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1

Tuberculosis Exposure Control 1.0 BACKGROUND  

E-print Network

1 Tuberculosis Exposure Control 1.0 BACKGROUND Since 1985, the rate of new cases of tuberculosis, more than 26,000 new cases of active tuberculosis were reported in the US. In New York City alone, 3,700 cases of active tuberculosis were reported in 1991. Tuberculosis is a contagious disease that causes

de Lijser, Peter

2

PCR diagnostics of Mycobacterium tuberculosis in historic human long bone remains from 18th century burials in Kaiserebersdorf, Austria  

Microsoft Academic Search

BACKGROUND: In the present pilot study we applied recently published protocols for detecting Mycobacterium tuberculosis in human remains. We screened long bones from an 18th century cemetery and skulls from the anatomical \\

Lutz Bachmann; Barbara Däubl; Charlotte Lindqvist; Luise Kruckenhauser; Maria Teschler-Nicola; Elisabeth Haring

2008-01-01

3

Can Chandra resolve the remaining cosmic X-ray background?  

E-print Network

The deepest extragalactic X-ray observation, the 2 Ms Chandra Deep Field North (CDF-N), resolves ~80% of the total extragalactic cosmic X-ray background (CXB) in the 1-2 keV band. Recent work has shown that 70% of the remaining CXB flux is associated with sources detected by the Hubble Space Telescope (HST). This paper uses the existing CDF-N data to constrain the X-ray flux distribution of these X-ray undetected HST sources, by comparing the number of 0.5-2 keV X-ray counts at the HST positions to those expected for model flux distributions. In the simple case where all the undetected HST X-ray sources have the same 0.5-2 keV flux, the data are best fit by 1.5-3 counts per source in 2 Ms, compared to a detection limit (at 10% completeness) of 9 counts. Assuming a more realistic power-law logN-logS distribution [N(>S) S^-alpha], the data favor a relatively steep flux distribution, with alpha=1.1^+0.5_-0.3 (limits are 99% confidence). This slope is very similar to that previously found for faint normal and starburst galaxies in the CDF-N. These results suggest deeper Chandra observations will detect a new population of faint X-ray sources, but extremely deep exposures are needed to resolve the remainder of the soft CXB. In the most optimistic scenario, when the HST sources have the flattest allowed flux distribution and all the sources without HST counterparts are detected, observations 5 times more sensitive than the existing ones would resolve at most ~60% of the remaining soft CXB.

Ryan C. Hickox; Maxim Markevitch

2007-11-27

4

For personal use. Only reproduce with permission from The Lancet Publishing Group. Mycobacterium tuberculosis remains a leading infectious  

E-print Network

tuberculosis remains a leading infectious cause of morbidity and mortality. While antibiotic resistance-resistant phenotypes may or may not have a predictable effect on the fitness of drug-resistant tuberculosis strains. Here, we review the literature on laboratory studies of the fitness of drug-resistant tuberculosis, we

Cohen, Ted

5

Remains  

NASA Technical Reports Server (NTRS)

10 March 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a variety of textures observed on a south middle-latitude plain east-southeast of Hellas Planitia. Dark streaks left by passing dust devils are practically ubiquitous across the scene, including the transition from the texturally-smooth area (the majority of the image) onto the circular, rough feature near the right (east) edge of the image. The circular feature might once have been the site of an impact crater; perhaps this is the remains of its floor, and the rest of the crater and the rock in which it formed was removed by erosion.

Location near: 4.0oS, 348.0oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Autumn

2006-01-01

6

Mycobacterium tuberculosis complex detection in human remains: tuberculosis spread since the 17th century in Rio de Janeiro, Brazil.  

PubMed

Paleogenetic analysis for tuberculosis (TB) was conducted on bone and sediment samples dating from the 17th to 19th centuries from the archeological site of Nossa Senhora do Carmo Church in Rio de Janeiro, Brazil. Forty samples were analyzed, corresponding to 32 individuals from 28 burials, 22 of primary type and 6 of secondary type. The samples were collected following strict paleogenetic investigation guidelines and submitted to ancient DNA (aDNA) extraction. In order to detect TB infection, aDNA hybridizations with the molecular targets of Mycobacterium tuberculosis complex (MTC) IS6110 and IS1081 were applied. Additionally, the ancestry of individuals was assessed by human mitochondrial DNA (mtDNA) analysis of hypervariable segment I (HVS-I) sequence polymorphisms. The results of aDNA hybridizations demonstrated varying levels of MTC intensity in 17/32 individuals (53.1%), using the IS6110 target. The IS1081 MTC target showed lower sensitivity, confirming TB positivity in 10/32 (31.2%) individuals. The mtDNA analysis allowed the recovery of HVS-I sequences in 23/32 individuals (71.8%). The majority of these individuals (21/23, 91.3%) were of European ancestry, especially in primary burials. Haplogroups U, J, V, T, K, N, H and R, were identified with haplogroup U being the most frequent at 6/23 (26.1%). African and Amerindian mtDNA haplogroups were observed in two individuals in secondary burials. In spite of the ecclesiastic and aristocratic bias of the population of the study, human ancestry analysis revealed the prominent contribution of Europeans in the introduction or spread of TB in the New World. PMID:21896337

Jaeger, Lauren Hubert; Leles, Daniela; Lima, Valdirene dos Santos; da Silva, Laura da Piedade; Dias, Ondemar; Iñiguez, Alena Mayo

2012-06-01

7

Chest Radiographic Predictors of Hiv\\/Aids in Childhood Pulmonary Tuberculosis-An African Study  

Microsoft Academic Search

Background: Tuberculosis remains a major public health problem in Nigeria and the world at large. Substantial number of cases of tuberculosis occurs in children, especially in this era of HIV pandemic. Chest radiograph is an important examination in evaluation for pulmonary tuberculosis. There is paucity of literature on the chest radiographic features predictive of HIV in pulmonary tuberculosis patients. Objective:

Mustapha MG

2012-01-01

8

Chest Radiographic Predictors of HIV\\/AIDS in Childhood Pulmonary Tuberculosis-An African Study  

Microsoft Academic Search

Background: Tuberculosis remains a major public health problem in Nigeria and the world at large. Substantial number of cases of tuberculosis occurs in children, especially in this era of HIV pandemic. Chest radiograph is an important examination in evaluation for pulmonary tuberculosis. There is paucity of literature on the chest radiographic features predictive of HIV in pulmonary tuberculosis patients. Objective:

Ahidjo A; Mustapha MG; Ashir GM; Alhaji MA; Adedokun T

2012-01-01

9

Primary gastric tuberculosis – report of 5 cases  

PubMed Central

Background Gastric tuberculosis is rare, and usually associated with pulmonary tuberculosis or an immunodeficient state. Here, we report five cases of gastric tuberculosis in immunocompetent patients without evidence of pulmonary involvement. Case presentation Three patients presented with gastric outlet obstruction that required surgery to relieve the obstruction as well as to confirm the diagnosis. The remaining two had involvement of gastroesophageal junction. All of them responded well to standard antitubercular treatment. Conclusion Though gastric tuberculosis is rare, it should be considered a possibility when patients present with gastric outlet obstruction or with endoscopic evidence of diffuse chronic inflammatory activity, particularly in areas endemic for tuberculosis. PMID:12703983

Amarapurkar, Deepak N; Patel, Nikhil D; Amarapurkar, Anjali D

2003-01-01

10

Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence  

E-print Network

Abstract Background Tuberculosis (TB) remains a major cause of mortality in developing countries, and in these countries diabetes prevalence is increasing rapidly. Diabetes increases the risk of TB. Our aim was to assess the potential impact...

Stevenson, Catherine R; Forouhi, Nita G; Roglic, Gojka; Williams, Brian G; Lauer, Jeremy A; Dye, Christopher; Unwin, Nigel

2007-09-06

11

PERSPECTIVE Candidate Mycobacterium tuberculosis genes  

E-print Network

PERSPECTIVE Candidate Mycobacterium tuberculosis genes targeted by human microRNAs WeiRui Guo1-wu@northwestern.edu (J. Y. Wu), weilp@mail.cbi.pku.edu.cn (L. Wei) Tuberculosis (TB) remains a major health issue in 1882, Mycobacterium tuberculosis (M. tuberculosis), the causative agent for tuberculosis, remains one

Wu, Jane Y.

12

Unique Transcriptome Signature of Mycobacterium tuberculosis in Pulmonary Tuberculosis  

Microsoft Academic Search

Although tuberculosis remains a substantial global threat, the mechanisms that enable mycobacterial persistence and replication within the human host are ill defined. This study represents the first genome-wide expression analysis of Mycobacterium tuberculosis from clinical lung samples, which has enabled the identifi- cation of M. tuberculosis genes actively expressed during pulmonary tuberculosis. To obtain optimal informa- tion from our DNA

Helmy Rachman; Michael Strong; Timo Ulrichs; Leander Grode; Johannes Schuchhardt; Hans Mollenkopf; George A. Kosmiadi; David Eisenberg; Stefan H. E. Kaufmann

2006-01-01

13

Delayed consultation among pulmonary tuberculosis patients: a cross sectional study of 10 DOTS districts of Ethiopia  

Microsoft Academic Search

BACKGROUND: Delays seeking care increase transmission of pulmonary tuberculosis and hence the burden of tuberculosis, which remains high in developing countries. This study investigates patterns of health seeking behavior and determines risk factors for delayed patient consultation at public health facilities in 10 districts of Ethiopia. METHODS: New pulmonary TB patients ? 15 years old were recruited at 18 diagnostic

Mengiste M Mesfin; James N Newell; John D Walley; Amanuel Gessessew; Richard J Madeley

2009-01-01

14

Genetic heterogeneity revealed by sequence analysis of Mycobacterium tuberculosis isolates from extra-pulmonary tuberculosis patients  

PubMed Central

Background Tuberculosis remains a major public health problem. Clinical tuberculosis manifests often as pulmonary and occasionally as extra-pulmonary tuberculosis. The emergence of drug resistant tubercle bacilli and its association with HIV is a formidable challenge to curb the spread of tuberculosis. There have been concerted efforts by whole genome sequencing and bioinformatics analysis to identify genomic patterns and to establish a relationship between the genotype of the organism and clinical manifestation of tuberculosis. Extra-pulmonary TB constitutes 15–20 percent of the total clinical cases of tuberculosis reported among immunocompetent patients, whereas among HIV patients the incidence is more than 50 percent. Genomic analysis of M. tuberculosis isolates from extra pulmonary patients has not been explored. Results The genomic DNA of 5 extra-pulmonary clinical isolates of M. tuberculosis derived from cerebrospinal fluid, lymph node fine needle aspirates (FNAC) / biopsies, were sequenced. Next generation sequencing approach (NGS) was employed to identify Single Nucleotide Variations (SNVs) and computational methods used to predict their consequence on functional genes. Analysis of distribution of SNVs led to the finding that there are mixed genotypes in patient isolates and that many SNVs are likely to influence either gene function or their expression. Phylogenetic relationship between the isolates correlated with the origin of the isolates. In addition, insertion sites of IS elements were identified and their distribution revealed a variation in number and position of the element in the 5 extra-pulmonary isolates compared to the reference M. tuberculosis H37Rv strain. Conclusions The results suggest that NGS sequencing is able to identify small variations in genomes of M. tuberculosis isolates including changes in IS element insertion sites. Moreover, variations in isolates of M. tuberculosis from non-pulmonary sites were documented. The analysis of our results indicates genomic heterogeneity in the clinical isolates. PMID:23773324

2013-01-01

15

Research on the occurrence of Mycobacterium tuberculosis antigens in the circulating immune complexes, isolated from serum of patients with tuberculosis  

PubMed Central

Background Tuberculosis is one of the most dangerous infectious diseases and has among the highest mortality rates of all infectious diseases. There are 9 million cases of active tuberculosis reported annually; however, an estimated one-third of the world’s population is infected with Mycobacterium tuberculosis and remains asymptomatic. Despite the great progress in its diagnosis and treatment, tuberculosis is still a serious health and social problem. The contact between the immune system and Mycobacterium tuberculosis initiates cell-specific (Th1) and humoral-specific (Th2) responses. Many studies about the presence of antituberculotic antibodies in the serum have produced inconsistent results because of a high proportion of false-positive or false-negative results. The purpose of this study was to confirm whether circulating immune complexes (CIC) isolated from the serum of patients with tuberculosis are accompanied by antigenic proteins typical of Mycobacterium tuberculosis. Material/Methods We assayed serum samples from 42 patients with tuberculosis. The control group consisted of the sera samples taken from 45 healthy subjects. The immunochemical analysis of dissociated immune complexes using the dot blot method demonstrated positive reaction on the presence of Mycobacterium tuberculosis antigens in all patients with tuberculosis. Results All patients with tuberculosis demonstrated a high serum concentration of CIC protein. The mean serum concentration of CIC protein was significantly higher in patients than in controls: 0.081 g/l in the control group and 0.211 g/l in the tuberculosis patients. Conclusions The analysis of CIC suggests that it may be a helpful test for patients with tuberculosis because of its quickness, simplicity of the idea, and limited invasiveness. PMID:24384554

Przybylski, Grzegorz; Go?da, Ryszard

2014-01-01

16

Update on Veterinary Tuberculosis Vaccines  

Technology Transfer Automated Retrieval System (TEKTRAN)

Educational Objective: At the conclusion of this presentation, the participant will know the current status of veterinary tuberculosis vaccine research and development, and understand the challenges which remain for the future introduction of tuberculosis vaccines intended for wildlife and livestock...

17

Impact of Previous ART and of ART Initiation on Outcome of HIV-Associated Tuberculosis  

PubMed Central

Background. Combination antiretroviral therapy (cART) has progressively decreased mortality of HIV-associated tuberculosis .To date, however, limited data on tuberculosis treatment outcomes among coinfected patients who are not ART-naive at the time of tuberculosis diagnosis are available. Methods. A multicenter, observational study enrolled 246 HIV-infected patients diagnosed with tuberculosis, in 96 Italian infectious diseases hospital units, who started tuberculosis treatment. A polytomous logistic regression model was used to identify baseline factors associated with the outcome. A Poisson regression model was used to explain the effect of ART during tuberculosis treatment on mortality, as a time-varying covariate, adjusting for baseline characteristics. Results. Outcomes of tuberculosis treatment were as follows: 130 (52.8%) were successfully treated, 36 (14.6%) patients died in a median time of 2 months (range: 0–16), and 80 (32.6%) had an unsuccessful outcome. Being foreign born or injecting drug users was associated with unsuccessful outcomes. In multivariable Poisson regression, cART during tuberculosis treatment decreased the risk of death, while this risk increased for those who were not ART-naive at tuberculosis diagnosis. Conclusions. ART during tuberculosis treatment is associated with a substantial reduction of death rate among HIV-infected patients. However, patients who are not ART-naive when they develop tuberculosis remain at elevated risk of death. PMID:22489253

Girardi, Enrico; Palmieri, Fabrizio; Angeletti, Claudio; Vanacore, Paola; Matteelli, Alberto; Gori, Andrea; Carbonara, Sergio; Ippolito, Giuseppe

2012-01-01

18

Orbital and adnexal tuberculosis: a case series from a South Indian population  

PubMed Central

Background Orbital tuberculosis (OTb) is rare and may be regarded as a manifestation of extrapulmonary tuberculosis. We report an interesting case series of six patients with varied presentations of orbital and adnexal tuberculosis in a South Indian patient population. Results A retrospective, interventional case series of six patients diagnosed with orbital and adnexal tuberculosis on the basis of clinical, radiological and histopathological evaluations between 2010 and 2013 was performed. Among the six patients with histopathologically proven OTb, five were women. The varied presentations included tubercular dacryoadenitis (two cases), classical periostitis (two cases), OTb with bone involvement (one case) and ocular adnexal tuberculosis (one case). Systemic involvement was seen in one case. All cases were treated with a regimen of antitubercular therapy (ATT). Conclusions OTb, though rare, should form a part of the differential diagnosis of orbital lesions in a high tuberculosis (TB) endemic country like ours. Biopsy still remains the mainstay of diagnosis. PMID:24940452

2014-01-01

19

Is Adipose Tissue a Place for Mycobacterium tuberculosis Persistence?  

E-print Network

Is Adipose Tissue a Place for Mycobacterium tuberculosis Persistence? Olivier Neyrolles1 of Electron Microscopy, Institut Pasteur, Paris, France Background. Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), has the ability to persist in its human host for exceptionally long

Paris-Sud XI, Université de

20

Spinal tuberculosis: with reference to the children of northern India  

Microsoft Academic Search

Background Tuberculosis is a necrotizing bacterial infection with protean manifestation and wide distribution. There has been a great fall in the prevalence of tuberculosis in the United States since 1990, although the impact of acquired immunodeficiency syndrome (AIDS) has increased the resurgence of tuberculosis (TB). Spinal tuberculosis is the commonest form of skeletal tuberculosis. In this article, an overview of

Raj Kumar

2005-01-01

21

Branchedchain amino acid aminotransferase and methionine formation in Mycobacterium tuberculosis  

Microsoft Academic Search

BACKGROUND: Tuberculosis remains a major world-wide health threat which demands the discovery and characterisation of new drug targets in order to develop future antimycobacterials. The regeneration of methionine consumed during polyamine biosynthesis is an important pathway present in many microorganisms. The final step of this pathway, the conversion of ketomethiobutyrate to methionine, can be performed by aspartate, tyrosine, or branched-chain

Erik S Venos; Marvin H Knodel; Cynthia L Radford; Bradley J Berger

2004-01-01

22

Spinal tuberculosis: A review  

PubMed Central

Spinal tuberculosis is a destructive form of tuberculosis. It accounts for approximately half of all cases of musculoskeletal tuberculosis. Spinal tuberculosis is more common in children and young adults. The incidence of spinal tuberculosis is increasing in developed nations. Genetic susceptibility to spinal tuberculosis has recently been demonstrated. Characteristically, there is destruction of the intervertebral disk space and the adjacent vertebral bodies, collapse of the spinal elements, and anterior wedging leading to kyphosis and gibbus formation. The thoracic region of vertebral column is most frequently affected. Formation of a ‘cold’ abscess around the lesion is another characteristic feature. The incidence of multi-level noncontiguous vertebral tuberculosis occurs more frequently than previously recognized. Common clinical manifestations include constitutional symptoms, back pain, spinal tenderness, paraplegia, and spinal deformities. For the diagnosis of spinal tuberculosis magnetic resonance imaging is more sensitive imaging technique than x-ray and more specific than computed tomography. Magnetic resonance imaging frequently demonstrates involvement of the vertebral bodies on either side of the disk, disk destruction, cold abscess, vertebral collapse, and presence of vertebral column deformities. Neuroimaging-guided needle biopsy from the affected site in the center of the vertebral body is the gold standard technique for early histopathological diagnosis. Antituberculous treatment remains the cornerstone of treatment. Surgery may be required in selected cases, e.g. large abscess formation, severe kyphosis, an evolving neurological deficit, or lack of response to medical treatment. With early diagnosis and early treatment, prognosis is generally good. PMID:22118251

Garg, Ravindra Kumar; Somvanshi, Dilip Singh

2011-01-01

23

Genomic insights into tuberculosis.  

PubMed

Prevalent since pre-history, human tuberculosis - caused by the pathogen Mycobacterium tuberculosis - remains a major source of death worldwide. Moreover, increasing drug resistance poses the threat of disease resurgence. However, the expanding application of genomic techniques is providing new avenues for combating this old foe. Whole-genome sequencing, comparative genomics and systems biology are generating new insights into the origins and ongoing evolution of M. tuberculosis, as well as the molecular basis for its pathogenicity. These have important implications for our perspective of the disease, development of new drugs and vaccines, and treatment of patients using existing therapeutics. PMID:24662221

Galagan, James E

2014-05-01

24

Tuberculosis in the elderly  

Microsoft Academic Search

Summary   Tuberculosis (TB) today remains one of the world’s most lethal infectious diseases. An estimated one-third of the world’s\\u000a population is infected with the tubercle bacillus-Mycobacterium tuberculosis (Mtb), and 7 to 8 million people develop TB disease each year (27). For purpose of clarity, TB infection (latent TB) is defined\\u000a as harboring Mtb without evidence of active infection, and TB

S. Rajagopalan; T. T. Yoshikawa

2000-01-01

25

Genomics and the evolution, pathogenesis, and diagnosis of tuberculosis  

PubMed Central

Tuberculosis kills nearly 2 million people annually, and current approaches to tuberculosis control are expensive, have limited efficacy, and are vulnerable to being overcome by extensively drug-resistant strains of Mycobacterium tuberculosis. Determination of the genome sequence of M. tuberculosis has revolutionized tuberculosis research, contributed to major advances in the understanding of the evolution and pathogenesis of M. tuberculosis, and facilitated development of new diagnostic tests with increased specificity for tuberculosis. In this review, we describe some of the major progress in tuberculosis research that has resulted from knowledge of the genome sequence and note some of the problems that remain unsolved. PMID:17607348

Ernst, Joel D.; Trevejo-Nuñez, Giraldina; Banaiee, Niaz

2007-01-01

26

Surgical Management of Tuberculosis-Related Hemoptysis  

Microsoft Academic Search

BackgroundTuberculosis is a disease that is often treated with chemotherapy. However, medical treatment usually fails in the management of tuberculosis-related hemoptysis. In this paper, we review our experience in the surgical treatment of tuberculosis-related hemoptysis.

Abdullah Erdogan; Arif Yegin; Gülsüm Gürses; Abid Demircan

2005-01-01

27

Assessment of the N-PCR Assay in Diagnosis of Pleural Tuberculosis: Detection of M.tuberculosis in Pleural Fluid and Sputum Collected in Tandem  

Microsoft Academic Search

BackgroundThe nonspecific clinical presentation and paucibacillary nature of tuberculous pleuritis remains a challenge for diagnosis. Diagnosis of tuberculous pleural effusion depends on the demonstration of the presence of tubercle bacilli in the sputum, pleural fluid, or pleural biopsy specimen, or demonstration of granuloma in pleura by histological examination. We examined the clinical utility of the diagnosis of pleural tuberculosis using

Parameet Kumar; Manas K. Sen; Devendra S. Chauhan; Vishwa M. Katoch; Sarman Singh; Hanumanthappa K. Prasad; Igor Mokrousov

2010-01-01

28

Inhibition of Mycobacterium tuberculosis Glutamine Synthetase as a Novel Antibiotic Strategy against Tuberculosis: Demonstration of Efficacy In Vivo  

Microsoft Academic Search

Tuberculosis remains one of humankind's greatest killers, and new therapeutic strategies are needed to combat the causative agent, Mycobacterium tuberculosis, which is rapidly developing resistance to conventional antibiotics. Using the highly demanding guinea pig model of pulmonary tuberculosis, we have investigated the feasibility of inhibiting M. tuberculosis glutamine synthetase (GS), an enzyme that plays a key role in both nitrogen

Gunter Harth; Marcus A. Horwitz

2003-01-01

29

Tuberculosis in the intensive care unit: A retrospective descriptive cohort study with determination of a predictive fatality score  

PubMed Central

BACKGROUND: Despite effective treatments, tuberculosis-related mortality remains high among patients requiring admission to the intensive care unit (ICU). OBJECTIVE: To determine prognostic factors of death in tuberculosis patients admitted to the ICU, and to develop a simple predictive scoring system. METHODS: A 10-year, retrospective study of 53 patients admitted consecutively to the Hôpitaux de Paris, Hôpital Lariboisière (Paris, France) ICU with confirmed tuberculosis, was conducted. A multivariate analysis was performed to identify risk factors for death. A predictive fatality score was determined. RESULTS: Diagnoses included pulmonary tuberculosis (96%) and tuberculous encephalomeningitis (26%). Patients required mechanical ventilation (45%) and vasopressor infusion (28%) on admission. Twenty patients (38%) died, related to direct tuberculosis-induced organ failure (n=5), pulmonary bacterial coinfections (n=14) and pulmonary embolism (n=1). Using a multivariate analysis, three independent factors on ICU admission were predictive of fatality: miliary pulmonary tuberculosis (OR 9.04 [95% CI 1.25 to 65.30]), mechanical ventilation (OR 11.36 [95% CI 1.55 to 83.48]) and vasopressor requirement (OR 8.45 [95% CI 1.29 to 55.18]). A score generated by summing these three independent variables was effective at predicting fatality with an area under the ROC curve of 0.92 (95% CI 0.85 to 0.98). CONCLUSIONS: Fatalities remain high in patients admitted to the ICU with tuberculosis. Miliary pulmonary tuberculosis, mechanical ventilation and vasopressor requirement on admission were predictive of death. PMID:24294270

Valade, Sandrine; Raskine, Laurent; Aout, Mounir; Malissin, Isabelle; Brun, Pierre; Deye, Nicolas; Baud, Frédéric J; Megarbane, Bruno

2012-01-01

30

Tuberculosis Fluoroscopy  

Cancer.gov

Follow-up though Dec 31, 2002 has been completed for a study of site-specific cancer mortality among tuberculosis patients treated with artificial lung collapse therapy in Massachusetts tuberculosis sanatoria (1930-1950).

31

[Tuberculosis in compromised hosts].  

PubMed

Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower in poorly-controlled DM patients than that in well-controlled DM patients and healthy subjects. Thus, these clinical data suggest that the high incidence of tuberculosis in DM patients is due to the impaired production of Th1-related cytokines. However, direct evidences to prove this possibility remain to be obtained. In 1980, Saiki and co-workers reported that host defense and delayed-type hypersensitivity response to M. tuberculosis was hampered in a mouse DM model established by injecting streptozotocin (Infect Immun. 1980; 28: 127-131). We followed their investigation with the similar observations. Interestingly, levels of IFN-gamma and IL-12 in serum, lung, liver and spleen after infection were significantly reduced in DM mice when compared with those in control mice. Considered collectively, these results strongly suggest that the reduced production of Th1-related cytokines leads to the susceptibility of DM to mycobacterial infection. However, it remains to be understood how DM hampers the synthesis of Th1-related cytokines. In our preliminary study, the production of these cytokines by PBMC from DM patients and healthy subjects was not affected under a high glucose condition. Thus, it is not likely that the increased level of glucose directly suppresses the cell-mediated immune responses. Further investigations are needed to make these points clear. 2. A study of gastrectomy cases in pulmonary tuberculosis patients: Takenori YAGI (Division of Thoracic Disease, National Chiba-Higashi Hospital). Patients who have undergone gastric resection are considered at increased risk of developing pulmonary tuberculosis. I have investigated the role played by gastrectomy in giving rise to pulmonary tuberculosis. Of 654 pulmonary tuberculosis patients admitted to National Chiba-Higashi Hospital from January 1999 to December 2001, 55 patients (31-84 years old, mean 63.5 +/- 12.5 years, 48 males and 7 females) had the history of gastric resection. The incidence of gastrectomy among patients with pulmonary tuberculosis was 8.4 percent. The mean age of gastric resection

2003-11-01

32

Bovine Tuberculosis  

Technology Transfer Automated Retrieval System (TEKTRAN)

Tuberculosis (TB) in animals and humans may result from exposure to bacilli within the Mycobacterium tuberculosis complex (i.e., M. tuberculosis, M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, or M. canetti). Mycobacterium bovis is the species most often isolated from tuberculous catt...

33

Tuberculosis Drug Resistance Mutation Database  

E-print Network

Tuberculosis (TB) remains the leading cause of death from a largely preventable and curable infectious disease, with an estimated 1.7 million deaths in 2006. Global prospects for TB control are challenged by the emergence ...

Church, George M.

34

Prevalent tuberculosis and mortality among HAART initiators  

PubMed Central

The effect of tuberculosis on mortality in people initiating highly active antiretroviral treatment (HAART) remains unclear; here, we strengthened a previous cohort analysis. Multivariate Cox proportional hazards models were used to assess the association of baseline tuberculosis and time to all-cause mortality among HAART initiators. In reanalysis, treatment for tuberculosis at time of HAART initiation remained unassociated with increased risks of all-cause mortality, with adjusted hazard ratios ranging from 1.00 to 1.09. PMID:22313956

Westreich, Daniel; Fox, Matthew P.; Van Rie, Annelies; Maskew, Mhairi

2012-01-01

35

CCL2 Responses to Mycobacterium tuberculosis Are Associated with Disease Severity in Tuberculosis  

Microsoft Academic Search

BackgroundLeucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFN?, TNF? and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity.MethodologyWe investigated live M. tuberculosis- and M. bovis BCG- induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and

Zahra Hasan; Jacqueline M. Cliff; Hazel M. Dockrell; Bushra Jamil; Muhammad Irfan; Mussarat Ashraf; Rabia Hussain; T. Mark Doherty

2009-01-01

36

A rapid assessment and response approach to review and enhance Advocacy, Communication and Social Mobilisation for Tuberculosis control in Odisha state, India  

Microsoft Academic Search

Background  Tuberculosis remains a major public health problem in India with the country accounting for 1 in 5 of all TB cases reported\\u000a globally. An advocacy, communication and social mobilisation project for Tuberculosis control was implemented and evaluated\\u000a in Odisha state of India. The purpose of the study was to identify the impact of project interventions including the use of\\u000a 'Interface

Vishnu Vardhan Kamineni; Tahir Turk; Nevin Wilson; Srinath Satyanarayana; Lakbir Singh Chauhan

2011-01-01

37

Tuberculosis of the head and neck – epidemiological and clinical presentation  

PubMed Central

Introduction The aim of our retrospective study was to review the clinical and epidemiological presentation of head and neck tuberculosis. Material and methods We analyzed the history of 73 patients with head and neck tuberculosis hospitalized in the Department of Otolaryngology, Medical University of Warsaw, between 1983 and 2009. Results We found that 26 (35.6%) patients presented with lymph node tuberculosis, 20 (27.4%) with laryngeal tuberculosis, 10 (13.7%) with oropharyngeal tuberculosis, 9 (12.3%) with salivary gland tuberculosis, 3 (4.1%) with tuberculosis of paranasal sinuses, 3 (4.1%) with aural tuberculosis, and 2 (2.7%) with skin tuberculosis in the head and neck region. Within the group of patients with lymph node tuberculosis in 15 cases there were infected lymph nodes of the 2nd and 3rd cervical region and in 11 infected lymph nodes of the 1st cervical region. In 5 cases of laryngeal tuberculosis there was detected coexistence of cancer. Oropharyngeal tuberculosis in 7 cases was localized in tonsils, where in 1 case coexisting cancer was diagnosed. Chest X-ray was performed in all cases and pulmonary tuberculosis was identified in 26 (35.6%) cases. Conclusions We conclude that tuberculosis still remains a problem and must be taken into consideration in the diagnostic process. The coincidence of tuberculosis and cancer is remarkable in the head and neck region.

Bruzgielewicz, Antoni; Osuch-Wójcikewicz, Ewa; Niemczyk, Kazimierz; Chmielewski, Rafa?

2013-01-01

38

Detection and Molecular Characterization of 9000-Year-Old Mycobacterium tuberculosis from a Neolithic Settlement in the Eastern Mediterranean  

PubMed Central

Background Mycobacterium tuberculosis is the principal etiologic agent of human tuberculosis. It has no environmental reservoir and is believed to have co-evolved with its host over millennia. This is supported by skeletal evidence of the disease in early humans, and inferred from M. tuberculosis genomic analysis. Direct examination of ancient human remains for M. tuberculosis biomarkers should aid our understanding of the nature of prehistoric tuberculosis and the host/pathogen relationship. Methodology/Principal Findings We used conventional PCR to examine bone samples with typical tuberculosis lesions from a woman and infant, who were buried together in the now submerged site of Atlit-Yam in the Eastern Mediterranean, dating from 9250-8160 years ago. Rigorous precautions were taken to prevent contamination, and independent centers were used to confirm authenticity of findings. DNA from five M tuberculosis genetic loci was detected and had characteristics consistent with extant genetic lineages. High performance liquid chromatography was used as an independent method of verification and it directly detected mycolic acid lipid biomarkers, specific for the M. tuberculosis complex. Conclusions/Significance Human tuberculosis was confirmed by morphological and molecular methods in a population living in one of the first villages with evidence of agriculture and animal domestication. The widespread use of animals was not a source of infection but may have supported a denser human population that facilitated transmission of the tubercle bacillus. The similarity of the M. tuberculosis genetic signature with those of today gives support to the theory of a long-term co-existence of host and pathogen. PMID:18923677

Minnikin, David E.; Besra, Gurdyal S.; Lee, Oona Y-C.; Gernaey, Angela M.; Galili, Ehud; Eshed, Vered; Greenblatt, Charles L.; Lemma, Eshetu; Bar-Gal, Gila Kahila; Spigelman, Mark

2008-01-01

39

Review article Classification of worldwide bovine tuberculosis risk factors  

E-print Network

Review article Classification of worldwide bovine tuberculosis risk factors in cattle: a stratified Tilman, Belgium 2 National and OIE/FAO Bovine Tuberculosis Reference Laboratories, Bacterial Zoonoses ­ The worldwide status of bovine tuberculosis (bTB) as a zoonosis remains of great concern. This article reviews

Paris-Sud XI, Université de

40

Origin, Spread and Demography of the Mycobacterium tuberculosis Complex  

E-print Network

Origin, Spread and Demography of the Mycobacterium tuberculosis Complex Thierry Wirth1,2 *, Falk of the Mycobacterium tuberculosis complex (MTBC), one of the most successful groups of bacterial pathogens, remains that the MTBC consists of two independent clades, one composed exclusively of M. tuberculosis lineages from

Wirth, Thierry

41

Structural and functional characterization of the Mycobacterium tuberculosis uridine monophosphate  

E-print Network

Structural and functional characterization of the Mycobacterium tuberculosis uridine monophosphate tuberculosis, which remains a major public health issue. Current treatment requires a therapy involving four to drug resistance (2). Indeed, multi-drug resistant tuberculosis (MDR-TB) emerged in the early 1990s

Paris-Sud XI, Université de

42

Latent tuberculosis: what the host “sees”?  

Microsoft Academic Search

Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB), is the most successful pathogen of mankind and remains a major threat to\\u000a global health as the leading cause of death due to a bacterial pathogen. Yet 90–95% of those who are infected with MTB remain\\u000a otherwise healthy. These people are classified as “latently infected,” but remain a reservoir from which

Hannah P. GideonJoAnne; JoAnne L. Flynn

2011-01-01

43

RESEARCH ARTICLE Open Access Bayesian mapping of pulmonary tuberculosis in  

E-print Network

RESEARCH ARTICLE Open Access Bayesian mapping of pulmonary tuberculosis in Antananarivo, Madagascar Bicout2 Abstract Background: Tuberculosis (TB), an infectious disease caused by the Mycobacterium tuberculosis is endemic in Madagascar. The capital, Antananarivo is the most seriously affected area. TB had

Paris-Sud XI, Université de

44

RESEARCH ARTICLE Open Access Molecular diversity of Mycobacterium tuberculosis  

E-print Network

RESEARCH ARTICLE Open Access Molecular diversity of Mycobacterium tuberculosis isolates from patients with tuberculosis in Honduras Senia Rosales1,2,3* , Lelany Pineda-García1 , Solomon Ghebremichael3,4 , Nalin Rastogi5 , Sven E Hoffner3,4 Abstract Background: Tuberculosis persists as a public health problem

Boyer, Edmond

45

Application of Pulsed Field Gel Electrophoresis for Study of Genetic Diversity in Mycobacterium tuberculosis Strains Isolated From Tuberculosis Patients  

PubMed Central

Background: Mycobacterium tuberculosis genotyping can effectively improve tuberculosis (TB) control programs by controlling disease transmission. Pulsed field gel electrophoresis (PFGE) is a particularly powerful tool for determination of clonal identity of bacteria providing information for understanding and controlling the spread of disease. Objectives: The aim of present study was to investigate the genetic diversity of M. tuberculosis strains in Khuzestan province by the PFGE technique. Patients and Methods: In total, 80 M. tuberculosis positive cultures were obtained from tuberculosis patients. PFGE was performed on 60 PCR-confirmed isolates by using DraI and XbaI restriction enzymes according to standard protocols. Plugs containing digested DNA were then loaded on agarose gels and run using contour-clamped homogenous electric fields. Results: Fifty distinct DNA banding patterns were obtained by digestion of DNA with DraI and 38 DNA banding patterns by digestion with XbaI restriction enzymes. The patterns comprised of 17 different clusters in which cluster I was the major one, containing six strains. Three clusters contained three strains each and the 13 remaining clusters comprised of two strains each. Digestion with DraI yielded 15-20 DNA fragments with 50-485 kb size, while digestion by XbaI produced DNA fragments with a size smaller than 50-242 kb. Conclusions: Despite the ability of PFGE for study of genetic diversity of many mycobacterial species and it being considered as a robust and useful tool, in this study we only found a 15% epidemiological relationship amongst the isolates. Thus, for higher discrimination of genotypic clusters among M. tuberculosis clinical isolates, the application of more sophisticated complementary techniques is required. PMID:25147723

Khosravi, Azar Dokht; Vatani, Shideh; Feizabadi, Mohammad Mehdi; Abasi Montazeri, Effat; Jolodar, Abbas

2014-01-01

46

[Unusual locations of tuberculosis: three case reports].  

PubMed

We report three cases of tuberculosis of unusual location in Malagasy patients. The first patient presented with intracardiac tuberculoma during pulmonary tuberculosis. The second patient who had no significant musculoskeletal past medical history presented with tuberculous polymyositis. The remaining one presented with tuberculous epididymitis without involvement of the urinary tract. Diagnosis was histopathological. The outcome was favorable in the two last patients with antituberculous therapy. This report emphasizes the necessary awareness of tuberculosis even in the presence of unusual manifestations in hyper-endemic area of tuberculosis. PMID:19233520

Ralandison, S; Rakotoarivelo, R; Rakotovao, M; Raobison, R; Andrianteloasy, S; Rakotoarimanana, S; Rapelanoro Rabenja, F

2009-10-01

47

Novel human genetic variants associated with extrapulmonary tuberculosis: a pilot genome wide association study  

Microsoft Academic Search

BACKGROUND: Approximately 5-10% of persons infected with M. tuberculosis develop tuberculosis, but the factors associated with disease progression are incompletely understood. Both linkage and association studies have identified human genetic variants associated with susceptibility to pulmonary tuberculosis, but few genetic studies have evaluated extrapulmonary disease. Because extrapulmonary and pulmonary tuberculosis likely have different underlying pathophysiology, identification of genetic mutations associated

Noffisat O Oki; Alison A Motsinger-Reif; Paulo RZ Antas; Shawn Levy; Steven M Holland; Timothy R Sterling

2011-01-01

48

[Extrapulmonary tuberculosis.  

PubMed

Each year, there are more than eight million new cases of tuberculosis and 1.3 million deaths. There is a renewed interest in extrapulmonary forms of tuberculosis as its relative frequency increases. Among extrapulmonary organs, pleura and lymph nodes are the most common. Their diagnosis is often difficult and is based on clinical, radiological, bacteriological and histological findings. Extrapulmonary lesions are paucibacillary and samplings, in most cases, difficult to obtain, so diagnosis is often simply presumptive. Nucleic acid amplification tests, which are fast and specific, have greatly facilitated the diagnosis of some forms of extrapulmonary tuberculosis. However, their sensitivity is poor and a negative test does not eliminate the diagnosis. Treatment is the same as for pulmonary forms, but its duration is nine to 12 months for central nervous system and for bone tuberculosis. Corticosteroids are indicated in meningeal and pericardial localizations. Complementary surgery is used for certain complicated forms. PMID:25131362

Ketata, W; Rekik, W K; Ayadi, H; Kammoun, S

2014-08-14

49

Sternal tuberculosis.  

PubMed

Extra-pulmonary tuberculosis constitutes 15-20% of total tuberculosis (TB) case load in immuno-competent patients. Affliction of the skeletal system is rare with still rarer presentation of sternal osteomyelitis even in endemic countries. A patient with primary sternal TB presenting with multiple cutaneous sinuses over the anterior chest wall is being reported. A high element of suspicion is needed more so in resource limited setting for early diagnosis and treatment. PMID:24349840

Sachdeva, R; Sachdeva, S; Arora, S

2013-11-01

50

The Prevalence and Drug Sensitivity of Tuberculosis among Patients Dying in Hospital in KwaZulu-Natal, South Africa: A Postmortem Study  

PubMed Central

Background Tuberculosis is the leading cause of death in South Africa by death notification, but accurate diagnosis of tuberculosis is challenging in this setting of high HIV prevalence. We conducted limited autopsies on young adults dying in a single public hospital in the province of KwaZulu-Natal between October 2008 and August 2009 in order to estimate the magnitude of deaths attributable to tuberculosis. Methods and Findings We studied a representative sample of 240 adult inpatients (aged 20–45 years) dying after admission to Edendale Hospital. Limited autopsies included collection of respiratory tract secretions and tissue by needle core biopsies of lung, liver, and spleen. Specimens were examined by fluorescent microscopy for acid-fast bacilli and cultured in liquid media; cultures positive for M. tuberculosis were tested for drug susceptibility to first- and second-line antibiotics. Ninety-four percent of our study cohort was HIV seropositive and 50% of decedents had culture-positive tuberculosis at the time of death. Fifty percent of the participants were on treatment for tuberculosis at the time of death and 58% of these treated individuals remained culture positive at the time of death. Of the 50% not receiving tuberculosis treatment, 42% were culture positive. Seventeen percent of all positive cultures were resistant to both isoniazid and rifampin (i.e., multidrug resistant); 16% of patients dying during the initiation phase of their first ever course of tuberculosis treatment were infected with multidrug-resistant bacilli. Conclusions Our findings reveal the immense toll of tuberculosis among HIV-positive individuals in KwaZulu-Natal. The majority of decedents who remained culture positive despite receiving tuberculosis treatment were infected with pan-susceptible M. tuberculosis, suggesting that the diagnosis of tuberculosis was made too late to alter the fatal course of the infection. There is also a significant burden of undetected multidrug-resistant tuberculosis among HIV-coinfected individuals dying in this setting. New public health approaches that improve early diagnosis of tuberculosis and accelerate the initiation of treatment are urgently needed in this setting. Please see later in the article for the Editors' Summary PMID:20582324

Cohen, Ted; Murray, Megan; Wallengren, Kristina; Alvarez, Gonzalo G.; Samuel, Elizabeth Y.; Wilson, Douglas

2010-01-01

51

Evolution and expansion of the Mycobacterium tuberculosis PE and PPE multigene families and their association with the duplication of the ESAT-6 (esx) gene cluster regions  

Microsoft Academic Search

BACKGROUND: The PE and PPE multigene families of Mycobacterium tuberculosis comprise about 10% of the coding potential of the genome. The function of the proteins encoded by these large gene families remains unknown, although they have been proposed to be involved in antigenic variation and disease pathogenesis. Interestingly, some members of the PE and PPE families are associated with the

Nicolaas C Gey van Pittius; Samantha L Sampson; Hyeyoung Lee; Yeun Kim; Paul D van Helden; Robin M Warren

2006-01-01

52

Prevalence of tuberculosis in pigs slaughtered at two abattoirs in Ethiopia and molecular characterization of Mycobacterium tuberculosis isolated from tuberculous-like lesions in pigs  

PubMed Central

Background Tuberculosis (TB) is an infectious, granulomatous disease caused by acid-fast bacilli of the genus Mycobacterium. The disease affects practically all species of vertebrates. Although mammalian tuberculosis has been nearly controlled in many developed countries, it is still a serious problem in humans and domestic animals including pigs in developing countries. In Ethiopia, the prevalence of TB in pigs is not known. Therefore, this study was designed to estimate the prevalence of TB in pigs in central Ethiopia and to characterize the causative agents using molecular techniques. Results The estimated prevalence of TB was 5.8% (49/841). Age and origin of pigs were significantly associated (P<0.001) with the prevalence. In contrast, an association of sex, floor type and water source with the prevalence could not be shown. Culture positivity was confirmed in 30.6% (15/49) of the tuberculous-like lesions. Of the 15 isolates, 12 were acid fast positive while five of the latter were confirmed by multiplex PCR as members of the M. tuberculosis complex. Speciation of the five isolates further confirmed that they were M. tuberculosis, belonging to SIT1088 (two isolates) and SIT1195 (one isolate). The remaining two isolates belong to an identical spoligotype, the pattern of which was not found in the spoligotype database (SpolDB4). Conclusions The isolation of M. tuberculosis from pigs suggests a possible risk of transmission between humans and pigs. Hence, establishing feasible control methods is required. PMID:23647845

2013-01-01

53

Tuberculosis: New Aspects of an Old Disease  

PubMed Central

Tuberculosis is an ancient infectious disease that remains a threat for public health around the world. Although the etiological agent as well as tuberculosis pathogenesis is well known, the molecular mechanisms underlying the host defense to the bacilli remain elusive. In this paper we focus on the innate immunity of this disease reviewing well-established and consensual mechanisms like Mycobacterium tuberculosis interference with phagosome maturation, less consensual mechanism like nitric oxide production, and new mechanisms, such as mycobacteria translocation to the cytosol, autophagy, and apoptosis/necrosis proposed mainly during the last decade. PMID:21760796

Jordao, Luisa; Vieira, Otilia V.

2011-01-01

54

Abdominal Tuberculosis  

Microsoft Academic Search

. Throughout the world tuberculosis is\\u000a \\u000a associated with poverty, deprivation, and human immunodeficiency virus\\u000a \\u000a infection. Abdominal tuberculosis is usually of insidious onset with\\u000a \\u000a diverse symptoms and signs. A few present with acute complications of\\u000a \\u000a perforation, obstruction, or bleeding. The diagnosis is difficult,\\u000a \\u000a especially in areas where the disease is less common, as many patients\\u000a \\u000a do not have evidence of pulmonary

Niall O. Aston

1997-01-01

55

Growth of Mycobacterium tuberculosis biofilms.  

PubMed

Mycobacterium tuberculosis, the etiologic agent of human tuberculosis, has an extraordinary ability to survive against environmental stresses including antibiotics. Although stress tolerance of M. tuberculosis is one of the likely contributors to the 6-month long chemotherapy of tuberculosis (1), the molecular mechanisms underlying this characteristic phenotype of the pathogen remain unclear. Many microbial species have evolved to survive in stressful environments by self-assembling in highly organized, surface attached, and matrix encapsulated structures called biofilms (2-4). Growth in communities appears to be a preferred survival strategy of microbes, and is achieved through genetic components that regulate surface attachment, intercellular communications, and synthesis of extracellular polymeric substances (EPS) (5,6). The tolerance to environmental stress is likely facilitated by EPS, and perhaps by the physiological adaptation of individual bacilli to heterogeneous microenvironments within the complex architecture of biofilms (7). In a series of recent papers we established that M. tuberculosis and Mycobacterium smegmatis have a strong propensity to grow in organized multicellular structures, called biofilms, which can tolerate more than 50 times the minimal inhibitory concentrations of the anti-tuberculosis drugs isoniazid and rifampicin (8-10). M. tuberculosis, however, intriguingly requires specific conditions to form mature biofilms, in particular 9:1 ratio of headspace: media as well as limited exchange of air with the atmosphere (9). Requirements of specialized environmental conditions could possibly be linked to the fact that M. tuberculosis is an obligate human pathogen and thus has adapted to tissue environments. In this publication we demonstrate methods for culturing M. tuberculosis biofilms in a bottle and a 12-well plate format, which is convenient for bacteriological as well as genetic studies. We have described the protocol for an attenuated strain of M. tuberculosis, mc(2)7000, with deletion in the two loci, panCD and RD1, that are critical for in vivo growth of the pathogen (9). This strain can be safely used in a BSL-2 containment for understanding the basic biology of the tuberculosis pathogen thus avoiding the requirement of an expensive BSL-3 facility. The method can be extended, with appropriate modification in media, to grow biofilm of other culturable mycobacterial species. Overall, a uniform protocol of culturing mycobacterial biofilms will help the investigators interested in studying the basic resilient characteristics of mycobacteria. In addition, a clear and concise method of growing mycobacterial biofilms will also help the clinical and pharmaceutical investigators to test the efficacy of a potential drug. PMID:22371116

Kulka, Kathleen; Hatfull, Graham; Ojha, Anil K

2012-01-01

56

[Tuberculosis--a neverending story].  

PubMed

It is estimated that over one third of the human population is now exposed or has been exposed in the past to Mycobacterium tuberculosis, and new infections occur in the world at a rate of one per second. The history of tuberculosis is long and very interesting, because before the isolation of mycobacteria and the finding of a cure, the disease mercilessly killed thousands of people and deprived doctors of hope. Robert Koch's momentous discovery was a major breakthrough in the fight against tuberculosis. Unfortunately, the disease has never been fully controlled. Tuberculosis is a chronic infectious disease localized in 90-95% of cases in the lungs, and therefore it is extremely difficult to diagnose unequivocally in paleopathological material. Only the form of osteo-arthritis leaves traces in archaeological material. The earliest evidence of tuberculosis (the location of the spine, Pott's disease) in the form of fossils is dated to before 8000 BC. Another very old trace is considered to be human remains from the Neolithic period (ca 5000 BC), found near Heidelberg, where changes in the thoracic spine are typical for spondylitis in tuberculosa. Constant growth in the incidence of new cases in the world can be observed today. Not everyone infected will develop the full-blown disease. The infection may remain dormant. However, one in ten latent infections will subsequently be activated, leading, if not treated, to the death of almost half of the patients. PMID:25026769

Dziecio?owska-Baran, Edyta; Gawlikowska-Sroka, Aleksandra

2013-01-01

57

A randomized controlled trial of standard versus intensified tuberculosis diagnostics on treatment decisions by physicians in Northern Tanzania  

PubMed Central

Background Routine tuberculosis culture remains unavailable in many high-burden areas, including Tanzania. This study sought to determine the impact of providing mycobacterial culture results over standard of care [unconcentrated acid-fast (AFB) smears] on management of persons with suspected tuberculosis. Methods Adults and children with suspected tuberculosis were randomized to standard (direct AFB smear only) or intensified (concentrated AFB smear and tuberculosis culture) diagnostics and followed for 8 weeks. The primary endpoint was appropriate treatment (i.e. antituberculosis therapy for those with tuberculosis, no antituberculous therapy for those without tuberculosis). Results Seventy participants were randomized to standard (n?=?37, 53%) or intensive (n?=?33, 47%) diagnostics. At 8 weeks, 100% (n?=?22) of participants in follow up randomized to intensive diagnostics were receiving appropriate care, vs. 22 (88%) of 25 participants randomized to standard diagnostics (p?=?0.14). Overall, 18 (26%) participants died; antituberculosis therapy was associated with lower mortality (9% who received antiuberculosis treatment died vs. 26% who did not, p?=?0.04). Conclusions Under field conditions in a high burden setting, the impact of intensified diagnostics was blunted by high early mortality. Enhanced availability of rapid diagnostics must be linked to earlier access to care for outcomes to improve. PMID:24552306

2014-01-01

58

In Mice, Tuberculosis Progression Is Associated with Intensive Inflammatory Response and the Accumulation  

E-print Network

In Mice, Tuberculosis Progression Is Associated with Intensive Inflammatory Response outcomes ranging from asymptomatic containment to rapidly progressing tuberculosis (TB). The mechanisms controlling TB progression in immunologically-competent hosts remain unclear. Methodology/Principal Findings

Utrecht, Universiteit

59

Tuberculosis and Diabetes  

MedlinePLUS

TUBERCULOSIS & DIABETES COLLABORATIVE FRAMEWORK FOR CARE AND CONTROL OF TUBERCULOSIS AND DIABETES © WHO Sept 2011 For more information: ... Recommended collaborative activities for prevention and care of diabetes and tuberculosis • Indicators for evaluating collaborative activities • Implementing collaborative activities ...

60

The Impact of Alcohol on BCG-Induced Immunity Against Mycobacterium tuberculosis  

PubMed Central

Background Alcoholics are at heightened risk for developing active tuberculosis. This study evaluates chronic alcohol consumption in a murine model of vaccination with Mycobacterium bovis Bacille-Calmette Guèrin (BCG) and subsequent pulmonary infection with virulent Mycobacterium tuberculosis. Methods BALB/c mice were administered the Lieber-DeCarli liquid ethanol diet (LED) or pair-fed the liquid control diet (LCD) for three weeks either before or after subcutaneous vaccination with M. bovis BCG. At least three weeks after BCG vaccination, groups of mice on the above diets were challenged with intratracheal infection with M. tuberculosis H37Rv. Lung mycobacterial burden, and lung and lung-associated lymph node CD4+ lymphocyte production of TB-specific interferon (IFN)-? were assayed. Popliteal lymph node lymphocytes from both dietary regimens undergoing BCG vaccination (in the absence of M. tuberculosis infection) were also evaluated for PPD-induced interferon (IFN)-? production by ELISpot assay. Results Mice begun on alcohol prior to vaccination with M. bovis BCG demonstrated impaired control of pulmonary challenge with virulent M. tuberculosis, as well as impaired lung CD4+ and popliteal lymph node T cell IFN-? responses. If BCG vaccination was delivered prior to initiation of alcohol feeding, the mice remained protected against a subsequent challenge with M. tuberculosis, and BCG-induced immunity was not impaired in either the lung or the popliteal lymph nodes. Conclusions Alcohol consumption blunts the development of the adaptive immune response to M. bovis BCG vaccination, which impairs the control of a secondary challenge with M. tuberculosis, but only if the alcohol exposure is begun prior to BCG vaccination. These results provide insight into mechanisms by which alcohol consumption impairs antimycobacterial immunity, including in response to vaccination and subsequent pathogenic challenge. PMID:22014229

Porretta, Elizabeth; Happel, Kyle I.; Teng, Xu S.; Ramsay, Alistair; Mason, Carol M.

2011-01-01

61

[Tuberculosis control of urban areas in Japan].  

