Publications

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performance of the g4 xpert(®) mtb/rif assay for the detection of mycobacterium tuberculosis and rifampin resistance: a retrospective case-control study of analytical and clinical samples from high- and low-tuberculosis prevalence settings.the xpert(®) mtb/rif (xpert) assay is a rapid pcr-based assay for the detection of mycobacterium tuberculosis complex dna (mtbc) and mutations associated with rifampin resistance (rif). an updated version introduced in 2011, the g4 xpert, included modifications to probe b and updated analytic software.201627993132
targeting dendritic cells to accelerate t-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy.the development of a tuberculosis (tb) vaccine that induces sterilizing immunity to mycobacterium tuberculosis infection has been elusive. absence of sterilizing immunity induced by tb vaccines may be due to delayed activation of mucosal dendritic cells (dcs), and subsequent delay in antigen presentation and activation of vaccine-induced cd4(+) t-cell responses. here we show that pulmonary delivery of activated m. tuberculosis antigen-primed dcs into vaccinated mice, at the time of m. tuberculos ...201628004802
tubercular sialadenitis of parotid gland - an extremely rare case series.tuberculosis is a potentially fatal infectious disease caused by mycobacterium tuberculosis. it most commonly involves the lungs (pulmonary tuberculosis), although it can involve any organ system in the body. however even in a country like india which has high burden of this disease, the tubercular invasion of parotid gland is extremely rare. here we describe two such cases. both patients were immune competent and presented with fever and swelling in the parotid region. they were diagnosed as tu ...201627998500
abdominal tuberculosis: a retrospective analysis of 45 cases.abdominal tuberculosis is defined as infection of the peritoneum, hollow or solid abdominal organs with mycobacterium tuberculosis. the peritoneum and the ileocaecal region are the most likely sites of infection and are involved in the majority of the cases by haematogenous spread or through swallowing of infected sputum from primary pulmonary tuberculosis. pulmonary tuberculosis is apparent in less than half of the patients. patients usually present with abdominal pain, and the cause is usually ...201627998492
[application of whole genome sequencing technology in the epidemiology of tuberculosis].objective: to delineate the application of whole genome sequencing technology in the epidemiology of tuberculosis. methods: from 2009 to 2012, nine mycobacterium tuberculosis that sharing identical variable number of tandem repeats genotype (vntr) patterns were reported from two tb cases designated hospitals. both whole-genome sequencing analysis (wgs) and epidemiologic investigations were performed to describe the transmission patterns of these mycobacterium tuberculosis. results: by wgs analys ...201627998414
mycobacterium tuberculosis as a cause of mandibular osteomyelitis in a young woman: a case report.tuberculosis is considered an emerging disease worldwide; in the last 10 years, its incidence has increased to more than 9.6 million cases of active tuberculosis. in 2014, it resulted in 1.5 million patient deaths. however, oral presentation with bone involvement occurs in less than 3% of all reported cases and rarely arouses clinical suspicion on initial presentation.201627998317
mycobacterium tuberculosis infections in cynomolgus monkey transplant recipients and institution of a screening program for the prevention and control of tuberculosis.tuberculosis is a major health concern in not only humans, but also in non-human primates. in this paper, we report recent cases of mycobacterium tuberculosis in cynomolgus monkeys from cambodia used in transplantation research in a korean facility and describe a program instituted to prevent and control subsequent infections.201627998279
immunogenicity and protective efficacy of the dar-901 booster vaccine in a murine model of tuberculosis.the development of a novel tuberculosis vaccine is a leading global health priority. srl172, an inactivated, whole-cell mycobacterial vaccine, was safe, immunogenic and reduced the incidence of culture-confirmed tuberculosis in a phase iii trial in hiv-infected and bcg immunized adults in tanzania. here we describe the immunogenicity and protective efficacy of dar-901, a booster vaccine against tuberculosis manufactured from the same seed strain using a new scalable method.201627997597
host immunity to mycobacterium tuberculosis and risk of tuberculosis: a longitudinal study among greenlanders.human immune responses to latent mycobacterium tuberculosis (mtb) infection (ltbi) may enable individuals to control mtb infection and halt progression to tuberculosis (tb), a hypothesis applied in several novel tb vaccines. we aimed to evaluate whether immune responses to selected ltbi antigens were associated with subsequent reduced risk of progression to tb.201627997344
transmissible mycobacterium tuberculosis strains share genetic markers and immune phenotypes.successful transmission of tuberculosis depends on the interplay of human behavior, host immune responses and mycobacterium tuberculosis virulence factors. previous studies have focused on identifying host risk factors associated with increased transmission, while the contribution of specific genetic variations in mycobacterial strains themselves are still unknown.201627997216
a first insight into the genetic diversity and drug susceptibility pattern of mycobacterium tuberculosis complex in zhejiang, china.in this study, our aim was to determine the predominant genotypes among the mycobacterium tuberculosis (mtb) strains circulating in zhejiang province. in addition, we also sought to determine the potential associations between mtb genotypes and susceptibility to first-line drugs. out of these isolates, 673 (71.6%) were classified into the beijing genotype, while the other 267 (28.4%) were from non-beijing families. the highest proportion of beijing genotype was found in huzhou (80.0%) and the lo ...201627995145
discovery and optimization of two eis inhibitor families as kanamycin adjuvants against drug-resistant m. tuberculosis.drug-resistant tuberculosis (tb) is a global threat and innovative approaches such as using adjuvants of anti-tb therapeutics are required to combat it. high-throughput screening yielded two lead scaffolds of inhibitors of mycobacterium tuberculosis (mtb) acetyltransferase eis, whose upregulation causes resistance to the anti-tb drug kanamycin (kan). chemical optimization on these scaffolds resulted in potent eis inhibitors. one compound restored the activity of kan in a kan-resistant mtb strain ...201627994767
