluate the performance of the genexpert mtb/rif test for the detection of mycobacterium tuberculosis complex (mtbc) in lymph node specimens and to show the place of mycobacterium bovis as a major cause of tb lymphadenitis.201526964807
a genome-wide association study for genetic susceptibility to mycobacterium bovis infection in dairy cattle identifies a susceptibility qtl on chromosome 23.bovine tuberculosis (btb) infection in cattle is a significant economic concern in many countries, with annual costs to the uk and irish governments of approximately €190 million and €63 million, respectively, for btb control. the existence of host additive and non-additive genetic components to btb susceptibility has been established.201626960806
interferon-gamma-dependent immunity in bacillus calmette-guérin vaccine osteitis survivors.inborn errors of interferon-gamma (ifn-γ)-mediated immunity underlie disseminated disease caused by mycobacterium bovis bacillus calmette-guérin (bcg) live vaccines. we hypothesized that some patients with osteitis after bcg vaccination may have an impaired ifn-γ immunity. our aim was to investigate interleukin (il)-12 and ifn-γ ex vivo production stimulated with bcg and bcg + ifn-γ or bcg + il-12, respectively, in bcg osteitis survivors.201626954602
molecular characterization of mycobacterium bovis in slaughtered cattle in north-central nigeria and the public health implications.the molecular biological techniques of polymerase chain reaction (pcr) are accurate and rapid diagnostic methods in the epidemiology of mycobacterium species in humans and animals, especially in developing countries.201426949786
investigation of the cause of geographic disparities in idexx elisa sensitivity in serum samples from mycobacterium bovis-infected cattle.accurately identifying mycobacterium bovis-infected cattle is critical for bovine tuberculosis prevention and control. one method for identifying infected cattle is an elisa developed by idexx laboratories, which detects antibodies to two m. bovis proteins, mpb70 and mpb83. the assay's sensitivity varies by geographic region, with sensitivities of 77%, 45%, and 9% in bovine serum samples from the united kingdom (n = 126), the united states (n = 146), and mexico (n = 128), respectively. we hypoth ...201626949166
possible airborne person-to-person transmission of mycobacterium bovis - nebraska 2014-2015.mycobacterium bovis, one of several mycobacteria of the m. tuberculosis complex, is a global zoonotic pathogen that primarily infects cattle. humans become infected by consuming unpasteurized dairy products from infected cows; possible person-to-person airborne transmission has also been reported. in april 2014, a man in nebraska who was born in mexico was determined to have extensive pulmonary tuberculosis (tb) caused by m. bovis after experiencing approximately 3 months of cough and fever. fou ...201626938831
application of fluorescent protein expressing strains to evaluation of anti-tuberculosis therapeutic efficacy in vitro and in vivo.the slow growth of mycobacterium tuberculosis (mtb), the causative agent of tuberculosis (tb), hinders development of new diagnostics, therapeutics and vaccines. using non-invasive real-time imaging technologies to monitor the disease process in live animals would facilitate tb research in all areas. we developed fluorescent protein (fp) expressing mycobacterium bovis bcg strains for in vivo imaging, which can be used to track bacterial location, and to quantify bacterial load in live animals. w ...201626934495
[spondilodyscitis with medullary and spinal abscess caused by bacillus calmette-guérin (bcg)].intravesical therapy with live-attenuated mycobacterium bovis strain have demonstrated to be effective in the treatment of recurrent and high-grade superficial bladder tumors. the use of this therapy is widely extended; however spreading of bacillus from the injection site could be one rare complication that may cause infection in different locations. an appropriate anamnesis is very important to establish an etiological diagnostic of possible infections caused by m. bovis bcg. laboratory diagno ...201526928510
in vitro and ex vivo antitubercular activity of diarylheptanoids from the rhizomes of alpinia officinarum hance.phytochemical investigation of methanol extract of the rhizomes of alpinia officinarum hance afforded four known diarylheptanoids 1,7-diphenylhept-4-en-3-one (1), 5-hydroxy-1,7-diphenyl-3-heptanone (2), 5-hydroxy-7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-3-heptanone (3), and 7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl heptan-3-one (4).the acetate derivative of (4), 7-(4″-actetate-3″-methoxy phenyl)-1-phenyl heptan-3-one (5), was prepared. these diarylheptanoids exhibited promising in vitro and ex vi ...201626927613
facile synthesis of 1,3-thiazolidin-4-ones as antitubercular agents.we have developed, highly efficient, one-pot, solvent-free, [et3nh][hso4] catalyzed multicomponent reaction protocol for the synthesis of 1,3-thiazolidin-4-ones in excellent yields. for the first time, the 1,3-thiazolidin-4-ones were evaluated in vitro for their antimycobacterial activity against mycobacterium tuberculosis dormant mtb h37ra and mycobacterium bovis bcg strains. among the synthesized basic 1,3-thiazolidin-4-ones, particularly the compounds 4c, 4d, 4e, 4f, 4h, 4i and 4j displays pr ...201626927426
the mycobacterium bovis bcg prime-rv0577 dna boost vaccination induces a durable th1 immune response in mice.tuberculosis remains a major global health problem and effective vaccines are urgently needed. in this study, we used the combined dna- and protein-based vaccines of immunodominant antigen rv0577 to boost bcg and evaluated their immunogenicity in balb/c mice. our data suggest that the booster vaccine may substantially enhance the immunogenicity of bcg and strengthen both cd4+ t cell-mediated th1 and cd8+ t cell-mediated cytolytic responses. compared with the protein-based vaccine, the dna-based ...201626922320
mycobacterial r32-kda antigen-specific t-cell responses correlate with successful treatment and a heightened anti-microbial response in human leprosy patients.immunological characterization of mycobacterial peptides may help not only in the preparation of a vaccine for leprosy but also in developing in vitro t-cell assays that could perhaps be used as an in vitro correlate for treatment outcome. the main goal of this study was to evaluate the use of mycobacterium bovis recombinant 32-kda protein (r32-kda) antigen-stimulated t-cell assay as a surrogate marker for treatment outcome and monitor vitamin d receptor (vdr)-mediated anti-microbial responses d ...201626921215
synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents.a series of indole and pyridine based 1,3,4-oxadiazole derivatives 5a-t were synthesized and evaluated for their in vitro antitubercular activity against mycobacterium tuberculosis h37ra (mtb) and mycobacterium bovis bcg both in active and dormant state. compounds 5b, 5e, 5g and 5q exhibited very good antitubercular activity. all the newly synthesized compounds 5a-t were further evaluated for anti-proliferative activity against hela, a549 and panc-1 cell lines using modified mtt assay and found ...201626920799
acyldepsipeptide antibiotics kill mycobacteria by preventing the physiological functions of the clpp1p2 protease.the clp protease complex in mycobacterium tuberculosis is unusual in its composition, functional importance and activation mechanism. whilst most bacterial species contain a single clpp protein that is dispensable for normal growth, mycobacteria have two clpps, clpp1 and clpp2, which are essential for viability and together form the clpp1p2 tetradecamer. acyldepsipeptide antibiotics of the adep class inhibit the growth of gram-positive firmicutes by activating clpp and causing unregulated protei ...201626919556
intravital fluorescence excitation in whole-animal optical imaging.whole-animal fluorescence imaging with recombinant or fluorescently-tagged pathogens or cells enables real-time analysis of disease progression and treatment response in live animals. tissue absorption limits penetration of fluorescence excitation light, particularly in the visible wavelength range, resulting in reduced sensitivity to deep targets. here, we demonstrate the use of an optical fiber bundle to deliver light into the mouse lung to excite fluorescent bacteria, circumventing tissue abs ...201626901051
molecular detection of mycobacterium bovis in cattle herds of the state of pernambuco, brazil.the present study aimed to direct detect mycobacterium bovis in milk (n = 401) and blood (n = 401) samples collected from 401 dairy cows of 20 properties located in the state of pernambuco, brazil, by real-time quantitative pcr (qpcr) targeting the region of difference 4 (rd4). risk factors possibly associated with bovine tuberculosis (btb) were also evaluated.201626897524
on the impact of masking and blocking hypotheses for measuring the efficacy of new tuberculosis vaccines.over the past 60 years, the mycobacterium bovis bacille calmette-guérin (bcg) has been used worldwide to prevent tuberculosis (tb). however, bcg has shown a very variable efficacy in different trials, offering a wide range of protection in adults against pulmonary tb. one of the most accepted hypotheses to explain these inconsistencies points to the existence of a pre-existing immune response to antigens that are common to environmental sources of mycobacterial antigens and mycobacterium tubercu ...201626893956
relationship of bovine tnf-α gene polymorphisms with the risk of bovine tuberculosis in holstein cattle.many studies suggest significant genetic variation in the resistance of cattle and humans to infection with mycobacterium bovis (m. bovis), the causative agent of zoonotic tuberculosis. tnf-α promotes inflammation and induces apoptosis in response to mycobacterial infection. the aim of the present study was to investigate the influence of single nucleotide polymorphisms of the tnf-α gene on bovine tuberculosis (btb) susceptibility. we genotyped the tnf-α gene in 74 btb-infected holstein cows and ...201626876219
demographic buffering and compensatory recruitment promotes the persistence of disease in a wildlife population.demographic buffering allows populations to persist by compensating for fluctuations in vital rates, including disease-induced mortality. using long-term data on a badger (meles meles linnaeus, 1758) population naturally infected with mycobacterium bovis, we built an integrated population model to quantify impacts of disease, density and environmental drivers on survival and recruitment. badgers exhibit a slow life-history strategy, having high rates of adult survival with low variance, and low ...201626868206
environmental presence of mycobacterium tuberculosis complex in aggregation points at the wildlife/livestock interface.the members of the mycobacterium tuberculosis complex (mtc) cause tuberculosis (tb). infection is transmitted within and between livestock and wildlife populations, thus hampering tb control. indirect transmission might be facilitated if mtc bacteria persist in the environment long enough to represent a risk of exposure to different species sharing the same habitat. we have, for the first time, addressed the relationship between environmental mtc persistence and the use of water resources in two ...201626865411
post-vaccination disseminated bacillus calmette guerin infection among children in southern iran.disseminated bacillus calmette guerin (bcg) infection is a rare but life threatening complication of bcg vaccination. it has been mainly seen in severe immune deficiency. a precise and rapid diagnosis is crucial for prompt initiation of an aggressive anti-mycobacterial treatment. polymerase chain reaction (pcr) is directly applicable to smear-positive clinical specimens, proven to be a rapid and specific diagnostic test.201526862381
evaluation of immunogenicity and protective efficacy elicited by mycobacterium bovis bcg overexpressing ag85a protein against mycobacterium tuberculosis aerosol infection.mycobacterium bovis bacillus calmette-guérin (bcg) is currently the only vaccine available for preventing tuberculosis (tb), however, bcg has varying success in preventing pulmonary tb. in this study, a recombinant bcg (rbcg::ag85a) strain overexpressing the immunodominant ag85a antigen was constructed, and its immunogenicity and protective efficacy were evaluated. our results indicated that the ag85a protein was successfully overexpressed in rbcg::ag85a, and the ag85a peptide-mhc complexes on d ...201626858942
first molecular detection of mycobacterium bovis in environmental samples from a french region with endemic bovine tuberculosis.the aim of the study was to determine the prevalence of mycobacterium bovis (the causative agent of bovine tuberculosis, btb) in environmental matrices within a french region (côte d'or) affected by this zoonotic disease.201626855378