PubMed

The rates of tuberculosis remain high in urban areas. The declining speed of tuberculosis incidence rate in urban areas has been slower than other areas. Efforts and resources to tuberculosis control must be concentrated on urban locations to eradicate tuberculosis in Japan. 1. Tuberculosis control in a public health center of urban area: Teru OGURA and Chiyo INOGUCHI (Toshima City, Ikebukuro Public Health Center, Tokyo Metropolitan) A wide range of TB control measures is implemented by public health centers, such as a patient registration, home-visit guidance, contact examination in urban areas. Directors of every health center have the direct responsibility for tuberculosis control measures in their jurisdiction. Ikebukuro is urban areas where there are many offices, shopping and amusement facilities. Urban people is often on the move looking for job, so public health centers are often not easy to carry out contact examinations as planned. In recent years, homelessness has been recognized as a growing urban social problem. Their incidence of tuberculosis is high. Special TB control program must be carried out in urban areas. 2. Tuberculosis Control in Tokyo Metropolitan: Kazumasa MATSUKI (Department of Infectious Diseases and Tuberculosis, Bureau of Public Health, Tokyo Metropolitan) There has been a steady decline in the TB wards. The beds for TB patients are running short and even smear positive TB cases cannot be put in a hospital without waiting several days. Staffs of an urban emergency department must protect tuberculosis infection by environmental controls of emergency room. Tokyo Metropolitan government supports the engineering improvements of emergency room to hospitals. Directly observed therapy for tuberculosis patients at a district has been implemented to complete their therapy. On DOT, a trained health worker observes the patient take anti-TB medication. 3. Usefulness of Molecular Epidemiologic approach on Tuberculosis Control: Atsushi HASE (Osaka City Institute Laboratory of Health and Environment) DNA fingerprinting establishes the genetic relatedness of Mycobacterium tuberculosis isolates and has become a powerful tool in tuberculosis epidemiology. To use DNA fingerprinting to assess the efficacy of current tuberculosis infection-control practices. Combining conventional epidemiologic techniques with DNA fingerprinting of M. tuberculosis can improve the understanding of how tuberculosis is transmitted. Patients were assigned to clusters based on mycobacterial isolates with identical DNA fingerprints. Clusters were assumed to have arisen from recent transmission. We analyzed M. tuberculosis isolates from patients reported to the tuberculosis registry by RFLP techniques. These results were interpreted along with demographic data. Patients infected with the same strains were identified according to their RFLP patterns, and patients with identical patterns were grouped in clusters. RFLP patterns of high incidence districts have more variations than other areas. This suggests that the source of tuberculosis infection are quite diverse and complicated. Tuberculosis patients may accumulate to high incidence districts from other places after infection. 4. Structure of High Incidence of Tuberculosis and Control Plan in Osaka City: Yoichi TATSUMI (Bureau of Infection Control, Osaka City Office) The case notification rate in Osaka City is the highest in Japan. That of all TB cases and smear positive TB cases was 1573 and 216 per 100,000 population in 1997 at Airin District in Osaka City. The main reason for this highest incidence rate is that there are many homeless people and it is a mobile population. Most of residents are daily laborers. They come from all over Japan and stay there, mainly in rented rooms, to look for jobs. Thousands of homeless people also live in tents on streets or in parks. We are making to new strategic plan to intensify tuberculosis control measures throughout the city. Osaka city government h PMID:11109777

2000-10-01

62

Duration of Anti-Tuberculosis Therapy and Timing of Antiretroviral Therapy Initiation: Association with Mortality in HIV-Related Tuberculosis  

PubMed Central

Background Antiretroviral therapy (ART) decreases mortality risk in HIV-infected tuberculosis patients, but the effect of the duration of anti-tuberculosis therapy and timing of anti-tuberculosis therapy initiation in relation to ART initiation on mortality, is unclear. Methods We conducted a retrospective observational multi-center cohort study among HIV-infected persons concomitantly treated with Rifamycin-based anti-tuberculosis therapy and ART in Latin America. The study population included persons for whom 6 months of anti-tuberculosis therapy is recommended. Results Of 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm3, 171 (68%) received >180 days of anti-tuberculosis therapy, 168 (66%) initiated anti-tuberculosis therapy before ART, and 43 (17%) died. In a multivariate Cox proportional hazards model that adjusted for CD4+ lymphocytes and HIV-1 RNA, tuberculosis diagnosed after ART initiation was associated with an increased risk of death compared to tuberculosis diagnosis before ART initiation (HR 2.40; 95% CI 1.15, 5.02; P = 0.02). In a separate model among patients surviving >6 months after tuberculosis diagnosis, after adjusting for CD4+ lymphocytes, HIV-1 RNA, and timing of ART initiation relative to tuberculosis diagnosis, receipt of >6 months of anti-tuberculosis therapy was associated with a decreased risk of death (HR 0.23; 95% CI 0.08, 0.66; P=0.007). Conclusions The increased risk of death among persons diagnosed with tuberculosis after ART initiation highlights the importance of screening for tuberculosis before ART initiation. The decreased risk of death among persons receiving > 6 months of anti-tuberculosis therapy suggests that current anti-tuberculosis treatment duration guidelines should be re-evaluated. PMID:24066096

Cortes, Claudia P.; Wehbe, Firas H.; McGowan, Catherine C.; Shepherd, Bryan E.; Duda, Stephany N.; Jenkins, Cathy A.; Gonzalez, Elsa; Carriquiry, Gabriela; Schechter, Mauro; Padgett, Denis; Cesar, Carina; Madero, Juan Sierra; Pape, Jean W.; Masys, Daniel R.; Sterling, Timothy R.

2013-01-01

63

Hepatobiliary tuberculosis.  

PubMed

Hepatobiliary tuberculosis refers to the localized form of hepatic tuberculosis and is a distinct entity in which hepatobiliary involvement overwhelmingly dominates the clinical picture. Presentations are often delayed, and manifestations can be nonspecific. Fever is the most common symptom followed by abdominal pain, and hepatomegaly is the most common abnormality found on clinical examination. Abnormalities of the liver function tests are non-specific and hence not diagnostic. Ultrasound or computed tomography reveals single or complex masses, and guided biopsy is diagnostic either by demonstrating caseating granuloma or the organism by staining and culture. Treatment is with standard first-line antituberculous drugs. Endoscopic stenting gives an excellent outcome for symptomatic biliary strictures. The outcome in patients infected with Human Immunodeficiency virus depends on the level of underlying immunosuppression. PMID:24640207

Bandyopadhyay, Sanjay; Maity, Pranab K

2013-06-01

64

Mycobacterium tuberculosis wears what it eats  

PubMed Central

Mycobacterium tuberculosis remains one of the most pernicious of human pathogens. Current vaccines are ineffective and drugs, although efficacious, require prolonged treatment with constant medical oversight. Overcoming these problems requires a greater appreciation of M. tuberculosis in the context of its host. Upon infection of either macrophages in culture or animal models, the bacterium re-aligns its metabolism in response to the new environments it encounters. Understanding these environments, and the stresses that they place on M. tuberculosis, should provide insights invaluable for the development of new chemo- and immuno-therapeutic strategies. PMID:20638643

Russell, David G.; VanderVen, Brian C.; Lee, Wonsik; Abramovitch, Robert B.; Kim, Mijeong; Homolka, Susanne; Niemann, Stefan; Rohde, Kyle H.

2010-01-01

65

TUBERCULOSIS: TIME FOR A NEW PERSPECTIVE?  

PubMed Central

Transmission of Mycobacterium tuberculosis (Mtb) continues uninterrupted. Pre-exposure vaccination remains a central focus of tuberculosis research but 25 years of follow up is needed to determine whether a novel childhood vaccination regime protects from adult disease, or like BCG assists Mtb dissemination by preventing childhood illness but not infective adult pulmonary tuberculosis. Therefore, different strategies to interrupt the life cycle of Mtb need to be explored. This personal perspective discusses alternative approaches that may be delivered in a shorter time frame. PMID:23415730

Elkington, Paul T

2013-01-01

66

Tuberculosis: time for a new perspective?  

PubMed

Transmission of Mycobacterium tuberculosis (Mtb) continues uninterrupted. Pre-exposure vaccination remains a central focus of tuberculosis research but 25 years of follow up is needed to determine whether a novel childhood vaccination regime protects from adult disease, or like BCG assists Mtb dissemination by preventing childhood illness but not infective adult pulmonary tuberculosis. Therefore, different strategies to interrupt the life cycle of Mtb need to be explored. This personal perspective discusses alternative approaches that may be delivered in a shorter time frame. PMID:23415730

Elkington, Paul T

2013-04-01

67

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects  

PubMed Central

Summary: Tuberculosis of the central nervous system (CNS) is a highly devastating form of tuberculosis, which, even in the setting of appropriate antitubercular therapy, leads to unacceptable levels of morbidity and mortality. Despite the development of promising molecular diagnostic techniques, diagnosis of CNS tuberculosis relies largely on microbiological methods that are insensitive, and as such, CNS tuberculosis remains a formidable diagnostic challenge. Insights into the basic neuropathogenesis of Mycobacterium tuberculosis and the development of an appropriate animal model are desperately needed. The optimal regimen and length of treatment are largely unknown, and with the rising incidence of multidrug-resistant strains of M. tuberculosis, the development of well-tolerated and effective antibiotics remains a continued need. While the most widely used vaccine in the world largely targets this manifestation of tuberculosis, the BCG vaccine has not fulfilled the promise of eliminating CNS tuberculosis. We put forth this review to highlight the current understanding of the neuropathogenesis of M. tuberculosis, to discuss certain epidemiological, clinical, diagnostic, and therapeutic aspects of CNS tuberculosis, and also to underscore the many unmet needs in this important field. PMID:18400795

Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K.

2008-01-01

68

Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities.  

PubMed

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics. PMID:22496353

McNerney, Ruth; Maeurer, Markus; Abubakar, Ibrahim; Marais, Ben; McHugh, Timothy D; Ford, Nathan; Weyer, Karin; Lawn, Steve; Grobusch, Martin P; Memish, Ziad; Squire, S Bertel; Pantaleo, Giuseppe; Chakaya, Jeremiah; Casenghi, Martina; Migliori, Giovanni-Batista; Mwaba, Peter; Zijenah, Lynn; Hoelscher, Michael; Cox, Helen; Swaminathan, Soumya; Kim, Peter S; Schito, Marco; Harari, Alexandre; Bates, Matthew; Schwank, Samana; O'Grady, Justin; Pletschette, Michel; Ditui, Lucica; Atun, Rifat; Zumla, Alimuddin

2012-05-15

69

Identification of gene targets against dormant phase Mycobacterium tuberculosis infections  

Microsoft Academic Search

Background  \\u000a Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects approximately 2 billion people worldwide and is the leading cause of mortality\\u000a due to infectious disease. Current TB therapy involves a regimen of four antibiotics taken over a six month period. Patient\\u000a compliance, cost of drugs and increasing incidence of drug resistant M. tuberculosis strains have added urgency to the

Dennis J Murphy; James R Brown

2007-01-01

70

Tuberculosis Epidemiology and Selection in an Autochthonous Siberian Population from the 16th  

E-print Network

Tuberculosis Epidemiology and Selection in an Autochthonous Siberian Population from the 16th -19th, Yakutsk, Russia Abstract Tuberculosis is one of most ancient diseases affecting human populations identification of ancient tuberculosis strains remains rare. Here, we describe a study of 140 ancient subjects

Paris-Sud XI, Université de

71

Research review paper Point-of-care assays for tuberculosis: Role of nanotechnology/microfluidics  

E-print Network

Research review paper Point-of-care assays for tuberculosis: Role of nanotechnology Keywords: Tuberculosis Point-of-care Nanotechnology Microfluidics Tuberculosis (TB) remains one of the most for TB diagnosis, and highlight the recent advances in nanotechnology and microfluidics that potentially

Demirci, Utkan

72

RAPID TEST FOR SEROLOGICAL DETECTION OF TUBERCULOSIS IN MULTIPLE ANIMAL SPECIES  

Technology Transfer Automated Retrieval System (TEKTRAN)

Tuberculosis remains a serious re-emerging disease in wildlife and zoo animals, as various species are susceptible to Mycobacterium bovis and/or M. tuberculosis. To improve tuberculosis control, new diagnostic tools that would be rapid, accurate, and host species-independent are needed. We propose n...

73

Diagnosis of Childhood Tuberculosis and Host RNA Expression in Africa  

PubMed Central

BACKGROUND Improved diagnostic tests for tuberculosis in children are needed. We hypothesized that transcriptional signatures of host blood could be used to distinguish tuberculosis from other diseases in African children who either were or were not infected with the human immunodeficiency virus (HIV). METHODS The study population comprised prospective cohorts of children who were undergoing evaluation for suspected tuberculosis in South Africa (655 children), Malawi (701 children), and Kenya (1599 children). Patients were assigned to groups according to whether the diagnosis was culture-confirmed tuberculosis, culture-negative tuberculosis, diseases other than tuberculosis, or latent tuberculosis infection. Diagnostic signatures distinguishing tuberculosis from other diseases and from latent tuberculosis infection were identified from genomewide analysis of RNA expression in host blood. RESULTS We identified a 51-transcript signature distinguishing tuberculosis from other diseases in the South African and Malawian children (the discovery cohort). In the Kenyan children (the validation cohort), a risk score based on the signature for tuberculosis and for diseases other than tuberculosis showed a sensitivity of 82.9% (95% confidence interval [CI], 68.6 to 94.3) and a specificity of 83.6% (95% CI, 74.6 to 92.7) for the diagnosis of culture-confirmed tuberculosis. Among patients with cultures negative for Mycobacterium tuberculosis who were treated for tuberculosis (those with highly probable, probable, or possible cases of tuberculosis), the estimated sensitivity was 62.5 to 82.3%, 42.1 to 80.8%, and 35.3 to 79.6%, respectively, for different estimates of actual tuberculosis in the groups. In comparison, the sensitivity of the Xpert MTB/RIF assay for molecular detection of M. tuberculosis DNA in cases of culture-confirmed tuberculosis was 54.3% (95% CI, 37.1 to 68.6), and the sensitivity in highly probable, probable, or possible cases was an estimated 25.0 to 35.7%, 5.3 to 13.3%, and 0%, respectively; the specificity of the assay was 100%. CONCLUSIONS RNA expression signatures provided data that helped distinguish tuberculosis from other diseases in African children with and those without HIV infection. (Funded by the European Union Action for Diseases of Poverty Program and others). PMID:24785206

Banwell, Claire M.; Chagaluka, George; Crampin, Amelia C.; Dockrell, Hazel M.; French, Neil; Hamilton, Melissa S.; Hibberd, Martin L.; Kern, Florian; Langford, Paul R.; Ling, Ling; Mlotha, Rachel; Ottenhoff, Tom H.M.; Pienaar, Sandy; Pillay, Vashini; Scott, J. Anthony G.; Twahir, Hemed; Wilkinson, Robert J.

2014-01-01

74

Point Prevalence and Incidence of Mycobacterium tuberculosis complex in captive elephants in the United States  

PubMed Central

Background Captive elephants infected with tuberculosis are implicated as an occupational source of zoonotic tuberculosis. However, accurate estimates of prevalence and incidence of elephant tuberculosis from well-defined captive populations are lacking in the literature. Studies published in recent years contain a wide range of prevalence estimates calculated from summary data. Incidence estimates of elephant tuberculosis in captive elephants are not available. Objective This study estimated the annual point prevalence, annual incidence, cumulative incidence, and incidence density of tuberculosis in captive elephants within the USA during the past 52 years. Animals and Methods We combined existing elephant census records from captive elephants in the USA with tuberculosis culture results obtained from trunk washes or at necropsy. This data set included 15 years where each elephant was screened annually. Results Between 1960 and 1996, the annual point prevalence of tuberculosis complex mycobacteria for both species was 0. From 1997 through 2011, the median point prevalence within the Asian elephant population was 5.1%, with a range from 0.3% to 6.7%. The incidence density was 9.7 cases/1000 elephant years (95% CI: 7.0–13.4). In contrast, the annual point prevalence during the same time period within the African elephant population remained 0 and the incidence density was 1.5 cases/1000 elephant years (95% CI: 0.7–4.0). Conclusions The apparent increase in new cases noted after 1996 resulted from a combination of both index cases and the initiation of mandatory annual tuberculosis complex (MTBC) screening in 1997 for all the elephants. This study found lower annual point prevalence estimates than previously reported in the literature. These discrepancies in prevalence estimates are primarily due to differences in terminology and calculation methods. Using the same intensive testing regime, the incidence of tuberculosis differed significantly between Asian and African elephants. Clinical Importance Accurate and species specific knowledge of prevalence and incidence will inform our efforts to mitigate occupational risks associated with captive elephants in the USA. PMID:23477422

Feldman, Melissa; Isaza, Ramiro; Prins, Cindy; Hernandez, Jorge

2013-01-01

75

Gr1intCD11b+ Myeloid-Derived Suppressor Cells in Mycobacterium tuberculosis Infection  

PubMed Central

Background Tuberculosis is one of the world’s leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1intCD11b+ cells are called myeloid-derived suppressor cells (MDSC) and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design. Methodology/Principal Findings We compared the bacterial burden, lung pathology and Gr1intCD11b+ myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1+ cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1+CD11b+ cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1hi and Gr1int populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1int populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1hi and Gr1int cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4+ T to Gr1+ cells increased. Our results illustrate a yet unrecognized interplay between Gr1+ cells and CD4+ T cells in tuberculosis. PMID:24224058

Obregón-Henao, Andrés; Henao-Tamayo, Marcela; Orme, Ian M.; Ordway, Diane J.

2013-01-01

76

TB Research at UT-Houston – A review of cord factor: new approaches to drugs, vaccines and the pathogenesis of tuberculosis  

Microsoft Academic Search

Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain

Robert L. Hunter; Lisa Armitige; Chinnaswamy Jagannath; Jeffrey K. Actor

2009-01-01

77

Challenges in tuberculosis management in Peru and England.  

PubMed

Tuberculosis (TB) is a serious but preventable and largely treatable disease caused by the bacterium Mycobacterium tuberculosis. Although there is evidence that the UK incidence remains stable, rates of the disease, particularly in some London boroughs, remain high, earning it the unenviable title of the 'tuberculosis capital of Europe'. In March 2014 Public Health England published a consultation document on a collaborative strategy for tackling tuberculosis in England. This highlights a growing concern surrounding the issue. In the 1990s, Peru's tuberculosis epidemic saw the country listed among the Pan-American Health Organisation's top 23 countries of heaviest burden. Since then overall rates, although remaining significantly higher than those of the UK, have fallen dramatically. This article uses the observations of a BSc Nursing student undertaking an international elective in Peru to highlight some of the challenges faced by nurses in managing TB and draws parallels with those faced in the UK. PMID:25382081

Ivany, Elena; Boulton, Jacqueline

2014-11-01

78

Transmission of Mycobacterium tuberculosis between Farmers and Cattle in Central Ethiopia  

PubMed Central

Background Transmission of Mycobacterium tuberculosis (M. tuberculosis) complex could be possible between farmers and their cattle in Ethiopia. Methodology/Principal Findings A study was conducted in mixed type multi-purposes cattle raising region of Ethiopia on 287 households (146 households with case of pulmonary tuberculosis (TB) and 141 free of TB) and 287 herds consisting of 2,033 cattle belonging to these households to evaluate transmission of TB between cattle and farmers. Interview, bacteriological examinations and molecular typing were used for human subjects while comparative intradermal tuberculin (CIDT) test, post mortem and bacteriological examinations, and molecular typing were used for animal studies. Herd prevalence of CIDT reactors was 9.4% and was higher (p<0.01) in herds owned by households with TB than in herds owned by TB free households. Animal prevalence was 1.8% and also higher (p<0.01) in cattle owned by households with TB case than in those owned by TB free households. All mycobacteria (141) isolated from farmers were M. tuberculosis, while only five of the 16 isolates from cattle were members of the M. tuberculosis complex (MTC) while the remaining 11 were members of non-tuberculosis mycobacteria (NTM). Further speciation of the five MTC isolates showed that three of the isolates were M. bovis (strain SB1176), while the remaining two were M. tuberculosis strains (SIT149 and SIT53). Pathology scoring method described by “Vordermeier et al. (2002)” was applied and the average severity of pathology in two cattle infected with M. bovis, in 11 infected with NTM and two infected with M. tuberculosis were 5.5, 2.1 and 0.5, respectively. Conclusions/Significance The results showed that transmission of TB from farmers to cattle by the airborne route sensitizes the cows but rarely leads to TB. Similarly, low transmission of M. bovis between farmers and their cattle was found, suggesting requirement of ingestion of contaminated milk from cows with tuberculous mastitis. PMID:24130804

Ameni, Gobena; Tadesse, Konjit; Hailu, Elena; Deresse, Yohannes; Medhin, Girmay; Aseffa, Abraham; Hewinson, Glyn; Vordermeier, Martin; Berg, Stefan

2013-01-01

79

Evolution and Diversity of Clonal Bacteria: The Paradigm of Mycobacterium tuberculosis  

E-print Network

Evolution and Diversity of Clonal Bacteria: The Paradigm of Mycobacterium tuberculosis Tiago Dos, Faculte´ de Me´dicine, Universite´ Paris V, Paris, France Background. Mycobacterium tuberculosis complexR) genes in a comprehensive selection of M. tuberculosis complex strains from across the world

Paris-Sud XI, Université de

80

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis  

E-print Network

tuberculosis H37Rv and the b-Ketoacyl-ACP Synthase mtFabH Qosay Al-Balas1 , Nahoum G. Anthony1 , Bilal Al of Birmingham, Edgebaston, Birmingham, United Kingdom Abstract Background: Tuberculosis (TB) is a disease which. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance

81

Modeling the Impact of Tuberculosis Control Strategies in Highly Endemic Overcrowded Prisons  

E-print Network

Modeling the Impact of Tuberculosis Control Strategies in Highly Endemic Overcrowded Prisons Judith, Fundac¸a~o Oswaldo Cruz, Rio de Janeiro, Brasil Abstract Background: Tuberculosis (TB) in prisons (2008) Modeling the Impact of Tuberculosis Control Strategies in Highly Endemic Overcrowded Prisons. PLo

82

Surveillance of pyrazinamide susceptibility among multidrug-resistant Mycobacterium tuberculosis isolates from Siriraj Hospital, Thailand  

Microsoft Academic Search

BACKGROUND: Susceptibility testing of pyrazinamide (PZA) against Mycobacterium tuberculosis is difficult to perform because the acidity of culture medium that is required for drug activity also inhibits the growth of bacteria. In Thailand, very limited information has been generated on PZA resistance, particularly among multidrug-resistant tuberculosis (MDR-TB) isolated from Thailand. Only two studies on PZA susceptibility among Thai M. tuberculosis

Jirarut Jonmalung; Therdsak Prammananan; Manoon Leechawengwongs; Angkana Chaiprasert

2010-01-01

83

Mycobacterium tuberculosis from chronic murine infections that grows in liquid but not on solid medium  

Microsoft Academic Search

BACKGROUND: Old, stationary cultures of Mycobacterium tuberculosis contain a majority of bacteria that can grow in broth cultures but cannot grow on solid medium plates. These may be in a non-replicating, dormant growth phase. We hypothesised that a similar population might be present in chronic, murine tuberculosis. METHODS: Estimates of the numbers of viable M. tuberculosis, strain H37Rv, in the

Jasvir Dhillon; Douglas B Lowrie; Denis A Mitchison

2004-01-01

84

Genetic Diversity of Mycobacterium tuberculosis in Peru and Exploration of Phylogenetic Associations with Drug  

E-print Network

Genetic Diversity of Mycobacterium tuberculosis in Peru and Exploration of Phylogenetic of America Abstract Background: There is limited available data on the strain diversity of M tuberculosis: Spoligotyping was undertaken on 794 strains of M tuberculosis collected between 1999 and 2005 from 553 community

Paris-Sud XI, Université de

85

Characterisation of methionine adenosyltransferase from Mycobacterium smegmatis and M. tuberculosis  

PubMed Central

Background Tuberculosis remains a serious world-wide health threat which requires the characterisation of novel drug targets for the development of future antimycobacterials. One of the key obstacles in the definition of new targets is the large variety of metabolic alterations that occur between cells in the active growth and chronic/dormant phases of tuberculosis. The ideal biochemical target should be active in both growth phases. Methionine adenosyltransferase, which catalyses the formation of S-adenosylmethionine from methionine and ATP, is involved in polyamine biosynthesis during active growth and is also required for the methylation and cyclopropylation of mycolipids necessary for survival in the chronic phase. Results The gene encoding methionine adenosyltransferase has been cloned from Mycobacterium tuberculosis and the model organism M. smegmatis. Both enzymes retained all amino acids known to be involved in catalysing the reaction. While the M. smegmatis enzyme could be functionally expressed, the M. tuberculosis homologue was insoluble and inactive under a large variety of expression conditions. For the M. smegmatis enzyme, the Vmax for S-adenosylmethionine formation was 1.30 ?mol/min/mg protein and the Km for methionine and ATP was 288 ?M and 76 ?M respectively. In addition, the enzyme was competitively inhibited by 8-azaguanine and azathioprine with a Ki of 4.7 mM and 3.7 mM respectively. Azathioprine inhibited the in vitro growth of M. smegmatis with a minimal inhibitory concentration (MIC) of 500 ?M, while the MIC for 8-azaguanine was >1.0 mM. Conclusion The methionine adenosyltransferase from both organisms had a primary structure very similar those previously characterised in other prokaryotic and eukaryotic organisms. The kinetic properties of the M. smegmatis enzyme were also similar to known prokaryotic methionine adenosyltransferases. Inhibition of the enzyme by 8-azaguanine and azathioprine provides a starting point for the synthesis of higher affinity purine-based inhibitors. PMID:12809568

Berger, Bradley J; Knodel, Marvin H

2003-01-01

86

Mycobacterium tuberculosis is the causative agent of tuberculosis in the southern ecological zones of Cameroon, as shown by genetic analysis  

PubMed Central

Background Tuberculosis (TB) is a major cause of mortality and suffering worldwide, with over 95% of TB deaths occurring in low- and middle-income countries. In recent years, molecular typing methods have been widely used in epidemiological studies to aid the control of TB, but this usage has not been the case with many African countries, including Cameroon. The aims of the present investigation were to identify and evaluate the diversity of the Mycobacterium tuberculosis complex (MTBC) isolates circulating in two ecological zones of Cameroon, seven years after the last studies in the West Region, and after the re-organization of the National TB Control Program (NTBCP). These were expected to shed light also on the transmission of TB in the country. The study was conducted from February to July 2009. During this period, 169 patients with symptomatic disease and with sputum cultures that were positive for MTBC were randomly selected for the study from amongst 964 suspected patients in the savannah mosaic zone (West and North West regions) and the tropical rainforest zone (Central region). After culture and diagnosis, DNA was extracted from each of the MTBC isolates and transported to the BecA-ILRI Hub in Nairobi, Kenya for molecular analysis. Methods Genetic characterization was done by mycobacterial interspersed repetitive unit–variable number tandem repeat typing (MIRU-VNTR) and Spoligotyping. Results Molecular analysis showed that all TB cases reported in this study were caused by infections with Mycobacterium tuberculosis (98.8%) and Mycobacterium africanum (M. africanum) (1.2%) respectively. We did not detect any M. bovis. Comparative analyses using spoligotyping revealed that the majority of isolates belong to major clades of M. tuberculosis: Haarlem (7.6%), Latin American-Mediterranean (34.4%) and T clade (26.7%); the remaining isolates (31.3%) where distributed among the minor clades. The predominant group of isolates (34.4%) corresponded to spoligotype 61, previously described as the “Cameroon family. Further analysis based on MIRU-VNTR profiles had greater resolving power than spoligotyping and defined additional genotypes in the same spoligotype cluster. Conclusion The molecular characterization of MTBC strains from humans in two ecological regions of Cameroon has shown that M. tuberculosis sensu stricto is the predominant agent of TB cases in the zones. Three decades ago, TB was reported to be caused by M. africanum in 56.0% of cases. The present findings are consistent with a major shift in the prevalence of M. tuberculosis in Cameroon. PMID:24028382

2013-01-01

87

GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosis metabolism  

Microsoft Academic Search

BACKGROUND: An impediment to the rational development of novel drugs against tuberculosis (TB) is a general paucity of knowledge concerning the metabolism of Mycobacterium tuberculosis, particularly during infection. Constraint-based modeling provides a novel approach to investigating microbial metabolism but has not yet been applied to genome-scale modeling of M. tuberculosis. RESULTS: GSMN-TB, a genome-scale metabolic model of M. tuberculosis, was

Tracy Hooper; Graham Stewart; Bhushan Bonde; Claudio Avignone-Rossa; Michael E Bushell; Paul Wheeler; Steffen Klamt; Andrzej M Kierzek; Johnjoe McFadden

2007-01-01

88

Hysterosalpingographic Appearances of Female Genital Tract Tuberculosis: Part II: Uterus  

PubMed Central

Female genital tuberculosis remains as a major cause of tubal obstruction leading to infertility, especially in developing countries. The global prevalence of genital tuberculosis has increased during the past two decades due to increasing acquired immunodeficiency syndrome. Genital tuberculosis (TB) is commonly asymptomatic and it is diagnosed during infertility investigations. Despite of recent advances in imaging tools such as computed tomography (CT) scan, magnetic resonance imaging (MRI) and ultrasongraphy, hysterosalpinography has been considered as the standard screening test for evaluation of tubal infertility and as a valuable tool for diagnosis of female genital tuberculosis. Tuberculosis gives rise to various appearances on hysterosalpingography (HSG) from non-specific changes to specific findings. The present pictorial review illustrates and describes specific and non-specific radiographic features of female genital tuberculosis in two parts. Part I presents specific findings of tuberculosis related to tubes such as "beaded tube", "golf club tube", "pipestem tube", "cobble stone tube" and the "leopard skin tube". Part II will describe adverse effects of tuberculosis on structure of endometrium and radiological specific findings, such as "T-shaped" tuberculosis uterus, "pseudo-unicornuate "uterus, "collar-stud abscess" and "dwarfed" uterus with lymphatic intravasation and occluded tubes which have not been encountered in the majority of non-tuberculosis cases. PMID:24696765

Ahmadi, Firoozeh; Zafarani, Fatemeh; Shahrzad, Gholam Shahrzad

2014-01-01

89

Clinical presentation of abdominal tuberculosis in HIV seronegative adults  

Microsoft Academic Search

BACKGROUND: The accurate diagnosis of abdominal tuberculosis usually takes a long time and requires a high index of suspicion in clinic practice. Eighty-eight immune-competent patients with abdominal tuberculosis were grouped according to symptoms at presentation and followed prospectively in order to investigate the effect of symptomatic presentation on clinical diagnosis and prognosis. METHODS: Based upon the clinical presentation, the patients

Cengiz Bolukbas; Fusun F Bolukbas; Tulin Kendir; Remzi A Dalay; Nihat Akbayir; Mehmet H Sokmen; Ali T Ince; Mithat Guran; Erkan Ceylan; Guray Kilic; Oya Ovunc

2005-01-01

90

Portrait of a Pathogen: The Mycobacterium tuberculosis Proteome In Vivo  

Microsoft Academic Search

BackgroundMycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is a facultative intracellular pathogen that can persist within the host. The bacteria are thought to be in a state of reduced replication and metabolism as part of the chronic lung infection. Many in vitro studies have dissected the hypothesized environment within the infected lung, defining the bacterial response to pH,

Nicole A. Kruh; Jolynn Troudt; Angelo Izzo; Jessica Prenni; Karen M. Dobos; Ramy K. Aziz

2010-01-01

91

Vitamin A Supplementary Effect on Immunologic Profiles in Tuberculosis Patients  

Microsoft Academic Search

Background: The effects of vitamins on human immune system have been well studied. Vitamin A deficiency and its effects on immune system in pulmonary tuberculosis (TB) patients have been established. This study was carried out to evaluate vitamin A supplementary effect on immunologic profile of tuberculosis patients. Materials and Methods: In a double-blind clinical trial, thirty-five patients with confirmed pulmonary

Somayeh Mohammadian; Jalil Baghdadchi; Ali Reza; Ostad Rahimi; Shahpour Shahghasempour; Majid Valiollahpour Amiri; Foroozan Mohammadi; Seyed Mehdi Mirsaiedi; Ali Akbar Velayati

92

Tuberculosis diagnostics: Challenges and opportunities.  

PubMed

Tuberculosis (TB) has been a disease affecting almost all parts of the world since ages. Lot many efforts came in the past for improving diagnosis and treatment. Also, an effective vaccine has been sought after for long. With the emergence of resistant strains of Mycobacterium tuberculosis, the causal organisms of tuberculosis, and complexities emerging due to other associated infections and disease conditions, there is a desperate need for further research input in the field. Be it the better medication and care or better resistance management, proper diagnostics holds the key to success. It has been observed that a high burden of the disease was accompanied by resource limitations and poor research set-up. The scenario remained like this for several decades. With the refreshed vision of resourceful countries and funding agencies, funding is being provided in many areas of research in tuberculosis diagnosis and treatment. This review has been written with an aim to bring forth the limitations of available methods in the field of diagnostics and making researchers aware about the changing scenario with better funding opportunities and support. The author visualizes an enthusiasm from all over the world for the development of better modalities and urges scientists to join the struggle at this very perfect time to take the challenge and come forward with innovations in this field. PMID:22919166

Nema, Vijay

2012-07-01

93

[A tuberculosis epidemic in one hospital].  

PubMed

A Tuberculosis epidemic occurred in a hospital in Fukushima prefecture, 1993. It was detected after the diagnosis of two tuberculosis cases among nurses working in the hospital. A contact survey in the hospital revealed two another cases of tuberculosis, one from the nurse, and the other one from the patient admitted to the hospital. In addition, two more nurses in the same hospital were suspected of having tuberculosis, but they do not yet started treatment by the time of the survey. Though the source of the infection could not be identified, the doctor's delay in detecting cases was suspected on the background of the epidemic. Deficiency in the health care system of nursing school was also suspected. PMID:8523850

Yamaguchi, Y; Suzuki, S

1995-10-01

94

Interpreting measures of tuberculosis transmission: a case study on the Portuguese population  

PubMed Central

Background Tuberculosis remains a high burden for Human society despite considerable investments in its control. Unique features in the history of infection and transmission dynamics of tuberculosis pose serious limitations on the direct interpretation of surveillance data and call for models that incorporate latent processes and simulate specific interventions. Methods A transmission model was adjusted to the dataset of active tuberculosis cases reported in Portugal between 2002 and 2009. We estimated key transmission parameters from the data (i.e. time to diagnosis, treatment length, default proportion, proportion of pulmonary TB cases). Using the adjusted model to the Portuguese case, we estimated the total burden of tuberculosis in Portugal. We further performed sensitivity analysis to heterogeneities in susceptibility to infection and exposure intensity. Results We calculated a mean time to diagnose of 2.81 months and treatment length of 8.80 months in Portugal. The proportion defaulting treatment was calculated as 0.04 and the proportion of pulmonary cases as 0.75. Using these values, we estimated a TB burden of 1.6 million infected persons, corresponding to more than 15% of the Portuguese population. We further described the sensitivity of these estimates to heterogeneity. Conclusions We showed that the model reproduces well the observed dynamics of the Portuguese data, thus demonstrating its adequacy for devising control strategies for TB and predicting the effects of interventions. PMID:24941996

2014-01-01

95

Genetic Polymorphism in Mycobacterium tuberculosis Isolates from Patients with Chronic Multidrug?Resistant Tuberculosis  

Microsoft Academic Search

Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem because treatment is complicated, cure rates are well below those for drug-susceptible tuberculosis (TB), and patients may remain infectious for months or years, despite receiving the best available therapy. To gain a better understanding of MDR-TB, we characterized serial isolates recovered from 13 human immunodeficiency virus-negative patients with MDR- TB, by

Barun Mathema; Karen Shean; Elena Shashkina; Gilla Kaplan

2004-01-01

96

Nosocomial transmission of Mycobacterium tuberculosis in kangaroo mother care units: A risk in tuberculosis-endemic areas  

Microsoft Academic Search

Background and aim: Kangaroo mother care (KMC) has become the standard of care for low-risk preterm babies born in developing countries. However, the potential risk of nosocomial transmission of Mycobacterium tuberculosis within KMC units, particularly in tuberculosis-endemic areas, has not been explored. We report an infant (sentinel case) who was admitted to our paediatric intensive care unit (PICU) with extensive

Louis Heyns; Robert P. Gie; Pierre Goussard; Nulda Beyers; Rob M. Warren; Ben J. Marais

2006-01-01

97

Multicentric Spinal Tuberculosis with Sternoclavicular Joint Involvement: A Rare Presentation  

PubMed Central

Background. Tuberculosis is a chronic disease which may have varied presentations. Though pulmonary tuberculosis is the commonest, extrapulmonary tuberculosis involving skeletal system is often seen. Individuals with poor nourishment and immunological status are especially susceptible for disseminated and multicentric tuberculosis. Case Report. We here present a case of tuberculosis involving multiple anatomical locations in an immune-competent patient which was diagnosed with radiological studies and confirmed with histological examination. Patient was put on multidrug antitubercular therapy and responded well to the treatment with improvement in clinical and radiological picture. Clinical Relevance. This report of a rare case makes us aware of the varied presentations which tuberculosis can present with. It should be kept as a differential diagnosis in patients with cough and fever but not responding to conventional treatment. This is even more important in countries with poor socioeconomic conditions. PMID:25389505

Meena, Umesh Kumar; Meena, Ramesh Chand

2014-01-01

98

Play the Tuberculosis Game  

MedlinePLUS

... Questionnaire Tuberculosis Play Tuberculosis Experiments & Discoveries About the game Discover and experience some of the classic methods ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

99

Male breast tuberculosis.  

PubMed Central

Tuberculosis of the breast is rare and tuberculosis of the male breast is not a recognised entity. We describe a man with tuberculosis of the breast which was clinically thought to be a malignancy. Images Figure 1 Figure 2 PMID:9338032

Jaideep, C.; Kumar, M.; Khanna, A. K.

1997-01-01

100

Tuberculosis: Medico-Legal Aspects  

PubMed Central

Tuberculosis is a diffusive infectious disease whose typical behaviour differentiates it from other infectious diseases spread by human-to-human transmission (flu, chicken pox, cholera, etc.) that follow a classic epidemic pattern. Indeed, in the presence of a known source of Koch bacilli that is capable of spreading the bacteria by air, not all exposed individuals inhale the bacteria, not all those who inhale them absorb them, not all those who absorb the bacteria are unable to eliminate them, not all who are able to eliminate them do so using delayed hypersensitivity, not all those who react with delayed hypersensitivity suffer lasting tissue damage (among other things, minor), not all who suffer tissue damage have anatomical sequelae, and not all those who have anatomical sequelae, however minimal, become carriers of bacilli in the latent period. The vast majority (90–95%) of the latter – which are in any case a portion, not the totality of those exposed – remain asymptomatic throughout their lives and never develop active tuberculosis. Based on these biological characteristics and the legal concepts of “epidemic” and “disease,” it becomes highly problematic, if not impossible, to assert both that tuberculosis can cause events of sufficient magnitude to be associated with the crime of “epidemic,” and that the mere diagnosis of a latent tuberculosis infection is sufficient to assume the presence of an illness legally prosecutable in criminal proceedings or a disability prosecutable in civil proceedings. Furthermore, clinically apparent tuberculosis is a temporarily—and in some cases permanently—disabling condition, and in certain work environments, even with the difficulties caused by the lack of available effective diagnostic tools and the insidious behaviour of the disease in the early stages, targeted monitoring to identify other persons who may become ill is appropriate. PMID:24804006

Vetrugno, G.; De-Giorgio, F.; D’Alessandro, F.; Scafetta, I.; Berloco, F.; Buonsenso, D.; Abbate, F.; Scalise, G.; Pascali, V.L.; Valentini, P

2014-01-01

101

The interface between the national tuberculosis control programme and district hospitals in Cameroon: missed opportunities for strengthening the local health system –a multiple case study  

PubMed Central

Background Tuberculosis remains a major public health problem in sub-Saharan Africa. District hospitals (DHs) play a central role in district-based health systems, and their relation with vertical programmes is very important. Studies on the impact of vertical programmes on DHs are rare. This study aims to fill this gap. Its purpose is to analyse the interaction between the National Tuberculosis Control Programme (NTCP) and DHs in Cameroon, especially its effects on the human resources, routine health information system (HIS) and technical capacity at the hospital level. Methods We used a multiple case study methodology. From the Adamaoua Region, we selected two DHs, one public and one faith-based. We collected qualitative and quantitative data through document reviews, semi-structured interviews with district and regional staff, and observations in the two DHs. Results The NTCP trained and supervised staff, designed and provided tuberculosis data collection and reporting tools, and provided anti-tuberculosis drugs, reagents and microscopes to DHs. However, these interventions were limited to the hospital units designated as Tuberculosis Diagnostic and Treatment Centres and to staff dedicated to tuberculosis control activities. The NTCP installed a parallel HIS that bypassed the District Health Services. The DH that performs well in terms of general hospital care and that is well managed was successful in tuberculosis control. Based on the available resources, the two hospitals adapt the organisation of tuberculosis control to their settings. The management teams in charge of the District Health Services are not involved in tuberculosis control. In our study, we identified several opportunities to strengthen the local health system that have been missed by the NTCP and the health system managers. Conclusion Well-managed DHs perform better in terms of tuberculosis control than DHs that are not well managed. The analysis of the effects of the NTCP on the human resources, HIS and technical capacity of DHs indicates that the NTCP supports, rather than strengthens, the local health system. Moreover, there is potential for this support to be enhanced. Positive synergies between the NTCP and district health systems can be achieved if opportunities to strengthen the district health system are seized. The question remains, however, of why managers do not take advantage of the opportunities to strengthen the health system. PMID:23521866

2013-01-01

102

[Advantages and drawbacks of expectoration decontamination methods for tuberculosis and anti-tuberculosis drug resistance diagnosis].  

PubMed

In the actual context of increasing tuberculosis and anti-tuberculosis drug resistance, the laboratory diagnosis of Mycobacterial infections remain the primordial objective of control and surveillance of human tuberculosis. The diagnosis and following of tuberculosis in resource limited settings are done by microscopy Ziehl-Neelsen method which is poor sensitive (20-53%) and have poor specificity because it's can't distinguish tuberculosis mycobacterium and atypical tuberculoid mycobacterium. Mycobacterium culture on solid media is the gold standard method for tuberculosis and anti-tuberculosis drug resistance diagnosis. Here, the challenge is that expectorations using for culture contain mycobacterium and others contaminating bacteria responsible of culture contamination. Many different methods of homogenization and decontamination of sputum specimens for culturing exist and each laboratory had to do a choice of the better method to optimize isolating of mycobacterium. This review is a summary of homogenization and decontamination methods described in literature and used by certain laboratories for diagnosis of TB by culture. However, it's essential for each laboratory to conduct evaluation of the different methods and do the choice of the appropriate one by taking into account factors such as the feasibility and cost effectively. Nine methods of decontaminations are described in this review taking account of their advantages, drawbacks and their feasibility in resource limited settings. PMID:23747665

Zingué, Dezemon; Hien, Hervé; Méda, Nicolas; Zida, Sylvie; Kaboré, Antoinette; Sanou, Adama; Ouédraogo, Abdoul-Salam; Gomgnimbou, Michel; Diandé, Souba; Tarnagda, Zékiba; Godreuil, Sylvain

2013-01-01

103

Interferon-? Release Assays for the Diagnosis of Tuberculosis and Tuberculosis Infection in HIV-Infected Adults: A Systematic Review and Meta-Analysis  

PubMed Central

Background Despite the widespread use of interferon-? release assays (IGRAs), their role in diagnosing tuberculosis and targeting preventive therapy in HIV-infected patients remains unclear. We conducted a comprehensive systematic review to contribute to the evidence-based practice in HIV-infected people. Methodology/Principal Findings We searched MEDLINE, Cochrane, and Biomedicine databases to identify articles published between January 2005 and July 2011 that assessed QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-SPOT®.TB (T-SPOT.TB) in HIV-infected adults. We assessed their accuracy for the diagnosis of tuberculosis and incident active tuberculosis, and the proportion of indeterminate results. The search identified 38 evaluable studies covering a total of 6514 HIV-infected participants. The pooled sensitivity and specificity for tuberculosis were 61% and 72% for QFT-GIT, and 65% and 70% for T-SPOT.TB. The cumulative incidence of subsequent active tuberculosis was 8.3% for QFT-GIT and 10% for T-SPOT.TB in patients tested positive (one study each), and 0% for QFT-GIT (two studies) and T-SPOT.TB (one study) respectively in those tested negative. Pooled indeterminate rates were 8.2% for QFT-GIT and 5.9% for T-SPOT.TB. Rates were higher in high burden settings (12.0% for QFT-GIT and 7.7% for T-SPOT.TB) than in low-intermediate burden settings (3.9% for QFT-GIT and 4.3% for T-SPOT.TB). They were also higher in patients with CD4+ T-cell count <200 (11.6% for QFT-GIT and 11.4% for T-SPOT.TB) than in those with CD4+ T-cell count ?200 (3.1% for QFT-GIT and 7.9% for T-SPOT.TB). Conclusions/Significance IGRAs have suboptimal accuracy for confirming or ruling out active tuberculosis disease in HIV-infected adults. While their predictive value for incident active tuberculosis is modest, a negative QFT-GIT implies a very low short- to medium-term risk. Identifying the factors associated with indeterminate results will help to optimize the use of IGRAs in clinical practice, particularly in resource-limited countries with a high prevalence of HIV-coinfection. PMID:22403663

Santin, Miguel; Muñoz, Laura; Rigau, David

2012-01-01

104

Tuberculosis: evidence review for newly arriving immigrants and refugees  

PubMed Central

Background: The foreign-born population bears a disproportionate health burden from tuberculosis, with a rate of active tuberculosis 20 times that of the non-Aboriginal Canadian-born population, and could therefore benefit from tuberculosis screening programs. We reviewed evidence to determine the burden of tuberculosis in immigrant populations, to assess the effectiveness of screening and treatment programs for latent tuberculosis infection, and to identify potential interventions to improve effectiveness. Methods: We performed a systematic search for evidence of the burden of tuberculosis in immigrant populations and the benefits and harms, applicability, clinical considerations, and implementation issues of screening and treatment programs for latent tuberculosis infection in the general and immigrant populations. The quality of this evidence was assessed and ranked using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). Results: Chemoprophylaxis with isoniazid is highly efficacious in decreasing the development of active tuberculosis in people with latent tuberculosis infection who adhere to treatment. Monitoring for hepatotoxicity is required at all ages, but close monitoring is required in those 50 years of age and older. Adherence to screening and treatment for latent tuberculosis infection is poor, but it can be increased if care is delivered in a culturally sensitive manner. Interpretation: Immigrant populations have high rates of active tuberculosis that could be decreased by screening for and treating latent tuberculosis infection. Several patient, provider and infrastructure barriers, poor diagnostic tests, and the long treatment course, however, limit effectiveness of current programs. Novel approaches that educate and engage patients, their communities and primary care practitioners might improve the effectiveness of these programs. PMID:20634392

Greenaway, Christina; Sandoe, Amelia; Vissandjee, Bilkis; Kitai, Ian; Gruner, Doug; Wobeser, Wendy; Pottie, Kevin; Ueffing, Erin; Menzies, Dick; Schwartzman, Kevin

2011-01-01

105

RAPID LATERAL-FLOW FOR BOVINE TUBERCULOSIS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Bovine tuberculosis remains a costly disease in many countries despite extensive eradication and control efforts. Multiple wildlife reservoirs of Mycobacterium bovis infection found in recent decades in the US, Europe, New Zealand, and South Africa play important roles fuelling high rates of disease...

106

Tuberculosis Facts - Exposure to TB  

MedlinePLUS

... STD, and TB Prevention Division of Tuberculosis Elimination Tuberculosis (TB) Facts Exposure to TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ...

107

Tuberculosis in the lung (image)  

MedlinePLUS

Tuberculosis is caused by a group of organisms Mycobacterium tuberculosis, M. bovis, M. africanum and a few other rarer subtypes. Tuberculosis usually appears as a lung (pulmonary) infection. However, ...

108

Tuberculosis Facts - Testing for TB  

MedlinePLUS

... STD, and TB Prevention Division of Tuberculosis Elimination Tuberculosis (TB) Facts Testing for TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ...

109

Molecular Epidemiology, Drug Susceptibility and Economic Aspects of Tuberculosis in Mubende District, Uganda  

PubMed Central

Background Tuberculosis (TB) remains a global public health problem whose effects have major impact in developing countries like Uganda. This study aimed at investigating genotypic characteristics and drug resistance profiles of Mycobacterium tuberculosis isolated from suspected TB patients. Furthermore, risk factors and economic burdens that could affect the current control strategies were studied. Methods TB suspected patients were examined in a cross-sectional study at the Mubende regional referral hospital between February and July 2011. A questionnaire was administered to each patient to obtain information associated with TB prevalence. Isolates of M. tuberculosis recovered during sampling were examined for drug resistance to first line anti-TB drugs using the BACTEC-MGIT960TMsystem. All isolates were further characterized using deletion analysis, spoligotyping and MIRU-VNTR analysis. Data were analyzed using different software; MIRU-VNTR plus, SITVITWEB, BioNumerics and multivariable regression models. Results M. tuberculosis was isolated from 74 out of 344 patients, 48 of these were co-infected with HIV. Results from the questionnaire showed that previously treated TB, co-infection with HIV, cigarette smoking, and overcrowding were risk factors associated with TB, while high medical related transport bills were identified as an economic burden. Out of the 67 isolates that gave interpretable results, 23 different spoligopatterns were detected, nine of which were novel patterns. T2 with the sub types Uganda-I and Uganda-II was the most predominant lineage detected. Antibiotic resistance was detected in 19% and multidrug resistance was detected in 3% of the isolates. Conclusion The study detected M. tuberculosis from 21% of examined TB patients, 62% of whom were also HIV positive. There is a heterogeneous pool of genotypes that circulate in this area, with the T2 lineage being the most predominant. High medical related transport bills and drug resistance could undermine the usefulness of the current TB strategic interventions. PMID:23741382

Muwonge, Adrian; Malama, Sydney; Johansen, Tone B.; Kankya, Clovice; Biffa, Demelash; Ssengooba, Willy; Godfroid, Jacques; Djønne, Berit; Skjerve, Eystein

2013-01-01

110

Genotypes and drug susceptibility of Mycobacterium tuberculosis Isolates in Shihezi, Xinjiang Province, China  

PubMed Central

Background Tuberculosis (TB) remains a major global health problem. To investigate the genotypes of Mycobacterium tuberculosis (MTB) and the distribution of Beijing family strains, molecular epidemiology technologies have been used widely. Methods From June 2010 to June 2011, 55?M. tuberculosis isolates from patients with pulmonary TB were studied by Beijing family-specific PCR (detection of the deletion of region of difference 105 [RD105]), and mycobacterial interspersed repetitive units variable number tandem repeat (MIRU-VNTR) analysis. Twenty-four MIRU-VNTR loci defined the genotypes and clustering characteristics of the local strains. All strains were subjected to a drug susceptibility test (DST) by the proportion method on Lowenstein-Jensen (LJ) culture media. Results Fifty-five clinical isolates of MTB were collected. Beijing family strains represented 85.5% of the isolates studied. Using 24 loci MIRU-VNTR typing categorized the strains into eight gene groups, 46 genotypes, and seven clusters. 83.6% (46/55) of the isolates belonged to the largest gene group. Thirty-six isolates (65.5%) were susceptible, nineteen (34.5%) were resistant to at least one drug, seven (12.8%) were Multidrug-Resistant Tuberculosis (MDR TB), and two (3.6%) were extremely drug-resistant tuberculosis (XDR-TB). Conclusion The results showed there were obvious polymorphisms of VNTRs of MTB clinical strains. Beijing family strains of MTB were predominant in the Shihezi region of Xinjiang province. There was no correlation between the drug-resistance and Beijing family strains of MTB. It is necessary to strengthen the monitoring, treatment, and management of drug-resistance TB in Shihezi region, Xinjiang. PMID:22713520

2012-01-01

111

Women and tuberculosis.  

PubMed

Tuberculosis is the leading infectious cause of death in women worldwide. The disease poses a major threat to women's health security. Population growth, the HIV epidemic, increasing poverty and rising levels of drug resistance will inevitably increase the burden of this disease in women. Women are at increased risk of progression to disease during their reproductive years. However, in most low-income countries, twice as many men are notified with tuberculosis as women. Biological mechanisms may account for most of this difference but socioeconomic and cultural factors leading to barriers in accessing health care may cause under-notification in women. Tuberculosis control programmes should be sensitive to the constraints faced by women in accessing health care, in order to empower women to commence and complete treatment. The fear and stigma associated with tuberculosis have a greater impact on women than on men, often leaving them in a more precarious social and economic position. Tuberculosis in women creates orphans, impoverished families and reduces the economic development of society. Tuberculosis is a major cause of preventable suffering and death in women. WHO's recommended tuberculosis control strategy, DOTS, represents a cost-effective response to the problem of tuberculosis in women. Tuberculosis is a major women's health issue. It is a global health priority that tuberculosis treatment be made available to women, particularly to those in low-income countries who are bearing the brunt of this epidemic. PMID:9050189

Connolly, M; Nunn, P

1996-01-01

112

First documented cure of a suggestive exogenous reinfection in polymyositis with same but multidrug resistant M. tuberculosis  

Microsoft Academic Search

BACKGROUND: MDR Mycobacterium tuberculosis is the major cause of treatment failure in tuberculosis patients, especially in immunosuppressed. We described a young polymyositis patient on immunosuppressive therapy who was started with antituberculosis therapy as a susceptible strain of M. tuberculosis was isolated from a single cutaneous abscess in his neck and from regional lymph nodes. CASE PRESENTATION: He had non-reactive miliary

Chiranjoy Mukhopadhyay; Ankita Garg; Archana Ayyagari

2004-01-01

113

Analysis of DNA relaxation and cleavage activities of recombinant Mycobacterium tuberculosis DNA topoisomerase I from a new expression and purification protocol  

PubMed Central

Background Mycobacterium tuberculosis DNA topoisomerase I is an attractive target for discovery of novel TB drugs that act by enhancing the accumulation of the topoisomerase-DNA cleavage product. It shares a common transesterification domain with other type IA DNA topoisomerases. There is, however, no homology between the C-terminal DNA binding domains of Escherichia coli and M. tuberculosis DNA topoisomerase I proteins. Results A new protocol for expression and purification of recombinant M. tuberculosis DNA topoisomerase I (MtTOP) has been developed to produce enzyme of much higher specific activity than previously characterized recombinant enzyme. MtTOP was found to be less efficient than E. coli DNA topoisomerase I (EcTOP) in removal of remaining negative supercoils from partially relaxed DNA. DNA cleavage by MtTOP was characterized for the first time. Comparison of DNA cleavage site selectivity with EcTOP showed differences in cleavage site preferences, but the preferred sites of both enzymes have a C nucleotide in the -4 position. Conclusion Recombinant M. tuberculosis DNA topoisomerase I can be expressed as a soluble protein and purified in high yield from E. coli host with a new protocol. Analysis of DNA cleavage with M. tuberculosis DNA substrate showed that the preferred DNA cleavage sites have a C nucleotide in the -4 position. PMID:19519900

Annamalai, Thirunavukkarasu; Dani, Neil; Cheng, Bokun; Tse-Dinh, Yuk-Ching

2009-01-01

114

Silent nucleotide polymorphisms and a phylogeny for Mycobacterium tuberculosis.  

PubMed

Much remains unknown of the phylogeny and evolution of Mycobacterium tuberculosis, an organism that kills 2 million people annually. Using a population-based approach that analyzes multiple loci around the chromosome, we demonstrate that neutral genetic variation in genes associated with antimicrobial drug resistance has sufficient variation to construct a robust phylogenetic tree for M. tuberculosis. The data describe a clonal population with a minimum of four distinct M. tuberculosis lineages, closely related to M. bovis. The lineages are strongly geographically associated. Nucleotide substitutions proven to cause drug resistance are distributed throughout the tree, whereas nonsynonymous base substitutions unrelated to drug resistance have a restricted distribution. The phylogenetic structure is concordant with all the previously described genotypic and phenotypic groupings of M. tuberculosis strains and provides a unifying framework for both epidemiologic and evolutionary analysis of M. tuberculosis populations. PMID:15498158

Baker, Lucy; Brown, Tim; Maiden, Martin C; Drobniewski, Francis

2004-09-01

115

CT of parenchymal and bronchial tuberculosis  

Microsoft Academic Search

.   Tuberculosis (TB) remains a common disease in the World. Its incidence has risen steadily since 1985, despite a preexisting\\u000a continuous decreasing of its frequency due to an effective chemotherapy. Nonwhite people, socioeconomically disadvantaged,\\u000a chronically debilitated groups and AIDS patients are the most concerned. Chest radiography remains the first imaging modality\\u000a to evaluate TB. Widely radiographic appearances can be encountered,

C. Beigelman; D. Sellami; M. Brauner

2000-01-01

116

Imipenem for Treatment of Tuberculosis in Mice and Humans  

PubMed Central

Chemotherapy of tuberculosis caused by multiple-drug-resistant (MDR) strains is problematic because of choices limited to relatively inefficacious and toxic drugs. Some beta-lactam antibiotics are active against Mycobacterium tuberculosis in vitro. We investigated the efficacy of imipenem in a mouse model of tuberculosis and in humans with MDR tuberculosis. Mice infected with M. tuberculosis strain H37Rv were treated with isoniazid or imipenem. Residual organisms in lung and spleen and survival of imipenem-treated mice were compared to those of untreated or isoniazid-treated mice. Ten patients with MDR tuberculosis also were treated with imipenem in combination with other first- or second-line agents; elimination of M. tuberculosis from sputum samples was measured by quantitative culture. Although it was less effective than isoniazid, imipenem significantly reduced the numbers of M. tuberculosis organisms in lungs and spleens and improved survival of mice. Eight of 10 patients with numerous risk factors for poor outcomes responded to imipenem combination therapy with conversion of cultures to negative. Seven remained culture-negative off of therapy. There were two deaths, one of which was due to active tuberculosis. Organisms were eliminated from the sputa of responders at a rate of 0.35 log10 CFU/ml/week. Relapse upon withdrawal of imipenem and development of resistance to imipenem in a nonresponder suggest that imipenem exerts antimycobacterial activity in humans infected with M. tuberculosis. Imipenem had antimycobacterial activity both in a mouse model and in humans at high risk for failure of treatment for MDR tuberculosis. PMID:15980354

Chambers, Henry F.; Turner, Joan; Schecter, Gisela F.; Kawamura, Masae; Hopewell, Philip C.