correlation of rpob mutations with minimal inhibitory concentration of rifampin and rifabutin in mycobacterium tuberculosis in an hiv/aids endemic setting, south africa.treatment of tuberculosis (tb) and hiv co-infections is often complicated by drug-to-drug interactions between anti-mycobacterial and anti-retroviral agents. rifabutin (rfb) is an alternative to rifampin (rif) for tb regimens and is recommended for hiv patients concurrently receiving protease inhibitors because of reduced induction of cyp3a4. this study sought to determine the proportion of rfb susceptible isolates among rif-resistant strains in a high hiv prevalence setting in south africa. in ...201627994580
diagnosis of pulmonary tuberculosis and detection of resistance to rifampin and isoniazid through direct molecular methods in stool samples.tuberculosis (tb) is an infectious disease that is caused by mycobacterium tuberculosis (m.tb). tb has high morbidity and mortality around the world.201627993874
emerging resistant clone of mycobacterium tuberculosis in west asia. 201627998587
a clinic-epidemiological study of head and neck tuberculosis - a single-center experience.extrapulmonary tuberculosis (eptb) accounts for less than 6% of all tuberculosis (tb) cases in poland, although in other countries (european in particular) this proportion is much higher. the study was undertaken to evaluate the clinical and epidemiological differences in patients hospitalized in one of otolaryngology departments in poland during 36 years.201628009032
pathogenic mycobacteria achieve cellular persistence by inhibiting the niemann-pick type c disease cellular pathway.tuberculosis remains a major global health concern. the ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including mycobacterium tuberculosis, achieve long-term persistence within host cells. the mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. host macrophages infected with persistent mycobacteria share phenotypic similarities with cells taken from patients suffering from niemann-pick disease ...201628008422
performance of real-time pcr xpert ®mtb/rif in diagnosing extrapulmonary tuberculosis.the real time pcr xpert ® mtb/rif is fundamental for rapid diagnosis in paucibacillary respiratory samples and for the detection of multidrug-resistant tb cases. this paper aimed to determine its performance on different extrapulmonary samples. we determined sensitivity, specificity, positive and negative predictive value on respiratory and non-respiratory samples collected from january 2010 to june 2014. the protocol for the xpert ® mtb/rif pcr suggested by cepheid was strictly followed for all ...201628011966
the variability and reproducibility of whole genome sequencing technology for detecting resistance to anti-tuberculous drugs.the emergence of resistance to anti-tuberculosis drugs is a serious and growing threat to public health. next-generation sequencing is rapidly gaining traction as a diagnostic tool for investigating drug resistance in mycobacterium tuberculosis to aid treatment decisions. however, there are few little data regarding the precision of such sequencing for assigning resistance profiles.201628003022
cholesterol metabolism: a potential therapeutic target in mycobacteria.tuberculosis (tb), although a curable disease, is still one of the most difficult infections to treat. mycobacterium tuberculosis infects 10 million people worldwide and kills 1.5 million people each year. reactivation of a latent infection is the major cause of tb. cholesterol is a critical carbon source during latent infection. catabolism of cholesterol contributes to the pool of propionyl-coa, a precursor that is incorporated into lipid virulence factors. the m. tuberculosis genome contains a ...201628002883
mycobacterium tuberculosis cell wall released fragments by the action of the human lung mucosa modulate macrophages to control infection in an il-10-dependent manner.mycobacterium tuberculosis (m.tb), the causative agent of tuberculosis, is a major public health challenge facing the world. during infection, m.tb is deposited in the lung alveolar space where it comes in contact with the lung mucosa, known as alveolar lining fluid (alf), an environment that m.tb encounters at different stages of the infection and disease. alf is abundant in homeostatic and antimicrobial hydrolytic enzymes, also known as hydrolases. here we demonstrate that alf hydrolases, at t ...201628000679
active tuberculosis patients have high levels of iga anti-alpha-crystallin and isocitrate lyase proteins.mexico city, mexico.201628000588
evaluation of omnigene®•sputum-stabilised sputum for long-term transport and xpert® mtb/rif testing in nepal.german nepal tb project, national tuberculosis reference laboratory, kathmandu, nepal.201628000586
ifn-γ promoter polymorphisms do not affect quantiferon® tb gold in-tube test results in a canadian population.several studies have shown polymorphisms within the interferon-gamma (ifn-γ) promoter influence cytokine expression. the interferon-gamma release assay (igra) relies on the ability to produce ifn-γ in response to tuberculosis (tb) specific antigens. this study determined the relationship between the ifn-γ +874 a/t promoter polymorphism and the performance of the quantiferon®-tb gold in-tube (qft-git) test in an ethnically diverse canadian population.201628000585
lyophilization of an adjuvanted mycobacterium tuberculosis vaccine in a single-chamber pharmaceutical cartridge.although substantial effort has been made in the development of next-generation recombinant vaccine systems, maintenance of a cold chain is still typically required and remains a critical challenge in effective vaccine distribution. the ability to engineer alternative containment systems that improve distribution and administration represents potentially significant enhancements to vaccination strategies. in this work, we evaluate the ability to successfully lyophilize a previously demonstrated ...201628000085
prothionamide susceptibility testing of mycobacterium tuberculosis using the resazurin microtitre assay and the bactecmgit 960 system.resazurin microtitre assay (rma) has been successfully used to detect minimal inhibitory concentrations (mics) of both first-line and several second-line drugs in drug susceptibility testing (dst) of mycobacterium tuberculosis (mtb). in this study, we firstly compared prothionamide (pth) susceptibility testing of mycobacterium tuberculosis (mtb) using resazurin microtitre assay (rma) and mgit. overall, the sensitivity and specificity of rma for detecting pth susceptibility was 96.5% [95% confide ...201628000029
