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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

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

3

Genetically susceptible mice remain proportionally more susceptible to tuberculosis after vaccination  

PubMed Central

DBA/2 mice are much more susceptible to infection with Mycobacterium tuberculosis than major histocompatibility complex-compatible BALB/c mice. It is shown here that, although vaccination provided mice of both strains with a capacity to reduce the level of infection in their lungs, vaccinated DBA/2 mice remained much more susceptible in this organ than vaccinated BALB/c mice. Consequently, the former mice developed more lung pathology and died much earlier than the latter. On the other hand, colony-forming unit counts and histology suggest that vaccination provided mice of both strains with an increased and equal ability to express immunity in the liver and spleen, thereby indicating that they possessed equal systemic levels of vaccine-induced immunity at the time of M. tuberculosis challenge. The results indicate that inefficient expression of immunity in the lungs is likely to prove an obstacle to successful vaccination against tuberculosis in resistant and susceptible mouse strains, but more so in the latter strains. PMID:10233673

Medina, E; North, R J

1999-01-01

4

Effect of Mutation and Genetic Background on Drug Resistance in Mycobacterium tuberculosis  

PubMed Central

Bacterial factors may contribute to the global emergence and spread of drug-resistant tuberculosis (TB). Only a few studies have reported on the interactions between different bacterial factors. We studied drug-resistant Mycobacterium tuberculosis isolates from a nationwide study conducted from 2000 to 2008 in Switzerland. We determined quantitative drug resistance levels of first-line drugs by using Bactec MGIT-960 and drug resistance genotypes by sequencing the hot-spot regions of the relevant genes. We determined recent transmission by molecular methods and collected clinical data. Overall, we analyzed 158 isolates that were resistant to isoniazid, rifampin, or ethambutol, 48 (30.4%) of which were multidrug resistant. Among 154 isoniazid-resistant strains, katG mutations were associated with high-level and inhA promoter mutations with low-level drug resistance. Only katG(S315T) (65.6% of all isoniazid-resistant strains) and inhA promoter ?15C/T (22.7%) were found in molecular clusters. M. tuberculosis lineage 2 (includes Beijing genotype) was associated with any drug resistance (adjusted odds ratio [OR], 3.0; 95% confidence interval [CI], 1.7 to 5.6; P < 0.0001). Lineage 1 was associated with inhA promoter ?15C/T mutations (OR, 6.4; 95% CI, 2.0 to 20.7; P = 0.002). We found that the genetic strain background influences the level of isoniazid resistance conveyed by particular mutations (interaction tests of drug resistance mutations across all lineages; P < 0.0001). In conclusion, M. tuberculosis drug resistance mutations were associated with various levels of drug resistance and transmission, and M. tuberculosis lineages were associated with particular drug resistance-conferring mutations and phenotypic drug resistance. Our study also supports a role for epistatic interactions between different drug resistance mutations and strain genetic backgrounds in M. tuberculosis drug resistance. PMID:22470121

Egger, Matthias; Bodmer, Thomas; Altpeter, Ekkehardt; Zwahlen, Marcel; Jaton, Katia; Pfyffer, Gaby E.; Borrell, Sonia; Dubuis, Olivier; Bruderer, Thomas; Siegrist, Hans H.; Furrer, Hansjakob; Calmy, Alexandra; Fehr, Jan; Stalder, Jesica Mazza; Ninet, Beatrice; Bottger, Erik C.; Gagneux, Sebastien

2012-01-01

5

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.

6

Background  

E-print Network

OCA is a group of autosomal recessive disorders characterized by hypopigmentation and abnormalities related to ocular development. Mutations in genes regulating melanin-biosynthesis cause four classical types of OCA (OCA 1-4). The clinical spectrum of OCA often depends on the pigmentation threshold of a patient, highlighting the importance of ethnic- specific SNPs. We aimed to understand the molecular bases of OCA in India, where it is one of the four major causes of childhood blindness. Materials and methods Blood samples were collected from OCA patients and family members, mostly from eastern and southern India. Seven pigmentation related genes were screened for variations. Relevant non-synonymous changes in tyrosinase (TYR) were functionally validated. Eighteen SNPs from three OCA genes were genotyped in 552 normal individuals covering various ethnic groups of India. Results Our data suggest that defects in TYR cause albinism in 58 % (36/62) of the cases [1] (and unpublished data; see Figure 1). Functional assays with missense mutations proved that none of mutants are enzymatically active and are retained in the endoplasmic reticulum [1]. Screening of the remaining cases (43%) revealed OCA2 to be the second common locus followed by SLC45A2 [2] (Figure 1). Evaluation of SNPs in TYR, OCA2 and SLC45A2 in normal population suggested definitive bias for some of the SNPs towards specific populations.

Kunal Ray; Mainak Sengupta; Moumita Chaki; Maitreyee Mondal; Swapan Samanta

7

Time Remains  

E-print Network

On one popular view, the general covariance of gravity implies that change is relational in a strong sense, such that all it is for a physical degree of freedom to change is for it to vary with regard to a second physical degree of freedom. At a quantum level, this view of "change as relative variation" leads to a "fundamentally timeless" formalism for quantum gravity. Here, we will show how one may avoid this acute `problem of time'. Under our view, duration is still regarded as relative, but temporal succession is taken to be absolute. Following our approach, which is presented in more formal terms in arXiv:1303.7139, it is possible to conceive of a genuinely dynamical theory of quantum gravity within which time, in a substantive sense, remains.

Sean Gryb; Karim Thebault

2014-08-12

8

The gene expression data of Mycobacterium tuberculosis based on Affymetrix gene chips provide insight into regulatory and hypothetical genes  

Microsoft Academic Search

BACKGROUND: Tuberculosis remains a leading infectious disease with global public health threat. Its control and management have been complicated by multi-drug resistance and latent infection, which prompts scientists to find new and more effective drugs. With the completion of the genome sequence of the etiologic bacterium, Mycobacterium tuberculosis, it is now feasible to search for new drug targets by sieving

Li M Fu; Casey S Fu-Liu

2007-01-01

9

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

10

Short communication How dormant is Mycobacterium tuberculosis during latency? A study  

E-print Network

Short communication How dormant is Mycobacterium tuberculosis during latency? A study integrating. Boulevard, DK-5000 Odense C, Denmark 1. Introduction Tuberculosis (TB) remains a leading infectious cause infected with Mycobacterium tuberculosis, people with latent tuberculosis infection (LTBI) represent

Rosenberg, Noah

11

Extensively drug resistant tuberculosis in a high income country: A report of four unrelated cases  

PubMed Central

Background Multi drug resistance of Mycobacterium tuberculosis (M. tuberculosis) remains a major threat to public health, reinforced by recent reports about the clinical course of patients infected with extensively drug resistant (XDR) strains in South Africa. There is little information about the clinical course of XDR tuberculosis patients in industrialised countries. Methods We evaluated all isolates of M. tuberculosis, in which drug susceptibility testing was performed at our institution since 1997, for multi and extensive drug resistance. Clinical courses of patients infected by strains fulfilling the recently revised criteria for XDR tuberculosis were analysed. Results Four XDR M. tuberculosis isolates were identified. All patients had immigrated to Germany from Russia, Georgia, and former Yugoslavia and none were infected by the human immunodeficiency virus. All patients where treated for tuberculosis for 5.5 to 15 years and for XDR tuberculosis for 1.9 to 2.5 years. They received inhospital treatment in Germany for 11 months, 4.5 years and twice for 6 years. Non-compliance was an important factor in all four patients, three patients had to be treated in Germanys only locked facility for tuberculosis treatment. One patient with XDR tuberculosis died, one patient had still open pulmonary tuberculosis at last contact and 2 patients were cured. Conclusion Cases of XDR tuberculosis have been treated in our region for several years. Even in a high income setting, XDR tuberculosis has a tremendous impact on quality of live, outcome and the total cost. All reasonable efforts to prevent the spread of XDR tuberculosis must be made and maintained. PMID:18454863

Blaas, Stefan H; Mutterlein, Ralf; Weig, Johannes; Neher, Albert; Salzberger, Bernd; Lehn, Norbert; Naumann, Ludmila

2008-01-01

12

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

13

RIFAMYCIN-RESISTANT TUBERCULOSIS IN THE UNITED STATES, 1998-2008; an Analysis of the National Tuberculosis Surveillance System.  

E-print Network

??RIFAMYCIN-RESISTANT TUBERCULOSIS IN THE UNITED STATES, 1998-2008; an Analysis of the National Tuberculosis Surveillance System By Lisa Sharling Background: Tuberculosis (TB) incidence rates in the… (more)

Sharling, Lisa

2011-01-01

14

Smear positive pulmonary tuberculosis and its risk factors among tuberculosis suspect in South East Ethiopia; a hospital based cross-sectional study  

PubMed Central

Background Tuberculosis remains a deadly infectious disease, affecting millions of people worldwide. Ethiopia ranks seventh among the twenty two high tuberculosis burden countries. The aim of this study was to determine the prevalence of smear positive pulmonary tuberculosis and its associated risk factors in Goba and Robe hospitals of Bale zone. Methods A cross-sectional study was conducted on tuberculosis suspected patients from February-May 2012. Sputum samples were examined for acid fast bacilli using Ziehl-Neelsen staining and interview was conducted for each patient. Descriptive statistics, binary logistic and multivariable logistic regression analyses were employed to identify factors associated with pulmonary tuberculosis infection. Result The prevalence of smear positive tuberculosis was 9.2%. Age >36 (AOR?=?3.54, 95% CI?=?1. 3–9.82), marital status (AOR?=?8.40, 95% CI?=?3.02-23.20), family size (AOR?=?4. 10, 95% CI?=?1.60-10.80), contact with active tuberculosis patient (AOR?=?5. 90; 95% CI?=?2. 30–15.30), smoking cigarette regularly (AOR?=?3. 90; 95% CI?=?1. 20–12.40), and human immunodeficiency virus sero-status (AOR?=?11. 70; 95% CI?=?4. 30–31.70) were significantly associated with smear positive pulmonary tuberculosis. Conclusion The prevalence of smear positive pulmonary tuberculosis was high in the study area. Age, marital status, family size, history of contact with active tuberculosis patient, smoking cigarettes, and HIV sero-status were among the risk factors significantly associated with acquiring tuberculosis. Hence, strict pulmonary tuberculosis screening of HIV patients and intensification of health education to avoid risk factors identified are recommended. PMID:24884870

2014-01-01

15

Comparison of Trends in Tuberculosis Incidence among Adults Living with HIV and Adults without HIV - Kenya, 1998-2012  

PubMed Central

Background In Kenya, the comparative incidences of tuberculosis among persons with and without HIV have not been described, and the differential impact of public health interventions on tuberculosis incidence in the two groups is unknown. Methods We estimated annual tuberculosis incidence stratified by HIV status during 2006–2012 based on the numbers of reported tuberculosis patients with and without HIV infection, the prevalence of HIV infection in the general population, and the total population. We also made crude estimates of annual tuberculosis incidence stratified by HIV status during 1998–2012 by assuming a constant ratio of HIV prevalence among tuberculosis patients compared to the general population. Results Tuberculosis incidence among both adults with HIV and adults without HIV increased during 1998–2004 then remained relatively stable until 2007. During 2007–2012, tuberculosis incidence declined by 28–44% among adults with HIV and by 11–26% among adults without HIV, concurrent with an increase in antiretroviral therapy uptake. In 2012, tuberculosis incidence among adults with HIV (1,839–1,936 cases/100,000 population) was still eight times as high as among adults without HIV (231–238 cases/100,000 population), and approximately one third of tuberculosis cases were attributable to HIV. Conclusions Although tuberculosis incidence has declined among adults with and without HIV, the persistent high incidence of tuberculosis among those with HIV and the disparity between the two groups are concerning. Early diagnosis of HIV, early initiation of antiretroviral therapy, regular screening for tuberculosis, and isoniazid preventive therapy among persons with HIV, as well as tuberculosis control in the general population, are required to address these issues. PMID:24937804

Yuen, Courtney M.; Weyenga, Herman O.; Kim, Andrea A.; Malika, Timothy; Muttai, Hellen; Katana, Abraham; Nganga, Lucy; Cain, Kevin P.; De Cock, Kevin M.

2014-01-01

16

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

17

Systemic Immune Activation and Microbial Translocation in Dual HIV/Tuberculosis-Infected Subjects  

PubMed Central

Background.?Systemic immune activation is a strong predictor of progression of human immunodeficiency virus type 1 (HIV-1) disease and a prominent feature of infection with Mycobacterium tuberculosis. Objective.?To understand the role of systemic immune activation and microbial translocation in HIV/tuberculosis dually infected patients over the full spectrum of HIV-1 immunodeficiency, we studied circulating sCD14 and lipopolysaccharide (LPS) and their relationship to HIV-1 activity. Methods.?Two cohorts of HIV/tuberculosis subjects defined by CD4 T-cell count at time of diagnosis of tuberculosis were studied: those with low (<350/?L) and those with high (?350/?L) CD4 T-cell count. Circulating soluble CD14 (sCD14) and LPS were assessed. Results.?Levels of sCD14 were higher in HIV/tuberculosis with high (?350/?L) as compared to low CD4 T-cell count (P < .001). Whereas sCD14 levels remained elevated in HIV/tuberculosis subjects with lower CD4 T-cell counts despite treatment of tuberculosis, in HIV/tuberculosis patients with higher CD4 T-cell count (?350/?L), levels declined regardless of whether highly active antiretroviral therapy (HAART) was included with the anti-tuberculosis regimen. Circulating LPS levels in HIV/tuberculosis patients with CD4 T-cell count ?350/?L were unaffected by treatment of tuberculosis with or without HAART. Conclusion.?During HIV/tuberculosis, systemic immune activation is dissociated from microbial translocation. Changes in circulating sCD14 and LPS are dependent on CD4 T-cell count. PMID:23479321

Toossi, Zahra; Funderburg, Nicholas T.; Sirdeshmuk, Sohani; Whalen, Christopher C.; Nanteza, Maria W.; Johnson, Denise F.; Mayanja-Kizza, Harriet; Hirsch, Christina S.

2013-01-01

18

Cutaneous Tuberculosis  

PubMed Central

Cutaneous tuberculosis occurs rarely, despite a high and increasing prevalence of tuberculosis worldwide. Mycobacterium tuberculosis, Mycobacterrium bovis, and the Bacille Calmette-Guérin vaccine can cause tuberculosis involving the skin. Cutaneous tuberculosis can be acquired exogenously or endogenously and present as a multitude of differing clinical morphologies. Diagnosis of these lesions can be difficult, as they resemble many other dermatological conditions that are often primarily considered. Further, microbiological confirmation is poor, despite scientific advances, such as the more frequent use of polymerase chain reaction. The authors report a case that illustrates the challenges faced by dermatologists when considering a diagnosis of cutaneous tuberculosis. PMID:20725570

Frankel, Amylynne; Penrose, Carolin

2009-01-01

19

Unique transcriptome signature of Mycobacterium tuberculosis in pulmonary tuberculosis.  

PubMed

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 identification of M. tuberculosis genes actively expressed during pulmonary tuberculosis. To obtain optimal information from our DNA array analyses, we analyzed the differentially expressed genes within the context of computationally inferred protein networks. Protein networks were constructed using functional linkages established by the Rosetta stone, phylogenetic profile, conserved gene neighbor, and operon computational methods. This combined approach revealed that during pulmonary tuberculosis, M. tuberculosis actively transcribes a number of genes involved in active fortification and evasion from host defense systems. These genes may provide targets for novel intervention strategies. PMID:16428773

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

2006-02-01

20

Lingual tuberculosis.  

PubMed

Oral tuberculosis is very rare and when present they are usually secondary to pulmonary tuberculosis. Tuberculous lesions of the tongue have become so infrequent that they are virtually a forgotten disease entity and may pose a diagnostic problem. The case reported in this paper emphasizes the importance of including tuberculosis in the differential diagnosis of any chronic oral ulcer. The low number of oral infections by M. tuberculosis could be due to underreporting. PMID:22670511

Mohanapriya, T; Singh, K Balaji; Arulappan, T; Dhanasekar, T

2012-01-01

21

Prevalence of Tuberculosis, HIV and Respiratory Symptoms in Two Zambian Communities: Implications for Tuberculosis Control in the Era of HIV  

Microsoft Academic Search

BackgroundThe Stop TB Partnership target for tuberculosis is to have reduced the prevalence of tuberculosis by 50% comparing 2015 to 1990. This target is challenging as few prevalence surveys have been conducted, especially in high burden tuberculosis and HIV countries. Current tuberculosis control strategies in high HIV prevalent settings are therefore based on limited epidemiological evidence and more evidence is

Helen Ayles; Albertus Schaap; Amos Nota; Charalambos Sismanidis; Ruth Tembwe; Petra de Haas; Monde Muyoyeta; Nulda Beyers; Madhukar Pai

2009-01-01

22

[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

23

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.

24

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

Microsoft Academic Search

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.

Senia Rosales; Lelany Pineda-García; Solomon Ghebremichael; Nalin Rastogi; Sven E Hoffner

2010-01-01

25

Comparison of Culture and PCR Methods for Diagnosis of Mycobacterium tuberculosis in Different Clinical Specimens  

PubMed Central

Background: Tuberculosis remains a global epidemic, especially in developing countries, including Iran. Rapid diagnosis of active Mycobacterium tuberculosis infection plays a critical role in controlling the spread of tuberculosis. Conventional methods may take up to several weeks or longer to produce results. In addition to multiplicity of steps involved in conventional detection, including isolation, identification and drug susceptibility testing, the slow growth rate of M. tuberculosis is also responsible for this lengthy time. Objectives: The aim of this study was to compare the polymerase chain reaction (PCR) and culture methods for the detection of M. tuberculosis in different clinical specimens. Materials and Methods: This study was performed on different samples (urine, gastric aspirate, bronchoalveolar lavage, pleural fluid, cerebrospinal fluid, ascetic fluid and joint fluid specimens) of tuberculosis suspected patients. M. tuberculosis DNA was extracted directly from different samples using two different protocols. Next, PCR was performed using three sets of specific primers to detect members of Mycobacterium genus, M. tuberculosis complex and non-tuberculosis Mycobacteria. The results were then compared with that of the culture method, which is considered as the gold standard method. Results: The concordance rate between the three sets of primers was calculated and IS6110/buffer PCR method showed good agreement with the LJ culture method (? = 0.627, P < 0.0001). The sensitivity of IS6110/buffer PCR was 58.33%, with specificity of 77.78%; the positive and negative predictive values were 100% and 78.26%, respectively. Buffer method for DNA extraction was proved to give a higher accuracy to PCR in comparison with the boiling method. Conclusions: PCR method is a valuable, cost-effective and alternative tool for quick diagnosis of active tuberculosis in different clinical specimens. PMID:25147673

Gholoobi, Aida; Masoudi-Kazemabad, Ali; Meshkat, Mojtaba; Meshkat, Zahra

2014-01-01

26

Genital Tuberculosis as the Cause of Tuboovarian Abscess in an Immunosuppressed Patient  

PubMed Central

Background. Although tuberculosis (TB) is a major health problem worldwide, primary extrapulmonary tuberculosis (EPTB), and in particular female genital tract infection, remains a rare event. Case Report. A 35-year-old human immunodeficiency virus (HIV) seropositive woman of African descent with lower abdominal pain and fever of two days duration underwent surgery due to left adnexal mass suggesting pelvic inflammatory disease. The surgical situs showed a four quadrant peritonitis, consistent with the clinical symptoms of the patient, provoked by a tuboovarian abscess (TOA) on the left side. All routine diagnostic procedures failed to determine the causative organism/pathogen of the infection. Histopathological evaluation identified a necrotic granulomatous salpingitis and specific PCR analysis corroborated Mycobacterium tuberculosis (M. Tb). Consequently, antituberculotic therapy was provided. Conclusion. In the differential diagnosis of pelvic inflammatory disease, internal genital tuberculosis should be considered. Moreover, physicians should consider tuberculous infections early in the work-up of patients when immunosuppressive conditions are present. PMID:20224814

Ilmer, M.; Bergauer, F.; Friese, K.; Mylonas, I.

2009-01-01

27

Hepatobiliary tuberculosis  

PubMed Central

Hepatobiliary tuberculosis is a rare manifestation of Mycobacterium tuberculosis infection and is usually secondary to tuberculosis of the lungs or gastrointestinal tract. Diagnosis is difficult pre-operatively in local (focal and tubular) forms because of its rarity and presentation in the form of non-specific symptoms and signs and lack of any defined criteria on imaging studies. Histopathological examination is necessary for definite diagnosis but in cases where there is suspicion of hepatobiliary tuberculosis, with PCR assay diagnosis it is possible pre-operatively. Recommended treatment is with conventional antituberculous drugs and surgical intervention in tuberculous abscess or granulomas. The disease is usually associated with good prognosis under complete antituberculous treatment. The author encountered 4 cases of hepatobiliary tuberculosis over 5 years. The aim of this article is to present current knowledge of hepatobiliary tuberculosis and to comprehensively review all the available literature. PMID:24976240

Chaudhary, Poras

2014-01-01

28

When Tuberculosis Comes Back: Who Develops Recurrent Tuberculosis in California?  

PubMed Central

Background Recurrent tuberculosis suggests potentially modifiable gaps in tuberculosis treatment and control activities. The frequency of late recurrences following treatment completion has not been well-studied. We determined the frequency of, and risk factors associated with, tuberculosis that recurs at least one year after completion of anti-tuberculosis therapy in California. Methods The study population included culture-positive, pulmonary tuberculosis patients reported to the California tuberculosis case registry from 1993 to 2007 who completed anti-tuberculosis therapy. A person with late recurrent tuberculosis was defined as an individual that appeared in the registry more than once, determined by match on name and date-of-birth, with at least one year between treatment completion of the first episode and treatment initiation of the second episode. Results Among 23,517 tuberculosis patients, 148 (0.63%) had a late recurrence. Independent risk factors for recurrence included: infection with a pyrazinamide mono-resistant isolate (adjusted hazard ratio, 2.93; p?=?0.019); initiation of an isoniazid- and rifampin-only treatment regimen (adjusted hazard ratio, 2.55; p?=?0.0412); sputum smear-positive disease (adjusted hazard ratio, 1.96; p?=?0.0003); human immunodeficiency virus infection (adjusted hazard ratio, 1.81; p?=?0.0149); and birth in the United States (adjusted hazard ratio, 1.88; p?=?0.0002). Infection with an isoniazid mono-resistant isolate was protective (adjusted hazard ratio, 0.25; p?=?0.0171). Conclusions The low frequency of late recurrent tuberculosis in California suggests that local TB control programs are largely successful at preventing this adverse outcome. Nonetheless, we identified subpopulations at increased risk of late tuberculosis recurrence that may benefit from additional medical or public health interventions. PMID:22069456

Pascopella, Lisa; DeRiemer, Kathryn; Watt, James P.; Flood, Jennifer M.

2011-01-01

29

Revisiting the Natural History of Tuberculosis  

Microsoft Academic Search

Once Mycobacterium tuberculosis infects a person it can persist for a long time in a process called latent tuberculosis infection (LTBI). LTBI has traditionally\\u000a been considered to involve the bacilli remaining in a non-replicating state (dormant) in old lesions but still retaining their\\u000a ability to induce reactivation and cause active tuberculosis (TB) once a disruption of the immune response takes

Pere-Joan Cardona

2010-01-01

30

targetTB: A target identification pipeline for Mycobacterium tuberculosis through an interactome, reactome and genome-scale structural analysis  

Microsoft Academic Search

BACKGROUND: Tuberculosis still remains one of the largest killer infectious diseases, warranting the identification of newer targets and drugs. Identification and validation of appropriate targets for designing drugs are critical steps in drug discovery, which are at present major bottle-necks. A majority of drugs in current clinical use for many diseases have been designed without the knowledge of the targets,

Karthik Raman; Kalidas Yeturu; Nagasuma Chandra

2008-01-01

31

Nitric oxide production in the exhaled air of patients with pulmonary tuberculosis in relation to HIV co-infection  

Microsoft Academic Search

BACKGROUND: Nitric oxide (NO) is essential for host defense in rodents, but the role of NO during tuberculosis (TB) in man remains controversial. However, earlier observations that arginine supplementation facilitates anti-TB treatment, supports the hypothesis that NO is important in the host defense against TB. Local production of NO measured in fractional exhaled air (FeNO) in TB patients with and

Jonna Idh; Anna Westman; Daniel Elias; Feleke Moges; Assefa Getachew; Aschalew Gelaw; Tommy Sundqvist; Tony Forslund; Addis Alemu; Belete Ayele; Ermias Diro; Endalkachew Melese; Yared Wondmikun; Sven Britton; Olle Stendahl; Thomas Schön

2008-01-01

32

Perinatal tuberculosis.  

PubMed

Perinatal tuberculosis is insufficiently understood. Its early diagnosis is essential but often difficult as the initial manifestations may be delayed. Improved screening of women at risk and sensitivity of the medical community are necessary. A coherent system of cooperation between the hospital and community services and between pediatricians and adult physicians is indispensable to find the index adult case to break the chain of contagion as well as to offer prophylactic therapy to the children at risk. We hereby report a baby with perinatal tuberculosis who was not offered any prophylactic therapy inspite of the mother being diagnosed to have pulmonary tuberculosis. PMID:11370442

Ray, M; Goraya, J S; Basu, S; Parmar, V

2001-04-01

33

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

34

The radiological diagnosis of tuberculosis of the adult spine  

Microsoft Academic Search

Tuberculosis remains endemic in the United States with an estimated incidence of 15.9 cases per 100,000 population. In North America and Saudi Arabia tuberculosis of the spine is primarily a disease of adults. In Saudi Arabia the average age on presentation is 41 years. Spinal tuberculosis begins classically in the anterior inferior portion of a vertebral body. The infection spreads

P. Weaver; R. M. Lifeso

1984-01-01

35

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

36

Factors and Global Gene Regulation in Mycobacterium tuberculosis  

Microsoft Academic Search

Tuberculosis remains a worldwide threat despite the avail- ability of the BCG vaccine and antibiotic treatment. It is esti- mated that its etiologic agent, Mycobacterium tuberculosis, in- fects almost a third of the human population and kills two million people every year (27). The recent human immunode- ficiency virus pandemic, the selection of multidrug-resistant strains of M. tuberculosis, and the

Riccardo Manganelli; Roberta Proveddi; Sebastien Rodrigue; Jocelyn Beaucher; Luc Gaudreau; Issar Smith

2004-01-01

37

Genetic Diversity and Population Structure of Mycobacterium tuberculosis in Casablanca, a Moroccan City with High Incidence of Tuberculosis  

Microsoft Academic Search

Although lower-resource countries have by far the highest burden of tuberculosis, knowledge of Mycobacte- rium tuberculosis population structure and genetic diversity in these regions remains almost nonexistent. In this paper, 150 Moroccan M. tuberculosis isolates circulating in Casablanca were genotyped by random amplified polymorphic DNA analysis using 10 different primers and by mycobacterial interspersed repetitive units- variable number of tandem

Loubna Tazi; Jamila El Baghdadi; Sarah Lesjean; Camille Locht; Philip Supply; Michel Tibayrenc; Anne-Laure Banuls

2004-01-01

38

Matrix metalloproteinases in tuberculosis.  

PubMed

Tuberculosis (TB) remains a global health pandemic. Infection is spread by the aerosol route and Mycobacterium tuberculosis must drive lung destruction to be transmitted to new hosts. Such inflammatory tissue damage is responsible for morbidity and mortality in patients. The underlying mechanisms of matrix destruction in TB remain poorly understood but consideration of the lung extracellular matrix predicts that matrix metalloproteinases (MMPs) will play a central role, owing to their unique ability to degrade fibrillar collagens and other matrix components. Since we proposed the concept of a matrix degrading phenotype in TB a decade ago, diverse data implicating MMPs as key mediators in TB pathology have accumulated. We review the lines of investigation that have indicated a critical role for MMPs in TB pathogenesis, consider regulatory pathways driving MMPs and propose that inhibition of MMP activity is a realistic goal as adjunctive therapy to limit immunopathology in TB. PMID:21659415

Elkington, P T; Ugarte-Gil, C A; Friedland, J S

2011-08-01

39

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

40

Sternal Tuberculosis  

PubMed Central

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

2013-01-01

41

A Case Report of Primary Duodenal Tuberculosis Mimicking a Malignant Tumor  

PubMed Central

Tuberculosis remains a serious infectious disease with primary features of pulmonary manifestation in Korea. However, duodenal tuberculosis is rare in gastrointestinal cases of extrapulmonary tuberculosis. Here, we report a case of primary duodenal tuberculosis mistaken as a malignant tumor and diagnosed with QuantiFERON-TB GOLD (Cellestis Ltd.) in an immunocompetent male patient. PMID:25133123

Jung, Ji Hye; Kim, Min Jeong; Cho, Young Kwan; Ahn, Sang Bong; Son, Byoung Kwan; Jo, Yun Ju; Park, Young Sook

2014-01-01

42

Time of Default in Tuberculosis Patients on Directly Observed Treatment  

PubMed Central

Background: Default remains an important challenge for the Revised National Tuberculosis Control Programme, which has achieved improved cure rates. Objectives: This study describes the pattern of time of default in patients on DOTS. Settings and Design: Tuberculosis Unit in District Tuberculosis Centre, Yavatmal, India; Retrospective cohort study. Materials and Methods: This analysis was done among the cohort of patients of registered at the Tuberculosis Unit during the year 2004. The time of default was assessed from the tuberculosis register. The sputum smear conversion and treatment outcome were also assessed. Statistical Analysis: Kaplan-Meier plots and log rank tests. Results: Overall, the default rate amongst the 716 patients registered at the Tuberculosis Unit was 10.33%. There was a significant difference in the default rate over time between the three DOTS categories (log rank statistic= 15.49, P=0.0004). Amongst the 331 smear-positive patients, the cumulative default rates at the end of intensive phase were 4% and 16%; while by end of treatment period, the default rates were 6% and 31% in category I and category II, respectively. A majority of the smear-positive patients in category II belonged to the group ‘treatment after default’ (56/95), and 30% of them defaulted during re-treatment. The sputum smear conversion rate at the end of intensive phase was 84%. Amongst 36 patients without smear conversion at the end of intensive phase, 55% had treatment failure. Conclusions: Patients defaulting in intensive phase of treatment and without smear conversion at the end of intensive phase should be retrieved on a priority basis. Default constitutes not only a major reason for patients needing re-treatment but also a risk for repeated default. PMID:20927282

Pardeshi, Geeta S

2010-01-01

43

Gender-related factors influencing tuberculosis control in shantytowns: a qualitative study  

Microsoft Academic Search

BACKGROUND: There is evidence that female gender is associated with reduced likelihood of tuberculosis diagnosis and successful treatment. This study aimed to characterize gender-related barriers to tuberculosis control in Peruvian shantytowns. METHODS: We investigated attitudes and experiences relating gender to tuberculosis using the grounded theory approach to describe beliefs amongst key tuberculosis control stakeholders. These issues were explored in 22

Dami A Onifade; Angela M Bayer; Rosario Montoya; Marie Haro; Jessica Alva; Jessica Franco; Rosario Sosa; Betty Valiente; Enit Valera; Carolyn M Ford; Colleen D Acosta; Carlton A Evans

2010-01-01

44

Molecular characterization of tlyA gene product, Rv1694 of Mycobacterium tuberculosis: A non-conventional hemolysin and a ribosomal RNA methyl transferase  

Microsoft Academic Search

BACKGROUND: Mycobacterium tuberculosis is a virulent bacillus causing tuberculosis, a disease responsible for million deaths each year worldwide. In order to understand its mechanism of pathogenesis in humans and to help control tuberculosis, functions of numerous Mycobacterium tuberculosis genes are being characterized. In this study we report the dual functionality of tlyA gene product of Mycobacterium tuberculosis annotated as Rv1694,

Aejazur Rahman; Saumya S Srivastava; Amita Sneh; Neesar Ahmed; Musti V Krishnasastry

2010-01-01

45

Extensively drug-resistant tuberculosis in India: A review  

PubMed Central

Background & objectives: Extensively drug resistant tuberculosis (XDR-TB) has become a new threat for the control of TB in many countries including India. Its prevalence is not known in India as there is no nation-wide surveillance. However, there have been some reports from various hospitals in the country. Methods: We have reviewed the studies/information available in the public domain and found data from 10 tertiary care centres in 9 cities in India. Results: A total of 598 isolates of XDR Mycobacterium tuberculosis have been reported in the studies included. However, the reliability of microbiological methods used in these studies was not checked and thus the XDR-TB data remained invalidated in reference laboratories. Interpretation & conclusions: Systematic surveillance and containment interventions are urgently needed. PMID:23168700

Michael, Joy Sarojini; John, T. Jacob

2012-01-01

46

Propellant-remaining modeling  

NASA Technical Reports Server (NTRS)

A successful satellite mission is predicted upon the proper maintenance of the spacecraft's orbit and attitude. One requirement for planning and predicting the orbit and attitude is the accurate estimation of the propellant remaining onboard the spacecraft. Focuss is on the three methods that were developed for calculating the propellant budget: the errors associated with each method and the uncertainties in the variables required to determine the propellant remaining that contribute to these errors. Based on these findings, a strategy is developed for improved propellant-remaining estimation. The first method is based on Boyle's law, which related the values of pressure, volume, and temperature (PVT) of an ideal gas. The PVT method is used for the monopropellant and the bipropellant engines. The second method is based on the engine performance tests, which provide data that relate thrust and specific impulse associated with a propellant tank to that tank's pressure. Two curves representing thrust and specific impulse as functions of pressure are then generated using a polynomial fit on the engine performance data. The third method involves a computer simulation of the propellant system. The propellant flow is modeled by creating a conceptual model of the propulsion system configuration, taking into account such factors as the propellant and pressurant tank characteristics, thruster functionality, and piping layout. Finally, a thrust calibration technique is presented that uses differential correction with the computer simulation method of propellant-remaining modeling. Thrust calibration provides a better assessment of thruster performance and therefore enables a more accurate estimation of propellant consumed during a given maneuver.

Torgovitsky, S.