2005-01-01

117

TUBERCULOSIS COMO ENFERMEDAD OCUPACIONAL  

PubMed Central

Existe evidencia suficiente para declarar a la tuberculosis como enfermedad ocupacional en diversos profesionales especialmente entre los trabajadores de salud. En el Perú están normados y reglamentados los derechos laborales inherentes a la tuberculosis como enfermedad ocupacional, como la cobertura por discapacidad temporal o permanente. Sin embargo, estos derechos aún no han sido suficientemente socializados. En este trabajo se presenta información sobre el riesgo de adquirir tuberculosis en el lugar de trabajo, se revisan las evidencias para declarar a la tuberculosis como enfermedad ocupacional en trabajadores de salud y se presenta la legislación peruana vigente al respecto. PMID:22858771

Mendoza-Ticona, Alberto

2014-01-01

118

Tuberculosis among American Indians of the contiguous United States.  

PubMed

Paleopathologic findings provide strong evidence for the existence of tuberculosis in Andean populations of pre-Columbian America. Indirect evidence is available also to suggest its possible endemicity among some American Indian tribes who lived within the present-day contiguous United States before the arrival of Europeans. The available data suggest that tuberculosis became a major health problem in some tribes with increased population density and cultural changes after increased contact with European civilization, paralleling the deterioration in living conditions after relocation of the tribes to reservations. By 1900, tuberculosis had become one of the most serious health problems among North American Indians. Tuberculosis control was hampered by the lack of a specific treatment, and only the advent of specific chemotherapy in an ambulatory setting brought a breakthrough. Mortality, morbidity, and risk of infection have all sharply decreased over the past three decades. However, tuberculosis incidence rates among American Indians remain well above rates in the white population. An intensified effort to identify those with tuberculosis and those at risk of tuberculosis as well as to develop compliance-enhancing strategies with treatment regimens will be necessary to eliminate tuberculosis from Indian reservations. PMID:2511601

Rieder, H L

1989-01-01

119

Of mice, men, and elephants: Mycobacterium tuberculosis cell envelope lipids and pathogenesis.  

PubMed

Mycolic acids and structures attached to them constitute a major part of the protective envelope of Mycobacterium tuberculosis, and for this reason, their role in tuberculosis pathogenesis has been extensively studied. In this issue of the JCI, Rao et al. examine the effect of trans-cyclopropanation of oxygenated mycolic acids attached to trehalose dimycolate (TDM) on the murine immune response to infection (see the related article beginning on page 1660). Surprisingly, they found that an M. tuberculosis mutant lacking trans-cyclopropane rings was hypervirulent in mice. The recent recognition of a hypervirulence phenotype in mice associated with laboratory and clinical M. tuberculosis strains with altered cell wall components has provided new insights into how M. tuberculosis may establish persistent infection. However, to date, characterization of these bioactive products in pathogenesis has been largely reductionistic; the relationship of their effects observed in mice to the persistent infection and tuberculosis caused by M. tuberculosis observed in humans remains obscure. PMID:16741572

Riley, Lee W

2006-06-01

120

TUBERCULOSIS 1 Tuberculosis in Aboriginal Populations in Canada  

E-print Network

TUBERCULOSIS 1 Tuberculosis in Aboriginal Populations in Canada: The Role of Health Care, PhD March 27, 2013 #12;TUBERCULOSIS 2 Abstract The persistent presence of infectious and increasingly). Tuberculosis is an infectious disease which is far more common in the Aboriginal population than the Canadian

Peak, Derek

121

Assessment of Diagnostic Techniques of Urinary Tuberculosis  

PubMed Central

Early diagnosis of active tuberculosis remains an elusive challenge. In addition, one third of the world’s population is latently infected with Mycobacterium tuberculosis (Mtb) and up to 10% of infected individuals develop tuberculosis (TB) in their lifetime. In this investigation, the incidence of urinary tuberculosis among renal patients was studied. Three hundreds urine samples were processed for detection of Mtb by Ziehl-Neelsen (ZN) smear examination, Lowenstein Jensen (LJ) medium, radiometric BACTEC460 system as well as polymerase chain reaction (PCR) followed by DNA Enzyme Immunoassay (DEIA) test. Out of 300 urine samples, 2 were positive by both ZN smears and LJ medium with incidence rate of 0.66 %, 3 positive samples by BACTEC460 culture system with incidence of 1%. PCR assay gave more positive results than smear and culture examination (i.e. 8 positive samples with incidence rate of 2.6%). The specificities were 25% for both ZN smears and LJ medium, 37.5% for BACTEC460 culture system, and 100% for PCR test, while sensitivities of all assays were 100%. Thus PCR is a rapid and sensitive method for the early diagnosis of urinary tuberculosis. PMID:23795272

Ghaleb, Khaled; Afifi, Magdy; El-Gohary, Mohamad

2013-01-01

122

Pyrosequencing assay for rapid identification of Mycobacterium tuberculosis complex species  

PubMed Central

Background Identification of the Mycobacterium tuberculosis complex organisms to the species level is important for diagnostic, therapeutic and epidemiologic perspectives. Indeed, isolates are routinely identified as belonging to the M. tuberculosis complex without further discrimination in agreement with the high genomic similarity of the M. tuberculosis complex members and the resulting complex available identification tools. Findings We herein develop a pyrosequencing assay analyzing polymorphisms within glpK, pykA and gyrB genes to identify members of the M. tuberculosis complex at the species level. The assay was evaluated with 22 M. tuberculosis, 21 M. bovis, 3 M. caprae, 3 M. microti, 2 M. bovis BCG, 2 M. pinnipedii, 1 M. canettii and 1 M. africanum type I isolates. The resulted pyrograms were consistent with conventional DNA sequencing data and successfully identified all isolates. Additionally, 127 clinical M. tuberculosis complex isolates were analyzed and were unambiguously identified as M. tuberculosis. Conclusion We proposed a pyrosequencing-based scheme for the rapid identification of M. tuberculosis complex isolates at the species level. The assay is robust, specific, rapid and can be easily introduced in the routine activity. PMID:22011383

2011-01-01

123

Spatial Analysis of Pulmonary Tuberculosis in Antananarivo Madagascar: Tuberculosis-Related Knowledge, Attitude and Practice  

PubMed Central

Introduction Tuberculosis infection may remain latent, but the disease is nevertheless a serious public health issue. Various epidemiological studies on pulmonary tuberculosis have considered the spatial component and taken it into account, revealing the tendency of this disease to cluster in particular locations. The aim was to assess the contribution of Knowledge Attitude and Practice (KAP) to the distribution of tuberculosis and to provide information for the improvement of the National Tuberculosis Program. Methods We investigated the role of KAP to distribution patterns of pulmonary tuberculosis in Antananarivo. First, we performed spatial scanning of tuberculosis aggregation among permanent cases resident in Antananarivo Urban Township using the Kulldorff method, and then we carried out a quantitative study on KAP, involving TB patients. The KAP study in the population was based on qualitative methods with focus groups. Results The disease still clusters in the same districts identified in the previous study. The principal cluster covered 22 neighborhoods. Most of them are part of the first district. A secondary cluster was found, involving 18 neighborhoods in the sixth district and two neighborhoods in the fifth. The relative risk was respectively 1.7 (p<10?6) in the principal cluster and 1.6 (p<10?3) in the secondary cluster. Our study showed that more was known about TB symptoms than about the duration of the disease or free treatment. Knowledge about TB was limited to that acquired at school or from relatives with TB. The attitude and practices of patients and the population in general indicated that there is still a stigma attached to tuberculosis. Conclusion This type of survey can be conducted in remote zones where the tuberculosis-related KAP of the TB patients and the general population is less known or not documented; the findings could be used to adapt control measures to the local particularities. PMID:25386655

Rakotosamimanana, Sitraka; Mandrosovololona, Vatsiharizandry; Rakotonirina, Julio; Ramamonjisoa, Joselyne; Ranjalahy, Justin Rasolofomanana; Randremanana, Rindra Vatosoa; Rakotomanana, Fanjasoa

2014-01-01

124

Genotypic characteristics of Mycobacterium tuberculosis isolated from household contacts of tuberculosis patients in the Philippines  

PubMed Central

Background The Philippines has an extremely high rate of tuberculosis but little is known about M. tuberculosis genotypes and transmission dynamics in this country. The aim of this study was to determine the proportion of household contacts who develop active TB due to direct transmission from an index case in that household. Methods Mycobacterium tuberculosis isolates from household contacts of tuberculosis patients in the Philippines were characterized using restriction-fragment-length polymorphism analysis, spoligotyping, and mycobacterial interspersed repetitive units – variable number tandem repeats typing (12-loci) to determine their utility in elucidating transmission in an area of high tuberculosis prevalence. Drug susceptibility patterns for these isolates were also determined. Results Spoligotyping and MIRU-VNTR typing results matched in 10 (62.5%) of 16 index patient-household contact pairs while IS6110 fingerprints matched in only six (37.5%) pairs. Only 3/16 (18.8%) index patient-household contact pairs had identical drug susceptibility results. Conclusions Strain typing of M. tuberculosis isolates from household contacts in the Philippines indicates that transmission of strains does not necessarily occur directly from the index patient living in close proximity in the same household but rather that community-based transmission also frequently occurs. Accurate susceptibility testing of all isolates is necessary to insure optimal care of both the index patients and any culture-positive household contacts. PMID:24308751

2013-01-01

125

Community Coauthoring: Whose Voice Remains?  

ERIC Educational Resources Information Center

This article examines how texts are collaboratively produced in community development work when coauthors come from multiple racial, ethnic, and class backgrounds as well as business and other work experiences. We found that the term "wordsmithing" became a discursive tool that limited resident input and shaped the Plan toward an external…

Larson, Joanne; Webster, Stephanie; Hopper, Mindy

2011-01-01

126

Rapid and accurate detection of RMP- and INH- resistant Mycobacterium tuberculosis in spinal tuberculosis specimens by CapitalBio™ DNA microarray: A prospective validation study  

PubMed Central

Background DNA microarrays can detect tuberculosis and its multi-drug resistant form in M. tuberculosis isolates and sputum specimens with high sensitivity and specificity. However, no performance data currently exists for its use in spinal tuberculosis specimens. This study was aimed to assess the performance of the CapitalBio™ DNA microarray in the detection of isoniazid (INH) and rifampicin (RMP) resistance in spinal tuberculosis compared with the BACT/MGIT 960 system. Methods From March 2009 to December 2011, 153 consecutive patients from Southwest Hospital, Chongqing with clinically and pathologically diagnosed spinal tuberculosis were enrolled into this study. Specimens collected during surgery from the tuberculosis patients were subjected to M. tuberculosis species identification and drug-resistance detection by the CapitalBio™ DNA microarray, and results were compared with those obtained from the absolute concentration drug susceptibility testing. Results The CapitalBio™ DNA microarray achieved 93.55% sensitivity for the correct M. tuberculosis species identification of the 93 specimens that tested positive for spinal tuberculosis through culture. In addition, twenty-seven additional patients (45.0%) were detected by the DNA microarray to be positive for M. tuberculosis among sixty spinal tuberculosis patients who were culture negative. Moreover, the DNA microarray had a sensitivity of 88.9% and a specificity of 90.7% for RMP resistance, and the microarray had a sensitivity of 80.0% and a specificity of 91.0% for INH resistance. The mean turn-around time of M. tuberculosis species identification and drug resistance detection using the DNA microarray was 5.8 (range, 4–9) hours. Conclusions The CapitalBio™ DNA microarray is a feasible and accurate tool for the species identification of M. tuberculosis and for directly detecting RMP and INH resistance from spinal tuberculosis specimens in fewer than 9 hours. PMID:23151186

2012-01-01

127

Tuberculosis: Latency and Reactivation  

Microsoft Academic Search

Tuberculosis is a major cause of death around the world, with most of the 1.5 million deaths per year attributable to the disease occurring in developing countries. This disease is caused by Mycobacterium tuberculosis, an acid-fast bacillus that is transmitted primarily via the respiratory route. Infection occurs in the lungs, but the organism can seed any organ via hematogenous spread.

JOANNE L. FLYNN; JOHN CHAN

2001-01-01

128

"Tuberculosis Case Management" Training.  

ERIC Educational Resources Information Center

The need to isolated health providers with critical knowledge in tuberculosis (TB) case management prompted the development of "Tuberculosis Case Management" CD-ROM. Features include "Learning Center,""Examination Room," and "Library." The combination of audio, video, and graphics allows participants to practice acquired skills in a simulated…

Knebel, Elisa; Kolodner, Jennifer

2001-01-01

129

Myths of tuberculosis.  

PubMed

Myths, or misconceptions, of disease and therapy are not confined to patients; they also affect those who practice medicine. Myths are particularly evident in a "dogma" that concerns diagnosis and treatment of tuberculosis. If the elimination of tuberculosis is to be achieved, we must first eliminate the myths, which impede prevention and control of the disease. PMID:1645402

Lanphear, B P; Snider, D E

1991-04-01

130

New hominin remains from Uzbekistan  

Microsoft Academic Search

Although the Paleolithic occupations of Uzbekistan and the neighboring foothill regions of Tajikistan and Kazakhstan are well-documented, almost no hominin fossil material has been discovered in the area since Teshik-Tash 1 in 1938. Here we describe and offer a preliminary comparative framework for hominin remains that were recovered in 2003 from two Middle Paleolithic sites in Uzbekistan, Obi-Rakhmat Grotto and

Michelle Glantz; Bence Viola; Patrick Wrinn; Tatiana Chikisheva; Anatoly Derevianko; Andrei Krivoshapkin; Uktur Islamov; Rustam Suleimanov; Terrence Ritzman

2008-01-01

131

Best practice in the diagnosis and management of urogenital tuberculosis  

PubMed Central

Tuberculosis (TB) is a current public health problem, remaining the most common worldwide cause of mortality from infectious diseases. Urogenital tuberculosis (UGTB) is the second most common form of extrapulmonary TB in countries with severe epidemic situations and the third most common form in regions with a low incidence of TB. In this article we present the terminology, epidemiology and classification of UGTB, as well as describing the laboratory findings and clinical features and approaches to chemotherapy as well as surgery. PMID:23730329

2013-01-01

132

Faecal calprotectin levels differentiate intestinal from pulmonary tuberculosis: An observational study from Southern India  

PubMed Central

Background Current methods to establish the diagnosis of intestinal tuberculosis are inadequate. Objectives We aimed to determine the clinical features of intestinal tuberculosis and evaluate inflammatory biomarkers in intestinal as well as pulmonary tuberculosis. Methods We recruited 38 intestinal tuberculosis patients, 119 pulmonary tuberculosis patients and 91 controls with functional gastrointestinal disorders between October 2009 and July 2012 for the investigation of clinical features, C-reactive protein (CRP), faecal and serum calprotectin. Faecal calprotectin ?200?µg/g was used as a cut-off to determine intestinal inflammation of clinical significance. Three patient categories were established: (a) pulmonary tuberculosis and faecal calprotectin <200?µg/g (isolated pulmonary tuberculosis); (b) pulmonary tuberculosis and faecal calprotectin ?200?µg/g (combined pulmonary and intestinal tuberculosis); (c) isolated intestinal tuberculosis. Results Common clinical features of intestinal tuberculosis were abdominal pain, fatigue, weight loss and watery diarrhoea. Intestinal tuberculosis patients had elevated median CRP (10.7?mg/l), faecal calprotectin (320?µg/g) and serum calprotectin (5.7?µg/ml). Complete normalisation of CRP (1.0?mg/L), faecal calprotectin (16?µg/g) and serum calprotectin (1.4?µg/ml)) was seen upon clinical remission. Patients with combined pulmonary and intestinal tuberculosis had the highest levels of CRP (53.8?mg/l) and serum calprotectin (6.5?µg/ml) and presented with signs of more severe disease. Conclusion Calprotectin analysis reveals intestinal tuberculosis in patients with pulmonary tuberculosis and pinpoints those in need of rigorous follow-up. PMID:25360318

Shenoy, Koticherry Thrivikrama; Ramasubramanian, Ramalingom; Thayumanavan, Lakshmikanthan; Balakumaran, Leena Kondarappassery; Bjune, Gunnar A; Moum, Bjørn A

2014-01-01

133

[HIV infection and tuberculosis].  

PubMed

The number of people infected with human immunodeficiency virus (HIV) is gradually increasing in Japan, and the morbidity rate from tuberculosis in the Japanese people is high. Accordingly, the number of cases with both infections is considered to increase in the future. Our hospital has already encountered 31 cases of HIV associated tuberculosis. HIV infects mainly CD4-positive cells. The extreme decrease in the cell count results in serious cellular immunological disorder. CD4-positive cell disorder induces disorders of B lymphocytes, cytotoxic T cells, natural killer cells, and macrophage functions. These destructive conditions show the state of immunodeficiency including macrophage that are most important for defense of acid-fast bacterial infection. Migration and activation of macrophages with cytokines derived from T cells are impaired to induce the following phenomena: hypoplasia of granuloma, failure of tubercule bacillus suppression, the spread to regional lymph nodes (hilar or mediastinal lymph nodes), and hematogenous dissemination. On this occasion, caseous necrosis and cavitation are unlikely to occur, and false-negative tuberculin reaction is often observed. The incidence of severe cases, which include miliary tuberculosis, tuberculous meningitis, etc., and extrapulmonary tuberculosis, are high among acquired immunodeficiency syndrome (AIDS)-associated tuberculosis cases. HIV-infected tuberculosis cases are generally regarded as endogenous exacerbation, but they include primary infection and reinfection as well. Even during the treatment for drug-sensitive strains particularly, some cases may have reinfection with multidrug-resistant bacteria, suggesting that caution should be taken against this point. Conversely, the association of tuberculosis is a factor for the poor prognosis of HIV infection, since it facilitates the development of HIV infection. If the bacteria belong to a drug-sensitive strain, the infection with them responds well to antituberculous drugs, the same as in tuberculosis cases without HIV infection, showing a favorable prognosis. However, the mortality rate of infection with multi-drug-resistant tuberculosis is extremely high. The combined use of a protease inhibitor, i.e., anti-HIV drug, with rifampicin is regarded as contraindication for the treatment because rifampicin strongly induces hepatic cytochrome P-450 and increases the metabolism of protease inhibitors and nonnucleoside reverse transcriptases to markedly decrease the blood concentrations. Accordingly, the treatment for tuberculosis should take priority over that for HIV infection in HIV-infected tuberculosis, and highly active antiretroviral therapy (HAART) may be administered after the treatment of tuberculosis. When HAART is necessary for the treatment during the tuberculosis treatment, rifampicin had better be exchanged to rifabutin because the effect of rifabutin to induce cytochrome P-450 is less potent than that of rifampicin. A report has recently shown that the exacerbation of pyrexia and chest X-ray findings was transiently observed approximately 2 weeks after potent anti-HIV therapy for HIV-infected tuberculosis, which included a protease inhibitor. The reason for the exacerbation has been believed to be that the impaired function of CD4-positive cells is improved by the administration of anti-HIV drugs to raise temporarily the reaction of the vital part to M. tuberculosis. A tuberculin skin test (TST) reaction size of > or = 5 mm of induration is considered positive (i.e., indicative of M. tuberculosis infection) in persons who are infected with HIV. Persons with a TST reaction size > or = 5 mm who have not previously received treatment for M. tuberculosis infection should receive tuberculosis preventive treatment. Prevention by BCG vaccination is regarded as contraindications for HIV-infected patients, because disseminated M. bovis infection may be associated with them. Many HIV-positive patients infected with tuberculosis show uneventful healing, when M. tuberculosis is the sensitive strain. However, since

Nagai, Hideaki

2003-01-01

134

Tuberculosis Epidemiology and Selection in an Autochthonous Siberian Population from the 16th-19th Century  

PubMed Central

Tuberculosis is one of most ancient diseases affecting human populations. Although numerous studies have tried to detect pathogenic DNA in ancient skeletons, the successful identification of ancient tuberculosis strains remains rare. Here, we describe a study of 140 ancient subjects inhumed in Yakutia (Eastern Siberia) during a tuberculosis outbreak, dating from the 16th–19th century. For a long time, Yakut populations had remained isolated from European populations, and it was not until the beginning of the 17th century that first contacts were made with European settlers. Subsequently, tuberculosis spread throughout Yakutia, and the evolution of tuberculosis frequencies can be tracked until the 19th century. This study took a multidisciplinary approach, examining historical and paleo-epidemiological data to understand the impact of tuberculosis on ancient Yakut population. In addition, molecular identification of the ancient tuberculosis strain was realized to elucidate the natural history and host-pathogen co-evolution of human tuberculosis that was present in this population. This was achieved by the molecular detection of the IS6110 sequence and SNP genotyping by the SNaPshot technique. Results demonstrated that the strain belongs to cluster PGG2-SCG-5, evocating a European origin. Our study suggests that the Yakut population may have been shaped by selection pressures, exerted by several illnesses, including tuberculosis, over several centuries. This confirms the validity and necessity of using a multidisciplinary approach to understand the natural history of Mycobacterium tuberculosis infection and disease. PMID:24587092

Dabernat, Henri; Thèves, Catherine; Bouakaze, Caroline; Nikolaeva, Dariya; Keyser, Christine; Mokrousov, Igor; Géraut, Annie; Duchesne, Sylvie; Gérard, Patrice; Alexeev, Anatoly N.; Crubézy, Eric; Ludes, Bertrand

2014-01-01

135

Tapering off of tuberculosis among the elderly.  

PubMed Central

Tuberculosis has long been prevalent among elderly people. When tubercle bacilli first enter human bodies they usually remain through the rest of their hosts' lives and are capable of causing clinical disease any time, even in old age. In 1900, a large percentage of people of all ages were harboring tubercle bacilli and high mortality and case rates obtained among elderly people. The only way to solve the problem among future old people was to protect infants, children, and youths from becoming infected and remain so throughout life. As far as possible that was accomplished by isolating and treating tuberculosis patients in sanatoriums and hospitals, with anti-tuberculosis drugs after 1946, and controlling the disease among cattle. In due time, large numbers of children entered adulthood uninfected. From year to year, they replaced those heavily infected as they advanced in years. By 1973 the mortality rate was only a fraction of 1.0 per 100,000 among people under 34 years but of those of 65 to 84 years it was 9.7. The case rate was 28.1 for those older than 45 years. Although tuberculosis among the elderly has tapered off phenomenally, much time and work are necessary to accomplish eradication. PMID:790983

Myers, J A

1976-01-01

136

Tuberculosis and subsequent risk of lung cancer in Xuanwei, China  

SciTech Connect

Tobacco and indoor air pollution from smoky coal are major causes of lung cancer in rural Xuanwei County, China. Tuberculosis has been suggested to increase lung cancer risk, but data from prior studies are limited. We conducted an analysis of data from a retrospective cohort study of 42,422 farmers in Xuanwei. In 1992, interviewers administered a standardized questionnaire that included lifetime medical history, including tuberculosis. Subjects were followed from 1976, with deaths from lung cancer ascertained through 1996. We used proportional hazards regression to assess the association between tuberculosis and subsequent lung cancer mortality. Tuberculosis was reported by 246 subjects (0.6%), and 2,459 (5.8%) died from lung cancer during follow-up. Lung cancer mortality was substantially higher in subjects with tuberculosis than in those without (25 vs. 3.1 per 1,000 person-years). The association was especially pronounced in the first 5 years after tuberculosis diagnosis (hazard ratios (HRs) ranging 6.7-13) but remained strong 5-9.9 years (HR 3.4, 95% CI 1.3-9.1) and 10+ years (HR 3.0, 95% CI 1.3-7.3) after tuberculosis. These associations were similar among men and women and among smoky coal users (70.5% of subjects). Adjustment for demographic characteristics, lung disease and tobacco use did not affect results. In Xuanwei, China, tuberculosis is an important risk factor for lung cancer. The increased lung cancer risk, persisting years after a tuberculosis diagnosis, could reflect the effects of chronic pulmonary inflammation and scarring arising from tuberculosis.

Engels, E.A.; Shen, M.; Chapman, R.S.; Pfeiffer, R.M.; Yu, Y.Y.; He, X.Z.; Lan, Q. [NCI, Rockville, MD (USA). Infectious and Immunoepidemiology Branch

2009-03-15

137

Mycobacterium tuberculosis Lipolytic Enzymes as Potential Biomarkers for the Diagnosis of Active Tuberculosis  

Microsoft Academic Search

BackgroundNew diagnosis tests are urgently needed to address the global tuberculosis (TB) burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy.

Belinda Brust; Mélanie Lecoufle; Edouard Tuaillon; Luc Dedieu; Stéphane Canaan; Viviane Valverde; Laurent Kremer; Volker Briken

2011-01-01

138

Adherence to anti-tuberculosis treatment among pulmonary tuberculosis patients: a qualitative and quantitative study  

Microsoft Academic Search

BACKGROUND: Tuberculosis (TB) patients have difficulty following a long-term treatment regimen. Efforts to improve treatment outcomes require better understanding of adherence as a complex behavioral issue and of the particular barriers to and facilitators of patient adherence. METHODS: This study was carried out in Jiangsu Province of China with both quantitative and qualitative approaches. For the quantitative study, 780 sputum-smear

Weiguo Xu; Wei Lu; Yang Zhou; Limei Zhu; Hongbing Shen; Jianming Wang

2009-01-01

139

New hominin remains from Uzbekistan.  

PubMed

Although the Paleolithic occupations of Uzbekistan and the neighboring foothill regions of Tajikistan and Kazakhstan are well-documented, almost no hominin fossil material has been discovered in the area since Teshik-Tash 1 in 1938. Here we describe and offer a preliminary comparative framework for hominin remains that were recovered in 2003 from two Middle Paleolithic sites in Uzbekistan, Obi-Rakhmat Grotto and Anghilak Cave. The description of Teshik-Tash as a Neandertal and the preponderance of lithic assemblages identified as Mousterian in character has supported the interpretation of the region as the eastern-most extent of the Neandertal range. The material from Obi-Rakhmat (OR-1), a subadult represented by part of a permanent maxillary dentition and a fragmentary cranium, expresses a relatively Neandertal-like dentition coupled with more ambiguous cranial anatomy. The remains from Anghilak Cave include a non-diagnostic, diminutive right fifth metatarsal (AH-1). These findings are important additions to the Central Asia hominin fossil record. PMID:18499228

Glantz, Michelle; Viola, Bence; Wrinn, Patrick; Chikisheva, Tatiana; Derevianko, Anatoly; Krivoshapkin, Andrei; Islamov, Uktur; Suleimanov, Rustam; Ritzman, Terrence

2008-08-01

140

Comparative radiological features of disseminated disease due to Mycobacterium tuberculosis vs non-tuberculosis mycobacteria among AIDS patients in Brazil  

Microsoft Academic Search

BACKGROUND: Disseminated mycobacterial disease is an important cause of morbidity and mortality in patients with HIV-infection. Nonspecific clinical presentation makes the diagnosis difficult and sometimes neglected. METHODS: We conducted a retrospective cohort study to compare the presentation of disseminated Mycobacterial tuberculosis (MTB) and non-tuberculous Mycobacterial (NTM) disease in HIV-positive patients from 1996 to 2006 in Brazil. RESULTS: Tuberculosis (TB) was

Rodrigo P dos Santos; Karin L Scheid; Denise MC Willers; Luciano Z Goldani

2008-01-01

141

Projected effects of tobacco smoking on worldwide tuberculosis control: mathematical modelling analysis  

PubMed Central

Objectives Almost 20% of people smoke tobacco worldwide—a percentage projected to rise in many poor countries. Smoking has been linked to increased individual risk of tuberculosis infection and mortality, but it remains unclear how these risks affect population-wide tuberculosis rates. Design We constructed a state transition, compartmental, mathematical model of tuberculosis epidemics to estimate the impact of alternative future smoking trends on tuberculosis control. We projected tuberculosis incidence, prevalence, and mortality in each World Health Organization region from 2010 to 2050, and incorporated changing trends in smoking, case detection, treatment success, and HIV prevalence. Results The model predicted that smoking would produce an excess of 18 million tuberculosis cases (standard error 16-20) and 40 million deaths from tuberculosis (39-41) between 2010 and 2050, if smoking trends continued along current trajectories. The effect of smoking was anticipated to increase the number of tuberculosis cases by 7% (274 million v 256 million) and deaths by 66% (101 million v 61 million), compared with model predictions that did not account for smoking. Smoking was also expected to delay the millennium development goal target to reduce tuberculosis mortality by half from 1990 to 2015. The model estimated that aggressive tobacco control (achieving a 1% decrease in smoking prevalence per year down to eradication) would avert 27 million smoking attributable deaths from tuberculosis by 2050. However, if the prevalence of smoking increased to 50% of adults (as observed in countries with high tobacco use), the model estimated that 34 million additional deaths from tuberculosis would occur by 2050. Conclusions Tobacco smoking could substantially increase tuberculosis cases and deaths worldwide in coming years, undermining progress towards tuberculosis mortality targets. Aggressive tobacco control could avert millions of deaths from tuberculosis. PMID:21972295

2011-01-01

142

Polymorphisms of SP110 Are Associated with both Pulmonary and Extra-Pulmonary Tuberculosis among the Vietnamese  

PubMed Central

Background Tuberculosis (TB) is an infectious disease that remains a major cause of morbidity and mortality worldwide, yet the reasons why only 10% of people infected with Mycobacterium tuberculosis go on to develop clinical disease are poorly understood. Genetically determined variation in the host immune response is one factor influencing the response to M. tuberculosis. SP110 is an interferon-responsive nuclear body protein with critical roles in cell cycling, apoptosis and immunity to infection. However association studies of the gene with clinical TB in different populations have produced conflicting results. Methods To examine the importance of the SP110 gene in immunity to TB in the Vietnamese we conducted a case-control genetic association study of 24 SP110 variants, in 663 patients with microbiologically proven TB and 566 unaffected control subjects from three tertiary hospitals in northern Vietnam. Results Five SNPs within SP110 were associated with all forms of TB, including four SNPs at the C terminus (rs10208770, rs10498244, rs16826860, rs11678451) under a dominant model and one SNP under a recessive model, rs7601176. Two of these SNPs were associated with pulmonary TB (rs10208770 and rs16826860) and one with extra-pulmonary TB (rs10498244). Conclusion SP110 variants were associated with increased susceptibility to both pulmonary and extra-pulmonary TB in the Vietnamese. Genetic variants in SP110 may influence macrophage signaling responses and apoptosis during M. tuberculosis infection, however further research is required to establish the mechanism by which SP110 influences immunity to tuberculosis infection. PMID:25006821

Fox, Gregory J.; Sy, Dinh Ngoc; Nhung, Nguyen Viet; Yu, Bing; Ellis, Magda K.; Van Hung, Nguyen; Cuong, Nguyen Kim; Thi Lien, Luu; Marks, Guy B.; Saunders, Bernadette M.; Britton, Warwick J.

2014-01-01

143

Hyperferritinemia in pulmonary tuberculosis.  

PubMed

High ferritin levels have been found to be associated with non infectious as well as infectious causes including tuberculosis. This is one case report of 41 year old male who presented with cough with expectoration. The patient had Multi drug resistant tuberculosis (MDRTB) and type 2 diabetes mellitus. The laboratory findings showed Iron 280 ?g/dl, Total iron binding capacity (TIBC) 61 ?g/dl, and ferritin 92,945 ng/ml which indicates that iron is an essential nutrient for the survival of the pathogen Mycobacterium tuberculosis. PMID:24426230

D'Souza, Benedicta; Sinha, Sulekha; Manjrekar, Poornima; D'Souza, Vivian

2013-07-01

144

Tuberculosis of the hand.  

PubMed

There has been recent interest in tuberculosis of the hand because of a rising incidence owing to increasing numbers of immigration, an aging population, and immunosuppressed people including affected patients with human immunodeficiency virus. In this article, we review the epidemiology, bacteriology, pathophysiology, diagnosis, and principles of treatment of tuberculosis of the hand. The second part of the report emphasizes the classification of hand tuberculosis (cutaneous lesions, tenosynovitis, bursitis, osteomyelitis, arthritis, and tuberculous hypersensitivity reactions) along with the classic presentations of each of these hand lesions. PMID:21764526

Al-Qattan, M M; Al-Namla, A; Al-Thunayan, A; Al-Omawi, M

2011-08-01

145

Tuberculosis of the breast with erythema nodosum: a case report  

PubMed Central

Introduction There has been an increasing number of tuberculosis cases worldwide, but tuberculosis of the breast remains rare. In rare cases this is seen with a cutaneous manifestation of erythema nodosum. Case presentation We report the case of a 33-year-old Chinese woman with tuberculosis of the left breast accompanied by erythema nodosum on the anterior aspect of both lower legs. Due to her poor clinical response to conventional therapy, and the histopathological findings of fine needle aspiration cytology, there were strong indications of tuberculosis. Her clinical diagnosis was confirmed by molecular detection of Mycobacterium tuberculosis complex by polymerase chain reaction. The diagnosis was further confirmed by a second polymerase chain reaction test of erythema nodosum which tested positive for Mycobacterium tuberculosis complex. She received anti-tuberculous therapy for 18 months, and finally underwent residual lumpectomy. During her follow-up examination after 12 months, no evidence of either residual or recurrent disease was present. Conclusion Histopathological features and a high index of clinical suspicion are necessary to confirm a diagnosis of tuberculosis of the breast. Anti-tuberculous therapy with or without simple surgical intervention is the core treatment. PMID:20429894

2010-01-01

146

Investigating the metabolic capabilities of Mycobacterium tuberculosis H37Rv using the in silico strain iNJ661 and proposing alternative drug targets  

Microsoft Academic Search

BACKGROUND:: Mycobacterium tuberculosis continues to be a major pathogen in the third world, killing almost 2 million people a year by the most recent estimates. Even in industrialized countries, the emergence of multi-drug resistant (MDR) strains of tuberculosis hails the need to develop additional medications for treatment. Many of the drugs used for treatment of tuberculosis target metabolic enzymes. Genome-scale

Neema Jamshidi; Bernhard Ø Palsson

2007-01-01

147

Predictors of pulmonary tuberculosis treatment outcomes in South Korea: a prospective cohort study, 2005-2012  

PubMed Central

Background Tuberculosis remains an important health concern in many countries. The aim of this study was to identify predictors of unfavorable outcomes at the end of treatment (EOT) and at the end of study (EOS; 40 months after EOT) in South Korea. Methods New or previously treated tuberculosis patients were recruited into a prospective observational cohort study at two hospitals in South Korea. To identify predictors of unfavorable outcomes at EOT and EOS, logistic regression analysis was performed. Results The proportion of multidrug-resistant tuberculosis (MDR-TB) was 8.2% in new cases and 57.9% in previously treated cases. Of new cases, 68.6% were cured, as were 40.7% of previously treated cases. At EOT, diabetes, ?3 previous TB episodes, ?1 significant regimen change, and MDR-TB were significantly associated with treatment failure or death. At EOS, age ?35, body-mass index (BMI) <18.5, diabetes, and MDR-TB were significantly associated with treatment failure, death, or relapse. Among cases that were cured at EOT, age ?50 and a BMI <18.5 were associated with subsequent death or relapse during follow-up to EOS. Treatment interruption was associated with service sector employees or laborers, bilateral lesions on chest X-ray, and previous treatment failure or treatment interruption history. Conclusions Risk factors for poor treatment outcomes at EOT and EOS include both patient factors (diabetes status, age, BMI) and disease factors (history of multiple previous treatment episodes, MDR-TB). In this longitudinal, observational cohort study, diabetes mellitus and MDR-TB were risk factors for poor treatment outcomes and relapse. Measures to help ensure that the first tuberculosis treatment episode is also the last one may improve treatment outcomes. Trial registration ClinicalTrials.gov ID: NCT00341601 PMID:24990578

2014-01-01

148

Failure to Recognize Nontuberculous Mycobacteria Leads to Misdiagnosis of Chronic Pulmonary Tuberculosis  

PubMed Central

Background Nontuberculous mycobacterial (NTM) infections cause morbidity worldwide. They are difficult to diagnose in resource-limited regions, and most patients receive empiric treatment for tuberculosis (TB). Our objective here is to evaluate the potential impact of NTM diseases among patients treated presumptively for tuberculosis in Mali. Methods We re-evaluated sputum specimens among patients newly diagnosed with TB (naïve) and those previously treated for TB disease (chronic cases). Sputum microscopy, culture and Mycobacterium tuberculosis drug susceptibility testing were performed. Identification of strains was performed using molecular probes or sequencing of secA1 and/or 16S rRNA genes. Results Of 142 patients enrolled, 61 (43%) were clinically classified as chronic cases and 17 (12%) were infected with NTM. Eleven of the 142 (8%) patients had NTM disease alone (8 M. avium, 2 M. simiae and 1 M. palustre). All these 11 were from the chronic TB group, comprising 11/61 (18%) of that group and all were identified as candidates for second line treatment. The remaining 6/17 (35.30%) NTM infected patients had coinfection with M. tuberculosis and all 6 were from the TB treatment naïve group. These 6 were candidates for the standard first line treatment regimen of TB. M. avium was identified in 11 of the 142 (8%) patients, only 3/11 (27.27%) of whom were HIV positive. Conclusions NTM infections should be considered a cause of morbidity in TB endemic environments especially when managing chronic TB cases to limit morbidity and provide appropriate treatment. PMID:22615839

Diallo, Souleymane; Diarra, Bassirou; Traoré, Brehima; Shea, Yvonne R.; Zelazny, Adrian M.; Dembele, Bindongo P. P.; Goita, Drissa; Kassambara, Hamadoun; Hammond, Abdulrahman S.; Polis, Michael A.; Tounkara, Anatole

2012-01-01

149

Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase  

Microsoft Academic Search

Mycobacterium tuberculosis claims more human lives each year than any other bacterial pathogen. Infection is maintained in spite of acquired immunity and resists eradication by antimicrobials. Despite an urgent need for new therapies targeting persistent bacteria, our knowledge of bacterial metabolism throughout the course of infection remains rudimentary. Here we report that persistence of M. tuberculosis in mice is facilitated

John D. McKinney; Kerstin Höner zu Bentrup; Ernesto J. Muñoz-Elías; Andras Miczak; Bing Chen; Wai-Tsing Chan; Dana Swenson; James C. Sacchettini; William R. Jacobs; David G. Russell

2000-01-01

150

Smoking increases the risk of relapse after successful tuberculosis treatment  

PubMed Central

Background Recent tobacco smoking has been identified as a risk factor for developing tuberculosis, and two studies which have investigated its association with relapse of tuberculosis after completion of treatment had conflicting results (and did not control for confounding). The objective of this study was to investigate risk factors for tuberculosis relapse, with emphasis on smoking. Methods A cohort of newly diagnosed TB cases was followed up from their discharge after completion of treatment (in 2001–2003) until October 2006 and relapses of tuberculosis ascertained during that period. A case of relapse was defined as a patient who started a second treatment during the follow up. Results Smoking (OR 2.53, 95% CI 1.23–5.21) and living in an area where the family health program was not implemented (OR 3.61, 95% CI 1.46–8.93) were found to be independently associated with relapse of tuberculosis. Conclusions Our results establish that smoking is associated with relapse of tuberculosis even after adjustment for the socioeconomic variables. Smoking cessation support should be incorporated in the strategies to improve effectiveness of Tuberculosis Control Programs. PMID:18556729

d’Arc Lyra Batista, Joanna; de Fátima Pessoa Militão de Albuquerque, Maria; de Alencar Ximenes, Ricardo Arraes; Rodrigues, Laura Cunha

2008-01-01

151

Cost-effectiveness of tuberculosis evaluation and treatment of newly-arrived immigrants  

PubMed Central

Background Immigrants to the U.S. are required to undergo overseas screening for tuberculosis (TB), but the value of evaluation and treatment following entry to the U.S. is not well understood. We determined the cost-effectiveness of domestic follow-up of immigrants identified as tuberculosis suspects through overseas screening. Methods Using a stochastic simulation for tuberculosis reactivation, transmission, and follow-up for a hypothetical cohort of 1000 individuals, we calculated the incremental cost-effectiveness of follow-up and evaluation interventions. We utilized published literature, California Reports of Verified Cases of Tuberculosis (RVCTs), demographic estimates from the California Department of Finance, Medicare reimbursement, and Medi-Cal reimbursement rates. Our target population was legal immigrants to the United States, our time horizon is twenty years, and our perspective was that of all domestic health-care payers. We examined the intervention to offer latent tuberculosis therapy to infected individuals, to increase the yield of domestic evaluation, and to increase the starting and completion rates of LTBI therapy with INH (isoniazid). Our outcome measures were the number of cases averted, the number of deaths averted, the incremental dollar cost (year 2004), and the number of quality-adjusted life-years saved. Results Domestic follow-up of B-notification patients, including LTBI treatment for latently infected individuals, is highly cost-effective, and at times, cost-saving. B-notification follow-up in California would reduce the number of new tuberculosis cases by about 6–26 per year (out of a total of approximately 3000). Sensitivity analysis revealed that domestic follow-up remains cost-effective when the hepatitis rates due to INH therapy are over fifteen times our best estimates, when at least 0.4 percent of patients have active disease and when hospitalization of cases detected through domestic follow-up is no less likely than hospitalization of passively detected cases. Conclusion While the current immigration screening program is unlikely to result in a large change in case rates, domestic follow-up of B-notification patients, including LTBI treatment, is highly cost-effective. If as many as three percent of screened individuals have active TB, and early detection reduces the rate of hospitalization, net savings may be expected. PMID:16784541

Porco, Travis C; Lewis, Bryan; Marseille, Elliot; Grinsdale, Jennifer; Flood, Jennifer M; Royce, Sarah E

2006-01-01

152

4. OVERALL VIEW OF ROUNDHOUSE: REMAINING FIVESTALL SECTION IN CENTER ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. OVERALL VIEW OF ROUNDHOUSE: REMAINING FIVE-STALL SECTION IN CENTER BACKGROUND, RUBBLE OF DEMOLISHED SECTION IN FOREGROUND. VIEW TO EAST. - Colorado & Southern Railway Denver Roundhouse Complex, Seventh Street, East of South Platte River, Denver, Denver County, CO

153

American Experience: We Shall Remain  

NSDL National Science Digital Library

Whether watching their TV shows on television or on the computer, PBS always provides a worthy presentation. With an extensive collection of PBS programs available online, the number of topics they cover be fully appreciated. The American Experience series titled "We Shall Remain" consists of five episodes "spanning three hundred years [that] tell the story of pivotal moments in U.S. history from the Native American perspective." The "Reel Native" and "Beyond Broadcast" tabs offer Native Americans telling their experiences and also provide activities for teachers. In addition to viewing the full episodes online, visitors to the website can go "Behind the Scenes" by clicking that tab, and can see such features as the "cast and crew", "featured videos", and "photo gallery". Furthermore, the "Get Involved" part of "Behind the Scenes" informs visitors of "native organizations and tribes, libraries, historical societies, museums, schools and other groups to plan and sponsor activities that promote understanding of local Native history and contemporary life." This area also provides an interactive map that allows a visitor to plot "shoot locations", "tribal colleges", "coalitions", and "native radio stations", by clicking on each corresponding tab.

154

Diversity of Mycobacterium tuberculosis Isolates from New Pulmonary Tuberculosis Cases in Addis Ababa, Ethiopia  

PubMed Central

Understanding the genetic diversity of Mycobacterium tuberculosis is needed for a better understanding of the epidemiology of TB and could have implications for the development of new diagnostics, drugs, and vaccines. M. tuberculosis isolates were characterized using spoligotyping and were compared with the SpoIDB4 database of the Pasteur Institute of Guadeloupe. A total of 53 different patterns were identified among 192 isolates examined. 169 of the isolates were classified into one of the 33 shared SITs, whereas the remaining 23 corresponded to 20 orphan patterns. 54% of the isolates were ascribed to the T family, a family which has not been well defined to date. Other prominent families were CAS, Haarlem, LAM, Beijing, and Unknown comprising 26%, 13%, 2.6%, 0.5%, and 2.1%, respectively. Among HIV-positive patients, 10 patterns were observed among 25 isolates. The T (38.5%), H (26.9%), and CAS (23.1%) families were the most common among HIV-positive individuals. The diversity of the M. tuberculosis strains found in this study is very high, and there was no difference in the distribution of families in HIV-positive and HIV-negative TB patients except the H family. Tuberculosis transmission in Addis Ababa is due to only the modern M. tuberculosis families (CAS, LAM, T, Beijing, Haarlem, and U). PMID:23227330

Mihret, Adane; Bekele, Yonas; Loxton, Andre G.; Jordan, Annemie M.; Yamuah, Lawrence; Aseffa, Abraham; Howe, Rawleigh; Walzl, Gerhard

2012-01-01

155

Tuberculosis of paranasal sinuses.  

PubMed

Nasal tuberculosis is very rare but much rarer is tuberculosis of paranasal sinuses. It involves especially the maxillary sinus and is usually unilateral. We report an unusual case of tuberculosis of frontal and maxillary sinus in a 68 years old male, who presented with a swelling above left medial canthus, with no other eye or nasal complaints. Clinical and radiological findings on our initial evaluation suggested that the patient had left frontal mucocoele with bilateral maxillary haziness. Diagnosis was established on FNAC report and subsequent Ziehl - Neelsen staining of nasal swabs and tuberculin skin test. Later chest x-ray examination was suggestive of pulmonary tuberculosis, which was the primary cause. Patient responded well to antituberculosis drug therapy. PMID:23120511

Sanehi, S; Dravid, Chandrashekhar; Chaudhary, Neena; Venkatachalam, V P

2008-03-01

156

Tuberculosis (For Parents)  

MedlinePLUS

... resolves on its own as a child develops immunity over a 6- to 10-week period. But ... conditions become favorable (for instance, due to lowered immunity), the bacteria become active. Tuberculosis in older kids ...

157

Multifocal tuberculosis verrucosa cutis.  

PubMed

Tuberculosis Verrucosa Cutis (TBVC), a verrucous form of cutaneous tuberculosis, occurs from inoculation of tubercle bacilli into the skin of a previously sensitized patient with moderate to high degree of immunity. This disease is now rare in western countries and in India; the incidence of cutaneous tuberculosis has fallen from 2% to 0.15%. However two recent studies from the Indian subcontinent have reported the prevalence of cutaneous tuebrculosis as 0.7% (Varshney et al) and 0.26% (Patra et al) This case is reported to demonstrate the indolent and extensive nature of tuberculosis verrucosa cutis in an immunocompetent individual and to highlight the importance of histopathology and empirical antitubercular therapy as an adjunct diagnostic tool. PMID:25612118

Chahar, Monica; Dhali, Tapan Kumar; D'souza, Paschal

2015-01-01

158

[The new tools of microbiological diagnosis of tuberculosis].  

PubMed

This review focuses on the role of new tools in the "modern" microbiological diagnosis of tuberculosis. Traditional techniques of microscopy and culture remain essential to diagnostic certainty, but some innovations replace daily the older techniques such as the identification of Mycobacterium tuberculosis complex by immunochromatography or mass spectrometry MALDI-TOF type from positive cultures, or susceptibility testing in liquid medium. New tools that use molecular techniques have become important. They all have in common to optimize the fight against tuberculosis by reducing diagnostic delay. They also allow rapid detection of drug resistance. However, the techniques of gene amplification directly from clinical samples are still less sensitive than culture. Bacteriological diagnosis of tuberculosis disease therefore still relies on the complementarities of different phenotypic and molecular techniques. PMID:25112804

Guillet-Caruba, C; Martinez, V; Doucet-Populaire, F

2014-12-01

159

Fit for consumption: zebrafish as a model for tuberculosis  

PubMed Central

Despite efforts to generate new vaccines and antibiotics for tuberculosis, the disease remains a public health problem worldwide. The zebrafish Danio rerio has emerged as a useful model to investigate mycobacterial pathogenesis and treatment. Infection of zebrafish with Mycobacterium marinum, the closest relative of the Mycobacterium tuberculosis complex, recapitulates many aspects of human tuberculosis. The zebrafish model affords optical transparency, abundant genetic tools and in vivo imaging of the progression of infection. Here, we review how the zebrafish–M. marinum system has been deployed to make novel observations about the role of innate immunity, the tuberculous granuloma, and crucial host and bacterial genes. Finally, we assess how these findings relate to human disease and provide a framework for novel strategies to treat tuberculosis. PMID:24973748

Cronan, Mark R.; Tobin, David M.

2014-01-01

160

In-Depth Molecular Characterization of Mycobacterium tuberculosis from New Delhi - Predominance of Drug Resistant Isolates of the `Modern' (TbD1-) Type  

Microsoft Academic Search

BackgroundIndia has the highest estimated burden of tuberculosis in the world, accounting for 21% of all tuberculosis cases world-wide. However, due to lack of systematic analysis using multiple markers the available information on the genomic diversity of Mycobacterium tuberculosis in India is limited.Methodology\\/Principal FindingsThus, 65 M. tuberculosis isolates from New Delhi, India were analyzed by spoligotyping, MIRU-VNTR, large deletion PCR

Ruth Stavrum; Vithal Prasad Myneedu; Virendra K. Arora; Niyaz Ahmed; Harleen M. S. Grewal; Geraldine Butler

2009-01-01

161

Direct susceptibility testing for multi drug resistant tuberculosis: A meta-analysis  

Microsoft Academic Search

BACKGROUND: One of the challenges facing the tuberculosis (TB) control programmes in resource-limited settings is lack of rapid techniques for detection of drug resistant TB, particularly multi drug resistant tuberculosis (MDR TB). Results obtained with the conventional indirect susceptibility testing methods come too late to influence a timely decision on patient management. More rapid tests directly applied on sputum samples

Freddie Bwanga; Sven Hoffner; Melles Haile; Moses L Joloba

2009-01-01

162

Silymarin protects liver against toxic effects of anti-tuberculosis drugs in experimental animals  

Microsoft Academic Search

BACKGROUND: The first line anti-tuberculosis drugs isoniazid (INH), rifampicin (RIF) and pyrazinamide (PZA) continues to be the effective drugs in the treatment of tuberculosis, however, the use of these drugs is associated with toxic reactions in tissues, particularly in the liver, leading to hepatitis. Silymarin, a standard plant extract with strong antioxidant activity obtained from S. marianum, is known to

Sude Eminzade; Fikriye Uras; Fikret V Izzettin

2008-01-01

163

Whole genome identification of Mycobacterium tuberculosis vaccine candidates by comprehensive data mining and bioinformatic analyses  

Microsoft Academic Search

BACKGROUND: Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects ~8 million annually culminating in ~2 million deaths. Moreover, about one third of the population is latently infected, 10% of which develop disease during lifetime. Current approved prophylactic TB vaccines (BCG and derivatives thereof) are of variable efficiency in adult protection against pulmonary TB (0%–80%), and directed essentially against early

Anat Zvi; Naomi Ariel; John Fulkerson; Jerald C Sadoff; Avigdor Shafferman

2008-01-01

164

Advances in the Diagnosis of Pulmonary Tuberculosis in HIV-Infected and HIV-Uninfected Children  

PubMed Central

The identification of improved diagnostic tests for tuberculosis has been identified as a global research priority. Over the past decade, there has been renewed interest in the development and validation of novel diagnostic tools for pulmonary tuberculosis that are applicable to resource-poor settings. These techniques are aimed primarily at improving detection of the organism or a specific host immune response. Although most studies have focused on determining the accuracy of novel tests in adults, it is likely they will also have the capacity to significantly improve the diagnosis of childhood tuberculosis. Improving the quality of clinical samples obtained from children with suspected tuberculosis remains an important research priority while awaiting validation of novel diagnostic tests. This review will focus on a number of recent developments for the diagnosis of tuberculosis, with a specific emphasis on the application of these new tests to children in settings where tuberculosis is endemic. PMID:21996697

Connell, Tom G.; Zar, Heather J.

2011-01-01

165

Aerosol Mycobacterium tuberculosis Infection Causes Rapid Loss of Diversity in Gut Microbiota  

PubMed Central

Mycobacterium tuberculosis is an important human pathogen, and yet diagnosis remains challenging. Little research has focused on the impact of M. tuberculosis on the gut microbiota, despite the significant immunological and homeostatic functions of the gastrointestinal tract. To determine the effect of M. tuberculosis infection on the gut microbiota, we followed mice from M. tuberculosis aerosol infection until death, using 16S rRNA sequencing. We saw a rapid change in the gut microbiota in response to infection, with all mice showing a loss and then recovery of microbial community diversity, and found that pre-infection samples clustered separately from post-infection samples, using ecological beta-diversity measures. The effect on the fecal microbiota was observed as rapidly as six days following lung infection. Analysis of additional mice infected by a different M. tuberculosis strain corroborated these results, together demonstrating that the mouse gut microbiota significantly changes with M. tuberculosis infection. PMID:24819223

Gupta, Shashank; Guo, Haidan; Fraser, Claire; Bishai, William

2014-01-01

166

Strain diversity, epistasis and the evolution of drug resistance in Mycobacterium tuberculosis  

PubMed Central

Mycobacterium tuberculosis harbours little DNA sequence diversity compared to other bacteria. However, there is mounting evidence that strain-to-strain variation in this organism has been underestimated. Here we review our current understanding of the genetic diversity among M. tuberculosis clinical strains and discuss the relevance of this diversity for the ongoing global epidemics of drug-resistant tuberculosis. Based on findings in other bacteria, we propose that epistatic interactions between pre-existing differences in strain genetic background, acquired drug resistance-conferring mutations and compensatory changes could play a role in the emergence and spread of drug-resistant M. tuberculosis. PMID:21682802

Borrell, Sònia; Gagneux, Sebastien

2011-01-01

167

A decade of skeletal tuberculosis.  

PubMed

Thirty-eight of 58 patients with skeletal tuberculosis (TB) reviewed were immigrants and 20 were of British indigenous origin. Spinal involvement i 28 cases was less common than involvement of peripheral joints, bones, or tendon sheaths (30 cases). Predisposing factors, including previous TB, were present in 70% of British patients and 31% of immigrants. Follow-up study of 23 cases showed that a complete clinical recovery of the skeletal disease was more likely in immigrants than indigenous cases and also in cases referred to hospital early. Immigrants presented usually within 5 years after arrival in Britain and at a younger age than indigenous cases; a quarter had within 5 sites of infection outside the skeletal system. Skeletal tuberculosis in the indigenous population remains very uncommon, and in half of these cases a history of previous TB was given. The need for continued awareness of skeletal TB is stressed, especially in immigrants, and also the importance of early diagnosis and institution of appropriate therapy. PMID:7065732

Halsey, J P; Reeback, J S; Barnes, C G

1982-02-01

168

Mycobacterium tuberculosis: Success through dormancy  

PubMed Central

Tuberculosis (TB) remains a major health threat, killing near to 2 million individuals around this globe, annually. The sole vaccine developed almost a century ago, provides limited protection only during childhood. After decades without the introduction of new antibiotics, several candidates are currently undergoing clinical investigation. Curing TB requires prolonged combination chemotherapy with several drugs. Moreover, monitoring the success of therapy is questionable due to the lack of reliable biomarkers. To substantially improve the situation, a detailed understanding of the crosstalk between human host and the pathogen Mycobacterium tuberculosis (Mtb) is vital. Principally, Mtb’s enormous success is based on three capacities: First, reprogramming of macrophages after primary infection/phagocytosis in order to prevent its own destruction; second, initiating the formation of well-organized granulomas, comprising different immune cells to create a confined environment for the host–pathogen standoff; third, the capability to shut down its own central metabolism, terminate replication and thereby transit into a stage of dormancy rendering itself extremely resistant to host defense and drug treatment. Here we review the molecular mechanisms underlying these processes, draw conclusions in a working model of mycobacterial dormancy and highlight gaps in our understanding to be addressed in future research. PMID:22320122

Gengenbacher, Martin; Kaufmann, Stefan H. E.