a perspective of the diagnosis and management of congenital tuberculosis.tuberculosis continues to be a prevalent disease in the world and a global public health issue in many countries. the disease is more complicated in pregnant women because it imperils unborn offspring and results in congenital tuberculosis later if undiagnosed and untreated. congenital tuberculosis is rare entity and an uncommon disease along with a high mortality rate. congenital tuberculosis, a severe clinical type of tuberculosis caused by mycobacterium tuberculosis, is a serious and fatal di ...201627999684
immunogenicity of a dna vaccine encoding ag85a-tb10.4 antigens from mycobacterium tuberculosis.tuberculosis is a life threatening disease that is partially prevented by bcg vaccine. development of more effective vaccines is an urgent priority in tb control. ag85a and tb10.4 are the members of culture filter protein (cfp) of m. tuberculosis that have high immunogenicity.201627999240
drug-resistant tuberculosis in naples, 2008-2013.drug-resistant tuberculosis (tb) is a serious threat in industrialized countries, but information from southern italy is lacking. here, we present the results of a retrospective study of tb cases diagnosed in 2008-2013 in naples, the largest city in southern italy.201627999235
a hr-ms based method for the determination of chorismate synthase activity.chorismate synthase (cs) catalyzes the last step of shikimate pathway involving a unique biochemical reaction of anti-1,4 elimination of 3-phosphate group and the c-(6pror) hydrogen from 5-enolpyruvylshikimate-3-phosphate (epsp) leading to the formation of chorismate, which is the common precursor for aromatic amino acid, ubiquinone, and folate biosynthesis in plants and several bacterial, fungal, and parasitic pathogens. absence of shikimate pathway in the vertebrate host, make cs an appealing ...201628017143
congenital miliary tuberculosis in an 18-day-old boy.congenital tuberculosis (tb) is a rare disease that is associated with high mortality. mycobacterium tuberculosis, the causative agent, may be transmitted from the infected mother to the fetus by the transplacental route or by aspiration of infected amniotic fluid. clinical symptoms and signs are not specific. miliary patterns are the most common findings in the chest x-rays of many infants with congenital tb. in this case, an 18-day-old boy had jaundice on the fifth day of birth, and fever and ...201628018449
adjunct strategies for tuberculosis vaccines: modulating key immune cell regulatory mechanisms to potentiate vaccination.tuberculosis (tb) remains a global health threat of alarming proportions, resulting in 1.5 million deaths worldwide. the only available licensed vaccine, bacillus calmette-guérin, does not confer lifelong protection against active tb. to date, development of an effective vaccine against tb has proven to be elusive, and devising newer approaches for improved vaccination outcomes is an essential goal. insights gained over the last several years have revealed multiple mechanisms of immune manipulat ...201628018344
immunological roles of elevated plasma levels of matricellular proteins in japanese patients with pulmonary tuberculosis.elevated matricellular proteins (mcps), including osteopontin (opn) and galectin-9 (gal-9), were observed in the plasma of patients with manila-type tuberculosis (tb) previously. here, we quantified plasma opn, gal-9, and soluble cd44 (scd44) by enzyme-linked immunosorbent assay (elisa), and another 29 cytokines by luminex assay in 36 patients with pulmonary tb, six subjects with latent tuberculosis (ltbi), and 19 healthy controls (hcs) from japan for a better understanding of the roles of mcps ...201628025511
glucosylglycerate metabolism, bioversatility and mycobacterial survival.despite the progressive decline in tuberculosis mortality, strains resistant to our dated antibiotics remain a global threat, as are the emerging nontuberculous mycobacteria, ubiquitous in natural and human environments. this pressing situation boosted by debilitated immune systems, chronic illness and the aged population calls for efficient strategies to fight these successful organisms, and identifying pathways critical for their survival is a crucial step towards this goal. in this context, t ...201628025249
beijing strains of mycobacterium tuberculosis in smear-positive tuberculosis patients in north-west and west of iran.tuberculosis (tb) is the leading cause of morbidity and mortality among chronic infectious diseases. the goal of this cross-sectional study (2012-2014) was to examine the prevalence of mycobacterium tb (mtb) beijing strains in regions near the iranian border and to identify any epidemiological links.201628028521
evaluation of direct colorimetric mtt assay for rapid detection of rifampicin and isoniazid resistance in mycobacterium tuberculosis.with the spread of multidrug-resistant tuberculosis (mdr-tb) strains there is an increasing need for new accurate and cost-effective methods for a rapid diagnostic and drug susceptibility testing (dst), particularly in low-income countries where tuberculosis is hyperendemic. a colorimetric assay using 3-(4, 5-dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide (mtt) has been suggested as a promising method for dst, especially to rifampicin. in this study, we standardized and evaluated the mt ...201628030634
isoniazid mono-resistant tuberculosis: impact on treatment outcome and survival of pulmonary tuberculosis patients in southern mexico 1995-2010.isoniazid mono-resistance (imr) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. there is no consensus on how these patients should be treated.201628030600
potential role for mycobacterium tuberculosis specific il-2 and ifn-γ responses in discriminating between latent infection and active disease after long-term stimulation.interferon gamma release assays (igras) could accurately diagnose mycobacterium tuberculosis (m.tuberculosis) infection. however, these assays do not discriminate between latent tuberculosis infection (ltbi) and active tuberculosis disease (atb). here, a total of 177 subjects, including 65 patients with atb, 43 subjects with ltbi, and 69 tb-uninfected controls (con group) were enrolled. the concentration of ifn-γ, ip-10, and il-2 was determined in peripheral blood mononuclear cells (pbmcs) after ...201628033330
the effects of first-line anti-tuberculosis drugs on the actions of vitamin d in human macrophages.tuberculosis (tb) is a major global health problem. patients with tb have a high rate of vitamin d deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. although data on the efficacy of vitamin d supplementation on mycobacterium tuberculosis (mtb) clearance is uncertain from randomized controlled trials (rcts), vitamin d enhances the expression of the anti-microbial peptide human cathelicidin (hcap18) in cultured macrophages in vitro. one possible explana ...201628111615