oral vaccination with a rough attenuated mutant of s. infantis increases post-wean weight gain and prevents clinical signs of salmonellosis in s. typhimurium challenged pigs.we show that oral inoculation of 14 day old conventional piglets with a rough attenuated salmonella enterica serovar infantis 1326/28ф(r) (serogroup c1), 24h prior to oral challenge with s. enterica serovar typhimurium 4/74 (serogroup b), resulted in significant weight gain (~10%) measured at 14 days post-weaning (38 days of age). two days after challenge the s. typhimurium induced stunting and, in some cases loss, of villi but this was prevented by pre-inoculation with the s. infantis strain. t ...201626850554
determining the persistence of mycobacterium bovis bacille calmette-guerin danish in select tissues of orally vaccinated feral swine (sus scrofa ssp.).mycobacterium bovis bacille calmette-guerin (bcg) is being considered for vaccination of feral swine (sus scrofa ssp.). since bcg is a live bacterium, evaluation of its safety and persistence in tissues is important. fifteen feral swine received approximately 4.5 × 10(6) colony forming units of bcg danish via oral bait. four animals received bait without bcg. at 1, 3, 6, and 9 months post-vaccination, four vaccinates were euthanized. non-vaccinates were euthanized at 9 months. clinical signs wer ...201626850536
new recombinant mycobacterium bovis bcg expression vectors: improving genetic control over mycobacterial promoters.the expression of many antigens, stimulatory molecules, or even metabolic pathways in mycobacteria such as mycobacterium bovis bcg or m. smegmatis was made possible through the development of shuttle vectors, and several recombinant vaccines have been constructed. however, gene expression in any of these systems relied mostly on the selection of natural promoters expected to provide the required level of expression by trial and error. to establish a systematic selection of promoters with a range ...201626850295
use of the salmonella mgtr peptide as an antagonist of the mycobacterium mgtc virulence factor.the mgtc virulence factor has been proposed as an attractive target for antivirulence strategies because it is shared by several important bacterial pathogens, including salmonella enterica and mycobacterium tuberculosis (mtb).201626849775
sequential bacillus calmette-guérin/electromotive drug administration of mitomycin c as the standard intravesical regimen in high risk nonmuscle invasive bladder cancer: 2-year outcomes.sequential bacillus calmette-guérin/electromotive drug administration of mitomycin c is reported to be superior to bacillus calmette-guérin alone but it has not been widely adopted. we aimed to determine the efficacy and tolerability of sequential bacillus calmette-guérin/electromotive drug administration of mitomycin c in high risk, nonmuscle invasive bladder cancer.201626845426
mycobacterium bovis osteomyelitis of the thoracic spine mimicking a metastatic lytic lesion in a patient exposed to intravesicular bacille calmette-guérin treatment.an 80-year-old man with previous intravesicular bacille calmette-guérin therapy developed mass lesions of the lower thoracic spine. metastatic disease was suspected. the patient underwent a course of radiation; however, biopsy later demonstrated fibrosis and cultures grew mycobacterium bovis. the patient was treated with a course of isoniazid, rifampin, and ethambutol.201426839794
dynamic prognostication using conditional recurrence and progression estimates for patients with nonmuscle invasive bladder cancer.conditional estimates provide a dynamic prediction of outcomes but to our knowledge there are no data on nonmuscle invasive bladder cancer. we assessed changes in conditional recurrence and progression rates after transurethral resection of the bladder and explored the prognostic impact of established factors and risk groups with time.201626835832
vaccines directed against microorganisms or their products present during biofilm lifestyle: can we make a translation as a broad biological model to tuberculosis?tuberculosis (tb) remains as a global public health problem. in recent years, experimental evidence suggesting the relevance of in vitro pellicle (a type of biofilm formed at the air-liquid interface) production as a phenotype mimicking aspects found by mycobacterium tuberculosis-complex bacteria during in vivo infection has started to accumulate. there are still opportunities for better diagnostic tools, therapeutic molecules as well as new vaccine candidates to assist in tb control programs wo ...201626834732
field application of immunoassays for the detection of mycobacterium bovis infection in the african buffalo (syncerus caffer).the african buffalo (syncerus caffer) is considered the most important maintenance host of bovine tuberculosis (btb) in wildlife in southern africa. the diagnosis of mycobacterium bovis infection in this species mostly relies on the single intradermal comparative tuberculin test (sictt). as an alternative, the bovigam® 1g, an interferon-gamma (ifn-γ) release assay, is frequently used. the test performance of cell-mediated immunity (cmi-) and humoral immunity (hi-) based assays for the detection ...201626827841
glutamate dehydrogenase is required by mycobacterium bovis bcg for resistance to cellular stress.we recently reported on our success to generate deletion mutants of the genes encoding glutamate dehydrogenase (gdh) and glutamine oxoglutarate aminotransferase (gogat) in m. bovis bcg, despite their in vitro essentiality in m. tuberculosis. we could use these mutants to delineate the roles of gdh and gogat in mycobacterial nitrogen metabolism by using m. bovis bcg as a model for m. tuberculosis specifically. here, we extended our investigation towards the involvement of gdh and gogat in other a ...201626824899
chronic gastrointestinal nematode infection mutes immune responses to mycobacterial infection distal to the gut.helminth infections have been suggested to impair the development and outcome of th1 responses to vaccines and intracellular microorganisms. however, there are limited data regarding the ability of intestinal nematodes to modulate th1 responses at sites distal to the gut. in this study, we have investigated the effect of the intestinal nematode heligmosomoides polygyrus bakeri on th1 responses to mycobacterium bovis bacillus calmette-guérin (bcg). we found that h. polygyrus infection localized t ...201626819205