1991-01-01

47

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

48

1453 December 2013 Background: Chronic pain remains a significant challenge  

E-print Network

within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = -0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0 a role for human brain imaging in the development, assessment, and personalized use of central- acting

Napadow, Vitaly

49

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

50

Hyperendemic pulmonary tuberculosis in peri-urban areas of Karachi, Pakistan  

PubMed Central

Background Currently there are very limited empirical data available on the prevalence of pulmonary tuberculosis among residents of marginalized settings in Pakistan. This study assessed the prevalence of pulmonary tuberculosis through active case detection and evaluated predictors of pulmonary tuberculosis among residents of two peri-urban neighbourhoods of Karachi, Pakistan. Methods A cross-sectional study was conducted in two peri-urban neighbourhoods from May 2002 to November 2002. Systematic sampling design was used to select households for inclusion in the study. Consenting subjects aged 15 years or more from selected households were interviewed and, whenever possible, sputum samples were obtained. Sputum samples were subjected to direct microscopy by Ziehl-Neelson method, bacterial culture and antibiotic sensitivity tests. Results The prevalence (per 100,000) of pulmonary tuberculosis among the subjects aged 15 years or more, who participated in the study was 329 (95% confidence interval (CI): 195 – 519). The prevalence (per 100,000) of pulmonary tuberculosis adjusted for non-sampling was 438 (95% CI: 282 – 651). Other than cough, none of the other clinical variables was significantly associated with pulmonary tuberculosis status. Analysis of drug sensitivity pattern of 15 strains of Mycobacterium tuberculosis revealed that one strain was resistant to isoniazid alone, one to streptomycin alone and one was resistant to isoniazid and streptomycin. The remaining 12 strains were susceptible to all five drugs including streptomycin, isoniazid, rifampicin, ethambutol, and pyrazinamide. Conclusion This study of previously undetected tuberculosis cases in an impoverished peri-urban setting reveals the poor operational performance of Pakistan's current approach to tuberculosis control; it also demonstrates a higher prevalence of pulmonary tuberculosis than current national estimates. Public health authorities may wish to augment health education efforts aimed at prompting health-seeking behaviour to facilitate more complete and earlier case detection. Such efforts to improve passive case-finding, if combined with more accessible DOTS infra-structure for treatment of detected cases, may help to diminish the high tuberculosis-related morbidity and mortality in marginalized populations. The economics of implementing a more active approach to case finding in resource-constrained setting also deserve further study. PMID:17477870

Akhtar, Saeed; White, Franklin; Hasan, Rumina; Rozi, Shafquat; Younus, Mohammad; Ahmed, Faiza; Husain, Sara; Khan, Bilquis Sana

2007-01-01

51

[Tuberculosis in Iceland. 1976].  

PubMed

Because of signs of tuberculous lesions in old skeletons it can be stated with certainty that tuberculosis has occurred in the country shortly after the settlement. From that time and up to the seventeenth century, little or nothing is known about the occurrence of the disease. A few preserved descriptions of diseases and deaths indicate that tuberculosis has existed in the country before the advent of qualified physicians in 1760. On the basis of papers and reports from the first physicians and the first tuberculosis registers the opinions is set forth that the disease has been rare up to the latter part of the nineteenth century. During the two last decades of that century the disease began to spread more rapidly and increased steadily up to the turn of the century. Although reporting of the disease was started in the last decade of the nineteenth century the reporting was first ordered by law with the passage of the first tuberculosis Act in the year 1903. With this legislation official measures for tuberculosis control work really started in the country. The first sanatorium was built in 1910. In 1921 the tuberculosis Act was revised and since then practically all the expenses for the hospitalization and treatment of tuberculous cases has been defrayed by the state. In the year 1935 organized tuberculosis control work was begun and a special physician appointed to direct it. From then on systematic surveys were made, partly in health centers i.e. tuberculosis clinics, which were established in the main towns, and partly by means of transportable X ray units in outlying rural areas of the country. In 1939 the tuberculosis Act was again revised with special reference to the surveys and the activities of the tuberculosis clinics. This act is still in force. Some items of it are described. The procedure of the surveys and the methods of examination are described. The great majority of subjects were tuberculin tested and all positive reactors X rayed. Furthermore, X ray examination was made in all cases where tuberculin examination had not been made or was incomplete. The negative reactors were not X rayed. The tuberculin tests were percutaneous, cutaneous and intracutaneous. The X ray examination during the first years was performed by means of fluoroscopy and roentgenograms were made in all doubtful cases. In 1945 when the survey of the capital city of Reykjavík was made and comprised a total of 43,595 persons photoroentgenograms were made. After 1948 only this method together with tuberculin testing was used in all the larger towns in the country. During the period 1940-1945 such surveys were carried out in 12 medical districts, or parts thereof and included 58,837 persons or 47 percent of the entire population. The attendance in these surveys ranged from 89.3 percent to 100 percent of those considered able to attend. In the capital city, Reykjavík, the attendance was 99.32 percent. The course and prevalence of tuberculosis in Iceland from 1911 to 1970 are traced on the basis of tuberculosis reporting registers, mortality records which were ordered by law in 1911, tuberculin surveys and post mortem examinations. The deficiencies of these sources are pointed out. Since 1939 the morbidity rates are accurate. The number of reported cases of tuberculosis increases steadily up to the year 1935, when 1.6 percent of the population is reported to have active tuberculosis at the end of that year. Thereafter it begins to decline gradually the first years but abruptly in 1939, then without doubt because of the revision of the tuberculosis legislation and more exact reporting regulations. After that year the fall is almost constant with rather small fluctuations as regards new cases, relapses and total number of reported cases remaining on register at the end of each year. In 1950 the new cases are down to 1.6 per thousand and at the end of the year the rate for those remaining on register is 6.9 per thousand. In the year 1954 there is a noteworthy drop both in new cases and the total number reported, doubtless because of the ne

Sigurdsson, Sigurdur

2005-01-01

52

[Situation of tuberculosis in the world and the role expected of Japan in the global fight against tuberculosis].  

PubMed

The whole world is divided into 3 groups by the magnitude of tuberculosis problem: namely, developed countries in which tuberculosis is already a minor health problem and continues to decline; NIES and some oil-producing countries in which tuberculosis started to decline significantly; and most developing countries in which tuberculosis is still highly prevalent and no or only a slow decline. Number of new smear positive pulmonary tuberculosis in the whole world in a year is estimated at about 4.5 million, and adding smear negative pulmonary tuberculosis and extra-pulmonary tuberculosis, total number of new tuberculosis patients amounts to 9 to 10 million, and nearly 3 million persons die every year from tuberculosis, and 97% of these cases occur in developing countries. Failure of tuberculosis control in most developing countries could be explained by slow economic development of financial crisis, which caused poor allocation of budget for health including tuberculosis programme and slow development of primary health care. Activities of tuberculosis supervisory teams are weak. Tuberculosis programmes succeeded in developed countries could not be implemented easily in developing countries. New obstacles to the rapid decline of tuberculosis are the epidemic of AIDS, movement of population and lowering concern on tuberculosis problems, and tuberculosis will remain as one of serious global health problems at least for coming several decades. Maintenance of research and training facilities for tuberculosis is needed, however, they have been disappearing in developed countries. Facilities in developing countries might have difficulties to maintain unless financial and technical support is given from developed countries. Japan is the second biggest economic power in the world, and it is our duty to increase ODA for developing countries. In the field of health, Dr. Nakajima started to work as the director-general of WHO since 1988. We have to intensify our technical cooperation in health. As we succeeded to control tuberculosis in the past 40 years and still maintain research and training facilities for tuberculosis, they should be used for the sake of developing countries. Multi-and bi-lateral cooperation in tuberculosis control should also be intensified. The author would like to urge members of the Japanese Society for Tuberculosis to talk about the importance of tuberculosis problem and role expected to Japan in the global fight against tuberculosis to people outside the society so as to have appropriate understanding on global tuberculosis problems. PMID:2593463

Shimao, T

1989-11-01

53

Oral tuberculosis.  

PubMed

Tuberculous lesions of the oral cavity have become so infrequent that it is virtually a forgotten disease entity and may pose a diagnostic problem. Fifteen patients with conditions that were histologically diagnosed as oral tuberculosis were reviewed. All were men ranging in age from 29 to 78 years. The most common clinical presentation was odynophagia with a duration from less than 1 week to several years. The most frequently affected sites were the tongue base and gingiva. The oral lesions took the form of an irregular ulceration or a discrete granular mass. Mandibular bone destruction was evident in two patients. Two patients had a fever, and four had cervical lymphadenopathy. Eight cases were clinically suspicious for malignancy before biopsy. Only four patients had a history of tuberculosis, but 14 of the 15 patients were later found to have active pulmonary tuberculosis. Acid-fast bacilli were demonstrated in all patients. Tuberculosis should be considered in patients with an inflamed ulcer lesion. A biopsy specimen for histologic study, acid-fast stains, and cultures should be obtained for confirmation and differential diagnosis with other conditions. If a tuberculous lesion is suspected, a chest radiograph is indicated to investigate the possibility of pulmonary involvement. PMID:8705586

Eng, H L; Lu, S Y; Yang, C H; Chen, W J

1996-04-01

54

Genotyping and clinical characteristics of multidrug and extensively drug-resistant tuberculosis in a tertiary care tuberculosis hospital in China  

PubMed Central

Background There is a lack of information on the clinical characteristics of multidrug-resistant (MDR) tuberculosis (TB) and extensively drug-resistant (XDR) TB in the Jiangxi Province of China; furthermore, data have not been reported on the utility of mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) analyses in genotyping Mycobacterium tuberculosis strains isolated from this region. The aim of this study was to analyse the clinical features of patients with MDR and XDR TB from Jiangxi Province and to evaluate the discriminatory power of the 15-loci MIRU-VNTR method. Methods A retrospective study was conducted on patients diagnosed with MDR and XDR TB at the Jiangxi Chest Hospital from July 2010 to June 2011. The RD105 deletion-targeted multiplex PCR (DTM-PCR) and the 15-loci MIRU-VNTR method were used to determine the genetic background of the identified MDR and XDR M. tuberculosis clinical isolates. Results Of 804?M. tuberculosis clinical isolates, 159 (159/804, 19.8%) of the isolates were identified as MDR with first-line drug susceptibility testing. Of the 123 available MDR isolates, 13 (13/123, 10.6%) were XDR. The RD105 deletion-targeted multiplex PCR method identified 85 (85/110, 77.3%) MDR and 12 (12/13, 92.3%) XDR isolates as the Beijing genotype. MIRU-VNTR cluster analysis demonstrated that 101 MDR and 13 XDR strains had unique genotype patterns; the remaining 9 MDR strains were in 4 clusters, namely 1 cluster with 3 strains and 3 clusters with 2 strains, resulting in a low clustering rate (4.06%). The Hunter-Gaston discriminatory index (HGDI) of the 15-loci MIRU-VNTR method was as high as 0.992. In addition, clinical surveys showed that 87 (87/110, 79.1%) MDR TB patients and 10 (10/13, 76.9%) XDR TB patients had been previously treated. Diabetes mellitus was the most common comorbidity in both MDR TB (16/110, 14.5%) and XDR TB (2/13, 15.4%) patients. Conclusions Based on our preliminary data, the MDR and XDR M. tuberculosis clinical isolates identified at the Jiangxi Chest Hospital were genetically diverse and clustered at a low frequency. The 15-loci MIRU-VNTR method showed high discriminatory power and may be used as a first-line genotyping tool in investigating the molecular epidemiology of M. tuberculosis in Jiangxi, China. Decisive measures are urgently needed to effectively prevent and manage MDR and XDR tuberculosis in this province. PMID:23849244

2013-01-01

55

Integration of Antiretroviral Therapy with Tuberculosis Treatment  

PubMed Central

Background We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious. Methods To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts <500 cells/mm3. Findings on the early therapy group (ART initiated within 4 weeks of tuberculosis treatment initiation, n=214) and late therapy group (ART initiated within the first 4 weeks of the continuation phase of tuberculosis treatment, n=215) are presented here. Results Median CD4+ count and viral load at baseline was 150 cells/mm3 and 161000 copies/ml, being similar in both groups. Incidence rate of AIDS or death was 6.9 (18/259.4) and 7.8 (19/244.2) per 100 person-years in the early and late therapy groups respectively (Incidence Rate Ratio (IRR)=0.89; 95%Confidence Interval (95%CI): 0.44,1.79; P=0.73). However, in patients with CD4+ counts <50 cells/mm3, the incidence rates of AIDS or death were 8.5 (early) and 26.3 (late) per 100 person-years (IRR=0.32; 95%CI: 0.07,1.13; P=0.06). Immune reconstitution inflammatory syndrome (IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; P<0.001). Adverse events requiring antiretroviral drug switches occurred in 10 (early) and 1 (late) patients (P=0.006). Conclusions The benefits of AIDS-free survival balanced against the risks of IRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher. PMID:22010915

Abdool Karim, Salim S.; Naidoo, Kogieleum; Grobler, Anneke; Padayatchi, Nesri; Baxter, Cheryl; Gray, Andrew L.; Gengiah, Tanuja; Gengiah, Santhanalakshmi; Naidoo, Anushka; Jithoo, Niraksha; Nair, Gonasagrie; El-Sadr, Wafaa M.; Friedland, Gerald; Abdool Karim, Quarraisha

2011-01-01

56

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

57

Molecular Epidemiology of Mycobacterium tuberculosis Complex in Singapore, 2006-2012  

PubMed Central

Background Tuberculosis remains common in Singapore, increasing in incidence since 2008. We attempted to determine the molecular epidemiology of Mycobacterium tuberculosis complex (MTC) isolates locally, identifying major circulating genotypes and obtaining a glimpse of transmission dynamics. Methodology Non-duplicate MTC isolates archived between 2006 and 2012 at the larger clinical tuberculosis laboratory in Singapore were sampled for spoligotyping and MIRU-VNTR typing, with case data obtained from the Singapore Tuberculosis Elimination Program registry database. Isolates between 2008 and 2012 were selected because of either multidrug-resistance or potential epidemiological linkage, whereas earlier isolates were randomly selected. Separate analyses were performed for the early (2006-2007) and later (2008-2012) study phases in view of potential selection bias. Principal Findings A total of 1,612 MTC isolates were typed, constituting 13.1% of all culture-positive tuberculosis cases during this period. Multidrug-resistance was present in 91 (5.6%) isolates – higher than the national prevalence in view of selection bias. The majority of isolates belonged to the Beijing (45.8%) and EAI (22.8%) lineages. There were 347 (30.7%) and 133 (27.5%) cases clustered by combined spoligotyping and MIRU-VNTR typing from the earlier and later phases respectively. Patients within these clusters tended to be of Chinese ethnicity, Singapore resident, and have isolates belonging to the Beijing lineage. A review of prior contact investigation results for all patients with clustered isolates failed to reveal epidemiological links for the majority, suggesting either unknown transmission networks or inadequate specificity of the molecular typing methods in a country with a moderate incidence of tuberculosis. Conclusion Our work demonstrates that Singapore has a large and heterogeneous distribution of MTC strains, and with possible cross-transmission over the past few years based on our molecular typing results. A universal MTC typing program coupled with enhanced contact investigations may be useful in further understanding the transmission dynamics of tuberculosis locally. PMID:24367667

Win, Wah; Chee, Cynthia Bin-Eng; Hsu, Li Yang; Mak, Estelle; Earnest, Arul; Ong, Marcus Eng-Hock; Cutter, Jeffery; Wang, Yee Tang

2013-01-01

58

Impaired Pulmonary Nitric Oxide Bioavailability in Pulmonary Tuberculosis: Association With Disease Severity and Delayed Mycobacterial Clearance With Treatment  

PubMed Central

Background.?Nitric oxide (NO), a key macrophage antimycobacterial mediator that ameliorates immunopathology, is measurable in exhaled breath in individuals with pulmonary tuberculosis. We investigated relationships between fractional exhale NO (FENO) and initial pulmonary tuberculosis severity, change during treatment, and relationship with conversion of sputum culture to negative at 2 months. Methods.?In Papua, we measured FENO in patients with pulmonary tuberculosis at baseline and serially over 6 months and once in healthy controls. Treatment outcomes were conversion of sputum culture results at 2 months and time to conversion of sputum microscopy results. Results.?Among 200 patients with pulmonary tuberculosis and 88 controls, FENO was lower for patients with pulmonary tuberculosis at diagnosis (geometric mean FENO, 12.7 parts per billion [ppb]; 95% confidence interval [CI], 11.6–13.8) than for controls (geometric mean FENO, 16.6 ppb; 95% CI, 14.2–19.5; P = .002), fell further after treatment initiation (nadir at 1 week), and then recovered by 6 months (P = .03). Lower FENO was associated with more-severe tuberculosis disease, with FENO directly proportional to weight (P < .001) and forced vital-capacity (P = .001) and inversely proportional to radiological score (P = .03). People whose FENO increased or remained unchanged by 2 months were 2.7-fold more likely to achieve conversion of sputum culture than those whose FENO decreased (odds ratio, 2.72; 95% CI, 1.05–7.12; P = .04). Conclusions.?Among patients with pulmonary tuberculosis, impaired pulmonary NO bioavailability is associated with more-severe disease and delayed mycobacterial clearance. Measures to increase pulmonary NO warrant investigation as adjunctive tuberculosis treatments. PMID:23737604

Ralph, Anna P.; Yeo, Tsin W.; Salome, Cheryl M.; Waramori, Govert; Pontororing, Gysje J.; Kenangalem, Enny; Sandjaja; Tjitra, Emiliana; Lumb, Richard; Maguire, Graeme P.; Price, Ric N.; Chatfield, Mark D.; Kelly, Paul M.; Anstey, Nicholas M.

2013-01-01

59

Natural history of tuberculosis. Epidemiology.  

PubMed

This Symposium honours the achievements of Dr Karel Styblo. In this presentation, specific epidemiologic insights are reviewed. Studies of the epidemiology of tuberculosis in Eskimos showed a picture of tuberculosis at the height of the epidemic. Very high incidence was observed in young people who experienced a high fatality rate. Application of specific control measures were accompanied by rapid decline in rates, greater than observed in any other human population, demonstrating that tuberculosis could be brought under control by specific intervention. Studies of the natural trend of tuberculosis in South India showed that, even in the absence of intervention, a decline was observed in the rates of this disease. In the absence of chemotherapy, 50 per cent of cases die within 5 years, 30 per cent recover spontaneously and 20 per cent remain sputum positive. Studies of the efficacy of BCG in Madras, enabled to study the impact of efficient case-finding associated with poor treatment results showing that such a situation multiplies the number of surviving, infectious cases in the community and, thus, actually deteriorates the epidemiological situation. These various basic studies have shown both how to create success and how to create failure in tuberculosis programmes. PMID:1687514

Grzybowski, S

1991-12-01

60

Hematological Profile in Pulmonary Tuberculosis ORIGINAL RESEARCH Hematological Profile in Pulmonary Tuberculosis  

E-print Network

Background: Tuberculosis is a major public health problem in India. There is a paucity of literature in the hematological changes associated with tuberculosis, though tuberculosis is a common condition. Objective: To evaluate the hematological parameters in pulmonary tuberculosis patients who are positive for Mycobacterium tuberculosis bacilli in sputum. Materials and Methods: One hundred patients of fresh pulmonary tuberculosis with sputum positive for acid fast bacilli (AFB) were included and AIDS patients, disseminated tuberculosis and patients receiving ATT drugs were excluded in this study. The various hematological parameters were studied by means of hemogram by automated cell counter and peripheral smear examination. Results: Anemia was seen in 74 % of patients. In spite of the infection, 71 patients had a normal leukocyte count. Leucocytosis as a response to infection was observed in 26 patients. Three patients had leucopenia. Thrombocytosis was observed in 24 patients while thrombocytopenia was observed in 9 patients. 99 % patients had increased erythrocyte sedimentation rate (ESR). Two patients had pancytopenia. Conclusion: Variety of hematological abnormalities has been demonstrated in patients with pulmonary tuberculosis in the present study. While many of them are consistent with reported literature and reinforce the fact that they can be valuable tools in monitoring pulmonary tuberculosis such as anemia and increased ESR. Other findings such as thrombocytosis and pancytopenia suggest the need for further studied in this field.

Toolhally Umashankar; Sadula Govindareddy

61

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

62

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

63

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

64

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

65

Tuberculosis: Epidemiology and Control  

PubMed Central

Tuberculosis (TB) is a major public health concern worldwide: despite a regular, although slow, decline in incidence over the last decade, as many as 8.6 million new cases and 1.3 million deaths were estimated to have occurred in 2012. TB is by all means a poverty-related disease, mainly affecting the most vulnerable populations in the poorest countries. The presence of multidrug-resistant strains of M. tuberculosis in most countries, with somewhere prevalence is high, is among the major challenges for TB control, which may hinder recent achievements especially in some settings. Early TB case detection especially in resource-constrained settings and in marginalized groups remains a challenge, and about 3 million people are estimated to remain undiagnosed or not notified and untreated. The World Health Organization (WHO) has recently launched a new global TB strategy for the “post-2015 era” aimed at “ending the global TB epidemic” by 2035. This strategy is based on the three pillars that emphasize patient-centred TB care and prevention, bold policies and supportive systems, and intensified research and innovation. This paper aims to provide an overview of the global TB epidemiology as well as of the main challenges that must be faced to eliminate the disease as a public health problem everywhere.

Sulis, Giorgia; Roggi, Alberto; Matteelli, Alberto; Raviglione, Mario C.

2014-01-01

66

Incidence of tuberculosis among Scandinavian immigrants in Canada.  

PubMed

Tuberculosis incidence in Finland is at least five times higher than in the other Scandinavian countries. A study of the incidence of tuberculosis in immigrants to Canada from Finland and the other Scandinavian countries shows a remarkable similarity between the rates of the immigrants and those who remained in their country of origin, even after 40 years of residence in the new country. The early experience of tuberculosis thus predetermines future susceptibility throughout the life span of the group. PMID:7439278

Enarson, D A; Sjögren, I; Grzybowski, S

1980-06-01

67

Abdominal tuberculosis.  

PubMed Central

The abdomen is involved in 10% to 30% of patients with pulmonary tuberculosis. The diagnosis is not difficult in societies where the disease is common and clinicians are aware of it. While previously rare in Western countries, the incidence is now rising among immigrants, and patients with AIDS. In HIV-infected patients, the disease is of a rapidly progressive nature, often fatal through usually treatable, but the diagnosis is difficult and often delayed. Treatment is essentially medical but occasionally surgical operation is necessary. PMID:8154817

Ahmed, M. E.; Hassan, M. A.

1994-01-01

68

Brainstem tuberculosis.  

PubMed

We present a case of a 38-year-old-man who presented with 1-week history of developing weakness of peripheral and cranial nerves. His MRI scan of the brain showed a large cavitating lesion at the brainstem and two further lesions of the right cerebral cortex and his CT chest showed features of old tuberculosis (TB). The identification of acid-fast bacilli was confirmed by analysis of bronchoalveolar lavage taken during bronchoscopy. He was started on anti-TB medications and repeat MRI 3 months later confirmed shrinkage of the cavitating lesion. PMID:23868024

Demetriou, George A

2013-01-01

69

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

70

NATURE MEDICINE VOLUME 13 | NUMBER 3 | MARCH 2007 299 Changing funding patterns in tuberculosis  

E-print Network

in tuberculosis Stefan H E Kaufmann & Shreemanta K Parida Exactly 125 years after the discovery of the etio- logical agent of tuberculosis (TB), the disease remains as threatening as ever.The insufficient control. The killer disease was tuberculosis (TB), and the scientist Robert Koch (1843­1910). Today, we have tools

Cai, Long

71

Early Bactericidal Activity of Moxifloxacin in Treatment of Pulmonary Tuberculosis: a Prospective, Randomized Study  

Microsoft Academic Search

Tuberculosis remains one of the deadliest diseases in the world. The World Health Organization (WHO) estimates that more than 8 million new cases of tuberculosis occur each year, and approximately 3 million people die from the disease. The emerging resistance of Mycobacterium tuberculosis to standard antituberculous drugs raises the need for the devel- opment of new agents. Fluoroquinolones are of

Mathias W. R. Pletz; Andres De Roux; Andreas Roth; Karl-Heinz Neumann; Harald Mauch; Hartmut Lode

2004-01-01

72

Measuring health-related quality of life in tuberculosis: a systematic review  

Microsoft Academic Search

INTRODUCTION: Tuberculosis remains a major public health problem worldwide. In recent years, increasing efforts have been dedicated to assessing the health-related quality of life experienced by people infected with tuberculosis. The objectives of this study were to better understand the impact of tuberculosis and its treatment on people's quality of life, and to review quality of life instruments used in

Na Guo; Fawziah Marra; Carlo A Marra

2009-01-01

73

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/microfluidics 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

74

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

75

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

E-print Network

A wireless sensor network to measure the health care workers exposure to tuberculosis Guillaume Care Workers (HCWs) exposure to tuberculosis in their work environment. Despite the progresses in treatment and prevention, tuberculosis remains a disease in expansion and represents the third cause

Paris-Sud XI, Université de

76

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

Obregon-Henao, Andres; Henao-Tamayo, Marcela; Orme, Ian M.; Ordway, Diane J.

2013-01-01

77

Epidemiology of Tuberculosis in a High HIV Prevalence Population Provided with Enhanced Diagnosis of Symptomatic Disease  

Microsoft Academic Search

BackgroundDirectly observed treatment short course (DOTS), the global control strategy aimed at controlling tuberculosis (TB) transmission through prompt diagnosis of symptomatic smear-positive disease, has failed to prevent rising tuberculosis incidence rates in Africa brought about by the HIV epidemic. However, rising incidence does not necessarily imply failure to control tuberculosis transmission, which is primarily driven by prevalent infectious disease. We

Elizabeth L. Corbett; Tsitsi Bandason; Yin Bun Cheung; Shungu Munyati; Peter Godfrey-Faussett; Richard Hayes; Gavin Churchyard; Anthony Butterworth; Peter Mason

2007-01-01

78

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

79

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

80

Time delays in diagnosis of pulmonary tuberculosis: a systematic review of literature  

Microsoft Academic Search

BACKGROUND: Delay in diagnosis of pulmonary tuberculosis results in increasing severity, mortality and transmission. Various investigators have reported about delays in diagnosis of tuberculosis. We aimed at summarizing the data on these delays in diagnosis of tuberculosis. METHODS: A systematic review of literature was carried out. Literature search was done in Medline and EMBASE from 1990 to 2008. We used

Chandrashekhar T Sreeramareddy; Kishore V Panduru; Joris Menten; J Van den Ende

2009-01-01

81

Tuberculosis screening and follow-up of asylum seekers in Norway: a cohort study  

Microsoft Academic Search

BACKGROUND: About 80% of new tuberculosis cases in Norway occur among immigrants from high incidence countries. On arrival to the country all asylum seekers are screened with Mantoux test and chest x-ray aimed to identify cases of active tuberculosis and, in the case of latent tuberculosis, to offer follow-up or prophylactic treatment. We assessed a national programme for screening, treatment

Ingunn Harstad; Einar Heldal; Sigurd L Steinshamn; Helge Garåsen; Geir W Jacobsen

2009-01-01

82

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

83

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

84

Insights into ancient leprosy and tuberculosis using metagenomics.  

PubMed

Leprosy and tuberculosis were widespread in the past and remain significant diseases today. Comparison of ancient and modern genomes of Mycobacterium leprae and Mycobacterium tuberculosis gives insight into their evolution and a calibration of the timescale for observed changes. Recently, whole genome sequencing has revealed genotypes and mixed-strain infections. PMID:23932433

Donoghue, Helen D

2013-09-01

85

IMMUNE MODULATION OF THE MYCOBACTERIUM TUBERCULOSIS GRANULOMATOUS RESPONSE  

Microsoft Academic Search

Tuberculosis (TB) remains a major public health burden. The immunocompetant host responds to Mycobacterium tuberculosis (MTB) infection by the formation of granulomas, which initially prevent uncontrolled bacterial proliferation and dissemination. However, increasing evidence suggests that granuloma formation promotes persistence of the organism by physically separating infected cells from effector lymphocytes and by inducing a state of non-replicating persistence in the

Kerry J Welsh

2011-01-01

86

Origin, Spread and Demography of the Mycobacterium tuberculosis Complex  

Microsoft Academic Search

The evolutionary timing and spread of the Mycobacterium tuberculosis complex (MTBC), one of the most successful groups of bacterial pathogens, remains largely unknown. Here, using mycobacterial tandem repeat sequences as genetic markers, we show that the MTBC consists of two independent clades, one composed exclusively of M. tuberculosis lineages from humans and the other composed of both animal and human

Thierry Wirth; Falk Hildebrand; Caroline Allix-Béguec; Florian Wölbeling; Tanja Kubica; Kristin Kremer; Dick van Soolingen; Sabine Rüsch-Gerdes; Camille Locht; Sylvain Brisse; Axel Meyer; Philip Supply; Stefan Niemann

2008-01-01

87

Current management options for latent tuberculosis: a review  

PubMed Central

Tuberculosis remains the world’s second leading infectious cause of death, with nearly one-third of the global population latently infected. Treatment of latent tuberculosis infection is a mainstay of tuberculosis-control efforts in low-to medium-incidence countries. Isoniazid monotherapy has been the standard of care for decades, but its utility is impaired by poor completion rates. However, new, shorter-course regimens using rifamycins improve completion rates and are cost-saving compared with standard isoniazid monotherapy. We review the currently available therapies for latent tuberculosis infection and their toxicities and include a brief economic comparison of the different regimens. PMID:23226700

Norton, Brianna L; Holland, David P

2012-01-01

88

Association between tumor necrosis factor alpha-238G/a polymorphism and tuberculosis susceptibility: a meta-analysis study  

PubMed Central

Background Tumor necrosis factor alpha (TNF-?) plays a key role in the containment of tuberculosis. The relationship between the TNF -238G/A polymorphism and tuberculosis susceptibility remains inconclusive. A comprehensive meta-analysis was made to provide a more precise estimate of the relationship between them. Methods Multiple search strategies were used. A fixed effect model was takentook to estimate pooled OR with 95% confidence interval (CI) for the association between the TNF -238G/A polymorphism and tuberculosis susceptibility. The Chi-squared-based Q-test and I-squaredI2 statistic were calculated to examine heterogeneity. Begg’s funnel plot and Egger’s test were used to assess publication bias. Results 9 case-control studies were included in this meta-analysis. No significant heterogeneity was demonstrated, and no obvious publication bias was detected among the included studies. The meta-analysis indicated that there was no significant association between the TNF -238G/A polymorphism and tuberculosis susceptibility (GA+AA versus GG model: OR=1.005, 95% CI: 0.765-1.319; A versus G model: OR=1.000, 95% CI: 0.769-1.300). In the subgroup analyses by ethnicity, types of TB and human immunodeficiency virus (HIV) status, no significant association were identified. Conclusions The meta-analysis involving 2723 subjects did not detect any association between the TNF -238G/A polymorphism and tuberculosis susceptibility. PMID:23192010

2012-01-01

89

Tuberculosis of sacrum mimicking as malignancy.  

PubMed

Tuberculosis has always been a menace for both clinicians and radiologists due to its often non-specific and protean manifestations. Isolated tubercular involvement of sacrum is very rare. The authors present the case of a 38-year-old man with history of low-grade fever, pain and swelling in the sacral region. Skiagram revealed an osteolytic lesion of sacrum leading to the provisional diagnosis of chordoma and osteoclastoma. However, MRI was suggestive of a chronic infective condition like tuberculosis and fine needle aspiration cytology was positive for acid-fast bacilli and revealed epitheloid granulomas with caseous necrosis. Culture was positive for Mycobacterium tuberculosis. Antitubercular therapy was commenced and surgical decompression of cold abscess was done and with good clinical response. This case highlights the importance of remaining cognisant of the manifestations and the importance of considering tuberculosis as a diagnosis at unusual sites of involvement. PMID:22605808

Shantanu, Kumar; Sharma, Vineet; Kumar, Santosh; Jain, Sonal

2012-01-01

90

Tuberculosis of sacrum mimicking as malignancy  

PubMed Central

Tuberculosis has always been a menace for both clinicians and radiologists due to its often non-specific and protean manifestations. Isolated tubercular involvement of sacrum is very rare. The authors present the case of a 38-year-old man with history of low-grade fever, pain and swelling in the sacral region. Skiagram revealed an osteolytic lesion of sacrum leading to the provisional diagnosis of chordoma and osteoclastoma. However, MRI was suggestive of a chronic infective condition like tuberculosis and fine needle aspiration cytology was positive for acid-fast bacilli and revealed epitheloid granulomas with caseous necrosis. Culture was positive for Mycobacterium tuberculosis. Antitubercular therapy was commenced and surgical decompression of cold abscess was done and with good clinical response. This case highlights the importance of remaining cognisant of the manifestations and the importance of considering tuberculosis as a diagnosis at unusual sites of involvement. PMID:22605808

Shantanu, Kumar; Sharma, Vineet; Kumar, Santosh; Jain, Sonal

2012-01-01

91

Virulence factors of the Mycobacterium tuberculosis complex  

PubMed Central

The Mycobacterium tuberculosis complex (MTBC) consists of closely related species that cause tuberculosis in both humans and animals. This illness, still today, remains to be one of the leading causes of morbidity and mortality throughout the world. The mycobacteria enter the host by air, and, once in the lungs, are phagocytated by macrophages. This may lead to the rapid elimination of the bacillus or to the triggering of an active tuberculosis infection. A large number of different virulence factors have evolved in MTBC members as a response to the host immune reaction. The aim of this review is to describe the bacterial genes/proteins that are essential for the virulence of MTBC species, and that have been demonstrated in an in vivo model of infection. Knowledge of MTBC virulence factors is essential for the development of new vaccines and drugs to help manage the disease toward an increasingly more tuberculosis-free world. PMID:23076359

Forrellad, Marina A.; Klepp, Laura I.; Gioffre, Andrea; Sabio y Garcia, Julia; Morbidoni, Hector R.; Santangelo, Maria de la Paz; Cataldi, Angel A.; Bigi, Fabiana

2013-01-01

92

Optimization of recombinant Mycobacterium tuberculosis RNA polymerase expression and purification.  