tuberculosis-associated hemophagocytic lymphohistiocytosis in an umbilical cord blood transplant recipient.hemophagocytic lymphohistiocytosis (hlh) is a rare and potentially fatal condition that can be primary or secondary. secondary hlh due to mycobacterium tuberculosis (tb) is uncommon. we report a case of tuberculosis-associated hlh in an umbilical cord blood transplant (ucbt) recipient and discuss its clinical characteristics and challenges.201628040556
post-delivery mycobacterium tuberculosis infection misdiagnosed as systemic lupus erythematosus.tuberculosis is a common infectious mycobacterial disease having a wide range of clinical and serological manifestations that are similar to rheumatic disease. differential diagnosis is a crucial aspect in any rheumatic disease as many other infectious diseases portray clinical similarities and autoantibody positivity. our case report illustrates of a young woman just after the delivery of a child presented an unusual case of extrapulmonary tuberculosis infection initially misdiagnosed as system ...201628036316
down-regulation of pe11, a cell wall associated esterase enhances the biofilm growth of mycobacterium tuberculosis and reduces cell wall virulence lipid levels.pe11 (rv1169c or lipx) is a cell wall associated esterase/lipase of mycobacterium tuberculosis(mtb). evidences suggest that pe11 is expressed by mtb both in vitro and in vivo. previous studies have shown that when expressed in the non-pathogenic surrogate m. smegmatis, pe11 leads to modification in cell wall lipid content and enhanced virulence. since cell wall lipids often play different roles in pathogenic and non-pathogenic mycobacteria, we investigated the role of pe11 in its host, mtb. mtb ...201628036246
performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.tuberculosis (tb) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. serological tests have the potentially to impact tb diagnosis, in particular in extreme clinical settings.201628066611
targeting innate-like t cells in tuberculosis.peptide-specific conventional t cells have been major targets for designing most antimycobacterial vaccines. immune responses mediated by conventional t cells exhibit a delayed onset upon primary infection and are highly variable in different human populations. in contrast, innate-like t cells quickly respond to pathogens and display effector functions without undergoing extensive clonal expansion. specifically, the activation of innate-like t cells depends on the promiscuous interaction of high ...201628066410
a fluorescent probe for detecting mycobacterium tuberculosis and identifying genes critical for cell entry.the conventional method for quantitating mycobacterium tuberculosis (mtb) in vitro and in vivo relies on bacterial colony forming unit (cfu) enumeration on agar plates. due to the slow growth rate of mtb, it takes 3-6 weeks to observe visible colonies on agar plates. imaging technologies that are capable of quickly quantitating both active and dormant tubercle bacilli in vitro and in vivo would accelerate research toward the development of anti-tb chemotherapies and vaccines. we have developed a ...201628066347
alternate efflux pump mechanism may contribute to drug resistance in extensively drug-resistant isolates of mycobacterium tuberculosis.extensively drug-resistant tuberculosis (xdr-tb) has emerged as one of the biggest threats to public health and tb control programs worldwide. xdr-tb is caused by mycobacterium tuberculosis (mtb) strains resistant to rifampin and isoniazid, as well as to a fluoroquinolone and to at least one injectable aminoglycoside. drug resistance in mtb has primarily been associated with single nucleotide polymorphisms (snps) in particular genes. however, it has also been shown that efflux pumps may play a r ...201628043640
identification of novel mycobacterium tuberculosis dihydrofolate reductase inhibitors through rational drug design.dihydrofolate reductase (dhfr) is one of the validated drug targets in mycobacterium tuberculosis (mtb) infection. dhfr inhibitors have been used to treat various life-threatening diseases such as cancer, malaria, and several bacterial infections. however, all clinically effective dhfr inhibitors are non-selective, and inhibit both human and pathogenic dhfrs more or less to a similar extent. the crystal structure of various dhfrs complexed with nicotinamide adenine dinucleotide phosphate and dif ...201628043639
activity of drugs against dormant mycobacterium tuberculosis.heterogeneous mixtures of cellular and caseous granulomas coexist in the lungs of tuberculosis (tb) patients, with mycobacterium tuberculosis (mtb) existing from actively replicating (ar) to dormant, nonreplicating (nr) stages. within cellular granulomas, the ph is estimated to be less than 6, whereas in the necrotic centres of hypoxic, cholesterol/triacylglycerol-rich, caseous granulomas, the ph varies between 7.2 and 7.4. to combat tb, we should kill both ar and nr stages of mtb. dormant mtb r ...201628043638
mycobacterial excretory secretory-31 protein with serine protease and lipase activities: an immunogen and drug target against tuberculosis infection.tuberculosis (tb) has been declared as a global emergency by the world health organization in 1993 and still remains one of the world's biggest threats. worldwide, 9.6 million people have been estimated to have fallen ill with tb in 2014: 5.4 million men, 3.2 million women, and 1.0 million children. to reduce this burden, detection and treatment gaps must be addressed and new tools developed (global tb report 2015).201628043634
effective testing for pulmonary tuberculosis using xpert mtb/rif assay for stool specimens in immunocompetent pakistani children.childhood tuberculosis (tb) is largely a paucibacillary disease and difficult to diagnose. it is difficult to obtain a sputum or gastric aspirate (ga) sample, and patients are often undiagnosed and treated empirically. stool is a noninvasive specimen not usually used for tb testing in pakistan. we investigated the value of xpert mtb/rif to diagnose mycobacterium tuberculosis (mtb) in children with pulmonary tb cases, by performing comparative testing of ga and stool samples.201628043630
paying attention to the details in mycobacterium tuberculosis: strain-specific single-nucleotide polymorphisms and clonal variants. 201628043627
comparison of two molecular methods and an automated liquid culture system for the early detection of mycobacterium tuberculosis from both pulmonary and extrapulmonary specimens in kuwait.molecular methods for the detection of mycobacterium tuberculosis (mtb) are widely used for the early diagnosis of tuberculosis (tb). the objectives of this study were to evaluate the performance of two molecular techniques for the detection of mtb for both pulmonary and extrapulmonary specimens in comparison with conventional culture techniques in kuwait and to correlate the results with clinical and histopathological diagnosis.201628043626