manipulation of bcg vaccine: a double-edged sword.mycobacterium bovis bacillus calmette-guérin (bcg), an attenuated vaccine derived from m. bovis, is the only licensed vaccine against tuberculosis (tb). despite its protection against tb in children, the protective efficacy in pulmonary tb is variable in adolescents and adults. in spite of the current knowledge of molecular biology, immunology and cell biology, infectious diseases such as tb and hiv/aids are still challenges for the scientific community. genetic manipulation facilitates the cons ...201626810060
tlr2-modulating lipoproteins of the mycobacterium tuberculosis complex enhance the hiv infectivity of cd4+ t cells.co-infection with mycobacterium tuberculosis accelerates progression from hiv to aids. our previous studies showed that m. tuberculosis complex, unlike m. smegmatis, enhances tlr2-dependent susceptibility of cd4+ t cells to hiv. the m. tuberculosis complex produces multiple tlr2-stimulating lipoproteins, which are absent in m. smegmatis. m. tuberculosis production of mature lipoproteins and tlr2 stimulation is dependent on cleavage by lipoprotein signal peptidase a (lspa). in order to determine ...201626807859
a species-specific activation of toll-like receptor signaling in bovine and sheep bronchial epithelial cells triggered by mycobacterial infections.pulmonary tuberculosis caused by a mycobacterium infection remains a major public health problem in most part of the world, in part owing to the transmission of its pathogens between hosts including human, domestic and wild animals. to date, molecular mechanisms of the pathogenesis of tb are still incompletely understood. in addition to alveolar macrophages, airway epithelial cells have also been recently recognized as main targets for mycobacteria infections. in an effort to understand the path ...201626802731
a modelling framework for predicting the optimal balance between control and surveillance effort in the local eradication of tuberculosis in new zealand wildlife.bovine tuberculosis (tb) impacts livestock farming in new zealand, where the introduced marsupial brushtail possum (trichosurus vulpecula) is the wildlife maintenance host for mycobacterium bovis. new zealand has implemented a campaign to control tb using a co-ordinated programme of livestock diagnostic testing and large-scale culling of possums, with the long-term aim of tb eradication. for management of the disease in wildlife, methods that can optimise the balance between control and surveill ...201626795464
assessment of safety and interferon gamma responses of mycobacterium bovis bcg vaccine in goat kids and milking goats.vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (tb). a trial under field conditions was conducted in a tb-free goat herd to assess the safety of the mycobacterium bovis bcg vaccine. eleven kids and 10 milking goats were vaccinated with bcg. bacterial shedding and interferon gamma (ifn-γ) responses were monitored throughout the study. comprehensive pathological examination and mycobacterial culture of target tissues were performed. ...201626795364
molecular analysis of the bacille calmette-guérin vaccine strain currently being used in iran.in developing countries, tuberculosis (tb) infection control remains a challenge. the bacille calmette-guérin (bcg) vaccine is the only effective vaccine available for tb control. iran uses a local bcg vaccine strain with an unknown substrain.201626792475
detailed chronological analysis of microevolution events in herds infected persistently by mycobacterium bovis.various studies have analyzed microevolution events leading to the emergence of clonal variants in human infections by mycobacterium tuberculosis. however, microevolution events in animal tuberculosis remain unknown. we performed a systematic analysis of microevolution events in eight herds that were chronically infected by mycobacterium bovis for more than 12 months. we analyzed 88 animals using a systematic screening procedure based on discriminatory miru-vntr genotyping at sequential time poi ...201626790941
infected aortic aneurysm caused by mycobacterium bovis after intravesical bacillus calmette-guérin treatment for bladder cancer.a 70-year-old man presented with lower back pain and cyanotic changes in his left lower extremity. he was diagnosed with infected aortic aneurysm and infectious spondylitis. he had received intravesical bacillus calmette-guérin (bcg) therapy up to 1 month before the onset of symptoms. the aneurysm was excised and an aorto-biiliac interposition graft was performed. mycobacterium tuberculosis complex was cultured in the surgical specimens. real-time polymerase chain reaction (pcr) targeting the se ...201526788410
comparison of lcd array and is6110-pcr with conventional techniques for detection of mycobacterium bovis isolated from egyptian cattle and buffaloes.bovine tuberculosis is a chronic bacterial and major infectious disease of cattle and buffaloes caused by mycobacterium bovis. rapid diagnosis of bovine tuberculosis is considered one of the cornerstones for worldwide control as it permits early epidemiological and therapeutic interventions. therefore, this study was designed to evaluate conventional techniques (tuberculin test, ziehl neelsen staining and culturing) in comparison with proven molecular laboratory techniques (lcd array and is6110 ...201426786488
identification of mycobacterium species following growth detection with the bactec mgit 960 system by dna line probe assay.the tuberculosis and infections caused by nontuberculous mycobacterial (ntm) species are increasing in patients presented with respiratory illness, and it is crucial to document the epidemiology of these infections.201426786328
mycotic aortic aneurysm due to intravesical bcg immunotherapy: clinical manifestations and diagnostic challenges.a live, attenuated form of mycobacterium bovis, bacillus calmette-guérin (bcg), is commonly used as intravesical immunotherapy for non-invasive urothelial bladder carcinoma. while complications are rare, dissemination can occur. a case of mycotic aortic aneurysm following bcg administration with recovery of mycobacterium bovis in culture is reported. a review of the published experience with this problem is also presented.201426786225