PubMed

Mycobacterium tuberculosis, the human pathogen that causes tuberculosis, warrants enormous attention due to the emergence of multi drug resistant and extremely drug resistant strains. RNA polymerase (RNAP), the key enzyme in gene regulation, is an attractive target for anti-TB drugs. Understanding the structure-function relationship of M. tuberculosis RNAP and the mechanism of gene regulation by RNAP in conjunction with different ? factors and transcriptional regulators would provide significant information for anti-tuberculosis drug development targeting RNAP. Studies with M. tuberculosis RNAP remain tedious because of the extremely slow-growing nature of the bacteria and requirement of special laboratory facility. Here, we have developed and optimized recombinant methods to prepare M. tuberculosis RNAP core and RNAP holo enzymes assembled in vivo in Escherichia coli. These methods yield high amounts of transcriptionally active enzymes, free of E. coli RNAP contamination. The recombinant M. tuberculosis RNAP is used to develop a highly sensitive fluorescence based in vitro transcription assay that could be easily adopted in a high-throughput format to screen RNAP inhibitors. These recombinant methods would be useful to set a platform for M. tuberculosis RNAP targeted anti TB drug development, to analyse the structure/function of M. tuberculosis RNAP and to analyse the interactions among promoter DNA, RNAP, ? factors, and transcription regulators of M. tuberculosis in vitro, avoiding the hazard of handling of pathogenic bacteria. PMID:24832563

Banerjee, Rajdeep; Rudra, Paulami; Prajapati, Ranjit Kumar; Sengupta, Shreya; Mukhopadhyay, Jayanta

2014-07-01

93

Rapid Differential Diagnosis between Extrapulmonary Tuberculosis and Focal Complications of Brucellosis Using a Multiplex Real-Time PCR Assay  

PubMed Central

Background Arduous to differ clinically, extrapulmonary tuberculosis and focal complications of brucellosis remain important causes of morbidity and mortality in many countries. We developed and applied a multiplex real-time PCR assay (M RT-PCR) for the simultaneous detection of Mycobacterium tuberculosis complex and Brucella spp. Methodology Conventional microbiological techniques and M RT-PCR for M. tuberculosis complex and Brucella spp were performed on 45 clinical specimens from patients with focal complications of brucellosis or extrapulmonary tuberculosis and 26 control samples. Fragments of 207 bp and 164 bp from the conserved region of the genes coding for an immunogenic membrane protein of 31 kDa of B. abortus (BCSP31) and the intergenic region SenX3-RegX3 were used for the identification of Brucella and M. tuberculosis complex, respectively. Conclusions The detection limit of the M RT-PCR was 2 genomes per reaction for both pathogens and the intra- and inter-assay coefficients of variation were 0.44% and 0.93% for Brucella and 0.58% and 1.12% for Mycobacterium. M RT-PCR correctly identified 42 of the 45 samples from patients with tuberculosis or brucellosis and was negative in all the controls. Thus, the overall sensitivity, specificity, PPV and NPV values of the M RT PCR assay were 93.3%, 100%, 100% and 89.7%, respectively, with an accuracy of 95.8% (95% CI, 91.1%–100%). Since M RT-PCR is highly reproducible and more rapid and sensitive than conventional microbiological tests, this technique could be a promising and practical approach for the differential diagnosis between extrapulmonary tuberculosis and focal complications of brucellosis. PMID:19225565

Queipo-Ortuno, Maria Isabel; Colmenero, Juan D.; Bermudez, Pilar; Bravo, Maria Jose; Morata, Pilar

2009-01-01

94

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

95

Isoniazid-Resistant Tuberculosis in Children: A Systematic Review  

PubMed Central

Background Isoniazid resistance is an obstacle to the treatment of tuberculosis disease and latent tuberculosis infection in children. We aim to summarize the literature describing the risk of isoniazid-resistant tuberculosis among children with tuberculosis disease. Methods We did a systematic review of published reports of children with tuberculosis disease who had isolates tested for susceptibility to isoniazid. We searched PubMed, Embase and LILACS online databasesuptoJanuary 12, 2012. Results Our search identified 3,403 citations, of which 95 studies met inclusion criteria. These studies evaluated 8,351 children with tuberculosis disease for resistance to isoniazid. The median proportion of children found to have isoniazid-resistant strains was 8%; the distribution was right-skewed (25th percentile: 0% and 75th percentile: 18%). Conclusions High proportions of isoniazid resistance among pediatric tuberculosis patients have been reported in many settings suggesting that diagnostics detecting only rifampin resistance are insufficient to guide appropriate treatment in this population. Many children are likely receiving sub-standard tuberculosis treatment with empirical isoniazid-based regimens, and treating latent tuberculosis infection with isoniazid may not be effective in large numbers of children. Work is needed urgently to identify effective regimens for the treatment of children sick with or exposed to isoniazid-resistant tuberculosis and to better understand the scope of this problem. PMID:23348808

Yuen, Courtney M.; Tolman, Arielle W.; Cohen, Ted; Parr, Jonathan B.; Keshavjee, Salmaan; Becerra, Mercedes C.

2013-01-01

96

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

97

Immunological biomarkers of tuberculosis  

Microsoft Academic Search

Currently there are no sufficiently validated biomarkers to aid the evaluation of new tuberculosis vaccine candidates, the improvement of tuberculosis diagnostics or the development of more effective and shorter treatment regimens. To date, the detection of Mycobacterium tuberculosis or its products has not been able to adequately address these needs. Understanding the interplay between the host immune system and M.

Katharina Ronacher; Willem Hanekom; Thomas J. Scriba; Alimuddin Zumla; Gerhard Walzl

2011-01-01

98

Mycobacterium tuberculosis complex drug resistance pattern and identification of species causing tuberculosis in the West and Centre regions of Cameroon  

PubMed Central

Background Data on the levels of resistance of Mycobacterium tuberculosis complex (MTBC) strains to first line anti-tuberculosis drugs in Cameroon, and on the species of MTBC circulating in the country are obsolete. The picture about 10 years after the last studies, and 6 years after the re-organisation of the National Tuberculosis (TB) Control Programme (NTBCP) is not known. Methods The study was conducted from February to July 2009 in the West and Centre regions of Cameroon. A total of 756 suspected patients were studied. MTBC species were detected by the standard Ziehl-Neelsen staining method. Bacterial susceptibility to the first line drugs [isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (SM)] were performed on cultures using the indirect proportion method. MTBC species were identified by standard biochemical and culture methods. Results Of the 756 suspected patients, 154 (20.37%) were positive by smear microscopy. Of these, 20.77% were HIV patients. The growth of Mycobacterium was observed with the sputa from 149 (96.75%) subjects. All the isolates were identified as either M. tuberculosis or M. africanum. Among these, 16 (10.73%) were resistant to at least one drug (13.3% for the West region and 8.1% for the Centre). The initial resistance rates were 7.35% for the Centre region and 11.29% for the West region, while the acquired resistance rates were 16.66% (1/6) for the Centre region and 23.07% (3/13) for the West. Within the two regions, the highest total resistance to one drug was obtained with INH and SM (2.68% each). Multidrug-resistance (MDR) was observed only in the West region at a rate of 6.67%. No resistance was recorded for EMB. Conclusions M. tuberculosis and M. africanum remain the MTBC species causing pulmonary TB in the West and Centre regions of Cameroon. Following the re-organisation of the NTBCP, resistance to all first line anti-TB drugs has declined significantly (p < 0.05 for West; and p < 0.01 for Centre) in comparison to previous studies. However, the general rates of anti-TB drug resistance remain high in the country, underscoring the need for greater enforcement of control strategies. PMID:21496268

2011-01-01

99

Global epidemiology of tuberculosis.  

PubMed

With 1.4 million deaths in 2011 and 8.7 million new cases, tuberculosis (TB) disease remains a global scourge. Global targets for reductions in the epidemiological burden of TB have been set for 2015 and 2050 within the context of the Millennium Development Goals (MDGs) and by the Stop TB Partnership. Achieving these targets is the focus of national and international efforts in TB control, and demonstrating whether or not they are achieved is of major importance to guide future and sustainable investments.This paper discusses the methods used to estimate the global burden of TB; estimates of incidence, prevalence, and mortality for 2011, combined with assessment of progress toward the 2015 targets for reductions in these indicators based on trends since 1990 and projections up to 2015; trends in TB notifications and in the implementation of the Stop TB Strategy; and prospects for elimination of TB by 2050. PMID:23460002

Glaziou, Philippe; Falzon, Dennis; Floyd, Katherine; Raviglione, Mario

2013-02-01

100

Tuberculosis revisited: Cytological perspective.  

PubMed

Tuberculosis is a major public health problem, especially in developing countries. The clinical manifestations of tuberculosis are very nonspecific and may mimic many other conditions. An accurate diagnosis is extremely important as the disease is treatable with antituberculous therapy. Cytological examination can provide useful diagnostic material for routine and ancillary techniques for rapid and accurate diagnosis of tuberculosis. Here we review the different morphological patterns of tuberculosis, challenges, and application of ancillary techniques for cytological diagnosis of tuberculosis. Diagn. Cytopathol. 2014;42:993-1001. © 2014 Wiley Periodicals, Inc. PMID:24975566

Chatterjee, Debajyoti; Dey, Pranab

2014-11-01

101

Attitudes about Tuberculosis Prevention in the Elimination Phase: A Survey among Physicians in Germany  

PubMed Central

Background Targeted and stringent measures of tuberculosis prevention are necessary to achieve the goal of tuberculosis elimination in countries of low tuberculosis incidence. Methods We ascertained the knowledge about tuberculosis risk factors and stringency of tuberculosis prevention measures by a standardized questionnaire among physicians in Germany involved in the care of individuals from classical risk groups for tuberculosis. Results 510 physicians responded to the online survey. Among 16 risk factors immunosuppressive therapy, HIV-infection and treatment with TNF-antagonist were thought to be the most important risk factors for the development of tuberculosis in Germany. Exposure to a patient with tuberculosis ranked on the 10th position. In the event of a positive tuberculin-skin-test or interferon-? release assay only 50%, 40%, 36% and 25% of physicians found that preventive chemotherapy was indicated for individuals undergoing tumor necrosis factor-antagonist therapy, close contacts of tuberculosis patients, HIV-infected individuals and migrants, respectively. Conclusions A remarkably low proportion of individuals with latent infection with Mycobacterium tuberculosis belonging to classical risk groups for tuberculosis are considered candidates for preventive chemotherapy in Germany. Better knowledge about the risk for tuberculosis in different groups and more stringent and targeted preventive interventions will probably be necessary to achieve tuberculosis elimination in Germany. PMID:25393241

Vollrath, Oliver; Lange, Christoph

2014-01-01

102

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, ...

103

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 ...

104

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 ...

105

Social scientists and the new tuberculosis  

Microsoft Academic Search

In much of the world, tuberculosis (TB) remains the leading killer of young adults, in spite of the fact that effective chemotherapy has existed for 50 years. The epidemiology of TB, with its persistence in poor countries and resurgence among the poor of many industrialized nations, causes consternation among those charged with protecting the public's health. Two factors, ostensibly biological

Paul Farmer

1997-01-01

106

Pulmonary tuberculosis diagnostic delays in Chad: a multicenter, hospital-based survey in Ndjamena and Moundou  

PubMed Central

Background Tuberculosis remains one of the leading causes of morbidity and mortality in low-resource countries. One contagious patient can infect 10 to 20 contacts in these settings. Delays in diagnosing TB therefore contribute to the spread of the disease and sustain the epidemic. Objectives The aim of this study was to assess delays in diagnosing tuberculosis and the factors associated with these delays in the public hospitals in Moundou and Ndjamena, Chad. Methods A structured questionnaire was administered to 286 new tuberculosis patients to evaluate patient delay (time from the onset of symptoms to the first formal or informal care), health-care system delay (time from the first health care to tuberculosis treatment) and total delay (sum of the patient and system delays). Logistic regression was used to identify risk factors associated with long diagnostic delays (defined as greater than the median). Results and discussion The median [interquartile range] patient delay, system delay and total delay were 15 [7–30], 36 [19–65] and 57.5 [33–95] days, respectively. Low economic status (aOR [adjusted odds ratio] =2.38 [1.08-5.25]), not being referred to a health service (aOR?=?1.75 [1.02- 3.02]) and a secondary level education (aOR?=?0.33 [0.12-0.92]) were associated with a long patient delay. Risk factors for a long system delay were a low level of education (aOR?=?4.71 [1.34-16.51]) and the belief that traditional medicine and informal care can cure TB (aOR?=?5.46 [2.37-12.60]). Conclusion Targeted strengthening of the health-care system, including improving patient access, addressing deficiencies in health-related human resources, and improving laboratory networks and linkages as well as community mobilization will make for better outcomes in tuberculosis diagnosis. PMID:22776241

2012-01-01

107

Chemotherapeutic Interventions Against Tuberculosis  

PubMed Central

Tuberculosis is the second leading cause of infectious deaths globally. Many effective conventional antimycobacterial drugs have been available, however, emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) has overshadowed the effectiveness of the current first and second line drugs. Further, currently available agents are complicated by serious side effects, drug interactions and long-term administration. This has prompted urgent research efforts in the discovery and development of new anti-tuberculosis agent(s). Several families of compounds are currently being explored for the treatment of tuberculosis. This review article presents an account of the existing chemotherapeutics and highlights the therapeutic potential of emerging molecules that are at different stages of development for the management of tuberculosis disease. PMID:24281707

Shakya, Neeraj; Garg, Gaurav; Agrawal, Babita; Kumar, Rakesh

2012-01-01

108

Immunodominant Tuberculosis CD8 Antigens Preferentially Restricted by HLA-B  

Microsoft Academic Search

CD8+ T cells are essential for host defense to intracellular bacterial pathogens such as Mycobacterium tuberculosis (Mtb), Salmonella species, and Listeria monocytogenes, yet the repertoire and dominance pattern of human CD8 antigens for these pathogens remains poorly characterized. Tuberculosis (TB), the disease caused by Mtb infection, remains one of the leading causes of infectious morbidity and mortality worldwide and is

Deborah A Lewinsohn; Ervina Winata; Gwendolyn M Swarbrick; Katie E Tanner; Matthew S Cook; Megan D Null; Meghan E Cansler; Alessandro Sette; John Sidney; David M Lewinsohn

2007-01-01

109

Obesity Remains Rampant Across America  

MedlinePLUS

... sharing features on this page, please enable JavaScript. Obesity Remains Rampant Across America Two new studies present ... September 4, 2014 Related MedlinePlus Pages Health Disparities Obesity Obesity in Children THURSDAY, Sept. 4, 2014 (HealthDay ...

110

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

111

[Spleen and medullary tuberculosis].  

PubMed

Spleen is a rare extra-pulmonary tuberculosis manifestation. The spleen tuberculosis is caused by the blood derivative dissemination of mycobacteria. The symptoms can suggest a hematological disease, but it is difficult to make a diagnosis, especially when there are no pulmonary changes. The case of a 27-year-old woman with unclear etiology bone marrow hypoplasia was presented. The patient experienced: fever, body weight loss, pancytopenia and spleen enlargement with numerous focal echographic changes. The splenectomy revealed in a histopathologic examination productiva caseosa tuberculosis. The bone marrow trepanobiopsy revealed as well tuberculosis changes. The antimycobacteria treatment caused an improvement of the clinical state and the regression of symptoms. PMID:20229713

B?achnio, Maria; Zielonka, Tadeusz M; Rzewuska, Ewa; Mioduszewska, Olga; Maryniak, Renata; B?achnio, Antoni

2009-01-01

112

Isolated pancreatic tuberculosis masquerading as pancreatic cancer  

PubMed Central

Isolated pancreatic tuberculosis (TB) remains a rarity despite the high incidence of tuberculosis in many of the African and Asian countries. Presentation as discrete pancreatic mass often masquerades as pancreatic neoplasm and diagnosis may require histology. Extra-hepatic portal hypertension due to splenic vein thrombosis complicating pancreatic TB has been reported in the literature. We report here a case of isolated pancreatic TB with pancreatic head mass mimicking neoplasm with extra-hepatic portal hypertension. The possibility of TB should be considered in the list of differential diagnoses of pancreatic mass and an endoscopic, ultrasound-guided biopsy might help to clinch the diagnosis of this potentially curable disease. PMID:24759351

Zacharia, George S.; Antony, Rajany; Kolassery, Sandesh; Ramachandran, Thazhath M.

2014-01-01

113

Bowel obstruction caused by intestinal tuberculosis: an update  

PubMed Central

Tuberculosis is one of the most important communicable diseases worldwide, with an increasing incidence within the UK. The abdomen is involved in 11% of patients with extra-pulmonary tuberculosis, and can provide a diagnostic challenge if not suspected. The authors report the case of a 31-year-old Sudanese female who presented with intestinal obstruction due to a mass caused by abdominal tuberculosis. Imaging revealed evidence of multifocal tuberculosis involving the ileo-caecal region with abdominal and mediastinal lymphadenopathy. She went on to have a limited right hemicolectomy and completed antitubercular therapy. It is important to consider abdominal tuberculosis when conditions such as Crohn’s disease or gastrointestinal malignancy are being entertained in those from a high-risk background. Since diagnosis can be difficult, if clinical suspicion is strong, surgery is a safe option. Recommended management combines up to 12 months of antitubercular therapy with conservative surgery. PMID:22673714

Patel, Nimesh; Ondhia, Chandni; Ahmed, Shabbir

2011-01-01

114

The Lyons Creek boat remains  

E-print Network

THE LYONS CREEK BOAT REMAINS A Thesis by ROBERT STEPHEN NEYLAND Submitted to the Office of Graduate Studies of Texas A a M University in partial fulfillment of the requirements for the degree of MASTER OF ARTS December 1990 Ma/or Subject...: Anthropology THE LYONS CREEK BOAT REMAINS A Thesis by ROBERT STEPHEN NEYLAND Approved as to style and content by: D. L. Hamilton (Chair of Co it e) J. Richard eff ( mber) John Canu (Member) ~i' . g Vaughn M. Bryant (Head of Department) December...

Neyland, Robert Stephen

2012-06-07

115

The Identification of Human Remains  

PubMed Central

The identification of human remains, especially if they have been mutilated or burnt, or occur in skeletal form, may pose a major problem for the forensic physician. It may involve the co-operation of coroner, police officer, forensic pathologist and forensic laboratory. It is first necessary to demonstrate that the remains are human, and that the tissue in question represents one, or more than one, body. A meticulous postmortem examination by the forensic pathologist will reveal all anatomical peculiarities for study and record. Photographs, radiographs, dental charts, fingerprints and blood type all contribute materially to the solution of the problem. PMID:14199110

Deadman, William J.

1964-01-01

116

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

117

Tuberculosis in the elderly.  

PubMed

Tuberculosis (TB) today remains one of the world's most lethal infectious diseases. An estimated one-third of the world's 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 as harboring Mtb without evidence of active infection, and TB disease is active infection without Mtb based on clinical and laboratory findings. Recognizing that TB has been one of the most neglected international health problems and that the TB epidemic is rampant in many parts of the world, the World Health Organization (WHO) declared TB to be a global health emergency in 1993 (23). Despite the steady decline in TB cases since this time resulting from the overall implementation of more effective infection control practices, directly observed therapy (DOT), and efforts to control the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) epidemic, preventive and control strategies among other high-risk populations such as the elderly evidently remain a clinical and epidemiological challenge. The geriatric population among all ethnic groups and both genders, represent the largest reservoir of TB infection, particularly in developed nations (9). Clinical features of TB in older adults may be atypical, non-specific, and confused with concomitant age-related diseases (28). Underlying acute or chronic diseases, malnutrition, and the biological changes with aging, can disrupt integumental barriers, impair microbial clearance mechanisms, and contribute to the expected age-associated decline in cellular immune responses to infecting agents such as Mtb. Diagnosis of TB can be difficult and consequently overlooked; this treatable infection may unfortunately be recognized only at autopsy. Furthermore, therapy of TB in the elderly is challenging because of the increased incidence of adverse drug reactions. Optimal treatment of associated chronic diseases, minimization of invasive procedures, limitation of polypharmacy, and adequate nutritional support are essential for this vulnerable population. The institutionalized elderly in addition are especially at high risk for reactivation of latent TB as well as susceptible to new TB infection. This article will discuss the global epidemiology, pathogenesis and immunologic aspects, unique clinical consideration, treatment and prevention of TB, briefly inclusive of the recent published guidelines for targeted tuberculin testing and treatment of latent TB infection as it pertains to the elderly. PMID:11130191

Rajagopalan, S; Yoshikawa, T T

2000-10-01

118

Immunotherapeutical Potential of Mycobacterium Vaccae on M. Tuberculosis Infection in Mice  

PubMed Central

Tuberculosis remains the worldwide infectious disease. To identify the therapeutic potential of M. vaccae in treating tuberculosis, M. vaccae was injected into Mycobacterium tuberculosis (M. tuberculosis) infected mice. The optimal dose of M. vaccae (22.5 µg/mouse) treated mice showed lower pathological change index, spleen weight index, lung weight index and vital M. tuberculosis count than those of the untreated group. Treatment with M. vaccae enhanced the percentages of CD3+ and CD4+ T cells, IFN-?+CD4+ T cells, innate immune cells including NK cells, NK1.1+ T cells and ?? T cells, and reduced the percentage of IL-4+CD4+ T cells. Therefore, M. vaccae could protect the mice from M. tuberculosis infection and improved mouse innate and adaptive cell-mediated immunity, suggesting that M. vaccae is a potential immunotherapeutic agent in pulmonary tuberculosis. PMID:19254482

Xu, Lijun; Wang, Yanyan; Zheng, Xiaodong; Gui, Xiangdong; Tao, Lifeng; Wei, Haiming

2009-01-01

119

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

120

Zebrafishing for tuberculosis infection  

Microsoft Academic Search

Mycobacterium tuberculosis, also known as Koch’s bacillus, is the causative microbe of human tuberculosis (TB) that mainly involves lungs. For centuries, pulmonary TB, known as “lao” disease in Chinese, had been a brutal killer to human beings, as no drug was available to fight it. In the second half of the twentieth century, with the discovery and clinical application of

Liwei Wang

2010-01-01

121

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

122

New drug candidates and therapeutic targets for tuberculosis therapy.  

PubMed

Despite advances in chemotherapy and the BCG (Bacillus Calmette-Guérin) vaccine, tuberculosis remains a significant infectious disease. Although it can be cured, the therapy takes at least 6-9 months, and the laborious and lengthy treatment brings with it dangers of noncompliance, significant toxicity and drug resistance. The increasing emergence of drug resistance and the problem of mycobacterial persistence highlight the need to develop novel TB drugs that are active against drug resistant bacteria but, more importantly, kill persistent bacteria and shorten the length of treatment. Recent new and exciting developments in tuberculosis drug discovery show good promise of a possible revolution in the chemotherapy of tuberculosis. PMID:16478687

Zhang, Ying; Post-Martens, Katrin; Denkin, Steven

2006-01-01

123

[Pulmonary tuberculosis discovered by methods other than radiophotography].  

PubMed

The retrospective analysis of the investigations carried out between 1969 and 1973 showed that for a total of 323 new cases of tuberculosis of the lungs recorded over this period of five years, 279 (86.37%) had been detected through radiophotography, while the remaining 13.63% were detected by other methods. Of these 67.74% were primary infection cases of tuberculosis and 32.53% were secondary tuberculosis. None of the newly discovered adults had been examined by radiophotography before (their absences were either motivated or not). Thus the cases discovered between the detections do not represent a failure of the radiophotographic method. PMID:171750

Bobohalma, N; Suroiu, E

1975-01-01

124

Dinosaur Remains Found in Oregon  

NSDL National Science Digital Library

Two amateur paleontologists kept their eyes to the ground in Oregon on one of their recent hikes and discovered what are believed to be the first remains of a marine reptile called the plesiosaur to be unearthed in the Pacific Northwest. This radio broadcast reports on the discovery and what it could mean to the understanding of dinosaurs in the area. The clip is 5 minutes and 6 seconds in length.

125

Divergent effect of bacillus Calmette-Guérin (BCG) vaccination on Mycobacterium tuberculosis infection in highly related macaque species: Implications for primate models in tuberculosis vaccine research  

Microsoft Academic Search

Despite the widespread use of bacillus Calmette-Guérin vaccination, Mycobacterium tuberculosis infection remains globally the leading cause of death from a single infectious disease. The complicated and often protracted dynamics of infection and disease make clinical trials to test new tuberculosis vaccines extremely complex. Preclinical selection of only the most promising candidates is therefore essential. Because macaque monkeys develop a disease

Jan A. M. Langermans; Peter Andersen; Dick van Soolingen; Richard A. W. Vervenne; Patrice A. Frost; Tridia van der Laan; Laurens A. H. van Pinxteren; Jan van den Hombergh; Saskia Kroon; Inge Peekel; Sandrine Florquin; Alan W. Thomas

2001-01-01

126

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.

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

2014-01-01

127

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; Theves, Catherine; Bouakaze, Caroline; Nikolaeva, Dariya; Keyser, Christine; Mokrousov, Igor; Geraut, Annie; Duchesne, Sylvie; Gerard, Patrice; Alexeev, Anatoly N.; Crubezy, Eric; Ludes, Bertrand

2014-01-01

128

Tuberculosis and leprosy in perspective.  

PubMed

Two of humankind's most socially and psychologically devastating diseases, tuberculosis and leprosy, have been the subject of intensive paleopathological research due to their antiquity, a presumed association with human settlement and subsistence patterns, and their propensity to leave characteristic lesions on skeletal and mummified remains. Despite a long history of medical research and the development of effective chemotherapy, these diseases remain global health threats even in the 21st century, and as such, their causative agents Mycobacterium tuberculosis and M. leprae, respectively, have recently been the subject of molecular genetics research. The new genome-level data for several mycobacterial species have informed extensive phylogenetic analyses that call into question previously accepted theories concerning the origins and antiquity of these diseases. Of special note is the fact that all new models are in broad agreement that human TB predated that in other animals, including cattle and other domesticates, and that this disease originated at least 35,000 years ago and probably closer to 2.6 million years ago. In this work, we review current phylogenetic and biogeographic models derived from molecular biology and explore their implications for the global development of TB and leprosy, past and present. In so doing, we also briefly review the skeletal evidence for TB and leprosy, explore the current status of these pathogens, critically consider current methods for identifying ancient mycobacterial DNA, and evaluate coevolutionary models. PMID:19890861

Stone, Anne C; Wilbur, Alicia K; Buikstra, Jane E; Roberts, Charlotte A

2009-01-01

129

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

130

Gender-related factors influencing tuberculosis control in shantytowns: a qualitative study  

PubMed Central

Background There is evidence that female gender is associated with reduced likelihood of tuberculosis diagnosis and successful treatment. This study aimed to characterize gender-related barriers to tuberculosis control in Peruvian shantytowns. Methods We investigated attitudes and experiences relating gender to tuberculosis using the grounded theory approach to describe beliefs amongst key tuberculosis control stakeholders. These issues were explored in 22 semi-structured interviews and in four focus group discussions with 26 tuberculosis patients and 17 healthcare workers. Results We found that the tuberculosis program was perceived not to be gender discriminatory and provided equal tuberculosis diagnostic and treatment care to men and women. This contrasted with stereotypical gender roles in the broader community context and a commonly expressed belief amongst patients and healthcare workers that female health inherently has a lower priority than male health. This belief was principally associated with men's predominant role in the household economy and limited employment for women in this setting. Women were also generally reported to experience the adverse psychosocial and economic consequences of tuberculosis diagnosis more than men. Conclusions There was a common perception that women's tuberculosis care was of secondary importance to that of men. This reflected societal gender values and occurred despite apparent gender equality in care provision. The greatest opportunities for improving women's access to tuberculosis care appear to be in improving social, political and economic structures, more than tuberculosis program modification. PMID:20587044

2010-01-01

131

Pyrosequencing identification of Mycobacterium tuberculosis W-Beijing  

Microsoft Academic Search

BACKGROUND: The worldwide expanding Mycobacterium tuberculosis W-Beijing family is associated with treatment failure and relapse. Its identification currently relies on spoligotyping and conventional sequencing. We developed pyrosequencing as an alternative method for its identification. FINDINGS: Pyrosequencing found a G\\/A substitution in the Rv0927c-pstS3 intergenic spacer and a RD105 deletion, identifying 8\\/104 M. tuberculosis isolates as W-Beijing isolates. In addition, pyrosequencing

Zoheira Djelouadji; Mireille Henry; Amine Bachtarzi; Nadège Foselle; Didier Raoult; Michel Drancourt

2009-01-01

132

Serodiagnosis of Tuberculosis in Children Using A60 Antigen  

Microsoft Academic Search

Background: Measurement of antimycobacterial antibody may be used as an accurate diagnostic tool in childhood tuberculosis. Materials and Methods: This study was conducted to evaluate the value of IgG, IgA, and IgM levels against A60 antigen by using ELISA method for diagnosis of tuberculosis. 238 children aged from 6 months to 18 years old, divided into 4 groups; group A(n=51),patients

Soheila Khalilzadeh; Mojgan Yazdanpanah; Mostafa Hosseini; Nooshin Baghaie; Ali Akbar Velayati; Mohammad Reza Masjedi

133

Mycobacterium tuberculosis interactome analysis unravels potential pathways to drug resistance  

Microsoft Academic Search

Background  Emergence of drug resistant varieties of tuberculosis is posing a major threat to global tuberculosis eradication programmes.\\u000a Although several approaches have been explored to counter resistance, there has been limited success due to a lack of understanding\\u000a of how resistance emerges in bacteria upon drug treatment. A systems level analysis of the proteins involved is essential\\u000a to gain insights into

Karthik Raman; Nagasuma Chandra

2008-01-01

134

Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis  

Microsoft Academic Search

BACKGROUND: Since the sterilising activity of new antituberculosis drugs is difficult to assess by conventional phase III studies, surrogate methods related to eventual relapse rates are required. METHODS: A suitable method is suggested by a retrospective analysis of viable counts of Mycobacterium tuberculosis in 12-hr sputum collections from 122 newly diagnosed patients with pulmonary tuberculosis in Nairobi, done pretreatment and

Richard Brindle; Joseph Odhiambo; Denis Mitchison

2001-01-01

135

Drug Resistant Mycobacterium tuberculosis of the Beijing Genotype Does Not Spread in Sweden  

Microsoft Academic Search

BackgroundDrug resistant (DR) and multi-drug resistant (MDR) tuberculosis (TB) is increasing worldwide. In some parts of the world 10% or more of new TB cases are MDR. The Beijing genotype is a distinct genetic lineage of Mycobacterium tuberculosis, which is distributed worldwide, and has caused large outbreaks of MDR-TB. It has been proposed that certain lineages of M. tuberculosis, such

Solomon Ghebremichael; Ramona Groenheit; Alexandra Pennhag; Tuija Koivula; Emmi Andersson; Judith Bruchfeld; Sven Hoffner; Victoria Romanus; Gunilla Källenius; Niyaz Ahmed

2010-01-01

136

Isolated Coccygeal Tuberculosis  

PubMed Central

Isolated tuberculosis of the coccyx is extremely rare. A 35-year-old man presented with a 3-month history of coccygeal and gluteal pain. Computed tomography and magnetic resonance imaging revealed osseous destruction and a large enhancing mass involving the coccyx with anterior and posterior extension. Pathologic examination of the surgical specimen revealed necrosis, chronic granulomatous inflammation, and multinucleated giant cells consistent with tuberculosis. This case highlights the importance of considering tuberculosis as a diagnosis even though unusual sites are involved. PMID:23323174

Kim, Do Un; Ju, Chang IL

2012-01-01

137

Attitudes towards tuberculosis and sources of tuberculosis-related information: study on patients in outpatient settings in Split, Croatia.  

PubMed

Attitudes towards tuberculosis may have severe impact on individuals and their families as well as on the effectiveness of tuberculosis control programs. The purpose of this study was to describe these attitudes and explore the sources of tuberculosis information available to the general population in Croatia through a cross-sectional survey based on structured questionnaire using convenience sampling among 386 subjects aged 18 years and over. Data were stratified by sex, age groups, educational background, personal monthly income and contact with tuberculosis patient. Being near to a tuberculosis patient would be uncomfortable for 39.9% of respondents and 26.4% of subjects would avoid any contact. If they were sick of tuberculosis, 9.6% of respondents would keep it from the society. Less than 10% of study subjects would be ashamed of their own or potential tuberculosis in their family. Almost twice less subjects with high education would hide the disease (P=0.049), or be ashamed if sick in comparison with less educated respondents (P=0.036). The subjects who were not in contact were less likely to feel uncomfortable about being near to a tuberculosis patient (P=0.042). As the source of tuberculosis information, 61% of the subjects reported TV, radio and journals. Internet was the least used source (13.2%). The subjects in contact received information from the family or friends (P=0.025), while those without contact were informed through mass media (P<0.001). Study results revealed high stigma-generating attitudes towards tuberculosis. The strong potential of mass media capable of reaching different population groups should be used as part of the stigma-reduction strategies. PMID:22034782

Jurcev-Savicevi?, Anamarija

2011-03-01

138

Unexplained Hypercalcemia: Atypical Presentation of (Disseminated) Miliary Tuberculosis  

PubMed Central

Introdution: Miliary tuberculosis may not present with typical chronic respiratory symptoms. Metabolic disturbances like hypercalcemia may be an important clue to its diagnosis. Case Report: We report an unusual case of miliary tuberculosis in a 77-year-old Filipino man with hypertension, diabetes mellitus type 2, and nephrolithiasis (status-post left nephrectomy), presenting with a one-month history of fever, generalized weakness, and weight loss. Laboratory data was significant for anemia, hypercalemia, and acute kidney injury. Chest radiograph showed ground glass opacities and interstitial infiltrates. Empiric antibiotics for community acquired pneumonia were initiated, however, fever persisted. Extensive workup was performed to evaluate fever and hypercalcemia. Malignancy, hormonal, and septic workup were all unremarkable. PPD skin test was negative. Sputum, pleural fluid, bronchoalveolar lavage, and cerebrospinal fluid were AFB smear negative. Remarkably, urine AFB smear was positive. Anti-tuberculosis therapy was initiated which lead to defervescence and clinical improvement. However, his hospital course was complicated by small bowel obstruction and respiratory failure. He subsequently developed loss of cardiac electrical activity and expired. Postmortem autopsy confirmed the presence of tuberculosis in multiple organs including his remaining kidney. Discussion: Diagnosis of miliary tuberculosis can be very challenging especially in patients with an unusual presentation. A high index of suspicion is warranted, and as in our case, miliary tuberculosis should always be one of the differential diagnoses of fever of unknown origin with hypercalcemia. Moreover, workup for renal tuberculosis with urine AFB should be done in high-risk patients with a history of kidney stones.