2012-01-01

169

Clinico-pathological features of tuberculosis due to Mycobacterium tuberculosis Uganda genotype in patients with tuberculous lymphadenitis: a cross sectional study  

PubMed Central

Background Tuberculous lymphadenitis is next to pulmonary tuberculosis as the most common cause of tuberculosis. Uganda genotype, one of the sub-lineages of Mycobacterium tuberculosis, is the most prevalent cause of pulmonary tuberculosis in Uganda. We here investigate the clinicopathological characteristics of patients with tuberculous lymphadenitis infected with M. tuberculosis Uganda genotype compared with those infected with M. tuberculosis non-Uganda genotype strains. Methods Between 2010 and 2012, we enrolled 121 patients (mean age 28.5 yrs, male 48%; female 52%) with tuberculous lymphadenitis, and categorized them by their M. tuberculosis genotypes. The clinical features and lymph node cytopathological parameters were compared between patients in the Uganda and non-Uganda categories using a crude and multivariable logistic regression model with adjustment for confounding factors. Results Of the 121participants, 56 (46%) were infected with strains of Uganda genotype. Patients infected with this genotype had significantly lower frequency of abdominal lymphadenopathy (odds ratio 0.4, p?=?0.046) after adjusting for sex, age and HIV. Abdominal lymphadenopathy was also significantly associated with abnormal chest X-ray (p?=?0.027). Conclusion Tuberculous lymphadenitis patients infected with M. tuberculosis Uganda genotype were significantly less prone to have abdominal lymphadenopathy indicating potential reduced ability to disseminate and supporting the concept that differences in M. tuberculosis genotype may have clinical implications. PMID:24690344

2014-01-01

170

Tuberculosis of the genitourinary system-Urinary tract tuberculosis: Renal tuberculosis-Part I  

PubMed Central

Tuberculosis (TB) remains a worldwide scourge and its incidence appears to be increasing due to various factors, such as the spread of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). The insidious onset and non-specific constitutional symptoms of genitourinary tuberculosis (GUTB) often lead to delayed diagnosis and rapid progression to a non-functioning kidney. Due to hematogenous dissemination of TB, there is a potential risk of involvement of the contralateral kidney too. Imaging plays an important role in the making of a timely diagnosis and in the planning of treatment, and thus helps to avoid complications such as renal failure. Imaging of GUTB still remains a challenge, mainly on account of the dearth of literature, especially related to the use of the newer modalities such as magnetic resonance imaging (MRI). This two-part article is a comprehensive review of the epidemiology, pathophysiology, and imaging findings in renal TB. Various imaging features of GUTB are outlined, from the pathognomonic lobar calcification on plain film, to finer early changes such as loss of calyceal sharpness and papillary necrosis on intravenous urography (IVU); to uneven caliectasis and urothelial thickening, in the absence of renal pelvic dilatation, as well as the hitherto unreported ‘lobar caseation’ on ultrasonography (USG). Well-known complications of GUTB such as sinus tracts, fistulae and amyloidosis are described, along with the relatively less well-known complications such as tuberculous interstitial nephritis (TIN), which may remain hidden because of its ‘culture negative’ nature and thus lead to renal failure. The second part of the article reviews the computed tomography (CT) and MRI features of GUTB and touches upon future imaging techniques along with imaging of TB in transplant recipients and in immunocompromised patients. PMID:23986618

Merchant, Suleman; Bharati, Alpa; Merchant, Neesha

2013-01-01

171

New approaches in the diagnosis and treatment of latent tuberculosis infection  

PubMed Central

With nearly 9 million new active disease cases and 2 million deaths occurring worldwide every year, tuberculosis continues to remain a major public health problem. Exposure to Mycobacterium tuberculosis leads to active disease in only ~10% people. An effective immune response in remaining individuals stops M. tuberculosis multiplication. However, the pathogen is completely eradicated in ~10% people while others only succeed in containment of infection as some bacilli escape killing and remain in non-replicating (dormant) state (latent tuberculosis infection) in old lesions. The dormant bacilli can resuscitate and cause active disease if a disruption of immune response occurs. Nearly one-third of world population is latently infected with M. tuberculosis and 5%-10% of infected individuals will develop active disease during their life time. However, the risk of developing active disease is greatly increased (5%-15% every year and ~50% over lifetime) by human immunodeficiency virus-coinfection. While active transmission is a significant contributor of active disease cases in high tuberculosis burden countries, most active disease cases in low tuberculosis incidence countries arise from this pool of latently infected individuals. A positive tuberculin skin test or a more recent and specific interferon-gamma release assay in a person without overt signs of active disease indicates latent tuberculosis infection. Two commercial interferon-gamma release assays, QFT-G-IT and T-SPOT.TB have been developed. The standard treatment for latent tuberculosis infection is daily therapy with isoniazid for nine months. Other options include therapy with rifampicin for 4 months or isoniazid + rifampicin for 3 months or rifampicin + pyrazinamide for 2 months or isoniazid + rifapentine for 3 months. Identification of latently infected individuals and their treatment has lowered tuberculosis incidence in rich, advanced countries. Similar approaches also hold great promise for other countries with low-intermediate rates of tuberculosis incidence. PMID:21126375

2010-01-01

172

Tuberculosis among Children in Alaska.  

ERIC Educational Resources Information Center

The incidence of tuberculosis among Alaskan children under 15 was more than twice the national rate, with Alaska Native children showing a much higher incidence. Children with household exposure to adults with active tuberculosis had a high risk of infection. About 22 percent of pediatric tuberculosis cases were identified through school…

Gessner, Bradford D.

1997-01-01

173

Tuberculosis: A Problem for Lifeguards?  

ERIC Educational Resources Information Center

Lifeguards run the risk of workplace infection by tuberculosis-carrying swimmers. Even if they work in ventilated, sunlit areas (which reduces risk), they can contract tuberculosis when performing respiratory resuscitation. Without appropriate precautions, lifeguards may be unnecessarily exposed. A tuberculosis infection control plan is needed in…

Skaros, Susan

1996-01-01

174

Primary tuberculosis of the retina.  

PubMed Central

A case of pseudoglioma diagnosed on histopathology to be retinal tuberculosis is presented with a general review of the literature on ocular tuberculosis. The case is peculiar in that retinal tuberculosis occurred without concomitant involvement of the choroid. Images PMID:3718917

Saini, J S; Mukherjee, A K; Nadkarni, N

1986-01-01

175

Childhood Tuberculosis, Still with Us...  

ERIC Educational Resources Information Center

The first section of this report on childhood tuberculosis in developed and developing countries discusses the epidemiology of tuberculosis in children. Information is presented on: (1) sources and prevalence of infection; (2) risks, frequency, and types of tuberculosis; (3) mortality rates; and (4) the relation of poverty and AIDS to…

Chaulet, Pierre; And Others

1992-01-01

176

Development of Extensively Drug-resistant Tuberculosis during Multidrug-resistant Tuberculosis Treatment  

E-print Network

Development of Extensively Drug-resistant Tuberculosis during Multidrug-resistant Tuberculosis of Public Health, Boston, Massachusetts; 6 Tomsk Oblast Tuberculosis Services, Tomsk, Russian Federation; 7 Siberia State Medical University, Tomsk, Russian Federation; 8 Tomsk Oblast Tuberculosis Hospital, Tomsk

Cohen, Ted

177

The Human Antibody Response to the Surface of Mycobacterium tuberculosis  

PubMed Central

Background Vaccine-induced human antibodies to surface components of Haemophilus influenzae and Streptococcus pneumonia are correlated with protection. Monoclonal antibodies to surface components of Mycobacterium tuberculosis are also protective in animal models. We have characterized human antibodies that bind to the surface of live M. tuberculosis. Methods Plasma from humans with latent tuberculosis (TB) infection (n?=?23), active TB disease (n?=?40), and uninfected controls (n?=?9) were assayed by ELISA for reactivity to the live M. tuberculosis surface and to inactivated M. tuberculosis fractions (whole cell lysate, lipoarabinomannan, cell wall, and secreted proteins). Results When compared to uninfected controls, patients with active TB disease had higher antibody titers to the surface of live M. tuberculosis (??=?0.72 log10), whole cell lysate (??=?0.82 log10), and secreted proteins (??=?0.62 log10), though there was substantial overlap between the two groups. Individuals with active disease had higher relative IgG avidity (??=?1.4 to 2.6) to all inactivated fractions. Surprisingly, the relative IgG avidity to the live M. tuberculosis surface was lower in the active disease group than in uninfected controls (??=?–1.53, p?=?0.004). Patients with active disease had higher IgG than IgM titers for all inactivated fractions (ratios, 2.8 to 10.1), but equal IgG and IgM titers to the live M. tuberculosis surface (ratio, 1.1). Higher antibody titers to the M. tuberculosis surface were observed in active disease patients who were BCG-vaccinated (??=?0.55 log10, p?=?0.008), foreign-born (??=?0.61 log10, p?=?0.004), or HIV-seronegative (??=?0.60 log10, p?=?0.04). Higher relative IgG avidity scores to the M. tuberculosis surface were also observed in active disease patients who were BCG-vaccinated (??=?1.12, p<0.001) and foreign-born (??=?0.87, p?=?0.01). Conclusions/Significance Humans with active TB disease produce antibodies to the surface of M. tuberculosis with low avidity and with a low IgG/IgM ratio. Highly-avid IgG antibodies to the M. tuberculosis surface may be an appropriate target for future TB vaccines. PMID:24918450

Perley, Casey C.; Frahm, Marc; Click, Eva M.; Dobos, Karen M.; Ferrari, Guido; Stout, Jason E.; Frothingham, Richard

2014-01-01

178

A wireless sensor network to measure the health care workers exposure to tuberculosis  

E-print Network

, 2009 In parallel to the advances in modern medicine, health sciences and public health policy, epidemic in treatment and prevention, tuberculosis remains a disease in expansion and represents the third cause

Paris-Sud XI, Université de

179

Urine PCR Evaluation to Diagnose Pulmonary Tuberculosis  

PubMed Central

Background: Culture and specific staining (including Zeil-Nelson and fluorescent methods) are standard measures for the diagnosis of tuberculosis (TB). These methods are time-consuming and sometimes have a low level of accuracy. In addition, in some cases obtaining samples for smear and culture involves invasive procedures; while in other cases there is no suitable sample for evaluation. Therefore, there is a need for faster and more accurate diagnostic methods. Objectives: The current study investigated the diagnostic value of tuberculosis-polymerase chain reaction (TB-PCR) of urine in the diagnosis of pulmonary tuberculosis (PTB). Patients and Methods: This case-control study included; 77 proven pulmonary tuberculosis cases (according to the national TB protocol), and 30 subjects who were completely healthy. The urine samples (50 mL) were mixed with 0.5 mL Ethylene diamine tetraacetic acid. DNA extraction and PCR testing were performed on all blood samples using SI 6110 primers. Mycobacterium tuberculosis was also cultivated in the sputum and urine samples of the patients. Results: Results of the current study indicated that 48 (62.3%) patients out of 77 had a positive sputum culture. Urine cultures and acid-fast smears were negative. Urine PCR-TB was positive in 48.0% (37/77) of the patients. The speci?c TBPCR complex was positive in 56.2% (27/48) of the positive cultures and 34.4% (10/29) of the negative culture PTB patients. The control group had negative urine PCR (sensitivity 56.2% and specificity 100%). Conclusions: With regard to the ease of urine sample preparation and the 100% specificity the PCR method, performing urine PCR could be used as a diagnostic aid in PTB cases obtaining sputum samples is problematic. PMID:25147688

Heydari, Ali Akbar; Movahhede Danesh, Masood Reza; Ghazvini, Kiarash

2014-01-01

180

Population Structure among Mycobacterium tuberculosis Isolates from Pulmonary Tuberculosis Patients in Colombia  

PubMed Central

Background Phylogeographic composition of M. tuberculosis populations reveals associations between lineages and human populations that might have implications for the development of strategies to control the disease. In Latin America, lineage 4 or the Euro-American, is predominant with considerable variations among and within countries. In Colombia, although few studies from specific localities have revealed differences in M. tuberculosis populations, there are still areas of the country where this information is lacking, as is a comparison of Colombian isolates with those from the rest of the world. Principal Findings A total of 414 M. tuberculosis isolates from adult pulmonary tuberculosis cases from three Colombian states were studied. Isolates were genotyped using IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, and 24-locus Mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTRs). SIT42 (LAM9) and SIT62 (H1) represented 53.3% of isolates, followed by 8.21% SIT50 (H3), 5.07% SIT53 (T1), and 3.14% SIT727 (H1). Composite spoligotyping and 24-locus MIRU- VNTR minimum spanning tree analysis suggest a recent expansion of SIT42 and SIT62 evolved originally from SIT53 (T1). The proportion of Haarlem sublineage (44.3%) was significantly higher than that in neighboring countries. Associations were found between M. tuberculosis MDR and SIT45 (H1), as well as HIV-positive serology with SIT727 (H1) and SIT53 (T1). Conclusions This study showed the population structure of M. tuberculosis in several regions from Colombia with a dominance of the LAM and Haarlem sublineages, particularly in two major urban settings (Medellín and Cali). Dominant spoligotypes were LAM9 (SIT 42) and Haarlem (SIT62). The proportion of the Haarlem sublineage was higher in Colombia compared to that in neighboring countries, suggesting particular conditions of co-evolution with the corresponding human population that favor the success of this sublineage. PMID:24747767

Realpe, Teresa; Correa, Nidia; Rozo, Juan Carlos; Ferro, Beatriz Elena; Gomez, Verónica; Zapata, Elsa; Ribon, Wellman; Puerto, Gloria; Castro, Claudia; Nieto, Luisa María; Diaz, Maria Lilia; Rivera, Oriana; Couvin, David; Rastogi, Nalin; Arbelaez, Maria Patricia; Robledo, Jaime

2014-01-01

181

Drug resistance of Mycobacterium tuberculosis isolates from tuberculosis lymphadenitis patients in Ethiopia  

PubMed Central

Background & objectives: The emergence of drug resistance tuberculosis (TB) is a significant challenge for TB control and prevention programmes, and the major problem is multidrug resistant tuberculosis (MDR-TB). The present study was carried out to determine the frequency of drug resistant Mycobacterium tuberculosis isolates among newly and retreated TB lymphadenitis patients and risk factors for acquiring this infection. Methods: Two hundred twenty five M. tuberculosis isolates from TB lymphadenitis patients who were diagnosed as new and retreated tuberculosis cases between April 2012 and May 2012 were included in this study. Isolates were tested for susceptibility to isoniazed (INH), rifampicin (RMP), streptomycin (SM), ethambutol (EMB) and pyrazinamide (PZA) using the BacT/AlerT 3D system protocol. Results: Among 225 isolates, 15 (6.7%) were resistant to at least one first line anti-TB drug. Three (1.3%) were MDR-TB. Resistance to INH, RMP, SM, and EMB was found in 8 (3.6%), 4 (1.8%), 10 (4.4%), and 4 (1.8%) isolates, respectively. Of the 212 new TB lymphadenitis cases three (1.4%) were MDR-TB. A rifampicin resistant M. tuberculosis isolate was diagnosed from smear and culture negative newly treated cases. All isolates were susceptible to PZA. Matted cervical lymph nodes were the prominent sites involved. Newly treated TB lymphadenitis patients had a greater risk for presenting resistance to anti-TB drugs (P=0.046). Interpretation & conclusions: Our study showed that TB lymphadenitis patients harboured drug resistant TB and MDR-TB, although at a low rate. Resistance was not associated with age, sex, patients’ education and contact history. Further research is required to determine transmission dynamics of drug resistant strains. PMID:25222786

Biadglegne, Fantahun; Tessema, Belay; Sack, Ulrich; Rodloff, Arne C.

2014-01-01

182

Resazurin Tube Method: Rapid, Simple, and Inexpensive Method for Detection of Drug Resistance in the Clinical Isolates of Mycobacterium Tuberculosis  

PubMed Central

Background: Tuberculosis (TB) remains a serious public health problem worldwide. The emergence of drug resistance and multidrug resistance (MDR) has become the main threat to TB treatment and control programs. Rapid detection is critical for the effective treatment of patients. In recent times, a new method using the colorimetric indicator resazurin has been proposed for drug susceptibility of Mycobacterium tuberculosis. Materials and Methods: In this study, the resazurin reduction assay was adapted to screw cap tubes. Using the Resazurin Tube Method (RTM), a total of 100 clinical isolates were tested against Rifampicin (RIF) and Isoniazide (INH). By visual reading, the minimum inhibitory concentrations (MICs) were obtained after eight days. The results obtained were compared with the gold standard proportion method. Results: Excellent results were obtained for RTM with a sensitivity of 100% for both RIF and INH, with a specificity of 98.7 and 95.3%, respectively. Kappa is the measure of agreement between the RTM and proportion method (PM) for RIF and INH, which was found to be 0.972 and 0.935 for RIF and INH, respectively. Conclusion: The RTM appears to be a reliable method for the rapid and simultaneous detection of MDR-TB and drug susceptibility testing (DST) of M. tuberculosis. It is simple, inexpensive, and with no biohazard risk involved.

Patil, Santosh S; Mohite, Shivajirao T; Kulkarni, Sunanda A; Udgaonkar, Usha S

2014-01-01

183

Tuberculosis diagnosis: primary health care or emergency medical services?  

PubMed Central

OBJECTIVE To assess primary health care and emergency medical services performance for tuberculosis diagnosis. METHODS Cross-sectional study were conducted with 90 health professionals from primary health care and 68 from emergency medical services, in Ribeirao Preto, SP, Southeastern Brazil, in 2009. A structured questionnaire based on an instrument of tuberculosis care assessment was used. The association between health service and the variables of structure and process for tuberculosis diagnosis was assessed by Chi-square test, Fisher's exact test (both with 5% of statistical significance) and multiple correspondence analysis. RESULTS Primary health care was associated with the adequate provision of inputs and human resources, as well as with the sputum test request. Emergencial medical services were associated with the availability of X-ray equipment, work overload, human resources turnover, insufficient availability of health professionals, unavailability of sputum collection pots and do not request sputum test. In both services, tuberculosis diagnosis remained as a physician's responsibility. CONCLUSIONS Emergencial medical services presented weaknesses in its structure to identify tuberculosis suspects. Gaps on the process were identified in both primary health care and emergencial medical services. This situation highlights the need for qualification of health services that are the main gateway to health system to meet sector reforms that prioritize the timely diagnosis of tuberculosis and its control. PMID:24626553

Andrade, Rubia Laine de Paula; Scatolin, Beatriz Estuque; Wysocki, Anneliese Domingues; Beraldo, Aline Ale; Monroe, Aline Aparecida; Scatena, Lúcia Marina; Villa, Tereza Cristina Scatena

2013-01-01

184

[Acute miliary tuberculosis or Isambert disease: a case report].  

PubMed

Pharynx tuberculosis consists in a set of active lesions in granulomatous-type mucosa, resulting from Mycobacterium tuberculosis infection. In an endemic context, this diagnosis should be raised in cases of head and neck disease. A recent observation of a case of acute miliary tuberculosis gave us the opportunity to conduct a literature review of this disorder. This 9-year-old girl presented with dysphagia associated with pharyngeal discomfort, snoring, and hoarseness lasting for 8 months. This pharyngeal syndrome occurred in the context of an impaired general condition. Clinical examination found a diffuse mucosal granulation aspect in the oropharynx. The workup showed an inflammatory syndrome with a strong positive intradermal tuberculin reaction. The biopsy found an aspect of giant cell granuloma with caseous necrosis. The course was favorable on antituberculous chemotherapy. Tuberculosis is a chronic bacterial infection caused by a bacterium belonging to the M. tuberculosis complex. Pharyngeal tuberculosis remains a rare disease, but several epidemiological parameters show an upsurge of this disease, prompting us to report this observation. PMID:23266174

Ziad, T; Nouri, H; Adny, A; Rochdi, Y; Aderdour, L; Raji, A

2013-01-01

185

The Singapore Tuberculosis Elimination Programme: the first five years.  

PubMed Central

The Singapore Tuberculosis Elimination Programme (STEP) was launched in 1997 because the incidence of the disease had remained between 49 and 56 per 100,000 resident population for the preceding 10 years. STEP involves the following key interventions: directly observed therapy (DOT) in public primary health care clinics; monitoring of treatment progress and outcome for all cases by means of a National Treatment Surveillance Registry; and preventive therapy for recently infected close contacts of infectious tuberculosis cases. Among other activities are the revamping of the National Tuberculosis Notification Registry, the discontinuation of BCG revaccination for schoolchildren, the tightening up of defaulter tracing, and the education of the medical community and the public. Future plans include an outreach programme for specific groups of patients who are unable to attend their nearest public primary care clinics for DOT, the detention of infectious recalcitrant defaulters for treatment under the Infectious Diseases Act, the molecular fingerprinting of tuberculosis isolates, and targeted screening of high-risk groups. The incidence of tuberculosis fell from 57 per 100,000 population in 1998 to 48 per 100,000 in 1999 and continued to decline to 44 per 100,000 in 2001. With political will and commitment and the support of the medical community and the public it is hoped that STEP will achieve further progress towards the elimination of tuberculosis in Singapore. PMID:12764518

Chee, Cynthia B. E.; James, Lyn

2003-01-01

186

Molecular Characterization of Isoniazid Resistance in Mycobacterium tuberculosis: Identification of a Novel Mutation in inhA  

Microsoft Academic Search

Multiplex allele-specific PCRs detecting katG codon 315 and mabA (bp 15) mutations could specifically identify 77.5% of isoniazid-resistant Mycobacterium tuberculosis strains in the South China region. One clinical isolate harboring InhA Ile194Thr was characterized to show strong association with isoniazid resistance in Mycobacterium tuberculosis. Tuberculosis (TB) remains a public health issue in many parts of the world (20). The situation

E. T. Y. Leung; P. L. Ho; K. Y. Yuen; W. L. Woo; T. H. Lam; R. Y. Kao; W. H. Seto; W. C. Yam

2006-01-01

187

Hypercalcaemia: atypical presentation of miliary tuberculosis.  

PubMed

We report an unusual case of miliary tuberculosis in a 77-year-old Filipino man with hypertension, diabetes mellitus, nephrolithiasis status-post left nephrectomy, presenting with 1 month of fever, generalised weakness and weight loss. Laboratory data were significant for anaemia, hypercalcaemia and acute kidney injury. Chest radiograph showed ground glass opacities and interstitial infiltrates. Extensive workup was performed to evaluate fever and hypercalcaemia. Malignancy, hormonal and septic workup were all unremarkable. Tuberculin skin test was negative. Sputum, pleural fluid, bronchoalveolar lavage and cerebrospinal fluid were acid-fast bacilli (AFB) smear negative. Remarkably, urine AFB smear was positive. Caseating granulomas were seen on transbronchial biopsy. Antituberculosis therapy was initiated which lead to defervescence and initial clinical improvement. However, hospital course became complicated by small bowel obstruction and respiratory failure. He subsequently developed pulseless electrical activity and expired. An autopsy confirmed the presence of tuberculosis in multiple organs including his remaining kidney. PMID:24569260

So, Edison; Bolger, Dennis Thomas

2014-01-01

188

[The diagnosis of pulmonary tuberculosis].  

PubMed

Mycobacterium tuberculosis (M. tuberculosis) infects all organs in the body; however, lung infection is the primary lesion. The total number of infections is decreasing, but the percentage of infections in older people is rising. Because this disease is due to infection with M. tuberculosis, the diagnosis requires the presence of M. tuberculosis. Chest X-ray and CT are very powerful tools to suggest the presence of M. tuberculosis infection. Pathological examination of the tissues also shows the typical findings of M. tuberculosis infection; however, the presence of the bacterium was not proven in certain cases of M. tuberculosis infection, and especially in cases of latent infection. Recently, the whole-blood interferon--gamma test (QuantiFERON-TB, QFT) became more popular than the tuberculin skin test. It is reported that the specificity and sensitivity of QFT are similar to or better than the tuberculin skin test. However, it should be noted that QFT positive does not automatically lead to a diagnosis of active M. tuberculosis infection and that QFT is one of the supplementary tests in the diagnosis of M. tuberculosis infection. Currently, massive infection with M. tuberculosis is increasing. The precise responsible linkage in massive infection with M. tuberculosis needs DNA polymorphism analysis using variable numbers of tandem repeats (VNTR) or restricted fragment length polymorphism (RFLP). PMID:23198540

Koyama, Sekiya; Sakaguchi, Nobuki; Hotta, Jyunnichi

2012-08-01

189

An integrated machine learning approach for predicting DosR-regulated genes in Mycobacterium tuberculosis  

E-print Network

Abstract Background DosR is an important regulator of the response to stress such as limited oxygen availability in Mycobacterium tuberculosis. Time course gene expression data enable us to dissect this response on the gene regulatory level. The m...

Zhang, Yi; Hatch, Kim A; Bacon, Joanna; Wernisch, Lorenz

2010-03-31

190

A Novel Murine Cytomegalovirus Vaccine Vector Protects against Mycobacterium tuberculosis  

PubMed Central

Tuberculosis remains a global health problem so that a more effective vaccine than bacillus Calmette–Guérin is urgently needed. Cytomegaloviruses persist lifelong in vivo and induce powerful immune and increasing (“inflationary”) responses, making them attractive vaccine vectors. We have used an m1–m16-deleted recombinant murine CMV (MCMV) expressing Mycobacterium tuberculosis Ag 85A to show that infection of mice with this recombinant significantly reduces the mycobacterial load after challenge with M. tuberculosis, whereas control empty virus has a lesser effect. Both viruses induce immune responses to H-2d–restricted epitopes of MCMV pp89 and M18 Ags characteristic of infection with other MCMVs. A low frequency of 85A-specific memory cells could be revealed by in vivo or in vitro boosting or after challenge with M. tuberculosis. Kinetic analysis of M. tuberculosis growth in the lungs of CMV-infected mice shows early inhibition of M. tuberculosis growth abolished by treatment with NK-depleting anti–asialo ganglio-N-tetraosylceramide Ab. Microarray analysis of the lungs of naive and CMV-infected mice shows increased IL-21 mRNA in infected mice, whereas in vitro NK assays indicate increased levels of NK activity. These data indicate that activation of NK cells by MCMV provides early nonspecific protection against M. tuberculosis, potentiated by a weak 85A-specific T cell response, and they reinforce the view that the innate immune system plays an important role in both natural and vaccine-induced protection against M. tuberculosis. PMID:25070842

Beverley, Peter C. L.; Ruzsics, Zsolt; Hey, Ariann; Hutchings, Claire; Boos, Simone; Bolinger, Beatrice; Marchi, Emanuele; O'Hara, Geraldine; Klenerman, Paul; Koszinowski, Ulrich H.

2014-01-01

191

Various hysterosalpingography findings of female genital tuberculosis: A case series  

PubMed Central

Background: Genital tuberculosis is a chorionic disease and mostly occurs by haematogenous spread from extra genital source like lungs, peritoneum, lymph nodes and bones. Transmission through a sexual intercourse is also possible. Since the majority of patients are in reproductive ages, involvement of fallopian tubes and endometrium cause infertility in patients. Cases: Reviewing 4 cases of female genital tuberculosis, which referred to an infertility treatment center with various symptoms, we encountered various appearances on hysterosalpingography (HSG). Conclusion: The genitourinary tract is the most common site of extra pulmonary TB. The primary focus of genital tuberculosis is fallopian tubes, which are almost always affected bilaterally but not symmetrically. Because of common involvement of fallopian tubes and endometrial cavity, disease causes infertility. Diagnosis is not easy because genital tuberculosis has a wide range of clinical and radiological manifestations with slow growing symptoms. Detailed hysterosalpingography finding may be helpful in better diagnosis of the disease. This case series aims to depict the various hystrosalpingographic appearances and pathology produced by tuberculosis and related literatures are reviewed in order to establish a better diagnostic evaluation of genital tuberculosis. PMID:24639787

Afzali, Nargess; Ahmadi, Firoozeh; Akhbari, Farnaz

2013-01-01

192

Disseminated tuberculosis after extracorporeal shock-wave lithotripsy in an AIDS patient presenting with urosepsis.  

PubMed

Haematogenous dissemination of undiagnosed urinary tuberculosis after performing extracorporeal shock-wave lithotripsy (ESWL) is extremely rare. Herein, we report a 41-year-old male who presented with urosepsis to the emergency room; catheterization was performed and retention resolved. He had a tattoo on his left arm and a five-year history of intravenous drug use. Blood tests indicated anaemia, leukocytosis, elevated CRP and ESR and mild hyponatraemia; haematuria, moderate bacteriuria and 2+ proteinuria on urinanalysis were observed. Chest X-ray revealed lesions suggestive of miliary tuberculosis, which was confirmed by chest CT scan. Brain CT and MRI suggested brain involvement in the setting of tuberculosis. On further investigations, HIV infection and hepatitis C seropositivity were detected and the patient remained in a coma for five days with a Glasgow Coma Scale of 6/15. Finally, the diagnosis of haematogenous dissemination of tuberculosis following lithotripsy was established. Anti-tuberculosis and anti-retroviral therapy were prescribed and monthly follow-up visits were scheduled. In conclusion, in a patient diagnosed with ureterolithiasis, a thorough history and physical examination, with specific attention to HIV and tuberculosis predisposing factors, should be carried out and preoperative screening tests considering the possibility of urinary tuberculosis are required. Finally, if urinary tuberculosis is detected, ESWL must be postponed until after appropriate treatment of tuberculosis. PMID:23970650

Tourchi, Ali; Ebadi, Maryam; Hosseinzadeh, Alireza; Shabaninia, Mahsa

2014-03-01

193

Tuberculosis Incidence in HIV/AIDS Patients in Israel, 1983–2010  

PubMed Central

Objectives People living with HIV/AIDS (PLWHA) who develop tuberculosis disease are at greater mortality-risk. This study aimed to assess tuberculosis disease incidence among all PLWHA in Israel and identify populations at high-risk for developing tuberculosis. Design and Methods Retrospective cohort-study based on the National HIV and Tuberculosis Registries, which were cross-matched and followed for the last 28-years. PLWHA who developed tuberculosis were compared to those who did not by the Cox-proportional analysis to generate hazard-ratios, and survival-analysis was performed by Log-Rank test. Results Of all the 6579 PLWHA reported between 1983 and 2010, corresponding to 55737 person-years, 384 (5.8%) developed tuberculosis. Of those, 14 were Israeli-born and 370 were non-Israeli born. The overall tuberculosis incidence-density was 6.9 cases/1000 person-years (95% CI 1.8–12.0). The cumulative tuberculosis-incidence among PLWHA in 2010 was 586 times higher than in HIV-negative individuals (3400 and 5.8 cases per 100000 population, respectively). Higher hazard-ratios to developing tuberculosis were found in migrant citizens PLWHA who were males, non-Israeli born, those who were diagnosed with HIV/AIDS after 1997, those who originated in high-tuberculosis prevalence country and those who acquired HIV by heterosexual or drug-injection transmission. PLWHA who developed tuberculosis had higher odds of dying than other PLWHA (36.5% and 16.6%, respectively, p<0.001, odds ratio?=?2.8, 95% confidence-interval 2.3–3.6). In survival-analysis, time to develop tuberculosis was shorter among males than females, in PLWHA who were reported with HIV after 1997, in heterosexual who originated in high-tuberculosis countries, followed by injecting drug-users, heterosexual from low-tuberculosis burden countries and men who have sex with men. Conclusion Tuberculosis-incidence is higher among non-Israeli born PLWHA, with decreasing trends from 1991. Despite the moderate TB-rate disease among PLWHA, it remains an important cause for severe morbidity and mortality. Tuberculosis in PLWHA reflects mainly the tuberculosis-burden in the originating country and possibly also the mode of HIV-transmission. PMID:24278157

Mor, Zohar; Lidji, Moshe; Cedar, Noa; Grotto, Itamar; Chemtob, Daniel

2013-01-01

194

Classification of intraocular tuberculosis.  

PubMed

Abstract Tuberculosis in the TB endemic countries commonly manifests in the eye as tuberculous uveitis. There is a wide spectrum of the clinical manifestations of intraocular tuberculosis (IOTB). For want of any gold standard diagnostic tests or diagnostic criteria, the estimates of IOTB prevalence have varied greatly. None of the previously suggested guidelines for diagnosis of IOTB have been validated. We give definitions of clinical signs and diagnostic tests that have been used in the literature. Based on these, we propose a classification of IOTB comprising "confirmed IOTB," "probable IOTB," and "possible IOTB." This of necessity needs consensus among experts before carrying out studies to validate this classification. PMID:25314361

Gupta, Amod; Sharma, Aman; Bansal, Reema; Sharma, Kusum

2015-02-01

195

Kinetics and Ligand-Binding Preferences of Mycobacterium tuberculosis Thymidylate Synthases, ThyA and ThyX  

Microsoft Academic Search

BackgroundMycobacterium tuberculosis kills approximately 2 million people each year and presents an urgent need to identify new targets and new antitubercular drugs. Thymidylate synthase (TS) enzymes from other species offer good targets for drug development and the M. tuberculosis genome contains two putative TS enzymes, a conventional ThyA and a flavin-based ThyX. In M. tuberculosis, both TS enzymes have been

Joshua H. Hunter; Ramesh Gujjar; Cullen K. T. Pang; Pradipsinh K. Rathod; Edathara Abraham

2008-01-01

196

Role for interferon-gamma release assays in latent tuberculosis screening before TNF-? antagonist therapy.  

PubMed

TNF-? antagonist therapy is associated with a risk of severe, extrapulmonary, disseminated tuberculosis, which is fatal in 10% of cases. The risk of tuberculosis is increased four-fold in patients on TNF-? antagonist therapy. The main risk factors are a history of untreated or inadequately treated primary tuberculosis, recent contact with a tuberculosis patient, and residence in or travel to a high-endemicity region. Infection surveillance agencies throughout the world have issued recommendations to ensure the detection and treatment of latent tuberculosis before TNF-? antagonist initiation. These recommendations have returned the incidence of tuberculosis to the level seen before the introduction of TNF-? antagonists. Nevertheless, there is still room for improvement. Recommendations about latent tuberculosis screening include the use of tuberculin skin tests. However, these tests are positive in individuals vaccinated with the BCG vaccine, which leads to overuse of tuberculosis chemoprophylaxis and, therefore, to unnecessary patient exposure to hepatotoxic effects. Furthermore, tuberculin skin tests may be falsely negative in immunosuppressed patients, leading to underuse of tuberculosis prophylaxis. These shortcomings of tuberculin skin tests have generated interest in interferon-gamma release assays (IGRAs). In patients with overt tuberculosis, IGRAs are more sensitive and more specific than tuberculin skin tests. However, the accuracy of IGRAs for diagnosing latent tuberculosis remains unknown, because no reference standard is available. In addition, patients taking immunosuppressant agents to treat systemic disease may exhibit anergia, which complicates the interpretation of IGRAs. Until additional data become available, caution requires that IGRAs be used only when a positive or negative result, as assessed on a case-by-case basis, will help to decide whether tuberculosis chemoprophylaxis is in order. PMID:21251863

Lioté, Huguette; Lioté, Frédéric

2011-07-01

197

HIV Seroprevalence among Tuberculosis Patients in India, 2006–2007  

PubMed Central

Background Little information exists regarding the burden of HIV among tuberculosis patients in India, and no population-based surveys have been previously reported. A community-based HIV prevalence survey was conducted among tuberculosis patients treated by the national tuberculosis control programme to evaluate the HIV prevalence among tuberculosis patients in India. Methodology/Principal Findings Fifteen districts (total population: 40.2 million) across 8 states were stratified by HIV prevalence in antenatal clinic HIV surveillance sites and randomly selected. From December 2006 to May 2007, remnant serum was collected from patients' clinical specimens taken after 2 months of anti-tuberculosis treatment and subjected to anonymous, unlinked HIV testing. Specimens were obtained and successfully tested for 5,995 (73%) of 8,217 tuberculosis patients eligible for the survey. HIV prevalence ranged widely among the 15 surveyed districts, from 1% in Koch Bihar, West Bengal, to 13.8% in Guntur, Andhra Pradesh. HIV infection was 1.3 times more likely among male TB patients than among female patients. Relative to smear-positive tuberculosis, HIV infection was 1.4 times more likely among smear-negative patients and 1.3 times more likely among extrapulmonary patients. In 4 higher-HIV prevalence districts, which had been previously surveyed in 2005–2006, no significant change in HIV prevalence was detected. Conclusions The burden of HIV among tuberculosis patients varies widely in India. Programme efforts to implement comprehensive TB-HIV services should be targeted to areas with the highest HIV burden. Surveillance through routine reporting or special surveys is necessary to detect areas requiring intensification of TB-HIV collaborative activities. PMID:18714335

Raizada, Neeraj; Chauhan, Lakbir Singh; Khera, Ajay; Sokhey, Jotna; Wares, D. Fraser; Sahu, Suvanand; Thakur, Rahul; Dewan, Puneet Kumar

2008-01-01

198

Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients  

PubMed Central

Background.Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies. Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression. Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome. Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis. PMID:22732925

Kunnath-Velayudhan, Shajo; Davidow, Amy L.; Wang, Hui-Yun; Molina, Douglas M.; Huynh, Vu T.; Salamon, Hugh; Pine, Richard; Michel, Gerd; Perkins, Mark D.; Xiaowu, Liang; Felgner, Philip L.; Flynn, JoAnne L.; Catanzaro, Antonino; Gennaro, Maria L.

2012-01-01

199

Mycobacterium tuberculosis evades host immunity by recruiting mesenchymal stem cells  

PubMed Central

Tuberculosis (TB) is the cause of 2 million deaths each year, which is the second highest cause of mortality from a single infectious disease worldwide. Resistance of these organisms to drugs has emerged as an important health concern. Alternative approaches to the prevention and treatment of tuberculosis are therefore urgently needed. Despite the generation of robust host immune responses, Mycobacterium tuberculosis (M. tb) successfully evades host immunity and establishes a persistent infection. The mechanism(s) by which M. tuberculosis manages to persist in the face of potent host immune responses remain(s) incompletely understood. Here, we demonstrate that M. tb suppresses T-lymphocyte responses by recruiting mesenchymal stem cells (MSCs) to the site of infection. We found that MSCs infiltrated tissues in mice containing M. tb organisms and T lymphocytes. We further demonstrate that MSCs suppressed T-cell responses by producing nitric oxide. Our findings reveal a key role of MSCs in the capacity of M. tb to evade host immune responses and identify these cells as unique targets for therapeutic intervention in tuberculosis. PMID:21135221

Raghuvanshi, Shilpa; Sharma, Pawan; Singh, Sarman; Van Kaer, Luc; Das, Gobardhan

2010-01-01

200

MUBII-TB-DB: a database of mutations associated with antibiotic resistance in Mycobacterium tuberculosis  

PubMed Central

Background Tuberculosis is an infectious bacterial disease caused by Mycobacterium tuberculosis. It remains a major health threat, killing over one million people every year worldwide. An early antibiotic therapy is the basis of the treatment, and the emergence and spread of multidrug and extensively drug-resistant mutant strains raise significant challenges. As these bacteria grow very slowly, drug resistance mutations are currently detected using molecular biology techniques. Resistance mutations are identified by sequencing the resistance-linked genes followed by a comparison with the literature data. The only online database is the TB Drug Resistance Mutation database (TBDReaM database); however, it requires mutation detection before use, and its interrogation is complex due to its loose syntax and grammar. Description The MUBII-TB-DB database is a simple, highly structured text-based database that contains a set of Mycobacterium tuberculosis mutations (DNA and proteins) occurring at seven loci: rpoB, pncA, katG; mabA(fabG1)-inhA, gyrA, gyrB, and rrs. Resistance mutation data were extracted after the systematic review of MEDLINE referenced publications before March 2013. MUBII analyzes the query sequence obtained by PCR-sequencing using two parallel strategies: i) a BLAST search against a set of previously reconstructed mutated sequences and ii) the alignment of the query sequences (DNA and its protein translation) with the wild-type sequences. The post-treatment includes the extraction of the aligned sequences together with their descriptors (position and nature of mutations). The whole procedure is performed using the internet. The results are graphs (alignments) and text (description of the mutation, therapeutic significance). The system is quick and easy to use, even for technicians without bioinformatics training. Conclusion MUBII-TB-DB is a structured database of the mutations occurring at seven loci of major therapeutic value in tuberculosis management. Moreover, the system provides interpretation of the mutations in biological and therapeutic terms and can evolve by the addition of newly described mutations. Its goal is to provide easy and comprehensive access through a client–server model over the Web to an up-to-date database of mutations that lead to the resistance of M. tuberculosis to antibiotics. PMID:24731071

2014-01-01

201

Tuberculosis Facts - TB and HIV/AIDS  

MedlinePLUS

... STD, and TB Prevention Division of Tuberculosis Elimination Tuberculosis (TB) Facts TB and HIV/AIDS What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ...

202

Tuberculosis Facts - You Can Prevent TB  

MedlinePLUS

... STD, and TB Prevention Division of Tuberculosis Elimination Tuberculosis (TB) Facts You Can Prevent TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ...

203

Tuberculosis Facts - TB Can Be Treated  

MedlinePLUS

... STD, and TB Prevention Division of Tuberculosis Elimination Tuberculosis (TB) Facts TB Can Be Treated What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ...

204

Parasitic infection may be associated with discordant responses to QuantiFERON and tuberculin skin test in apparently healthy children and adolescents in a tuberculosis endemic setting, Ethiopia  

PubMed Central

Background M. tuberculosis remains one of the world’s deadliest pathogens in part because of its ability to establish persistent, latent infections, which can later reactivate to cause disease. In regions of the globe where disease is endemic, as much as 50% of the population is thought to be latently infected, complicating diagnosis and tuberculosis control. The tools most commonly used for diagnosis of latent M. tuberculosis infection are the tuberculin skin test and the newer interferon-gamma release assays, both of which rely on an antigen-specific memory response as an indicator of infection. It is clear that the two tests, do not always give concordant results, but the factors leading to this are only partially understood. Methods In this study we examined 245 healthy school children aged from 12 to 20 years from Addis Ababa, a tuberculosis-endemic region, characterised them with regard to response in the tuberculin skin test and QuantIFERON™ test and assessed factors that might contribute to discordant responses. Results Although concordance between the tests was generally fair (90% concordance), there was a subset of children who had a positive QuantIFERON™ result but a negative tuberculin skin test. After analysis of multiple parameters the data suggest that discordance was most strongly associated with the presence of parasites in the stool. Conclusions Parasitic gut infections are frequent in most regions where M. tuberculosis is endemic. This study, while preliminary, suggests that the tuberculin skin test should be interpreted with caution where this may be the case. PMID:23738853

2013-01-01

205

A case of skeletal tuberculosis and psoas abscess: disease activity evaluated using 18?F-fluorodeoxyglucose positron emission tomography-computed tomography  

PubMed Central

Background Psoas abscess complicating tuberculous spondylitis is a rare morbidity in extrapulmonary tuberculosis. There are no established guidelines for evaluating the clinical response of psoas abscess. Although several studies have shown that positron emission tomography-computed tomography with 18?F-fluorodeoxyglucose can play a potential role in diagnosing multifocal tuberculosis and monitoring the clinical response of pulmonary tuberculosis, to our knowledge, this is the first report demonstrating that positron emission tomography-computed tomography is useful for evaluating local inflammation and disease activity of a tuberculous psoas abscess. Case presentation We report a case of multifocal bone and lymph node tuberculosis with concomitant lumbar psoas abscess in a 77-year-old man, along with a literature review. An initial positron emission tomography-computed tomography scan showed intense 18?F-fluorodeoxyglucose accumulation in the sternum, ribs, vertebrae, and lymph nodes. The patient was successfully treated with antitubercular agents and computed tomography-guided drainage therapy. A follow-up positron emission tomography-computed tomography after abscess drainage and 9 months of antitubercular drug treatment revealed that the majority of lesions improved; however, protracted inflammation surrounding the psoas abscess was still observed. These results indicate that disease activity of psoas abscess can remain, even after successful drainage and antitubercular medication regime of appropriate duration. Conclusion We have successfully followed up the extent of skeletal tuberculosis complicated with psoas abscess by positron emission tomography-computed tomography. In this patient, positron emission tomography-computed tomography is useful for evaluating the disease activity of tuberculous psoas abscess and for assessing the appropriate duration of antitubercular drug therapy in psoas abscess. PMID:24225333

2013-01-01

206

Genetic vaccination against tuberculosis  

Microsoft Academic Search

New weapons are needed in the fight against tuberculosis. Recent research indicates that a vaccine better than BCG may be within reach. A diverse range of protein antigens can give encouragingly high levels of protective immunity in animal models when administered with adjuvants or as DNA vaccines. Accelerated arrest of bacterial multiplication followed by sustained decline in bacterial numbers are

Douglas B. Lowrie; Celio L. Silvan; Ricardo E. Tascon

1997-01-01

207

Extrapulmonary Tuberculosis: An Overview  

Microsoft Academic Search

In the 1980s, after a steady decline during preceding decades, there was a resurgence in the rate of tuberculosis in the United States that coincided with the acquired immunodeficiency syn- drome epidemic. Disease patterns since have changed, with a higher incidence of disseminated and extrapulmonary disease now found. Extrapulmonary sites of infection commonly include lymph nodes, pleura, and osteoarticular areas,

MARJORIE P. GOLDEN; R. VIKRAM

208

Molecular epidemiology and transmission dynamics of Mycobacterium tuberculosis in Northwest Ethiopia: new phylogenetic lineages found in Northwest Ethiopia  

PubMed Central

Background Although Ethiopia ranks seventh among the world’s 22 high-burden tuberculosis (TB) countries, little is known about strain diversity and transmission. In this study, we present the first in-depth analysis of the population structure and transmission dynamics of Mycobacterium tuberculosis strains from Northwest Ethiopia. Methods In the present study, 244 M. tuberculosis isolates where analysed by mycobacterial interspersed repetitive unit - variable number tandem repeat 24-loci typing and spoligotyping methods to determine phylogenetic lineages and perform cluster analysis. Clusters of strains with identical genotyping patterns were considered as an indicator for the recent transmission. Results Of 244 isolates, 59.0% were classified into nine previously described lineages: Dehli/CAS (38.9%), Haarlem (8.6%), Ural (3.3%), LAM (3.3%), TUR (2.0%), X-type (1.2%), S-type (0.8%), Beijing (0.4%) and Uganda II (0.4%). Interestingly, 31.6% of the strains were grouped into four new lineages and were named as Ethiopia_3 (13.1%), Ethiopia_1 (7.8%), Ethiopia_H37Rv like (7.0%) and Ethiopia_2 (3.7%) lineages. The remaining 9.4% of the isolates could not be assigned to the known or new lineages. Overall, 45.1% of the isolates were grouped in clusters, indicating a high rate of recent transmission. Conclusions This study confirms a highly diverse M. tuberculosis population structure, the presence of new phylogenetic lineages and a predominance of the Dehli/CAS lineage in Northwest Ethiopia. The high rate of recent transmission indicates defects of the TB control program in Northwest Ethiopia. This emphasizes the importance of strengthening laboratory diagnosis of TB, intensified case finding and treatment of TB patients to interrupt the chain of transmission. PMID:23496968

2013-01-01

209

Rapid Immunochromatographic Test for the Identification and Discrimination of Mycobacterium tuberculosis Complex Isolates from Non-tuberculous Mycobacteria  

PubMed Central

Background: A new rapid Immunochromatographic test (ICT) kit (SDBioline TB Ag MPT64RAPID®) developed by Standard Diagnostics, South Korea was evaluated for rapid differentiation of M. tuberculosis from non tuberculous mycobacteria (NTM). It detects MPT 64 antigen in M. tuberculosis isolates using mouse monoclonal MPT 64 antibody. The kit was assessed for routine identification of the Acid Fast Bacilli(AFB) isolated in our laboratory. Materials and Methods: Two hundred eight culture isolates of Mycobacteria were tested using ICT test kit for detection of MPT 64 antigen from liquid and solid culture. H37Rv strain was employed as the positive reference control. Any negative result was referred for confirmation by Gen Probe Accu Probe assay for MTB Complex (Gen-Probe, San Diego, Calif.). Speciation of NTM was performed using genotypic Mycobacterium CM assay (Hain’s life sciences, Germany). Results: Of the 208 culture positive isolates tested, 182 (87.5%) were found positive for Mycobacterium tuberculosis Complex and remaining 26 (12.5%) were considered as NTM. These results were further confirmed by Gen Probe Accu probe assay that served as the reference method for detection of MTBC. H37Rv reference strain was taken as a control for ICT test and molecular tests. The reference strain showed the presence of MPT64 antigen band in the ICT test. Similar bands were formed in all MTBC (182) isolates tested, proving 100 per cent sensitivity and no bands were detected in 48 (100%) NTM isolates tested, proving 100 per cent specificity of the ICT kit. Conclusion: Tuberculosis is a global pandemic. Rapid identification of Mycobacteria as MTB complex or non-tuberculous Mycobacteria from culture is important for treatment of infected cases and drug susceptibility testing of the culture isolate. MPT 64 TB antgen detection using SD Bioline Immunochromatographic test is a simple and cost effective method for differentiation of Mycobacterial cultures as MTB complex from non- tuberculous Mycobacteria. PMID:24959442

Mukhopadhyay, Chiranjay

2014-01-01

210

Comparative evaluation of intranasal and subcutaneous route of immunization for development of mucosal vaccine against experimental tuberculosis  

Microsoft Academic Search

Activation of mucosal immunity in the respiratory tract is crucial for protection against respiratory infections. Whether the intranasal route of vaccination imparts better protection against pulmonary tuberculosis than that of subcutaneous vaccination remains a debatable issue. In this study, we have investigated the effect of the routes of immunization on the induction of immunoprotection against experimental tuberculosis employing mycobacterial culture

Pramod K. Giri; Suraj B. Sable; Indu Verma; Gopal K. Khuller

2005-01-01

211

APPLICATION OF MAPIA (MULTIPLE ANTIGEN PRINT IMMUNOASSAY) AND RAPID LATERAL FLOW TECHNOLOGY FOR TUBERCULOSIS TESTING OF ELEPHANTS  

Technology Transfer Automated Retrieval System (TEKTRAN)

Tuberculosis (TB) remains a serious re-emerging disease in wildlife and zoo animals. Mycobacterium tuberculosis has been isolated from 30 captive Asian elephant (Elephas maximus within 14 herds in the U.S. (1994-2004) and Mycobacterium bovis has been isolated from one African elephant (Loxodonta afr...

212

Assessing the validity of tuberculosis surveillance data in California  

Microsoft Academic Search

BACKGROUND: The Centers for Disease Control and Prevention (CDC) convened a workgroup to revise the tuberculosis (TB) case report in the United States of America (U.S.). The group proposed substantial revisions. Study objectives were to systematically assess the validity and completeness of reported TB case surveillance data in California and to inform TB case report revision process. METHODS: A sample

Joan E Sprinson; Elizabeth S Lawton; Travis C Porco; Jennifer M Flood; Janice L Westenhouse

2006-01-01

213

New diagnostics for tuberculosis: fulfilling patient needs first  

Microsoft Academic Search

ABSTRACT: BACKGROUND: An effective tuberculosis (TB) control programme requires early diagnosis and immediate initiation of treatment. Any delays in diagnosing TB not only impair a patient's prognosis, but also increase the risks of transmitting the disease within the community. Unfortunately, the most recent TB diagnostic tools still depend on high-infrastructure laboratories, making them poorly adapted for use in resource-limited settings.

Jean-François Lemaire; Martina Casenghi

2010-01-01

214

Strategies for potentiation of ethionamide and folate antagonists against Mycobacterium tuberculosis  

PubMed Central

Antifolates inhibit de novo folate biosynthesis, whereas ethionamide targets the mycolate synthetic pathway in Mycobacterium tuberculosis. These antibiotics are effective against M. tuberculosis but their use has been hampered by concerns over toxicity and low therapeutic indexes. With the increasing spread of drug-resistant forms, interest in using old drugs for tuberculosis treatment has been renewed. Specific inhibitors targeting resistance mechanisms could sensitize M. tuberculosis to these available, clinically approved drugs. This review discusses recently developed strategies to boost the antituberculous activity of ethionamide and antifolates. These approaches might help broaden the currently limited chemotherapeutic options of not only drug-resistant but also drug-susceptible tuberculosis, which still remains one of the most common infectious diseases in the developing world. PMID:23106273

Wolff, Kerstin A; Nguyen, Liem

2014-01-01

215

Strategies for potentiation of ethionamide and folate antagonists against Mycobacterium tuberculosis.  

PubMed

Antifolates inhibit de novo folate biosynthesis, whereas ethionamide targets the mycolate synthetic pathway in Mycobacterium tuberculosis. These antibiotics are effective against M. tuberculosis but their use has been hampered by concerns over toxicity and low therapeutic indexes. With the increasing spread of drug-resistant forms, interest in using old drugs for tuberculosis treatment has been renewed. Specific inhibitors targeting resistance mechanisms could sensitize M. tuberculosis to these available, clinically approved drugs. This review discusses recently developed strategies to boost the antituberculous activity of ethionamide and antifolates. These approaches might help broaden the currently limited chemotherapeutic options of not only drug-resistant but also drug-susceptible tuberculosis, which still remains one of the most common infectious diseases in the developing world. PMID:23106273

Wolff, Kerstin A; Nguyen, Liem

2012-09-01

216

Does M. tuberculosis genomic diversity explain disease diversity?  

PubMed Central

The outcome of tuberculosis infection and disease is highly variable. This variation has been attributed primarily to host and environmental factors, but better understanding of the global genomic diversity in the M. tuberculosis complex (MTBC) suggests that bacterial factors could also be involved. Review of nearly 100 published reports shows that MTBC strains differ in their virulence and immunogenicity in experimental models, but whether this phenotypic variation plays a role in human disease remains unclear. Given the complex interactions between the host, the pathogen and the environment, linking MTBC genotypic diversity to experimental and clinical phenotypes requires an integrated systems epidemiology approach embedded in a robust evolutionary framework. PMID:21076640

Coscolla, Mireilla; Gagneux, Sebastien

2010-01-01

217

Clinical aspects of tonsillar tuberculosis.  

PubMed

A clinical analysis of 6 patients with pathologically confirmed tonsillar tuberculosis was carried out retrospectively. The subjects comprised three men and three women, ranging in age from 20 to 74 years. All of the patients presented with a sore throat and 5 had lymphadenopathy. Ulcerations, masses and white patches characterized the tonsillar lesions; the pathological findings included caseous granuloma with positive acid-fast bacilli (AFB) in 5 patients and chronic granulomatous inflammation with negative AFB in one patient. Four of the six patients had pulmonary tuberculosis. The three patients who received complete treatment responded well. The presenting symptoms and abnormal tonsillar findings associated with tonsillar tuberculosis are similar to those of malignant tumors and therefore it is difficult to differentiate the two pathologies; moreover, tonsillar tuberculosis often occurs with pulmonary tuberculosis and AIDS and therefore, a chest X-ray and HIV-screening are recommended for all patients with tonsillar tuberculosis. PMID:12118442

Srirompotong, Somchai; Yimtae, Kwanchanok; Srirompotong, Supaporn

2002-03-01

218

Investigation of geo-spatial hotspots for the occurrence of tuberculosis in Almora district, India, using GIS and spatial scan statistic  

PubMed Central

Background The World Health Organization has declared tuberculosis a global emergency in 1993. It has been estimated that one third of the world population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. The emergence of TB/HIV co-infection poses an additional challenge for the control of tuberculosis throughout the world. The World Health Organization is supporting many developing countries to eradicate tuberculosis. It is an agony that one fifth of the tuberculosis patients worldwide are in India. The eradication of tuberculosis is the greatest public health challenge for this developing country. The aim of the present population based study on Mycobacterium tuberculosis is to test a large set of tuberculosis cases for the presence of statistically significant geographical clusters. A spatial scan statistic is used to identify purely spatial and space-time clusters of tuberculosis. Results Significant (p < 0.05 for primary clusters and p < 0.1 for secondary clusters) high rate spatial and space-time clusters were identified in three areas of the district. Conclusion There is sufficient evidence about the existence of statistically significant tuberculosis clusters in Almora district of Uttaranchal, India. The spatial scan statistics methodology used in this study has a potential use in surveillance of tuberculosis for detecting the true clusters of the disease. PMID:16901341

Tiwari, Neeraj; Adhikari, CMS; Tewari, Ajoy; Kandpal, Vineeta

2006-01-01

219

resistant strains of Mycobacterium tuberculosis  

Microsoft Academic Search

Drug-resistant Mycobacterium tuberculosis poses a significant threat to the treatment of tuberculosis (TB). The current susceptibility testing for the first-line TB drug pyrazinamide (PZA) is not only time-consuming but also difficult, due to the requirement for acid pH for drug activity. Predominantly, resistance to PZA in M. tuberculosis is caused by mutations in the pncA gene, and the detection of

Ying Zhang; Steven Denkin; Dmitriy Volokhov; Vladimir Chizhikov

220

Alcohol Exacerbates Murine Pulmonary Tuberculosis  

Microsoft Academic Search

Alcohol consumption has been described as a risk factor for infection with Mycobacterium tuberculosis, but its contribution to tuberculosis has been difficult to isolate from other adverse socioeconomic factors. Our objec- tive was to evaluate the impact of alcohol consumption on pulmonary infection with M. tuberculosis in a murine model. BALB\\/c mice were maintained on the Lieber-DeCarli liquid ethanol diet

Carol M. Mason; Elizabeth Dobard; Ping Zhang; Steve Nelson

2004-01-01

221

Long distance travelling and financial burdens discourage tuberculosis DOTs treatment initiation and compliance in Ethiopia: a qualitative study  

PubMed Central

Background Timely tuberculosis treatment initiation and compliance are the two key factors for a successful tuberculosis control program. However, studies to understand patents’ perspective on tuberculosis treatment initiation and compliance have been limited in Ethiopia. The aim of this study is to attempt to do that in rural Ethiopia. Methods This qualitative, phenomenological study conducted 26 in-depth interviews with tuberculosis patients. A thematic content analysis of the interviews was performed using the Open Code software version 3.1. Results We found that lack of geographic access to health facilities, financial burdens, use of traditional healing systems and delay in diagnosis by health care providers were the main reasons for not initiating tuberculosis treatment timely. Lack of geographic access to health facilities, financial burdens, quality of health services provided and social support were also identified as the main reasons for failing to fully comply with tuberculosis treatments. Conclusions This study highlighted complexities surrounding tuberculosis control efforts in Dabat District. Challenges of geographic access to health care facilities and financial burdens were factors that most influenced timely tuberculosis treatment initiation and compliance. Decentralization of tuberculosis diagnosis and treatment services to peripheral health facilities, including health posts is of vital importance to make progress toward achieving tuberculosis control targets in Ethiopia. PMID:23634650

2013-01-01

222

An unconventional hexacoordinated flavohemoglobin from Mycobacterium tuberculosis.  