emerging clones of mycobacterium tuberculosis in russia and former soviet union countries: beijing genotype and beyond. 201628043622
whole genome sequencing as the ultimate tool to diagnose tuberculosis.in the past two decades, dna techniques have been increasingly used in the laboratory diagnosis of tuberculosis (tb). the (sub) species of the mycobacterium tuberculosis complex are usually identified using reverse line blot techniques. the resistance is predicted by the detection of mutations in genes associated with resistance. nevertheless, all cases are still subjected to cumbersome phenotypic resistance testing. the production of a strain-characteristic dna fingerprint, to investigate the e ...201628043616
emotional distress patients with several types of tuberculosis. a pilot study with patients from the sanatorium hospital of huambo.there is growing evidence that emotional distress expressed in terms of anxiety and depression it is very high among tuberculosis (tb) patients.201628043613
new options in tuberculosis care: visions for the future are crucial for controlling the disease.the current strategies for controlling tuberculosis (tb) are not sufficient. improved prophylactic and diagnostic tools are imperative, being crucial for decreasing tb incidence and mortality and for preventing outbreaks. furthermore, new and better drugs are badly needed, particularly considering the increase in cases with multidrug-resistant strains. the current tb vaccine-the bacillus calmette-guérin vaccine-has a preventive impact on disseminated tb in children, but little effect on the most ...201628043608
what is in a cough?the aims of this talk are to: (a) provide an overview of our method of collecting, quantifying, and sizing infectious aerosols of mycobacterium tuberculosis; and (b) to review data indicating that cough aerosol cultures of m. tuberculosis are the best predictors of infection and incident disease among household contacts of persons with active tuberculosis (tb). new infection was defined as tuberculin skin test conversion.201628043607
ethambutol-resistance testing by mutation detection using mtbdrsl.despite the successes in managing drug-susceptible tb, drug-resistant (dr) tuberculosis is a major challenge to the effectiveness of national tuberculosis program in armenia, placing the country in the list of 18 high-burden countries for mdr-tb in the who european region. estimated burden of mdr-tb in 2012 was 9.4 (7-12) and 43 (38-49) among retreatment tb cases. a total of 92 laboratory confirmed cases had been reported to the who (57 new and 35 previously treated) out of 511 cases tested for ...201628043606
xpert mtb/rif for rapid detection of rifampicin-resistant mycobacterium tuberculosis from pulmonary tuberculosis patients in southwest ethiopia.accurate and rapid detection of drug-resistant strains of tuberculosis (tb) is critical for early initiation of treatment and for limiting the transmission of drug-resistant tb. here, we investigated the accuracy of xpert mtb/rif for detection of rifampicin (rif) resistance, and whether this detection predicts the presence of multidrug resistant (mdr) tb in southwest ethiopia.201628043605
best approaches to drug-resistance surveillance at the country level.in 2014, the world health organization (who) recommendation to include the endorsed rapid molecular technologies (xpert mtb/rif, line probe assays) into surveillance systems and surveys allowed the testing of more tuberculosis (tb) patients for drug resistance at country level than ever before. the whole genome sequencing (wgs) approach is emerging as a more powerful tool for epidemiological and drug-resistant routine surveillances, promising a rapid and simultaneous screening of all the clinica ...201628043601
genetic diversity, transmission dynamics, and drug resistance of mycobacterium tuberculosis in luanda, angola.despite the important role that the african region plays in a global tuberculosis (tb) epidemiological context, many countries in the region still lack data on the prevalence of specific mycobacterium tuberculosis strains and drug resistance. this is the case for angola, which presently lacks any data concerning drug-resistance rates and prevalence of specific m. tuberculosis genotypes and respective population structure. in this study, we made the first characterization of the genetic diversity ...201628043599
reaching consensus on drug resistance conferring mutations.molecular-based, rapid drug-susceptibility tests are needed to guide the appropriate use of new drugs and new therapeutic regimens at the programmatic level, and to prevent a further increase in the incidence of drug-resistant tuberculosis (tb). experts have recognized the need for a global, curated, and standardized analysis and data-sharing platform that provides a one-stop data source for clinically relevant genotypic and phenotypic information on mycobacterium tuberculosis.201628043595
next-generation sequencing-based user-friendly platforms for drug-resistant tuberculosis diagnosis: a promise for the near future.since 2002, there has been a gradual worldwide 1.3% annual decrease in the incidence of tuberculosis (tb). this is an encouraging statistic; however, it will not achieve the world health organization's goal of eliminating tb by 2050, and it is being compounded by the persistent global incidence of drug-resistant tuberculosis (dr-tb) acquired by transmission and by treatment pressure. one key to effectively control tuberculosis and the spread of multiresistant strains is accurate information pert ...201628043592
use of wgs in mycobacterium tuberculosis routine diagnosis.whole genome sequencing (wgs) is becoming affordable with overall costs comparable to other tests currently in use to perform the diagnosis of drug-resistant tuberculosis (tb) and cluster analysis. the wgs approach allows an "all-in-one" approach providing results on expected sensitivity of the strains, genetic background, epidemiological data, and indication of risk of laboratory cross-contamination.201628043590
characterization of the cd4 and cd8 t-cell response in the quantiferon-tb gold plus kit.quantiferon-tb gold in-tube (qft-git, qiagen, hilden, germany) is an interferon-γ (ifn-γ) release assay designed to detect latent tuberculosis infection (ltbi). although qft-git has several advantages (mainly that it is not affected by the bacille calmette-guérin vaccination), it has a poor sensitivity in immune-compromised individuals as it involves an immune response-based detection. recently, quantiferon-tb gold plus (qft-plus) assay has been proposed as a new generation of qft-git. qft-plus ...201628043588