Bolger, Dennis

2014-01-01

139

Nanoparticle Delivery of Anti-Tuberculosis Chemotherapy as a Potential Mediator Against Drug-Resistant Tuberculosis  

PubMed Central

Drug-resistant tuberculosis is quickly emerging as one of the largest threats to the global health community. Current chemotherapy for tuberculosis dates back to the 1950s and is arduous, lengthy, and remains extremely difficult to complete in many of the highest burdened areas. This causes inadequate or incomplete treatment, resulting in genetic selection of drug-resistant strains. With a dearth of novel anti-TB drug candidates in the development pipeline, nanoparticle technology allows us to take current chemotherapies and deliver them more efficaciously, reducing the frequency and duration of treatment and increasing bioavailability. This approach can improve patient adherence, reduce pill burden, and shorten time to completion, all which are at the heart of drug resistance. This review examines the multiple advantages of nanoparticle drug delivery of tuberculosis chemotherapy and summarizes the challenges in implementation. PMID:22180674

Smith, Jonathan Paul

2011-01-01

140

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.

141

[Cutaneous tuberculosis: case report].  

PubMed

Cutaneous tuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis. It is not very frequent and particularly difficult to diagnose. It incidence ranges between 1.5 and 4% of all extrapulmonary tuberculosis, according to bibliography. The clinic presentations depend on the arrival via of the bacillus to the skin, the patient's immune state and the environment. We show a cutaneous tuberculosis on a child with chronic dermatologic lesions, with torpid evolution, without response to treatments; the skin biopsy showed caseous granulomas. The aim is to show a patient with an infrequent clinic presentation of this disease, to emphasize the importance of an early recognition and treatment, avoiding the appearance of complications and sequels. PMID:24862824

Bisero, Elsa; Luque, Graciela; Melillo, Karina; Favier, María Inés; Zapata, Alejandra; Cuello, María Soledad

2014-06-01

142

Update on cutaneous tuberculosis*  

PubMed Central

Tuberculosis continues to draw special attention from health care professionals and society in general. Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin. Depending on individual immunity, environmental factors and the type of inoculum, it may present varied clinical and evolutionary aspects. Patients with HIV and those using immunobiological drugs are more prone to infection, which is a great concern in centers where the disease is considered endemic. This paper aims to review the current situation of cutaneous tuberculosis in light of this new scenario, highlighting the emergence of new and more specific methods of diagnosis, and the molecular and cellular mechanisms that regulate the parasite-host interaction. PMID:25387498

Dias, Maria Fernanda Reis Gavazzoni; Bernardes Filho, Fred; Quaresma, Maria Victoria; do Nascimento, Leninha Valerio; Nery, Jose Augusto da Costa; Azulay, David Rubem

2014-01-01

143

Update on cutaneous tuberculosis.  

PubMed

Tuberculosis continues to draw special attention from health care professionals and society in general. Cutaneous tuberculosis is an infection caused by M. tuberculosis complex, M. bovis and bacillus Calmette-Guérin. Depending on individual immunity, environmental factors and the type of inoculum, it may present varied clinical and evolutionary aspects. Patients with HIV and those using immunobiological drugs are more prone to infection, which is a great concern in centers where the disease is considered endemic. This paper aims to review the current situation of cutaneous tuberculosis in light of this new scenario, highlighting the emergence of new and more specific methods of diagnosis, and the molecular and cellular mechanisms that regulate the parasite-host interaction. PMID:25387498

Dias, Maria Fernanda Reis Gavazzoni; Bernardes Filho, Fred; Quaresma, Maria Victória; Nascimento, Leninha Valério do; Nery, José Augusto da Costa; Azulay, David Rubem

2014-12-01

144

Global Tuberculosis (TB)  

MedlinePLUS

... Peru, Philippines, Russia, Rwanda, South Africa, Thailand, and Vietnam. Learn More » Data and Statistics Reported Tuberculosis in ... Lesotho Mozambique Peru Philippines Rwanda South Africa Thailand Vietnam TB Disease Screening and Diagnosis in People with ...

145

[Epidemiologic trends in tuberculosis].  

PubMed

More than 90% of all tuberculosis cases occur in developing countries. Incidence rates estimated by WHO vary from 23 per 100,000 in industrialized countries to 191 per 100,000 in Africa and 237 per 100,000 in South East Asia. the downward trend observed in most industrialized counties in the 1970's and 1980's caused a neglect that nearly made tuberculosis a forgotten disease among the medical profession and policy makers. Ths neglect has led to a catastrophe in certain large cities in the United States. The resurgence of tuberculosis can not be attributed to the HIV/AIDS epidemic alone but also to the dismantling of health care structures responsible for tuberculosis control in certain countries. PMID:8794615

Billo, N E

1996-06-01

146

Tuberculosis in tropical Africa  

PubMed Central

Up to the end of the nineteenth century the tubercle bacillus apparently had little opportunity of disseminating among the rather isolated tribes of tropical Africa. With the creation of large centres of trade and industry in the wake of European colonization, tuberculosis seems to have spread rapidly over the continent and is today found everywhere. In a number of tuberculosis prevalence surveys conducted by WHO during 1955-60, randomly selected population groups were tuberculin tested, X-rayed and had sputa examined by direct microscopy. The three methods of examination were applied independently of one another. Data collected during the surveys have been analysed with a view to discovering common epidemiological features of tuberculosis in tropical Africa, assessing the reliability of the diagnostic methods employed and discussing their usefulness in future tuberculosis control programmes. PMID:14178027

Roelsgaard, E.; Iversen, E.; Bløcher, C.

1964-01-01

147

Genotyping of Mycobacterium tuberculosis clinical isolates in two cities of Turkey: Description of a new family of genotypes that is phylogeographically specific for Asia Minor  

Microsoft Academic Search

BACKGROUND: Population-based bacterial genetics using repeated DNA loci is an efficient approach to study the biodiversity and phylogeographical structure of human pathogens, such as Mycobacterium tuberculosis, the agent of tuberculosis. Indeed large genetic diversity databases are available for this pathogen and are regularly updated. No population-based polymorphism data were yet available for M. tuberculosis in Turkey, at the crossroads of

Thierry Zozio; Caroline Allix; Selami Gunal; Zeynep Saribas; Alpaslan Alp; Riza Durmaz; Maryse Fauville-Dufaux; Nalin Rastogi; Christophe Sola

2005-01-01

148

Prevalence of Latent and Active Tuberculosis among Dairy Farm Workers Exposed to Cattle Infected by Mycobacterium bovis  

PubMed Central

Background Human tuberculosis caused by M. bovis is a zoonosis presently considered sporadic in developed countries, but remains a poorly studied problem in low and middle resource countries. The disease in humans is mainly attributed to unpasteurized dairy products consumption. However, transmission due to exposure of humans to infected animals has been also recognized. The prevalence of tuberculosis infection and associated risk factors have been insufficiently characterized among dairy farm workers (DFW) exposed in settings with poor control of bovine tuberculosis. Methodology/Principal Findings Tuberculin skin test (TST) and Interferon-gamma release assay (IGRA) were administered to 311 dairy farm and abattoir workers and their household contacts linked to a dairy production and livestock facility in Mexico. Sputa of individuals with respiratory symptoms and samples from routine cattle necropsies were cultured for M. bovis and resulting spoligotypes were compared. The overall prevalence of latent tuberculosis infection (LTBI) was 76.2% (95% CI, 71.4–80.9%) by TST and 58.5% (95% CI, 53.0–64.0%) by IGRA. Occupational exposure was associated to TST (OR 2.72; 95% CI, 1.31–5.64) and IGRA (OR 2.38; 95% CI, 1.31–4.30) adjusting for relevant variables. Two subjects were diagnosed with pulmonary tuberculosis, both caused by M. bovis. In one case, the spoligotype was identical to a strain isolated from bovines. Conclusions We documented a high prevalence of latent and pulmonary TB among workers exposed to cattle infected with M. bovis, and increased risk among those occupationally exposed in non-ventilated spaces. Interspecies transmission is frequent and represents an occupational hazard in this setting. PMID:23638198

Torres-Gonzalez, Pedro; Soberanis-Ramos, Orbelin; Martinez-Gamboa, Areli; Chavez-Mazari, Barbara; Barrios-Herrera, Ma Teresa; Torres-Rojas, Martha; Cruz-Hervert, Luis Pablo; Garcia-Garcia, Lourdes; Singh, Mahavir; Gonzalez-Aguirre, Adrian; Ponce de Leon-Garduno, Alfredo; Sifuentes-Osornio, Jose; Bobadilla-del-Valle, Miriam

2013-01-01

149

Use of Isoniazid for Latent Tuberculosis Infection in a Public Health Clinic  

Microsoft Academic Search

Isoniazid is an efficacious treatment for latent tuberculosis. Con- cerns remain, however, regarding hepatotoxicity associated with this medication. In addition, adherence may be suboptimal because at least 6 months of treatment is required. We extracted information from our latent tuberculosis treatment database to determine ad- verse effects and treatment completion rates associated with the use of isoniazid at a county

Philip A. LoBue; Kathleen S. Moser

150

The Past and Future of Tuberculosis Research  

Microsoft Academic Search

Renewed efforts in tuberculosis (TB) research have led to important new insights into the biology and epidemiology of this devastating disease. Yet, in the face of the modern epidemics of HIV\\/AIDS, diabetes, and multidrug resistance—all of which contribute to susceptibility to TB—global control of the disease will remain a formidable challenge for years to come. New high-throughput genomics technologies are

Iñaki Comas; Sebastien Gagneux

2009-01-01

151

Indoleamides are active against drug-resistant Mycobacterium tuberculosis.  

PubMed

Responsible for nearly two million deaths each year, the infectious disease tuberculosis remains a serious global health challenge. The emergence of multidrug- and extensively drug-resistant strains of Mycobacterium tuberculosis confounds control efforts, and new drugs with novel molecular targets are desperately needed. Here we describe lead compounds, the indoleamides, with potent activity against both drug-susceptible and drug-resistant strains of M. tuberculosis by targeting the mycolic acid transporter MmpL3. We identify a single mutation in mmpL3, which confers high resistance to the indoleamide class while remaining susceptible to currently used first- and second-line tuberculosis drugs, indicating a lack of cross-resistance. Importantly, an indoleamide derivative exhibits dose-dependent antimycobacterial activity when orally administered to M. tuberculosis-infected mice. The bioavailability of the indoleamides, combined with their ability to kill tubercle bacilli, indicates great potential for translational developments of this structure class for the treatment of drug-resistant tuberculosis. PMID:24352433

Lun, Shichun; Guo, Haidan; Onajole, Oluseye K; Pieroni, Marco; Gunosewoyo, Hendra; Chen, Gang; Tipparaju, Suresh K; Ammerman, Nicole C; Kozikowski, Alan P; Bishai, William R

2013-01-01

152

Cost-effectiveness in the diagnosis of tuberculosis: choices in developing countries.  

PubMed

Tuberculosis remains one of the major causes of global death from a single infectious agent. This situation is worsened by the HIV/AIDS pandemic because one-third of HIV/AIDS patients are co-infected with Mycobacterium tuberculosis. 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 manner, allowing continued M. tuberculosis transmission within communities. Diagnosis of tuberculosis can be made using indirect and direct methods. The indirect tests, such as interferon-gamma release assays, provide a new diagnostic method for M. tuberculosis infection, but do not discriminate between infection and active disease. The most common direct method for diagnosing TB worldwide is sputum smear microscopy (developed more than 100 years ago), where bacteria are observed in sputum samples examined under a microscope. In countries with more developed laboratory capacities, cases of tuberculosis may also be diagnosed using culture methods (the current gold standard) or, increasingly, using rapid molecular tests. In this review, we discuss the traditional methods for the diagnosis of tuberculosis. We also discuss other inexpensive assays that can be used to detect the presence of M. tuberculosis. PMID:24423709

Molicotti, Paola; Bua, Alessandra; Zanetti, Stefania

2014-01-01

153

[Pulmonary manifestations of tuberculosis in children].  

PubMed

The occurrence of tuberculosis in children is dependent on a contagious bacillus carrying adult. Among 500 cases notified annually, perhaps 5 or 6% of the total infectious reservoir in France, 75% have parenchymal pulmonary disease and/or lymph nodes. These tuberculous diseases only represent 10% of the pulmonary disorders: 90% remain primary infections (PI active) or latent infections. These are most often asymptomatic (PI Latent) or of low grade activity (PI active). The CT scanner and fibreoptic bronchoscopy are indispensable complementary investigations in tuberculous disease. Whatever the clinical picture the diagnosis rests on bacteriological confirmation (but only 30% of cultures are positive) and most often rests on a body of evidence: for example a contagious adult living in proximity or a contagious family, or other risk factors are present. The evidence of a child with whatever form of pulmonary tuberculosis, even a latent primary infection, requires treatment which is adapted in such a way to enable a cure and to protect against subsequent endogenous re-activation. A coherent system of co-operation between the hospital and community service and between paediatricians and adult physicians is indispensable to find the index adult case to break the chain of contagion. There are two specific aspects in children, first congenital tuberculosis when a diagnosis is difficult and secondly tuberculosis in a child who is HIV positive when the management can be delicate. PMID:9496592

Olivier, C

1997-12-01

154

Review of cigarette smoking and tuberculosis in China: intervention is needed for smoking cessation among tuberculosis patients  

Microsoft Academic Search

BACKGROUND: As a risk factor of tuberculosis (TB), tobacco smoking has increased substantially over the past three decades, especially in developing countries. However, the association between smoking and TB, which has been shown to exist in different studies with different ethnic background, has not yet received sufficient attention in terms of TB care standards and research in China. METHODS: An

Jianming Wang; Hongbing Shen

2009-01-01

155

Tuberculosis part 3: HIV-tuberculosis co-infection.  

PubMed

Tuberculosis is the most common opportunistic infection in HIV-seropositive persons. Tuberculosis may occur at any stage of HIV disease but the prevalence of TB increases with the progressive diminution of CD4+ T cell numbers. There is a synergistic relationship between tuberculosis and HIV infection as each accelerates the progression of the other. PMID:20034289

Feller, L; Wood, N H; Chikte, U M E; Khammissa, R A G; Meyerov, R; Lemmer, J

2009-09-01

156

1. SOUTHWEST FRONT AND SOUTHEAST SIDE OF BLACKSMITH SHOP REMAINS, ...  

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

1. SOUTHWEST FRONT AND SOUTHEAST SIDE OF BLACKSMITH SHOP REMAINS, TENANT HOUSE IN BACKGROUND - Mount Etna Iron Works, Blacksmith Shop, East of U.S. Route 22 on T.R. 463, Williamsburg, Blair County, PA

157

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

158

Development and analysis of an in vivo-compatible metabolic network of Mycobacterium tuberculosis  

Microsoft Academic Search

BACKGROUND: During infection, Mycobacterium tuberculosis confronts a generally hostile and nutrient-poor in vivo host environment. Existing models and analyses of M. tuberculosis metabolic networks are able to reproduce experimentally measured cellular growth rates and identify genes required for growth in a range of different in vitro media. However, these models, under in vitro conditions, do not provide an adequate description

Xin Fang; Anders Wallqvist; Jaques Reifman

2010-01-01

159

Prevalence and risk factors of latent tuberculosis infection among health care workers in Malaysia  

Microsoft Academic Search

BACKGROUND: Health care workers are exposed to patients with tuberculosis and are at risk of nosocomial infection. The aim of this study was to determine the prevalence and factors associated with latent tuberculosis infection among health care workers in Malaysia and also to evaluate the agreement between Quantiferon TB Gold in tube test with Tuberculin Skin Test. METHODS: A cross

Shaharudin Rafiza; Krishna Gopal Rampal; Aris Tahir

2011-01-01

160

The role of entry screening in case finding of tuberculosis among asylum seekers in Norway  

Microsoft Academic Search

BACKGROUND: Most new cases of active tuberculosis in Norway are presently caused by imported strains and not transmission within the country. Screening for tuberculosis with a Mantoux test of everybody and a chest X-ray of those above 15 years of age is compulsory on arrival for asylum seekers. We aimed to assess the effectiveness of entry screening of a cohort

Ingunn Harstad; Geir W Jacobsen; Einar Heldal; Brita A Winje; Saeed Vahedi; Anne-Sofie Helvik; Sigurd L Steinshamn; Helge Garåsen

2010-01-01

161

Quality Control of Sputum Smears Examination by Re-Reading in a Tuberculosis Screening  

Microsoft Academic Search

Background: Sputum smear examination is the basis of diagnosis of tuberculosis and quality control for the correct diagno- sis of tuberculosis is necessary. This study was a method survey and performed with 930 smears with the aim to compare the confidence rate of sputum smear examination reported by one laboratory technician with the findings reported by two technicians in a

F Majlessi; A Sekhavati; K Qazi Saeedi; A Poorreza

162

Assessment of the Amount of Knowledge and Attitude of Tehran High School Students Regarding Tuberculosis  

Microsoft Academic Search

Background: Tuberculosis (TB) is a chronic infectious disease which is still a global health hazard. With the emergence of new more effective drugs, tuberculosis was expected to be completely eradicated; but, global reports show results to the contrary. It seems that, in addition to drug regimens, individual health and social factors, should be taken into consideration. This is not achievable

Mohammad Ali Emam Hadi; Maryam Jalilvand; Mina Hadian

163

Tuberculosis Surveillance Using a Hidden Markov Model  

PubMed Central

Background: Routinely collected data from tuberculosis surveillance system can be used to investigate and monitor the irregularities and abrupt changes of the disease incidence. We aimed at using a Hidden Markov Model in order to detect the abnormal states of pulmonary tuberculosis in Iran. Methods: Data for this study were the weekly number of newly diagnosed cases with sputum smear-positive pulmonary tuberculosis reported between April 2005 and March 2011 throughout Iran. In order to detect the unusual states of the disease, two Hidden Markov Models were applied to the data with and without seasonal trends as baselines. Consequently, the best model was selected and compared with the results of Serfling epidemic threshold which is typically used in the surveillance of infectious diseases. Results: Both adjusted R-squared and Bayesian Information Criterion (BIC) reflected better goodness-of-fit for the model with seasonal trends (0.72 and ?1336.66, respectively) than the model without seasonality (0.56 and ?1386.75). Moreover, according to the Serfling epidemic threshold, higher values of sensitivity and specificity suggest a higher validity for the seasonal model (0.87 and 0.94, respectively) than model without seasonality (0.73 and 0.68, respectively). Conclusion: A two-state Hidden Markov Model along with a seasonal trend as a function of the model parameters provides an effective warning system for the surveillance of tuberculosis. PMID:23304666

Rafei, A; Pasha, E; Jamshidi Orak, R

2012-01-01

164

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

165

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

166

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

167

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

168

EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS  

PubMed Central

1. Ultraviolet irradiation of the air of a room exercises a protective influence against natural air-borne contagion of tuberculosis in rabbits. 2. When the radiant energy is of low intensity it reduces considerably the incidence of tuberculosis. (a) It completely protects rabbits of high natural resistance from acquiring demonstrable disease though they become tuberculin sensitive. (b) It fails to protect a small proportion of rabbits of low natural resistance from fatal tuberculosis. 3. When the radiant energy is of high intensity all rabbits, whether of high or of low natural resistance, are almost completely protected from a contagion so severe that it is fatal to the great majority of rabbits of the same genetic constitution not protected by these rays. The protected rabbits do not develop tuberculin sensitivity. 4. The contagion of tuberculosis in these studies is air-borne and the radiant energy exercises its protective influence by its bactericidal properties. It is probable that ultraviolet irradiation may control air-borne contagion of human tuberculosis. PMID:19871387

Lurie, Max B.

1944-01-01

169

Detection of Mycobacterium tuberculosis directly from sputum by using a prototype automated Q-beta replicase assay.  

PubMed Central

We have adapted an assay for the direct detection of Mycobacterium tuberculosis using a prototype automated instrument platform in which probes are amplified with Q-beta replicase. The assay was based on amplification of specific detector probe following four cycles of background reduction (reversible target capture) in a closed disposable pack. The assay signal was the time required for fluorescence to exceed background levels (response time [RT]). RT was inversely related to the number of M. tuberculosis rRNA target molecules in the sample. Equivalent signals and noises were observed in assays containing either sputum or buffer. All mock samples containing > or = 10 CFU of M. tuberculosis responded in the assay (average RT, 13.91 min), while most (83%) samples containing as many as 10(7) CFU of Mycobacterium avium gave no response during a 25-min amplification reaction. The samples containing M. avium which did respond had an average RT of 17.04 min. Seventy-five percent (167 of 223) of samples containing no target gave no responses; the remaining 25% had an average RT of 15.53 min. Eighty-three frozen sputum samples were tested to develop a candidate cutoff RT for the assay prior to more extensive clinical testing. After resolution of discrepant results and with a 14-min RT cutoff, 30 of 38 M. tuberculosis-positive samples were positive by the assay; 1 of 45 negative samples responded within 14 min. Assay sensitivity, specificity, and positive and negatives predictive values in this pilot study were 79, 98, 97, and 85%, respectively. PMID:9163466

Smith, J H; Buxton, D; Cahill, P; Fiandaca, M; Goldston, L; Marselle, L; Rigby, S; Olive, D M; Hendricks, A; Shimei, T; Klinger, J D; Lane, D J; Mahan, D E

1997-01-01

170

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

171

CT appearances of abdominal tuberculosis.  

PubMed

The purpose of this article is to review and illustrate the spectrum of computed tomography (CT) appearances of abdominal tuberculosis. Tuberculosis can affect any organ or tissue in the abdomen, and can be mistaken for other inflammatory or neoplastic conditions. The most common sites of tuberculosis in the abdomen include lymph nodes, genitourinary tract, peritoneal cavity and gastrointestinal tract. The liver, spleen, biliary tract, pancreas and adrenals are rarely affected, but are more likely in HIV-seropositive patients and in miliary tuberculosis. This article should alert the radiologist to consider abdominal tuberculosis in the correct clinical setting to ensure timely diagnosis and enable appropriate treatment. PMID:22212637

Lee, W-K; Van Tonder, F; Tartaglia, C J; Dagia, C; Cazzato, R L; Duddalwar, V A; Chang, S D

2012-06-01

172

Tuberculosis in Quebec: a Review of Trends  

PubMed Central

Abstract The aim of this research was to conduct a thorough review on the literature of tuberculosis in Canada and the Province of Quebec. To achieve this aim, an exhaustive literature review of tuberculosis in the Province of Quebec was undertaken. Data was collected with the goal of creating an epidemiological and public health evidence base to forecast the spread of tuberculosis. A keyword search strategy was used to find relevant articles from the peer-reviewed literature using the electronic search engine PubMed and a search of other relevant federal and provincial government databases. Twenty-nine peer-reviewed publications and twenty government reports containing information about the incidence or prevalence of tuberculosis in the Province of Quebec were included in the analysis. An analysis of the data revealed that while tuberculosis rates have been decreasing in both Canada and Quebec with an overall incidence below 3 per 100,000 of population in 2007, among immigrants and the Inuit communities in Quebec, the incidence and prevalence of the disease still remains high and reached 18 per 100,000 and 100 per 100,000, respectively in 2007. In general, while tuberculosis does not pose a significant burden to the general population, it does continue to affect certain sub-groups disproportionately, including select immigrants and Inuit communities in Quebec. Efforts to ensure that cost-effective healthcare interventions are delivered in a timely fashion should be pursued to reduce the associated morbidity and mortality of tuberculosis in the Province of Quebec. Acknowledgments Funding for this research was provided to Medmetrics Inc., by McGill University, Montreal, Quebec, Génome Québec and the Ministère de Développement Economique, Innovation et Exportation du Gouvernement du Québec. The authors also wish to thank Drs. John White and Marcel Behr, both of McGill University and Dr Suneil Malik of the Infectious Disease Program in the Office of Biotechnology, Genomics and Population Health at the Public Health Agency of Canada for comments and suggestions on earlier drafts of this manuscript.

Klotz, Alexander; Harouna, Abdoulaye; Smith, Andrew F.

2012-01-01

173

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

174

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

175

The global emergency of tuberculosis: what is the cause?  

PubMed

The treatment of tuberculosis is cheap and highly effective, yet worldwide the disease remains a serious cause of illness and death; so serious as to have been declared a 'global emergency' in 1993. It is principally a disease of poverty, with 95% of cases and 98% of deaths occurring in developing countries. The incidence of tuberculosis is increasing worldwide, partly due to poverty and inequity and partly to the HIV/AIDS pandemic, which greatly increases the risk of infection proceeding to overt disease. Around 30% of AIDS-related deaths are due to tuberculosis. The emergence of multidrug resistant tuberculosis (MDRTB) is an increasing threat to tuberculosis control. Although treatable with alternative drugs, the cost is enormous and, accordingly, not undertaken in many poor nations. While the overall global incidence of MDRTB is low, it occurs in certain 'hotspots' including Russian prisons. Due to adverse socio-economic factors, London has not escaped the general rise in incidence and, without the introduction of active control strategies, there could be a serious epidemic as occurred in New York City ten years ago which required an enormous financial outlay for its control. In view of the global emergency of tuberculosis, the WHO 'Stop TB' campaign has called for the universal adoption of its directly observed therapy, short course (DOTS) strategy. Also, though the Massive Effort Against Diseases of Poverty, several international agencies are urging the establishment of effective control programmes worldwide. London should take the lead and set an example. PMID:12134771

Grange, J M; Zumla, A

2002-06-01

176

Simple Model for Testing Drugs against Nonreplicating Mycobacterium tuberculosis? †  

PubMed Central

Nonreplicating or dormant cells of Mycobacterium tuberculosis constitute a challenge to tuberculosis (TB) therapy because of their tolerance or phenotypic resistance to most drugs. Here, we propose a simple model for testing drugs against nongrowing cells that exploits the 18b strain of M. tuberculosis, a streptomycin (STR)-dependent mutant. Optimal conditions were established that allowed 18b cells to replicate in the presence of STR and to survive, but not multiply, following withdrawal of STR. In the presence of the antibiotic, M. tuberculosis 18b was susceptible to the currently approved TB drugs, isoniazid (INH) and rifampin (RIF), and to the experimental drugs TMC207, PA-824, meropenem (MER), benzothiazinone (BTZ), and moxifloxacin (MOXI). After STR depletion, the strain displayed greatly reduced susceptibility to the cell wall inhibitors INH and BTZ but showed increased susceptibility to RIF and PA-824, while MOXI and MER appeared equipotent under both conditions. The same potency ranking was found against nonreplicating M. tuberculosis 18b after in vivo treatment of chronically infected mice with five of these drugs. Despite the growth arrest, strain 18b retains significant metabolic activity in vitro, remaining positive in the resazurin reduction assay. Upon adaption to a 96-well format, this assay was shown to be suitable for high-throughput screening with strain 18b to find new inhibitors of dormant M. tuberculosis. PMID:20679505

Sala, Claudia; Dhar, Neeraj; Hartkoorn, Ruben C.; Zhang, Ming; Ha, Young Hwan; Schneider, Patricia; Cole, Stewart T.

2010-01-01

177

Anal tuberculosis complicating anti-TNF? therapy.  

PubMed

A 42-year-old man receiving anti-tumour necrosis factor ? (anti-TNF?) therapy with adalimumab due to psoriatic arthritis presented with a 2-month-old anal ulcer. An apical right lung infiltrate was found in his chest X-ray, although he had no pulmonary symptoms. Two biopsies of the ulcer were taken and reported as granulomatous, necrotising, with chronic inflammation (first), and as hyperplasic epidermis with linfocitary infiltrate and the presence of plenty of plasmatic cells (second). Histochemical techniques, including Ziehl-Neelsen, Grocott and periodic acid-Schiff stains, and PCR for Mycobacterium tuberculosis on both biopsies were negative. Serology for HIV, syphilis and hepatitis were also negative. In the second biopsy culture, moderate colonies of M. tuberculosis finally grew. The patient started a four-drug antituberculosis regimen. Adalimumab was discontinued and etanercept introduced after 2?months of antituberculosis therapy. The patient remained on therapy for 9?months with complete ulcer resolution. PMID:25422341

Luquín, Nuria; Masiá, Mar; Noguera, Raúl; Gutiérrez, Félix

2014-01-01

178

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

179

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

180

Expression of TNF-Alpha-Dependent Apoptosis-Related Genes in the Peripheral Blood of Malagasy Subjects with Tuberculosis  

PubMed Central

The majority of Mycobacterium tuberculosis (Mtb) infections remain asymptomatic with only up to 10% progressing to clinical tuberculosis. However, the constituents of the effective “protective immunity” against tuberculosis responsible for containing most infections remain unknown. Evaluating gene transcriptional profiles in tuberculosis clinical cohorts is one approach to understanding the spectrum of tuberculosis progression. It is clear that apoptosis plays a role in the control of tuberculosis but the utility of apoptosis-related genes as surrogate markers of protection against tuberculosis has not been well investigated. To characterize potential surrogate markers that could discriminate different phases of the clinical tuberculosis spectrum, we investigated gene expression of several TNF-alpha dependent apoptotic genes (TNFR1, TNFR2, FLICE, FLIPs) by real-time RT-PCR of peripheral blood cells from cohorts of individuals with active tuberculosis or potential exposure to tuberculosis. Newly diagnosed tuberculosis patients (n?=?23), their close household contacts (n?=?80), and community controls (n?=?46) were tested at intervals over a period of up to two years. Latent infection or previous Mtb contact was assessed by ELISPOT and TST and complete blood counts were performed during the follow up. Results showed significant upregulation of FLIPs expression by infected individuals regardless of clinical status at entry to the study. A higher percentage of lymphocytes was found in the infected household contacts that remained healthy. In contrast, in individuals with active TB, a significant upregulation of TNFR2 expression, a significantly higher percentage of monocytes and a significantly decreased lymphocyte count were seen, compared to subjects that remained healthy. Moreover, the household contacts who subsequently developed signs of TB also had a significantly high number of monocytes. These data suggest tuberculosis may be associated with decreased T-cell survival (perhaps due to apoptosis) while inhibition of apoptosis in monocytes could lead to a relative increase in these cells: a situation predicted to favour Mtb. PMID:23593415

Rakotosamimanana, Niaina; Doherty, T. Mark; Andriamihantasoa, Lova H.; Richard, Vincent; Gicquel, Brigitte; Soares, Jean-Louis; Zumla, Alimuddin; Razanamparany, Voahangy Rasolofo

2013-01-01

181

Background stratospheric aerosol layer  

SciTech Connect

Balloonborne aerosol particle counter measurements are used in studying the stratospheric sulfate layer at Laramie, Wyoming, during 1978 and 1979, a 2-year volcanically quiescent period in which the layer appears to have been in a near equilibrium background state. Subtracting the background aerosol concentration from data obtained during an earlier volcanically active period indicates that the actual decay rate of volcanic aerosol is over 30% faster than one would obtain without this correction. At background, the aerosol size distribution is found to remain remarkably constant between the tropopause and an altitude of approx.25 km, with a sudden transition to a distribution dominated by smaller particles above this altitude. The observations, in some respects, compare favorably with equilibrium one-dimensional stratospheric aerosol models and thus to some extent support the concept of relatively inert tropospheric sulfurous gases, such as carbonyl sulfide and carbon disulfide, as the main background stratospheric aerosol sulfur source. Models which incorporate sulfur chemistry are apparently not able to predict the observed variation of particle size with altitude. The 2-year background period is not long enough in itself to establish long-term trends. The eruption of Mt. St. Helens in May 1980 has considerably disrupted the background stratospheric aerosol which will probably not recover for several years. A comparison of the 1978--79 observations with Junge's original measurements made some 20 years earlier, also during a period void of volcanic perturbations, does not preclude a long-term increase in the background stratospheric aerosol level.

Hofmann, D.J.; Rosen, J.M.

1981-01-01

182

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

183

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

184

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

E-print Network

of America Abstract Background: There is limited available data on the strain diversity of M tuberculosis different spoligotypes. Of these there were 27 strains (3.4%) with novel, unique orphan spoligotypes. 498

Paris-Sud XI, Université de

185

Distribution of Spoligotyping Defined Genotypic Lineages among Drug-Resistant Mycobacterium tuberculosis Complex Clinical Isolates in Ankara, Turkey  

Microsoft Academic Search

BackgroundInvestigation of genetic heterogeneity and spoligotype-defined lineages of drug-resistant Mycobacterium tuberculosis clinical isolates collected during a three-year period in two university hospitals and National Tuberculosis Reference and Research Laboratory in Ankara, Turkey.Methods and FindingsA total of 95 drug-resistant M. tuberculosis isolates collected from three different centers were included in this study. Susceptibility testing of the isolates to four major antituberculous

Ozgul Kisa; Gulnur Tarhan; Selami Gunal; Ali Albay; Riza Durmaz; Zeynep Saribas; Thierry Zozio; Alpaslan Alp; Ismail Ceyhan; Ahmet Tombak; Nalin Rastogi

2012-01-01

186

Molecular modeling and in silico characterization of Mycobacterium tuberculosis TlyA: Possible misannotation of this tubercle bacilli-hemolysin  

Microsoft Academic Search

Background  The TlyA protein has a controversial function as a virulence factor in Mycobacterium tuberculosis (M. tuberculosis). At present, its dual activity as hemolysin and RNA methyltransferase in M. tuberculosis has been indirectly proposed based on in vitro results. There is no evidence however for TlyA relevance in the survival of tubercle bacilli inside host cells or whether\\u000a both activities are

Nelson E Arenas; Luz M Salazar; Carlos Y Soto; Carolina Vizcaíno; Manuel E Patarroyo; Manuel A Patarroyo; Arley Gómez

2011-01-01

187

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 ...