PubMed

Being an obligate aerobe, Mycobacterium tuberculosis faces a number of energetic challenges when it encounters hypoxia and environmental stress during intracellular infection. Consequently, it has evolved innovative strategies to cope with these unfavorable conditions. Here, we report a novel flavohemoglobin (MtbFHb) from M. tuberculosis that exhibits unique features within its heme and reductase domains distinct from conventional FHbs, including the absence of the characteristic hydrogen bonding interactions within the proximal heme pocket and mutations in the FAD and NADH binding regions of the reductase domain. In contrast to conventional FHbs, it has a hexacoordinate low-spin heme with a proximal histidine ligand lacking imidazolate character and a distal heme pocket with a relatively low electrostatic potential. Additionally, MtbFHb carries a new FAD binding site in its reductase domain similar to that of D-lactate dehydrogenase (D-LDH). When overexpressed in Escherichia coli or Mycobacterium smegmatis, MtbFHb remained associated with the cell membrane and exhibited D-lactate:phenazine methosulfate reductase activity and oxidized D-lactate into pyruvate by converting the heme iron from Fe(3+) to Fe(2+) in a FAD-dependent manner, indicating electron transfer from D-lactate to the heme via FAD cofactor. Under oxidative stress, MtbFHb-expressing cells exhibited growth advantage with reduced levels of lipid peroxidation. Given the fact that D-lactate is a byproduct of lipid peroxidation and that M. tuberculosis lacks the gene encoding D-LDH, we propose that the novel D-lactate metabolizing activity of MtbFHb uniquely equips M. tuberculosis to balance the stress level by protecting the cell membrane from oxidative damage via cycling between the Fe(3+)/Fe(2+) redox states. PMID:22437825

Gupta, Sanjay; Pawaria, Sudesh; Lu, Changyuan; Hade, Mangesh Dattu; Singh, Chaahat; Yeh, Syun-Ru; Dikshit, Kanak L

2012-05-11

223

Tuberculosis in camelids: a review.  

PubMed

Tuberculosis is a chronic, contagious, granulomatous disease caused by mycobacterial species belonging to the Mycobacterium tuberculosis complex. Camelids were not considered highly susceptible to tuberculosis, but in recent years increased numbers of cases have been experienced in some countries. In most of the cases, transmission probably occurs through contact with infected cattle or wildlife. None of the ante-mortem tests currently available can consistently provide accurate diagnosis of the infection in live camelids. Recently developed serological assays have the potential for rapid and accurate diagnosis of tuberculosis but still need to be validated. PMID:23520743

Wernery, U; Kinne, J

2012-12-01

224

The dynamics of tuberculosis epidemiology.  

PubMed

A conceptual framework to study the epidemiologic basis of tuberculosis control is provided. The basic model to discuss the epidemiology of tuberculosis is based on a classification of tuberculosis based on its pathogenesis with exposure, latent infection, tuberculosis, and death from tuberculosis, showing the conditional probabilities leading from one to the next step in the chain of events. Historical data are utilized to demonstrate how the dynamics of tuberculosis over multiple decades have contributed to shape the present. It is shown that the key concept to understand the dynamics is related to current and past incidence and prevalence of latent infection with M. tuberculosis. The dynamics of the epidemic are shaped both by the behaviour of the causative organism of tuberculosis as well as the population structure and changes that take place in parallel in which M. tuberculosis thrives. Both the present and the future shape of the epidemic, as well as the principles applied to its control lie very much in the past of a society. While new risk factors such as HIV or diabetes have been or are emerging more strongly, it is noted that the majority of all new cases emerging cannot be pinned to one or the other such factor. It is the historical experience of a population that offers the most valuable key to understanding the present and the future. PMID:24640341

Rieder, Hans L

2014-01-01

225

Background Notes  

NSDL National Science Digital Library

Country Background Notes, distributed on the DOSBACK list, are updated periodically and include information on US bilateral relations with foreign countries and on their governments, political conditions, and foreign relations. You can expect the DOSBACK list to generate about 3-4 email messages per month. Via DOSBACK you will receive the full-text version of newly released Background Notes. Archives of these two lists are also available at the Department of State Foreign Affairs Network (DOSFAN) gopher at the University of Illinois-Chicago.

226

Comparative Clinical Study of Different Multiplex Real Time PCR Strategies for the Simultaneous Differential Diagnosis between Extrapulmonary Tuberculosis and Focal Complications of Brucellosis  

PubMed Central

Background Both brucellosis and tuberculosis are chronic-debilitating systemic granulomatous diseases with a high incidence in many countries in Africa, Central and South America, the Middle East and the Indian subcontinent. Certain focal complications of brucellosis and extrapulmonary tuberculosis are very difficult to differentiate clinically, biologically and radiologically. As the conventional microbiological methods for the diagnosis of the two diseases have many limitations, as well as being time-consuming, multiplex real time PCR (M RT-PCR) could be a promising and practical approach to hasten the differential diagnosis and improve prognosis. Methodology/Principal Findings We designed a SYBR Green single-tube multiplex real-time PCR protocol targeting bcsp31 and the IS711 sequence detecting all pathogenic species and biovars of Brucella genus, the IS6110 sequence detecting Mycobacterium genus, and the intergenic region senX3-regX3 specifically detecting Mycobacterium tuberculosis complex. The diagnostic yield of the M RT-PCR with the three pairs of resultant amplicons was then analyzed in 91 clinical samples corresponding to 30 patients with focal complications of brucellosis, 24 patients with extrapulmonary tuberculosis, and 36 patients (Control Group) with different infectious, autoimmune or neoplastic diseases. Thirty-five patients had vertebral osteomyelitis, 21 subacute or chronic meningitis or meningoencephalitis, 13 liver or splenic abscess, eight orchiepididymitis, seven subacute or chronic arthritis, and the remaining seven samples were from different locations. Of the three pairs of amplicons (senX3-regX3+ bcsp3, senX3-regX3+ IS711 and IS6110+ IS711) only senX3-regX3+ IS711 was 100% specific for both the Brucella genus and M. tuberculosis complex. For all the clinical samples studied, the overall sensitivity, specificity, and positive and negative predictive values of the M RT-PCR assay were 89.1%, 100%, 85.7% and 100%, respectively, with an accuracy of 93.4%, (95% CI, 88.3—96.5%). Conclusions/Significance In this study, a M RT-PCR strategy with species-specific primers based on senX3-regX3+IS711 sequences proved to be a sensitive and specific test, useful for the highly efficient detection of M. tuberculosis and Brucella spp in very different clinical samples. It thus represents an advance in the differential diagnosis between some forms of extrapulmonary tuberculosis and focal complications of brucellosis. PMID:24349599

Sanjuan-Jimenez, Rocio; Morata, Pilar; Bermúdez, Pilar; Bravo, M. José; Colmenero, Juan D.

2013-01-01

227

Pyrazinamide-monoresistant Mycobacterium tuberculosis in the United States.  

PubMed

Mycobacterium bovis is naturally resistant to the antituberculosis drug pyrazinamide (PZA). To determine whether all Mycobacterium tuberculosis complex isolates demonstrating PZA monoresistance were truly M. bovis, we examined the phenotype and genotype of isolates reported as PZA monoresistant in five counties in California from January 1996 through June 1999. Isolates reported by local laboratories to be PZA monoresistant were sent to the state reference laboratory for repeat susceptibility testing using the BACTEC radiometric method and to the Centers for Disease Control and Prevention for pncA sequencing and PCR-restriction fragment length polymorphism (RFLP) analysis of the oxyR gene. Of 1,916 isolates, 14 were reported as PZA monoresistant and 11 were available for retesting. On repeat testing, 6 of the 11 isolates were identified as PZA-susceptible M. tuberculosis, 1 was identified as PZA-monoresistant M. bovis, and 1 was identified as M. bovis BCG. The three remaining isolates were identified as PZA-monoresistant M. tuberculosis. Sequencing of the pncA and oxyR genes genotypically confirmed the two M. bovis and the six susceptible M. tuberculosis species. Each of the three PZA-monoresistant M. tuberculosis isolates had different, previously unreported, pncA gene mutations: a 24-bp deletion in frame after codon 88, a base substitution at codon 104 (Ser104Cys), and a base substitution at codon 90 (Ile90Ser). This study demonstrates that PZA monoresistance is not an absolute marker of M. bovis species but may also occur in M. tuberculosis, associated with a number of different mutational events in the pncA gene. It is the first report of PZA-monoresistant M. tuberculosis in the United States. PMID:11158123

Hannan, M M; Desmond, E P; Morlock, G P; Mazurek, G H; Crawford, J T

2001-02-01

228

Molecular diversity of Mycobacterium tuberculosis isolates from patients with tuberculosis in Honduras  

PubMed Central

Background Tuberculosis persists as a public health problem in Honduras. A better knowledge of the molecular characteristics of Mycobacterium tuberculosis strains will contribute to understand the transmission dynamics of the disease within the country. The aim of this study was to provide an insight of the genetic biodiversity of M. tuberculosis clinical isolates collected in Honduras between 1994 and 2002. Genotyping was performed using spoligotyping and RFLP. The spoligotypes obtained were compared with the SITVIT2 proprietary database of the Pasteur Institute of Guadeloupe. Results Spoligotyping grouped 84% of the isolates into 27 clusters (2 to 43 strains per cluster). Of the 44 shared international types (SITs) identified among the Honduran stains, 8 SITs were newly identified either within the present study or after match with an orphan type previously identified in the SITVIT2 database. In addition, 16 patterns corresponded to orphan, previously unreported isolates. The Latin American Mediterranean (LAM) lineage was the most common in this study; 55% of the strains belonged to this family. Other genotypes found were Haarlem (16%), T (16%), X-clade (6%), Unknown signature (5%) and S (1%). Only one Beijing strain was identified (0.5%). We observed a high degree of diversity after characterizing the 43 isolates belonging to the main spoligotyping cluster (SIT 33, LAM3) with IS6110-RFLP. A total of 35 different RFLP-fingerprints were detected, of which 6 patterns corresponded to the same number of clusters comprising 14 strains. Conclusions The findings obtained in this study show that tuberculosis transmission in Honduras is due to modern M. tuberculosis lineages with high level of biodiversity. PMID:20678242

2010-01-01

229

Tuberculosis in an Urban Area in China: Differences between Urban Migrants and Local Residents  

PubMed Central

Background The increase in urban migrants is one of major challenges for tuberculosis control in China. The different characteristics of tuberculosis cases between urban migrants and local residents in China have not been investigated before. Methodology/Principal Findings We performed a retrospective study of all pulmonary tuberculosis patients reported in Songjiang district, Shanghai, to determine the demographic, clinical and microbiological characteristics of tuberculosis cases between urban migrants and local residents. We calculated the odds ratios (OR) and performed multivariate logistic regression to identify the characteristics that were independently associated with tuberculosis among urban migrants. A total of 1,348 pulmonary tuberculosis cases were reported during 2006–2008, among whom 440 (32.6%) were local residents and 908 (67.4%) were urban migrants. Urban migrant (38.9/100,000 population) had higher tuberculosis rates than local residents (27.8/100,000 population), and the rates among persons younger than age 35 years were 3 times higher among urban migrants than among local residents. Younger age (adjusted OR per additional year at risk?=?0.92, 95% CI: 0.91–0.94, p<0.001), poor treatment outcome (adjusted OR?=?4.12, 95% CI: 2.65–5.72, p<0.001), and lower frequency of any comorbidity at diagnosis (adjusted OR?=?0.20, 95% CI: 0.13–0.26, p?=?0.013) were significantly associated with tuberculosis patients among urban migrants. There were poor treatment outcomes among urban migrants, mainly from transfers to another jurisdiction (19.3% of all tuberculosis patients among urban migrants). Conclusions/Significance A considerable proportion of tuberculosis cases in Songjiang district, China, during 2006–2008 occurred among urban migrants. Our findings highlight the need to develop and implement specific tuberculosis control strategies for urban migrants, such as more exhaustive case finding, improved case management and follow-up, and use of directly observed therapy (DOT). PMID:23226479

Shen, Xin; Xia, Zhen; Li, Xiangqun; Wu, Jie; Wang, Lili; Li, Jing; Jiang, Yuan; Guo, Juntao; Chen, Jing; Hong, Jianjun; Yuan, Zheng’an; Pan, Qichao; DeRiemer, Kathryn; Sun, Guomei; Gao, Qian; Mei, Jian

2012-01-01

230

Prevalence of self-reported tuberculosis, knowledge about tuberculosis transmission and its determinants among adults in India: results from a nation-wide cross-sectional household survey  

PubMed Central

Background Knowledge about symptoms and transmission of tuberculosis determines health seeking behavior and helps in prevention of tuberculosis transmission in the community. Such data is useful for policy makers to formulate information, education and communication strategies for tuberculosis control. Methods A secondary data analysis of India demographic and health survey, 2005/6 was carried out. Questions about self-reported tuberculosis, transmission and curability of tuberculosis were analysed. Correct knowledge (without misconceptions) about tuberculosis transmission was used as a dependant variable and the explanatory variables tested were: demographic data, education, wealth quintiles, frequency of exposure to media and the curability of tuberculosis. Determinants of correct knowledge without misconceptions were tested by univariate and multivariate analyses using national weighting factor to adjust for complex sampling design. Results A total of 109,070 households (response rate of 93.5%) and 198,718 participants (response rate of 91.6%) completed the survey. The samples of men and women interviewed were 74,360 and 124,358 respectively. Prevalence rate of self-reported tuberculosis was 445 per 100,000 usual household residents and 4.60 per 1,000 participants. The number of respondents who had “heard of an illness called tuberculosis” was 177,423 (89.3%). Of these 47,487 (26.8%) participants did not know and 55.5% knew about the correct mode of tuberculosis transmission i.e. “Through the air when coughing or sneezing”. The common misconceptions about transmission were “Through food” (32.4%), “Sharing utensils” (18.2%), and “Touching a person with tuberculosis” (12.3%). Only 52,617 (29.7%) participants had correct knowledge without misconceptions. Being male (aOR 1.17, 95% CIs 1.14, 1.21), being a Hindu (aOR 1.20, 95% CIs 1.14, 1.26) or Muslim (aOR 1.26, 95% CIs 1.18, 1.34), listening to radio (aOR 1.08, 95% CIs 1.04, 1.13) and “Tuberculosis can be cured” (aOR 1.47, 95% CIs 1.41, 1.53) were associated with correct knowledge without misconceptions. Conclusions Knowledge about tuberculosis transmission is very poor and misconceptions still exist. Among the traditional mass media, the frequency of listening to radio was associated with correct knowledge about tuberculosis transmission. Strategies to deliver information, education and communication campaigns could be improved. PMID:23324535

2013-01-01

231

Barriers in the Management of Tuberculosis in Rawalpindi, Pakistan: A Qualitative Study  

PubMed Central

Background Tuberculosis (TB) is a contagious, airborne disease and remains a major global public health hazard. TB is a major cause of mortality and is affecting millions of people in low-income and middle-income countries. Worldwide, one person out of three is infected with the Mycobacterium tuberculosis. Timely diagnosis and treatment are the two key factors for better outcomes. Non-adherence to TB treatment is an important barrier for TB control programs. This study was designed to understand the barriers encountered by TB patients when seeking health care. Materials and Methods A qualitative study was conducted during the months of August and December 2010 on 15 health facilities. In-depth interviews were conducted with 23 TB patients (13 males and 10 females) aged 15-65 years. In addition, 15 health personnel were also interviewed. Results Most patients were found to be well informed about the idea of taking TB medications under direct supervision and its overall importance. However, many of them were not convinced with either drugs or treatment protocols. We found that limited knowledge of patients, loss of employment, financial burden, social stigma and long distance from health facility were the main barriers for TB adherence. Conclusion More patient-centred interventions and attention to the barriers are required to improve the treatment adherence. Direct observation of patients and regular home visits by health workers can reduce the risk of non-adherence. PMID:25191481

Qadeer, Ejaz; Mørkve, Odd

2013-01-01

232

Characterization of a Novel Esterase Rv0045c from Mycobacterium tuberculosis  

PubMed Central

Background It was proposed that there are at least 250 enzymes in M. tuberculosis involved in lipid metabolism. Rv0045c was predicted to be a hydrolase by amino acid sequence similarity, although its precise biochemical characterization and function remained to be defined. Methodology/Principal Findings We expressed the Rv0045c protein to high levels in E. coli and purified the protein to high purity. We confirmed that the prepared protein was the Rv0045c protein by mass spectrometry analysis. Circular dichroism spectroscopy analysis showed that the protein possessed abundant ?-sheet secondary structure, and confirmed that its conformation was stable in the range pH 6.0–10.0 and at temperatures ?40°C. Enzyme activity analysis indicated that the Rv0045c protein could efficiently hydrolyze short chain p-nitrophenyl esters (C2–C8), and its suitable substrate was p-nitrophenyl caproate (C6) with optimal catalytic conditions of 39°C and pH 8.0. Conclusions/Significance Our results demonstrated that the Rv0045c protein is a novel esterase. These experiments will be helpful in understanding ester/lipid metabolism related to M. tuberculosis. PMID:20957207

Xu, Lipeng; Liu, Zhongyuan; Xu, Kehui; Li, Shentao; Wen, Tingyi; Liu, Siguo; Pang, Hai

2010-01-01

233

Differences Between Pediatric Extra-Pulmonary and Pulmonary Tuberculosis: a Warning Sign for the Future  

PubMed Central

Background Tuberculosis (TB) remains a major global health problem. The childhood tuberculosis has some unique features different which makes the diagnosis more complicated. Here we described the epidemiologic, clinical and microbiologic features of children with extra pulmonary and pulmonary TB. Methods The data of the patients <14 years with active TB were collected and compared in pulmonary (PTB) and extrapulmonary TB (EXPTB) patients. Results A total of 128 cases was included. Forty-two cases occurred in children were < 5 years of age; 41 cases between 6–10 years and 45 cases > 10 years. PTB was present in 75,0% of the cases, and EXPTB was present in 25% of cases. There was no significant difference between the EXPTB and PTB by means of distribution of age groups (p=0,201). The rate of patients free of constitutional symptoms were significantly higher in EXPTB compared to PTB(p=0,000). There was no significant difference between EXPTB and PTB by means of sources detection(p=0,069). Conclusion TB is still a major public health problem. EXPTB has an insidious and silent onset without any constitutional symptoms, and both microbiological confirmation and the source by an adult are not frequently found. Moreover, detection of the adult source is mandatory for controlling the TB disease in children PMID:25237471

Devrim, ?lker; Aktürk, Hüseyin; Bayram, Nuri; Apa, Hur?it; Tulumo?lu, ?ener; Devrim, Fatma; Erdem, Tülin; Gulfidan, Gamze; Ayhan, Yüce; Tamsel, ?pek; Can, Demet; Alper, Hüdaver

2014-01-01

234

Pathogen-derived biomarkers for active tuberculosis diagnosis  

PubMed Central

Tuberculosis (TB) is an infectious disease caused by members of Mycobacterium tuberculosis complex. Despite the availability of effective treatments, TB remains a major public health concern in most low and middle-income countries, representing worldwide the second leading cause of death from an infectious disease. Inadequate case detection and failures to classify the disease status hamper proper TB control. The limitations of the conventional diagnostic methods have encouraged much research activities in this field, but there is still an urgent need for an accurate point of care test for active TB diagnosis. A rapid, precise, and inexpensive TB diagnostic test would allow an earlier implementation of an appropriate treatment and the reduction of disease transmission. Pathogen-derived molecules present in clinical specimens of affected patients are being validated for that purpose. This short review aims to summarize the available data regarding biomarkers derived from M. tuberculosis, and their current usage in active TB diagnosis. PMID:25368609

Tucci, Paula; González-Sapienza, Gualberto; Marin, Monica

2014-01-01

235

Advances in Mycobacterium tuberculosis therapeutics discovery utlizing structural biology  

PubMed Central

In 2012, tuberculosis (TB) remains a global health threat and is exacerbated both by the emergence of drug resistant Mycobacterium tuberculosis strains and its synergy with HIV infection. The waning effectiveness of current treatment regimens necessitates the development of new or repurposed anti-TB therapeutics for improved combination therapies against the disease. Exploiting atomic resolution structural information of proteins in complex with their substrates and/or inhibitors can facilitate structure-based rational drug design. Since our last review in 2009, there has been a wealth of new M. tuberculosis protein structural information. Once again, we have compiled the most promising structures with regards to potential anti-TB drug development and present them in this updated review. PMID:23167715

Chim, Nicholas; Owens, Cedric P.; Contreras, Heidi; Goulding, Celia W.

2013-01-01

236

1. VIEW OF CRUSHING PLANT (FEATURE 19). THE REMAINS OF ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. VIEW OF CRUSHING PLANT (FEATURE 19). THE REMAINS OF THE FINE ORE MILL (FEATURE 20) ARE IN THE BACKGROUND ON LEFT. CONCRETE RESERVOIR (FEATURE 22) IS SHOWN AT THE RIGHT EDGE OF PHOTOGRAPH FACING SOUTHWEST. - Copper Canyon Camp of the International Smelting & Refining Company, Crushing Plant, Copper Canyon, Battle Mountain, Lander County, NV

237

Scaling up interventions to achieve global tuberculosis control: progress and new developments.  

PubMed

Tuberculosis is still one of the most important causes of death worldwide. The 2010 Lancet tuberculosis series provided a comprehensive overview of global control efforts and challenges. In this update we review recent progress. With improved control efforts, the world and most regions are on track to achieve the Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception is Africa. Despite these advances, full scale-up of tuberculosis and HIV collaborative activities remains challenging and emerging drug-resistant tuberculosis is a major threat. Recognition of the effect that non-communicable diseases--such as smoking-related lung disease, diet-related diabetes mellitus, and alcohol and drug misuse--have on individual vulnerability, as well as the contribution of poor living conditions to community vulnerability, shows the need for multidisciplinary approaches. Several new diagnostic tests are being introduced in endemic countries and for the first time in 40 years a coordinated portfolio of promising new tuberculosis drugs exists. However, none of these advances offer easy solutions. Achievement of international tuberculosis control targets and maintenance of these gains needs optimum national health policies and services, with ongoing investment into new approaches and strategies. Despite growing funding in recent years, a serious shortfall persists. International and national financial uncertainty places gains at serious risk. Perseverance and renewed commitment are needed to achieve global control of tuberculosis, and ultimately, its elimination. PMID:22608339

Raviglione, Mario; Marais, Ben; Floyd, Katherine; Lönnroth, Knut; Getahun, Haileyesus; Migliori, Giovanni B; Harries, Anthony D; Nunn, Paul; Lienhardt, Christian; Graham, Steve; Chakaya, Jeremiah; Weyer, Karin; Cole, Stewart; Kaufmann, Stefan H E; Zumla, Alimuddin

2012-05-19

238

Background & Publications  

E-print Network

Home Background & Projects Calendar Publications Staff Directory Station Videos Links Search Northern Michigan FruitNet 2008 Weekly Update NW Michigan Horticultural Research Station Nikki Rothwell maggot from growers. European red mites and two-spotted spider mites have reached threshold levels

239

Epidemiological basis of tuberculosis eradication in an advanced country  

PubMed Central

The first section of the report provides a background for the long-range epidemiological studies being conducted by the Danish Tuberculosis Index. An outline is given of the main indices of tuberculosis and the changing tuberculosis situation in Denmark during the past several decades with respect to prevalence of infection, morbidity and mortality. Difficulties encountered in international comparisons are briefly discussed. The prevalence of tuberculous infection in children and the prevalence of bacillary cases of pulmonary tuberculosis in adults are suggested as the most valuable indices of eradication. The second section describes the nation-wide mass campaign of 1950-52, which was planned and conducted as a combined service and research programme under the direction of the Danish Tuberculosis Index. With a view to the follow-up studies, details are given of the results of tuberculin tests of the unvaccinated, the documented vaccinated and mixed groups in the population examined. A survey is made of the results of X-ray examination and of the relation between vaccination status, tuberculin reaction and X-ray findings. The results of the first follow-up period are analysed in the final section of the report in terms of new cases of pulmonary tuberculosis appearing in the adult population. Seventy-five per cent of the new cases appeared among the unvaccinated tuberculin-positive population, and among this population groups of persons with widely different risks of developing tuberculosis could be identified on the basis of X-ray findings and reactions to the intradermal 10 TU tuberculin test. A proposal is made to reduce the number of routine repetitive examinations for adults and to concentrate efforts on preventive measures for the high-risk groups. PMID:13829735

Groth-Petersen, E.; Knudsen, Jørgen; Wilbek, Erik

1959-01-01

240

Recombinant Reporter Assay Using Transcriptional Machinery of Mycobacterium tuberculosis.  

PubMed

Development of an in vivo gene reporter assay to assess interactions among the components of the transcription machinery in Mycobacterium tuberculosis remains a challenge to scientists due to the tediousness of generation of mutant strains of the extremely slow-growing bacterium. We have developed a recombinant mCherry reporter assay that enables us to monitor the interactions of Mycobacterium tuberculosis transcriptional regulators with its promoters in vivo in Escherichia coli. The assay involves a three-plasmid expression system in E. coli wherein two plasmids are responsible for M. tuberculosis RNA polymerase (RNAP) production and the third plasmid harbors the mCherry reporter gene expression cassette under the control of either a ? factor or a transcriptional regulator-dependent promoter. We observed that the endogenous E. coli RNAP and ? factor do not interfere with the assay. By using the reporter assay, we found that the functional interaction of M. tuberculosis cyclic AMP receptor protein (CRP) occurs with its own RNA polymerase, not with the E. coli polymerase. Performing the recombinant reporter assay in E. coli is much faster than if performed in M. tuberculosis and avoids the hazard of handling the pathogenic bacterium. The approach could be expanded to develop reporter assays for other pathogenic and slow-growing bacterial systems. PMID:25448818

Banerjee, Rajdeep; Rudra, Paulami; Saha, Abinit; Mukhopadhyay, Jayanta

2015-02-01

241

Spoligotyping of Mycobacterium tuberculosis complex isolates using hydrogel oligonucleotide microarrays.  

PubMed

Mycobacterium tuberculosis remains a leading cause of morbidity and mortality worldwide. This circumstance underscores the relevance of population studies of tuberculosis for transmission dynamics control. In this study, we describe a conversion of the spoligotyping of M.tuberculosis complex isolates on a platform of custom designed hydrogel microarrays (biochips). An algorithm of automated data processing and interpretation of hybridization results using online database was proposed. In total, the 445 samples were tested. Initially, 97 samples representing multiple species of M.tuberculosis complex and nontuberculous mycobacteria were used for protocol optimization and cut-off settings. The developed assay was further evaluated on the out-group of the 348 mycobacterial samples. Results showed high concordance with the conventional membrane-based spoligotyping method. Diagnostic sensitivity and diagnostic specificity of the spoligo-biochip assay were 99.1% and 100%, respectively. The analytical sensitivity was determined to be 500 genomic equivalents of mycobacterial DNA. The high sensitivity and specificity, ease of operation procedures, and the automatic processing of measured data make the developed assay a useful tool for the rapid and accurate genotyping of M. tuberculosis. PMID:24815729

Bespyatykh, Julia A; Zimenkov, Danila V; Shitikov, Egor A; Kulagina, Elena V; Lapa, Sergey A; Gryadunov, Dmitry A; Ilina, Elena N; Govorun, Vadim M

2014-08-01

242

Dermatomyositis masquerading musculoskeletal tuberculosis.  

PubMed

Dermatomyositis is a rare rheumatic disease which predominantly affects the muscles and skin requiring a protracted course of immunosuppressants which may predispose the patients to opportunistic infections. A 49-year-old lady was diagnosed to have dermatomyositis in August 2010 based on history, significantly raised creatine kinase level and muscle biopsy findings. She had recurrent admissions due to fever, myalgia and muscle weakness. She had spiking temperature despite high dose steroids, broad-spectrum antibiotics and antifungal agents. This prompted extensive investigation which leads us to the additional diagnosis of disseminated tuberculosis involving the lungs, muscles and bones. This case demonstrates the challenge in controlling the disease activity of dermatomyositis with immunosuppressants in the setting of disseminated tuberculosis. PMID:22675098

Rajalingham, Sakthiswary; Said, Mohd Shahrir Mohd; Shaharir, Syahrul Sazliyana; AbAziz, Aini; Periyasamy, Petrick; Anshar, Fauzi Md

2011-01-01

243

Dermatomyositis masquerading musculoskeletal tuberculosis  

PubMed Central

Dermatomyositis is a rare rheumatic disease which predominantly affects the muscles and skin requiring a protracted course of immunosuppressants which may predispose the patients to opportunistic infections. A 49-year-old lady was diagnosed to have dermatomyositis in August 2010 based on history, significantly raised creatine kinase level and muscle biopsy findings. She had recurrent admissions due to fever, myalgia and muscle weakness. She had spiking temperature despite high dose steroids, broad-spectrum antibiotics and antifungal agents. This prompted extensive investigation which leads us to the additional diagnosis of disseminated tuberculosis involving the lungs, muscles and bones. This case demonstrates the challenge in controlling the disease activity of dermatomyositis with immunosuppressants in the setting of disseminated tuberculosis. PMID:22675098

Rajalingham, Sakthiswary; Mohd Said, Mohd Shahrir; Shaharir, Syahrul Sazliyana; AbAziz, Aini; Periyasamy, Petrick; Md Anshar, Fauzi

2011-01-01

244

Tuberculosis of spine  

PubMed Central

Tuberculosis of the spine is one of the most common spine pathology in India. Over last 4 decades a lot has changed in the diagnosis, medical treatment and surgical procedures to treat this disorder. Further developments in diagnosis using molecular genetic techniques, more effective antibiotics and more aggressive surgical protocols have become essential with emergence of multidrug resistant TB. Surgical procedures such as single stage anterior and posterior stabilization, extrapleral dorsal spine anterior stabilization and endoscopic thoracoscopic surgeries have reduced the mortality and morbidity of the surgical procedures. is rapidly progressing. It is a challenge to treat MDR-TB Spine with late onset paraplegia and progressive deformity. Physicians must treat tuberculosis of spine on the basis of Culture and sensitivity. PMID:21572628

Agrawal, Vinod; Patgaonkar, P. R.; Nagariya, S. P.

2010-01-01

245

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.  

Code of Federal Regulations, 2013 CFR

...tuberculosis and provides epidemiological information on this disease. Mycobacterium tuberculosis is the common causative organism in human tuberculosis, a chronic infectious disease characterized by formation of tubercles (small...

2013-04-01

246

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.  

Code of Federal Regulations, 2010 CFR

...tuberculosis and provides epidemiological information on this disease. Mycobacterium tuberculosis is the common causative organism in human tuberculosis, a chronic infectious disease characterized by formation of tubercles (small...

2010-04-01

247

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.  

Code of Federal Regulations, 2012 CFR

...tuberculosis and provides epidemiological information on this disease. Mycobacterium tuberculosis is the common causative organism in human tuberculosis, a chronic infectious disease characterized by formation of tubercles (small...

2012-04-01

248

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.  

...tuberculosis and provides epidemiological information on this disease. Mycobacterium tuberculosis is the common causative organism in human tuberculosis, a chronic infectious disease characterized by formation of tubercles (small...

2014-04-01

249

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.  

Code of Federal Regulations, 2011 CFR

...tuberculosis and provides epidemiological information on this disease. Mycobacterium tuberculosis is the common causative organism in human tuberculosis, a chronic infectious disease characterized by formation of tubercles (small...

2011-04-01

250

M. tuberculosis in Lymph Node Biopsy Paraffin-Embedded Sections  

PubMed Central

Background. Tuberculosis lymphadenitis is one of the most common forms of all extrapulmonary tuberculosis. Objective. To evaluate the magnitude of M. tuberculosis from lymph node biopsy paraffin-embedded sections among suspected patients visiting the Jimma University Specialized Hospital. Method. A cross-sectional study design of histological examination among lymph node biopsy paraffin-embedded sections by Ziehl-Neelsen and hematoxylin/eosin staining technique was conducted from December, 2009, to October, 2010, at the Department of Medical Laboratory Science and Pathology. Result. Histopathological examination of the specimens by hematoxylin and eosin staining technique revealed the presence of granulomas. But for the caseation and necrosis they were present in 85% cases of nodal tissue biopsies. From those, 56.7% were from females. The presence of acid-fast bacilli was microscopically confirmed by ZN staining in 37 (61.7%) of the nodal tissue biopsies. Conclusion and Recommendation. Tuberculosis lymphadenitis is significantly more common in females. Hence, attention should be given for control and prevention of extrapulmonary tuberculosis. PMID:22567262

Eshete, Abdurehman; Zeyinudin, Ahmed; Ali, Solomon; Abera, Solomon; Mohammed, Mona

2011-01-01

251

Characteristics of multidrug-resistant tuberculosis in Namibia  

PubMed Central

Background To describe the epidemiology and possible risk factors for the development of multidrug-resistant tuberculosis (MDR-TB) in Namibia. Methods Using medical records and patient questionnaires, we conducted a case-control study among patients diagnosed with TB between January 2007 and March 2009. Cases were defined as patients with laboratory-confirmed MDR-TB; controls had laboratory-confirmed drug-susceptible TB or were being treated with WHO Category I or Category II treatment regimens. Results We enrolled 117 MDR-TB cases and 251 TB controls, of which 100% and 2% were laboratory-confirmed, respectively. Among cases, 97% (113/117) had been treated for TB before the current episode compared with 46% (115/251) of controls (odds ratio [OR] 28.7, 95% confidence interval [CI] 10.3–80.5). Cases were significantly more likely to have been previously hospitalized (OR 1.9, 95% CI 1.1–3.5) and to have had a household member with MDR-TB (OR 5.1, 95% CI 2.1–12.5). These associations remained significant when separately controlled for being currently hospitalized or HIV-infection. Conclusions MDR-TB was associated with previous treatment for TB, previous hospitalization, and having had a household member with MDR-TB, suggesting that TB control practices have been inadequate. Strengthening basic TB control practices, including expanding laboratory confirmation, directly observed therapy, and infection control, are critical to the prevention of MDR-TB. PMID:23273024

2012-01-01

252

Multidrug-Resistant Mycobacterium tuberculosis: Molecular Perspectives  

Microsoft Academic Search

Multidrug-resistant strains of Mycobacterium tuberculosis seriously threaten tuberculosis (TB) control and prevention efforts. Molecular studies of the mechanism of action of antitubercular drugs have elucidated the genetic basis of drug resistance in M. tuberculosis. Drug resistance in M. tuberculosis is attributed primarily to the accumulation of mutations in the drug target genes; these mutations lead either to an altered target

Ashok Rattan; Awdhesh Kalia; Nishat Ahmad

1998-01-01

253

ORIGINAL ARTICLE Mycobacterium tuberculosis secretory proteins  

E-print Network

ORIGINAL ARTICLE Mycobacterium tuberculosis secretory proteins CFP-10, ESAT-6 and the CFP10:ESAT6, Dinakar M Salunke2 and Pawan Sharma1 Mycobacterium tuberculosis (Mtb) causes death of 2­3 million people; lipopolysaccharide; NF-kB; ROS Tuberculosis is a global health problem caused by Mycobacterium tuberculosis (Mtb

Cai, Long

254

Ghost Remains After Black Hole Eruption  

NASA Astrophysics Data System (ADS)

NASA's Chandra X-ray Observatory has found a cosmic "ghost" lurking around a distant supermassive black hole. This is the first detection of such a high-energy apparition, and scientists think it is evidence of a huge eruption produced by the black hole. This discovery presents astronomers with a valuable opportunity to observe phenomena that occurred when the Universe was very young. The X-ray ghost, so-called because a diffuse X-ray source has remained after other radiation from the outburst has died away, is in the Chandra Deep Field-North, one of the deepest X-ray images ever taken. The source, a.k.a. HDF 130, is over 10 billion light years away and existed at a time 3 billion years after the Big Bang, when galaxies and black holes were forming at a high rate. "We'd seen this fuzzy object a few years ago, but didn't realize until now that we were seeing a ghost", said Andy Fabian of the Cambridge University in the United Kingdom. "It's not out there to haunt us, rather it's telling us something - in this case what was happening in this galaxy billions of year ago." Fabian and colleagues think the X-ray glow from HDF 130 is evidence for a powerful outburst from its central black hole in the form of jets of energetic particles traveling at almost the speed of light. When the eruption was ongoing, it produced prodigious amounts of radio and X-radiation, but after several million years, the radio signal faded from view as the electrons radiated away their energy. HDF 130 Chandra X-ray Image of HDF 130 However, less energetic electrons can still produce X-rays by interacting with the pervasive sea of photons remaining from the Big Bang - the cosmic background radiation. Collisions between these electrons and the background photons can impart enough energy to the photons to boost them into the X-ray energy band. This process produces an extended X-ray source that lasts for another 30 million years or so. "This ghost tells us about the black hole's eruption long after it has died," said co-author Scott Chapman, also of Cambridge University. "This means we don't have to catch the black holes in the act to witness the big impact they have." This is the first X-ray ghost ever seen after the demise of radio-bright jets. Astronomers have observed extensive X-ray emission with a similar origin, but only from galaxies with radio emission on large scales, signifying continued eruptions. In HDF 130, only a point source is detected in radio images, coinciding with the massive elliptical galaxy seen in its optical image. This radio source indicates the presence of a growing supermassive black hole. People Who Read This Also Read... Milky Way's Super-efficient Particle Accelerators Caught in The Act NASA Joins "Around the World in 80 Telescopes" Celebrate the International Year of Astronomy Galaxies Coming of Age in Cosmic Blobs "This result hints that the X-ray sky should be littered with such ghosts," said co-author Caitlin Casey, also of Cambridge, "especially if black hole eruptions are as common as we think they are in the early Universe." The power contained in the black hole eruption was likely to be considerable, equivalent to about a billion supernovas. The energy is dumped into the surroundings and transports and heats the gas. "Even after the ghost disappears, most of the energy from the black hole's eruption remains", said Fabian. "Because they're so powerful, these eruptions can have profound effects lasting for billions of years." The details of Chandra's data of HDF 130 helped secure its true nature. For example, in X-rays, HDF 130 has a cigar-like shape that extends for some 2.2 million light years. The linear shape of the X-ray source is consistent with the shape of radio jets and not with that of a galaxy cluster, which is expected to be circular. The energy distribution of the X-rays is also consistent with the interpretation of an X-ray ghost. NASA's Marshall Space Flight Center in Huntsville, Ala., manages the Chandr

2009-05-01

255

Where do those remains come from?  

PubMed

Part of the study of skeletal remains or corpses in advance decay located in the field involves determining their origin. They may be the result of criminal activity, accident, unearthed because of erosion, or they may also have originated from a cemetery. The discovery site, condition of the remains, and the associated artifacts, are factors that could be helpful for the forensic anthropologist to identify the origin of the remains. In order to contribute to this recognition, an analysis was made of the exhumations of 168 unclaimed human remains from the cemetery of Terrassa (Catalonia, Spain). This investigation presents a description of artifacts and conditions of remains that could indicate that the human remains may have originated from a cemetery. PMID:25459276

Nociarová, Dominika; Adserias, M Jose; Malgosa, Assumpció; Galtés, Ignasi

2014-10-14

256

Tuberculosis in association with travel  

Microsoft Academic Search

Throughout history, tuberculosis has been spread by the movement of human populations. Modern travel continues to be associated with risk of tuberculosis infection and disease. TB transmission has been documented on commercial aircraft, from personnel or passengers to other personnel and passengers, but the risk of transmission is low. As in other settings, the likelihood of transmission is proportional to

Hamdan Al-Jahdali; Ziad A Memish; Dick Menzies

2003-01-01

257

Thyroid Tuberculosis: Diagnosis and Treatment  

Microsoft Academic Search

Objective: It was the aim of this study to report clinical characteristics and treatment of thyroid tuberculosis (TT). Methods: During 16 years, 2,426 patients have been operated on the thyroid in the surgical department ‘A’ in Ibn Sina Hospital, Rabat, Morocco. Anatomopathological results of the removed thyroid were analyzed for evidence of tuberculosis. Results: Eight cases of TT were diagnosed.

H. O. El Malki; R. Mohsine; K. Benkhraba; M. Amahzoune; A. Benkabbou; M. El Absi; L. Ifrine; A. Belkouchi; S. Balafrej

2006-01-01

258

pncA Mutations in Pyrazinamide-Resistant Mycobacterium tuberculosis Isolates in Portugal  

Microsoft Academic Search

Portugal remains the country with the highest rate of noti- fied cases of Mycobacterium tuberculosis in the European Union. In 2002, the Portuguese Health Authorities reported a tuberculosis (TB) incidence of 39.5 cases per 100,000 people nationwide and that 2.3% of primary TB cases involved multi- drug resistance (MDR-TB cases) (Programa Nacional de Con- trolo da Tuberculose, Ponto da situacao

Isabel Portugal; Luís Barreiro; J. Moniz-Pereira; L. Brum

2004-01-01

259

Non-human sources of Mycobacterium tuberculosis.  

PubMed

Mycobacterium tuberculosis is a successful pathogen responsible for the vast majority of deadly tuberculosis cases in humans. It rests in a dormant form in contaminated people who constitute the reservoir with airborne interhuman transmission during pulmonary tuberculosis. M. tuberculosis is therefore regarded majoritary as a human pathogen. Here, we review the evidence for anthroponotic M. tuberculosis infection in non-human primates, other mammals and psittacines. Some infected animals may be sources for zoonotic tuberculosis caused by M. tuberculosis, with wild life trade and zoos being amplifying factors. Moreover, living animals and cadavers can scatter M. tuberculosis in the environment where it could survive for extended periods of time in soil where amoebae could play a role. Although marginal in the epidemiology of human tuberculosis, these data indicate that M. tuberculosis is not uniquely adapted to humans. PMID:24119770

Ghodbane, Ramzi; Drancourt, Michel

2013-11-01

260

Tuberculosis in Sudan: a study of Mycobacterium tuberculosis strain genotype and susceptibility to anti-tuberculosis drugs  

PubMed Central

Background Sudan is a large country with a diverse population and history of civil conflict. Poverty levels are high with a gross national income per capita of less than two thousand dollars. The country has a high burden of tuberculosis (TB) with an estimated 50,000 incident cases during 2009, when the estimated prevalence was 209 cases per 100,000 of the population. Few studies have been undertaken on TB in Sudan and the prevalence of drug resistant disease is not known. Methods In this study Mycobacterium tuberculosis isolates from 235 patients attending three treatment centers in Sudan were screened for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by spoligotyping. Demographic details of patients were recorded using a structured questionnaire. Statistical analyses were conducted to examine the associations between drug resistance with risk ratios computed for a set of risk factors (gender, age, case status - new or relapse, geographic origin of the patient, spoligotype, number of people per room, marital status and type of housing). Results Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95% CI: 14,34) of previously treated patients. Drug resistance was associated with previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB. Resistance was also associated with the geographic region of origin of the patient, being most frequently observed in patients from the Northern region and least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: < 0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR-TB. The major genotype observed was of the Central Asia spoligotype family (CAS1_Delhi), representing 49% of the 232 isolates examined. Conclusions We conclude that emergence of drug resistant tuberculosis has the potential to be a serious public health problem in Sudan and that strengthened tuberculosis control and improved monitoring of therapy is needed. Further surveillance is required to fully ascertain the extent of the problem. PMID:21846389

2011-01-01

261

Oral tuberculosis: unusual radiographic findings  

PubMed Central

Oral tuberculosis and its radiographic findings are not commonly encountered in an oral and maxillofacial radiology practice. Literature has occasional mention of the radiographic findings of oral tuberculosis, which are still ambiguous. When affected, it is manifested majorly in the oral mucosa and rarely in the jaw bones. Here, we report certain unusual radiographic findings of oral tuberculosis which have been rarely mentioned in the literature. Four illustrative cases describe bony resorption, condylar resorption, resorption of the inferior border of the mandible and rarefaction of the alveolar bone as radiographic findings of oral tuberculosis. Follow up of the first case demonstrated regeneration of the condylar head after anti-Kochs therapy was completed, a hitherto unreported phenomenon. The importance of including tuberculosis in the differential diagnosis of some of the unusual radiographic manifestations is emphasized. PMID:21493882

Sansare, K; Gupta, A; Khanna, V; Karjodkar, F

2011-01-01

262

Metabolism of the anti-tuberculosis drug ethionamide by mouse and human FMO1, FMO2 and FMO3 and mouse and human lung microsomes  

Microsoft Academic Search

Tuberculosis (TB) results from infection with Mycobacterium tuberculosis and remains endemic throughout the world with one-third of the world's population infected. The prevalence of multi-drug resistant strains necessitates the use of more toxic second-line drugs such as ethionamide (ETA), a pro-drug requiring bioactivation to exert toxicity. M. tuberculosis possesses a flavin monooxygenase (EtaA) that oxygenates ETA first to the sulfoxide

Marilyn C. Henderson; Lisbeth K. Siddens; Jeffrey T. Morré; Sharon K. Krueger; David E. Williams

2008-01-01

263

Evaluation and identification of dismembered human remains.  

PubMed

On occasion, pathologists are confronted with cases involving dismembered human remains. Such cases present unique and interesting problems of postmortem identification. Four cases involving dismembered human remains are presented here and practical suggestions on how identification can be achieved are provided. PMID:1807138

Hyma, B A; Rao, V J

1991-12-01

264

Triosephosphate isomerase is dispensable in vitro yet essential for Mycobacterium tuberculosis to establish infection.  

PubMed

ABSTRACT Triosephosphate isomerase (TPI) catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). This reaction is required for glycolysis and gluconeogenesis, and tpi has been predicted to be essential for growth of Mycobacterium tuberculosis. However, when studying a conditionally regulated tpi knockdown mutant, we noticed that depletion of TPI reduced growth of M. tuberculosis in media containing a single carbon source but not in media that contained both a glycolytic and a gluconeogenic carbon source. We used such two-carbon-source media to isolate a tpi deletion (?tpi) mutant. The ?tpi mutant did not survive with single carbon substrates but grew like wild-type (WT) M. tuberculosis in the presence of both a glycolytic and a gluconeogenic carbon source. (13)C metabolite tracing revealed the accumulation of TPI substrates in ?tpi and the absence of alternative triosephosphate isomerases and metabolic bypass reactions, which confirmed the requirement of TPI for glycolysis and gluconeogenesis in M. tuberculosis. The ?tpi strain was furthermore severely attenuated in the mouse model of tuberculosis, suggesting that M. tuberculosis cannot simultaneously access sufficient quantities of glycolytic and gluconeogenic carbon substrates to establish infection in mice. IMPORTANCE The importance of central carbon metabolism for the pathogenesis of M. tuberculosis has recently been recognized, but the consequences of depleting specific metabolic enzymes remain to be identified for many enzymes. We investigated triosephosphate isomerase (TPI) because it is central to both glycolysis and gluconeogenesis and had been predicted to be essential for growth of M. tuberculosis. This work identified metabolic conditions that make TPI dispensable for M. tuberculosis growth in culture and proved that M. tuberculosis relies on a single TPI enzyme and has no metabolic bypass for the TPI-dependent interconversion of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate in glycolysis and gluconeogenesis. Finally, we demonstrate that TPI is essential for growth of the pathogen in mouse lungs. PMID:24757211

Trujillo, Carolina; Blumenthal, Antje; Marrero, Joeli; Rhee, Kyu Y; Schnappinger, Dirk; Ehrt, Sabine

2014-01-01

265

A Bayesian Change point model for differential gene expression patterns of the DosR regulon of Mycobacterium tuberculosis  

E-print Network

Abstract Background Low oxygen availability has been shown previously to stimulate M. tuberculosis to establish non-replicative persistence in vitro. The two component sensor/regulator dosRS is a major mediator in the transcriptional response of M...

Zhang, Yi; Hatch, Kim A; Wernisch, Lorenz; Bacon, Joanna

2008-02-22

266

Using affinity propagation for identifying subspecies among clonal organisms: lessons from M. tuberculosis  

Microsoft Academic Search

Background  Classification and naming is a key step in the analysis, understanding and adequate management of living organisms. However,\\u000a where to set limits between groups can be puzzling especially in clonal organisms. Within the Mycobacterium tuberculosis complex (MTC), the etiological agent of tuberculosis (TB), experts have first identified several groups according to their\\u000a pattern at repetitive sequences, especially at the CRISPR

Claudio Borile; Mathieu Labarre; Silvio Franz; Christophe Sola; Guislaine Refrégier

2011-01-01

267

A Single-Step Sequencing Method for the Identification of Mycobacterium tuberculosis Complex Species  

Microsoft Academic Search

BackgroundThe Mycobacterium tuberculosis complex (MTC) comprises closely related species responsible for strictly human and zoonotic tuberculosis. Accurate species determination is useful for the identification of outbreaks and epidemiological links. Mycobacterium africanum and Mycobacterium canettii are typically restricted to Africa and M. bovis is a re-emerging pathogen. Identification of these species is difficult and expensive.Methodology\\/Principal FindingsThe Exact Tandem Repeat D (ETR-D;

Zoheira Djelouadji; Didier Raoult; Mamadou Daffé; Michel Drancourt

2008-01-01

268

Is IP10 a Better Biomarker for Active and Latent Tuberculosis in Children than IFN??  

Microsoft Academic Search

BackgroundThe blood based interferon-gamma release assays (IGRA) for the diagnosis of tuberculosis do not discriminate between active TB disease and latent TB infection (LTBI). The search for distinguishing biomarkers therefore continues, as the accurate diagnosis of tuberculosis is particularly challenging in children. IFN-?-inducible protein 10 (IP-10\\/CXCL10) has recently been evaluated as a marker for active TB in adults with promising

Elizabeth Whittaker; Andrea Gordon; Beate Kampmann

2008-01-01

269

Mycobacterium tuberculosis infection of human dendritic cells decreases integrin expression, adhesion and migration to chemokines  

PubMed Central

Tuberculosis (TB) remains a major global health problem accounting for millions of deaths annually. Approximately one-third of the world's population is infected with the causative agent Mycobacterium tuberculosis. The onset of an adaptive immune response to M. tuberculosis is delayed compared with other microbial infections. This delay permits bacterial growth and dissemination. The precise mechanism(s) responsible for this delay have remained obscure. T-cell activation is preceded by dendritic cell (DC) migration from infected lungs to local lymph nodes and synapsis with T cells. We hypothesized that M. tuberculosis may impede the ability of DCs to reach lymph nodes and initiate an adaptive immune response. We used primary human DCs to determine the effect of M. tuberculosis on expression of heterodimeric integrins involved in cellular adhesion and migration. We also evaluated the ability of infected DCs to adhere to and migrate through lung endothelial cells, which is necessary to reach lymph nodes. We show by flow cytometry and confocal microscopy that M. tuberculosis-infected DCs exhibit a significant reduction in surface expression of the ?2 (CD18) integrin. Distribution of integrin ?2 is also markedly altered in M. tuberculosis-infected DCs. A corresponding reduction in the ?L (CD11a) and ?M (CD11b) subunits that associate with integrin ?2 was also observed. Consistent with reduced integrin surface expression, we show a significant reduction in adherence to lung endothelial cell monolayers and migration towards lymphatic chemokines when DCs are infected with M. tuberculosis. These findings suggest that M. tuberculosis modulates DC adhesion and migration to increase the time required to initiate an adaptive immune response. PMID:23981064

Roberts, Lawton L; Robinson, Cory M

2014-01-01

270

Highly structured genetic diversity of the Mycobacterium tuberculosis population in  

E-print Network

Highly structured genetic diversity of the Mycobacterium tuberculosis population in Djibouti S, Djibouti Ville, Djibouti Abstract Djibouti is an East African country with a high tuberculosis incidence with pulmonary tuberculosis (TB) were included. Genetic characterization of Mycobacterium tuberculosis, using

Choisy, Marc

271

Re-thinking global health sector efforts for HIV and tuberculosis epidemic control: promoting integration of programme activities within a strengthened health system  

Microsoft Academic Search

BACKGROUND: The global financial crisis threatens global health, particularly exacerbating diseases of inequality, e.g. HIV\\/AIDS, and diseases of poverty, e.g. tuberculosis. The aim of this paper is to reconsider established practices and policies for HIV and tuberculosis epidemic control, aiming at delivering better results and value for money. This may be achieved by promoting greater integration of HIV and tuberculosis

Dermot Maher

2010-01-01

272

Basis for treatment of tuberculosis among HIV-infected patients in Tanzania: the role of chest x-ray and sputum culture  

Microsoft Academic Search

BACKGROUND: Active tuberculosis (TB) is common among HIV-infected persons living in tuberculosis endemic countries, and screening for tuberculosis (TB) is recommended routinely. We sought to determine the role of chest x-ray and sputum culture in the decision to treat for presumptive TB using active case finding in a large cohort of HIV-infected patients. METHODS: Ambulatory HIV-positive subjects with CD4 counts

Muhammad Bakari; Robert D Arbeit; Lillian Mtei; Johnson Lyimo; Richard Waddell; Mecky Matee; Bernard F Cole; Susan Tvaroha; C Robert Horsburgh; Hanna Soini; Kisali Pallangyo; C Fordham von Reyn

2008-01-01

273

Whole Genome Sequencing of Mycobacterium tuberculosis Reveals Slow Growth and Low Mutation Rates during Latent Infections in Humans  

PubMed Central

Very little is known about the growth and mutation rates of Mycobacterium tuberculosis during latent infection in humans. However, studies in rhesus macaques have suggested that latent infections have mutation rates that are higher than that observed during active tuberculosis disease. Elevated mutation rates are presumed risk factors for the development of drug resistance. Therefore, the investigation of mutation rates during human latency is of high importance. We performed whole genome mutation analysis of M. tuberculosis isolates from a multi-decade tuberculosis outbreak of the New Zealand Rangipo strain. We used epidemiological and phylogenetic analysis to identify four cases of tuberculosis acquired from the same index case. Two of the tuberculosis cases occurred within two years of exposure and were classified as recently transmitted tuberculosis. Two other cases occurred more than 20 years after exposure and were classified as reactivation of latent M. tuberculosis infections. Mutation rates were compared between the two recently transmitted pairs versus the two latent pairs. Mean mutation rates assuming 20 hour generation times were 5.5X10?10 mutations/bp/generation for recently transmitted tuberculosis and 7.3X10?11 mutations/bp/generation for latent tuberculosis. Generation time versus mutation rate curves were also significantly higher for recently transmitted tuberculosis across all replication rates (p?=?0.006). Assuming identical replication and mutation rates among all isolates in the final two years before disease reactivation, the u20hr mutation rate attributable to the remaining latent period was 1.6×10?11 mutations/bp/generation, or approximately 30 fold less than that calculated during the two years immediately before disease. Mutations attributable to oxidative stress as might be caused by bacterial exposure to the host immune system were not increased in latent infections. In conclusion, we did not find any evidence to suggest elevated mutation rates during tuberculosis latency in humans, unlike the situation in rhesus macaques. PMID:24618815

Colangeli, Roberto; Arcus, Vic L.; Cursons, Ray T.; Ruthe, Ali; Karalus, Noel; Coley, Kathy; Manning, Shannon D.; Kim, Soyeon; Marchiano, Emily; Alland, David

2014-01-01

274

Association Study of Genes Controlling IL-12-dependent IFN-? Immunity: STAT4 Alleles Increase Risk of Pulmonary Tuberculosis in Morocco  

PubMed Central

Background.?Only a minority of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis. Genetic epidemiological evidence suggests that pulmonary tuberculosis has a strong human genetic component. Previous genetic findings in Mendelian predisposition to more severe mycobacterial infections, including by M. tuberculosis, underlined the importance of the interleukin 12 (IL-12)/interferon ? (IFN-?) circuit in antimycobacterial immunity. Methods.?We conducted an association study in Morocco between pulmonary tuberculosis and a panel of single-nucleotide polymorphisms (SNPs) covering 14 core IL-12/IFN-? circuit genes. The analyses were performed in a discovery family-based sample followed by replication in a case-control population. Results.?Out of 228 SNPs tested in the family-based sample, 6 STAT4 SNPs were associated with pulmonary tuberculosis (P = .0013–.01). We replicated the same direction of association for 1 cluster of 3 SNPs encompassing the promoter region of STAT4. In the combined sample, the association was stronger among younger subjects (pulmonary tuberculosis onset <25 years) with an odds ratio of developing pulmonary tuberculosis at rs897200 for GG vs AG/AA subjects of 1.47 (1.06–2.04). Previous functional experiments showed that the G allele of rs897200 was associated with lower STAT4 expression. Conclusions.?Our present findings in a Moroccan population support an association of pulmonary tuberculosis with STAT4 promoter-region polymorphisms that may impact STAT4 expression. PMID:24610875

Sabri, Ayoub; Grant, Audrey V.; Cosker, Kristel; El Azbaoui, Safa; Abid, Ahmed; Abderrahmani Rhorfi, Ismail; Souhi, Hicham; Janah, Hicham; Alaoui-Tahiri, Kebir; Gharbaoui, Yasser; Benkirane, Majid; Orlova, Marianna; Boland, Anne; Deswarte, Caroline; Migaud, Melanie; Bustamante, Jacinta; Schurr, Erwin; Boisson-Dupuis, Stephanie; Casanova, Jean-Laurent; Abel, Laurent; El Baghdadi, Jamila

2014-01-01

275

Hypercholesterolemia Impairs Immunity to Tuberculosis ?  