alteration of human macrophages microrna expression profile upon infection with mycobacterium tuberculosis.mycobacterium tuberculosis (mtb) has evolved multiple mechanisms to manipulate its cellular niche for its own advantage. many efforts have been made to understand basal mechanisms of mycobacterial infections. however, the underlying molecular regulation is not fully understood. recently, a new class of non-coding, small rnas, called micrornas (mirnas), has emerged as important regulators in biological processes, and their involvement in mycobacterial infection has been identified, thus opening a ...201326785980
extracellular forms of mycobacterium bovis bcg in the mucosal lymphatic tissues following oral vaccination.oral vaccination with bcg provides protective systemic immunity against pathogenic mycobacterial challenge. in this study, the anatomical distribution of mycobacterium bovis bcg following oral vaccination was investigated. replicating bacteria in the peyer's patches and mesenteric lymph nodes were present as solitary rods or clusters of two to three bacteria, the majority of which were isolated ex vivo as extracellular forms. only a minority were shown to be associated with typical antigen-prese ...201326785788
generation of transgenic cattle expressing human β-defensin 3 as an approach to reducing susceptibility to mycobacterium bovis infection.bovine tuberculosis results from infection with mycobacterium bovis, a member of the mycobacterium tuberculosis family. worldwide, m. bovis infections result in economic losses in the livestock industry; cattle production is especially hard-hit by this disease. generating m. bovis-resistant cattle may potentially mitigate the impact of this disease by reducing m. bovis infections. in this study, we used transgenic somatic cell nuclear transfer to generate cattle expressing the gene encoding huma ...201626782926
effect of culling and vaccination on bovine tuberculosis infection in a european badger (meles meles) population by spatial simulation modelling.the control of bovine tuberculosis (btb) in cattle herds in the republic of ireland (roi) is partially hindered by spill-back infection from wild badgers (meles meles). the aim of this study was to determine the relative effects of interventions (combinations of culling and/or vaccination) on btb dynamics in an irish badger population. a spatial agent-based stochastic simulation model was developed to evaluate the effect of various control strategies for bovine tuberculosis in badgers: single co ...201626774448
down regulated lncrna meg3 eliminates mycobacteria in macrophages via autophagy.small non-coding rna play a major part in host response to bacterial agents. however, the role of long non-coding rna (lncrna) in this context remains unknown. lncrna regulate gene expression by acting e.g. as transcriptional coactivators, rna decoys or microrna sponges. they control development, differentiation and cellular processes such as autophagy in disease conditions. here, we provide an insight into the role of lncrna in mycobacterial infections. human macrophages were infected with myco ...201626757825
risk factors associated with mycobacterium bovis skin positivity in cattle and buffalo in peshawar, pakistan.a cross-sectional study was carried out to determine the prevalence of bovine tuberculosis (btb) and associated risk factors in cattle and buffalo in peshawar, pakistan. cattle and buffalo, randomly selected from all four towns of district peshawar, were screened for bovine tuberculosis using comparative cervical intradermal tuberculin test (ccit). for obtaining data on risk factors, sociodemographic condition, animal characteristics, and management, interviewer administered pretested questionna ...201626754290
respiratory tract infection caused by mycobacterium bovis in a black swan (cygnus atratus).a 3-year-old male black swan (cygnus atratus), belonging to a private collection, died suddenly and was subjected to post mortem examination. at necropsy, caseous exudate was observed in the lungs and air sacs; granulomatous lesions characterized by epithelioid macrophages and abundant mycobacteria were observed microscopically. avian tuberculosis associated with mycobacterium bovis was confirmed by bacteriologic isolation, biochemical tests and molecular methods. the organism was identified as ...201626743683
diagnosis of tuberculosis in groups of badgers: an exploration of the impact of trapping efficiency, infection prevalence and the use of multiple tests.accurate detection of infection with mycobacterium bovis in live badgers would enable targeted tuberculosis control. practical challenges in sampling wild badger populations mean that diagnosis of infection at the group (rather than the individual) level is attractive. we modelled data spanning 7 years containing over 2000 sampling events from a population of wild badgers in southwest england to quantify the ability to correctly identify the infection status of badgers at the group level. we exp ...201626733317
the case of an apds patient: defects in maturation and function and decreased in vitro anti-mycobacterial activity in the myeloid compartment.activated pi3-kinase delta syndrome (apds) was recently reported as a novel primary immunodeficiency caused by heterozygous gain-of-function mutations in pik3cd gene. here we describe immunological studies in a 19year old apds patient for whom genetic diagnosis was discovered by whole exome sequencing (wes) analysis. in addition to the progressive lymphopenia and defective antibody production we showed that the ability of the patient's b cells to differentiate in vitro is severely reduced. an in ...201526732860
ebp50 induces apoptosis in macrophages by upregulating nitric oxide production to eliminate intracellular mycobacterium tuberculosis.mycobacterium bovis bcg is known to have the capacity to inhibit the positioning of inos on bcg-containing phagosomes by interfering with ebp50, a scaffolding protein that controls the recruitment of inducible nitric oxide synthase (inos) at the vicinity of phagosomes in macrophages. however, knockdown of the expression of ebp50 still facilitates the intracellular survival of bcg, which suggested that ebp50 may have some other unknown antimycobacterial properties. in this study we show that over ...201626729618
evaluation of a novel commercial quaternary ammonium compound for eradication of mycobacteria, hcv and hbv in egypt.endoscopes are a common source of outbreaks of healthcare-associated infections. it is therefore important to identify high-level disinfectants capable of eliminating or killing all vegetative bacteria, mycobacteria, and viruses. aldehydebased disinfectants are most commonly used in clinical practice but resistance has recently been detected and side effects associated with these disinfectants are well documented. in this study, we evaluated virusolve+® eds, a novel quaternary ammonium compound ...201626727900