188

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 ...

189

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 ...

190

Pyrosequencing for rapid detection of Tuberculosis resistance in clinical isolates and Sputum samples from re-treatment Pulmonary Tuberculosis patients  

PubMed Central

Background Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. Early diagnosis of MDR-TB patients is essential for minimizing the risk of Mycobacterium tuberculosis (MTB) transmission. The conventional drug susceptibility testing (DST) methods for detection of drug-resistant M.tuberculosis are laborious and cannot provide the rapid detection for clinical practice. Methods The aim of this study was to develop a pyrosequencing approach for the simultaneous detection of resistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (SM), ofloxacin (OFL) and amikacin (AMK) in M. tuberculosis clinical isolates and sputum samples from re-treatment pulmonary tuberculosis (PTB) patients. We identified the optimum conditions for detection mutation of rpoB, katG, rpsl, embB, gyrA and rrs gene by pyrosequencing. Then this approach was applied to detect 205 clinical isolates and 24 sputum samples of M. tuberculosis from re-treatment PTB patients. Results The mutations of rpoB and gyrA gene were detected by pyrosequencig with the SQA mode, and the mutations of katG, rpsl, embB, gyrA and rrs gene were detected by pyrosequencing with SNP mode. Compared with the Bactec MGIT 960 mycobacterial detection system, the accuracy of pyrosequencing for the detection of RIF, INH, EMB, SM, AMK and OFL resistance in clinical isolates was 95.0%, 79.2%, 70.3%, 84.5%, 96.5% and 91.1%, respectively. In sputum samples the accuracy was 83.3%, 83.3%, 60.9%, 83.3%, 87.5% and 91.7%, respectively. Conclusions The newly established pyrosequencing assay is a rapid and high-throughput method for the detection of resistance to RIF, INH, SM, EMB, OFL and AMK in M.tuberculosis. Pyrosequencing can be used as a practical molecular diagnostic tool for screening and predicting the resistance of re-treatment pulmonary tuberculosis patients. PMID:24725975

2014-01-01

191

Proteomic analysis of purified protein derivative of Mycobacterium tuberculosis  

PubMed Central

Background Purified protein derivative (PPD) has been used for more than half a century as an antigen for the diagnosis of tuberculosis infection based on delayed type hypersensitivity. Although designated as “purified,” in reality, the composition of PPD is highly complex and remains ill-defined. In this report, high resolution mass spectrometry was applied to understand the complexity of its constituent components. A comparative proteomic analysis of various PPD preparations and their functional characterization is likely to help in short-listing the relevant antigens required to prepare a less complex and more potent reagent for diagnostic purposes. Results Proteomic analysis of Connaught Tuberculin 68 (PPD-CT68), a tuberculin preparation generated from M. tuberculosis, was carried out in this study. PPD-CT68 is the protein component of a commercially available tuberculin preparation, Tubersol, which is used for tuberculin skin testing. Using a high resolution LTQ-Orbitrap Velos mass spectrometer, we identified 265 different proteins. The identified proteins were compared with those identified from PPD M. bovis, PPD M. avium and PPD-S2 from previous mass spectrometry-based studies. In all, 142 proteins were found to be shared between PPD-CT68 and PPD-S2 preparations. Out of the 354 proteins from M. tuberculosis–derived PPDs (i.e. proteins in either PPD-CT68 or PPD-S2), 37 proteins were found to be shared with M. avium PPD and 80 were shared with M. bovis PPD. Alignment of PPD-CT68 proteins with proteins encoded by 24 lung infecting bacteria revealed a number of similar proteins (206 bacterial proteins shared epitopes with 47 PPD-CT68 proteins), which could potentially be involved in causing cross-reactivity. The data have been deposited to the ProteomeXchange with identifier PXD000377. Conclusions Proteomic and bioinformatics analysis of different PPD preparations revealed commonly and differentially represented proteins. This information could help in delineating the relevant antigens represented in various PPDs, which could further lead to development of a lesser complex and better defined skin test antigen with a higher specificity and sensitivity. PMID:23870090

2013-01-01

192

Drug resistance of strains of Mycobacterium tuberculosis isolated in Brazil 1 1 Present address: Departamento de Microbiología, Medicina Preventiva y Salud Pública, Facultad de Medicina Domingos Miral SN50009, Universidad de Zaragoza, Spain  

Microsoft Academic Search

Tuberculosis remains a serious public health problem, worsened by an increased frequency of multidrug-resistant Mycobacterium tuberculosis. We report here a retrospective study of resistance to antituberculosis drugs of 170 strains of M. tuberculosis isolated from the state of Rio Grande do Sul, Brazil. The frequency of resistance to at least one drug was 34%, while 22% were resistant to more than

Pedro E. Almeida da Silva; Marta Osório; Marcelo C. Reinhardt; Leila de Souza Fonseca; Odir A. Dellagostin

2001-01-01

193

Isoniazid Blood Levels in Patients with Pulmonary Tuberculosis at a Tuberculosis Referral Center  

Microsoft Academic Search

Background: Serum concentrations of isoniazid (INH) were evaluated in Iranian patients admitted to the Tuberculosis Ward of Masih Daneshvari Hospital, Tehran, Iran. Factors correlated to plasma INH levels were determined. Methods: Blood samples were obtained 2 h after ingestion of 5 mg\\/kg INH in 82 patients (1 sample\\/patient) on days 3–15 of treatment. The following variables were investigated: INH plasma

Fanak Fahimi; Farzad Kobarfard; Payam Tabarsi; Shabnam Hemmati; Jamshid Salamzadeh; Shadi Baniasadi

2011-01-01

194

First report of Mycobacterium bovis DNA in human remains from the Iron Age.  

PubMed

Tuberculosis has plagued humankind since prehistoric times, as is evident from characteristic lesions on human skeletons dating back to the Neolithic period. The disease in man is due predominantly to infection with either Mycobacterium tuberculosis or Mycobacterium bovis, both members of the M. tuberculosis (MTB) complex. A number of studies have shown that when conditions permit, surviving mycobacterial DNA may be amplified from bone by PCR. Such ancient DNA (aDNA) analyses are subject to stringent tests of authenticity and, when feasible, are invariably limited by DNA fragmentation. Using PCRs based on single-nucleotide polymorphic loci and regions of difference (RDs) in the MTB complex, a study was made of five Iron Age individuals with spinal lesions recovered from the cemetery of Aymyrlyg, South Siberia. A sensitive screening PCR for MTB complex mycobacteria was positive in four out of the five cases. Genotyping evidence indicated that all four cases were due to infection with M. bovis rather than M. tuberculosis and the data were consistent with the proposed phylogenetic model of the MTB complex. This is believed to be the first report of M. bovis causing Pott's disease in archaeological human remains. The study shows that genotyping of ancestral strains of MTB complex mycobacteria from contexts of known date provides information which allows the phylogeny of the model to be tested. Moreover, it shows that loss of DNA from RD4, which defines classic M. bovis, had already occurred from the genome over 2000 years before the present. PMID:17379733

Taylor, G Michael; Murphy, Eileen; Hopkins, Richard; Rutland, Paul; Chistov, Yuri

2007-04-01

195

Advances in ante-mortem diagnosis of tuberculosis in cattle  

Microsoft Academic Search

The tuberculin skin test is effective in the early detection of pre-clinical cases of Mycobacterium bovis infection in cattle. This allows the rapid removal of infected animals, thus limiting transmission of the disease, and has resulted in the eradication of bovine tuberculosis (Tb) from many countries. This test is very likely to remain the primary screening test for M. bovis

BM Buddle; PG Livingstone; GW de Lisle

2009-01-01

196

Cattle movements and bovine tuberculosis in Great Britain  

Microsoft Academic Search

For 20 years, bovine tuberculosis (BTB) has been spreading in Great Britain (England, Wales and Scotland) and is now endemic in the southwest and parts of central England and in southwest Wales, and occurs sporadically elsewhere. Although its transmission pathways remain poorly understood, the disease's distribution was previously modelled statistically by using environmental variables and measures of their seasonality. Movements

M. Gilbert; A. Mitchell; D. Bourn; J. Mawdsley; R. Clifton-Hadley; W. Wint

2005-01-01

197

Characterization of Mycobacterium tuberculosis Beijing isolates from the Mediterranean area  

Microsoft Academic Search

BACKGROUND: The Beijing lineage of Mycobacterium tuberculosis is causing concern due to its global distribution and its involvement in severe outbreaks. Studies focused on this lineage are mainly restricted to geographical settings where its prevalence is high, whereas those in other areas are scarce. In this study, we analyze Beijing isolates in the Mediterranean area, where this lineage is not

M. Alonso; N. Alonso Rodriguez; C. Garzelli; M. Martínez Lirola; M. Herranz; S. Samper; M. J. Ruiz Serrano; E. Bouza; D. García de Viedma

2010-01-01

198

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

199

Draft Genome Sequence of the Mycobacterium tuberculosis Clinical Isolate C2, Belonging to the Latin American-Mediterranean Family.  

PubMed

Tuberculosis remains a major infectious disease in Taiwan. Here we present the draft genome sequence of the Mycobacterium tuberculosis C2 strain, belonging to the Latin American-Mediterranean lineage. The draft genome sequence comprises 4,453,307 bp with a G+C content of 65.6%, revealing 4,390 coding genes and 45 tRNA genes. PMID:24903871

Liao, Yu-Chieh; Chen, Yih-Yuan; Lin, Hsin-Hung; Chang, Jia-Ru; Su, Ih-Jen; Huang, Tsi-Shu; Dou, Horng-Yunn

2014-01-01

200

Investigation of the prevalence of female genital tract tuberculosis and its relation to female infertility:An observational analytical study  

PubMed Central

Background: Genital tuberculosis is a common entity in gynecological practice particularly among infertile patients. It is rare in developed countries but is an important cause of infertility in developing countries. Objective: The present study has investigated the prevalence of female genital tract tuberculosis (FGT) among infertile patients, which was conducted at the Obstetrics and Gynecology Unit-I, Allied Hospital, affiliated with Punjab Medical College, Faisalabad, Pakistan. Materials and Methods: 150 infertile women who were referred to infertility clinic were selected randomly and enrolled in our study. Patients were scanned for possible presence of FGT by examination and relevant investigation. We evaluated various aspects (age, symptoms, signs, and socio-economic factors) of the patients having tuberculosis. Results: Very high frequency of FGT (20%) was found among infertile patients. While, a total of 25 patients out of 30 (83.33%) showed primary infertility and the remaining 5 cases (16.67%) had secondary infertility. Among secondary infertility patients, the parity ranged between 1 and 2. A total of 40% of patients (12 cases) were asymptomatic but infertile. Evidence of family history was found in 4 out of a total of 30 patients (13.3%), respectively. According to histopathological and bacteriological examination of endometrial biopsy and laparotomy, tuberculous endometritis was found in 20 out of a total of 25 (80%) cases, while tuberculous salpingitis and tuberculous oophoritis were found both in 2 (8%) of the cases, respectively. Only one case (4%) of tuberculosis cervicitis was found in the present study. Conclusion: Although infertility is not a disease in classical sense, but it is an extremely important personal concern for many couples and a significant health problem for our profession. So, it is worthwhile to identify and evaluate the factors contributing to infertility.

Shahzad, Sughra

2012-01-01

201

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

202

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

203

Tuberculosis transmission across the United States-Mexico border.  

PubMed

In this era of increasing drug resistance among infectious diseases such as tuberculosis (TB), the complex population dynamics of border areas must be monitored more extensively. TB remains a major public health threat; its antimicrobial treatment is long; and the only vaccine licensed in the world, live-attenuated Mycobacterium bovis Bacille Calmette-Guérin (BCG), exhibits varying efficacy. In addition to epidemiological surveillance, the underlying determinants contributing to the health and wellbeing of populations are of key importance. Although it received heightened attention in the past, tuberculosis transmission in the United States-Mexico border area demands renewed interest. Lessons learned should be applied to similar areas around the globe. PMID:21390421

Fitchett, Joseph Robert; Vallecillo, Antonio Javier; Espitia, Clara

2011-01-01

204

Molecular detection of rifabutin-susceptible Mycobacterium tuberculosis.  

PubMed

Rapid assays are still needed to detect rifabutin (RFB) susceptibility for proper tuberculosis treatment. To assess the use of the GenoType MTBDRplus assay and subsequent rpoB gene sequencing on detection of RFB susceptibility, we analyzed 800 multidrug-resistant Mycobacterium tuberculosis isolates, and 13% (104/800) were RFB susceptible. Of the 104 RFB-susceptible isolates, 71 (68.3%) isolates were rapidly identified using two molecular assays, while the remaining isolates could be determined using conventional drug-susceptibility testing according to the clinician's decision. PMID:22442316

Chen, Huang-Yao; Yu, Ming-Chih; Huang, Wei-Lun; Wu, Mei-Hua; Chang, Yung-Lin; Che, Chien-Rai; Jou, Ruwen

2012-06-01

205

Differential diagnosis of Crohn's disease versus ileal tuberculosis.  

PubMed

Both intestinal tuberculosis and Crohn's disease are chronic granulomatous inflammatory diseases of the bowel having overlap of clinical, endoscopic, radiological, and histological features. Differentiating between the two disorders is relevant not only in Asian countries but also in the West. In spite of diagnostic criteria for both diseases being available, still the dilemma of segregating the two diseases remains. Nearly one third of the patients with Crohn's disease may receive anti-tuberculosis treatment also. Diagnosis should be based on the combination of all disease-specific and corroborative evidences. PMID:25277043

Sood, Ajit; Midha, Vandana; Singh, Arshdeep

2014-11-01

206

Pilot study of directional airflow and containment of airborne particles in the size of Mycobacterium tuberculosis in an operating room  

Microsoft Academic Search

Background: Containment of airborne microorganisms to prevent transmission in a positively pressured operating room (OR) is challenging. Occupational transmission of Mycobacterium tuberculosis (M tuberculosis) to perioperative personnel has occurred, but protection of the surgical site is of equal importance. High-efficiency particulate air (HEPA) filters can mitigate occupational exposure and improve air quality. Smoke plumes and submicron particulates were released to

Russell N. Olmsted

2008-01-01

207

M. tuberculosis genotypic diversity and drug susceptibility pattern in HIV infected and non-HIVinfected patients in northern Tanzania  

Microsoft Academic Search

BACKGROUND: Tuberculosis (TB) is a major health problem and HIV is the major cause of the increase in TB. Sub-Saharan Africa is endemic for both TB and HIV infection. Determination of the prevalence of M. tuberculosis strains and their drug susceptibility is important for TB control. TB positive culture, BAL fluid or sputum samples from 130 patients were collected and

Gibson S Kibiki; Bert Mulder; Wil MV Dolmans; Jessica L de Beer; Martin Boeree; Noel Sam; Dick van Soolingen; Christophe Sola; Adri GM van der Zanden

2007-01-01

208

Obstacles for optimal tuberculosis case detection in primary health centers (PHC) in Sidoarjo district, East Java, Indonesia  

Microsoft Academic Search

BACKGROUND: Pulmonary tuberculosis (TB) is a major health problem worldwide. Detection of the most infectious cases of tuberculosis – sputum smear-positive pulmonary cases – by passive case finding is an essential component of TB control. The district of Sidoarjo in East Java reported a low case detection rate (CDR) of 14% in 2003. We evaluated the diagnostic process for TB

Chatarina U Wahyuni; Budiono; Lutfia Dwi Rahariyani; Muji Sulistyowati; Tety Rachmawati; Djuwari; Sri Yuliwati; Marieke J van der Werf

2007-01-01

209

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

210

[Antimicrobial resistance in tuberculosis].  

PubMed

Although drug resistance in tuberculosis is by no means a new problem, multiple drug resistance is a cause of increasing concern. This study investigated first-line drug resistance in Mycobacterium tuberculosis strains isolated in a hospital environment and strains submitted as the Reference Center from 2000 to 2010. A total of 650 cultures were tested against first-line using the BACTEC MGIT 960 system. Resistance to first-line drugs was detected in 142 strains, (21.85%). A total of 2% were multiresistant (MDR). Of the strains resistant to first-line drugs, the greatest resistance was found to isoniazid (7.38 %) followed by rifampin and streptomycin (3.85%), pyracinamide (2%), and ethambutol 1.23%. Only one strain was resistant to four drugs. Values. In view of the resistance observed, careful surveillance of drug resistance is recommended. PMID:24399346

Gutiérrez-Aroca, Juan Bautista; Ruiz, Pilar; Casal, Manuel

2013-12-01

211

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

212

Bacteremic Disseminated Tuberculosis in Sub-Saharan Africa: A Prospective Cohort Study  

PubMed Central

Background.?Disseminated tuberculosis is a major health problem in countries where generalized human immunodeficiency virus (HIV) infection epidemics coincide with high tuberculosis incidence rates; data are limited on patient outcomes beyond the inpatient period. Methods.?We enrolled consecutive eligible febrile inpatients in Moshi, Tanzania, from 10 March 2006 through 28 August 2010; those with Mycobacterium tuberculosis bacteremia were followed up monthly for 12 months. Survival, predictors of bacteremic disseminated tuberculosis, and predictors of death were assessed. Antiretroviral therapy (ART) and tuberculosis treatment were provided. Results.?A total of 508 participants were enrolled; 29 (5.7%) had M. tuberculosis isolated by blood culture. The median age of all study participants was 37.4 years (range, 13.6–104.8 years). Cough lasting >1 month (odds ratio [OR], 13.5; P < .001), fever lasting >1 month (OR, 7.8; P = .001), weight loss of >10% (OR, 10.0; P = .001), lymphadenopathy (OR 6.8; P = .002), HIV infection (OR, undefined; P < .001), and lower CD4 cell count and total lymphocyte count were associated with bacteremic disseminated tuberculosis. Fifty percent of participants with M. tuberculosis bacteremia died within 36 days of enrollment. Lower CD4 cell count (OR, 0.88; P = .049) and lower total lymphocyte count (OR, 0.76; P = .050) were associated with death. Magnitude of mycobacteremia tended to be higher among those with lower CD4 cell counts, but did not predict death. Conclusions.?In the era of free ART and access to tuberculosis treatment, almost one half of patients with M. tuberculosis bacteremia may die within a month of hospitalization. Simple clinical assessments can help to identify those with the condition. Advanced immunosuppression predicts death. Efforts should focus on early diagnosis and treatment of HIV infection, tuberculosis, and disseminated disease. PMID:22511551

Crump, John A.; Ramadhani, Habib O.; Morrissey, Anne B.; Saganda, Wilbrod; Mwako, Mtumwa S.; Yang, Lan-Yan; Chow, Shein-Chung; Njau, Boniface N.; Mushi, Godfrey S.; Maro, Venance P.; Reller, L. Barth; Bartlett, John A.

2012-01-01

213

Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis  

PubMed Central

Background Tuberculosis is a leading cause of death worldwide, yet the determinants of death are not well understood. We sought to determine risk factors for mortality during treatment of drug-susceptible pulmonary tuberculosis under program settings. Methods Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001. Results Of 565 patients meeting eligibility criteria, 37 (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis listed as a contributing factor. In multivariate analysis controlling for follow-up time, four characteristics were independently associated with mortality: HIV co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR = 1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis therapy (HR = 3.15, p = 0.002). The association between treatment interruption and risk of death was due to non-adherence during the intensive phase of treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption did not differ significantly in either intensive or continuation phases between those who died and survived (23 versus 18 days, and 37 versus 29 days, respectively). No deaths were directly attributed to adverse drug reactions. Conclusions In addition to advanced age, HIV and characteristics of advanced tuberculosis, experiencing an interruption in anti-tuberculosis therapy, primarily due to non-adherence, was also independently associated with increased risk of death. Improving adherence early during treatment for tuberculosis may both improve tuberculosis outcomes as well as decrease mortality. PMID:21199579

2011-01-01

214

Sensing the Killer - Tuberculosis  

NSDL National Science Digital Library

Thirty-fourth monthly installment of our "What A Year!" website project, introducing life science breakthroughs to middle and high school students and their teachers. About 2 billion people are walking around infected by tuberculosis. But they don't it, because they don't have any symptoms of this terrible disease. The trick with TB is to catch it early and prevent ever-widening circles of infection.

2010-01-04

215

Chemotherapy of tuberculosis  

Microsoft Academic Search

Summary  In order to fit the sulphonamides and sulphones out better for use in the chemotherapy of tuberculosis and leprosy, synthesis\\u000a has been effected of a series ofo-phthalic ando-toluic acid derivatives of well-known sulphonamides and disubstituted diphenyl sulphones as possible mycobacterial antagonists.\\u000a \\u000a Phthalic ando-toluic acid derivatives were chosen for synthesis in view of the recent theory advanced by Shemiakin that the

C. V. Deliwala; S. Rajagopalan

1950-01-01

216

Tuberculosis in children.  

PubMed

Tuberculosis (TB) is a major, but often unrecognised, cause of disease and death in young children from countries with high TB incidence rates among adults. It is also relevant to paediatricians in low-incidence countries, such as Australia, because of increased international travel, immigration and refugee resettlement. This manuscript provides a brief overview of the global TB disease burden, the natural history of disease in children, and offers guidance on the prevention, diagnosis and treatment of TB in children. PMID:24548085

Marais, Ben J

2014-10-01

217

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

218

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; Gonzalez-Sapienza, Gualberto; Marin, Monica

2014-01-01

219

Bioaerosol Mass Spectrometry for Rapid Detection of Individual Airborne Mycobacterium tuberculosis H37Ra Particles  

PubMed Central

Single-particle laser desorption/ionization time-of-flight mass spectrometry, in the form of bioaerosol mass spectrometry (BAMS), was evaluated as a rapid detector for individual airborne, micron-sized, Mycobacterium tuberculosis H37Ra particles, comprised of a single cell or a small number of clumped cells. The BAMS mass spectral signatures for aerosolized M. tuberculosis H37Ra particles were found to be distinct from M. smegmatis, Bacillus atrophaeus, and B. cereus particles, using a distinct biomarker. This is the first time a potentially unique biomarker was measured in M. tuberculosis H37Ra on a single-cell level. In addition, M. tuberculosis H37Ra and M. smegmatis were aerosolized into a bioaerosol chamber and were sampled and analyzed using BAMS, an aerodynamic particle sizer, a viable Anderson six-stage sampler, and filter cassette samplers that permitted direct counts of cells. In a background-free environment, BAMS was able to sample and detect M. tuberculosis H37Ra at airborne concentrations of >1 M. tuberculosis H37Ra-containing particles/liter of air in 20 min as determined by direct counts of filter cassette-sampled particles, and concentrations of >40 M. tuberculosis H37Ra CFU/liter of air in 1 min as determined by using viable Andersen six-stage samplers. This is a first step toward the development of a rapid, stand-alone airborne M. tuberculosis particle detector for the direct detection of M. tuberculosis bioaerosols generated by an infectious patient. Additional instrumental development is currently under way to make BAMS useful in realistic environmental and respiratory particle backgrounds expected in tuberculosis diagnostic scenarios. PMID:16204525

Tobias, Herbert J.; Schafer, Millie P.; Pitesky, Maurice; Fergenson, David P.; Horn, Joanne; Frank, Matthias; Gard, Eric E.

2005-01-01

220

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis.  

PubMed

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis, several of which are currently in clinical trials. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis. PMID:23913123

Pethe, Kevin; Bifani, Pablo; Jang, Jichan; Kang, Sunhee; Park, Seijin; Ahn, Sujin; Jiricek, Jan; Jung, Juyoung; Jeon, Hee Kyoung; Cechetto, Jonathan; Christophe, Thierry; Lee, Honggun; Kempf, Marie; Jackson, Mary; Lenaerts, Anne J; Pham, Ha; Jones, Victoria; Seo, Min Jung; Kim, Young Mi; Seo, Mooyoung; Seo, Jeong Jea; Park, Dongsik; Ko, Yoonae; Choi, Inhee; Kim, Ryangyeo; Kim, Se Yeon; Lim, SeungBin; Yim, Seung-Ae; Nam, Jiyoun; Kang, Hwankyu; Kwon, Haejin; Oh, Chun-Taek; Cho, Yoojin; Jang, Yunhee; Kim, Junghwan; Chua, Adeline; Tan, Bee Huat; Nanjundappa, Mahesh B; Rao, Srinivasa P S; Barnes, Whitney S; Wintjens, René; Walker, John R; Alonso, Sylvie; Lee, Saeyeon; Kim, Jungjun; Oh, Soohyun; Oh, Taegwon; Nehrbass, Ulf; Han, Sung-Jun; No, Zaesung; Lee, Jinhwa; Brodin, Priscille; Cho, Sang-Nae; Nam, Kiyean; Kim, Jaeseung

2013-09-01

221

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; Bermudez, Pilar; Bravo, M. Jose; Colmenero, Juan D.

2013-01-01

222

SMS reminders to improve the tuberculosis cure rate in developing countries (TB-SMS Cameroon): a protocol of a randomised control study  

PubMed Central

Background Tuberculosis is a public health problem in Cameroon, just like in many other countries in the world. The National Tuberculosis Control Programme (PNLT) put in place by the state, aims to fight tuberculosis through the implementation of international directives (Directly Observed Treatment Short, DOTS). Despite the deployment of this strategy across the world, its implementation is difficult in the context of low-resource countries. Some expected results are not achieved. In Cameroon, the cure rate for patients with sputum positive pulmonary tuberculosis (TPM+) after 6 months is only about 65%, 20% below the target. This is mainly due to poor patient adherence to treatment. By relying on the potential of mobile Health, the objective of this study is to evaluate the effect of SMS reminders on the cure rate of TPM?+?patients, measured using 6-month bacilloscopy. Methods/design This is a blinded, randomised controlled multicentre study carried out in Cameroon. The research hypothesis is that sending daily SMS messages to remind patients to take their prescribed tuberculosis medication, together with the standard DOTS strategy, will increase the cure rate from 65% (control group: DOTS, no SMS intervention) to 85% (intervention group: DOTS, with SMS intervention) in a group of new TPM?+?patients. In accordance with each treatment centre, the participants will be randomly allocated into the two groups using a computer program: the intervention group and the control group. A member of the research team will send daily SMS messages. Study data will be collected by health professionals involved in the care of patients. Data analysis will be done by the intention-to-treat method. Discussion The achieving of expected outcomes by the PNLT through implementation of DOTS requires several challenges. Although it has been demonstrated that the DOTS strategy is effective in the fight against tuberculosis, its application remains difficult in developing countries. This study explores the potential of mHealth to support DOTS strategy. It will gather new evidence on the effectiveness of mHealth-based interventions and SMS reminders in the improvement of treatment adherence and the cure rate of tuberculosis patients, especially in a low-resource country such as Cameroon. Trial registration The trial is registered on the Pan-African Clinical Trials Registry (http://www.pactr.org) under unique identification number: PACTR201307000583416. PMID:24460827

2014-01-01

223

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 false Mycobacterium tuberculosis immunofluorescent reagents... § 866.3370 Mycobacterium tuberculosis immunofluorescent reagents...Identification. Mycobacterium tuberculosis immunofluorescent...

2011-04-01

224

21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.  

...2014-04-01 false Mycobacterium tuberculosis immunofluorescent reagents... § 866.3370 Mycobacterium tuberculosis immunofluorescent reagents...Identification. Mycobacterium tuberculosis immunofluorescent...

2014-04-01

225

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

226

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

227

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

Devrim, Ilker; Akturk, Huseyin; Bayram, Nuri; Apa, Hursit; Tulumoglu, Sener; Devrim, Fatma; Erdem, Tulin; Gulfidan, Gamze; Ayhan, Yuce; Tamsel, Ipek; Can, Demet; Alper, Hudaver

2014-01-01

228

A case of emphysematous cystitis complicated with miliary tuberculosis  

PubMed Central

Summary Background: Emphysematous cystitis occurs mostly in diabetics with poor glycemic control or in immunocompromised patients. In most cases, diabetes mellitus correlates with the occurrence of emphysematous cystitis. The risk of relapse after tuberculosis cure or treatment completion is high among patients with diabetes mellitus. Case Report: A 64-year-old diabetic man suffering from high fever and lower abdominal pain was admitted to the emergency ward. Due to the results of radiographic examinations, he was diagnosed with an emphysematous cystitis. Although the emphysematous cystitis improved with urinary drainage and antibiotic therapy, the high fever recurred and respiratory symptoms appeared. This patient was diagnosed with a crisis of the pulmonary tuberculosis. He was started on the antituberculosis therapy, and he recovered. Conclusions: This is the first report of a case of emphysematous cystitis that was complicated with pulmonary tuberculosis. PMID:23569536

Soga, Hideo; Imanishi, Osamu

2012-01-01

229

Female genital tract tuberculosis presenting as ovarian cancer  

PubMed Central

Background: Tuberculosis (TB) is still a major worldwide concern. There is no pathognomonic clinical feature or imaging findings for definite diagnosis of extra pulmonary TB. Therefore, TB involvement of Gastrointestinal or Genitourinary tract can be easily confused with peritoneal carcinomatosis and advanced ovarian carcinoma. Our aim is to emphasize the importance of considering the disease based upon the epidemiologic clues of the patients, while interpreting the positive results for a suspicious ovarian malignancy. Cases: This paper illustrates 8 cases of ovarian or peritoneal tuberculosis, whose initial diagnoses were malignant processes of the GU tract. Conclusion: Tuberculosis (TB) should be always being considered in the differential diagnosis of advanced ovarian cancer, especially in the regions that are endemic for the disease. PMID:24778675

Hasanzadeh, Malihe; Naderi, Hamid Reza; Hoshyar, Azamossadat Hoseine; Shabane, Shima; Shahidsales, Soodabeh

2014-01-01

230

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

231

Tuberculosis of the urachal cyst  

PubMed Central

Urachal cysts are uncommon. Rarely, these cysts can become infected. Tuberculosis of the urachal cyst is exceedingly rare, with only one case reported previously in the English language literature. Here we report the case of a 23-year-old male who presented with an infra-umbilical mass that turned out to be tuberculosis of the urachal cyst. PMID:23346004

Kamal, Mir Reza; Jha, Jayesh Kumar

2013-01-01

232

Molecular evolution of Mycobacterium tuberculosis  

Microsoft Academic Search

Tuberculosis continues to be the main cause of death from a single infectious agent in developing countries. The causative agent, Mycobacterium tuberculosis, is thought to have diverged from its common ancestor as recently as 15 000 years ago. Subsequently, various genetic elements have evolved over time at different rates and can be used to elucidate patterns of infection. When individual

C. Arnold

2006-01-01

233

Diagnosis of tuberculosis in camelids: old problems, current solutions and future challenges.  