increased mycobacterium tuberculosis antigen-induced gene expression of interferon-gamma, tumor necrosis factor alpha and interleukin-6 in patients with diabetes.pakistan ranks fifth in high tuberculosis (tb)-burden countries and seventh among countries with high prevalence rates of diabetes mellitus (dm). dm is a risk factor for tb and worsens disease outcomes. furthermore, mycobacterium tuberculosis (mtb) infection can induce glucose intolerance and worsen glycemic control in diabetes. suppressor of cytokine signaling (socs)-1 and -3 molecules regulate cytokine signaling and are important in maintaining an immune balance. in tb, interleukin (il)-6 upre ...201628043584
common features of tuberculosis and sarcoidosis.tuberculosis (tb) is a disease caused by mycobacterium tuberculosis. despite the availability of novel therapeutic approaches, tb is considered as one of the leading causes of death due to infectious diseases worldwide. alveolar macrophages are the first line of defense against m. tuberculosis; they ingest and sequester the bacilli within granulomatous structures. control and resolution of the infection requires activated t lymphocytes as well as th1 cytokines. there are two forms of tb: active ...201628043581
deletion of region of difference 181 in mycobacterium tuberculosis beijing strains.the region of differences (rds) polymorphisms is a potential molecular epidemiology method to distinguish origins of mycobacterium tuberculosis. to date, 68 rds have been identified in m. tuberculosis. this study was designed to determine the frequency of rd deletions in m. tuberculosis strains that were isolated from patients with pulmonary tuberculosis who were referred to the national research institute of tuberculosis and lung disease for diagnosis and treatment. therefore, highly polymorphi ...201628043579
immunohistochemical findings of the granulomatous reaction associated with tuberculosis.the histological diagnosis of mycobacterium tuberculosis (mtb) has long been a diagnostic challenge in the anatomical pathology field despite availability of different laboratory methods. immunohistochemistry (ihc) could not only confirm granulomatous tissue involvement but also demonstrate mtb antigen immunolocalization. this study tries to clarify the details of ihc staining for mtb with pabbcg.201628043576
comparison of histopathology, acid fast bacillus smear and real-time polymerase chain reaction for detection of mycobacterium tuberculosis in anal fistula in 161 patients: a prospective controlled trial.mycobacterium tuberculosis (mtb) is a known cause of refractory and recurrent fistula-in-ano. histopathology of fistula tract and acid fast bacillus (afb) smear of the pus are the standard procedures employed to diagnose mtb. however, they have some drawbacks. nontubercular mycobacteria (ntm) has also been detected to cause fistula-in-ano and these methods cannot differentiate between mtb and ntm. secondly, as these methods have low sensitivity, they could possibly be missing out mtb patients. r ...201628043558
role of socio-demographical factors on tuberculosis outcome in yemen.tuberculosis (tb) is an infection disease caused by an organism called mycobacterium tuberculosis (tubercle bacilli). tuberculosis remains the most common infection worldwide (organization & world health organization, 2013). yemen situated in who eastern mediterranean region and ranked as intermediate tb-burdened countries. tb considers as one of the main health problems; it ranks as the fourth in the priority of the public health issue (ntcp, 2010). the study was conducted to evaluate the socio ...201628043552
predominance of beijing lineage among pre-extensively drug-resistant and extensively drug-resistant strains of mycobacterium tuberculosis: a tertiary care center experience.increasing resistance to various first-line and second-line drugs has become a major concern in india. however, it is not known if some genotypes are more associated with second-line drug resistance. thus, the main aim of this study was to find out the predominant genotype associated with second-line drug resistance.201628043550
restriction fragment length polymorphism pattern of mycobacterium isolates from rodents in infected cattle farms.mycobacterium tuberculosis, the etiologic agent of tuberculosis, causes large-scale morbidity and mortality, particularly in developing countries. in recent years, there has been a significant increase in the drug-resistant ability of m. tuberculosis, triggering a major public health crisis. a detailed analysis of the evolution of the mycobacterial genome helps to better understand the genotype-phenotype relationship in this bacterium. different strain typing methods have already revealed the wo ...201628043547
molecular identification of mycobacterium tuberculosis complex isolated by region of differentiation (rd) typing from tuberculosis patients in khorasan razavi.tuberculosis has long been recognized as a zoonotic disease and remains one of the most life-threatening diseases worldwide. in spite of the successful treatment of this disease, the world health organization considers it as a disease with the highest priority in 1993, and it is now the second leading cause of infectious mortality. since the identification of mycobacterium tuberculosis complex species is of special importance, the aim of this study was to identify the species from the submitted ...201628043545
mixed metal oxide nanoparticles inhibit growth of mycobacterium tuberculosis into thp-1 cells.humans have been in a constant battle with tuberculosis (tb). currently, overuse of antibiotics has resulted in the spread of multidrug-resistant mycobacterium tuberculosis (mdr), leading to antibiotic ineffectiveness at controlling the spread of tb infection in host cells and especially macrophages. additionally, the mycobacterium tuberculosis (mtb) has developed methods to evade the immune system and survive. with the discovery of nanoparticle (np)-based drugs, it is necessary to research thei ...201628043541
nationwide hiv-, mdr-tb survey in japan and collaborative study in the philippines.although the prevalence of pulmonary tuberculosis (tb) and hiv infection in japan is low, careful monitoring of these two diseases is necessary. we conducted a nationwide survey on multidrug resistant (mdr)-tb (2011-2013) and hiv-tb (2007-2014) to understand the mode of prevention and the effect of therapy. a study on mdr-tb and hiv in san lazaro hospital (slh) in the philippines was also conducted. these studies introduced an international collaborative study against the global epidemics of hiv ...201628043540
murine model of tb meningitis.central nervous system (cns) infections caused by mycobacterium tuberculosis (mtb) are the most severe forms of extrapulmonary tb (eptb) due to high levels of mortality and neurological morbidity. limited studies are available on cns-tb animal-model development, despite the steady rise in cerebral-tb cases in india over the past decade. this study describes the development of a murine model of cns-tb using a clinical strain (c3) isolated from the cerebrospinal fluid (csf) of cns-tb patients.201628043538