evidence of co-infection with mycobacterium bovis and tick-borne pathogens in a naturally infected sheep flock.ticks are responsible for the transmission of pathogens of veterinary importance, including those affecting sheep. the current study was designed to investigate co-infections with tick-borne and other pathogens in a naturally infected sheep flock with poor health condition using serology and pcr. infection with anaplasma ovis was detected by serology and pcr in 56% of the animals. the presence of rickettsia spp. of the spotted fever group (sfg) was detected by pcr and sequence analysis in 31% of ...201626726806
mycobacterium bovis infection in a wild sow (sus scrofa): first case in korea.mycobacterium (m.) bovis causes tuberculosis and has a broad host range, including humans, livestock, and wild animals. m. bovis infection of wild boar has been reported in several european countries. we report here the first case of m. bovis infection in a domesticated wild sow in korea. granulomatous and necrotizing lesions with small numbers of acid-fast bacilli were observed in nodules of the lung of wild sow. furthermore, the m. bovis isolate from the wild sow had spoligotype sb0140 and a n ...026726026
improving the immunogenicity of the mycobacterium bovis bcg vaccine by non-genetic bacterial surface decoration using the avidin-biotin system.current strategies to improve the current bcg vaccine attempt to over-express genes encoding specific m. tuberculosis (mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape bcg in many ways. however, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous dna. as an alternative, we develop ...201526716832
genotyping and resolution of a case of osteomyelitis in a 16-month-old boy of hispanic/african american ethnicity.most cases of osteomyelitis in children are caused by staphylococcus aureus, although kingella kingae, various streptococci, and salmonella species also underlie this condition. organisms such as mycobacterium, histoplasma, and cryptococcus are much less commonly identified as etiologic agents in osteomyelitis. this case report describes a 16-month-old boy of hispanic/african american ethnicity who had extensive inflammation of and discharge from his right ankle. imaging studies supported a diag ...201626715611
inhibition of neutral sphingomyelinase protects mice against systemic tuberculosis.tuberculosis is one of the most serious infectious diseases worldwide. the initial pulmonal localization of the pathogens often develops into systemic infection with high lethality. we investigated the role of the mammalian neutral sphingomyelinase (nsm)/ceramide system in systemic infection of mice and murine macrophages with mycobacterium bovis bacillus calmette-guerin (bcg). our results demonstrate that bcg infection of raw cells, a macrophage cell line, results in rapid activation of nsm but ...201626709664
precision methylome characterization of mycobacterium tuberculosis complex (mtbc) using pacbio single-molecule real-time (smrt) technology.tuberculosis (tb) remains one of the most common infectious diseases caused by mycobacterium tuberculosis complex (mtbc). to panoramically analyze mtbc's genomic methylation, we completed the genomes of 12 mtbc strains (mycobacterium bovis; m. bovis bcg; m. microti; m. africanum; m. tuberculosis h37rv; h37ra; and 6 m. tuberculosis clinical isolates) belonging to different lineages and characterized their methylomes using single-molecule real-time (smrt) technology. we identified three (m6)a sequ ...201626704977
molecular epidemiology of mycobacterium bovis in humans and cattle.bovine tuberculosis (btb), caused by mycobacterium bovis (m. bovis), is a serious re-emerging disease in both animals and humans. the evolution of the multi- and extensively drug-resistant m. bovis strains (mdr-tb and xdr-tb) represents a global threat to public health. worldwide, the disease is responsible for great economic losses in the veterinary field, serious threat to the ecosystem, and about 3.1% of human tb cases, up to 16% in tanzania. only thorough investigation to understand the path ...201626684712
bovine tuberculosis in domestic pigs: genotyping and distribution of isolates in argentina.bovine tuberculosis is caused by mycobacterium bovis and affects primarily cattle, among many other mammal species. in this study, 250 isolates of m. bovis collected from pigs slaughtered in argentina were typed by spoligotyping. over half of the isolates (66%) grouped into two spoligotypes. moreover, sb0140 was the most frequent spoligotype detected in the three performed samplings. in addition, 195 isolates were typed through variable number of tandem repeats (vntr) by selecting 7 loci (miru 1 ...201526679794
interleukin-17a as a biomarker for bovine tuberculosis.t helper 17 (th17)-associated cytokines are integral to the immune responses to tuberculosis, initiating both protective and harmful inflammatory responses. the aim of the present study was to evaluate applied aspects of interleukin-17 (il-17) biology in the context of mycobacterium bovis infection of cattle. using transcriptome sequencing (rna-seq), numerous th17-associated cytokine genes (including il-17a, il-17f, il-22, il-19, and il-27) were upregulated >9-fold in response to purified protei ...201526677202
mycobacterium bovis hip bursitis in a lung transplant recipient.we present a report of extrapulmonary mycobacterium bovis infection in a lung transplant recipient. m. bovis is acquired predominantly by zoonotic transmission, particularly from consumption of unpasteurized foods. we discuss epidemiologic exposure, especially as relates to the mexico-us border, clinical characteristics, resistance profile, and treatment.201626671334
in vitro gene expression profile of bovine peripheral blood mononuclear cells in early mycobacterium bovis infection.the intracellular parasite mycobacterium bovis (m. bovis) causes tuberculosis in cattle and humans. understanding the interactions between m. bovis and host cells is essential in developing tools for the prevention, detection, and treatment of m. bovis infection. gene expression profiles provide a large amount of information regarding the molecular mechanisms underlying these interactions. the present study analyzed changes in gene expression in bovine peripheral blood mononuclear cells (pbmcs) ...201526668602