PubMed Central

We demonstrate that apolipoprotein E -deficient (ApoE?/?) mice are highly susceptible to tuberculosis and that their susceptibility depends on the severity of hypercholesterolemia. Wild-type (WT) mice and ApoE?/? mice fed a low-cholesterol (LC) or high-cholesterol (HC) diet were infected with ?50 CFU Mycobacterium tuberculosis Erdman by aerosol. ApoE?/? LC mice were modestly more susceptible to tuberculosis than WT LC mice. In contrast, ApoE?/? HC mice were extremely susceptible, as evidenced by 100% mortality after 4 weeks with tuberculosis. The lung pathology of ApoE?/? HC mice was remarkable for giant abscess-like lesions, massive infiltration by granulocytes, elevated inflammatory cytokine production, and a mean bacterial load ?2 log units higher than that of WT HC mice. Compared to WT HC mice, the gamma interferon response of splenocytes restimulated ex vivo with M. tuberculosis culture filtrate protein was delayed in ApoE?/? HC mice, and they failed to control M. tuberculosis growth in the lung. OT-II cells adoptively transferred into uninfected ApoE?/? HC mice had a weak proliferative response to their antigen, indicating impaired priming of the adaptive immune response. Our studies show that ApoE?/? deficiency is associated with delayed expression of adaptive immunity to tuberculosis caused by defective priming of the adaptive immune response and that elevated serum cholesterol is responsible for this effect. PMID:18505807

Martens, Gregory W.; Arikan, Meltem Cevik; Lee, Jinhee; Ren, Fucheng; Vallerskog, Therese; Kornfeld, Hardy

2008-01-01

276

Tuberculosis in the AIDS era.  

PubMed Central

A resurgence of tuberculosis has occurred in recent years in the United States and abroad. Deteriorating public health services, increasing numbers of immigrants from countries of endemicity, and coinfection with the human immunodeficiency virus (HIV) have contributed to the rise in the number of cases diagnosed in the United States. Outbreaks of resistant tuberculosis, which responds poorly to therapy, have occurred in hospitals and other settings, affecting patients and health care workers. This review covers the pathogenesis, epidemiology, clinical presentation, laboratory diagnosis, and treatment of Mycobacterium tuberculosis infection and disease. In addition, public health and hospital infection control strategies are detailed. Newer approaches to epidemiologic investigation, including use of restriction fragment length polymorphism analysis, are discussed. Detailed consideration of the interaction between HIV infection and tuberculosis is given. We also review the latest techniques in laboratory evaluation, including the radiometric culture system, DNA probes, and PCR. Current recommendations for therapy of tuberculosis, including multidrug-resistant tuberculosis, are given. Finally, the special problem of prophylaxis of persons exposed to multidrug-resistant tuberculosis is considered. PMID:7621399

Sepkowitz, K A; Raffalli, J; Riley, L; Kiehn, T E; Armstrong, D

1995-01-01

277

Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis  

PubMed Central

The inherent drug susceptibility of microorganisms is determined by multiple factors, including growth state, the rate of drug diffusion into and out of the cell, and the intrinsic vulnerability of drug targets with regard to the corresponding antimicrobial agent. Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains a significant source of global morbidity and mortality, further exacerbated by its ability to readily evolve drug resistance. It is well accepted that drug resistance in M. tuberculosis is driven by the acquisition of chromosomal mutations in genes encoding drug targets/promoter regions; however, a comprehensive description of the molecular mechanisms that fuel drug resistance in the clinical setting is currently lacking. In this context, there is a growing body of evidence suggesting that active extrusion of drugs from the cell is critical for drug tolerance. M. tuberculosis encodes representatives of a diverse range of multidrug transporters, many of which are dependent on the proton motive force (PMF) or the availability of ATP. This suggests that energy metabolism and ATP production through the PMF, which is established by the electron transport chain (ETC), are critical in determining the drug susceptibility of M. tuberculosis. In this review, we detail advances in the study of the mycobacterial ETC and highlight drugs that target various components of the ETC. We provide an overview of some of the efflux pumps present in M. tuberculosis and their association, if any, with drug transport and concomitant effects on drug resistance. The implications of inhibiting drug extrusion, through the use of efflux pump inhibitors, are also discussed. PMID:24614376

Black, Philippa A.; Warren, Robin M.; Louw, Gail E.; van Helden, Paul D.; Victor, Thomas C.

2014-01-01

278

Molecular diagnostics in tuberculosis: basis and implications for therapy.  

PubMed

The processing of clinical specimens in the mycobacterial diagnostic laboratory has undergone remarkable improvements during the last decade. While microscopy and culture are still the major backbone for laboratory diagnosis of tuberculosis on a worldwide basis, new methods including molecular diagnostic tests have evolved over the last two decades. The majority of molecular tests have been focused on (i) detection of nucleic acids, both DNA and RNA, that are specific to Mycobacterium tuberculosis, by amplification techniques such as polymerase chain reaction (PCR); and (ii) detection of mutations in the genes that are associated with resistance to antituberculosis drugs by sequencing or nucleic acid hybridization. Recent developments in direct and rapid detection of mycobacteria, with emphasis on M. tuberculosis species identification by 16S rRNA gene sequence analysis or oligohybridization and strain typing, as well as detection of drug susceptibility patterns, all contribute to these advances. Generally, the balance between genome instability and genome maintenance as the basis for evolutionary development, strain diversification and resistance development is important, because it cradles the resulting M. tuberculosis phenotype. At the same time, semi-automated culture systems have contributed greatly to the increased sensitivity and reduced turnaround time in the mycobacterial analysis of clinical specimens. Collectively, these advances are particularly important for establishing the diagnosis of tuberculosis in children. More basic and operational research to appraise the impact and cost effectiveness of new diagnostic technologies must, however, be carried out. Furthermore, the design and quality of clinical trials evaluating new diagnostics must be improved to allow clinical and laboratory services that would provide rapid response to test results. Thus, important work remains before the new diagnostic tools can be meaningfully integrated into national tuberculosis control programs of high-burden countries. PMID:19650669

Balasingham, Seetha V; Davidsen, Tonje; Szpinda, Irena; Frye, Stephan A; Tønjum, Tone

2009-01-01

279

The Genotypic Population Structure of Mycobacterium tuberculosis Complex from Moroccan Patients Reveals a Predominance of Euro-American Lineages  

PubMed Central

Background Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circulating Mycobacterium tuberculosis genotypic lineages, important to understand the dynamic of the disease, was hereby addressed for the first time at a national level. Methodology/Principal Findings Spoligotyping was performed on a panel of 592 M. tuberculosis complex strains covering a 2-year period (2004–2006). It identified 129 patterns: 105 (n?=?568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1– ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2– modern/TbD1?/PGG1 group (Beijing, CAS), group 3– evolutionary recent/TbD1?/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n?=?5, CAS n?=?1), and 3 strains (BOV_1 n?=?2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n?=?114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%. Conclusion The M. tuberculosis population structure in Morocco is highly homogeneous, and is characterized by the predominance of the Euro-American lineages, namely LAM, Haarlem, and T, which belong to the “evolutionary recent” TbD1?/PGG2/3 phylogenetic group. The combination of spoligotyping and MIRUs decreased the clustering rate significantly, and should now be systematically applied in larger studies. The methods used in this study appear well suited to monitor the M. tuberculosis population structure for an enhanced TB management program in Morocco. PMID:23077552

Lahlou, Ouafae; Millet, Julie; Chaoui, Imane; Sabouni, Radia; Filali-Maltouf, Abdelkarim; Akrim, Mohammed; El Mzibri, Mohammed; Rastogi, Nalin; El Aouad, Rajae

2012-01-01

280

Molecular diversity of Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in Mozambique  

PubMed Central

Background Mozambique is one of the countries with the highest burden of tuberculosis (TB) in Sub-Saharan Africa, and information on the predominant genotypes of Mycobacterium tuberculosis circulating in the country are important to better understand the epidemic. This study determined the predominant strain lineages that cause TB in Mozambique. Results A total of 445 M. tuberculosis isolates from seven different provinces of Mozambique were characterized by spoligotyping and resulting profiles were compared with the international spoligotyping database SITVIT2. The four most predominant lineages observed were: the Latin-American Mediterranean (LAM, n = 165 or 37%); the East African-Indian (EAI, n = 132 or 29.7%); an evolutionary recent but yet ill-defined T clade, (n = 52 or 11.6%); and the globally-emerging Beijing clone, (n = 31 or 7%). A high spoligotype diversity was found for the EAI, LAM and T lineages. Conclusions The TB epidemic in Mozambique is caused by a wide diversity of spoligotypes with predominance of LAM, EAI, T and Beijing lineages. PMID:20663126

2010-01-01

281

Hepatobiliary and pancreatic tuberculosis: A two decade experience  

PubMed Central

Background Isolated hepatobiliary or pancreatic tuberculosis (TB) is rare and preoperative diagnosis is difficult. We reviewed our experience over a period two decades with this rare site of abdominal tuberculosis. Methods The records of 18 patients with proven histological diagnosis of hepatobiliary and pancreatic tuberculosis were reviewed retrospectively. The demographic features, sign and symptoms, imaging, cytology/histopathology, procedures performed, outcome and follow up data were obtained from the departmental records. The diagnosis of tuberculosis was based on granuloma with caseation necrosis on histopathology or presence of acid fast bacilli. Results Of 18 patients (11 men), 11 had hepatobiliary TB while 7 had pancreatic TB. Two-thirds of the patients were < 40 years (mean: 42 yrs; range 19–70 yrs). The duration of the symptoms varied between 2 weeks to 104 weeks (mean: 20 weeks). The most common symptom was pain in the abdomen (n = 13), followed by jaundice (n = 10), fever, anorexia and weight loss (n = 9). Five patients (28%) had associated extra-abdominal TB which helped in preoperative diagnosis in 3 patients. Imaging demonstrated extrahepatic bile duct obstruction in the patients with jaundice and in addition picked up liver, gallbladder and pancreatic masses with or without lymphadenopathy (peripancreatic/periportal). Preoperative diagnosis was made in 4 patients and the other 14 were diagnosed after surgery. Two patients developed significant postoperative complications (pancreaticojejunostomy leak [1] intraabdominal abscess [1]) and 3 developed ATT induced hepatotoxicity. No patient died. The median follow up period was 12 months (9 – 96 months). Conclusion Tuberculosis should be considered as a differential diagnosis, particularly in young patients, with atypical signs and symptoms coming from areas where tuberculosis is endemic and preoperative tissue and/or cytological diagnosis should be attempted before labeling them as hepatobiliary and pancreatic malignancy. PMID:17588265

Saluja, Sundeep S; Ray, Sukanta; Pal, Sujoy; Kukeraja, Manu; Srivastava, Deep N; Sahni, Peush; Chattopadhyay, Tushar K

2007-01-01

282

Tuberculosis: Past, Present and Future  

PubMed Central

Observation and statistics are offered on treatment of tuberculosis in sanatoria during the lifespan of those institutions with special reference to one where the first author's medical life was mainly spent as patient, physician, surgeon and superintendent. Despite the rapid decrease in morbidity and mortality of tuberculosis, the change in direction, and the change in treatment programs, vigilance is still required. It is only because of the commitment of those involved over the many years in the treatment of tuberculosis that we are now at this enviable position. Imagesp[57]-ap56-a PMID:21301581

Paine, A. L.; Hershfield, Earl S.

1979-01-01

283

T lymphocytes in pulmonary tuberculosis.  

PubMed

T cells and their sub-populations were evaluated with respect to reactive, intermediate and unreactive forms of tuberculosis as classified by Lenzini. Significant CD4 lymphopenia and a reduction of CD4/CD8 ratios were found in patients with reactive tuberculosis. It was observed that there was a B lymphocytosis, CD8 lymphocytosis and a reduction of CD4/CD8 ratio in patients with intermediate and unreactive forms of tuberculosis. The T lymphocytes and CD4 subset were unchanged. There was no significant difference in the lymphocytes and sub-populations among the intermediate and unreactive groups. PMID:8486403

Ashtekar, M D; Samuel, A M; Kadival, G V; Sakhalkar, V; Rajadhyaksha, S; Virdi, S S

1993-01-01

284

Diagnosis and Management of Tuberculosis  

PubMed Central

The incidence of pulmonary tuberculosis in technically advanced and economically well-developed countries is decreasing, and the disease has become more subtle in presentation. In a recent study from British Columbia, about half the deaths from tuberculosis were diagnosed at autopsy. Most of these patients had died in hospital and their mean duration of stay was 14.5 days. The chemotherapeutic agents available today can cure most cases and prevent further spread of infection. The appropriate use of chemoprophylaxis can substantially reduce the size of the infected pool at risk of developing tuberculosis. PMID:21286560

Ahmad, Dildar

1982-01-01

285

A role for IL-18 in protective immunity against Mycobacterium tuberculosis  

PubMed Central

Tuberculosis remains the most hazardous bacterial infection worldwide. The causative agent, Mycobacterium tuberculosis, is a facultative intracellular pathogen of resting M?. IFN-? secreted by natural killer, CD4 Th 1 and CD8 T cells upon instruction by IL-12 and -18 activates M? to restrict mycobacterial growth. Production of both cytokines is induced by TLR signalling in DC and M?. Mice deficient for the TLR adaptor, MyD88, are highly susceptible to M. tuberculosis infection. Shared usage of MyD88 by signalling cascades for TLR and receptors for IL-1 and IL-18 prompted us to revisit the role of IL-18 during experimental infection with M. tuberculosis. We show that mice deficient for IL-18 and MyD88 but not for IL-18 receptor promptly succumbed to M. tuberculosis infection in contrast to WT or TLR-2/-4 double KO mice indicating that lack of IL-18 contributes to the high susceptibility of MyD88 KO mice to M. tuberculosis. Without IL-18, the protective Th1 response was decreased and hence, mycobacterial propagation was favoured. Neutrophil-driven lung immunopathology concomitant with unrestrained growth of tubercle bacilli are most likely responsible for the premature death of IL-18 KO mice. Thus, IL-18 plays a decisive role in protective immunity against tuberculosis. PMID:19950174

Schneider, Bianca E.; Korbel, Daniel; Hagens, Kristine; Koch, Markus; Raupach, Bärbel; Enders, Jana; Kaufmann, Stefan H. E.; Mittrücker, Hans-Willi; Schaible, Ulrich E.

2011-01-01

286

cor, a Novel Carbon Monoxide Resistance Gene, Is Essential for Mycobacterium tuberculosis Pathogenesis  

PubMed Central

ABSTRACT Tuberculosis, caused by Mycobacterium tuberculosis, remains a devastating human infectious disease, causing two million deaths annually. We previously demonstrated that M. tuberculosis induces an enzyme, heme oxygenase (HO1), that produces carbon monoxide (CO) gas and that M. tuberculosis adapts its transcriptome during CO exposure. We now demonstrate that M. tuberculosis carries a novel resistance gene to combat CO toxicity. We screened an M. tuberculosis transposon library for CO-susceptible mutants and found that disruption of Rv1829 (carbon monoxide resistance, Cor) leads to marked CO sensitivity. Heterologous expression of Cor in Escherichia coli rescued it from CO toxicity. Importantly, the virulence of the cor mutant is attenuated in a mouse model of tuberculosis. Thus, Cor is necessary and sufficient to protect bacteria from host-derived CO. Taken together, this represents the first report of a role for HO1-derived CO in controlling infection of an intracellular pathogen and the first identification of a CO resistance gene in a pathogenic organism. PMID:24255121

Zacharia, Vineetha M.; Manzanillo, Paolo S.; Nair, Vidhya R.; Marciano, Denise K.; Kinch, Lisa N.; Grishin, Nick V.; Cox, Jeffery S.; Shiloh, Michael U.

2013-01-01

287

Reducing deaths from tuberculosis in antiretroviral treatment programmes in sub-Saharan Africa  

PubMed Central

Mortality rates are high in antiretroviral therapy (ART) programmes in sub-Saharan Africa, especially during the first few months of treatment. Tuberculosis (TB) has been identified as a major underlying cause. Under routine programme conditions, between 5% and 40% of adult patients enrolling in ART services have a baseline diagnosis of TB. There is also a high TB incidence during the first few months of ART (much of which is prevalent disease missed by baseline screening) and long-term rates remain several-fold higher than background. We identify three groups of patients entering ART programmes for which different interventions are required to reduce TB-related deaths. First, diagnostic screening is needed in patients who have undiagnosed active TB so that timely anti-tuberculosis treatment can be started. This may be greatly facilitated by new diagnostic assays such as the Xpert MTB/RIF assay. Second, patients with a diagnosis of active TB need optimised case management, which includes early initiation of ART (with timing now defined by randomised controlled trials), trimethoprim-sulphamethoxazole prophylaxis and treatment of co-morbidity. Third, all remaining patients who are TB-free at enrolment have high ongoing risk of developing TB and require optimised immune recovery (with ART ideally started early in the course of HIV infection), isoniazid preventive therapy and infection control to reduce infection risk. Further specific measures are needed to address multi-drug resistant TB (MDR-TB). Finally, scale-up of all these interventions requires nationally and locally tailored models of care that are patient-centred and provide integrated health care delivery for TB, HIV and other co-morbidities. PMID:22695302

Lawn, Stephen D.; Harries, Anthony D.; Meintjes, Graeme; Getahun, Haileyesus; Havlir, Diane V.; Wood, Robin

2013-01-01

288

Clinical peculiarities of tuberculosis  

PubMed Central

The ongoing spread of tuberculosis (TB) in poor resource countries and the recently increasing incidence in high resource countries lead to the need of updated knowledge for clinicians, particularly for pediatricians. The purpose of this article is to provide an overview on the most important peculiarities of TB in children. Children are less contagious than adults, but the risk of progression to active disease is higher in infants and children as compared to the subsequent ages. Diagnosis of TB in children is more difficult than in adults, because few signs are associated with primary infection, interferon-gamma release assays and tuberculin skin test are less reliable in younger children, M. tuberculosis is more rarely detected in gastric aspirates than in smears in adults and radiological findings are often not specific. Treatment of latent TB is always necessary in young children, whereas it is recommended in older children, as well as in adults, only in particular conditions. Antimycobacterial drugs are generally better tolerated in children as compared to adults, but off-label use of second-line antimycobacterial drugs is increasing, because of spreading of multidrug resistant TB worldwide. Given that TB is a disease which often involves more than one member in a family, a closer collaboration is needed between pediatricians and clinicians who take care of adults. PMID:24564419

2014-01-01

289

A Care Pathway Analysis of Tuberculosis Patients in Benin: Highlights on Direct Costs and Critical Stages for an Evidence-Based Decision-Making  

PubMed Central

Background Free tuberculosis control fail to protect patients from substantial medical and non-medical expenditure, thus a greater degree of disaggregation of patient cost is needed to fully capture their context and inform policymaking. Methods A retrospective cross-sectional study was conducted on a convenience sample of six health districts of Southern Benin. From August 2008 to February 2009, we recruited all smear-positive pulmonary tuberculosis patients treated under the national strategy in the selected districts. Direct out-of-pocket costs associated with tuberculosis, time delays, and care-seeking pattern were collected from symptom onset to end of treatment. Results Population description and outcome data were reported for 245 patients of whom 153 completed their care pathway. For them, the median overall direct cost was USD 183 per patient. Payments to traditional healers, self-medication drugs, travel, and food expenditures contributed largely to this cost burden. Patient, provider, and treatment delays were also reported. Pre-diagnosis and intensive treatment stages were the most critical stages, with median expenditure of USD 43 per patient and accounting for 38% and 29% of the overall direct cost, respectively. However, financial barriers differed depending on whether the patient lived in urban or rural areas. Conclusions This study delivers new evidence about bottlenecks encountered during the TB care pathway. Financial barriers to accessing the free-of-charge tuberculosis control strategy in Benin remain substantial for low-income households. Irregular time delays and hidden costs, often generated by multiple visits to various care providers, impair appropriate patient pathways. Particular attention should be paid to pre-diagnosis and intensive treatment. Cost assessment and combined targeted interventions embodied by a patient-centered approach on the specific critical stages would likely deliver better program outcomes. PMID:24810007

Laokri, Samia; Amoussouhui, Arnaud; Ouendo, Edgard M.; Hounnankan, Athanase Cossi; Anagonou, Séverin; Gninafon, Martin; Kassa, Ferdinand; Tawo, Léon; Dujardin, Bruno

2014-01-01

290

Adequate Expression of Protective Immunity in the Absence of Granuloma Formation in Mycobacterium tuberculosis-Infected Mice with a Disruption in the Intracellular Adhesion Molecule 1 Gene  

Microsoft Academic Search

It remains unknown whether the expression of cell-mediated protective immunity and the capacity to mount a delayed-type hypersensitivity (DTH) reaction in tuberculosis infection represent two manifestations of a basic response or are dissociable events. In this study, we present data in favor of the latter hypothesis, by showing that tuberculosis infection in the lungs of mice possessing only a truncated

CHRISTINE M. JOHNSON; ANDREA M. COOPER; ANTHONY A. FRANK; IAN M. ORME

1998-01-01

291

Genetic Diversity of Mycobacterium tuberculosis Isolates from Tibetans in Tibet, China  

PubMed Central

Background Tuberculosis (TB) is a serious health problem in Tibet where Tibetans are the major ethnic group. Although genotyping of Mycobacterium tuberculosis (M. tuberculosis) isolates is a valuable tool for TB control, our knowledge of population structure of M. tuberculosis circulating in Tibet is limited. Methodology/Principal Findings In our study, a total of 576 M. tuberculosis isolates from Tibetans in Tibet, China, were analyzed via spoligotyping and 24-locus MIRU-VNTR. The Beijing genotype was the most prevalent family (90.63%, n?=?522). Shared-type (ST) 1 was the most dominant genotype (88.89%, n?=?512). We found that there was no association between the Beijing genotype and sex, age and treatment status. In this sample collection, 7 of the 24 MIRU-VNTR loci were highly or moderately discriminative according to their Hunter-Gaston discriminatory index. An informative set of 12 loci had similar discriminatory power with 24 loci set. Conclusions/Significance The population structure of M. tuberculosis isolates in Tibetans is homogeneous and dominated by Beijing genotype. The analysis of 24-locus MIRU-VNTR data might be useful to select appropriate VNTR loci for the genotyping of M. tuberculosis. PMID:22479472

Zhao, Xiuqin; Sang, Ba; Lv, Bing; Liu, Zhiguang; Wan, Kanglin

2012-01-01

292

Mycobacterium tuberculosis Induces an Atypical Cell Death Mode to Escape from Infected Macrophages  

PubMed Central

Background Macrophage cell death following infection with Mycobacterium tuberculosis plays a central role in tuberculosis disease pathogenesis. Certain attenuated strains induce extrinsic apoptosis of infected macrophages but virulent strains of M. tuberculosis suppress this host response. We previously reported that virulent M. tuberculosis induces cell death when bacillary load exceeds ?20 per macrophage but the precise nature of this demise has not been defined. Methodology/Principal Findings We analyzed the characteristics of cell death in primary murine macrophages challenged with virulent or attenuated M. tuberculosis complex strains. We report that high intracellular bacillary burden causes rapid and primarily necrotic death via lysosomal permeabilization, releasing hydrolases that promote Bax/Bak-independent mitochondrial damage and necrosis. Cell death was independent of cathepsins B or L and notable for ultrastructural evidence of damage to lipid bilayers throughout host cells with depletion of several host phospholipid species. These events require viable bacteria that can respond to intracellular cues via the PhoPR sensor kinase system but are independent of the ESX1 system. Conclusions/Significance Cell death caused by virulent M. tuberculosis is distinct from classical apoptosis, pyroptosis or pyronecrosis. Mycobacterial genes essential for cytotoxicity are regulated by the PhoPR two-component system. This atypical death mode provides a mechanism for viable bacilli to exit host macrophages for spreading infection and the eventual transition to extracellular persistence that characterizes advanced pulmonary tuberculosis. PMID:21483832

Lee, Jinhee; Repasy, Teresa; Papavinasasundaram, Kadamba; Sassetti, Christopher; Kornfeld, Hardy

2011-01-01

293

Procollagen III N-terminal Propeptide and Desmosine are Released by Matrix Destruction in Pulmonary Tuberculosis  

PubMed Central

Background.?Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover products as correlates of lung pathology. Methods.?Induced sputum and plasma were collected prospectively from human immunodeficiency virus (HIV) positive and negative patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in 2 patient cohorts. Results.?Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIV-uninfected tuberculosis patients compared to controls and desmosine, released during elastin degradation, was 2.4-fold higher. PIIINP was elevated in plasma of tuberculosis patients. Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction. In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was increased 3.0-fold above controls (P < .001). Plasma matrix metalloproteinase-8 concentrations were also higher in tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P < .001). Conclusions.?In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products. PMID:23922364

Seddon, Jo; Kasprowicz, Victoria; Walker, Naomi F.; Yuen, Ho Ming; Sunpath, Henry; Tezera, Liku; Meintjes, Graeme; Wilkinson, Robert J.; Bishai, William R.; Friedland, Jon S.; Elkington, Paul T.

2013-01-01

294

Factors associated with tuberculosis among patients attending a treatment centre in Zaria, North-west Nigeria, 2010  

PubMed Central

Introduction Tuberculosis remains a global public health problem. In 2011, tuberculosis incidence was 133 per 100,000 in Nigeria. In Nigeria, little is known about the factors associated with tuberculosis, especially in the northern part and only few studies have characterized the Mycobacterium species that cause tuberculosis infection in humans. This study determined factors associated with tuberculosis and identified Mycobacterium species causing human tuberculosis in North-West, Nigeria. Methods We conducted a hospital based case control study between April and July 2010 in Zaria. Cases were newly diagnosed sputum smear-positive tuberculosis patients >15 years while controls were patients >15 years attending the hospital for other reasons but were negative for tuber-culosis. We used a structured questionnaire to obtain information on demographics, knowledge of transmission of tuberculosis, and exposure to some factors. We preformed descriptive, bivariate and backward elimination logistic regression. Sputa from cases were analyzed by multiplex polymerase chain reaction (PCR) based on genomic regions of difference. Results The mean ages of the cases and controls were 36, standard deviation (SD) 9.0 and 36, SD 9.7 respectively. Only 10 (9.8%) and nine (8.8%) of cases and controls respectively had a good knowledge of the transmission of tuberculosis. Contact with a tuberculosis patient (adjusted odds ratio (AOR) 12.3, 95% confidence interval (CI) 5.2-28.8), consumption of unpasteurized milk (AOR 6.4, CI 2.4-17.2), keeping pets (AOR 5.6, CI 2.3-13.7), associating closely with cattle (AOR 5.6, CI 1.3-6.8), and overcrowding (AOR 4.8, CI 1.8-13.1) were significantly associated with tuberculosis. Of the 102 sputa analyzed, 91 (89%) were M. tuberculosis, 8 (7.8%) were M africanum. Conclusion We identified possible opportunities for intervention to limit the spread of tuberculosis. We recommend that the Nigeria tuberculosis control program consider some of these factors as a way to mitigate the spread of tuberculosis in Nigeria. PMID:25328624

Waziri, Ndadilnasiya Endie; Cadmus, Simeon; Nguku, Patrick; Fawole, Olufunmilayo; Owolodun, Olajide Adewale; Waziri, Hyelshilni; Ibrahim, Luka; Biya, Oladayo; Gidado, Saheed; Badung, Samuel; Kumbish, Peterside; Nsubuga, Peter

2014-01-01

295

Orchestration of pulmonary T cell immunity during Mycobacterium tuberculosis infection: Immunity interruptus.  

PubMed

Despite the introduction almost a century ago of Mycobacterium bovis BCG (BCG), an attenuated form of M. bovis that is used as a vaccine against Mycobacterium tuberculosis, tuberculosis remains a global health threat and kills more than 1.5 million people each year. This is mostly because BCG fails to prevent pulmonary disease - the contagious form of tuberculosis. Although there have been significant advances in understanding how the immune system responds to infection, the qualities that define protective immunity against M. tuberculosis remain poorly characterized. The ability to predict who will maintain control over the infection and who will succumb to clinical disease would revolutionize our approach to surveillance, control, and treatment. Here we review the current understanding of pulmonary T cell responses following M. tuberculosis infection. While infection elicits a strong immune response that contains infection, M. tuberculosis evades eradication. Traditionally, its intracellular lifestyle and alteration of macrophage function are viewed as the dominant mechanisms of evasion. Now we appreciate that chronic inflammation leads to T cell dysfunction. While this may arise as the host balances the goals of bacterial sterilization and avoidance of tissue damage, it is becoming clear that T cell dysfunction impairs host resistance. Defining the mechanisms that lead to T cell dysfunction is crucial as memory T cell responses are likely to be subject to the same subject to the same pressures. Thus, success of T cell based vaccines is predicated on memory T cells avoiding exhaustion while at the same time not promoting overt tissue damage. PMID:25311810

Behar, Samuel M; Carpenter, Stephen M; Booty, Matthew G; Barber, Daniel L; Jayaraman, Pushpa

2014-12-01

296

13C-Flux Spectral Analysis of Host-Pathogen Metabolism Reveals a Mixed Diet for Intracellular Mycobacterium tuberculosis  

PubMed Central

Summary Whereas intracellular carbon metabolism has emerged as an attractive drug target, the carbon sources of intracellularly replicating pathogens, such as the tuberculosis bacillus Mycobacterium tuberculosis, which causes long-term infections in one-third of the world’s population, remain mostly unknown. We used a systems-based approach—13C-flux spectral analysis (FSA) complemented with manual analysis—to measure the metabolic interaction between M. tuberculosis and its macrophage host cell. 13C-FSA analysis of experimental data showed that M. tuberculosis obtains a mixture of amino acids, C1 and C2 substrates from its host cell. We experimentally confirmed that the C1 substrate was derived from CO2. 13C labeling experiments performed on a phosphoenolpyruvate carboxykinase mutant revealed that intracellular M. tuberculosis has access to glycolytic C3 substrates. These findings provide constraints for developing novel chemotherapeutics. PMID:23911587

Beste, Dany J.V.; Nöh, Katharina; Niedenführ, Sebastian; Mendum, Tom A.; Hawkins, Nathaniel D.; Ward, Jane L.; Beale, Michael H.; Wiechert, Wolfgang; McFadden, Johnjoe

2013-01-01

297

New insights into the pathogenesis of tuberculosis revealed by Mycobacterium marinum: the zebrafish model from the systems biology perspective.  

PubMed

Tuberculosis remains a worldwide health concern, largely due to the emergence of multi-drug-resistant (MDR) and extensive-drug-resistant (XDR) Mycobacterium tuberculosis co-infection with HIV. The exact mechanism of Mycobacterium virulence, pathogenesis, and persistence is not fully understood. The hallmark of tuberculosis, granulomas are promoted by Mycobacterium virulence factors, and they have long been considered a structural advantage to the host. However, this traditional view has been challenged recently, largely due to the evidence originating from the M. marinum-zebrafish model. As a genetically tractable model, zebrafish provide unprecedented opportunities to address the pathogenesis of tuberculosis from a systems biology perspective. The latest data from this model are summarized in this review, special attention is given to the shared pathway and network between zebrafish and humans. This research serves to deepen our understanding of this complex process and to promote the discovery of better countermeasures against tuberculosis. PMID:22181703

Deng, Wanyan; Tang, Xiemei; Hou, Manmei; Li, Chunmei; Xie, Jianping

2011-01-01

298

Tuberculosis care: an evaluability study  

PubMed Central

OBJECTIVE: to verify whether the tuberculosis control program (TCP) is evaluable and to examine the feasibility of building an evaluation model in apriority municipality for the control of tuberculosis. METHOD: this evaluability study was conducted in a municipality in northeastern Brazil. For data collection, documental analysis and interviews with key informants were performed. For indicator validation, the nominal group technique was adopted. RESULTS: the details of TCP were described, and both the logical model and the classification framework for indicators were developed and agreed up on, with the goal of characterizing the structural elements of the program, defining the structure and process indicators, and formulating the evaluation questions. CONCLUSION: TCP is evaluable. Based on logical operational analysis, it was possible to evaluate the adequacy of the program goals for the control of tuberculosis. Therefore, the performance of a summative evaluation is recommended, with a focus on the analysis of the effects of tuberculosis control interventions on decreasing morbidity and mortality. PMID:25493675

Coelho, Ardigleusa Alves; Martiniano, Cláudia Santos; Brito, Ewerton Willian Gomes; Negrão, Oswaldo Gomes Corrêa; Arcêncio, Ricardo Alexandre; Uchôa, Severina Alice da Costa

2014-01-01

299

Complete tuberculosis treatment for all.  

PubMed

Lead nurse Hanna Kaur has seen her priorities develop in the 18 months since she joined the Birmingham and Solihull tuberculosis (TB) service, part of Heart of England NHS Foundation Trust. PMID:25408051

2014-11-19

300

Unusual locations of osteoarticular tuberculosis.  

PubMed

Tuberculosis continues to occur frequently in some underdeveloped regions. Bone and joint tuberculosis is less common than the pulmonary form. Fourteen cases of bone and joint tuberculosis in unusual locations are presented. Tuberculostatic treatment and surgical approach were associated in all the patients. In 6 cases an arthrodesis of the affected joint was carried out. A surgical debridement was done in 6 patients and a needle biopsy in 2 patients in order to obtain samples for pathology and bacteriology. Twelve of the 14 patients recovered. One patient who was affected by atlanto-axial tuberculosis died within the immediate postoperative period. A second one affected by the acquired immunodefiency syndrome died 4 months after surgery. PMID:9266032

García, S; Combalía, A; Serra, A; Segur, J M; Ramón, R

1997-01-01

301

Inhibition of the in-vitro growth of Mycobacterium tuberculosis by a phytosiderophore.  

PubMed

Non-compliance by patients and poor clinical management due to the use of incorrect regimens are the main reasons for the development of drug resistance by mycobacterial strains. New strategies for the control of multi-drug-resistant mycobacterial strains have become a necessity for proper management of tuberculosis, which, according to the WHO report (1997), is estimated to remain among the top 10 mortality-causing diseases of the twenty-first century. One of the strategies is the use of iron-sequestering agents like siderophores as active therapeutic agents in the treatment of tuberculosis. This report describes for the first time the inhibition of the growth of Mycobacterium tuberculosis H37Ra in vitro by a phytosiderophore isolated from the root washings of Tephrosia purpurea. This finding may help in the establishment of a new drug regimen which will be more effective in the treatment of tuberculosis. PMID:11599742

Rajiv, J; Dam, T; Kumar, S; Bose, M; Aggarwal, K K; Babu, C R

2001-10-01

302

Vitamin D levels in Indian children with intrathoracic tuberculosis  

PubMed Central

Background & objectives: Deficiency of vitamin D, an immunomodulator agent, is associated with increased susceptibility to tuberculosis in adults, but only limited studies are available in the paediatric age group, especially regarding association of vitamin D with type and outcome of tuberculosis. We conducted this study to determine the baseline 25-hydroxy vitamin D levels in children suffering from intrathoracic tuberculosis and its association with type and outcome of tuberculosis. Methods: Children with intrathoracic tuberculosis, diagnosed on the basis of clinico-radiological criteria, were enrolled as part of a randomized controlled trial on micronutrient supplementation in paediatric tuberculosis patients. Levels of 25-hydroxy vitamin D were measured in serum samples collected prior to starting antitubercular therapy by chemiluminescent immunoassay technology. Results: Two hundred sixty six children (mean age of 106.9 ± 43.7 months; 57.1% girls) were enrolled. Chest X-ray was suggestive of primary pulmonary complex, progressive disease and pleural effusion in 81 (30.5%), 149 (56%) and 36 (13.5%) subjects, respectively. Median serum 25-hydroxy vitamin D level was 8 ng/ml (IQR 5, 12). One hundred and eighty six (69.9%) children were vitamin D deficient (serum 25-hydroxy vitamin D <12 ng/ml), 55 (20.7%) were insufficient (12 to <20 ng/ml) and 25 (9.4%) were vitamin D sufficient (? 20 ng/ml). Levels of 25-hydroxy vitamin D were similar in all three types of intrathoracic tuberculosis, and in microbiologically confirmed and probable cases. Levels of 25-hydroxy vitamin D did not significantly affect outcome of the disease. Children who were deficient or insufficient were less likely to convert (become smear/culture negative) at two months as compared to those who were 25-hydroxy vitamin D sufficient (P<0.05). Interpretation & conclusions: Majority of Indian children with newly diagnosed intrathoracic tuberculosis were deficient in vitamin D. Type of disease or outcome was not affected by 25-hydroxy vitamin D levels in these children. However, children who did not demonstrate sputum conversion after intensive phase of antitubercular therapy had lower baseline 25-hydroxy vitamin D levels as compared to those who did. PMID:25488448

Khandelwal, Deepchand; Gupta, Nandita; Mukherjee, Aparna; Lodha, Rakesh; Singh, Varinder; Grewal, Harleen M.S.; Bhatnagar, Shinjini; Singh, Sarman; Kabra, S.K.

2014-01-01

303

The non-clonality of drug resistance in Beijing-genotype isolates of Mycobacterium tuberculosis from the Western Cape of South Africa  

Microsoft Academic Search

BACKGROUND: The Beijing genotype of M. tuberculosis is a virulent strain that is disseminating worldwide and has a strong association with drug resistance. In the Western Cape of South Africa, epidemiological studies have identified the R220 cluster of the Beijing genotype as a major contributor to a recent outbreak of drug-resistant tuberculosis. Although the outbreak is considered to be due

Thomas R Ioerger; Yicheng Feng; Xiaohua Chen; Karen M Dobos; Thomas C Victor; Elizabeth M Streicher; Robin M Warren; Nicolaas C Gey van Pittius; Paul D Van Helden; James C Sacchettini

2010-01-01

304

High Rates of Potentially Infectious Tuberculosis and Multidrug-Resistant Tuberculosis (MDR-TB) among  

E-print Network

High Rates of Potentially Infectious Tuberculosis and Multidrug-Resistant Tuberculosis (MDR, Massachusetts, United States of America, 3 KwaZulu-Natal Research Institute for Tuberculosis and HIV Research (K) and multidrug-resistant (MDR-TB) tuberculosis at Church of Scotland Hospital (CoSH), in KwaZulu-Natal (KZN

Cohen, Ted

305

Pre-Multidrug-Resistant Mycobacterium tuberculosis Beijing Strain Associated with Disseminated Tuberculosis in a Pet Dog  

PubMed Central

Resistance to isoniazid, ethambutol, and streptomycin was detected in a Mycobacterium tuberculosis strain, belonging to the Beijing family lineage, isolated from two nodule exudates of a Yorkshire terrier with generalized tuberculosis. This report alerts medical practitioners to the risk of dissemination of pre-multidrug-resistant tuberculosis (preMDR-TB) through exposure to M. tuberculosis-shedding pets. PMID:24153119

Perdigão, João; Canto, Ana; Albuquerque, Teresa; Leal, Nuno; Macedo, Rita; Portugal, Isabel; Cunha, Mónica V.

2014-01-01

306

Tuberculosis information on the Web.  

PubMed

After years of decline, tuberculosis has reemerged as a serious public health problem worldwide. Factors contributing to this resurgence include the HIV epidemic and immigration of people from countries with a high incidence of tuberculosis. In 1993, the World Health Organization (WHO) declared it to be a 'global emergency' and according to a recent WHO report, there were 7.96 million new cases in 1996, with two million deaths. Comprehensive up-to-date information is available via the Internet, which has emerged as an essential tool for information on a wide variety of subjects including tuberculosis. However, looking for the right information on tuberculosis can be laborious, especially with the enormous number of tuberculosis websites established. It is always helpful to know which ones to visit to avoid wasting valuable time. This article provides readers with a list of websites that provide information on tuberculosis. All sites quoted here have been tested and proven to be valuable and informative for both the public and scientific community alike. PMID:12134772

Abu-Amero, K

2002-06-01

307

Isoxyl Activation Is Required for Bacteriostatic Activity against Mycobacterium tuberculosis?  

PubMed Central

Isoxyl (ISO), a thiourea derivative that was successfully used for the clinical treatment of tuberculosis during the 1960s, is an inhibitor of the synthesis of oleic and mycolic acids in Mycobacterium tuberculosis. Its effect on oleic acid synthesis has been shown to be attributable to its inhibitory activity on the stearoyl-coenzyme A desaturase DesA3, but its enzymatic target(s) in the mycolic acid pathway remains to be identified. With the goal of elucidating the mode of action of ISO, we have isolated a number of spontaneous ISO-resistant mutants of M. tuberculosis and undertaken their genotypic characterization. We report here the characterization of a subset of these strains carrying mutations in the monooxygenase gene ethA. Through complementation studies, we demonstrate for the first time that the EthA-mediated oxidation of ISO is absolutely required for this prodrug to inhibit its lethal enzymatic target(s) in M. tuberculosis. An analysis of the metabolites resulting from the in vitro transformation of ISO by purified EthA revealed the occurrence of a formimidamide allowing the formulation of an activation pathway in which the oxidation of ISO catalyzed by EthA is followed by chemical transformations involving extrusion or elimination and, finally, hydrolysis. PMID:17785510

Korduláková, Jana; Janin, Yves L.; Liav, Avraham; Barilone, Nathalie; Dos Vultos, Tiago; Rauzier, Jean; Brennan, Patrick J.; Gicquel, Brigitte; Jackson, Mary

2007-01-01

308

C-type lectins in immunity to Mycobacterium tuberculosis.  

PubMed

Tuberculosis (TB) remains one of the leading causes of death due to a single infectious agent, Mycobacterium tuberculosis, with nearly 2 million deaths per year (1). Most individuals exposed to the bacillus develop a nonpathological form, latent TB, with only a small minority (5 to 10%) developing active disease. It is estimated that one third of the human population worldwide may have latent M. tuberculosis infection. Latent TB is characterized by an efficient immune response that contains the infection in a nonpathological and noncontagious state, within a specific, dynamic structure called the granuloma. Interactions between M. tuberculosis and the immune system play a crucial role in determining the outcome of the disease, and are mediated by various pattern recognition receptors (PRRs) expressed in cells of the innate immune system and in nonimmune cells. These interactions may modulate the immune response in favor of the bacillus, by allowing it to persist within host phagocytes. They may also favor the host, by inducing immune defenses, such as autophagy, phagosome maturation, apoptosis and various bactericidal mechanisms. PMID:21622262

Tanne, Antoine; Neyrolles, Olivier

2011-01-01

309

Tuberculosis Outbreak Investigations in the United States, 2002–2008  

PubMed Central

To understand circumstances of tuberculosis transmission that strain public health resources, we systematically reviewed Centers for Disease Control and Prevention (CDC) staff reports of US outbreaks in which CDC participated during 2002–2008 that involved >3 culture-confirmed tuberculosis cases linked by genotype and epidemiology. Twenty-seven outbreaks, representing 398 patients, were reviewed. Twenty-four of the 27 outbreaks involved primarily US-born patients; substance abuse was another predominant feature of outbreaks. Prolonged infectiousness because of provider- and patient-related factors was common. In 17 outbreaks, a drug house was a notable contributing factor. The most frequently documented intervention to control the outbreak was prioritizing contacts according to risk for infection and disease progression to ensure that the highest risk contacts were completely evaluated. US-born persons with reported substance abuse most strongly characterized the tuberculosis outbreaks in this review. Substance abuse remains one of the greatest challenges to controlling tuberculosis transmission in the United States. PMID:21392433

Oeltmann, John E.; Ijaz, Kashef; Haddad, Maryam B.

2011-01-01

310

Molecular Biology of Drug Resistance in Mycobacterium tuberculosis  

PubMed Central

Tuberculosis (TB) has become a curable disease thanks to the discovery of antibiotics. However, it has remained one of the most difficult infections to treat. Most current TB regimens consist of six to nine months of daily doses of four drugs that are highly toxic to patients. The purpose of these lengthy treatments is to completely eradicate Mycobacterium tuberculosis, notorious for its ability to resist most antibacterial agents, thereby preventing the formation of drug resistant mutants. On the contrary, the prolonged therapies have led to poor patient adherence. This, together with a severe limit of drug choices, has resulted in the emergence of strains that are increasingly resistant to the few available antibiotics. Here we review our current understanding of molecular mechanisms underlying the profound drug resistance of M. tuberculosis. This knowledge is essential for the development of more effective antibiotics that not only are potent against drug resistant M. tuberculosis strains but also help shorten the current treatment courses required for drug susceptible TB. PMID:23179675

Smith, Tasha; Wolff, Kerstin A.; Nguyen, Liem

2014-01-01

311

Towards a new tuberculosis drug: pyridomycin – nature's isoniazid  

PubMed Central

Tuberculosis, a global threat to public health, is becoming untreatable due to widespread drug resistance to frontline drugs such as the InhA-inhibitor isoniazid. Historically, by inhibiting highly vulnerable targets, natural products have been an important source of antibiotics including potent anti-tuberculosis agents. Here, we describe pyridomycin, a compound produced by Dactylosporangium fulvum with specific cidal activity against mycobacteria. By selecting pyridomycin-resistant mutants of Mycobacterium tuberculosis, whole-genome sequencing and genetic validation, we identified the NADH-dependent enoyl- (Acyl-Carrier-Protein) reductase InhA as the principal target and demonstrate that pyridomycin inhibits mycolic acid synthesis in M. tuberculosis. Furthermore, biochemical and structural studies show that pyridomycin inhibits InhA directly as a competitive inhibitor of the NADH-binding site, thereby identifying a new, druggable pocket in InhA. Importantly, the most frequently encountered isoniazid-resistant clinical isolates remain fully susceptible to pyridomycin, thus opening new avenues for drug development. PMID:22987724

Hartkoorn, Ruben C; Sala, Claudia; Neres, João; Pojer, Florence; Magnet, Sophie; Mukherjee, Raju; Uplekar, Swapna; Boy-Röttger, Stefanie; Altmann, Karl-Heinz; Cole, Stewart T

2012-01-01

312

Interferon gamma production in the course of Mycobacterium tuberculosis infection.  

PubMed

It is not clear why some individuals with unknown predisposition develop tuberculosis, while others remain healthy in spite of heavy exposure. Interferon gamma (IFNgamma) is considered to be the key cytokine responsible for resistance to M. tuberculosis infection, as confirmed by increased susceptibility to mycobacterial infections in rare inherited defects in IL-12-IFNgamma axis. The aim of this study was to assess the IFNgamma production by peripheral blood lymphocytes from immunocompetent tuberculosis (TB) patients. The study group included 51 TB patients. In all cases, TB was confirmed by culture. Twenty healthy TB contacts were considered as control group. Commercially available ELISA-based assays were used to measure IFNgamma in the supernatant of whole blood cell cultures after stimulation with PWM (Phytolacca Americana), PHA (phytohemagglutynin), and PPD (purified protein derivative). No difference in IFNgamma secretion between the patients and control group was found when blood cells were stimulated by PWM or PHA. PPD-induced IFNgamma formation was higher in TB patients than in controls. The secretion of IFNgamma after non-specific stimulation varied in different clinical and radiological presentation of tuberculosis and it was lower in most advanced and extensive forms of the disease. It is unclear whether the difference in formation and release of IFNgamma is a primary or secondary phenomenon in the course of the disease. PMID:19218702

Winek, J; Rowinska-Zakrzewska, E; Demkow, U; Szopinski, J; Szolkowska, M; Filewska, M; Jagodzinski, J; Roszkowski-Sliz, K

2008-12-01

313

Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) in HIV Patients with Culture Confirmed Pulmonary Tuberculosis in India and the Potential Role of IL-6 in Prediction  

PubMed Central

Background The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. Methods HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. Results Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14–47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7–16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9–23). Two patients died due to CNS TB-IRIS. Lower CD4+ T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. Conclusion Paradoxical TB–IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions. PMID:23691062

Porter, Brian O.; Chandrasekhar, Chockalingam; Venkatesan, Perumal; Menon, Pradeep A.; Subramanian, Sudha; Anbalagan, Selvaraj; Bhavani, Kannabiran P.; Sekar, Sathiyavelu; Padmapriyadarshini, Chandrasekaran; Kumar, Satagopan; Ravichandran, Narayanan; Raja, Krishnaraj; Bhanu, Kesavamurthy; Mahilmaran, Ayyamperumal; Sekar, Lakshmanan; Sher, Alan; Sereti, Irini; Swaminathan, Soumya

2013-01-01

314

Broad Adaptive Immune Responses to M. tuberculosis Antigens Precede TST Conversion in Tuberculosis Exposed Household Contacts in a TB-Endemic Setting  

PubMed Central

Background The identification of Mycobacterium-tuberculosis (Mtb) infected individuals remains a challenge due to an insufficient understanding of immune responses detected with the current diagnostic tests for latent tuberculosis i.e. the tuberculin skin test (TST) or IFN–? release assays (IGRAs) and an inability to distinguish infection stages with current immunologic assays. Further classification based on markers other than IFN–? may help to define markers of early Mtb infection. Methods We assessed the TST status of Mtb-exposed household contacts at baseline and at 6 months. Contacts were classified into those with initial positive TST (TST+); those with baseline negative TST but TST conversion at 6 months (TST converters, TSTC) and those with persistently negative TST (PTST?). We assessed their short- and long-term immune responses to PPD and ESAT–6/CFP–10 (EC) via IFN–? ELISPOT and a multiplex cytokine array in relation to TST status and compared them to those of TB cases to identify immune profiles associated with a spectrum of infection stages. Results After 1 and 6 days stimulation with EC, 12 cytokines (IFN–?, IL–2, IP–10, TNF–?, IL–13, IL–17, IL–10, GMCSF, MIP–1?, MCP–3, IL–2RA and IL–1A) were not different in TSTC compared to TST+ suggesting that robust adaptive Mtb-specific immune responses precede TST conversion. Stratifying contacts by baseline IFN–? ELISPOT to EC in combination with TST results revealed that IP–10 and IL–17 were highest in the group of TST converters with positive baseline ELISPOT, suggesting they might be markers for recent infection. Conclusion We describe a detailed analysis of Mtb-specific biomarker profiles in exposed household contacts in a TB endemic area that provides insights into the dynamic immune responses to Mtb infection and may help to identify biomarkers for ‘at-risk’ populations beyond TST and IGRA. PMID:25549338

Buchwald, Ulrike K.; Adetifa, Ifedayo M. O.; Bottomley, Christian; Owiafe, Patrick K.; Donkor, Simon; Bojang, Adama L.; Sutherland, Jayne S.

2014-01-01

315

Odor analysis of decomposing buried human remains  

Microsoft Academic Search

This study, conducted at the University of Tennessee's Anthropological Research Facility (ARF), lists and ranks the primary chemical constituents which define the odor of decomposition of human remains as detected at the soil surface of shallow burial sites. Triple sorbent traps were used to collect air samples in the field and revealed eight major classes of chemicals which now contain

Arpad Alexander Vass; Rob R. Smith; Cyril V. Thompson; Michael N. Burnett; Nishan Dulgerian; Brian A. Eckenrode

2008-01-01

316

Armament remains from His Majesty's sloop Boscawen  

E-print Network

His Majesty's Sloop Boscawen was built on Lake Champlain by British forces in 1759 as part of their successful campaign to drive the French Army from the Champlain Valley. This thesis describes and analyzes the armament remains found in and around...

Carter, Brinnen Stiles

2012-06-07

317

Odor analysis of decomposing buried human remains  

SciTech Connect

This study, conducted at the University of Tennessee's Anthropological Research Facility (ARF), lists and ranks the primary chemical constituents which define the odor of decomposition of human remains as detected at the soil surface of shallow burial sites. Triple sorbent traps were used to collect air samples in the field and revealed eight major classes of chemicals which now contain 478 specific volatile compounds associated with burial decomposition. Samples were analyzed using gas chromatography-mass spectrometry (GC-MS) and were collected below and above the body, and at the soil surface of 1.5-3.5 ft. (0.46-1.07 m) deep burial sites of four individuals over a 4-year time span. New data were incorporated into the previously established Decompositional Odor Analysis (DOA) Database providing identification, chemical trends, and semi-quantitation of chemicals for evaluation. This research identifies the 'odor signatures' unique to the decomposition of buried human remains with projected ramifications on human remains detection canine training procedures and in the development of field portable analytical instruments which can be used to locate human remains in shallow burial sites.