PubMed

In spite of great efforts for its control and eradication, tuberculosis remains one of the most important zoonosis worldwide. Its causative agents, the members of the Mycobacterium tuberculosis complex, have a wide host range that complicates the epidemiology of this disease. Among susceptible species to these pathogens, camelids from the New World (llama, alpaca and vicuña) and Old World (Bactrian camel and dromedary) are acquiring an increasing importance in several European countries because of its growing number and could act as reservoirs of the disease for livestock and humans in their natural habitat. In addition, tuberculosis caused by a number of M. tuberculosis complex members is a life-threatening disease in these animal species. Although tuberculosis has been known to affect camelids for a long time, ante-mortem diagnosis is still challenging because of the lack of standardized diagnostic techniques and the limited sensitivity and specificity of the most widely applied tests. However, in recent years, several techniques that can at least partially overcome these limitations have been developed. This paper reviews the results and advances achieved in tuberculosis diagnosis in camelids in the last decade as well as the progresses on ongoing investigations, with special attention to the remaining challenges that still have to be faced to assure the availability of reliable tools for the detection of tuberculosis-infected animals and herds. PMID:21635699

Alvarez, J; Bezos, J; Juan, L de; Vordermeier, M; Rodriguez, S; Fernandez-de-Mera, I G; Mateos, A; Domínguez, L

2012-02-01

234

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

235

Three-Year Longitudinal Study of Genotypes of Mycobacterium tuberculosis Isolates in Tuscany, Italy  

Microsoft Academic Search

The genetic diversity of 829 strains of Mycobacterium tuberculosis isolated during a 3-year period in Tuscany, Italy, a country with a low prevalence of tuberculosis, from 480 Italian-born and 349 foreign-born patients was determined by spoligotyping. The predominant spoligotype families were T (30.2% of isolates), Haarlem (19.9%), and the Latino-American and Mediterranean family (LAM) (11.2%); the remaining isolates were distributed

Nicoletta Lari; Laura Rindi; Daniela Bonanni; Nalin Rastogi; Christophe Sola; Enrico Tortoli; Carlo Garzelli; Morne Joliviere; Ospedale Careggi

2007-01-01

236

Molecular analysis of Mycobacterium tuberculosis DNA from a family of 18th century Hungarians  

Microsoft Academic Search

Thenaturallymummified remainsofamotherandtwo daughtersfoundinan18thcenturyHungarian crypt were analysed, using multiple molecular genetic techniques to examine the epidemiology and evolution of tuberculosis. DNA was amplified from a number of targets on the Mycobacterium tuberculosis genome, including DNA from IS6110, gyrA, katG codon 463, oxyR, dnaA-dnaN, mtp40, plcD and the direct repeat (DR) region. The strains present in the mummified remains were identified as

Helen A. Fletcher; Helen D. Donoghue; G. Michael Taylor; Mark Spigelman

2003-01-01

237

Clonal Expansion of a Globally Disseminated Lineage of Mycobacterium tuberculosis with Low IS6110 Copy Numbers  

Microsoft Academic Search

Knowledge of the clonal expansion of Mycobacterium tuberculosis and accurate identification of predominant evolutionary lineages in this species remain limited, especially with regard to low-IS6110-copy-number strains. In this study, 170 M. tuberculosis isolates with < 6I S6110 insertions identified in Cape Town, South Africa, were characterized by principal genetic grouping, restriction fragment length polymorphism analysis, spoligotyping, IS6110 insertion site mapping,

R. M. Warren; T. C. Victor; E. M. Streicher; M. Richardson; G. D. van der Spuy; R. Johnson; V. N. Chihota; C. Locht; P. Supply; P. D. van Helden

2004-01-01

238

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

239

Relationship between mutation of serine residue at 315th position in M. tuberculosis catalase-peroxidase enzyme and Isoniazid susceptibility: An in silico analysis  

Microsoft Academic Search

Remarkable advances have been made in the drug therapy of tuberculosis. However much remains to be learned about the molecular\\u000a and structural basis of drug resistance in Mycobacterium tuberculosis. It is known that, activation of Isoniazid (INH) is mediated by Mycobacterium tuberculosis catalase-peroxidase (MtBKatG) and mutation at position 315 (serine to threonine) leads to resistance. We have conducted studies on

Rituraj Purohit; Vidya Rajendran; Rao Sethumadhavan

2011-01-01

240

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

241

Tuberculosis Behind Bars in Israel: Policy Making Within a Dynamic Situation  

Microsoft Academic Search

Background: The crowded environment of correctional facilities may enhance infectious diseases transmission, such as tuberculosis. Objectives: To define the tuberculosis burden in prisons in Israel, a country of low TB incidence (7.9 cases:100,000 population in 2004), in which about 13,000 inmates are being incarcerated annually, and to recommend policy adaptations for TB control. Methods: All prison clinic lung records from

Zohar Mor; Alex Adler; Alex Leventhal; Irina Volovic; Edna Rosenfeld; Mark N. Lobato; Daniel Chemtob

2008-01-01

242

Comparison of Mantoux and Tine Tuberculin Skin Tests in BCG-Vaccinated Children Investigated for Tuberculosis  

Microsoft Academic Search

BackgroundTuberculin skin tests (TSTs) are long-established screening methods for tuberculosis (TB). We aimed to compare agreement between the intradermal Mantoux and multipuncture percutaneous Tine methods and to quantify risk factors for a positive test result.Methodology\\/Principal Findings1512 South African children younger than 5 years of age who were investigated for tuberculosis (TB) during a Bacille Calmette Guerin (BCG) trial were included

Wenli Pan; Lyness Matizirofa; Lesley Workman; Tony Hawkridge; Willem Hanekom; Hassan Mahomed; Gregory Hussey; Mark Hatherill; Madhukar Pai

2009-01-01

243

Improved efficiency in detecting cellular immunity towards M. tuberculosis in patients receiving immunosuppressive drug therapy  

Microsoft Academic Search

Background. Reactivation of a latent Mycobacterium tuberculosis infection in immunocompromised individ- uals is associated with significant morbidity and mortality. The limited sensitivity of the established tuberculin skin-test in identifying latently infected patients on immunosuppressive drug therapy repre- sents a major obstacle to better tuberculosis control after transplantation. Methods. In this study, a quantitative flow-cytometric whole-blood assay and the skin-test were

Urban Sester; Heike Junker; Tobias Hodapp; Alexandra Schutz; Bernhard Thiele; Andreas Meyerhans; Hans Kohler; Martina Sester

2006-01-01

244

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

Microsoft Academic Search

Background. Mycobacterium tuberculosis complex species display relatively static genomes and 99.9% nucleotide sequence identity. Studying the evolutionary history of such monomorphic bacteria is a difficult and challenging task. Principal Findings. We found that single-nucleotide polymorphism (SNP) analysis of DNA repair, recombination and replication (3R) genes in a comprehensive selection of M. tuberculosis complex strains from across the world, yielded surprisingly

Tiago Dos Vultos; Olga Mestre; Jean Rauzier; Marcin Golec; Nalin Rastogi; Voahangy Rasolofo; Tone Tonjum; Christophe Sola; Ivan Matic; Brigitte Gicquel

2008-01-01

245

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

246

Isoniazid prophylactic therapy for tuberculosis in HIV-seropositive patients--a least-cost analysis.  

PubMed

The expected upsurge in the number of new cases of tuberculosis resulting from the HIV/AIDS epidemic prompted an examination of the feasibility of prevention strategies to limit the increase in clinical tuberculosis. A computer spreadsheet model was developed to estimate the costs and benefits that would result from isoniazid chemoprophylaxis for tuberculosis in a hypothetical cohort of 100,000 HIV-seropositive people in South Africa over a period of 8 years. At a 50% prevalence of tuberculosis infection among those at high background risk, and 5-10% among those at low risk, there would have been 34,000 cases of active tuberculosis in the cohort and their contacts if no prophylactic therapy had been used. On the other hand, a chemoprophylaxis policy would have meant only 12,200 cases of tuberculosis, if a patient compliance rate of 68.5% had been assumed. Such a policy would have prevented 21,800 cases of active tuberculosis. The estimated total discounted cost of a chemoprophylaxis programme would have been R51.3 million. In the absence of preventive therapy the discounted cost of treating patients with active tuberculosis would have been R91.9 million over the 8-year period. Therefore, if the benefits of chemoprophylaxis were defined in terms of averted health care costs, such a policy would have resulted in net savings of R40.6 million. This study did not estimate losses in production associated with tuberculosis treatment or the value of preventing tuberculosis per se, though such indirect costs would have increased the benefit of the prevention programme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7597538

Masobe, P; Lee, T; Price, M

1995-02-01

247

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

248

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

249

Treatment Outcome of Tuberculosis Patients Registered at DOTS Centre in Ogbomoso, Southwestern Nigeria: A 4-Year Retrospective Study  

PubMed Central

Background Information. Monitoring outcome of tuberculosis treatment and understanding the specific reasons for unsuccessful treatment outcome are important in evaluating the effectiveness of tuberculosis control program. This study investigated tuberculosis treatment outcomes and predictors for unsuccessful treatment outcome in Ogbomoso town, Southwestern Nigeria. Methodology. Medical records of all tuberculosis patients registered from January 2008 to December 2011 in 5 Local Government areas, Ogbomoso, Southwestern Nigeria, were reviewed. Treatment outcome and tuberculosis type were categorized according to the national tuberculosis control guideline. Bivariate analysis was used to analyse the association between treatment outcome and potential predictor variables. Results. Out of the 965 total TB patients (579 males and 386 females) with mean age 42.4 ± 1.9 years, 866 (89.74%) were categorized as pulmonary tuberculosis and 109 (11.30%) as extrapulmonary tuberculosis. Treatment outcome among total 914 subjects was as follows: 304 (33.26%) patients got cured, 477 (52.19%) completed treatment, 87 (9.52%) died, 9 (0.98%) defaulted, and 1 (0.11%) failed treatment while 36 (3.94%) were transferred out. Higher treatment success rate was associated with those on Category 1 treatment (P < 0.05). Conclusion. The treatment success rate of tuberculosis patients was high (85.45%) compared to national target. However, certain proportion of patients died (9.52%) and defaulted (0.98%), which is a serious public health concern that needs to be addressed urgently. PMID:25328702

Sunday, Olarewaju; Oladimeji, Olanrewaju; Ebenezer, Folorunso; Akintunde, Babatunde; Abiola, Temitayo-Oboh; Saliu, Abdulsalam; Abiodun, Oluwatoyin

2014-01-01

250

Genome-wide Mycobacterium tuberculosis variation (GMTV) database: a new tool for integrating sequence variations and epidemiology  

PubMed Central

Background Tuberculosis (TB) poses a worldwide threat due to advancing multidrug-resistant strains and deadly co-infections with Human immunodeficiency virus. Today large amounts of Mycobacterium tuberculosis whole genome sequencing data are being assessed broadly and yet there exists no comprehensive online resource that connects M. tuberculosis genome variants with geographic origin, with drug resistance or with clinical outcome. Description Here we describe a broadly inclusive unifying Genome-wide Mycobacterium tuberculosis Variation (GMTV) database, (http://mtb.dobzhanskycenter.org) that catalogues genome variations of M. tuberculosis strains collected across Russia. GMTV contains a broad spectrum of data derived from different sources and related to M. tuberculosis molecular biology, epidemiology, TB clinical outcome, year and place of isolation, drug resistance profiles and displays the variants across the genome using a dedicated genome browser. GMTV database, which includes 1084 genomes and over 69,000 SNP or Indel variants, can be queried about M. tuberculosis genome variation and putative associations with drug resistance, geographical origin, and clinical stages and outcomes. Conclusions Implementation of GMTV tracks the pattern of changes of M. tuberculosis strains in different geographical areas, facilitates disease gene discoveries associated with drug resistance or different clinical sequelae, and automates comparative genomic analyses among M. tuberculosis strains. PMID:24767249

2014-01-01

251

Common types of tuberculosis and co-infection with HIV at private health institutions in Ethiopia: a cross sectional study  

PubMed Central

Background Tuberculosis is a global emergency predominantly affecting developing countries. HIV has been the single most important reason for acquisition of tuberculosis for many patients. Conversely, tuberculosis can result in rapid progression of HIV disease. Ethiopia is a country affected seriously by HIV and tuberculosis. The main aim of this study is assessment of the types of tuberculosis and the extent of HIV infection among tuberculosis patients visiting private health institutions in Amhara region of Ethiopia. Methods The study used a cross sectional method with data collected using well structured pretested questionnaires containing socio-demographic and clinical variables including HIV serostatus. The setting is tuberculosis treatment sites situated at 15 private health institutions in Amhara region. Results A total of 1153 TB patients were included. The proportions of smear positive pulmonary TB, smear negative pulmonary TB, isolated extrapulmonary TB and disseminated TB cases were found to be 29.6%, 22.2%, 43.9% and 2.9%, respectively. TB lymphadenitis accounted for about 61% of the extrapulmonary cases followed by TB pleurisy (10.6%). Seventy percent of the patients had undergone HIV test, and 20% of them were HIV positive. Marital status, patient residence and type of TB are the major determinants of co-infection. Conclusion The occurrence of pulmonary tuberculosis is relatively low. Tuberculosis/HIV co-infection is also lower than other reports. PMID:24708793

2014-01-01

252

Tuberculosis - Nobel Prize Educational Game  

NSDL National Science Digital Library

The Tuberculosis educational game and related reading, are based on the 1905 Nobel Prize in Physiology or Medicine, which was awarded for investigations and discoveries concerning the disease tuberculosis, "TB". In this game you will try to repeat Robert Koch's remarkable successes. Carry out your own experiments using Koch's methods and discover the bacteria causing tuberculosis. Rather than scoring points and doing things quickly, this game rewards figuring out what to do in the correct order to allow you to move on and reach the end!

2009-01-01

253

Nasal tuberculosis: a forgotten entity.  

PubMed

Tuberculosis of the nose has become so infrequent that it is virtually a forgotten disease entity among younger practitioners in this country. Nevertheless, it can occur in all segments of our population and may present a confusing diagnostic problem. Two cases of primary nasal tuberculosis have been diagnosed and treated at The Cleveland Clinic Foundation since 1975. The differential diagnosis of nasal granulomatous disease usually includes Wegener's granulomatosis, midline malignant reticulosis, and sarcoidosis. We point out the necessity of including tuberculosis in this differential diagnosis. The definitive work-up and treatment are also discussed. PMID:7453457

Waldman, S R; Levine, H L; Sebek, B A; Parker, W; Tucker, H M

1981-01-01

254

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

255

Energy metabolism and drug efflux in Mycobacterium tuberculosis.  

PubMed

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; Kana, Bavesh D

2014-05-01

256

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

257

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

258

Immunology of Tuberculosis  

PubMed Central

MTB ranks as the first worldwide pathogen latently infecting one third of the population and the second leading cause of death from a single infectious agent, after the human immunodeficiency virus (HIV). The development of vigorous and apparently appropriate immune response upon infection with M. tuberculosis in humans and experimental animals conflict with failure to eradicate the pathogen itself and with its ability to undergo clinical latency from which it may exit. From a clinical standpoint, our views on MTB infection may take advantage from updating the overall perspective, that has quite changed over the last decade, following remarkable advances in our understanding of the manipulation of the immune system by M. tuberculosis and of the role of innate components of the immune response, including macrophages, neutrophils, dendritic cells and NK cells in the initial spread of MTB and its exit from latency. Scope of this review is to highlight the major mechanisms of MTB escape from immune control and to provide a supplementary translational perspective for the interpretation of innate immune mechanisms with particular impact on clinical aspects. PMID:24804000

Bozzano, Federica; Marras, Francesco; De Maria, Andrea

2014-01-01

259

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

260

[Tuberculosis and traveling].  

PubMed

The traveler faces two types of specific risks for tuberculosis: that of a possible contagion through the unexpected contact with an infected person during a commercial flight (the available studies dealing mostly with cases of transmission during flights, the chapter will deal mainly with this question) and that of a possible contamination during a stay in a country with strong prevalence of TB. The ventilation in airliners is designed to limit movements of air to the front or the back of the aircraft. Moreover, studies have shown that the transmission of M. tuberculosis from passenger to passenger was observed only within the same cabin. Consequently, it is usually admitted that only passengers sitting next to the patient (3 rows ahead and behind, and 3 seats on the right and on the left of the infected passenger, depending on the aircraft's seat set-up) as well as the members of crew working in this same cabin must be warned of the potential risk a posteriori. The recommendations which follow are to be considered all the more carefully that the duration of stay is long, that the country or the geographical area is more at the risk (for example urban environment in a highly endemic zone), that the traveler is more fragile (infants and elderly people, immunodepression, etc.) and that activities during the stay will be more at risk. PMID:15622988

2004-01-01

261

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

262

Small Molecule-directed Immunotherapy against Recurrent Infection by Mycobacterium tuberculosis*  

PubMed Central

Tuberculosis remains the biggest infectious threat to humanity with one-third of the population infected and 1.4 million deaths and 8.7 million new cases annually. Current tuberculosis therapy is lengthy and consists of multiple antimicrobials, which causes poor compliance and high treatment dropout, resulting in the development of drug-resistant variants of tuberculosis. Therefore, alternate methods to treat tuberculosis are urgently needed. Mycobacterium tuberculosis evades host immune responses by inducing T helper (Th)2 and regulatory T (Treg) cell responses, which diminish protective Th1 responses. Here, we show that animals (Stat-6?/?CD4-TGF?RIIDN mice) that are unable to generate both Th2 cells and Tregs are highly resistant to M. tuberculosis infection. Furthermore, simultaneous inhibition of these two subsets of Th cells by therapeutic compounds dramatically reduced bacterial burden in different organs. This treatment was associated with the generation of protective Th1 immune responses. As these therapeutic agents are not directed to the harbored organisms, they should avoid the risk of promoting the development of drug-resistant M. tuberculosis variants. PMID:24711459

Bhattacharya, Debapriya; Dwivedi, Ved Prakash; Maiga, Mamoudou; Maiga, Mariama; Van Kaer, Luc; Bishai, William R.; Das, Gobardhan

2014-01-01

263

Small molecule-directed immunotherapy against recurrent infection by Mycobacterium tuberculosis.  

PubMed

Tuberculosis remains the biggest infectious threat to humanity with one-third of the population infected and 1.4 million deaths and 8.7 million new cases annually. Current tuberculosis therapy is lengthy and consists of multiple antimicrobials, which causes poor compliance and high treatment dropout, resulting in the development of drug-resistant variants of tuberculosis. Therefore, alternate methods to treat tuberculosis are urgently needed. Mycobacterium tuberculosis evades host immune responses by inducing T helper (Th)2 and regulatory T (Treg) cell responses, which diminish protective Th1 responses. Here, we show that animals (Stat-6(-/-)CD4-TGF?RIIDN mice) that are unable to generate both Th2 cells and Tregs are highly resistant to M. tuberculosis infection. Furthermore, simultaneous inhibition of these two subsets of Th cells by therapeutic compounds dramatically reduced bacterial burden in different organs. This treatment was associated with the generation of protective Th1 immune responses. As these therapeutic agents are not directed to the harbored organisms, they should avoid the risk of promoting the development of drug-resistant M. tuberculosis variants. PMID:24711459

Bhattacharya, Debapriya; Dwivedi, Ved Prakash; Maiga, Mamoudou; Maiga, Mariama; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

2014-06-01

264

Exosomes carrying mycobacterial antigens can protect mice against Mycobacterium tuberculosis infection.  

PubMed

Approximately 2 billion people are infected with Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), and an estimated 1.5 million individuals die annually from TB. Presently, Mycobacterium bovis BCG remains the only licensed TB vaccine; however, previous studies suggest its protective efficacy wanes over time and fails in preventing pulmonary TB. Therefore, a safe and effective vaccine is urgently required to replace BCG or boost BCG immunizations. Our previous studies revealed that mycobacterial proteins are released via exosomes from macrophages infected with M. tuberculosis or pulsed with M. tuberculosis culture filtrate proteins (CFP). In the present study, exosomes purified from macrophages treated with M. tuberculosis CFP were found to induce antigen-specific IFN-? and IL-2-expressing CD4(+) and CD8(+) T cells. In exosome-vaccinated mice, there was a similar TH1 immune response but a more limited TH2 response compared to BCG-vaccinated mice. Using a low-dose M. tuberculosis mouse aerosol infection model, exosomes from CFP-treated macrophages were found to both prime a protective immune response as well as boost prior BCG immunization. The protection was equal to or superior to BCG. In conclusion, our findings suggest that exosomes might serve as a novel cell-free vaccine against an M. tuberculosis infection. PMID:23943377

Cheng, Yong; Schorey, Jeffery S

2013-12-01

265

[Abdominal tuberculosis: clinical and therapeutic evaluation].  

PubMed

In this paper we present our experience concerning abdominal tuberculosis. The aim of this study is to evaluate various methods and to establish therapeutic approach to patients with abdominal tuberculosis. There were six patients (3 males and 3 females), aged between 22 and 67 years old, such as: 2 patients developed peritoneal tuberculosis, 3 patients developed intestinal tuberculosis and one patient developed mesenteric lymph node tuberculosis. We concluded that early diagnosis is often impossible and laboratory report was non-specific. Because surgical treatment in abdominal tuberculosis was made in complicate forms, we concluded that enterostomy "a minima" is the best therapeutic method. PMID:15675286

Me?in?, C; Pa?alega, M; Vâlcea, D; Vasile, I

2004-01-01

266

Weight concerns affect motivation to remain abstinent from smoking postpartum  

Microsoft Academic Search

Background: Although many women quit smoking during pregnancy, most resume smoking postpartum. One factor that may be important in postpartum\\u000a relapse is a pregnant woman's motivation to remain abstinent after delivery.Purpose: We assessed motivation for postpartum abstinence among pregnant women who had quit smoking and examined the relationship\\u000a of weight concerns and mood to abstinence motivation.Methods: Pregnant former smokers, recruited

Michele D. Levine; Marsha D. Marcus; Melissa A. Kalarchian; Lisa Weissfeld; Li Qin

2006-01-01

267

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

268

Tuberculosis in ageing: high rates, complex diagnosis and poor clinical outcomes  

PubMed Central

Background: worldwide, the frequency of tuberculosis among older people almost triples that observed among young adults. Objective: to describe clinical and epidemiological consequences of pulmonary tuberculosis among older people. Methods: we screened persons with a cough lasting more than 2 weeks in Southern Mexico from March 1995 to February 2007. We collected clinical and mycobacteriological information (isolation, identification, drug-susceptibility testing and IS6110-based genotyping and spoligotyping) from individuals with bacteriologically confirmed pulmonary tuberculosis. Patients were treated in accordance with official norms and followed to ascertain treatment outcomes, retreatment, and vital status. Results: eight hundred ninety-three tuberculosis patients were older than 15 years of age; of these, 147 (16.5%) were 65 years of age or older. Individuals ?65 years had significantly higher rates of recently transmitted and reactivated tuberculosis. Older age was associated with treatment failure (OR = 5.37; 95% CI: 1.06–27.23; P = 0.042), and death due to tuberculosis (HR = 3.52; 95% CI: 1.78–6.96; P < 0.001) adjusting for sociodemographic and clinical variables. Conclusions: community-dwelling older individuals participate in chains of transmission indicating that tuberculosis is not solely due to the reactivation of latent disease. Untimely and difficult diagnosis and a higher risk of poor outcomes even after treatment completion emphasise the need for specific strategies for this vulnerable group. PMID:22431155

Cruz-Hervert, Luis Pablo; Garcia-Garcia, Lourdes; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Cano-Arellano, Bulmaro; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Baez-Saldana, Renata; Tellez-Vazquez, Norma; Nava-Mercado, Ariadna; Juarez-Sandino, Luis; Delgado-Sanchez, Guadalupe; Fuentes-Leyra, Cesar Alejandro; Montero-Campos, Rogelio; Martinez-Gamboa, Rosa Areli; Small, Peter M.; Sifuentes-Osornio, Jose; Ponce-de-Leon, Alfredo

2012-01-01

269

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

270

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

271

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, Severin; Gninafon, Martin; Kassa, Ferdinand; Tawo, Leon; Dujardin, Bruno

2014-01-01

272

Phylogenetic reconstruction within Mycobacterium tuberculosis Beijing genotype in northwestern Russia  

Microsoft Academic Search

A selection of genetic markers was used to study the evolution of Mycobacterium tuberculosis Beijing family strains in northwestern Russia. A total of 221 of 434 epidemiologically unlinked isolates studied in 1996–2001 belonged to the Beijing family as determined by standard spoligotyping (signals 35–43). Ninety-six percent of these Beijing isolates (“typical”) were closely related in IS6110-RFLP (D > 0.85) while 9 remaining

Igor Mokrousov; Olga Narvskaya; Tatiana Otten; Anna Vyazovaya; Elena Limeschenko; Lidia Steklova; Boris Vyshnevskyi

2002-01-01

273

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

274

A Case of Mass-Forming Splenic Tuberculosis: MRI Findings with Emphasis of Diffusion-Weighted Imaging Characteristics  

PubMed Central

Tuberculosis remains one of the most prevalent and fatal infectious diseases in spite of considerable improvements in medical science. The diagnosis and treatment of extrapulmonary tuberculosis involving the abdomen is still complicated owing to vague or non-specific clinical features. Although rare, isolated splenic involvement is one of the important manifestations of extrapulmonary tuberculosis, and imaging suspicion of the disease is essential. We report a case of surgically confirmed mass-forming splenic tuberculosis showing a layered pattern consisting of caseous necrosis with profound restriction of water molecules surrounded by an irregular rind of granulation tissue with less diffusion restriction on diffusion-weighted magnetic resonance imaging (DWI). In the differential diagnosis of neoplastic or non-neoplastic mass-forming lesions involving the spleen, this unique DWI feature could be helpful in characterizing splenic tuberculosis. The patient has been in clinically disease free status for nearly 20 months after splenectomy. PMID:21394320

Lim, Jihe; Hong, Soon Won; Chung, Jae-Joon; Kim, Joo Hee; Kim, Ki Whang

2011-01-01

275

Novel insights into Mycobacterium antigen Ag85 biology and implications in countermeasures for M. tuberculosis.  

PubMed

Tuberculosis remains one of the most prevalent and deadly infectious diseases, largely due to the emergence of multidrug-resistant and extensive drug-resistant Mycobacterium tuberculosis, especially the coinfection with HIV. Mycobacterium Ag85 complex (Ag85A, B, and C), with a carboxylesterase consensus sequence and conserved surface catalysis residues, involves in cell wall biosynthesis and the trigger of the host immune response. The physiological function, structures, distributions, and molecular mechanisms of regulations as well as their implications in novel vaccines and diagnostics against tuberculosis are summarized. Special focus is the regulation underlying the Ag85 expression. This will facilitate in-depth understanding of the role of Ag85 and developing better novel measures against M. tuberculosis infection. PMID:23140159

Tang, XieMei; Deng, Wanyan; Xie, Jianping

2012-01-01

276

HIV-Associated Tuberculosis  

PubMed Central

The intersecting HIV and Tuberculosis epidemics in countries with a high disease burden of both infections pose many challenges and opportunities. For patients infected with HIV in high TB burden countries, the diagnosis of TB, ARV drug choices in treating HIV-TB coinfected patients, when to initiate ARV treatment in relation to TB treatment, managing immune reconstitution, minimising risk of getting infected with TB and/or managing recurrent TB, minimizing airborne transmission, and infection control are key issues. In addition, given the disproportionate burden of HIV in women in these settings, sexual reproductive health issues and particular high mortality rates associated with TB during pregnancy are important. The scaleup and resource allocation to access antiretroviral treatment in these high HIV and TB settings provide a unique opportunity to strengthen both services and impact positively in meeting Millennium Development Goal 6. PMID:20871843

Naidoo, Kogieleum; Naidoo, Kasavan; Padayatchi, Nesri; Abdool Karim, Quarraisha

2011-01-01

277

Multidrug-resistant tuberculosis.  

PubMed

Despite the efforts made worldwide to reduce the number of cases of drug-susceptible tuberculosis, multidrug-resistant tuberculosis (MDR-TB) constitutes an important public health issue. Around 440,000 new cases of MDR-TB are estimated annually, although in 2008 only 7% of these (29,423 cases) were notified. The laboratory tests for diagnosing resistance may be phenotypic (based on culture growth in the presence of drugs) or genotypic (i.e. identification of the presence of mutations that confer resistance). The urgent need for a rapid means of detecting resistance to anti-TB drugs has resulted in the development of many genotypic methods over recent years. The treatment of MDR-TB is expensive, complex, prolonged (18-24 months) and associated with a higher incidence of adverse reactions. Some basic principles must be observed when prescribing an adequate treatment regimen for MDR-TB: (a) the association of at least four drugs (three of which should not have been used previously); (b) use of a fluoroquinolone; and (c) use of an injectable anti-TB drug. In Brazil, the therapeutic regimen for MDR-TB has been standardized and consists of five drugs: terizidone, levofloxacin, pyrazinamide, ethambutol and an aminoglycoside (streptomycin or amikacin). Pulmonary resection is an important tool in the coadjuvant treatment of MDR-TB. While a recent meta-analysis revealed an average cure rate of MDR-TB of 69%, clinical studies are currently being conducted with new drugs and with drugs already available on the market but with a new indication for TB, with encouraging results that will enable more effective treatment regimens to be planned in the future. PMID:23477764

Lemos, Antônio Carlos Moreira; Matos, Eliana Dias

2013-01-01

278

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

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

2007-01-01

279

Enhanced Specialized Transduction Using Recombineering in Mycobacterium tuberculosis  

PubMed Central

ABSTRACT Genetic engineering has contributed greatly to our understanding of Mycobacterium tuberculosis biology and has facilitated antimycobacterial and vaccine development. However, methods to generate M. tuberculosis deletion mutants remain labor-intensive and relatively inefficient. Here, methods are described that significantly enhance the efficiency (greater than 100-fold) of recovering deletion mutants by the expression of mycobacteriophage recombineering functions during the course of infection with specialized transducing phages delivering allelic exchange substrates. This system has been successfully applied to the CDC1551 strain of M. tuberculosis, as well as to a ?recD mutant generated in the CDC1551 parental strain. The latter studies were undertaken as there were precedents in both the Escherichia coli literature and mycobacterial literature for enhancement of homologous recombination in strains lacking RecD. In combination, these measures yielded a dramatic increase in the recovery of deletion mutants and are expected to facilitate construction of a comprehensive library of mutants with every nonessential gene of M. tuberculosis deleted. The findings also open up the potential for sophisticated genetic screens, such as synthetic lethal analyses, which have so far not been feasible for the slow-growing mycobacteria. PMID:24865558

Tufariello, JoAnn M.; Malek, Adel A.; Vilcheze, Catherine; Cole, Laura E.; Ratner, Hannah K.; Gonzalez, Pablo A.; Jain, Paras; Hatfull, Graham F.; Larsen, Michelle H.

2014-01-01

280

Bovine tuberculosis in Canadian wildlife: An updated history  

PubMed Central

Mycobacterium bovis infection in wild animals attracted little attention in Canada until the disease was almost eliminated from domestic livestock. Tuberculosis was endemic in plains bison and occurred in elk, moose, and mule deer in Buffalo National Park (BNP), Alberta during the 1920s and 1930s. Bison were moved from BNP to Wood Buffalo National Park (WBNP), where tuberculosis became, and remains, endemic in bison, posing a risk to efforts to restore bison in northern Canada. Tuberculosis was found in a white-tailed deer in Ontario in 1959, and in an infected elk near Riding Mountain National Park (RMNP), Manitoba in 1992. Intense surveillance has resulted in detection of 40 elk, 8 white-tailed deer, and 7 cattle herds infected between 1997 and 2008 in the RMNP area. The strains of M. bovis in the RMNP area are different from strains tested from cattle and bison elsewhere in Canada. Management of tuberculosis in cattle and wild animals is challenging because of uncertainty about the ecology of the disease in various species, difficulty in obtaining samples and population data from wildlife, lack of validated tests, overlapping jurisdictions and authority, and conflicting values and opinions among stakeholders. PMID:20119541

Wobeser, Gary

2009-01-01

281

Towards a new tuberculosis drug: pyridomycin - nature's isoniazid.  

PubMed

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. ?See accompanying article http://dx.doi.org/10.1002/emmm.201201811. 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

2012-10-01

282

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

283

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, Joao; Pojer, Florence; Magnet, Sophie; Mukherjee, Raju; Uplekar, Swapna; Boy-Rottger, Stefanie; Altmann, Karl-Heinz; Cole, Stewart T

2012-01-01

284

Predicting the remaining service life of concrete  

SciTech Connect

Nuclear power plants are providing, currently, about 17 percent of the U.S. electricity and many of these plants are approaching their licensed life of 40 years. The U.S. Nuclear Regulatory Commission and the Department of Energy`s Oak Ridge National Laboratory are carrying out a program to develop a methodology for assessing the remaining safe-life of the concrete components and structures in nuclear power plants. This program has the overall objective of identifying potential structural safety issues, as well as acceptance criteria, for use in evaluations of nuclear power plants for continued service. The National Institute of Standards and Technology (NIST) is contributing to this program by identifying and analyzing methods for predicting the remaining life of in-service concrete materials. This report examines the basis for predicting the remaining service lives of concrete materials of nuclear power facilities. Methods for predicting the service life of new and in-service concrete materials are analyzed. These methods include (1) estimates based on experience, (2) comparison of performance, (3) accelerated testing, (4) stochastic methods, and (5) mathematical modeling. New approaches for predicting the remaining service lives of concrete materials are proposed and recommendations for their further development given. Degradation processes are discussed based on considerations of their mechanisms, likelihood of occurrence, manifestations, and detection. They include corrosion, sulfate attack, alkali-aggregate reactions, frost attack, leaching, radiation, salt crystallization, and microbiological attack.

Clifton, J.F.

1991-11-01

285

Juveniles' Motivations for Remaining in Prostitution  

ERIC Educational Resources Information Center

Qualitative data from in-depth interviews were collected in 1990-1991, 1992, and 2000 with 49 prostituted juveniles remanded to two rehabilitation centers in Taiwan. These data are analyzed to explore Taiwanese prostituted juveniles' feelings about themselves and their work, their motivations for remaining in prostitution, and their difficulties…

Hwang, Shu-Ling; Bedford, Olwen

2004-01-01

286

The case for fencing remains intact.  

PubMed

Creel et al. argue against the conservation effectiveness of fencing based on a population measure that ignores the importance of top predators to ecosystem processes. Their statistical analyses consider, first, only a subset of fenced reserves and, second, an incomplete examination of 'costs per lion.' Our original conclusions remain unaltered. PMID:23962143

Packer, C; Swanson, A; Canney, S; Loveridge, A; Garnett, S; Pfeifer, M; Burton, A C; Bauer, H; MacNulty, D

2013-11-01

287

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

288

Identification of ancient remains through genomic sequencing  

PubMed Central

Studies of ancient DNA have been hindered by the preciousness of remains, the small quantities of undamaged DNA accessible, and the limitations associated with conventional PCR amplification. In these studies, we developed and applied a genomewide adapter-mediated emulsion PCR amplification protocol for ancient mammalian samples estimated to be between 45,000 and 69,000 yr old. Using 454 Life Sciences (Roche) and Illumina sequencing (formerly Solexa sequencing) technologies, we examined over 100 megabases of DNA from amplified extracts, revealing unbiased sequence coverage with substantial amounts of nonredundant nuclear sequences from the sample sources and negligible levels of human contamination. We consistently recorded over 500-fold increases, such that nanogram quantities of starting material could be amplified to microgram quantities. Application of our protocol to a 50,000-yr-old uncharacterized bone sample that was unsuccessful in mitochondrial PCR provided sufficient nuclear sequences for comparison with extant mammals and subsequent phylogenetic classification of the remains. The combined use of emulsion PCR amplification and high-throughput sequencing allows for the generation of large quantities of DNA sequence data from ancient remains. Using such techniques, even small amounts of ancient remains with low levels of endogenous DNA preservation may yield substantial quantities of nuclear DNA, enabling novel applications of ancient DNA genomics to the investigation of extinct phyla. PMID:18426903

Blow, Matthew J.; Zhang, Tao; Woyke, Tanja; Speller, Camilla F.; Krivoshapkin, Andrei; Yang, Dongya Y.; Derevianko, Anatoly; Rubin, Edward M.

2008-01-01

289

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 Jose Guardao

2013-01-01

290

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

291

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

Microsoft Academic Search

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.

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

2009-01-01

292

INHIBITOR STUDIES ON MYCOBACTERIUM TUBERCULOSIS MALATE SYNTHASE  

E-print Network

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant...

Owen, Joshua

2008-08-03

293

Global Alliance for Tuberculosis Drug Development  

MedlinePLUS

... and development of better, faster-acting, and affordable tuberculosis drugs that are available to those who need ... we are making progress in the fight against tuberculosis. Learn More About Our Work > Our Pipeline The ...

294

Extrapulmonary tuberculosis: are statistical reports accurate?  

PubMed Central

Before discussing the epidemiology of extrapulmonary tuberculosis (EPTB) and particularly urogenital tuberculosis (UGTB), unification of the terminology is necessary. The term ‘urogenital tuberculosis’ is preferable to ‘genitourinary tuberculosis’, as renal and urinary tract tuberculosis is more common than genital tuberculosis. Some understand the term ‘extrapulmonary tuberculosis’ as a specific tuberculosis (TB) lesion of all organs excluding the bronchus, lungs, pleura and intrathoracic bronchopulmonary lymph nodes, but others consider pleural TB as one form of EPTB – and it is a reason for very different proportions in the spectrum of EPTB. Enigmatic tendencies have also been revealed in patients' distribution – in neighbouring regions the incidence rate may differ significantly. Although there is no clear explanation for these tendencies, careful study of the epidemiology of EPTB in different conditions will improve early diagnosis. PMID:25165556

2014-01-01

295

Tuberculosis disease diagnosis using artificial neural networks.  