whole-genome sequence of mycobacterium bovis w-1171, isolated from the laryngopharyngeal lymph node of a wild boar in south korea.mycobacterium bovis w-1171 was isolated from a wild boar living in a free-ranging field in gyeonggido, south korea. the whole-genome sequence of this strain was determined in 50 contigs, which was 4,304,865 bp with a 65.57% g+c content. in total 3,945 protein-coding genes were predicted from this assembly.201526659693
a thoracic tuberculous spondylodisctis after intravesical bcg immunotherapy of bladder cancer - case report and literature review.we report a rare case of tuberculosis of the thoracic spine caused by mycobacterium bovis infection as a complication of bcg (bacillus calmette-guérin) intravesical immunotherapy, which is a well known and acknowledged treatment of superficial bladder cancers applied since 1976. although this therapy is broadly used in urology and considered to be safe and well tolerated, one should be aware of the potential local and systemic side effects as in the case of our patient, who developed tuberculous ...201526652884
a birth cohort study of maternal and infant serum pcb-153 and dde concentrations and responses to infant tuberculosis vaccination.reasons for the highly variable and often poor protection conferred by the mycobacterium bovis bacille calmette-guérin (bcg) vaccine are multifaceted and poorly understood.201626649893
[immunotherapy of urothelial carcinoma of the bladder -  from bcg vaccines to targeted therapy].bladder cancer has high prevalence in men and women. bladder cancer usually originates from urothelium. more than 75% of cases are classified as nonmuscle invasive bladder cancer. urothelial bladder carcinoma is usually managed by transurethral resection of the bladder tumor. role of transurethral resection of the bladder tumor is also essential in bladder cancer staging. local prophylaxis is used in nonmuscle invasive bladder cancer to reduce risk of recurrence. while local chemoprophylaxis is ...201526647897
variable virulence and efficacy of bcg vaccine strains in mice and correlation with genome polymorphisms.bacille calmette-guérin (bcg), an attenuated strain of mycobacterium bovis, is the only vaccine available for tuberculosis (tb) control. however, bcg is not an ideal vaccine and has two major limitations: bcg exhibits highly variable effectiveness against the development of tb both in pediatric and adult populations and can cause disseminated bcg disease in immunocompromised individuals. bcg comprises a number of substrains that are genetically distinct. whether and how these genetic differences ...201626643797
new verapamil analogs inhibit intracellular mycobacteria without affecting the functions of mycobacterium-specific t cells.there is a growing interest in repurposing mycobacterial efflux pump inhibitors, such as verapamil, for tuberculosis (tb) treatment. to aid in the design of better analogs, we studied the effects of verapamil on macrophages and mycobacterium tuberculosis-specific t cells. macrophage activation was evaluated by measuring levels of nitric oxide, tumor necrosis factor alpha (tnf-α), interleukin-1 beta (il-1β), and gamma interferon (ifn-γ). since verapamil is a known autophagy inducer, the roles of ...201526643325
identification of new molecular entities (nmes) as potential leads against tuberculosis from open source compound repository.the purpose of this study was to provide a number of diverse and promising early-lead compounds that will feed into the drug discovery pipeline for developing new antitubercular agents. the results from the phenotypic screening of the open-source compound library against mycobacterium smegmatis and mycobacterium bovis (bcg) with hit validation against m. tuberculosis (h37rv) have identified novel potent hit compounds. to determine their druglikeness, a systematic analysis of physicochemical prop ...201526642200
mycobacterium spp. in wild game in slovenia.wildlife species are an important reservoir of mycobacterial infections that may jeopardise efforts to control and eradicate bovine tuberculosis (btb), caused by mycobacterium bovis. slovenia is officially free of btb, but no data on the presence of mycobacteria in wild animals has been reported. in this study, samples of liver and lymph nodes were examined from 306 apparently healthy free-range wild animals of 13 species in slovenia belonging to the families cervidae, suidae, canidae, mustelida ...201626639827
[differential sensitivity of microorganisms to polyhexamethyleneguanidine].factors identified that affect the sensitivity of microorganisms to polyhexamethyleneguanidine (phmg). salts of phmg chloride, valerate, maleate, succinate was to use. test strains of esherichia coli, staphylococcus aureus, bacillus cereus, leptospira interrogans, paenibacillus larvae, mycobacterium bovis, m. avium, m. fortuitum, aspergillus niger and some strains of viruses are taken as objects of research. we have determined that the cytoplasm membrane phospholipids is main "target" for the po ...201526638480
deep sequencing analysis of the heterogeneity of seed and commercial lots of the bacillus calmette-guérin (bcg) tuberculosis vaccine substrain tokyo-172.bcg, only vaccine available to prevent tuberculosis, was established in the early 20th century by prolonged passaging of a virulent clinical strain of mycobacterium bovis. bcg tokyo-172, originally distributed within japan in 1924, is one of the currently used reference substrains for the vaccine. recently, this substrain was reported to contain two spontaneously arising, heterogeneous subpopulations (types i and ii). the proportions of the subpopulations changed over time in both distributed se ...201526635118
world health organization estimates of the global and regional disease burden of 22 foodborne bacterial, protozoal, and viral diseases, 2010: a data synthesis.foodborne diseases are important worldwide, resulting in considerable morbidity and mortality. to our knowledge, we present the first global and regional estimates of the disease burden of the most important foodborne bacterial, protozoal, and viral diseases.201526633831
evaluation of an interferon gamma release assay to detect tuberculosis infection in children in san diego, california.quantiferon-tb gold in-tube (qft-git) and tuberculin skin test (tst) results are reported in 23 children with active tuberculosis due to mycobacterium tuberculosis and mycobacterium bovis. overall qft-git (96%) was more sensitive than tst (74%) for detecting tuberculosis infection in these patients.201226618694