Vass, Arpad Alexander [ORNL; Smith, Rob R [ORNL; Thompson, Cyril V [ORNL; Burnett, Michael N [ORNL; Dulgerian, Nishan [ORNL; Eckenrode, Brian A [ORNL

2008-01-01

318

Body size prediction from juvenile skeletal remains  

Microsoft Academic Search

There are currently no methods for pre- dicting body mass from juvenile skeletal remains and only a very limited number for predicting stature. In this study, stature and body mass prediction equations are generated for each year from 1 to 17 years of age using a subset of the Denver Growth Study sample, fol- lowed longitudinally (n ¼ 20 individuals,

Christopher Ruff

2007-01-01

319

Remaining useful performance analysis of batteries  

Microsoft Academic Search

A method for remaining useful performance (RUP) analysis for lithium-ion batteries is presented using Dempster- Shafer theory (DST) and Bayesian Monte Carlo (BMC). First, an empirical model is developed, which can provide a good fit to the battery fade data. Then, the parameters of the empirical model are initialized by combining sets of training data based on DST. When data

Wei He; Nicholas Williard; Michael Osterman; Michael Pecht

2011-01-01

320

Explosives remain preferred methods for platform abandonment  

Microsoft Academic Search

Economics and safety concerns indicate that methods involving explosives remain the most practical and cost-effective means for abandoning oil and gas structures in the Gulf of Mexico. A decade has passed since 51 dead sea turtles, many endangered Kemp`s Ridleys, washed ashore on the Texas coast shortly after explosives helped remove several offshore platforms. Although no relationship between the explosions

A. Pulsipher; W. IV Daniel; J. E. Kiesler; V. Mackey

1996-01-01

321

Unsuspected and extensive transmission of a drug-susceptible Mycobacterium tuberculosis strain  

PubMed Central

Background A large and unsuspected tuberculosis outbreak involving 18.7% of the total of the tuberculosis cases studied, was detected in a population-based molecular epidemiological study performed in Zaragoza (Spain) from 2001 to 2004. Methods The Mycobacterium tuberculosis drug-susceptible strain, named MTZ strain, was genetically characterized by IS6110-RFLP, Spoligotyping and by MIRU-VNTR typing and the genetic patterns obtained were compared with those included in international databases. The characteristics of the affected patients, in an attempt to understand why the MTZ strain was so highly transmitted among the population were also analyzed. Results The genetic profile of the MTZ strain was rare and not widely distributed in our area or elsewhere. The patients affected did not show any notable risk factor for TB. Conclusion The M. tuberculosis strain MTZ, might have particular transmissibility or virulence properties, and we believe that greater focus should be placed on stopping its widespread dissemination. PMID:19144198

López-Calleja, Ana Isabel; Gavín, Patricia; Lezcano, Ma Antonia; Vitoria, Ma Asunción; Iglesias, Ma José; Guimbao, Joaquín; Lázaro, Ma Ángeles; Rastogi, Nalin; Revillo, Ma José; Martín, Carlos; Samper, Sofia

2009-01-01

322

Rapid Reagentless Detection of M. tuberculosis H37Ra in Respiratory Effluents  

SciTech Connect

Two similar mycobacteria, Mycobacteria tuberculosis H37Ra and Mycobacteria smegmatis are rapidly detected and identified within samples containing a complex background of respiratory effluents using Single Particle Aerosol Mass Spectrometry (SPAMS). M. tuberculosis H37Ra (TBa), an avirulent strain, is used as a surrogate for virulent tuberculosis (TBv); M. smegmatis (MSm) is utilized as a near neighbor confounder for TBa. Bovine lung surfactant and human exhaled breath condensate are used as first-order surrogates for infected human lung expirations from patients with pulmonary tuberculosis. This simulated background sputum is mixed with TBa or MSm and nebulized to produce conglomerate aerosol particles, single particles that contain a bacterium embedded within a background respiratory matrix. Mass spectra of single conglomerate particles exhibit ions associated with both respiratory effluents and mycobacteria. Spectral features distinguishing TBa from MSm in pure and conglomerate particles are shown. SPAMS pattern matching alarm algorithms are able to distinguish TBa containing particles from background matrix and MSm for >50% of the test particles, which is sufficient to enable a high probability of detection and a low false alarm rate if an adequate number of such particles are present. These results indicate the potential usefulness of SPAMS for rapid, reagentless tuberculosis screening.

Adams, K L; Steele, P T; Bogan, M J; Sadler, N M; Martin, S; Martin, A N; Frank, M

2008-01-29

323

Development of a proof of concept immunochromatographic lateral flow assay for point of care diagnosis of Mycobacterium tuberculosis  

PubMed Central

Background Despite major public health initiatives and the existence of efficacious treatment regimes, tuberculosis (TB) remains a threat, particularly in resource-limited settings. A significant part of the problem is the difficulty of rapidly identifying infected individuals, and as a result, there has been renewed interest in developing better diagnostics for infection or disease caused by Mycobacterium tuberculosis. Many of the existing tools, however, have limitations such as poor sensitivity or specificity, or the need for well-equipped laboratories to function effectively. Serodiagnostic approaches in particular have long drawn attention, due to their potential utility in large field studies, particularly in resource-poor settings. Unfortunately none of the serodiagnostic approaches have so far proven useful under field conditions. Results We screened a large panel of antigens with serodiagnostic potential by ELISA and selected a subpanel that was strongly and broadly recognised by TB patients, but not by controls. These antigens were then formulated into a simple immuno-chromatographic lateral flow assay format, suitable for field use, and tested against panels of plasma and blood samples from individuals with different clinical status (confirmed TB patients, household contacts, and apparently healthy community controls), recruited from Ethiopia (a highly TB-endemic country) and Turkey (a TB meso-endemic country). While specificity was good (97-100% in non TB-endemic controls), the sensitivity was not as high as expected (46-54% in pulmonary TB, 25-29% in extra-pulmonary TB). Conclusions Though below the level of sensitivity the consortium had set for commercial development, the assay specifically identified M. tuberculosis-infected individuals, and provides a valuable proof of concept. PMID:23688126

2013-01-01

324

Predictors of tuberculosis and human immunodeficiency virus co-infection: a case-control study  

PubMed Central

OBJECTIVES: The human immunodeficiency virus (HIV) and Mycobacterium tuberculosis co-infection is a major global challenge. It is not clear why some HIV-positive people are co-infected with tuberculosis (TB) while others are not. This study addressed that question. METHODS: This case-control study was conducted in Tehran, Iran in June 2004, enrolling 2,388 HIV-positive people. Cases were selected from those who were co-infected with TB and controls from those without TB. Multiple logistic regression analysis was performed to assess the association between M. tuberculosis/HIV co-infection and several predictors. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. RESULTS: In this study, 241 cases were compared with 2,147 controls. Sex, age, marital status, educational level, imprisonment, smoking, narcotic use, route of HIV transmission, previous TB infection, isoniazid preventive therapy (IPT), antiretroviral therapy (ART), and low CD4 count (<350 cells/mm3) were independently associated with M. tuberculosis/HIV co-infection (p<0.001). However, after adjusting for all other variables in the model, only the association between M. tuberculosis/HIV co-infection and the following predictors remained statistically significant: imprisonment (odds ratio [OR], 3.82; 95% confidence interval [CI], 2.11-6.90), previous TB infection (OR, 5.54; 95% CI, 1.99-15.39), IPT (OR, 0.13; 95% CI, 0.06-0.31), ART (OR, 1.81; 95% CI, 1.26-2.61), and CD4 count <350 cells/mm3 (OR, 2.34; 95% CI, 1.36-4.02). CONCLUSIONS: Several predictors are associated with M. tuberculosis/HIV co-infection, but only a few indicators were significantly associated with M. tuberculosis/HIV co-infection. It is estimated that a number of predictors of M. tuberculosis/HIV co-infection remain unknown and require further investigation. PMID:25358465

Molaeipoor, Leila; Poorolajal, Jalal; Mohraz, Minoo; Esmailnasab, Nader

2014-01-01

325

Tuberculosis vaccines: beyond bacille Calmette–Guérin  

PubMed Central

Tuberculosis (TB) disease caused by Mycobacterium tuberculosis (M. tb) remains one of the leading infectious causes of death and disease throughout the world. The only licensed vaccine, Mycobacterium bovis bacille Calmette–Guérin (BCG) confers highly variable protection against pulmonary disease. An effective vaccination regimen would be the most efficient way to control the epidemic. However, BCG does confer consistent and reliable protection against disseminated disease in childhood, and most TB vaccine strategies being developed incorporate BCG to retain this protection. Cellular immunity is necessary for protection against TB and all the new vaccines in development are focused on inducing a strong and durable cellular immune response. There are two main strategies being pursued in TB vaccine development. The first is to replace BCG with an improved whole organism mycobacterial priming vaccine, which is either a recombinant BCG or an attenuated strain of M. tb. The second is to develop a subunit boosting vaccine, which is designed to be administered after BCG vaccination, and to enhance the protective efficacy of BCG. This article reviews the leading candidate vaccines in development and considers the current challenges in the field with regard to efficacy testing. PMID:21893541

McShane, Helen

2011-01-01

326

Spatial Dependency of Tuberculosis Incidence in Taiwan  

PubMed Central

Tuberculosis (TB) disease can be caused by either recent transmission from infectious patients or reactivation of remote latent infection. Spatial dependency (correlation between nearby geographic areas) in tuberculosis incidence is a signature for chains of recent transmission with geographic diffusion. To understand the contribution of recent transmission in the TB endemic in Taiwan, where reactivation has been assumed to be the predominant mode of pathogenesis, we used spatial regression analysis to examine whether there was spatial dependency between the TB incidence in each township and in its neighbors. A total of 90,661 TB cases from 349 townships in 2003–2008 were included in this analysis. After adjusting for the effects of confounding socioeconomic variables, including the percentages of aboriginals and average household income, the results show that the spatial lag parameter remains positively significant (0.43, p<0.001), which indicates that the TB incidences of neighboring townships had an effect on the TB incidence in each township. Townships with substantial spatial spillover effects were mainly located in the northern, western and eastern parts of Taiwan. Spatial dependency implies that recent transmission plays a significant role in the pathogenesis of TB in Taiwan. Therefore, in addition to the current focus on improving the cure rate under directly observed therapy programs, more resource need to be allocated to active case finding in order to break the chain of transmission. PMID:23226371

Ng, In-Chan; Wen, Tzai-Hung; Wang, Jann-Yuan; Fang, Chi-Tai

2012-01-01

327

Renal Tuberculosis in the Modern Era  

PubMed Central

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis. The disease remains as an important public health problem in developing countries. Extrapulmonary TB became more common with the advent of infection with human immunodeficiency virus and by the increase in the number of organ transplantation, which also leads to immunosuppression of thousand of persons. Urogenital TB represents 27% of extrapulmonary cases. Renal involvement in TB can be part of a disseminated infection or a localized genitourinary disease. Renal involvement by TB infection is underdiagnosed in most health care centers. Most patients with renal TB have sterile pyuria, which can be accompanied by microscopic hematuria. The diagnosis of urinary tract TB is based on the finding of pyuria in the absence of common bacterial infection. The first choice drugs include isoniazide, rifampicin, pirazinamide, ethambutol, and streptomycin. Awareness of renal TB is urgently needed by physicians for suspecting this disease in patients with unexplained urinary tract abnormalities, mainly in those with any immunosuppression and those coming from TB-endemic areas. PMID:23303798

De Francesco Daher, Elizabeth; Bezerra da Silva Junior, Geraldo; Barros, Elvino José Guardão

2013-01-01

328

Macrophages in Tuberculosis: Friend or Foe  

PubMed Central

Tuberculosis (TB) remains one of the greatest threats to human health. The causative bacterium, Mycobacterium tuberculosis (Mtb) is acquired by the respiratory route. It is exquisitely human-adapted and a prototypic intracellular pathogen of macrophages, with alveolar macrophages (AMs) being the primary conduit of infection and disease. The outcome of primary infection is most often a latently infected healthy human host, in whom the bacteria are held in check by the host immune response. Such individuals can develop active TB later in life with impairment in the immune system. In contrast, in a minority of infected individuals, the host immune response fails to control the growth of bacilli, and progressive granulomatous disease develops, facilitating spread of the bacilli via infectious aerosols coughed out into the environment and inhaled by new hosts. The molecular details of the Mtb-macrophage interaction continue to be elucidated. However, it is clear that a number of complex processes are involved at the different stages of infection that may benefit either the bacterium or the host. Macrophages demonstrate tremendous phenotypic heterogeneity and functional plasticity which, depending on the site and stage of infection, facilitate the diverse outcomes. Moreover, host responses vary depending on the specific characteristics of the infecting Mtb strain. In this chapter, we describe a contemporary view of the behavior of AMs and their interaction with various Mtb strains in generating unique immunologic lung specific responses. PMID:23864058

Guirado, Evelyn; Schlesinger, Larry S.; Kaplan, Gilla

2013-01-01

329

Imaging features of extraaxial musculoskeletal tuberculosis  

PubMed Central

Tuberculosis (TB) continues to be a public health problem in both developing and industrialized countries. TB can involve pulmonary as well as extrapulmonary sites. The musculoskeletal system is involved in 1–3% of patients with tuberculosis. Although musculoskeletal TB has become uncommon in the Western world, it remains a huge problem in Asia, Africa, and many developing countries. Tuberculous spondylitis is the most common form of musculoskeletal TB and accounts for approximately 50% of cases. Extraspinal musculoskeletal TB shows a predilection for large joints (hip and knee) and para-articular areas; isolated soft tissue TB is extremely rare. Early diagnosis and prompt treatment are mandatory to prevent serious destruction of joints and skeletal deformity. However, due to the nonspecific and often indolent clinical presentation, the diagnosis may be delayed. Radiological assessment is often the first step in the diagnostic workup of patients with musculoskeletal TB and further investigations are decided by the findings on radiography. Both the radiologist and the clinician should be aware of the possibility of this diagnosis. In this manuscript we review the imaging features of extraspinal bone, joint, and soft tissue TB. PMID:19881081

Vanhoenacker, Filip M; Sanghvi, Darshana A; De Backer, Adelard I

2009-01-01

330

Malaria Infections Do Not Compromise Vaccine-Induced Immunity against Tuberculosis in Mice  

PubMed Central

Background Given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. To further assess the effectiveness of these new immunization strategies, we investigated whether co-infection with malaria would impact the anti-tuberculosis protection induced by four different types of TB vaccines in a mouse model of pulmonary tuberculosis. Principal Findings Here we show that the anti-tuberculosis protective immunity induced by four different tuberculosis vaccines was not impacted by a concurrent infection with Plasmodium yoelii NL, a nonlethal form of murine malaria. After an aerogenic challenge with virulent M. tuberculosis, the lung bacterial burdens of vaccinated animals were not statistically different in malaria infected and malaria naïve mice. Multi-parameter flow cytometric analysis showed that the frequency and the median fluorescence intensities (MFI) for specific multifunctional T (MFT) cells expressing IFN-?, TNF-?, and/or IL-2 were suppressed by the presence of malaria parasites at 2 weeks following the malaria infection but was not affected after parasite clearance at 7 and 10 weeks post-challenge with P. yoelii NL. Conclusions Our data indicate that the effectiveness of novel TB vaccines in protecting against tuberculosis was unaffected by a primary malaria co-infection in a mouse model of pulmonary tuberculosis. While the activities of specific MFT cell subsets were reduced at elevated levels of malaria parasitemia, the T cell suppression was short-lived. Our findings have important relevance in developing strategies for the deployment of new TB vaccines in malaria endemic areas. PMID:22205939

Parra, Marcela; Derrick, Steven C.; Yang, Amy; Tian, JinHua; Kolibab, Kristopher; Oakley, Miranda; Perera, Liyanage P.; Jacobs, William R.; Kumar, Sanjai; Morris, Sheldon L.

2011-01-01

331

Lessons from Africa: developing a global human rights framework for tuberculosis control and prevention.  

PubMed

BackgroundTuberculosis is a highly contagious disease, and there has been a rise in recent years of drug-resistant cases no longer responding to standard treatment.In order to address this threat and contain possible transmission of drug-resistant cases, some countries have taken strong action, including the compulsory detention of non-adherent drug-resistant patients. These measures have been strongly criticized by human rights advocates, and they raise the question of how to legally protect both citizens and the community.DiscussionFollowing discussions with National Tuberculosis Programs in Africa (the continent with the highest incidence rates of tuberculosis worldwide), we show that of all the countries surveyed, all but one (Swaziland) had either no specific policy addressing tuberculosis, or only general policies regarding public health applicable to tuberculosis. Six countries also reported having policies that address non-adherence to treatment with containment (isolation in health facilities or incarceration), but laws are not adequately enforced. If the international community wants to effectively respond to the threat of tuberculosis transmission, there is a need to go beyond national tuberculosis policies and to implement an international framework for tuberculosis control, inspired by the Framework Convention on Tobacco Control, a key model for future public health treaties that address global burdens of disease. The framework, for which we clarify the conditions and procedures in this piece, would define the rights and responsibilities of the different stakeholders involved: patients, doctors, pharmaceutical firms and public authorities. To facilitate the governance of the national obligations under the Convention, a coordinating body should be set up, under the leadership of the World Health Organization and the Stop TB Partnership.SummarySuccessfully implementing policies for tuberculosis that simultaneously address patients¿ rights and communities¿ wellbeing will have positive implications for those affected by the disease and serve as a basis for other global health conventions to truly ensure the global right to health. PMID:25465597

Slagle, Tracy; Ben Youssef, Mehdi; Calonge, Golda; Ben Amor, Yanis

2014-12-01

332

A Molecular Biological and Biochemical Investigation on Mycobacterium tuberculosis MutT Protein  

PubMed Central

Background: Mycobacterium tuberculosis is a vicious microbe co-existing with the infected host. This pathogen exploited opportunities to spread during periods of urbanization and social upheaval, and got retreated with improved hygiene. Objectives: This investigation was designed to clone and characterize M. tuberculosis mutT gene, a homologue of a DNA repair protein in Escherichia coli. The aim was to depict the possible role of this homologue in the virulent microbe. Materials and Methods: A DNA fragment of the mutT gene was amplified with PCR from the genomic DNA of strain H37Rv M. tuberculosis. The expression vector was transformed into E. coli strains BL21 (DE3) and MK602 (DE3) (mutT-). The protein activity assay was performed by biochemical methods. Results: M. tuberculosis MutT shares 23% identity with the E. coli MutT protein. The mutT gene DNA fragment was subcloned into the expression vector pET28a(+) and the recombinant plasmid was overexpressed in E. coli. Purified and refolded M. tuberculosis MutT possesses a dGTPase activity, which is one of the most well-known preference nucleotidase activities of MutT in E. coli. This study also showed that the dGTPase activity of M. tuberculosis MutT was enhanced by magnesium and inhibited by Ni2+ or EDTA. Endogenous MutT protein in M. tuberculosis lysate displayed a smear pattern in the Western blot, suggesting instability of this protein in the bacteria similar to the important proteins, such as P53 protein, tightly regulated by protein degradation. Conclusions: The cloned M. tuberculosis mutT gene and MutT protein were characterized. M. tuberculosis MutT has a dGTPase activity, which is one of the most well-known preference nucleotidase activities of MutT in E. coli. These findings provide further understanding about the vicious bacterium. PMID:25147690

Huang, Hsiu-Lin; Su, Ho-Ting; Wu, Chung-Hsiun Herbert; Tsai-Wu, Jyy-Jih

2014-01-01

333

Nosocomial Transmission of Extensively Drug-Resistant Tuberculosis in a Rural Hospital in South Africa  

PubMed Central

Background.?Extensively drug-resistant tuberculosis (XDR-tuberculosis) is a global public health threat, but few data exist elucidating factors driving this epidemic. The initial XDR-tuberculosis report from South Africa suggested transmission is an important factor, but detailed epidemiologic and molecular analyses were not available for further characterization. Methods.?We performed a retrospective, observational study among XDR-tuberculosis patients to identify hospital-associated epidemiologic links. We used spoligotyping, IS6110-based restriction fragment–length polymorphism analysis, and sequencing of resistance-determining regions to identify clusters. Social network analysis was used to construct transmission networks among genotypically clustered patients. Results.?Among 148 XDR-tuberculosis patients, 98% were infected with human immunodeficiency virus (HIV), and 59% had smear-positive tuberculosis. Nearly all (93%) were hospitalized while infectious with XDR-tuberculosis (median duration, 15 days; interquartile range: 10–25 days). Genotyping identified a predominant cluster comprising 96% of isolates. Epidemiologic links were identified for 82% of patients; social network analysis demonstrated multiple generations of transmission across a highly interconnected network. Conclusions.?The XDR-tuberculosis epidemic in Tugela Ferry, South Africa, has been highly clonal. However, the epidemic is not the result of a point-source outbreak; rather, a high degree of interconnectedness allowed multiple generations of nosocomial transmission. Similar to the outbreaks of multidrug-resistant tuberculosis in the 1990s, poor infection control, delayed diagnosis, and a high HIV prevalence facilitated transmission. Important lessons from those outbreaks must be applied to stem further expansion of this epidemic. PMID:23166374

Gandhi, Neel R.; Weissman, Darren; Moodley, Prashini; Ramathal, Melissa; Elson, Inga; Kreiswirth, Barry N.; Mathema, Barun; Shashkina, Elena; Rothenberg, Richard; Moll, Anthony P.; Friedland, Gerald; Sturm, A. Willem; Shah, N. Sarita

2013-01-01

334

Tuberculosis pharmacotherapy: strategies to optimize patient care  

PubMed Central

The treatment of tuberculosis (TB) is a mature discipline, with over 60 years of clinical experience accrued across the globe. The requisite multidrug treatment of drug-susceptible TB, however, lasts six months and has never been optimized according to current standards. Multi-drug resistant tuberculosis and tuberculosis in individuals coinfected with HIV present additional treatment challenges. This article reviews the role that existing drugs and new compounds could have in shortening or improving treatment for tuberculosis. The key to treatment shortening appears to be sterilizing activity, or the ability of drugs to kill mycobacteria that persist after the initial days of multidrug treatment. Among existing anti-TB drugs, the rifamycins hold the greatest potential for shortening treatment and improving outcomes, in both HIV-infected and HIV-uninfected populations, without dramatic increases in toxicity. Clinical studies underway or being planned, are supported by in vitro, animal, and human evidence of increased sterilizing activity–without significant increases in toxicity–at elevated daily doses. Fluoroquinolones also appear to have significant sterilizing activity. At least two class members are currently under evaluation for treatment shortening with different combinations of first-line drugs. However, in light of apparent rapid selection for fluoroquinolone-resistant mutants, relative frequency of serious adverse events, and a perceived need to ‘reserve’ fluoroquinolones for the treatment of drug-resistant TB, their exact role in TB treatment remains to be determined. Other possible improvements may come from inhaled delivery or split dosing (linezolid) of anti-TB drugs for which toxicity (ethionamide) or lack of absorption (aminoglycosides and polypeptides) precludes delivery of maximally effective, oral doses, once daily. New classes of drugs with novel mechanisms of action, nitroimidazopyrans and a diarylquinoline, among others, may soon provide opportunities for improving treatment of drug-resistant TB and/or shortening treatment of drug-susceptible TB. More potential options for improved TB treatment currently exist than at any other time in the last 30 years. The challenge in TB pharmacotherapy is to devise well-tolerated, efficacious, short-duration regimens that can be used successfully against drug-resistant and drug-resistant TB in a heterogeneous population of patients. PMID:19191677

Mitnick, Carole D.; McGee, Bryan; Peloquin, Charles A.

2009-01-01

335

Forecasting Tuberculosis Incidence in Iran Using Box-Jenkins Models  

PubMed Central

Background: Predicting the incidence of tuberculosis (TB) plays an important role in planning health control strategies for the future, developing intervention programs and allocating resources. Objectives: The present longitudinal study estimated the incidence of tuberculosis in 2014 using Box-Jenkins methods. Materials and Methods: Monthly data of tuberculosis cases recorded in the surveillance system of Iran tuberculosis control program from 2005 till 2011 was used. Data was reviewed regarding normality, variance equality and stationary conditions. The parameters p, d and q and P, D and Q were determined, and different models were examined. Based on the lowest levels of AIC and BIC, the most suitable model was selected among the models whose overall adequacy was confirmed. Results: During 84 months, 63568 TB patients were recorded. The average was 756.8 (SD = 11.9) TB cases a month. SARIMA (0,1,1)(0,1,1)12 with the lowest level of AIC (12.78) was selected as the most adequate model for prediction. It was predicted that the total nationwide TB cases for 2014 will be about 16.75 per 100,000 people. Conclusions: Regarding the cyclic pattern of TB recorded cases, Box-Jenkins and SARIMA models are suitable for predicting its prevalence in future. Moreover, prediction results show an increasing trend of TB cases in Iran. PMID:25031852

Moosazadeh, Mahmood; Nasehi, Mahshid; Bahrampour, Abbas; Khanjani, Narges; Sharafi, Saeed; Ahmadi, Shanaz

2014-01-01

336

Tuberculosis pathogenesis and immunity.  

PubMed

Despite the development of potentially curative chemotherapy, tuberculosis (TB) continues to cause increasing worldwide morbidity and is a leading cause of human mortality in the developing world. Recent advances in bacterial molecular genetics, immunology, and human genetics have yielded insight into the molecular determinants of virulence, the immune responses that are essential for restricting progressive disease, and the determinants of immunopathology in TB. Despite these advances, a large knowledge gap still exists that limits the development and testing of new interventions, including novel drugs and efficacious vaccines. This review focuses on our current knowledge of TB pathogenesis and immunity that has been derived from in vitro and in vivo studies. In addition, it highlights topics that need to be better understood to provide improved means of controlling TB worldwide. PMID:22054143

Philips, Jennifer A; Ernst, Joel D

2012-01-01

337

Tuberculosis: 11. Nosocomial  

E-print Network

The tuberculosis (TB) series, which has been running in CMAJ sinceMarch 1999, has already reviewed the changes in populations at risk1and the emergence of HIV-related2 and multidrug-resistant3 TB in Canada. Since the occurrence of several highly publicized outbreaks of mul-tidrug-resistant TB in US hospitals,4 the transmission of TB within hospitals and other institutions has been increasingly recognized as a hazard for patients and workers. Using a fictitious case for illustration, this article reviews the major de-terminants of nosocomial transmission of TB, as well as the key administrative, engineering and personal measures that can be taken to minimize transmission of the disease in health care facilities.

Kevin Schwartzman; Mph Dick Menzies

338

Incidence of HIV-Associated Tuberculosis among Individuals Taking Combination Antiretroviral Therapy: A Systematic Review and Meta-Analysis  

PubMed Central

Background Knowledge of tuberculosis incidence and associated factors is required for the development and evaluation of strategies to reduce the burden of HIV-associated tuberculosis. Methods Systematic literature review and meta-analysis of tuberculosis incidence rates among HIV-infected individuals taking combination antiretroviral therapy. Results From PubMed, EMBASE and Global Index Medicus databases, 42 papers describing 43 cohorts (32 from high/intermediate and 11 from low tuberculosis burden settings) were included in the qualitative review and 33 in the quantitative review. Cohorts from high/intermediate burden settings were smaller in size, had lower median CD4 cell counts at study entry and fewer person-years of follow up. Tuberculosis incidence rates were higher in studies from Sub-Saharan Africa and from World Bank low/middle income countries. Tuberculosis incidence rates decreased with increasing CD4 count at study entry and duration on combination antiretroviral therapy. Summary estimates of tuberculosis incidence among individuals on combination antiretroviral therapy were higher for cohorts from high/intermediate burden settings compared to those from the low tuberculosis burden settings (4.17 per 100 person-years [95% Confidence Interval (CI) 3.39–5.14 per 100 person-years] vs. 0.4 per 100 person-years [95% CI 0.23–0.69 per 100 person-years]) with significant heterogeneity observed between the studies. Conclusions Tuberculosis incidence rates were high among individuals on combination antiretroviral therapy in high/intermediate burden settings. Interventions to prevent tuberculosis in this population should address geographical, socioeconomic and individual factors such as low CD4 counts and prior history of tuberculosis. PMID:25393281

Kufa, Tendesayi; Mabuto, Tonderai; Muchiri, Evans; Charalambous, Salome; Rosillon, Dominique; Churchyard, Gavin; Harris, Rebecca C.

2014-01-01

339

Demonstration of Mycobacterium Tuberculosis in Sputum and Saliva Smears of Tuberculosis Patients Using Ziehl Neelsen and Flurochrome Staining- A Comparative Study  

PubMed Central

Background: Early detection of tuberculosis is important for reducing its morbidity and mortality especially in the patients with non-productive cough. To overcome the cumbersome process involved in collection and processing of the sputum specimen, the time consumed for reporting of sputum by Ziehl Neelsen (ZN) method and to introduce a routine screening test in suspected, symptomless tuberculosis patients, the present study was designed using saliva as diagnostic medium and Auramine Rhodamine (AR) as staining method. On review of literature, there was no study which has tried diagnosing tuberculosis using saliva with flurochrome stain; hence the present study was designed. Aim: To introduce a routine screening test for tuberculosis patient using saliva and to determine the diagnostic efficacy of routine ZN staining method and AR fluorescent staining method in sputum and saliva smears of pulmonary tuberculosis patients. Settings and Design: Laboratory settings and Experimental design. Materials and Method: Fifty smears samples of sputum and saliva of known cases of pulmonary tuberculosis were stained with routine ZN stain and other with AR fluorescent stain. All the specimens were inoculated into Lowenstein-Jensen culture media. The smears were subjected for scanning of Mycobacterium tuberculous bacilli under X 1000 magnification for ZN stain and X 400 magnification for AR stain by grid pattern proposed by National tuberculosis institute and graded by RNTCP grading system. Results: All 50 sputum samples showed 100% positivity by ZN and AR stain while only 76% positivity was seen by culture. Of the 50 saliva samples 10% cases were positive by ZN, 76% were positive by AR & 70% by culture method. Statistical analysis using chi square test was done, and the value was found to be statistically highly significant for AR staining technique. (p<0.001) Conclusion: Saliva can prove to be an important tool for the diagnosis as well as screening of the patients with pulmonary tuberculosis when aided with flurochrome staining method. PMID:25177636

Ganvir, Sindhu M; Shah, Nishat N; Bansode, Shriram C; Shende, Ishali; Jawade, Rashmi; Bijjargi, Shobha C

2014-01-01

340

Towards an empowerment approach in tuberculosis treatment in Cape Town, South Africa: a qualitative analysis of programmatic change  

PubMed Central

Background Tuberculosis rates in the world remain high, especially in low- and middle-income countries. International tuberculosis (TB) policy generally recommends the use of directly observed therapy (DOT) to ensure treatment adherence. Objective This article examines a change in TB treatment support that occurred in 2005 in South Africa, from DOT to the enhanced TB adherence programme (ETA). Design Seven key individuals representing academics, policy makers and service providers involved in the development of the ETA programme or knowledgeable about the issue were purposively sampled and interviewed, and participant observation was conducted at ETA programme steering group meetings. Qualitative content analysis was used to analyse the data, drawing on the Kingdon model of agenda setting. This model suggests that three independent streams – problem, policy and politics – come together at a certain point, often facilitated by policy entrepreneurs, to provide an opportunity for an issue to enter the policy agenda. Results The results suggest the empowerment-oriented programme emerged through the presence of policy entrepreneurs with access to resources. Policy entrepreneurs were influenced by a number of simultaneously occurring challenges including problems within the existing programme; a perceived mismatch between patient needs and the existing TB treatment model; and the TB-HIV co-epidemic. Policy entrepreneurs saw the ART approach as a possible solution to these challenges. Conclusions The Kingdon model contributed to describing the process of policy change. Research evidence seemed to influence this change diffusely, through the interaction of policy entrepreneurs and academics. PMID:22902052

Atkins, Salla; Lewin, Simon; Ringsberg, Karin C.; Thorson, Anna

2012-01-01

341

Tuberculosis, advanced - chest x-rays (image)  

MedlinePLUS

Tuberculosis is an infectious disease that causes inflammation, the formation of tubercules and other growths within tissue, ... death. These chest x-rays show advanced pulmonary tuberculosis. There are multiple light areas (opacities) of varying ...

342

Prevalence of depression in tuberculosis patients in comparison with non-tuberculosis family contacts visiting the DOTS clinic in a Nigerian tertiary care hospital and its correlation with disease pattern  

PubMed Central

Background Individuals with chronic diseases such as tuberculosis often have comorbid de-pression that requires frequent hospitalisations. This poses great challenges to the care of such patients. Objective This study aimed at determining the prevalence of depression in tuberculosis patients in comparison with non-tuberculosis controls, and its correlation with disease pattern. Method Eighty-eight patients with tuberculosis and 81 family members visiting the DOTS Centre at University College Hospital Ibadan Centre were screened for depression. Severity of depression was assessed using the Hamilton Depression Scale and was compared with severity of pulmonary tuberculosis. Results The prevalence of depression was 45.5% among patients and 13.4% among family members. Depression was more prevalent among patients that were elderly (P = 0.001), with extensive disease (P = 0.01), of long duration (P = 0.03), those with category 2 tuberculosis (P = 0.003), those from a nuclear family (P = 0.01) and patients that were unmarried (P = 0.02). Conclusion The impact of chronic diseases such as tuberculosis extends beyond physical impairment. It includes behavioural consequences, in this instance depression, for both the patient and the primary care givers. Thus, the care of patients with tuberculosis should be comprehensive and include consultative–liaison psychiatric care. PMID:23205064

2011-01-01

343

High levels of multidrug resistant tuberculosis in new and treatment-failure patients from the Revised National Tuberculosis Control Programme in an urban metropolis (Mumbai) in Western India  

PubMed Central

Background India, China and Russia account for more than 62% of multidrug resistant tuberculosis (MDRTB) globally. Within India, locations like urban metropolitan Mumbai with its burgeoning population and high incidence of TB are suspected to be a focus for MDRTB. However apart from sporadic surveys at watched sites in the country, there has been no systematic attempt by the Revised National Tuberculosis Control Programme (RNTCP) of India to determine the extent of MDRTB in Mumbai that could feed into national estimates. Drug susceptibility testing (DST) is not routinely performed as a part of programme policy and public health laboratory infrastructure, is limited and poorly equipped to cope with large scale testing. Methods From April 2004 to January 2007 we determined the extent of drug resistance in 724 {493 newly diagnosed, previously untreated and 231 first line treatment failures (sputum-smear positive at the fifth month after commencement of therapy)} cases of pulmonary tuberculosis drawn from the RNTCP in four suboptimally performing municipal wards of Mumbai. The observations were obtained using a modified radiorespirometric Buddemeyer assay and validated by the Swedish Institute for Infectious Disease Control, Stockholm, a supranational reference laboratory. Data was analyzed utilizing SPSS 10.0 and Epi Info 2002. Results This study undertaken for the first time in RNTCP outpatients in Mumbai reveals a high proportion of MDRTB strains in both previously untreated (24%) and treatment-failure cases (41%). Amongst new cases, resistance to 3 or 4 drug combinations (amplified drug resistance) including isoniazid (H) and rifampicin (R), was greater (20%) than resistance to H and R alone (4%) at any point in time during the study. The trend for monoresistance was similar in both groups remaining highest to H and lowest to R. External quality control revealed good agreement for H and R resistance (k = 0.77 and 0.76 respectively). Conclusion Levels of MDRTB are much higher in both previously untreated and first line treatment-failure cases in the selected wards in Mumbai than those projected by national estimates. The finding of amplified drug resistance suggests the presence of a well entrenched MDRTB scenario. This study suggests that a wider set of surveillance sites are needed to obtain a more realistic view of the true MDRTB rates throughout the country. This would assist in the planning of an adequate response to the diagnosis and care of MDRTB. PMID:19563647

D'souza, Desiree TB; Mistry, Nerges F; Vira, Tina S; Dholakia, Yatin; Hoffner, Sven; Pasvol, Geoffrey; Nicol, Mark; Wilkinson, Robert J

2009-01-01

344

An Update on Global Tuberculosis (TB)  

PubMed Central

Tuberculosis globally results in almost 2 million human deaths annually, with 1 in 4 deaths from tuberculosis being human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)-related. Primarily a pathogen of the respiratory system, aerobic Mycobacterium tuberculosis complex (MTBC) infects the lungs via the inhalation of infected aerosol droplets generated by people with pulmonary disease through coughing. This review focuses on M. tuberculosis transmission, epidemiology, detection methods and technologies. PMID:24847176

Talip, Balkis A.; Sleator, Roy D.; Lowery, Colm J.; Dooley, James S.G.; Snelling, William J.

2013-01-01

345

An update on lower urinary tract tuberculosis  

Microsoft Academic Search

Tuberculosis of the genitourinary tract presents with atypical manifestations. Only 20% to 30% of patients with genitourinary\\u000a tuberculosis have a history of pulmonary infection. Tuberculosis often affects the lower genitourinary system rather than\\u000a the kidney. Tuberculosis of the lower genitourinary tract most commonly affects the epididymis and the testis, followed by\\u000a bladder, ureter, prostate, and penis. Use of bacillus Calmette-Guérin

Gilbert J. Wise; Alex Shteynshlyuger

2007-01-01

346

Explosives remain preferred methods for platform abandonment  

SciTech Connect

Economics and safety concerns indicate that methods involving explosives remain the most practical and cost-effective means for abandoning oil and gas structures in the Gulf of Mexico. A decade has passed since 51 dead sea turtles, many endangered Kemp`s Ridleys, washed ashore on the Texas coast shortly after explosives helped remove several offshore platforms. Although no relationship between the explosions and the dead turtles was ever established, in response to widespread public concern, the US Minerals Management Service (MMS) and National Marine Fisheries Service (NMFS) implemented regulations limiting the size and timing of explosive charges. Also, more importantly, they required that operators pay for observers to survey waters surrounding platforms scheduled for removal for 48 hr before any detonations. If observers spot sea turtles or marine mammals within the danger zone, the platform abandonment is delayed until the turtles leave or are removed. However, concern about the effects of explosives on marine life remains.

Pulsipher, A.; Daniel, W. IV [Louisiana State Univ., Baton Rouge, LA (United States); Kiesler, J.E. [Kiesler (James E.), Morgan City, LA (United States); Mackey, V. III [Chevron Petroleum Technology Co., Houston, TX (United States)

1996-05-06

347

38 CFR 3.959 - Tuberculosis.  

...2014-07-01 2014-07-01 false Tuberculosis. 3.959 Section 3.959 Pensions...Compensation Protection § 3.959 Tuberculosis. Any veteran who, on August...for active or inactive (arrested) tuberculosis may receive compensation under...

2014-07-01

348

www.elsevierhealth.com/journals/tube Tuberculosis  

E-print Network

www.elsevierhealth.com/journals/tube Tuberculosis Direct lung delivery of para-aminosalicylic acid potentially be used for the delivery of additional anti- tuberculosis agents such as rifampicin, aminoglucosides or fluoroquinolones. & 2003 Elsevier Ltd. All rights reserved. KEYWORDS Tuberculosis treatment

349

38 CFR 3.959 - Tuberculosis.  

Code of Federal Regulations, 2012 CFR

...2012-07-01 2012-07-01 false Tuberculosis. 3.959 Section 3.959 Pensions...Compensation Protection § 3.959 Tuberculosis. Any veteran who, on August...for active or inactive (arrested) tuberculosis may receive compensation under...

2012-07-01

350

38 CFR 3.959 - Tuberculosis.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Tuberculosis. 3.959 Section 3.959 Pensions...Compensation Protection § 3.959 Tuberculosis. Any veteran who, on August...for active or inactive (arrested) tuberculosis may receive compensation under...

2013-07-01

351

38 CFR 3.959 - Tuberculosis.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 2010-07-01 false Tuberculosis. 3.959 Section 3.959 Pensions...Compensation Protection § 3.959 Tuberculosis. Any veteran who, on August...for active or inactive (arrested) tuberculosis may receive compensation under...

2010-07-01

352

www.elsevierhealth.com/journals/tube Tuberculosis  

E-print Network

www.elsevierhealth.com/journals/tube Tuberculosis Visualization of microarray results to assist on Mycobacterium tuberculosis were used to develop and evaluate the visualization tool and initiate the development. All rights reserved. doi:10.1016/j.tube.2003.12.012 Tuberculosis (2004) 84, 275­281 #12;define

Sergot, Marek

353

Mycobacterium tuberculosis as viewed through a computer  

E-print Network

Mycobacterium tuberculosis as viewed through a computer Denise Kirschner and Simeone Marino of Mycobacterium tuberculosis and the immune system. Different mathematical models were formulated on the basis that contribute to the success of M. tuberculosis as a human pathogen. Our goal is to stimulate experimentation

Kirschner, Denise

354

38 CFR 3.959 - Tuberculosis.  

Code of Federal Regulations, 2011 CFR

...2011-07-01 2011-07-01 false Tuberculosis. 3.959 Section 3.959 Pensions...Compensation Protection § 3.959 Tuberculosis. Any veteran who, on August...for active or inactive (arrested) tuberculosis may receive compensation under...

2011-07-01

355

Miliary tuberculosis and adult respiratory distress syndrome  

Microsoft Academic Search

Although, miliary tuberculosis is an unusual cause of severe acute respiratory failure, we describe nine patients with miliary tuberculosis who developed adult respiratory distress syndrome. This complication occurred in seven patients despite treatment with antituberculous drugs. In two patients who developed the syndrome, miliary tuberculosis was diagnosed only at postmortem. The presence of pulmonary hypertension in all cases and disseminated

A. Roglan Piqueras; L. Marruecos; A. Artigas; C. Rodriguez

1987-01-01

356

Immune Reconstitution Inflammatory Syndrome following Antiretroviral Therapy Initiation in Tuberculosis Patients: Findings from the SAPiT Trial  

PubMed Central

Background Concerns about immune reconstitution inflammatory syndrome (IRIS) remain a barrier to antiretroviral therapy (ART) initiation during anti-tuberculosis treatment in co-infected patients. Objective We assessed IRIS incidence, severity, and outcomes relative to timing of ART initiation in patients with HIV-related tuberculosis (HIV-TB). Setting An outpatient clinic in Durban, South Africa Patients 642 HIV-TB co-infected patients Design In a secondary analysis of the SAPiT trial, IRIS was assessed in patients randomized to initiate ART either within four weeks of tuberculosis treatment initiation (early integrated-treatment arm), within four weeks of completion of the intensive phase of tuberculosis treatment (late integrated-treatment arm) or within four weeks after tuberculosis therapy completion (sequential-treatment arm). IRIS was defined as new onset or worsening symptoms, signs or radiographic manifestations temporally related to treatment initiation accompanied by a treatment response. IRIS severity, hospitalization and time to resolution were monitored. Results IRIS incidence was 19.5 (n=43), 7.5 (n=18) and 8.1 (n=19) per 100 person-years in the early integrated-, late integrated-, and sequential-treatment arms, respectively; P < 0.001, and 45.5, 9.7 and 19.7 per 100 person-years in patients with baseline CD4+ counts <50 cells/mm3, P = 0.004. IRIS incidence was higher in the early integrated- compared to the late integrated- (incidence rate ratio (IRR) = 2.6, 95%confidence interval (CI): 1.5 to 4.8; P < 0.001) or sequential-treatment arm (IRR=2.4, 95%CI: 1.4 to 4.4; P < 0.001). IRIS cases in the early integrated-treatment arm were more severe (34.9% vs. 18.9%, P = 0.18); had significantly higher hospitalization rates (18/43 vs. 5/37; P = 0.01), and longer time to resolution (70.5 vs. 29.0 days; P = 0.001) compared to IRIS cases in the other two arms. Limitation IRIS could not be assessed, due to LTFU, withdrawal or death within 6 months of scheduled ART initiation, in more patients from the sequential treatment arm (n=74) than in the late integrated treatment arm (n=50) and in the early integrated treatment arm (n=32). This study did not assess IRIS risk in non-ambulant patients and in patients with extra-pulmonary and smear negative pulmonary tuberculosis. Conclusion Initiation of ART early during tuberculosis treatment resulted in significantly higher IRIS rates, with longer time to resolution, and more severe cases of IRIS requiring hospitalization. These findings, particularly relevant to patients initiating ART with CD4+ counts < 50 cells/mm3, need to be considered together with the increased survival benefit of early ART initiation in this group. Clintrials.gov: NCT00398996 PMID:22944873

Naidoo, Kogieleum; Yende-Zuma, Nonhlanhla; Padayatachi, Nesri; Naidoo, Kasavan; Jithoo, Niraksha; Nair, Gonasagrie; Bamber, Sheila; Gengiah, Santhana; El-Sadr, Wafaa M.; Friedland, Gerald; Karim, Salim Abdool

2012-01-01

357

A home-based approach to managing multi-drug resistant tuberculosis in Uganda: a case report  

PubMed Central

This case report describes an HIV-positive patient with recurrent tuberculosis in Uganda. After several failed courses of treatment, the patient was diagnosed with multi-drug resistant tuberculosis (MDR-TB). As adequate in-patient facilities were unavailable, we advised the patient to remain at home, and he received treatment at home via his family and a community nurse. The patient had a successful clearance of tuberculosis. This strategy of home-based care represents an important opportunity for treatment of patients in East Africa, where human resource constraints and inadequate hospital facilities exist for complex patients at high risk of infection to others. PMID:22524486

2012-01-01

358

Tuberculosis and Drug Use: Review and Update  

PubMed Central

Illicit drug users continue to be a group at high risk for tuberculosis (TB) infection and disease. In this article, we present an updated review on the relationship between TB and drug use, summarizing more than a decade of new research. Drug users, and injection drug users in particular, have driven TB epidemics in a number of countries. The successful identification and treatment of TB among drug users remains an important component of a comprehensive TB strategy, but drug users present a unique set of challenges for TB diagnosis and control. New diagnostic modalities, including interferon-? release assays (IGRAs), offer potential for improved diagnosis and surveillance among this group, alongside proven treatment strategies which incorporate the use of directly-observed therapy (DOT) with treatment for drug abuse. Special considerations, including co-infection with viral hepatitis and the Rifampin/methadone drug interaction, warrant clinical attention and are also updated here. PMID:19046064

Deiss, Robert G.; Rodwell, Timothy C.; Garfein, Richard S.

2011-01-01

359

Lake in Cameroon remains a hazard  

NASA Astrophysics Data System (ADS)

Carbon dioxide levels remain dangerous in Lake Nyos, the lake in Cameroon that released a deadly cloud of the gas last August, according to the final report of the U.S. scientific team sent by the Agency for International Development (AID) to investigate the disaster. The scientists recommended that a system be constructed to pipe the lake's CO2-saturated bottom water to the surface at a controlled rate. The team also said that the CO2 concentration of other volcanic lakes in the region should be monitored.

Katzoff, Judith A.

360

Tuberculosis diagnosed during pregnancy: a prospective study from London  

PubMed Central

BACKGROUND—A study was undertaken to characterise the presentation of tuberculosis in pregnancy and the difficulties in diagnosis in an area of the UK with a high incidence of tuberculosis.?METHODS—A prospective case series was investigated at Northwick Park Hospital, a university affiliated district general hospital in Brent and Harrow health authority in north-west London which incorporates a regional infectious diseases unit. Patients diagnosed with tuberculosis over the study period were included if the onset of symptoms occurred during pregnancy.?RESULTS—Thirteen patients were diagnosed during a 30 month period from December 1995 to May 1998 during which 9069 mothers were delivered, a prevalence of 143.3/100 000 deliveries. Symptoms began at a median of 22 weeks gestation (range 9-40 weeks). All patients were recent immigrants of Indian subcontinent or Somali origin and their median duration of residence in the UK was 31 months (range 1-72). Prevalence broken down for racial origin of mothers was 466.3/100 000 for mothers of black African origin and 239.1/100 000 for mothers of Indian origin. Nine of the 13 patients had extrapulmonary tuberculosis. Four patients with widely disseminated disease had a negative Mantoux response and five with localised disease had a strongly positive Mantoux response. HIV co-infection was absent. The median delay between the onset of symptoms and diagnosis was seven weeks (range 2-30). The response to standard treatment was excellent and all patients were cured.?CONCLUSIONS—Tuberculosis occurring in pregnancy is common in recent immigrants. Diagnosis during pregnancy is delayed because the disease is frequently extrapulmonary with few symptoms.?? PMID:10639530

Llewelyn, M.; Cropley, I.; Wilkinson, R.; Davidson, R.

2000-01-01

361

Revisiting the essentiality of glutamate racemase in Mycobacterium tuberculosis.  

PubMed

Glutamate racemase (MurI) converts l-glutamate into d-glutamate which is an essential component of peptidoglycan in bacteria. The gene encoding glutamate racemase, murI has been shown to be essential for the growth of a number of bacterial species including Escherichia coli. However, in some Gram-positive species d-amino acid transaminase (Dat) can also convert l-glutamate into d-glutamate thus rendering MurI non-essential for growth. In a recent study the murI gene of Mycobacterium tuberculosis was shown to be non-essential. As d-glutamate is an essential component of peptidoglycan of M. tuberculosis, either Dat or MurI has to be essential for its survival. Since, a Dat encoding gene has not been reported in M. tuberculosis genome sequence, the reported non-essentiality of murI was unexplainable. In order to resolve this dilemma we tried to knockout murI in the presence of single and two copies of murI, in wild type and merodiploid strains respectively. It was found that murI could not be inactivated in the wild type background indicating that it could be an essential gene. Also, inactivation of murI could not be achieved in the presence of externally supplied d-glutamate in 7H9 medium suggesting that M. tuberculosis is unable to take up d-glutamate under the conditions tested. However we could generate murI knockout strains at high frequency when two copies of the gene were present indicating that at least one murI gene is required for cellular viability. The essential nature of MurI in M. tuberculosis H37Rv suggests that it could be a potential drug target. PMID:25447907

Morayya, Sapna; Awasthy, Disha; Yadav, Reena; Ambady, Anisha; Sharma, Umender

2015-01-25

362

[Choroidal tuberculosis: reports of 3 cases].  

PubMed

Tuberculosis is a chronic infection with a high incidence in Morocco. Ocular involvement is rare. We report three cases of choroidal tuberculosis. Case no 1: A 24-year-old female with tuberculous meningitis, multifocal choroiditis in the right eye and choroidal granuloma in the left eye. Case no 2: A 22-year-old female with multifocal tuberculosis. The ocular examination showed a choroidal granuloma. Case no 3: A 25-year-old male with HIV infection and miliary tuberculosis. Ocular involvement consisted in a choroidal granuloma. Ocular involvement in tuberculosis is uncommon. Choroidal granuloma is a characteristic manifestation. PMID:20108570

Baha Ali, T; Benhaddou, R; Hajj, I; Khoumiri, R; Guelzim, H; Moutaouakil, A

2009-01-01

363

The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis  

PubMed Central

Type 2 diabetes mellitus is an established risk factor for tuberculosis but the underlying mechanisms are largely unknown. We examined the effects of hyperglycaemia, a hallmark of diabetes, on the cytokine response to and macrophage infection with Mycobacterium tuberculosis. Increasing in vitro glucose concentrations from 5 to 25 mmol/L had marginal effects on cytokine production following stimulation of peripheral blood mononuclear cells (PBMCs) with M. tuberculosis lysate, LPS or Candida albicans, while 40 mmol/L glucose increased production of TNF-?, IL-1?, IL-6 and IL-10, but not of IFN-?, IL-17A and IL-22. Macrophage differentiation under hyperglycaemic conditions of 25 mmol/L glucose was also associated with increased cytokine production upon stimulation with M. tuberculosis lysate and LPS but in infection experiments no differences in M. tuberculosis killing or outgrowth was observed. The phagocytic capacity of these hyperglycaemic macrophages also remained unaltered. The fact that only very high glucose concentrations were able to significantly influence cytokine production by macrophages suggests that hyperglycaemia alone cannot fully explain the increased susceptibility of diabetes mellitus patients to tuberculosis. PMID:25664765

Wilson, Louis G.; Joosten, Simone A.; Netea, Mihai G.; Ottenhoff, Tom H.; van Crevel, Reinout

2015-01-01

364

Linking the Transcriptional Profiles and the Physiological States of Mycobacterium tuberculosis during an Extended Intracellular Infection  

PubMed Central

Intracellular pathogens such as Mycobacterium tuberculosis have evolved strategies for coping with the pressures encountered inside host cells. The ability to coordinate global gene expression in response to environmental and internal cues is one key to their success. Prolonged survival and replication within macrophages, a key virulence trait of M. tuberculosis, requires dynamic adaptation to diverse and changing conditions within its phagosomal niche. However, the physiological adaptations during the different phases of this infection process remain poorly understood. To address this knowledge gap, we have developed a multi-tiered approach to define the temporal patterns of gene expression in M. tuberculosis in a macrophage infection model that extends from infection, through intracellular adaptation, to the establishment of a productive infection. Using a clock plasmid to measure intracellular replication and death rates over a 14-day infection and electron microscopy to define bacterial integrity, we observed an initial period of rapid replication coupled with a high death rate. This was followed by period of slowed growth and enhanced intracellular survival, leading finally to an extended period of net growth. The transcriptional profiles of M. tuberculosis reflect these physiological transitions as the bacterium adapts to conditions within its host cell. Finally, analysis with a Transcriptional Regulatory Network model revealed linked genetic networks whereby M. tuberculosis coordinates global gene expression during intracellular survival. The integration of molecular and cellular biology together with transcriptional profiling and systems analysis offers unique insights into the host-driven responses of intracellular pathogens such as M. tuberculosis. PMID:22737072

Rohde, Kyle H.; Veiga, Diogo F. T.; Caldwell, Shannon; Balázsi, Gábor; Russell, David G.

2012-01-01

365

LprG-Mediated Surface Expression of Lipoarabinomannan Is Essential for Virulence of Mycobacterium tuberculosis  

PubMed Central

Mycobacterium tuberculosis employs various virulence strategies to subvert host immune responses in order to persist and cause disease. Interaction of M. tuberculosis with mannose receptor on macrophages via surface-exposed lipoarabinomannan (LAM) is believed to be critical for cell entry, inhibition of phagosome-lysosome fusion, and intracellular survival, but in vivo evidence is lacking. LprG, a cell envelope lipoprotein that is essential for virulence of M. tuberculosis, has been shown to bind to the acyl groups of lipoglycans but the role of LprG in LAM biosynthesis and localization remains unknown. Using an M. tuberculosis lprG mutant, we show that LprG is essential for normal surface expression of LAM and virulence of M. tuberculosis attributed to LAM. The lprG mutant had a normal quantity of LAM in the cell envelope, but its surface was altered and showed reduced expression of surface-exposed LAM. Functionally, the lprG mutant was defective for macrophage entry and inhibition of phagosome-lysosome fusion, was attenuated in macrophages, and was killed in the mouse lung with the onset of adaptive immunity. This study identifies the role of LprG in surface-exposed LAM expression and provides in vivo evidence for the essential role surface LAM plays in M. tuberculosis virulence. Findings have translational implications for therapy and vaccine development. PMID:25232742

Blumenthal, Antje; Bhamidi, Suresh; Gibbs, Sara; Jackson, Mary; Zare, Richard N.; Ehrt, Sabine; Ernst, Joel D.; Banaei, Niaz

2014-01-01

366

LprG-mediated surface expression of lipoarabinomannan is essential for virulence of Mycobacterium tuberculosis.  

PubMed

Mycobacterium tuberculosis employs various virulence strategies to subvert host immune responses in order to persist and cause disease. Interaction of M. tuberculosis with mannose receptor on macrophages via surface-exposed lipoarabinomannan (LAM) is believed to be critical for cell entry, inhibition of phagosome-lysosome fusion, and intracellular survival, but in vivo evidence is lacking. LprG, a cell envelope lipoprotein that is essential for virulence of M. tuberculosis, has been shown to bind to the acyl groups of lipoglycans but the role of LprG in LAM biosynthesis and localization remains unknown. Using an M. tuberculosis lprG mutant, we show that LprG is essential for normal surface expression of LAM and virulence of M. tuberculosis attributed to LAM. The lprG mutant had a normal quantity of LAM in the cell envelope, but its surface was altered and showed reduced expression of surface-exposed LAM. Functionally, the lprG mutant was defective for macrophage entry and inhibition of phagosome-lysosome fusion, was attenuated in macrophages, and was killed in the mouse lung with the onset of adaptive immunity. This study identifies the role of LprG in surface-exposed LAM expression and provides in vivo evidence for the essential role surface LAM plays in M. tuberculosis virulence. Findings have translational implications for therapy and vaccine development. PMID:25232742

Gaur, Rajiv L; Ren, Kangning; Blumenthal, Antje; Bhamidi, Suresh; Gibbs, Sara; Jackson, Mary; Zare, Richard N; Ehrt, Sabine; Ernst, Joel D; Banaei, Niaz

2014-09-01

367

Proteome-wide lysine acetylation profiling of the human pathogen Mycobacterium tuberculosis.  