PubMed

Tuberculosis is an infectious disease, caused in most cases by microorganisms called Mycobacterium tuberculosis. Tuberculosis is a great problem in most low income countries; it is the single most frequent cause of death in individuals aged fifteen to forty-nine years. Tuberculosis is important health problem in Turkey also. In this study, a study on tuberculosis diagnosis was realized by using multilayer neural networks (MLNN). For this purpose, two different MLNN structures were used. One of the structures was the MLNN with one hidden layer and the other was the MLNN with two hidden layers. A general regression neural network (GRNN) was also performed to realize tuberculosis diagnosis for the comparison. Levenberg-Marquardt algorithms were used for the training of the multilayer neural networks. The results of the study were compared with the results of the pervious similar studies reported focusing on tuberculosis diseases diagnosis. The tuberculosis dataset were taken from a state hospital's database using patient's epicrisis reports. PMID:20503614

Er, Orhan; Temurtas, Feyzullah; Tanrikulu, A Cetin

2010-06-01

296

Challenges of Loss to Follow-up in Tuberculosis Research  

Microsoft Academic Search

BackgroundIn studies evaluating methods for diagnosing tuberculosis (TB), follow-up to verify the presence or absence of active TB is crucial and high dropout rates may significantly affect the validity of the results. In a study assessing the diagnostic performance of the QuantiFERON®-TB Gold In-Tube test in TB suspect children in Tanzania, factors influencing patient adherence to attend follow-up examinations and

Thomas N. Nissen; Michala V. Rose; Godfather Kimaro; Ib C. Bygbjerg; Sayoki G. Mfinanga; Pernille Ravn

2012-01-01

297

Excess lung function decline in gold miners following pulmonary tuberculosis  

Microsoft Academic Search

BackgroundFew if any studies of the association between pulmonary tuberculosis (TB) and lung function loss have had access to premorbid lung function values.MethodsUsing a retrospective cohort design, the study recruited employed South African gold miners who had undergone a pulmonary function test (PFT) between January 1995 and August 1996. The ‘exposed’ group comprised 185 miners treated for pulmonary TB after

J Ross; R I Ehrlich; E Hnizdo; N White; G J Churchyard

2010-01-01

298

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

Lopez-Calleja, Ana Isabel; Gavin, Patricia; Lezcano, Ma Antonia; Vitoria, Ma Asuncion; Iglesias, Ma Jose; Guimbao, Joaquin; Lazaro, Ma Angeles; Rastogi, Nalin; Revillo, Ma Jose; Martin, Carlos; Samper, Sofia

2009-01-01

299

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

300

Tuberculosis Incidence Correlates with Sunshine: An Ecological 28-Year Time Series Study  

PubMed Central

Background Birmingham is the largest UK city after London, and central Birmingham has an annual tuberculosis incidence of 80 per 100,000. We examined seasonality and sunlight as drivers of tuberculosis incidence. Hours of sunshine are seasonal, sunshine exposure is necessary for the production of vitamin D by the body and vitamin D plays a role in the host response to tuberculosis. Methods We performed an ecological study that examined tuberculosis incidence in Birmingham from Dec 1981 to Nov 2009, using publicly-available data from statutory tuberculosis notifications, and related this to the seasons and hours of sunshine (UK Meteorological Office data) using unmeasured component models. Results There were 9,739 tuberculosis cases over the study period. There was strong evidence for seasonality, with notifications being 24.1% higher in summer than winter (p<0.001). Winter dips in sunshine correlated with peaks in tuberculosis incidence six months later (4.7% increase in incidence for each 100 hours decrease in sunshine, p<0.001). Discussion and Conclusion A potential mechanism for these associations includes decreased vitamin D levels with consequent impaired host defence arising from reduced sunshine exposure in winter. This is the longest time series of any published study and our use of statutory notifications means this data is essentially complete. We cannot, however, exclude the possibility that another factor closely correlated with the seasons, other than sunshine, is responsible. Furthermore, exposure to sunlight depends not only on total hours of sunshine but also on multiple individual factors. Our results should therefore be considered hypothesis-generating. Confirmation of a potential causal relationship between winter vitamin D deficiency and summer peaks in tuberculosis incidence would require a randomized-controlled trial of the effect of vitamin D supplementation on future tuberculosis incidence. PMID:23483924

Koh, Gavin C. K. W.; Hawthorne, Gemma; Turner, Alice M.; Kunst, Heinke; Dedicoat, Martin

2013-01-01

301

Spoligotyping and Drug Resistance Analysis of Mycobacterium tuberculosis Strains from National Survey in China  

PubMed Central

Background Tuberculosis (TB), caused by Mycobacterium tuberculosis complex (MTBC), is one of the major causes of death in the world today. Although China has the second largest global case rate of tuberculosis, a systematic study of TB prevalence in China has not been completed. From 2006 to 2007, the base line surveillance of tuberculosis was carried out by Ministry of Health, and more than 4000 representative strains were selected from 31 provinces in China. Methodology/Principal Findings The aim of the present research was to survey the genotypes of representative Mycobacterium tuberculosis (M. tuberculosis) strains from China using spacer oligonucleotide typing (spoligotyping), and to analyze the relationship between genotype and drug resistance for the first time. A total of 4017 clinical isolates were collected from 2007 to 2008 throughout China. Among those M. tuberculosis isolates, 2500 (62.2%) isolates were Beijing genotypes. The percentage of Beijing genotypes in northern China was higher than in southern China (76.5% vs. 53.2%). Additionally, the frequencies of rifampin-resistant, ofloxacin-resistant and multidrug-resistant isolates were significantly higher in Beijing genotype strains than non-Beijing strains. Furthermore, a novel genotype named “China Southern genotype (CS)” was only isolated from Fujian and Guangdong provinces. Hence, it is very practical to uncover the reason for prevalence of the CS type in southern China. Conclusions/Significance In conclusion, Beijing family genotypes were still the predominant genotype throughout China, which exhibited a greater correlation with rifampin-resistance, ofloxacin-resistance and MDR phenotypes than other TB spoligotypes, and some regions of China showed several unique characters in the distribution of M. tuberculosis genotypes. Our research represents an important contribution for the TB control and research community, which completes broad pictures on drug resistance levels and distribution of M. tuberculosis strain types over China. PMID:22412962

Liu, Guan; Jiang, Guanglu; Xia, Hui; Song, Yuanyuan; Shang, Yuanyuan; Wang, Shengfen; Zhao, Yan-lin

2012-01-01

302

Gamma/delta T lymphocytes in Mycobacterium tuberculosis infection  

PubMed Central

BACKGROUND: Data on the percentage of gamma/delta T lymphocytes in the peripheral blood of patients infected with Mycobacterium tuberculosis are few and contradictory. The percentage of gamma/delta T lymphocytes in the peripheral blood of tuberculin positive and tuberculin negative patients with Mycobacterium tuberculosis infection and healthy controls was compared. METHODS: Thirty six patients infected with Mycobacterium tuberculosis and 11 healthy controls were studied. Lymphocytes were separated, cytocentrifuged onto glass microscope slides, and reacted with anti-gamma/delta monoclonal antibody. The percentage of gamma/delta positive cells was determined by microscopic counting of 300 lymphocytes. RESULTS: No difference was found in the percentage of gamma/delta T lymphocytes between patients and controls. However, when the patients were divided into two groups according to reactivity or non-reactivity in the Mantoux skin reaction a higher percentage of gamma/delta T lymphocytes was found in the peripheral blood of patients with tuberculin anergy than in tuberculin positive patients or controls. CONCLUSIONS: Higher gamma/delta T cell counts are found in tuberculin negative patients with tuberculosis than in tuberculin positive patients or tuberculin positive controls. The high gamma/delta T cell counts in tuberculin anergic patients may reflect a shift in the immune response in a Th2 direction characterised by increased antibody production and decreased cell mediated responses. ??? PMID:9196523

Baliko, Z.; Szereday, L.; Szekeres-Bartho, J.

1997-01-01

303

Infection with Helicobacter pylori Is Associated with Protection against Tuberculosis  

E-print Network

Background: Helicobacter pylori, a lifelong and typically asymptomatic infection of the stomach, profoundly alters gastric immune responses, and may benefit the host in protection against other pathogens. We explored the hypothesis that H. pylori contributes to the control of infection with Mycobacterium tuberculosis. Methodology/Principal Findings: We first examined M. tuberculosis-specific IFN-c and H. pylori antibody responses in 339 healthy Northern Californians undergoing routine tuberculin skin testing. Of 97 subjects (29%) meeting criteria for latent tuberculosis (TB) infection (LTBI), 45 (46%) were H. pylori seropositive. Subjects with LTBI who were H. pylori-seropositive had 1.5-fold higher TB antigen-induced IFN-c responses (p = 0.04, ANOVA), and a more Th-1 like cytokine profile in peripheral blood mononuclear cells, compared to those who were H. pylori seronegative. To explore an association between H. pylori infection and clinical outcome of TB exposure, we evaluated H. pylori seroprevalence in baseline samples from two high risk TB case-contact cohorts, and from cynomolgus macaques experimentally challenged with M. tuberculosis. Compared to 513 household contacts who did not progress to active disease during a median 24 months follow-up, 120 prevalent TB cases

Sharon Perry; Bouke C. De Jong; Jay V. Solnick; Maria De La Luz Sanchez; Shufang Yang; Ling Lin; Lori M. Hansen; Najeeha Talat; Philip C. Hill; Rabia Hussain; Richard A. Adegbola; Don Canfield; Julie Parsonnet

304

Native New Zealand plants with inhibitory activity towards Mycobacterium tuberculosis  

PubMed Central

Background Plants have long been investigated as a source of antibiotics and other bioactives for the treatment of human disease. New Zealand contains a diverse and unique flora, however, few of its endemic plants have been used to treat tuberculosis. One plant, Laurelia novae-zelandiae, was reportedly used by indigenous Maori for the treatment of tubercular lesions. Methods Laurelia novae-zelandiae and 44 other native plants were tested for direct anti-bacterial activity. Plants were extracted with different solvents and extracts screened for inhibition of the surrogate species, Mycobacterium smegmatis. Active plant samples were then tested for bacteriostatic activity towards M. tuberculosis and other clinically-important species. Results Extracts of six native plants were active against M. smegmatis. Many of these were also inhibitory towards M. tuberculosis including Laurelia novae-zelandiae (Pukatea). M. excelsa (Pohutukawa) was the only plant extract tested that was active against Staphylococcus aureus. Conclusions Our data provide support for the traditional use of Pukatea in treating tuberculosis. In addition, our analyses indicate that other native plant species possess antibiotic activity. PMID:20537175

2010-01-01

305

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

306

Linkage disequilibrium between minisatellite loci supports clonal evolution of Mycobacterium tuberculosis in a high tuberculosis incidence area.  

PubMed

Deciphering the structure of pathogen populations is instrumental for the understanding of the epidemiology and history of infectious diseases and for their control. Although Mycobacterium tuberculosis is the most widespread infectious agent in humans, its actual population structure has remained hypothetical until now because: (i) its structural genes are poorly polymorphic; (ii) adequate samples and appropriate statistics for population genetic analysis have not been considered. To investigate this structure, we analysed the statistical associations (linkage disequilibrium) between 12 independent M. tuberculosis minisatellite-like loci by high-throughput genotyping within a model population of 209 isolates representative of the genetic diversity in an area with a very high incidence of tuberculosis. These loci contain variable number tandem repeats (VNTRs) of genetic elements named mycobacterial interspersed repetitive units (MIRUs). Highly significant linkage disequilibrium was detected among the MIRU-VNTR loci in this model. This linkage disequilibrium was also evident when the MIRU-VNTR types were compared with the IS6110 restriction fragment length polymorphism types. These results support a predominant clonal evolution of M. tuberculosis. PMID:12519202

Supply, Philip; Warren, Robin M; Bañuls, Anne-Laure; Lesjean, Sarah; Van Der Spuy, Gian D; Lewis, Lee-Anne; Tibayrenc, Michel; Van Helden, Paul D; Locht, Camille

2003-01-01

307

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

308

Primary Perianal Tuberculosis in a Diabetic Patient  

PubMed Central

Primary perianal tuberculosis is a rare form of extra pulmonary tuberculosis. We present a case of perianal tuberculosis without any pulmonary or gastrointestinal involvement in a diabetic patient. Histopathological examination of perianal lesion demonstrated loose granulomas and positive staining for Erlich-Ziehl-Neelsen (EZN) stain. PMID:24404369

Chadha, Tandra; Adlekha, Shashikant

2013-01-01

309

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

310

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

311

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

312

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

313

9 CFR 311.2 - Tuberculosis.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Tuberculosis. 311.2 Section 311.2 Animals...ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The following principles shall...the difference in the pathogenesis of tuberculosis in swine, cattle, sheep,...

2010-01-01

314

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

315

9 CFR 311.2 - Tuberculosis.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false Tuberculosis. 311.2 Section 311.2 Animals...ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The following principles shall...the difference in the pathogenesis of tuberculosis in swine, cattle, sheep,...

2013-01-01

316

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

317

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

318

[Variability and diagnosis of pulmonary tuberculosis].  

PubMed

Five hundred-ninety new cases of tuberculosis were analyzed in Republic Santariskiu Tuberculosis and Lung Disease Hospital during 06 1997-06 2001. Mean age of patients - 47+/-30 years. All cases were classified based on international tuberculosis classification: pulmonary tuberculosis (A15, A16) - 409 cases; tuberculosis pleurisy (A15.6, A16.5) - 169; miliary tuberculosis (A19) - 11; generalized tuberculous lymphadenitis (A18.5) - 1. Pulmonary tuberculosis confirmed by sputum smear (A15.0) was prevalent in the structure of new tuberculosis cases (26.4%); pulmonary tuberculosis was confirmed by culture (A15.1) in 14.1%; by histology (A15.2) - in 10.3%. Unconfirmed pulmonary tuberculosis (A16) and tuberculous pleurisy (A16.5) amounted to 28.5%. Liver biopsy and positive sputum cultures for mycobacterias mostly confirmed tuberculosis diagnosis in miliary tuberculosis cases. From all tuberculous pleurisy cases in 65% the diagnosis was confirmed by bacteriology and/or histology. PMID:12552162

Kaminskaite, Ausra

2002-01-01

319

Decreased Frequencies of Circulating CD4+ T Follicular Helper Cells Associated with Diminished Plasma IL-21 in Active Pulmonary Tuberculosis  

PubMed Central

Background Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4+ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored. Aims/Methodology To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n?=?30) and latent TB (LTB; n?=?20) individuals, using the markers CXCR5, PD-1 and ICOS. Results We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFN?. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro. Conclusions Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets. PMID:25343703

Kumar, Nathella Pavan; Sridhar, Rathinam; Hanna, Luke E.; Banurekha, Vaithilingam V.; Nutman, Thomas B.; Babu, Subash

2014-01-01

320

Correlates of Delayed Diagnosis among Human Immunodeficiency Virus-Infected Pulmonary Tuberculosis Suspects in a Rural HIV Clinic, South Africa  

PubMed Central

Background. Delay in pulmonary tuberculosis (PTB) diagnosis is one of the major factors that affect outcome and threatens continued spread of tuberculosis. This study aimed at determining factors associated with delayed PTB diagnosis among human immunodeficiency virus (HIV) infected individuals. Methods. A retrospective observational study was done using clinic records of HIV-infected PTB suspects attending an HIV/AIDS clinic at Tintswalo rural hospital in South Africa (SA) between January 2006 and December 2007. Using routine clinic registers, 480 records were identified. Results. PTB diagnosis delay was found among 77/176 (43.8%) of the patients diagnosed with PTB. The mean delay of PTB diagnosis was 170.6 days; diagnosis delay ranged 1–30 days in 27 (35.1%) patients, 31–180 days in 24 (33.8%) patients; 24 (31.2%) patients remained undiagnosed for ?180 days. Independent factors associated with delayed diagnosis were: older age >40 years (Odds Ratio (OR) 3.43, 95% CI 1.45–8.08) and virological failure (OR 2.72, 95% CI 1.09–6.74). Conclusion. There is a considerable delayed PTB diagnosis among HIV-infected patients in rural SA. Older patients as well as patients with high viral load are at a higher risk of PTB diagnosis delay. Therefore efforts to reduce PTB diagnosis delay need to emphasised. PMID:22778946

Boniface, Respicious; Moshabela, Mosa; Zulliger, Rose; MacPherson, Peter; Nyasulu, Peter

2012-01-01

321

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

322

Pancreatic Tuberculosis or Autoimmune Pancreatitis  

PubMed Central

Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis. PMID:24839445

Saif, Muhammad Wasif

2014-01-01

323

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

324

51-L Challenger Crew Remains Transferred  

NASA Technical Reports Server (NTRS)

The Challenger crewmember remains are being transferred from 7 hearse vehicles to a MAC C-141 transport plane at the Kennedy Space Center's Shuttle Landing Facility for transport to Dover Air Force Base, Delaware. The STS-51L crew consisted of: Mission Specialist, Ellison S. Onizuka, Teacher in Space Participant Sharon Christa McAuliffe, Payload Specialist, Greg Jarvis and Mission Specialist, Judy Resnik. In the front row from left to right: Pilot Mike Smith, Commander, Dick Scobee and Mission Specialist, Ron McNair.

1988-01-01

325

Shotgun microbial profiling of fossil remains.  

PubMed

Millions to billions of DNA sequences can now be generated from ancient skeletal remains thanks to the massive throughput of next-generation sequencing platforms. Except in cases of exceptional endogenous DNA preservation, most of the sequences isolated from fossil material do not originate from the specimen of interest, but instead reflect environmental organisms that colonized the specimen after death. Here, we characterize the microbial diversity recovered from seven c. 200- to 13 000-year-old horse bones collected from northern Siberia. We use a robust, taxonomy-based assignment approach to identify the microorganisms present in ancient DNA extracts and quantify their relative abundance. Our results suggest that molecular preservation niches exist within ancient samples that can potentially be used to characterize the environments from which the remains are recovered. In addition, microbial community profiling of the seven specimens revealed site-specific environmental signatures. These microbial communities appear to comprise mainly organisms that colonized the fossils recently. Our approach significantly extends the amount of useful data that can be recovered from ancient specimens using a shotgun sequencing approach. In future, it may be possible to correlate, for example, the accumulation of postmortem DNA damage with the presence and/or abundance of particular microbes. PMID:24612293

Der Sarkissian, C; Ermini, L; Jónsson, H; Alekseev, A N; Crubezy, E; Shapiro, B; Orlando, L

2014-04-01

326

The identification of submerged skeletonized remains.  

PubMed

Examination was undertaken of skeletonized remains contained within 2 rubber boots dredged by a fishing boat from a depth of 145 m, approximately 185 km off the southern Australian coast in the Great Australian Bight. The boots had been manufactured in Australia in July 1993 and were of a type commonly used by local fishermen. Examination of the lower legs and feet revealed well-preserved bones with arthritic changes in keeping with an older male. DNA analyses using reference samples taken from relatives of fishermen who had disappeared in the area resulted in the identification of the victim as a 52-year-old prawn fisherman who had been swept off a boat over a decade earlier. DNA stability had been maintained by the low light, cold temperatures, and alkaline pH of the ocean floor. Integration of pathologic, anthropologic, and biologic analyses with police investigations enabled a positive identification to be made despite the unusual nature of the location of the remains and the time lapse since the disappearance of the victim. PMID:19749621

Byard, Roger W; Both, Katrin; Simpson, Ellie

2008-03-01

327

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

328

The Most Predominant Spoligopatterns of Mycobacterium tuberculosis Isolates among Iranian, Afghan-Immigrant, Pakistani and Turkish Tuberculosis Patients: A Comparative Analysis  

Microsoft Academic Search

Background: The aim of this study was to identify prevalent spoligopatterns of Mycobacterium tuberculosis (MTB) strains within Iran and its neighboring countries. Methods: The spacer oligonucleotide typing (spoligotyping) was performed on 1,742 MTB strains isolated from Iranian and Afghan patients. Subsequently, these results were compared with published results of Pakistan and Turkey. Results: Based on the international spoligotyping database T,

Muayad A. Merza; Parissa Farnia; Ahmad M. Salih; Mohammad Reza Masjedi; Ali Akbar Velayati

2010-01-01

329

Diagnosis & treatment of tuberculosis in HIV co-infected patients  

PubMed Central

Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice-versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection. PMID:22310818

Padmapriyadarsini, C.; Narendran, G.; Swaminathan, Soumya

2011-01-01

330

A case of extensive multifocal tuberculosis verrucosa cutis.  

PubMed

Tuberculosis is probably as old as the human race itself. Cutaneous tuberculosis constitutes a very small proportion of extra pulmonary tuberculosis. Extensive, multifocal involvement of cutaneous tuberculosis is a very rare manifestation. We report one such case of extensive, multifocal tuberculosis verrucosa cutis in a 30-year-old immunocompetent male patient in the absence of any primary tubercular focus. PMID:25071280

Verma, Rajesh; Vasudevan, Biju; Pragasam, Vijendran; Badad, Ambresh

2014-07-01

331

A Case of Extensive Multifocal Tuberculosis Verrucosa Cutis  

PubMed Central

Tuberculosis is probably as old as the human race itself. Cutaneous tuberculosis constitutes a very small proportion of extra pulmonary tuberculosis. Extensive, multifocal involvement of cutaneous tuberculosis is a very rare manifestation. We report one such case of extensive, multifocal tuberculosis verrucosa cutis in a 30-year-old immunocompetent male patient in the absence of any primary tubercular focus. PMID:25071280

Verma, Rajesh; Vasudevan, Biju; Pragasam, Vijendran; Badad, Ambresh

2014-01-01

332

The male suburethral sling: remaining questions.  

PubMed

The AdVance transobturator sling represents an important treatment option for male stress urinary incontinence. Accordingly, recent data suggests AdVance to yield success rates of 62%-77% through 3 year follow up.1,2 Although experience to date is favorable, many questions exist. Foremost, the ideal technique for intraoperative placement and tensioning remains a topic of discussion. The exact mechanism by which sling placement restores continence is unknown, but is hypothesized to comprise an elevation of the bulbar urethra both ventrally and cranially. This "repositioning" may then lead to improved urethral coaptation. Concurrently, urodynamic investigation suggests that sling action does not involve an obstructive effect.3 Despite these findings, other investigation highlights the questions that remain regarding sling mechanism of action and the role that urethral compression may place in continence restoration. Accordingly, study of postoperative MRI findings suggests that urethral bulb indentation may be associated with postoperative continence.4 Further, acute urinary retention (AUR) is frequently observed following sling placement, seen in 12%-21% of cases.2,5 Although it is hypothesized that the high rate of AUR may relate to a detrusor muscle deconditioned during prolonged periods of low outlet resistance, a role of urethral compression cannot be excluded. The authors seek to investigate the hypothesis that postoperative AUR may actually be associated with improved continence outcomes. The authors identify continence rates of 100% and 26% in comparison of patients experiencing postoperative AUR versus patients undergoing successful void trial, respectively.6 While this finding is of value, several issues are important to mention. Foremost, additional research is needed to confirm the primary study finding given that prior multivariate analysis has demonstrated that AUR presence/absence was not an independent risk factor for sling failure.7 Second, given some data suggesting that sling success rates deteriorate over time, longitudinal long term investigation is important to determine whether postoperative AUR may be a predictor for durable success rates.8 Finally, assessment of urgency outcomes following male sling placement is important. De novo irritative symptoms and voiding dysfunction following midurethral sling placement in women are a significant concern. Such adverse effects are thought to arise due to an obstructive or irritative effect of the sling. Although the mechanism of action of the AdVance sling is likely different, data regarding urgency outcomes is nonetheless important. This is especially true of patients experiencing AUR postoperatively, even if transient. Despite the many questions that remain, the primary study finding of improved outcomes in patients experiencing AUR is important. Anecdotally, I have observed this tendency in my own practice and believe this to be an observation warranting investigation. PMID:25171277

Rapp, David E

2014-08-01

333

The Endothelin System Has a Significant Role in the Pathogenesis and Progression of Mycobacterium tuberculosis Infection.  

PubMed

Tuberculosis (TB) remains a major global health problem, and although multiple studies have addressed the relationship between Mycobacterium tuberculosis and the host on an immunological level, few studies have addressed the impact of host physiological responses. Proteases produced by bacteria have been associated with important alterations in the host tissues, and a limited number of these enzymes have been characterized in mycobacterial species. M. tuberculosis produces a protease called Zmp1, which appears to be associated with virulence and has a putative action as an endothelin-converting enzyme. Endothelins are a family of vasoactive peptides, of which 3 distinct isoforms exist, and endothelin 1 (ET-1) is the most abundant and the best-characterized isoform. The aim of this work was to characterize the Zmp1 protease and evaluate its role in pathogenicity. Here, we have shown that M. tuberculosis produces and secretes an enzyme with ET-1 cleavage activity. These data demonstrate a possible role of Zmp1 for mycobacterium-host interactions and highlights its potential as a drug target. Moreover, the results suggest that endothelin pathways have a role in the pathogenesis of M. tuberculosis infections, and ETA or ETB receptor signaling can modulate the host response to the infection. We hypothesize that a balance between Zmp1 control of ET-1 levels and ETA/ETB signaling can allow M. tuberculosis adaptation and survival in the lung tissues. PMID:25267836

Correa, Andre F; Bailão, Alexandre M; Bastos, Izabela M D; Orme, Ian M; Soares, Célia M A; Kipnis, Andre; Santana, Jaime M; Junqueira-Kipnis, Ana Paula

2014-12-01

334

New drugs to treat tuberculosis  

PubMed Central

Tuberculosis (TB) has been a leading cause of death for more than a century. While effective therapies exist, treatment is long and cumbersome. Tuberculosis control is complicated by the overlapping problems created by global inadequacy of public health infrastructures, the interaction of the TB and human immunodeficiency virus epidemics, and the emergence of drug-resistant TB. After a long period of neglect, there is now significant progress in development of TB diagnostics and therapeutics. Focusing on treatment for active TB, we review the new pathways to TB regimen development, and the new and repurposed anti-TB agents in clinical development. PMID:22719795

2012-01-01

335

Increased Incidence of Tuberculosis in Zimbabwe, in Association with Food Insecurity, and Economic Collapse: An Ecological Analysis  

PubMed Central

Background Zimbabwe underwent a socioeconomic crisis and resultant increase in food insecurity in 2008–9. The impact of the crisis on Tuberculosis (TB) incidence is unknown. Methods Prospective databases from two mission hospitals, which were geographically widely separated, and remained open during the crisis, were reviewed. Results At the Howard Hospital (HH) in northern Zimbabwe, TB incidence increased 35% in 2008 from baseline rates in 2003–2007 (p<0.01) and remained at that level in 2009. Murambinda Hospital (MH) in Eastern Zimbabwe also demonstrated a 29% rise in TB incidence from 2007 to 2008 (p<0.01) and remained at that level in 2009. Data collected post-crisis at HH showed a decrease of 33% in TB incidence between 2009 to 2010 (p<0.001) and 2010/2011 TB incidence remained below that of the crisis years of 2008/2009 (p<0.01). Antenatal clinic HIV seroprevalence at HH decreased between 2001(23%) to 2011(11%) (p<0.001). Seasonality of TB incidence was analyzed at both MH and HH. There was a higher TB incidence in the dry season when food is least available (September-November) compared to post harvest (April-June) (p<0.001). Conclusion This study suggests that an epidemic of TB mirrored socioeconomic collapse and recovery in Zimbabwe. The seasonal data suggests that food security may have been associated with TB incidence both annually and during the crisis in this high HIV prevalence country. PMID:24505245

Thistle, Paul; Katumbe, Lovemore; Jetha, Arif; Schwarz, Dan; Bolotin, Shelly; Barker, R. D.; Simor, Andrew; Silverman, Michael

2014-01-01

336

Correlations of mutations in katG, oxyR-ahpC and inhA genes and in vitro susceptibility in Mycobacterium tuberculosis clinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America  

Microsoft Academic Search

BACKGROUND: Mutations associated with resistance to rifampin or streptomycin have been reported for W\\/Beijing and Latin American Mediterranean (LAM) strain families of Mycobacterium tuberculosis. A few studies with limited sample sizes have separately evaluated mutations in katG, ahpC and inhA genes that are associated with isoniazid (INH) resistance. Increasing prevalence of INH resistance, especially in high tuberculosis (TB) prevalent countries

Elis R Dalla Costa; Marta O Ribeiro; Márcia SN Silva; Liane S Arnold; Diana C Rostirolla; Patricia I Cafrune; Roger C Espinoza; Moises Palaci; Maria A Telles; Viviana Ritacco; Philip N Suffys; Maria L Lopes; Creuza L Campelo; Silvana S Miranda; Kristin Kremer; Pedro E Almeida da Silva; Leila Fonseca; John L Ho; Afrânio L Kritski; Maria LR Rossetti

2009-01-01

337

Outlook remains dim for waste solution  

SciTech Connect

When Congress selected Yucca Mountain as the proposed site for storing the nation`s high-level nuclear waste, this isolated piece of real estate in Nevada became the focus of national debate about the long-term safety and feasibility of underground storage, writes Frank L. Parker, a professor in environmental engineering at Vanderbilt University. {open_quotes}While scientific knowledge will increase in the future, it is unlikely that we will ever achieve full understanding of the long-term movement of radioactive waste that must remain buried for hundreds of thousands of years,{close_quotes} says Parker. Parker maintains that the battle over the future of Yucca Mountain has proved that local communities should have a strong voice in the site-selection process, and, once a site is chosen, people who live nearby should be compensated for the burden they bear.

Parker, F.L.

1994-12-31

338

Remaining competitive in refining and basic petrochemicals  

SciTech Connect

Companies involved in petroleum refining and basic petrochemicals production represent a major segment of the largest (Fortune 20) US corporations and account for a substantial share of the country's wealth. The 1980's have presented turbulent times for these businesses, causing massive restructuring which has not resulted in a return to former levels of financial performance. The refining and petrochemical industries will continue to play a major role in the American economy over the next few decades, but they are currently struggling to achieve the performance necessary to remain viable over the long term. Since chemical engineers are prominent professionals in petrochemical and refining companies, the Government Programs Steering Committee of the American Institute of Chemical Engineers has prepared this analysis to inform federal, state, and local government officials about the future viability of these basic industries. 2 refs., 7 figs., 2 tabs.

Cobb, C.

1988-03-01

339

Thoracic surgery for haemoptysis in the context of tuberculosis: what is the best management approach?  

PubMed Central

Haemoptysis is not an unusual finding in patients with old or active pulmonary tuberculosis. Because of bronchial artery or a branch of pulmonary artery erosion due to cavitary infiltration, bronchiectasis, fungus ball, broncholithiasis or destroyed lung, the bleeding can sometimes be a life-threatening situation. Assessment of the patient and finding the exact site of bleeding can be difficult especially in a patient with disseminated lung disease. Chest computerized tomography and bronchoscopy remain the methods of choice for lateralization of the disease. Some patients can be treated successfully with endobronchial interventions. Bronchial artery embolization can be rewarding in some patients but the recurrence rate is higher in tuberculosis than other etiologies of haemoptysis. Surgical resection of the lung, mainly lobectomy, remains a life-saving procedure but it should be performed very selectively to avoid higher postoperative morbidity and mortality. Different management options of haemoptysis in patients with pulmonary tuberculosis are discussed in this manuscript. PMID:24624281

Okur, Erdal

2014-01-01

340

A role for systems epidemiology in tuberculosis research  

PubMed Central

Despite being a curable disease, tuberculosis (TB) killed more people in 2009 than during any previous year in history. Progress in TB research has been slow, and remains burdened by important gaps in our knowledge of the basic biology of Mycobacterium tuberculosis, the causative agent of TB, and its interaction with the human host. Fortunately, major systems biology initiatives have recently been launched that will help fill some of these gaps. However, to fully comprehend TB, and control this disease globally, current systems biological approaches will not suffice. The influence of host and pathogen diversity, changes in human demography, and socioeconomic and environmental factors will also need to be considered. Such a multidisciplinary approach might be best described as ‘systems epidemiology’ in an effort to overcome the traditional boundaries between basic biology and classical epidemiology. PMID:21831640

Comas, Inaki; Gagneux, Sebastien

2011-01-01

341

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

342

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

343

Bacterial Thymidine Kinase as a Non-Invasive Imaging Reporter for Mycobacterium tuberculosis in Live Animals  

PubMed Central

Background Bacteria can be selectively imaged in experimentally-infected animals using exogenously administered 1-(2?deoxy-2?-fluoro-?-D-arabinofuranosyl)-5-[125I]-iodouracil ([125I]-FIAU), a nucleoside analog substrate for bacterial thymidine kinase (TK). Our goal was to use this reporter and develop non-invasive methods to detect and localize Mycobacterium tuberculosis. Methodology/Principal Findings We engineered a M. tuberculosis strain with chromosomally integrated bacterial TK under the control of hsp60 - a strong constitutive mycobacterial promoter. [125I]FIAU uptake, antimicrobial susceptibilities and in vivo growth characteristics were evaluated for this strain. Using single photon emission computed tomography (SPECT), M. tuberculosis Phsp60 TK strain was evaluated in experimentally-infected BALB/c and C3HeB/FeJ mice using the thigh inoculation or low-dose aerosol infection models. M. tuberculosis Phsp60 TK strain actively accumulated [125I]FIAU in vitro. Growth characteristics of the TK strain and susceptibility to common anti-tuberculous drugs were similar to the wild-type parent strain. M. tuberculosis Phsp60 TK strain was stable in vivo and SPECT imaging could detect and localize this strain in both animal models tested. Conclusion We have developed a novel tool for non-invasive assessment of M. tuberculosis in live experimentally-infected animals. This tool will allow real-time pathogenesis studies in animal models of TB and has the potential to simplify preclinical studies and accelerate TB research. PMID:19606217

Davis, Stephanie L.; Be, Nicholas A.; Lamichhane, Gyanu; Nimmagadda, Sridhar; Pomper, Martin G.; Bishai, William R.; Jain, Sanjay K.