usefulness of is6110-based restriction fragment length polymorphism analysis in fingerprinting of mycobacterium tuberculosis isolates in north india.world health organization estimates that approximately one-third of the global community is infected with mycobatcerium tuberculosis (mtb). various molecular epidemiology methods were developed and found very promising for assessing the genetic diversity among mtb complex strain. the two major tools restriction fragment length polymorphism (rflp) and spoligotyping were commonly used in various studies. some indian studies raise the question about the utility of is6110-rflp in india due to the pr ...201628043537
assessing genetic diversity of mycobacterium tuberculosis by spoligotyping and is6110-based restriction fragment length polymorphism in north india.molecular epidemiology methods are very useful for differentiating between strains, assessing their diversity, and measuring the prevalence of the most circulating strain in an area. various molecular typing methods using different molecular markers have been utilized worldwide, such as restriction fragment length polymorphism (rflp), spoligotyping, mycobacterial interspersed repetitive unit - variable number of tandem repeat (miru-vntr), and double repetitive element-pcr (dre-pcr) typing, for s ...201628043536
nontubercular mycobacteria (ntm) in fistula-in-ano: a new finding and its implications.nontubercular mycobacteria (ntm) is not known to be associated with fistula-in-ano.201628043534
evaluation of sodium hydroxide-n-acetyl-l-cysteine and 0.7% chlorhexidine decontamination methods for recovering mycobacterium tuberculosis from sputum samples: a comparative analysis (the gambia experience).to determine the culture yield and time to detection of mycobacterial growth between samples decontaminated using 0.7% chlorhexidine and sodium hydroxide-n-acetyl-l-cysteine (naoh-nalc) and cultured on the löwenstein-jensen (lj) medium. we also aimed to determine the contamination rate between the 0.7% chlorhexidine and naoh-nalc decontamination methods.201628043532
rapid detection of mycobacterium tuberculosis complex in sputum samples using pure tb-lamp assay.lack of rapid and accurate diagnostic testing is a critical obstacle to global tuberculosis (tb) control. sensitivity of sputum smear microscopy (ssm) is not optimal; however, it remains the most prevalent tool for tb confirmation in poor countries. as a part of passive case finding of tb detection, this study was conducted to determine the clinical performance of pure tb-lamp assay using liquid culture medium as the gold standard.201628043530
relation between smear positivity and imaging findings in children with pulmonary tuberculosis.we investigated the relationship between high-resolution computed tomography (hrct) imaging manifestation of tuberculosis (tb) in childhood and the results of sputum smear. the aim of this study was to identify an alternative indicator of infectivity to prevent disease transmission through special isolation methods in children who have a clinical condition that suggests tb.201628043529
childhood tuberculosis in qatar.childhood tuberculosis (tb) has been long neglected but has gained attention in recent years. in 2012, the world health organization annual report included an estimate for childhood tb for the first time, and in the following year, the tb alliance received a grant from unitaid (international drug purchase facility) to develop pediatric tb formulations. qatar is a low-incidence country. in this observational study, laboratory-confirmed cases of tb were analyzed from 2013 to 2015 and included pati ...201628043528
molecular genetics of mycobacterium tuberculosis resistant to aminoglycosides and cyclic peptide testing by mtbdrsl in armenia.the genotype mtbdrsl test rapidly detects resistance to ethambutol, fluoroquinolones, second-line aminoglycosides (amikacin [amk] and kanamycin [kan]), and cyclic peptides (capreomycin [cap]) in mycobacterium tuberculosis. according to data from global drug resistance surveillance report (2007), armenia is counted as a high-burden country for multidrug-resistant tuberculosis (mdr-tb). the estimated burden of mdr-tb in 2012 was 9.4 (7-12) and 43 (38-49) among retreatment tb cases. a total of 92 l ...201628043525
molecular characterization of mycobacterium tuberculosis strains resistant to isoniazid.tuberculosis is a major public health problem and the emergence of drug resistance complicates the situation even more. it is therefore crucial to implement all conclusions from the studies that aim at a better understanding of the molecular mechanisms which govern the emergence and the evolution of drug resistance. the aim of this study is to assess the degree of involvement of the inha and katg genes in the acquisition of isoniazid resistance in clinical strains of mycobacterium tuberculosis.201628043520
increased expression of efflux pump genes in extensively drug-resistant isolates of mycobacterium tuberculosis.extensively drug-resistant tuberculosis (xdr-tb) is defined as tuberculosis (tb) caused by mycobacterium tuberculosis (mtb) strains that are multidrug resistant (mdr) and also resistant to a fluoroquinolone and to one injectable aminoglycoside or capreomycin. whilst resistance in mtb has been associated with single nucleotide polymorphisms (snps), efflux pumps are thought to play a role in conferring resistance to mtb but little is known about them.201628043519
evaluation of genotype mtbdrplus assay for rapid detection of isoniazid and rifampicin resistance in mycobacterium tuberculosis clinical isolates from pakistan.genotype mtbdrplus is a molecular assay for detection of mycobacterium tuberculosis resistance to isoniazid (inh) and rifampicin (rmp), the two major anti-tuberculosis (tb) drugs. identification of inh resistance is largely based on the occurrence of mutations in the katg gene, coding for the catalase-peroxidase, or in the promoter region of the inha gene, coding for the nadh-dependent enoyl-acp reductase. for testing the rmp resistance, mutations in the rpob gene, coding for the rna polymerase ...201628043516
evaluation of rifampicin resistance and 81-bp rifampicin resistant determinant region of rpob gene mutations of mycobacterium tuberculosis detected with xpertmtb/rif in cross river state, nigeria.world health organization tuberculosis (tb) indices from 2014 to 2016 showed that nigeria had the 6th highest prevalence, 4th highest incidence, and the highest mortality rate globally. in efforts to improve tb care, the xpertmtb/rif (genexpert) technology, cepheid, sunnyvale, california, usa, which has revolutionized tb detection with concomitant rifampicin-resistance molecular detection, was introduced in cross river state, south-south nigeria, in 2014. the genexpert uses molecular beacons to ...201628043515