PubMed

N(?)-Acetylation of lysine residues represents a pivotal post-translational modification used by both eukaryotes and prokaryotes to modulate diverse biological processes. Mycobacterium tuberculosis is the causative agent of tuberculosis, one of the most formidable public health threats. Many aspects of the biology of M. tuberculosis remain elusive, in particular the extent and function of N(?)-lysine acetylation. With a combination of anti-acetyllysine antibody-based immunoaffinity enrichment with high-resolution mass spectrometry, we identified 1128 acetylation sites on 658 acetylated M. tuberculosis proteins. GO analysis of the acetylome showed that acetylated proteins are involved in the regulation of diverse cellular processes including metabolism and protein synthesis. Six types of acetylated peptide sequence motif were revealed from the acetylome. Twenty lysine-acetylated proteins showed homology with acetylated proteins previously identified from Escherichia coli, Salmonella enterica, Bacillus subtilis and Streptomyces roseosporus, with several acetylation sites highly conserved among four or five bacteria, suggesting that acetylated proteins are more conserved. Notably, several proteins including isocitrate lyase involved in the persistence, virulence and antibiotic resistance are acetylated, and site-directed mutagenesis of isocitrate lyase acetylation site to glutamine led to a decrease of the enzyme activity, indicating major roles of KAc in these proteins engaged cellular processes. Our data firstly provides a global survey of M. tuberculosis acetylation, and implicates extensive regulatory role of acetylation in this pathogen. This may serve as an important basis to address the roles of lysine acetylation in M. tuberculosis metabolism, persistence and virulence. PMID:25456444

Xie, Longxiang; Wang, Xiaobo; Zeng, Jie; Zhou, Mingliang; Duan, Xiangke; Li, Qiming; Zhang, Zhen; Luo, Hongping; Pang, Lei; Li, Wu; Liao, Guojian; Yu, Xia; Li, Yunxu; Huang, Hairong; Xie, Jianping

2015-02-01

368

Development of a novel anti ESAT-6 monoclonal antibody for screening of Mycobacterium tuberculosis  

PubMed Central

Tuberculosis (TB) is a major global public health problem with an estimated one-third of the world’s population infected with Mycobacterium tuberculosis, thus necessitating fast and accurate diagnosis of TB. However, the diagnosis of latent infection remains difficult due to the lack of a simple, reliable test for M. tuberculosis infection. The objective of the current study was to generate and characterize a novel monoclonal antibody (mAb) that specifically target the early secretory antigenic target 6 (ESAT-6) protein for tuberculosis (TB) immunological diagnosis. The BALB/c mice were immunized by a peptide with 13 amino acids (amino acid residues 24 to 36) of ESAT-6 protein. Stable hybridomas cell lines were established and mAb was identified by Western Blot, immunoprecipitation (IP) and Enzyme linked immunosorbent assay (ELISA). In addition, this mouse mAb was used to coat plates, and biotin-labelled polyclonal antibodies were used to detect the antigens. Finally, the antibody was verified in 280 patient sputum culture supernatants and pleural effusion aspirates. The positive detection rate of the generated ESAT-6 mAb was 91% in the clinical diagnosis of tuberculosis pleural effusion, and this mAb had a sensitivity of 92.4% and a specificity of 100% in all M. tuberculosis cases. Our data indicated that the mAb generated in this study can potentially serve as a tool in the laboratory diagnosis of TB. PMID:25550937

Leng, Jianhang; Ding, Yu; Shou, Chengmin; Wu, Zhigang; Zhuo, Guangchao; Wang, Keyi; Shen, Junya; Huang, Sheng

2014-01-01

369

Bovine tuberculosis in domestic and wild mammals in an area of Dorset. II. The badger population, its ecology and tuberculosis status.  

PubMed Central

Following a major outbreak of tuberculosis in cattle on a farm in Dorset, badgers were discovered to be infected with Mycobacterium bovis. Two hundred and forty sets were found in the 1200 hectares of the study area. The sets were found predominantly in areas of Portland Sand. A high prevalence of tuberculosis was found in the badger population which was removed and repopulation prevented for 3 years. The removal of the infected badgers led to the resolution of the problem in cattle. Re-colonization of the area has progressed slowly and the cattle have remained free from infection for a period of 5 years. PMID:6752271

Little, T. W.; Swan, C.; Thompson, H. V.; Wilesmith, J. W.

1982-01-01

370

A comparative examination of tuberculosis immigration medical screening programs from selected countries with high immigration and low tuberculosis incidence rates  

PubMed Central

Background Tuberculosis (TB) in migrants is an ongoing challenge in several low TB incidence countries since a large proportion of TB in these countries occurs in migrants from high incidence countries. To meet these challenges, several countries utilize TB screening programs. The programs attempt to identify and treat those with active and/or infectious stages of the disease. In addition, screening is used to identify and manage those with latent or inactive disease after arrival. Between nations, considerable variation exists in the methods used in migration-associated TB screening. The present study aimed to compare the TB immigration medical examination requirements in selected countries of high immigration and low TB incidence rates. Methods Descriptive study of immigration TB screening programs Results 16 out of 18 eligible countries responded to the written standardized survey and phone interview. Comparisons in specific areas of TB immigration screening programs included authorities responsible for TB screening, the primary objectives of the TB screening program, the yield of detection of active TB disease, screening details and aspects of follow up for inactive pulmonary TB. No two countries had the same approach to TB screening among migrants. Important differences, common practices, common problems, evidence or lack of evidence for program specifics were noted. Conclusions In spite of common goals, there is great diversity in the processes and practices designed to mitigate the impact of migration-associated TB among nations that screen migrants for the disease. The long-term goal in decreasing migration-related introduction of TB from high to low incidence countries remains diminishing the prevalence of the disease in those high incidence locations. In the meantime, existing or planned migration screening programs for TB can be made more efficient and evidenced based. Cooperation among countries doing research in the areas outlined in this study should facilitate the development of improved screening programs. PMID:21205318

2011-01-01

371

LED-Fluorescence Microscopy for Diagnosis of Pulmonary Tuberculosis under Programmatic Conditions in India  

PubMed Central

Background Light-emitting diode fluorescence microscopy (LED-FM) has been shown to be more sensitive than conventional bright field microscopy using Ziehl-Neelsen (ZN) stain in detecting sputum smear positive tuberculosis in controlled laboratory conditions. In 2012, Auramine O staining based LED-FM replaced conventional ZN microscopy in 200 designated microscopy centres (DMC) of medical colleges operating in collaboration with India’s Revised National Tuberculosis Control Programme. We aimed to assess the impact of introduction of LED-FM services on sputum smear positive case detection under program conditions. Methods This was a before and after comparison study. In 15 randomly selected medical college DMCs, all presumptive TB patients who underwent sputum smear examination in the years 2011 (before LED-FM) and 2012 (after LED-FM) were compared. An additional 15 comparable DMCs that implemented conventional ZN sputum smear microscopy were also selected for comparison between 2011 and 2012. Results The proportion of presumptive TB patients (PTP)found sputum smear positive increased by 30%- from 13.6% (3432/25159) in 2011 to 17.8% (4706/26426) in 2012 (P value <0.01) in the sites that implemented LED-FM microscopy, whereas in DMCs where the ZN staining procedure is followed the proportion of sputum smear positive had remained unchanged (13.0%versus 12.6%;P value0.31). Conclusion Use of LED-FM significantly increased the proportion of smear positive cases among presumptive TB patients under routine program conditions in high workload laboratories. The study provides operational evidence needed to scale-up the use of LED-FM in similar settings in India and beyond. PMID:24130719

Reza, Lord Wasim; Satyanarayna, Srinath; Enarson, Donald A.; Kumar, Ajay M. V.; Sagili, Karuna; Kumar, Sujeet; Prabhakar, Levi Anand; Devendrappa, N. M.; Pandey, Ashish; Wilson, Nevin; Chadha, Sarabjit; Thapa, Badri; Sachdeva, Kuldeep Singh; Kohli, Mohan P.

2013-01-01

372

Optimal intervention strategies for tuberculosis  

NASA Astrophysics Data System (ADS)

This paper deals with the problem of optimal control of a deterministic model of tuberculosis (abbreviated as TB for tubercle bacillus). We first present and analyze an uncontrolled tuberculosis model which incorporates the essential biological and epidemiological features of the disease. The model is shown to exhibit the phenomenon of backward bifurcation, where a stable disease-free equilibrium co-exists with one or more stable endemic equilibria when the associated basic reproduction number is less than the unity. Based on this continuous model, the tuberculosis control is formulated and solved as an optimal control problem, indicating how control terms on the chemoprophylaxis and detection should be introduced in the population to reduce the number of individuals with active TB. Results provide a framework for designing the cost-effective strategies for TB with two intervention methods.

Bowong, Samuel; Aziz Alaoui, A. M.

2013-06-01

373

[Job's syndrome and miliary tuberculosis].  

PubMed

The hyper Immunoglobulin E syndrome, also known as Job's syndrome, is a rare primary immunodeficiency, its mechanisms of inheritance maybe recessive or dominant autosomal. It is characterized by high levels of IgE, eosinophilia, skin abscesses, eczema, chronic mucocutaneous candidiasis and recurrent pulmonary infections all of which contribute to the development of pneumatoceles and bronchiectasis. The most frequently isolated bacteria is Staphylococcus aureus. Currently, despite the highest survival of patients, lymphomas and other opportunistic infections have been reported. There are few reports of patients with Mycobacterium tuberculosis infection associated with hyper IgE syndrome. Therefore it is relevant that we report a case history of a patient with pulmonary tuberculosis, presenting miliary tuberculosis and severe respiratory compromise, who responded positively to standard anti-tuberculous treatment with first line drugs. PMID:25188660

Gamberale, Ana; Moreira, Ileana; Bartoletti, Bruno; Cruz, Víctor; Bezrodnik, Liliana; Alberti, Federico; Catro Zorrilla, Liliana; Palmero, Domingo

2014-01-01

374

Concentrations of CXCL8, CXCL9 and sTNFR1 in plasma of patients with pulmonary tuberculosis undergoing treatment  

Microsoft Academic Search

.\\u000a Background:  Chemokines are a class of cytokines with chemotactic properties shown to be induced by M. tuberculosis or its antigens in\\u000a vitro and in experimental infection in vivo. A few studies have also demonstrated the expression of chemokines in clinical\\u000a samples of patients with active tuberculosis (TB). In the present work, we measured the concentration of chemokines in plasma\\u000a samples

A. L. Alessandri; A. L. Souza; S. C. Oliveira; G. C. Macedo; M. M. Teixeira; A. L. Teixeira

2006-01-01

375

Antigen 85C Inhibition Restricts Mycobacterium tuberculosis Growth through Disruption of Cord Factor Biosynthesis  

PubMed Central

The antigen 85 (Ag85) protein family, consisting of Ag85A, -B, and -C, is vital for Mycobacterium tuberculosis due to its role in cell envelope biogenesis. The mycoloyl transferase activity of these proteins generates trehalose dimycolate (TDM), an envelope lipid essential for M. tuberculosis virulence, and cell wall arabinogalactan-linked mycolic acids. Inhibition of these enzymes through substrate analogs hinders growth of mycobacteria, but a link to mycolic acid synthesis has not been established. In this study, we characterized a novel inhibitor of Ag85C, 2-amino-6-propyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile (I3-AG85). I3-AG85 was isolated from a panel of four inhibitors that exhibited structure- and dose-dependent inhibition of M. tuberculosis division in broth culture. I3-AG85 also inhibited M. tuberculosis survival in infected primary macrophages. Importantly, it displayed an identical MIC against the drug-susceptible H37Rv reference strain and a panel of extensively drug-resistant/multidrug-resistant M. tuberculosis strains. Nuclear magnetic resonance analysis indicated binding of I3-AG85 to Ag85C, similar to its binding to the artificial substrate octylthioglucoside. Quantification of mycolic acid-linked lipids of the M. tuberculosis envelope showed a specific blockade of TDM synthesis. This was accompanied by accumulation of trehalose monomycolate, while the overall mycolic acid abundance remained unchanged. Inhibition of Ag85C activity also disrupted the integrity of the M. tuberculosis envelope. I3-AG85 inhibited the division of and reduced TDM synthesis in an M. tuberculosis strain deficient in Ag85C. Our results indicate that Ag85 proteins are promising targets for novel antimycobacterial drug design. PMID:22290959

Warrier, Thulasi; Tropis, Marielle; Werngren, Jim; Diehl, Anne; Gengenbacher, Martin; Schlegel, Brigitte; Schade, Markus; Oschkinat, Hartmut; Daffe, Mamadou; Hoffner, Sven; Eddine, Ali Nasser

2012-01-01

376

Paediatric Multidrug-Resistant Tuberculosis with HIV Coinfection: A Case Report.  

PubMed

Background. Tuberculosis is a major public health problem, and its control has been facing a lot of challenges with emergence of HIV. The occurrence of multidrug-resistant strain has also propounded the problem especially in children where diagnosis is difficult to make. Multidrug-resistant tuberculosis (MDR-TB) is in vitro resistant to isoniazid (H) and rifampicin (R). Paediatric multi-drug resistant tuberculosis with HIV coinfection is rare, and there is no documented report from Nigeria. Objective. To report a case of paediatric MDR-TB in Nigeria about it. Methods. The case note of the patient was retrieved, and relevant data were extracted and summarized. Results. A 9-year-old female HIV-positive pupil with a year history of recurrent cough, 3 months history of recurrent fever, and generalized weight loss was diagnosed and treated for tuberculosis but failed after retreatment. She was later diagnosed with MDR-TB and is presently on DOT-Plus regimen. Conclusion. Paediatric MDR-TB with HIV co-infection is rare. Early diagnosis and treatment is important to prevent spread of the disease. The use of Isoniazid preventive therapy is recommended for children who come in contact with patients with active tuberculosis and also for HIV patients without active tuberculosis. PMID:23424597

Nwokeukwu, Huldah I; Okafor, Paulinus N; Okorie, Onuka; Ukpabi, Ihuoma K

2013-01-01

377

Paediatric Multidrug-Resistant Tuberculosis with HIV Coinfection: A Case Report  

PubMed Central

Background. Tuberculosis is a major public health problem, and its control has been facing a lot of challenges with emergence of HIV. The occurrence of multidrug-resistant strain has also propounded the problem especially in children where diagnosis is difficult to make. Multidrug-resistant tuberculosis (MDR-TB) is in vitro resistant to isoniazid (H) and rifampicin (R). Paediatric multi-drug resistant tuberculosis with HIV coinfection is rare, and there is no documented report from Nigeria. Objective. To report a case of paediatric MDR-TB in Nigeria about it. Methods. The case note of the patient was retrieved, and relevant data were extracted and summarized. Results. A 9-year-old female HIV-positive pupil with a year history of recurrent cough, 3 months history of recurrent fever, and generalized weight loss was diagnosed and treated for tuberculosis but failed after retreatment. She was later diagnosed with MDR-TB and is presently on DOT-Plus regimen. Conclusion. Paediatric MDR-TB with HIV co-infection is rare. Early diagnosis and treatment is important to prevent spread of the disease. The use of Isoniazid preventive therapy is recommended for children who come in contact with patients with active tuberculosis and also for HIV patients without active tuberculosis. PMID:23424597

Nwokeukwu, Huldah I.; Okafor, Paulinus N.; Okorie, Onuka; Ukpabi, Ihuoma K.

2013-01-01

378

Associations Between Human Leukocyte Antigen Class I Variants and the Mycobacterium tuberculosis Subtypes Causing Disease  

PubMed Central

Background.?The development of active tuberculosis disease has been shown to be multifactorial. Interactions between host and bacterial genotype may influence disease outcome, with some studies indicating the adaptation of M. tuberculosis strains to specific human populations. Here we investigate the role of the human leukocyte antigen (HLA) class I genes in this biological process. Methods.?Three hundred patients with tuberculosis from South Africa were typed for their HLA class I alleles by direct sequencing. Mycobacterium tuberculosis genotype classification was done by IS6110 restriction fragment length polymorphism genotyping and spoligotyping. Results.?We showed that Beijing strain occurred more frequently in individuals with multiple disease episodes (P < .001) with the HLA-B27 allele lowering the odds of having an additional episode (odds ratio, 0.21; P = .006). Associations were also identified for specific HLA types and disease caused by the Beijing, LAM, LCC, and Quebec strains. HLA types were also associated with disease caused by strains from the Euro-American or East Asian lineages, and the frequencies of these alleles in their sympatric human populations identified potential coevolutionary events between host and pathogen. Conclusions.?This is the first report of the association of human HLA types and M. tuberculosis strain genotype, highlighting that both host and pathogen genetics need to be taken into consideration when studying tuberculosis disease development. PMID:23945374

Salie, Muneeb; van der Merwe, Lize; Möller, Marlo; Daya, Michelle; van der Spuy, Gian D.; van Helden, Paul D.; Martin, Maureen P.; Gao, Xiao-jiang; Warren, Robin M.; Carrington, Mary; Hoal, Eileen G.

2014-01-01

379

Tuberculosis in Pregnancy  

PubMed Central

Tuberculosis (TB) during pregnancy and in the perinatal period was once considered to be an infrequent event in the United States. After a decade of steady decline, however, the disease has begun a resurgence. According to the CDC, a 20% increase in the number of reported cases occurred between 1985 and 1992. The factors associated with this increase are the emergence of human immunodeficiency virus (HIV) infection, the development of drug-resistant organisms, substance abuse, homelessness, and immigration. Environmental factors promoting transmission can be found in overcrowded areas such as correctional facilities, nursing homes, hospitals, and migrant-worker camps. For a large number of medically underserved women, the obstetrician is the only interface with medical care, as most of these patients do not have primary-care providers. It is important, therefore, that health-care providers recognize the clinical symptoms of TB and follow the recognized guidelines for antenatal screening for TB because the omission of these steps can lead to potentially disastrous sequelae in the fetus and neonate. PMID:18476074

Apuzzio, Joseph J.

1996-01-01

380

Field Friendly Tuberculosis Biosensor  

NASA Astrophysics Data System (ADS)

Tuberculosis (TB) is a fading threat in the United States, but in the developing world it is still a major health-care concern. Given the rising number of cases and lack of resources, there is a desperate need for an affordable, portable detection system. We are working towards the development of a field-friendly immunological biosensor that utilizes florescence microscopy to undertake this task. We observe fluorescently labeled antibodies/antigens as they bind to a glass slide treated with polyethylene glycol (PEG) in order to inhibit non-specific adsorption. Antibodies against the antigens of interest are bound to the PEGylated glass slides via biotin-streptavidin interactions. Then, fluorescently labeled antibodies are mixed with different concentrations of TB antigens and this solution is incubated on the treated glass slides for 30 minutes. The slides are thoroughly rinsed with water following the incubation period. The antigens are then detected by fluorescence using a low-cost biosensor. Our system includes a ``supermarket-scanner'' HeNe laser, home-built electronics, off-the-shelf optics and a Si photodiode. Work is underway to incorporate a flow-cell into the system, in a small portable box.

Proper, N.; Scherman, M. S.; Jevsevar, K. L.; Stone, J.; McNeil, M. R.; Krapf, D.

2009-10-01

381

Central nervous system tuberculosis.  

PubMed

Tuberculosis (TB) has shown a resurgence in nonendemic populations in recent years and accounts for 8 million deaths annually in the world. Central nervous system involvement is one of the most serious forms of this infection, acting as a prominent cause of morbidity and mortality in developing countries. The rising number of cases in developed countries is mostly attributed to factors such as the pandemic of acquired immunodeficiency syndrome and increased migration in a globalized world. Mycobacterium TB is responsible for almost all cases of tubercular infection in the central nervous system. It can manifest in a variety of forms as tuberculous meningitis, tuberculoma, and tubercular abscess. Spinal infection may result in spondylitis, arachnoiditis, and/or focal intramedullary tuberculomas. Timely diagnosis of central nervous system TB is paramount for the early institution of appropriate therapy, because delayed treatment is associated with severe morbidity and mortality. It is therefore important that physicians and radiologists understand the characteristic patterns, distribution, and imaging manifestations of TB in the central nervous system. Magnetic resonance imaging is considered the imaging modality of choice for the study of patients with suspected TB. Advanced imaging techniques including magnetic resonance perfusion and diffusion tensor imaging may be of value in the objective assessment of therapy and to guide the physician in the modulation of therapy in these patients. PMID:24887691

Torres, Carlos; Riascos, Roy; Figueroa, Ramon; Gupta, Rakesh K

2014-06-01

382

Role of Interleukin 6 in Innate Immunity to Mycobacterium tuberculosis Infection  

PubMed Central

Background.?Mycobacterium tuberculosis can grow in the hostile intracellular environment of macrophages by actively evading macrophage-associated antibacterial activities. The stress response factor SigH contributes to this process by modulating ?-chemokine and interleukin 6 (Il6) expression. Hence, Il6 is of critical importance for acquired immunity against M. tuberculosis infection. Here, we attempted to better characterize the role of Il6 in the immune response to M. tuberculosis infection. Methods.?A small interfering RNA–based approach was used to silence expression of the Il6 transcript in host macrophages infected with a wild-type strain of M. tuberculosis or an attenuated mutant strain of M. tuberculosis (Mtb:?-sigH). The outcome was measured by the analysis of bacterial burden and transcriptome-wide analysis of host gene expression. Transcriptome results were confirmed via quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Results.?Wild type and Mtb:?-sigH infection of host macrophages in which Il6 had been silenced resulted in increased expression of interferon-inducible genes, especially those involved in type I interferon signaling. The expression of Ly-6 genes was significantly higher in cells infected with Mtb:?-sigH, compared with those infected with the wild-type strain (P < .05). Conclusions.?M. tuberculosis regulates host Il6 production to inhibit type I interferon signaling and, consequently, disease progression. Mtb:?-sigH is associated with delayed activation of macrophages, compared with the wild-type strain, and with delayed inflammatory stimuli as consequence. These findings have important implications for improving understanding of the mechanisms behind M. tuberculosis virulence and pathogenesis and provide an initial road map to further investigate the mechanisms that may account for the deleterious effects of type I interferons in M. tuberculosis infection. PMID:23359591

Martinez, Alejandra N.; Mehra, Smriti; Kaushal, Deepak

2013-01-01

383

Tuberculosis infection and disease among schoolchildren: the influence of the HIV epidemic and of other factors  

PubMed Central

BACKGROUND: The HIV/AIDS epidemic has caused an excess of tuberculosis cases in Spain and in other countries, but its impact on tuberculosis infection is less well understood. This study presents a massive screening undertaken to estimate the prevalence of tuberculous infection in a cohort of primary school entrants. The evolution of the risk of infection is studied by comparison with previous data in the same population. METHODS: Tuberculin skin test screening with 2TU of PPD RT 23 of first grade students in the primary schools of Barcelona, in the 1994-95 school year (cohort born in 1988). Information was also sought from families of unscreened children. Contacts of PPD+ children were traced to locate index cases. The results were also linked to the case registry of the tuberculosis control programme. RESULTS: The prevalence of tuberculin reactors free of BCG vaccination among the 11,080 schoolchildren screened belonging to the 1988 cohort was 0.76%. A 3% annual decline in the annual risk of infection is estimated by comparison with previous data. The identification of 24 cases with a previous history of tuberculosis disease and of 13 cases with active disease diagnosed after the screening was possible by the follow up of these tuberculin positive children and of the information provided by families of unscreened pupils. The screening detected 1.5 new cases of tuberculosis per 1000 tuberculin tests performed. Tuberculosis infection could be traced to HIV infected tuberculosis cases for at least 6% of the positive schoolchildren. CONCLUSIONS: The decline of the annual risk of infection continues in Barcelona, although at a slower pace than before the HIV/AIDS epidemic, probably attributable to the influence of injecting drug users with smear positive tuberculosis and HIV/AIDS.   PMID:10396472

Villalbi, J. R.; Galdos-Tanguis, H.; Cayla, J. A.; Casanas, P.; Ferrer, A.; Nebot, M.

1999-01-01

384

MODS for Tuberculosis Screening Prior to Isoniazid Preventive Therapy in HIV-Infected Persons  

PubMed Central

Background Active tuberculosis (TB) must be excluded before initiating isoniazid preventive therapy (IPT) in HIV-infected persons, but currently used screening strategies suffer from poor sensitivity and specificity and high patient attrition rates. Liquid TB culture is now recommended for the detection of Mycobacterium tuberculosis in TB suspects. This study compared the efficacy, effectiveness and speed of the microscopic-observation drug-susceptibility (MODS) assay with currently used strategies for tuberculosis screening prior to IPT in HIV-infected persons. Methods 471 HIV-infected IPT candidates at three hospitals in Lima, Peru, were enrolled into a prospective comparison of tuberculosis screening strategies, including laboratory, clinical and radiographic assessments. Results Of 435 patients who provided two sputum samples, M. tuberculosis was detected in 27 (6.2%) by MODS, 22 (5.1%) by Lowenstein-Jensen culture and 7 (1.6%) by smear. Of patients with any positive microbiological test, a MODS culture was positive in 96% by 14 days and 100% by 21 days. MODS simultaneously detected multidrug-resistant tuberculosis in two patients. Screening strategies involving combinations of clinical assessment, chest radiograph and sputum smear were less effective than two liquid TB cultures in accurately diagnosing and excluding tuberculosis (p<0.01). Screening strategies that included non-culture tests had poor sensitivity and specificity. Conclusions MODS identified, and reliably excluded, cases of pulmonary tuberculosis more accurately than other screening strategies, while providing results significantly faster than Lowenstein-Jensen culture. The streamlining of TB rule-out through the use of liquid culture-based strategies could help facilitate the massive upscaling of IPT required to reduce HIV and TB morbidity and mortality. PMID:20192727

Reddy, Krishna P.; Brady, Mark F.; Gilman, Robert H.; Coronel, Jorge; Ñavincopa, Marcos; Ticona, Eduardo; Chavez, Gonzalo; Sánchez, Eduardo; Rojas, Christian; Solari, Lely; Valencia, Jorge; Pinedo, Yvett; Benites, Carlos; Friedland, Jon S.; Moore, David A.J.

2010-01-01

385

Clinical response of newly diagnosed HIV seropositive & seronegative pulmonary tuberculosis patients with the RNTCP Short Course regimen in Pune, India  

PubMed Central

Background & objectives In the Revised National Tuberculosis Control Programme (RNTCP) in India prior to 2005, TB patients were offered standard DOTS regimens without knowledge of HIV status. Consequently such patients did not receive anti-retroviral therapy (ART) and the influence of concomitant HIV infection on the outcome of anti-tuberculosis treatment remained undetermined. This study was conducted to determine the results of treatment of HIV seropositive pulmonary tuberculosis patients with the RNTCP (DOTS) regimens under the programme in comparison with HIV negative patients prior to the availability of free ART in India. Methods Between September 2000 and July 2006, 283 newly diagnosed pulmonary TB patients were enrolled in the study at the TB Outpatient Department at the Talera Hospital in the Pimpri Chinchwad Municipal Corporation area at Pune (Maharashtra): they included 121 HIV seropositive and 162 HIV seronegative patients. They were treated for tuberculosis as per the RNTCP in India. This study was predominantly conducted in the period before the free ART become available in Pune. Results At the end of 6 months of anti-TB treatment, 62 per cent of the HIV seropositive and 92 per cent of the HIV negative smear negative patients completed treatment and were asymptomatic; among smear positive patients, 70 per cent of the HIV-seropositive and 81 per cent of HIV seronegative pulmonary TB patients were cured. Considering the results in the smear positive and smear negative cases together, treatment success rates were substantially lower in HIV positive patients than in HIV negative patients, (66% vs 85%). Further, 29 per cent of HIV seropositive and 1 per cent of the HIV seronegative patients expired during treatment. During the entire period of 30 months, including 6 months of treatment and 24 months of follow up, 61 (51%) of 121 HIV positive patients died; correspondingly there were 6 (4%) deaths among HIV negative patients. Interpretation & conclusions The HIV seropositive TB patients responded poorly to the RNTCP regimens as evidenced by lower success rates with chemotherapy and high mortality rates during treatment and follow up. There is a need to streamline the identification and management of HIV associated TB patients in the programme with provision of ART to achieve high cure rates for TB, reducing mortality rates and ensuring a better quality of life. PMID:21623038

Tripathy, S.; Anand, A.; Inamdar, V.; Manoj, M.M.; Khillare, K.M.; Datye, A.S.; Iyer, R.; Kanoj, D.M.; Thakar, M.; Kale, V.; Pereira, M.; Risbud, A.R.

2011-01-01

386

Extrapulmonary Tuberculosis: Mycobacterium tuberculosis Strains and Host Risk Factors in a Large Urban Setting in Brazil  

PubMed Central

Background Factors related to the development of extrapulmonary forms of tuberculosis (EPTB) are still poorly understood, particularly in high-endemic countries like Brazil. The objective of the paper is to determine host and Mycobacterium tuberculosis (MTB) strain-related factors associated with the development of EPTB in Espírito Santo state, Brazil. Methods and Findings We conducted a retrospective laboratory-based surveillance study of new tuberculosis (TB) cases diagnosed in Espírito Santo state, Brazil between 1998 and 2007. We genotyped 612 isolates of MTB from 606 TB patients using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) typing and compared sociodemographic and clinical characteristics of patients with pulmonary TB (PTB) and EPTB. Among 606 patients, 464 (77%) had PTB, 79 (13%) had EPTB, 51 (8%) had both, and 12 (2%) had miliary TB. The IS6110 RFLP analysis demonstrated that 250 (41%) isolates belonged to clustered RFLP patterns, 27 (11%) of which were from EPTB. We identified 73 clusters including 35 (48%) composed of 2 isolates each. By spoligotyping, 506 (83%) MTB isolates fell into known patterns and 106 (17%) fell into patterns with no family assignment; 297 (48%) isolates belonged to the Latin-American Mediterranean family. Higher school level (4-7 years OR: 0.16 95% CI 0.34-0.73 and > 8 years of education, OR 0.06 95% CI 0.009-0.50) white ethnicity (OR: 2.54 95% CI 1.03-6.25) and HIV infection (OR: 16.83 95% CI 5.23-54.18) were associated with EPTB. No specific strain lineage or percentage of clustering was associated with EPTB. Conclusions These results demonstrate that risk factors for EPTB are related more to host than to MTB strain lineage characteristics. PMID:24098337

Gomes, Teresa; Vinhas, Solange Alves; Reis-Santos, Bárbara; Palaci, Moisés; Peres, Renata Lyrio; Aguiar, Paola P.; Ribeiro, Fabiola Karla Correa; Marques, Hebert Silva; Dettoni, Valdério do Valle; Johnson, John L.; Riley, Lee W.; Maciel, Ethel Leonor

2013-01-01

387

Genetic Diversity of Mycobacterium tuberculosis in Peru and Exploration of Phylogenetic Associations with Drug Resistance  

PubMed Central

Background There is limited available data on the strain diversity of M tuberculosis in Peru, though there may be interesting lessons to learn from a setting where multidrug resistant TB has emerged as a major problem despite an apparently well-functioning DOTS control programme. Methods Spoligotyping was undertaken on 794 strains of M tuberculosis collected between 1999 and 2005 from 553 community-based patients and 241 hospital-based HIV co-infected patients with pulmonary tuberculosis in Lima, Peru. Phylogenetic and epidemiologic analyses permitted identification of clusters and exploration of spoligotype associations with drug resistance. Results Mean patient age was 31.9 years, 63% were male and 30.4% were known to be HIV+. Rifampicin mono-resistance, isoniazid mono-resistance and multidrug resistance (MDR) were identified in 4.7%, 8.7% and 17.3% of strains respectively. Of 794 strains from 794 patients there were 149 different spoligotypes. Of these there were 27 strains (3.4%) with novel, unique orphan spoligotypes. 498 strains (62.7%) were clustered in the nine most common spoligotypes: 16.4% SIT 50 (clade H3), 12.3% SIT 53 (clade T1), 8.3% SIT 33 (LAM3), 7.4% SIT 42 (LAM9), 5.5% SIT 1 (Beijing), 3.9% SIT 47 (H1), 3.0% SIT 222 (clade unknown), 3.0% SIT1355 (LAM), and 2.8% SIT 92 (X3). Amongst HIV-negative community-based TB patients no associations were seen between drug resistance and specific spoligotypes; in contrast HIV-associated MDRTB, but not isoniazid or rifampicin mono-resistance, was associated with SIT42 and SIT53 strains. Conclusion Two spoligotypes were associated with MDR particularly amongst patients with HIV. The MDR-HIV association was significantly reduced after controlling for SIT42 and SIT53 status; residual confounding may explain the remaining apparent association. These data are suggestive of a prolonged, clonal, hospital-based outbreak of MDR disease amongst HIV patients but do not support a hypothesis of strain-specific propensity for the acquisition of resistance-conferring mutations. PMID:23826083

Sheen, Patricia; Couvin, David; Grandjean, Louis; Zimic, Mirko; Dominguez, Maria; Luna, Giannina; Gilman, Robert H.; Rastogi, Nalin; Moore, David A. J.

2013-01-01

388

Genotypic detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis strains by DNA sequencing: a randomized trial  

PubMed Central

Background Tuberculosis is a growing international health concern. It is the biggest killer among the infectious diseases in the world today. Early detection of drug resistance allows starting of an appropriate treatment. Resistance to drugs is due to particular genomic mutations in specific genes of Mycobacterium tuberculosis(MTB). The aim of this study was to identify the presence of Isoniazid (INH) and Rifampicin(RIF) drug resistance in new and previously treated tuberculosis (TB) cases using DNA sequencing. Methods This study was carried out on 153 tuberculous patients with positive Bactec 460 culture for acid fast bacilli. Results Of the 153 patients, 105 (68.6%) were new cases and 48 (31.4%) were previously treated cases. Drug susceptibility testing on Bactec revealed 50 resistant cases for one or more of the first line antituberculous. Genotypic analysis was done only for rifampicin resistant specimens (23 cases) and INH resistant specimens (26 cases) to detect mutations responsible for drug resistance by PCR amplification of rpoB gene for rifampicin resistant cases and KatG gene for isoniazid resistant cases. Finally, DNA sequencing was done for detection of mutation within rpoB and KatG genes. Genotypic analysis of RIF resistant cases revealed that 20/23 cases (86.9%) of RIF resistance were having rpoB gene mutation versus 3 cases (13.1%) having no mutation with a high statistical significant difference between them (P < 0.001). Direct sequencing of Kat G gene revealed point mutation in 24/26 (92.3%) and the remaining 2/26 (7.7%) had wild type KatG i.e. no evidence of mutation with a high statistical significant difference between them (P < 0.001). Conclusion We can conclude that rifampicin resistance could be used as a useful surrogate marker for estimation of multidrug resistance. In addition, Genotypic method was superior to that of the traditional phenotypic method which is time-consuming taking several weeks or longer. PMID:19183459

Abdelaal, Amina; El-Ghaffar, Hassan Abd; Zaghloul, Mohammad Hosam Eldeen; El mashad, Noha; Badran, Ehab; Fathy, Amal

2009-01-01

389

The Calf Model of Immunity for Development of a Vaccine Against Tuberculosis  

Technology Transfer Automated Retrieval System (TEKTRAN)

Abstract: Tuberculosis (TB) remains a major public health threat and can be considered a reemerging disease due to many factors and is especially problematic in developing countries where co-infection with HIV significantly increases morbidity and mortality. Vaccination is a low cost and effective ...

390

Tumor necrosis factor-? is required in the protective immune response against mycobacterium tuberculosis in mice  

Microsoft Academic Search

Understanding the immunological mechanisms of protection and pathogenesis in tuberculosis remains problematic. We have examined the extent to which tumor necrosis factor-? (TNF?) contributes to this disease using murine models In which the action of TNF? is inhibited. TNFa was neutralized In vivo by monoclonal antibody; in addition, a mouse strain with a disruption in the gene for the 55

JoAnne L. Flynn; Marsha M. Goldstein; John Chan; Karla J. Triebold; Klaus Pfeffer; Charles J. Lowenstein; Robert Schrelber; Tak W. Mak; Barry R. Bloom

1995-01-01

391

An in vitro model of the leukocyte interactions associated with granuloma formation in Mycobacterium tuberculosis infection  

Microsoft Academic Search

The principal defense of the human host against a Mycobacterium tuberculosis infection is the formation of granulomas, organized collections of activated macrophages, including epithelioid and multinucleated giant cells, surrounded by lymphocytes. This granuloma can sequester and contain the bacteria preventing active disease, and if the granuloma is maintained, these bacteria may remain latent for a person's lifetime. Secretion of a

Kristin A Birkness; Jeannette Guarner; Suraj B Sable; Ralph A Tripp; Kathryn L Kellar; Jeanine Bartlett; Frederick D Quinn

2007-01-01

392

Functional Correlations of Pathogenesis-Driven Gene Expression Signatures in Tuberculosis  

Microsoft Academic Search

Tuberculosis remains a major health threat and its control depends on improved measures of prevention, diagnosis and treatment. Biosignatures can play a significant role in the development of novel intervention measures against TB and blood transcriptional profiling is increasingly exploited for their rational design. Such profiles also reveal fundamental biological mechanisms associated with the pathology of the disease. We have

Jeroen Maertzdorf; Martin Ota; Dirk Repsilber; Hans J. Mollenkopf; January Weiner; Philip C. Hill; Stefan H. E. Kaufmann

2011-01-01

393

New old challenges in tuberculosis: Potentially effective nanotechnologies in drug delivery  

Microsoft Academic Search

Tuberculosis (TB) is the second most deadly infectious disease. Despite potentially curative pharmacotherapies being available for over 50years, the length of the treatment and the pill burden can hamper patient lifestyle. Thus, low compliance and adherence to administration schedules remain the main reasons for therapeutic failure and contribute to the development of multi-drug-resistant (MDR) strains. Pediatric patients constitute a high

Alejandro Sosnik; Ángel M. Carcaboso; Romina J. Glisoni; Marcela A. Moretton; Diego A. Chiappetta

2010-01-01

394

Hypoadrenalism is not associated with early mortality during tuberculosis treatment in Malawi  

Microsoft Academic Search

SETTING: In the developing world, early mortality within 1 month of commencing tuberculosis (TB) treatment is high, particularly with human immunodeficiency virus (HIV) co-infection. In Malawi, 40% of those who die do so in the first month of treatment. Reasons remain unclear and may include delayed diagnosis, opportunistic infections, immune restoration inflammatory syndrome (IRIS) or malnutrition. One possible contributing factor

M. B. Beadsworth; J. J. van Oosterhout; M. J. Diver; E. B. Faragher; A. Shenkin; H. C. Mwandumba; S. Khoo; T. O'Dempsey; S. B. Squire; E. E. Zijlstra

2008-01-01

395

45 CFR 96.127 - Requirements regarding tuberculosis.  

Code of Federal Regulations, 2010 CFR

...2010-10-01 false Requirements regarding tuberculosis. 96.127 Section 96.127 Public...96.127 Requirements regarding tuberculosis. (a) States shall require...with the State Department of Health/Tuberculosis Control Officer, which address how...

2010-10-01

396

45 CFR 96.127 - Requirements regarding tuberculosis.  

Code of Federal Regulations, 2011 CFR

...2011-10-01 false Requirements regarding tuberculosis. 96.127 Section 96.127 Public...96.127 Requirements regarding tuberculosis. (a) States shall require...with the State Department of Health/Tuberculosis Control Officer, which address how...

2011-10-01

397

45 CFR 96.127 - Requirements regarding tuberculosis.  

Code of Federal Regulations, 2012 CFR

...2012-10-01 false Requirements regarding tuberculosis. 96.127 Section 96.127 Public...96.127 Requirements regarding tuberculosis. (a) States shall require...with the State Department of Health/Tuberculosis Control Officer, which address how...

2012-10-01

398

45 CFR 96.127 - Requirements regarding tuberculosis.  

Code of Federal Regulations, 2013 CFR

...2013-10-01 false Requirements regarding tuberculosis. 96.127 Section 96.127 Public...96.127 Requirements regarding tuberculosis. (a) States shall require...with the State Department of Health/Tuberculosis Control Officer, which address how...

2013-10-01

399

Truman State University Student Health Center Tuberculosis Screening Form  

E-print Network

Truman State University Student Health Center Tuberculosis Screening Form Name been exposed to Tuberculosis since your last TB skin test? Yes No If yes, when and where did the exposure occur? ________________________________________ Have you ever been treated for Tuberculosis? Yes

Gering, Jon C.

400

45 CFR 96.127 - Requirements regarding tuberculosis.  

...2014-10-01 false Requirements regarding tuberculosis. 96.127 Section 96.127 Public...96.127 Requirements regarding tuberculosis. (a) States shall require...with the State Department of Health/Tuberculosis Control Officer, which address how...

2014-10-01

401

A Defined Tuberculosis Vaccine Candidate Boosts BCG and Protects Against Multidrug Resistant Mycobacterium tuberculosis  

PubMed Central

Despite the widespread use of Mycobacterium bovis bacillus Calmette-Guerin (BCG) childhood vaccine, tuberculosis (TB) remains a serious global health problem. A successful vaccine against TB that replaces or boosts BCG will include antigens that induce or recall appropriate T cell responses. Four Mycobacterium tuberculosis (Mtb) antigens, including members of the virulence factor families PE/PPE and EsX, or antigens associated with latency were produced as a single recombinant fusion protein. When administered with the adjuvant GLA-SE, a stable oil-in-water nanoemulsion, the fusion protein ID93 was immunogenic in mice, guinea pigs, and cynomolgus monkeys. In mice, ID93/GLA-SE combination induced polyfunctional CD4 TH1-cell responses characterized by antigen-specific IFN-gamma, tumor necrosis factor and interleukin-2, as well as a reduction in the number of bacteria in the lungs of animals subsequently infected with virulent or multidrug resistant Mtb strains. Furthermore, boosting BCG-vaccinated guinea pigs with ID93/GLA-SE resulted in reduced pathology and fewer bacilli, and prevented the death of animals challenged with virulent Mtb. Finally, ID93 elicited polyfunctional effector CD4 and CD8 T-cell responses in BCG-vaccinated or Mtb-exposed human peripheral blood mononuclear cells. This study establishes that the protein subunit vaccine ID93/GLA-SE protects against TB and MDR-TB in animals, and is a candidate for boosting the protective efficacy of the childhood BCG vaccine. PMID:20944089

Bertholet, Sylvie; Ireton, Gregory C.; Ordway, Diane J.; Windish, Hillarie Plessner; Pine, Samuel O.; Kahn, Maria; Phan, Tony; Orme, Ian M.; Vedvick, Thomas S.; Baldwin, Susan L.; Coler, Rhea N.; Reed, Steven G.

2011-01-01

402

High Prevelance of Rifampin-Monoresistant Tuberculosis: A Retrospective Analysis among Iranian Pulmonary Tuberculosis Patients  

PubMed Central

We determined the prevalence of rifampin-monoresistant tuberculosis (RMR-TB) in Iran. Because development of RMR-TB is not common, we also identified the major risk factors associated with RMR-TB reported from different provinces of Iran. Data for 3,020 TB patients who remained or became smear positive after two, four, six, and nine months of standard first-line chemotherapy were retrospectively analyzed. Of 3,020 patients, 1,242 patients (41.1%) were culture and DNA positive for Mycobacterium tuberculosis. Of these patients, 73 (7.4%) patients had monoresistant isolates to rifampin, which was significantly higher than that for multidrug-resistant TB (5.8%). The average rate of RMR-TB in the studied population ranged from 5% to 10%. Classical investigation showed that 33.6% of patients had either a previous or family history of TB. Molecular epidemiology methods (i.e., spoligotyping and Mycobacterium intespersed repetitive unit–variable number tandem repeat), defined transmission link in three clusters (13%). These results outline the urgent need for a comprehensive plan for detection and treatment of RMR-TB cases. PMID:24189362

Velayati, Ali Akbar; Farnia, Parissa; Mozafari, Mohadese; Sheikholeslami, Maryam Fatemeh; Karahrudi, Mona Afraei; Tabarsi, Payam; Hoffner, Sven

2014-01-01

403

New tuberculosis vaccines.  

PubMed

The current tuberculosis (TB) vaccine, bacille Calmette-Guerin (BCG), is a live vaccine used worldwide, as it protects against severe forms of the disease, saving thousands of lives every year, but its efficacy against pulmonary forms of TB, responsible for transmission of the diseases, is variable. For more than 80 years now no new TB vaccines have been successfully developed. Over the last decade the effort of the scientific community has resulted in the design and construction of promising vaccine candidates. The goal is to develop a new generation of vaccines effective against respiratory forms of the disease. We will focus this review on new prophylactic vaccine candidates that aim to prevent TB diseases. Two are the main strategies used to improve the immunity conferred by the current BCG vaccine, by boosting it with new subunit vaccines, and a second strategy is focused on the construction of new more effective live vaccines, capable to replace the current BCG and to be used as prime vaccines. After rigorous preclinical studies in different animal models new TB vaccine candidates enter in clinical trials in humans. First, a small Phase I for safety followed by immunological evaluation in Phase II trials and finally evaluated in large population Phase III efficacy trials in endemic countries. At present BCG prime and boost with different subunit vaccine candidates are the more advanced assessed in Phase II. Two prime vaccines (based on recombinant BCG) have been successfully evaluated for safety in Phase I trials. A short number of live attenuated vaccines are in advance preclinical studies and the candidates ready to enter Phase I safety trials are produced under current good manufacturing practices. PMID:21420568

Martín Montañés, Carlos; Gicquel, Brigitte

2011-03-01

404

HIV and tuberculosis in India.  

PubMed

The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as the leading cause of death. Further,there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. The diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography,which has problems of specificity. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resourc-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping drug toxicities,risk of immune reconstitution inflammatory syndrome (IRIS) and challenges related to adherence. From a programmatic point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control programs, in India. PMID:19208978

Swaminathan, Soumya; Nagendran, G

2008-11-01

405

Epidemiological basis of tuberculosis eradication  

PubMed Central

As knowledge of the epidemiology of tuberculosis in Greenland has increased, it has become evident that the majority of cases develop long after the primary infection and that it would therefore be valuable from the public health point of view if the disease rate among naturally infected persons could be reduced. To examine the possibility of achieving this, a double-blind drug trial with isoniazid and a placebo was conducted among some 70% of the adult population of western Greenland. The results show that throughout the six years of the study the incidence of tuberculosis was lower in the group treated with isoniazid and that this reduction occurred whether the initial X-rays pictures were normal or showed suspicious or healed lesions. It is concluded that chemoprophylaxis programmes should probably be administered only to selected groups of the population. The delimitation of such groups is discussed on the basis of their tuberculosis risk and of the expected yield in terms of reduction in tuberculosis prevalence. PMID:5335457

Horwitz, Ole; Payne, Penelope G.; Wilbek, Erik

1966-01-01

406

[Recent advances in tuberculosis immunity].  

PubMed

Primary tuberculosis infection is acquired by the inhalation of droplets containing Mycobacterium tuberculosis (MTB) bacilli. Only 5-10% of those individuals infected by MTB develop clinical diseases, and disease presentation itself is heterogeneous, suggesting that host factors play a large role in disease susceptibility. Protective immunity in the lung against MTB consist of the innate immunity in which alveolar macrophages play an central role, and the acquired immunity including various type of effector T cells. Recent studies show that the important roles of the receptors which recognize MTB for the development of protective immunity, the difference in the anti-MTB activity of macrophages between human and mice, the macrophage-heterogeneity that affects the anti-MTB activity, the role of IL-10 in the activation of anti-MTB activity of human macrophages, and the role of Th17/IL-17, Th22/ IL-22 and TNF in the protective immunity against human tuberculosis. In this review, these recent advances in tuberculosis immunity will be described. PMID:22514942

Akagawa, Kiyoko S

2012-02-01

407

Tuberculosis Prevention in College Students  

ERIC Educational Resources Information Center

To help college health services in all parts of the country improve their approach to latent tuberculosis, two Listservs were provided for them to post their questions on dealing with TB infection. In this article, the authors present some of the questions posted in the Listservs and their corresponding answers. In their answers, the authors have…

Lerman, Stephen J.; Bernardo, John; Daly, Jennifer S.; Husson, Robert

2004-01-01

408

A tuberculosis survey in Kenya*  

PubMed Central

The Government of Kenya, wanting to assess the extent of the tuberculosis problem in the Colony and Protectorate as an essential preliminary to a control programme, requested the assistance of WHO in carrying out a survey. The purpose was to establish the over-all prevalence for Kenya of tuberculous infection and pulmonary tuberculosis. From a population of about six million people, 8700 were selected at random for tuberculin testing, chest X-ray and bacteriological examination. The results of examination of this small sample indicate that among the 3.5 million Africans aged 10 years and over there are approximately 110 000 cases and suspected cases of pulmonary tuberculosis, and that 3% of the children aged 0-4 years and 13% of those aged 5-9 are infected. The problem of tuberculosis control in Kenya is undoubtedly a big one, the population being scattered over vast areas. However, the excellent co-operation of the population throughout the present survey suggests that mass control measures might meet with considerable success. PMID:14493266

Roelsgaard, E.; Nyboe, J.

1961-01-01

409

[An unusual presentation of tuberculosis].  

PubMed

A 67-year-old male was hospitalized because of nonspecific symptoms and bilateral pleural effusions. He gave no history of cough, dyspnea or thoracic pain. The blood counts showed moderate anemia and high-grade lymphopenia. The tuberculin test and the anergy-panel were both negative. Testing for HIV was negative. Analysis of pleural fluid showed an exudate with 47% lymphocytes and absence of acid-fast bacilli on Ziehl-Neelsen smear. On histologic examination, the pleural tissue showed no evidence of granuloma. However, cultures for mycobacteria of pleural tissue yielded M. tuberculosis. In this case of pleural tuberculosis, leading symptoms were absent and the tuberculin test was negative in the presence of active tuberculosis. In addition, the cells in the pleural effusion were not predominantly lymphocytic. Patients presenting with unclear effusion should undergo extensive investigations, including a tuberculin test, and anergy panel, pleural fluid cultures, and pleural biopsy with cultures for microorganisms, with the object of establishing or ruling out pleural tuberculosis. PMID:9011935

Lefkovits, M; Reusser, P

1996-12-28

410

Childhood Tuberculosis in General Practice.  

PubMed

Tuberculosis (TB) in children is a common cause of morbidity. Diagnosis is difficult because of paucibacillary nature of illness and difficulty in obtaining appropriate samples. Children presenting with poor weight gain, fever with or without cough for more than two weeks or contact with an adult in family with pulmonary tuberculosis should be investigated for TB. In all suspected cases of tuberculosis initial investigations include radiograph of chest (CXR) and Mantoux test. If CXR is suggestive of TB, an ambulatory gastric aspirate and induced sputum for acid fast bacilli (AFB) smear may be carried out in two days. Children with AFB positive or abnormal CXR with positive Mantoux test should be started on Antitubercular therapy (ATT). Rest of the patients require more investigations and should be referred to a specialist. All children with newly diagnosed tuberculosis should be treated with 6 mo of ATT (two months with 4 drugs, followed by four months with 2 drugs). Children on ATT should be monitored for improvement in symptoms and weight gain along with side effects of medications. CXR should be done after completion of treatment. PMID:25280927

Kumar, Prawin; Kumar, Amber; Lodha, Rakesh; Kabra, S K

2014-10-01

411

Multidrug resistant to extensively drug resistant tuberculosis: What is next?  

Microsoft Academic Search

Drug resistant tuberculosis is a man made problem. While tuberculosis is hundred percent curable, multidrug resistant tuberculosis\\u000a (MDR-TB) is difficult to treat. Inadequate and incomplete treatment and poor treatment adherence has led to a newer form of\\u000a drug resistance known as extensively drug resistant tuberculosis (XDR-TB). XDR-TB is defined as tuberculosis caused by Mycobacterium tuberculosis strain, which is resistant to

Amita Jain; Pratima Dixit

2008-01-01

412

Tuberculosis Screening at 2 San Diego High Schools With High-Risk Populations  

Microsoft Academic Search

Background: High immigration rates contribute to the high incidence of pediatric tuberculosis (TB) in San Diego, Calif. Adolescents frequently have poor access to health care and may not receive appropriate TB screening. School-based screening has been ineffective in detect- ing TB in other parts of the country. Objective: To determine the prevalence of TB infec- tion and disease in a

Alice L. Pong; Bronwen J. Anders; Kathleen S. Moser; Monica Starkey; Almut Gassmann; Richard E. Besser

1998-01-01

413

Assessing vaccination as a control strategy in an ongoing epidemic: Bovine tuberculosis in African buffalo  

Microsoft Academic Search

Bovine tuberculosis (BTB) is an exotic disease invading the buffalo population (Syncerus caffer) of the Kruger National Park (KNP), South Africa. We used a sex and age-structured epidemiological model to assess the effectiveness of a vaccination program and define important research directions. The model allows for dispersal between a focal herd and background population and was parameterized with a combination

Paul C. Cross; Wayne M. Getz

2006-01-01

414

Cost-effectiveness of novel vaccines for tuberculosis control: a decision analysis study  

Microsoft Academic Search

BACKGROUND: The development of a successful new tuberculosis (TB) vaccine would circumvent many limitations of current diagnostic and treatment practices. However, vaccine development is complex and costly. We aimed to assess the potential cost effectiveness of novel vaccines for TB control in a sub-Saharan African country - Zambia - relative to the existing strategy of directly observed treatment, short course

Chia-Lin Tseng; Olivia Oxlade; Dick Menzies; Anne Aspler; Kevin Schwartzman

2011-01-01

415

A systematic review of delay in the diagnosis and treatment of tuberculosis  

Microsoft Academic Search

BACKGROUND: Early diagnosis and immediate initiation of treatment are essential for an effective tuberculosis (TB) control program. Delay in diagnosis is significant to both disease prognosis at the individual level and transmission within the community. Most transmissions occur between the onset of cough and initiation of treatment. METHODS: A systematic review of 58 studies addressing delay in diagnosis and treatment

DagGundersen Gundersen Storla; Solomon Yimer; Gunnar Aksel Bjune

2008-01-01

416

Tuberculosis vaccine strain Mycobacterium bovis BCG Russia is a natural recA mutant  

Microsoft Academic Search

BACKGROUND: The current tuberculosis vaccine is a live vaccine derived from Mycobacterium bovis and attenuated by serial in vitro passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy. RESULTS: As a RecA phenotype increases genetic stability and may contribute restricting the

Peter M Keller; Erik C Böttger; Peter Sander

2008-01-01

417

Inositol monophosphate phosphatase genes of Mycobacterium tuberculosis  

PubMed Central

Background Mycobacteria use inositol in phosphatidylinositol, for anchoring lipoarabinomannan (LAM), lipomannan (LM) and phosphatidylinosotol mannosides (PIMs) in the cell envelope, and for the production of mycothiol, which maintains the redox balance of the cell. Inositol is synthesized by conversion of glucose-6-phosphate to inositol-1-phosphate, followed by dephosphorylation by inositol monophosphate phosphatases (IMPases) to form myo-inositol. To gain insight into how Mycobacterium tuberculosis synthesises inositol we carried out genetic analysis of the four IMPase homologues that are present in the Mycobacterium tuberculosis genome. Results Mutants lacking either impA (Rv1604) or suhB (Rv2701c) were isolated in the absence of exogenous inositol, and no differences in levels of PIMs, LM, LAM or mycothiol were observed. Mutagenesis of cysQ (Rv2131c) was initially unsuccessful, but was possible when a porin-like gene of Mycobacterium smegmatis was expressed, and also by gene switching in the merodiploid strain. In contrast, we could only obtain mutations in impC (Rv3137) when a second functional copy was provided in trans, even when exogenous inositol was provided. Experiments to obtain a mutant in the presence of a second copy of impC containing an active-site mutation, in the presence of porin-like gene of M. smegmatis, or in the absence of inositol 1-phosphate synthase activity, were also unsuccessful. We showed that all four genes are expressed, although at different levels, and levels of inositol phosphatase activity did not fall significantly in any of the mutants obtained. Conclusions We have shown that neither impA, suhB nor cysQ is solely responsible for inositol synthesis. In contrast, we show that impC is essential for mycobacterial growth under the conditions we used, and suggest it may be required in the early stages of mycothio