reactivation of mycobacterium bovis infection and tumor necrosis factor inhibitors. a mexican case. 201626616568
abdominal cocoon syndrome caused by mycobacterium bovis from consumption of unpasteurised cow's milk. 201526607132
chemical characterization and evaluation of antibacterial, antifungal, antimycobacterial, and cytotoxic activities of talinum paniculatum.in this study, the bioactivity of talinum paniculatum was evaluated, a plant widely used in folk medicine. the extract from the t. paniculatum leaves (le) was obtained by percolation with ethanol-water and then subjecting it to liquid-liquid partitions, yielding hexane (hx), ethyl acetate (etoac), butanol (buoh), and aqueous (aq) fractions. screening for antimicrobial activity of the le and its fractions was evaluated in vitro through broth microdilution method, against thirteen pathogenic and n ...201726603226
mycobacterium tuberculosis causing tuberculous lymphadenitis in maputo, mozambique.the zoonosis bovine tuberculosis (tb) is known to be responsible for a considerable proportion of extrapulmonary tb. in mozambique, bovine tb is a recognised problem in cattle, but little has been done to evaluate how mycobacterium bovis has contributed to human tb. we here explore the public health risk for bovine tb in maputo, by characterizing the isolates from tuberculous lymphadenitis (tbln) cases, a common manifestation of bovine tb in humans, in the pathology service of maputo central hos ...201526589993
prevalence and risk factors for bovine tuberculosis in minas gerais state, brazil.the aim of the present study was to estimate the prevalence and regional spread of bovine tuberculosis in the state of minas gerais, brazil, to identify herd-level risk factors, and to provide guidance for disease control and mitigation of its impact in public health. the study comprised a large-scale random sample survey of 22,990 animals and 1586 herds, distributed in seven regions. a questionnaire was applied on each farm to collect epidemiological and herd management data. overall, 5.04 % of ...201626584941
comparative genomics of field isolates of mycobacterium bovis and m. caprae provides evidence for possible correlates with bacterial viability and virulence.mycobacteria of the mycobacterium tuberculosis complex (mtbc) greatly affect humans and animals worldwide. the life cycle of mycobacteria is complex and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. recently, comparative genomics analyses have provided new insights into the evolution and adaptation of the mtbc to survive inside the host. however, most of this information has been obtained using m. tuberculosis but not other members of the mtb ...201526583774
development of an improved esat-6 and cfp-10 peptide-based cytokine flow cytometric assay for bovine tuberculosis.control of bovine tuberculosis (btb) continues to be a problem world-wide because of difficulties in identifying infected animals at all stages of infection. the use of the ifn-γ release assays (igra) as an ancillary test with the tuberculin skin tests has improved the ability to identify infected animals. however, infected animals may still be missed. the objective of the present study was to evaluate a rapid flow-cytometric assay based on intracellular cytokine staining as an alternative to th ...201526577191
a quasi-universal medium to break the aerobic/anaerobic bacterial culture dichotomy in clinical microbiology.in the mid-19th century, the dichotomy between aerobic and anaerobic bacteria was introduced. nevertheless, the aerobic growth of strictly anaerobic bacterial species such as ruminococcus gnavus and fusobacterium necrophorum, in a culture medium containing antioxidants, was recently demonstrated. we tested aerobically the culture of 623 bacterial strains from 276 bacterial species including 82 strictly anaerobic, 154 facultative anaerobic, 31 aerobic and nine microaerophilic bacterial species as ...201626577141
myobacterium bovis peri-prosthetic hip infection with successful prosthesis retention following intravesical bcg therapy for bladder carcinoma.systemic dissemination and peri-prosthetic infection of mycobacterium bovis (m. bovis) following intravesical bacillus calmette-guerin (bcg) therapy presents a rare but significant complication of treatment for non-muscle invasive bladder carcinoma. we present a patient with mycobacterium bovis infection of a prosthetic hip nine months following bcg therapy for bladder cancer. the debridement and (implant) prosthesis retention approach in conjunction with anti-tuberculous medication (dair) emplo ...201526576201
thioridazine in plga nanoparticles reduces toxicity and improves rifampicin therapy against mycobacterial infection in zebrafish.encapsulating antibiotics such as rifampicin in biodegradable nanoparticles provides several advantages compared to free drug administration, including reduced dosing due to localized targeting and sustained release. consequently, these characteristics reduce systemic drug toxicity. however, new nanoformulations need to be tested in complex biological systems to fully characterize their potential for improved drug therapy. tuberculosis, caused by infection with the bacterium mycobacterium tuberc ...201626573343
a new screen for tuberculosis drug candidates utilizing a luciferase-expressing recombinant mycobacterium bovis bacillus calmette-guéren.tuberculosis (tb) is a serious infectious disease caused by a bacterial pathogen. mortality from tuberculosis was estimated at 1.5 million deaths worldwide in 2013. development of new tb drugs is needed to not only to shorten the medication period but also to treat multi-drug resistant and extensively drug-resistant tb. mycobacterium tuberculosis (mtb) grows slowly and only multiplies once or twice per day. therefore, conventional drug screening takes more than 3 weeks. additionally, a biosafety ...201526571296
whole-genome sequence of mycobacterium bovis bcg-1 (russia).bcg vaccine (mycobacterium bovis bcg-1 [russia]) is the most important component of tuberculosis prophylaxis in russia. this study represents the complete genome sequence and genetic characteristics of m. bovis bcg-1 (russia), which has been used to manufacture bcg vaccine in russia and in some other countries.201526564042
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