modulation of cd4 and cd8 response to quantiferon-tb plus in patients with active tuberculosis and latent tuberculosis infection followed over time during treatment.interferon (ifn)-γ release assays (igra) are designed for diagnosing tuberculosis (tb) infection. the new igra, quantiferon-tb plus (qft-plus), is based on the enzyme-linked immunosorbent assay detection of ifn-γ after stimulation with mycobacterium tuberculosis tb1 and tb2 antigens. tb1 elicits a cellular-mediated immune (cmi) response by cd4 t cells, and tb2 contains peptides recognized by both cd4 and cd8 t cells. the aim of the study is to characterize the cmi to qft-plus peptides in active ...201628043513
mutations in embb gene associated with resistance to ethambutol in mycobacterium tuberculosis strains isolated from tb patients in the west of iran (2014-15).mutations in embb gene, especially those in ethambutol resistance-determining region (erdr), are known as "hot spots". these mutations have frequently been reported in emb-resistant m. tuberculosis isolates, using the sequence analysis as a precise and effective method. the aim of this study was to detect mutations in embb gene associated with resistance to ethambutol in mycobacterium tuberculosis strains isolated from tb patients in the west of iran (2014-15).201628043512
susceptibility to pulmonary tuberculosis: host genetic deficiency in tumor necrosis factor alpha (tnf-α) gene and tumor necrosis factor receptor 2 (tnfr2).the susceptibility to tuberculosis (tb) depends upon different factors, and the risk of developing diseases after infection with mycobacterium tuberculosis ranges from 5% to 10%. this suggests that besides the mycobacterial itself, the host genetic factors may determine the differences in host susceptibility to tb. among the important risk factors, cytokines and especially tumor necrosis factor alpha (tnf-α) genes, are thought to be responsible for regulating the protective immune responses. the ...201628043509
proteome-scale mdr-tb-antibody responses for identification of putative biomarkers for the diagnosis of drug-resistant mycobacterium tuberculosis.multidrug-resistant tuberculosis (mdr-tb) is caused by mycobacterium tuberculosis strains that do not respond to isoniazid and rifampicin, the two most effective first-line anti-tb drugs. here, we designed and produced antibodies based on biomarkers that exist only in mdr-tb.201628043508
t cell cytokine responses in peripheral blood mononuclear cells from patients with multidrug-resistant tuberculosis following stimulation with proteins purified from mycobacterium tuberculosis mdr clinical isolates.tuberculosis (tb) is a devastating disease that remains a major health threat worldwide. the appearance of mycobacterium tuberculosis strains resistance to current antibiotics is a growing problem, both in the third world and in developed countries. completion of genomic sequencing of m. tuberculosis provides a strong foundation for subsequent identification of proteins to aid the understanding of protein function and the discovery of new drug targets or a tb vaccine. this study employed a prote ...201628043507
drug resistance pattern of mycobacterium tuberculosis in the province with highest incidence of tuberculosis in iran.incidence of tuberculosis (tb) in golestan province is consistently higher than other provinces of iran. this study aimed to determine the rate of drug resistance to first-line antibiotics in mycobacterium tuberculosis (mtb) isolates recovered from new cases in this province.201628043506
isoniazid resistance among rifampicin-susceptible mycobacterium tuberculosis isolates from tuberculosis patients.with the introduction of novel molecular techniques that rely on rifampicin (rif) susceptibility, resistance to isoniazid (inh) or other first-line drugs remains undetected. such patients are prescribed first-line antituberculosis therapy and are on rif monodrug therapy during the continuation phase, which may lead to therapeutic failure and emergence of multidrug resistance. we aimed to study inh resistance among rif-susceptible mycobacterium tuberculosis (mtb) isolates from retreatment patient ...201628043503
genotypic analysis of multidrug-resistant tuberculosis isolates from extra pulmonary tuberculosis cases in tertiary care centers in northern india.multidrug-resistant tuberculosis (mdr-tb) is a major public health problem. the diagnosis of mdr-tb is of paramount importance in establishing appropriate clinical management and infection control measures. rapid detection of mdr-tb allows the establishment of an effective treatment regimen, minimizes the risk of further resistance, and limits the spread of drug-resistant strains. the aim of this study is to determine the genotypic characterization of mdr-tb isolates from extra pulmonary tubercu ...201628043502
comparative proteomic analysis of sequential isolates of mycobacterium tuberculosis sensitive and resistant beijing type from a patient with pulmonary tuberculosis.in india, tuberculosis (tb) is a foremost health problem, and the emergence of multidrug-resistant (mdr) and extensively drug resistant (xdr) strains of mycobacterium tuberculosis (m. tuberculosis) has further complicated the situation. although various mechanisms have been proposed to elucidate the emergence of resistance, our knowledge remains insufficient. the formation of a very complex network and drugs of proteins are countered by their efflux/modification or target over-expression/modific ...201628043501
design and development of novel inhibitors for the treatment of latent tuberculosis."the captain of all these men of death", is the apt sobriquet for the age-old disease tuberculosis (tb). despite the availability of many drugs, cases of increasing resistance in the forms of multi-drug and extensively drug-resistant tb and persistence [characteristic of mycobacterium tuberculosis (mtb)] make the eradication of tb a nightmare. approval of bedaquiline by the food and drug administration focused attention on quinoline scaffolds for development of new anti-tb agents. lysine ε-amino ...201628043500
multidrug-resistant tuberculosis in ethiopian settings and its association with previous antituberculosis treatment: a systematic review and meta-analysis.efforts to control the global burden of tuberculosis (tb) epidemic have now been jeopardized by the rapid evolution of drug-resistant mycobacterium tuberculosis (mtb), which are resistant to one or more anti-tb drugs. multidrug resistant (mdr) tb in ethiopia may be more prevalent than previously appreciated; thus, up-to-date national drug resistance studies are critically needed. therefore, this meta-analysis aimed, first, to determine pooled prevalence of mdr tb among newly diagnosed and previo ...201628043498
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