2009-01-01

344

Antigen 85C inhibition restricts Mycobacterium tuberculosis growth through disruption of cord factor biosynthesis.  

PubMed

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; Kaufmann, Stefan H E

2012-04-01

345

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

346

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

347

Oesophageal tuberculosis mimicking a tumour during treatment for nodal tuberculosis.  

PubMed Central

A patient with cervical lymph node tuberculosis developed a tubercular ulcer in the oesophagus eight weeks after starting treatment. This was probably due to a drug related hypersensitivity reaction in an adjacent mediastinal lymph node and subsided with continued treatment. Images PMID:8153930

Kaur, U; Katariya, S; Bhusnurmath, S R; Bambery, P; Dilawari, J B

1993-01-01

348

Factors Associated with AntiTuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru  

Microsoft Academic Search

BackgroundLong-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use.Methodology and ResultsA case-control study was performed using information from Peruvian TB Programme. A case was defined

Kocfa Chung-Delgado; Alejandro Revilla-Montag; Sonia Guillen-Bravo; Eduardo Velez-Segovia; Andrea Soria-Montoya; Alexandra Nuñez-Garbin; Wilmer Silva-Caso; Antonio Bernabe-Ortiz

2011-01-01

349

Changes in Mycobacterium tuberculosis Genotype Families Over 20 Years in a Population-Based Study in Northern Malawi  

Microsoft Academic Search

BackgroundDespite increasing interest in possible differences in virulence and transmissibility between different genotypes of M. tuberculosis, very little is known about how genotypes within a population change over decades, or about relationships to HIV infection.Methods and Principal FindingsIn a population-based study in rural Malawi we have examined smears and cultures from tuberculosis patients over a 20-year period using spoligotyping. Isolates

Judith R. Glynn; Saad Alghamdi; Kim Mallard; Ruth McNerney; Richard Ndlovu; Lumbani Munthali; Rein M. Houben; Paul E. M. Fine; Neil French; Amelia C. Crampin; Ben Marais

2010-01-01

350

Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-gamma responses in the serial testing of health care workers  

Microsoft Academic Search

BACKGROUND: Data on the performance of Mycobacterium-tuberculosis-specific interferon-(IFN)-? release assays (IGRAs) in the serial testing of health care workers (HCWs) is limited. The objective of the present study was to determine the frequency of IGRA conversions and reversions and to identify predictors of persistent IGRA positivity among serially tested German HCWs in the absence of recent extensive tuberculosis (TB) exposure.

Felix C Ringshausen; Albert Nienhaus; Anja Schablon; Stephan Schlösser; Gerhard Schultze-Werninghaus; Gernot Rohde

2010-01-01

351

Comparative analysis of mycobacterium and related actinomycetes yields insight into the evolution of mycobacterium tuberculosis pathogenesis  

PubMed Central

Background The sequence of the pathogen Mycobacterium tuberculosis (Mtb) strain H37Rv has been available for over a decade, but the biology of the pathogen remains poorly understood. Genome sequences from other Mtb strains and closely related bacteria present an opportunity to apply the power of comparative genomics to understand the evolution of Mtb pathogenesis. We conducted a comparative analysis using 31 genomes from the Tuberculosis Database (TBDB.org), including 8 strains of Mtb and M. bovis, 11 additional Mycobacteria, 4 Corynebacteria, 2 Streptomyces, Rhodococcus jostii RHA1, Nocardia farcinia, Acidothermus cellulolyticus, Rhodobacter sphaeroides, Propionibacterium acnes, and Bifidobacterium longum. Results Our results highlight the functional importance of lipid metabolism and its regulation, and reveal variation between the evolutionary profiles of genes implicated in saturated and unsaturated fatty acid metabolism. It also suggests that DNA repair and molybdopterin cofactors are important in pathogenic Mycobacteria. By analyzing sequence conservation and gene expression data, we identify nearly 400 conserved noncoding regions. These include 37 predicted promoter regulatory motifs, of which 14 correspond to previously validated motifs, as well as 50 potential noncoding RNAs, of which we experimentally confirm the expression of four. Conclusions Our analysis of protein evolution highlights gene families that are associated with the adaptation of environmental Mycobacteria to obligate pathogenesis. These families include fatty acid metabolism, DNA repair, and molybdopterin biosynthesis. Our analysis reinforces recent findings suggesting that small noncoding RNAs are more common in Mycobacteria than previously expected. Our data provide a foundation for understanding the genome and biology of Mtb in a comparative context, and are available online and through TBDB.org. PMID:22452820

2012-01-01

352

Differential Contribution of the Repeats to Heparin Binding of HBHA, a Major Adhesin of Mycobacterium tuberculosis  

PubMed Central

Background Tuberculosis remains one of the most important causes of global mortality and morbidity, and the molecular mechanisms of the pathogenesis are still incompletely understood. Only few virulence factors of the causative agent Mycobacterium tuberculosis are known. One of them is the heparin-binding haemagglutinin (HBHA), an important adhesin for epithelial cells and an extrapulmonary dissemination factor. HBHA mediates mycobacterial adherence to epithelial cells via the interactions of its C-terminal, lysine rich repeat domain with sulfated glycoconjugates on the surface of epithelial cells. Methodology/Principal Findings Using defined heparin sulfate (HS) analogs, we determined the minimal heparin fragment length for HBHA binding and structural adaptations of the HBHA heparin-binding domain (HBD) upon binding to heparin. The NMR studies show significant shifts of all residues in the HBD upon interaction with heparin, with stronger shifts in the last repeats compared to the upstream repeats, and indicated that the HS fragments with 14 sugar units cover the entire C-terminal lysine-rich domain of HBHA. The differential implication of the repeats is determined by the relative position of prolines and lysines within each repeat, and may contribute to binding specificity. GAG binding induces a non-homogeneous structural rearrangement in the HBD, with stabilization of a nascent ?-helix only in the last penta-repeats. Conclusion/Significance Mycobacterial HBHA undergoes structural adaptation upon interaction with GAGs, which is likely involved in binding specificities of the adhesin, and mycobacterial pathogens may use HBD polymorphisms for host or organ specificity. Further studies will aim at decoding the complementarity between HBD repeats and HS sequence. PMID:22403657

Lebrun, Pierre; Raze, Dominique; Fritzinger, Bernd; Wieruszeski, Jean-Michel; Biet, Franck; Dose, Alexander; Carpentier, Mathieu; Schwarzer, Dirk; Allain, Fabrice

2012-01-01

353

Reconstructing Tuberculosis Services after Major Conflict: Experiences and Lessons Learned in East Timor  

PubMed Central

Background Tuberculosis (TB) is a major public health problem in developing countries. Following the disruption to health services in East Timor due to violent political conflict in 1999, the National Tuberculosis Control Program was established, with a local non-government organisation as the lead agency. Within a few months, the TB program was operational in all districts. Methods and Findings Using the East Timor TB program as a case study, we have examined the enabling factors for the implementation of this type of communicable disease control program in a post-conflict setting. Stakeholder analysis was undertaken, and semi-structured interviews were conducted in 2003 with 24 key local and international stakeholders. Coordination, cooperation, and collaboration were identified as major contributors to the success of the TB program. The existing local structure and experience of the local non-government organisation, the commitment among local personnel and international advisors to establishing an effective program, and the willingness of international advisers and local counterparts to be flexible in their approach were also important factors. This success was achieved despite major impediments, including mass population displacement, lack of infrastructure, and the competing interests of organisations working in the health sector. Conclusions Five years after the conflict, the TB program continues to operate in all districts with high notification rates, although the lack of a feeling of ownership by government health workers remains a challenge. Lessons learned in East Timor may be applicable to other post-conflict settings where TB is highly prevalent, and may have relevance to other disease control programs. PMID:16933956

Martins, Nelson; Kelly, Paul M; Grace, Jocelyn A; Zwi, Anthony B

2006-01-01

354

Time delays in diagnosis of pulmonary tuberculosis: a systematic review of literature  

PubMed Central

Background Delay in diagnosis of pulmonary tuberculosis results in increasing severity, mortality and transmission. Various investigators have reported about delays in diagnosis of tuberculosis. We aimed at summarizing the data on these delays in diagnosis of tuberculosis. Methods A systematic review of literature was carried out. Literature search was done in Medline and EMBASE from 1990 to 2008. We used the following search terms: delay, tuberculosis, diagnosis, and help-seeking/health-seeking behavior without language restrictions. In addition, indices of four major tuberculosis journals were hand-searched. Subject experts in tuberculosis and authors of primary studies were contacted. Reference lists, review articles and text book chapters were also searched. All the studies were assessed for methodological quality. Only studies carried out on smear/culture-positive tuberculosis patients and reporting about total, patient and health-care system delays were included. Results A total of 419 potential studies were identified by the search. Fifty two studies qualified for the review. The reported ranges of average (median or mean) total delay, patient delay, health system delay were 25–185 days, 4.9–162 days and 2–87 days respectively for both low and high income countries. Average patient delay was similar to health system delay (28.7 versus 25 days). Both patient delay and health system delay in low income countries (31.7 days and 28.5 days) were similar to those reported in high income countries (25.8 days and 21.5 days). Conclusion The results of this review suggest that there is a need for revising case-finding strategies. The reported high treatment success rate of directly observed treatment may be supplemented by measures to shorten the delay in diagnosis. This may result in reduction of infectious cases and better tuberculosis control. PMID:19519917

2009-01-01

355

A web-based laboratory information system to improve quality of care of tuberculosis patients in Peru: functional requirements, implementation and usage statistics  

E-print Network

Background: Multi-drug resistant tuberculosis patients in resource-poor settings experience large delays in starting appropriate treatment and may not be monitored appropriately due to an overburdened laboratory system, ...

Shin, Sonya S.

356

Can Brazil play a more important role in global tuberculosis drug production? An assessment of current capacity and challenges  

PubMed Central

Background Despite the existence of effective treatment, tuberculosis is still a global public health issue. The World Health Organization recommends a six-month four-drug regimen in fixed-dose combination formulation to treat drug sensitive tuberculosis, and long course regimens with several second-line drugs to treat multi-drug resistant tuberculosis. To achieve the projected tuberculosis elimination goal by 2050, it will be essential to ensure a non-interrupted supply of quality-assured tuberculosis drugs. However, quality and affordable tuberculosis drug supply is still a significant challenge for National Tuberculosis Programs. Discussion Quality drug production requires a combination of complex steps. The first challenge is to guarantee the quality of tuberculosis active pharmaceutical ingredients, then ensure an adequate manufacturing process, according to international standards, to guarantee final product´s safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are expected in a close future. Summary International manufacturers of raw material for tuberculosis treatment should undergo certification and pre-qualify their active pharmaceutical ingredients as a first step to ensure quality of tuberculosis drugs. At the country level, Brazilian public manufacturers should apply for international certification and tuberculosis drugs should be pre-qualified by international organisms. Finally, only with political commitment and large-scale production will Brazilian public sector manufacturers be able to partially supply the global market. PMID:23537151

2013-01-01

357

Tuberculosis and Pregnancy  

MedlinePLUS

... Rapid Molecular Testing to Detect Drug-Resistant TB in the US Executive Summary Introduction Background on Tests for Molecular ... Behavioral & Social Science Research Data & Statistics Reported TB in the US, Surveillance Report Archived Surveillance Reports and Slide Sets ...

358

Tuberculosis spine: Therapeutically refractory disease  

PubMed Central

Background: India ranks second amongst the high-burden multi drug resistant tuberculosis (MDR-TB) countries, with an estimated incidence of 2.3% MDR-TB cases amongst the new cases and 17.2% amongst the previously treated cases. The diagnosis and treatment protocol for MDR-TB of the spine are not clearly established. We report outcome of a series of 15 cases of TB spine who were suspected to be therapeutically refractory cases (MDR-TB) on the basis of clinicoradiological failures of initial treatment. Materials and Methods: Fifteen cases of TB spine from C2 to L5 spine were suspected to be the cases of MDR-TB (therapeutically refractory cases) on the basis of failures of adequate clinicoradiological healing response at 5 months or more on antitubercular treatment (ATT). None of the patient was immunocompromised. Thirteen out of 15 patients had tissue samples sent for histopathology, culture and sensitivity, smear, BACTEC, and polymerase chain reaction (PCR). All patients were put on second line ATT and followed up fortnightly with regular liver and kidney function tests, erythrocyte sedimentation rate (ESR), and plain X-ray. Healing was documented as subjective improvement of symptoms, reduction in ESR, and observations on contrast enhanced magnetic resonance imaging (MRI) such as resolution of marrow edema, fatty replacement of bone marrow and resolution of abscesses. Ambiguous MRI observations in a few patients were resolved on positron emission tomography (PET) scan. Patients were monitored continuously for 2 years after stopping ATT. Results: We could demonstrate a positive culture in three cases. Two of them had multi drug resistance. We could achieve healing status in 13 out of 14 patients after starting second line drugs, one patient is still on treatment while other patient with no drug resistance is responding well on ATT. Conclusions: The suspicion of therapeutically refractory case is of paramount importance. Once suspected, surgery to procure tissue for diagnosis and culture is to be undertaken. The demonstration of drug resistance on culture may not be achieved in all TB spine cases and empiric drug regimen for MDR-TB is to be started. We have achieved the healed status with immunomodulation and second line ATT. The length of treatment needs to be monitored with MRI and PET scan. PMID:22448055

Jain, Anil K; Dhammi, Ish K; Modi, Prashant; Kumar, Jaswant; Sreenivasan, Ravi; Saini, Namita Singh

2012-01-01

359

Forum in immunology Live attenuated mutants of Mycobacterium tuberculosis  

E-print Network

Forum in immunology Live attenuated mutants of Mycobacterium tuberculosis as candidate vaccines against tuberculosis Vasan K. Sambandamurthy, William R. Jacobs Jr. * Department of Microbiology to manipulate Mycobacterium tuberculosis have led to the construction of defined mutants and to the study

360

The Guinea-Bissau Family of Mycobacterium tuberculosis Complex Revisited  

E-print Network

The Guinea-Bissau Family of Mycobacterium tuberculosis Complex Revisited Ramona Groenheit1, 8 WHO Supranational TB Reference Laboratory, Tuberculosis and Mycobacteria Unit, Institut Pasteur de of the Mycobacterium tuberculosis complex that, although genotypically closely related, phenotypically demonstrates

Paris-Sud XI, Université de

361

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.

362

Epidemiology of tuberculosis in Montreal  

Microsoft Academic Search

Objective: To identify the epidemiologic caracteristics of tuberculosis (TB) in Mon- treal and the patterns of resistance to antituberculous drugs in order to improve TB control in the region. Design: Descriptive analysis of surveillance data for TB cases reported in Montreal by physicians and laboratories between 1992 and 1995. Setting: Region of Montreal, population 1 775 899. Participants: All cases

Paul Rivest; Terry Tannenbaum; Lucie Bédard

363

Acid Resistance in Mycobacterium tuberculosis  

Microsoft Academic Search

Responses to acid have been studied extensively in enteric pathogens, such as Escherichia coli, Vibrio cholerae, and Heli- cobacter pylori that encounter the extremely low pH (pH 2 to 3) of the stomach during ingestion. In contrast, much less is known about how obligate or facultative intracellular bacterial pathogens like Mycobacterium tuberculosis respond, resist, and persist in the moderately acid

Omar H. Vandal; Carl F. Nathan; Sabine Ehrt

2009-01-01

364

High prevelance of rifampin-monoresistant tuberculosis: a retrospective analysis among Iranian pulmonary tuberculosis patients.  

PubMed

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 interspersed 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

365

Impact of Co-Infections and BCG Immunisation on Immune Responses among Household Contacts of Tuberculosis Patients in a Ugandan Cohort  

PubMed Central

Background Tuberculosis incidence in resource poor countries remains high. We hypothesized that immune modulating co-infections such as helminths, malaria, and HIV increase susceptibility to latent tuberculosis infection (LTBI), thereby contributing to maintaining the tuberculosis epidemic. Methods Adults with sputum-positive tuberculosis (index cases) and their eligible household contacts (HHCs) were recruited to a cohort study between May 2011 and January 2012. HHCs were investigated for helminths, malaria, and HIV at enrolment. HHCs were tested using the QuantiFERON-TB Gold In-Tube (QFN) assay at enrolment and six months later. Overnight whole blood culture supernatants from baseline QFN assays were analyzed for cytokine responses using an 11-plex Luminex assay. Associations between outcomes (LTBI or cytokine responses) and exposures (co-infections and other risk factors) were examined using multivariable logistic and linear regression models. Results We enrolled 101 index cases and 291 HHCs. Among HHCs, baseline prevalence of helminths was 9% (25/291), malaria 16% (47/291), HIV 6% (16/291), and LTBI 65% (179/277). Adjusting for other risk factors and household clustering, there was no association between LTBI and any co-infection at baseline or at six months: adjusted odds ratio (95% confidence interval (CI); p-value) at baseline for any helminth, 1.01 (0.39–2.66; 0.96); hookworm, 2.81 (0.56–14.14; 0.20); malaria, 1.06 (0.48–2.35; 0.87); HIV, 0.74 (0.22–2.47; 0.63). HHCs with LTBI had elevated cytokine responses to tuberculosis antigens but co-infections had little effect on cytokine responses. Exploring other risk factors, Th1 cytokines among LTBI-positive HHCs with BCG scars were greatly reduced compared to those without scars: (adjusted geometric mean ratio) IFN? 0.20 (0.09–0.42), <0.0001; IL-2 0.34 (0.20–0.59), <0.0001; and TNF? 0.36 (0.16–0.79), 0.01. Conclusions We found no evidence that co-infections increase the risk of LTBI, or influence the cytokine response profile among those with LTBI. Prior BCG exposure may reduce Th1 cytokine responses in LTBI. PMID:25372043

Biraro, Irene A.; Egesa, Moses; Toulza, Frederic; Levin, Jonathan; Cose, Stephen; Joloba, Moses; Smith, Steven; Dockrell, Hazel M.; Katamba, Achilles; Elliott, Alison M.

2014-01-01

366

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

367

Systemic glucocorticoid and anti-tuberculosis therapy in a patient with coexisting tuberculosis and anthracosis.  

PubMed

Background: Tuberculous lymphadenitis is a common condition in underdeveloped and developing countries. Anthracosis is the black pigmentation of bronchi caused by the deposition of carbon, silica and quartz particles in the macrophages of the bronchial mucosa and submucosa. There is a potential relationship between bronchial anthracofibrosis and tuberculosis (TB). Objectives: A 66 year old woman was referred to a chest diseases clinic when non-productive cough was noticed during a preoperative examination. Computerized tomography (CT) of thorax showed an infiltration in the right upper lobe and a lesion in the right apical lobe adjacent to the trachea. Extensive diagnostic tests including mediastinoscopic lymph node excision were performed. Anthracosis and coexisting tuberculosis were diagnosed.Results: Directly observed anti-TB therapy was immediately initiated. Systemic prednisolone was initiated at a dose of 30 mg/day and tapered slowly to the maintenance dose. Control thorax CT taken two months after the initiation of therapy revealed that the right upper lobe bronchus was open and atelectasis of the right upper lobe was resolved. Mediastinal calcified lymph nodes and fibrotic changes of both apical regions were observed. Being in the 10th month of the therapy, the patient is still totally asymptomatic in follow-ups. Conclusions: Glucocorticoid therapy may raise some concerns in patients with TB. Here, we present a case with anthracosis and coexistent TB, who responded very well to simultaneous anti-TB and glucocorticoid therapy. PMID:24351622

Tutluer, Seda; Tanriover, M D; Emri, S

2013-01-01

368

Tuberculosis Incidence in Prisons: A Systematic Review  

PubMed Central

Background Transmission of tuberculosis (TB) in prisons has been reported worldwide to be much higher than that reported for the corresponding general population. Methods and Findings A systematic review has been performed to assess the risk of incident latent tuberculosis infection (LTBI) and TB disease in prisons, as compared to the incidence in the corresponding local general population, and to estimate the fraction of TB in the general population attributable (PAF%) to transmission within prisons. Primary peer-reviewed studies have been searched to assess the incidence of LTBI and/or TB within prisons published until June 2010; both inmates and prison staff were considered. Studies, which were independently screened by two reviewers, were eligible for inclusion if they reported the incidence of LTBI and TB disease in prisons. Available data were collected from 23 studies out of 582 potentially relevant unique citations. Five studies from the US and one from Brazil were available to assess the incidence of LTBI in prisons, while 19 studies were available to assess the incidence of TB. The median estimated annual incidence rate ratio (IRR) for LTBI and TB were 26.4 (interquartile range [IQR]: 13.0–61.8) and 23.0 (IQR: 11.7–36.1), respectively. The median estimated fraction (PAF%) of tuberculosis in the general population attributable to the exposure in prisons for TB was 8.5% (IQR: 1.9%–17.9%) and 6.3% (IQR: 2.7%–17.2%) in high- and middle/low-income countries, respectively. Conclusions The very high IRR and the substantial population attributable fraction show that much better TB control in prisons could potentially protect prisoners and staff from within-prison spread of TB and would significantly reduce the national burden of TB. Future studies should measure the impact of the conditions in prisons on TB transmission and assess the population attributable risk of prison-to-community spread. Please see later in the article for the Editors' Summary PMID:21203587

Baussano, Iacopo; Williams, Brian G.; Nunn, Paul; Beggiato, Marta; Fedeli, Ugo; Scano, Fabio

2010-01-01

369

Function and Potentials of M. tuberculosis Epitopes  

PubMed Central

Study of the function of epitopes of Mycobacterium tuberculosis antigens contributed significantly toward better understanding of the immunopathogenesis and to efforts for improving infection and disease control. Characterization of genetically permissively presented immunodominant epitopes has implications for the evolution of the host–parasite relationship, development of immunodiagnostic tests, and subunit prophylactic vaccines. Knowledge of the determinants of cross-sensitization, relevant to other pathogenic or environmental mycobacteria and to host constituents has advanced. Epitope-defined IFN? assay kits became established for the specific detection of infection with tubercle bacilli both in humans and cattle. The CD4 T-cell epitope repertoire was found to be more narrow in patients with active disease than in latently infected subjects. However, differential diagnosis of active TB could not be made reliably merely on the basis of epitope recognition. The mechanisms by which HLA polymorphism can influence the development of multibacillary tuberculosis (TB) need further analysis of epitopes, recognized by Th2 helper cells for B-cell responses. Future vaccine development would benefit from better definition of protective epitopes and from improved construction and formulation of subunits with enhanced immunogenicity. Epitope-defined serology, due to its operational advantages is suitable for active case finding in selected high disease incidence populations, aiming for an early detection of infectious cases and hence for reducing the transmission of infection. The existing knowledge of HLA class I binding epitopes could be the basis for the construction of T-cell receptor-like ligands for immunotherapeutic application. Continued analysis of the functions of mycobacterial epitopes, recognized by T cells and antibodies, remains a fertile avenue in TB research. PMID:24715888

Ivanyi, Juraj

2014-01-01

370

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

E-print Network

by diabetes are fully exposed to the tuberculosis risk. One underlying risk factor for tuberculosis that may not be equally distributed between those with and without dia- betes in India is poverty. Consistent with this a recent case control study from India... the death rate from tuberculo- sis, and improving its detection and treatment. It is widely recognised that HIV makes a substantial contribution to the global tuberculosis crisis. It is also known that cooper- ation to target HIV and tuberculosis...

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

2007-09-06

371

Cosmic Microwave Background Tutorials  

NSDL National Science Digital Library

Probing whether space is curved or flat, cosmologists have been searching for clues in ripples in the universe's microwave background left from the big bang. These tutorials explain the cosmic microwave background for neophytes, as well as more advanced readers.

Hu, Wayne

2003-10-10

372

World Health Organization Group 5 Drugs for the Treatment of Drug-Resistant Tuberculosis: Unclear Efficacy or Untapped Potential?  

PubMed Central

Background.?Treatment of multidrug-resistant or extensively drug-resistant tuberculosis (DR-tuberculosis) is challenging because commonly used second-line drugs are poorly efficacious and highly toxic. Although World Health Organization group 5 drugs are not recommended for routine use because of unclear activity, some may have untapped potential as more efficacious or better tolerated alternatives. Methods.?We conducted an exhaustive review of in vitro, animal, and clinical studies of group 5 drugs to identify critical research questions that may inform their use in current treatment of DR-tuberculosis and clinical trials of new DR-tuberculosis regimens. Results.?Clofazimine may contribute to new short-course DR-tuberculosis regimens. Beta-lactams merit further evaluation—specifically optimization of dose and schedule. Linezolid appears to be effective but is frequently discontinued due to toxicity. Thiacetazone is too toxic to warrant further evaluation. Mycobacterium tuberculosis has intrinsic inducible resistance to clarithromycin. Conclusions.?Clofazimine and beta-lactams may have unrealized potential in the treatment of DR-tuberculosis and warrant further study. Serious toxicities or intrinsic resistance limit the utility of other group 5 drugs. For several group 5 compounds, better understanding of structure-toxicity relationships may lead to better-tolerated analogs. PMID:22807518

Dooley, Kelly E.; Obuku, Ekwaro A.; Durakovic, Nadza; Belitsky, Vera; Mitnick, Carole; Nuermberger, Eric L.

2013-01-01

373

Tuberculosis transmission in a high incidence area: A retrospective molecular epidemiological study of Mycobacterium tuberculosis  

E-print Network

Tuberculosis transmission in a high incidence area: A retrospective molecular epidemiological study of Mycobacterium tuberculosis in Casablanca, Morocco Loubna Tazi a,*, Ralf Reintjes b,c , Anne-Laure Ban in most developing countries, tuberculosis represents a major public health problem in Morocco. This paper

374

Building Background Knowledge  

ERIC Educational Resources Information Center

This article make a case for the importance of background knowledge in children's comprehension. It suggests that differences in background knowledge may account for differences in understanding text for low- and middle-income children. It then describes strategies for building background knowledge in the age of common core standards.

Neuman, Susan B.; Kaefer, Tanya; Pinkham, Ashley

2014-01-01

375

Tobacco Smoke, Indoor Air Pollution and Tuberculosis: A Systematic Review and Meta-Analysis  

Microsoft Academic Search

Background Tobacco smoking, passive smoking, and indoor air pollution from biomass fuels have been implicated as risk factors for tuberculosis (TB) infection, disease, and death. Tobacco smoking and indoor air pollution are persistent or growing exposures in regions where TB poses a major health risk. We undertook a systematic review and meta-analysis to quantitatively assess the association between these exposures

Hsien-Ho Lin; Majid Ezzati; Megan Murray

2007-01-01

376

Tobacco Smoke, Indoor Air Pollution and Tuberculosis: A Systematic Review and Meta-Analysis  

Microsoft Academic Search

BackgroundTobacco smoking, passive smoking, and indoor air pollution from biomass fuels have been implicated as risk factors for tuberculosis (TB) infection, disease, and death. Tobacco smoking and indoor air pollution are persistent or growing exposures in regions where TB poses a major health risk. We undertook a systematic review and meta-analysis to quantitatively assess the association between these exposures and

Hsien-Ho Lin; Majid Ezzati; Megan Murray

2007-01-01

377

Barriers and enablers in the management of tuberculosis treatment in Addis Ababa, Ethiopia: a qualitative study  

Microsoft Academic Search

BACKGROUND: Non-adherence to tuberculosis (TB) treatment is an important barrier for TB control programs because incomplete treatment may result in prolonged infectiousness, drug resistance, relapse, and death. The aim of the present study is to explore enablers and barriers in the management of TB treatment during the first five months of treatment in Addis Ababa, Ethiopia. METHODS: Qualitative study which

Mette Sagbakken; Jan C Frich; Gunnar Bjune

2008-01-01

378

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

379

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

380

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

381

Bovine Tuberculosis Prevalence Survey on Cattle in the Rural Livestock System of Torodi (Niger)  

Microsoft Academic Search

BackgroundBovine tuberculosis (BTB) is a widespread zoonosis in developing countries but has received little attention in sub-Saharan Africa, especially in Niger. Recent investigations confirmed the high incidence of the disease in cattle slaughtered in an abattoir in Niamey. The fact that most of the animals in which M. bovis has been identified were from the rural area of Torodi implied

Abdou Razac Boukary; Eric Thys; Emmanuel Abatih; Djibo Gamatié; Issoufou Ango; Alhassane Yenikoye; Claude Saegerman

2011-01-01

382

Phylogenetic detection of horizontal gene transfer during the step-wise genesis of Mycobacterium tuberculosis  

Microsoft Academic Search

BACKGROUND: In the past decade, the availability of complete genome sequence data has greatly facilitated comparative genomic research aimed at addressing genetic variability within species. More recently, analysis across species has become feasible, especially in genera where genome sequencing projects of multiple species have been initiated. To understand the genesis of the pathogen Mycobacterium tuberculosis within a genus where the

Frédéric Veyrier; Daniel Pletzer; Christine Turenne; Marcel A Behr

2009-01-01

383

Geographic prediction of tuberculosis clusters in Fukuoka, Japan, using the space-time scan statistic  

Microsoft Academic Search

BACKGROUND: Tuberculosis (TB) has reemerged as a global public health epidemic in recent years. Although evaluating local disease clusters leads to effective prevention and control of TB, there are few, if any, spatiotemporal comparisons for epidemic diseases. METHODS: TB cases among residents in Fukuoka Prefecture between 1999 and 2004 (n = 9,119) were geocoded at the census tract level (n

Daisuke Onozuka; Akihito Hagihara

2007-01-01

384

Pulmonary Tuberculoma and Miliary Tuberculosis in Silicosis  

PubMed Central

Tuberculosis is a disease with protean manifestations. We present a case which was initially suspected as bronchogenic carcinoma with lymphangitic carcinomatosis, based on radiological appearance but later diagnosed as pulmonary tuberculoma with military tuberculosis and silicosis after thoracotomy and open lung biopsy. The patient was treated successfully with Antituberculosis Therapy (ATT). Rarity of presentation in form of pulmonary tuberculoma co-existing with histological features of miliary tuberculosis and silicosis, led us to report this case. PMID:23543249

Verma, Sanjeev Kumar; Karmakar, Saurabh

2013-01-01

385

Wasting among Uganda men with pulmonary tuberculosis is associated with linear regain in lean tissue mass during and after treatment in contrast to women with wasting who regain fat tissue mass: prospective cohort study  

PubMed Central

Background Nutritional changes during and after tuberculosis treatment have not been well described. We therefore determined the effect of wasting on rate of mean change in lean tissue and fat mass as measured by bioelectrical impedance analysis (BIA), and mean change in body mass index (BMI) during and after tuberculosis treatment. Methods In a prospective cohort study of 717 adult patients, BMI and height-normalized indices of lean tissue (LMI) and fat mass (FMI) as measured by BIA were assessed at baseline, 3, 12, and 24 months. Results Men with wasting at baseline regained LMI at a greater rate than FMI (4.55 kg/m2 (95% confidence interval (CI): 1.26, 7.83 versus 3.16 (95% CI: 0.80, 5.52)) per month, respectively during initial tuberculosis therapy. In contrast, women with wasting regained FMI at greater rate than LMI (3.55 kg/m2 (95% CI: 0.40, 6.70) versus 2.07 (95% CI: -0.74, 4.88)), respectively. Men with wasting regained BMI at a rate of 6.45 kg/m2 (95% CI: 3.02, 9.87) in the first three months whereas women, had a rate of 3.30 kg/m2 (95% CI: -0.11, 6.72). There were minimal changes in body composition after month 3 and during months 12 to 24. Conclusion Wasted tuberculosis patients regain weight with treatment but the type of gain differs by gender and patients may remain underweight after the initial phase of treatment. PMID:24410970

2014-01-01

386

Genotyping of ancient Mycobacterium tuberculosis strains reveals historic genetic diversity  

PubMed Central

The evolutionary history of the Mycobacterium tuberculosis complex (MTBC) has previously been studied by analysis of sequence diversity in extant strains, but not addressed by direct examination of strain genotypes in archaeological remains. Here, we use ancient DNA sequencing to type 11 single nucleotide polymorphisms and two large sequence polymorphisms in the MTBC strains present in 10 archaeological samples from skeletons from Britain and Europe dating to the second–nineteenth centuries AD. The results enable us to assign the strains to groupings and lineages recognized in the extant MTBC. We show that at least during the eighteenth–nineteenth centuries AD, strains of M. tuberculosis belonging to different genetic groups were present in Britain at the same time, possibly even at a single location, and we present evidence for a mixed infection in at least one individual. Our study shows that ancient DNA typing applied to multiple samples can provide sufficiently detailed information to contribute to both archaeological and evolutionary knowledge of the history of tuberculosis. PMID:24573854

Muller, Romy; Roberts, Charlotte A.; Brown, Terence A.

2014-01-01

387

Molecular epidemiology and genotyping of Mycobacterium tuberculosis isolated in Baghdad.  

PubMed

Tuberculosis (TB) remains a major health problem in Iraq but the strains responsible for the epidemic have been poorly characterized. Our aim was to characterize the TB strains circulating in Bagdad (Iraq). A total of 270 Mycobacterium tuberculosis complex (MTBC) strains isolated between 2010 and 2011 from TB patients attending the Center of Chest and Respiratory diseases in Baghdad were analyzed by Spoligotyping. The analysis indicated that 94.1% of the isolates belong to known genotype clades: CAS 39.6%, ill-defined T clade 29.6%, Manu 7.4%, Haarlem 7%, Ural 4.1%, LAM 3.3%, X 0.7%, LAM7-TUR 0.7%, EAI 0.7%, S 0.7%, and unknown 5.9%. Comparison with the international multimarker database SITVIT2 showed that SIT 309 (CAS1-Delhi) and SIT1144 (T1) were the most common types. In addition, 44 strains were included in SITVIT2 database under 16 new Spoligotype International Types (SITs); of these, 6 SITs (SIT3346, SIT3497, SIT3708, SIT3790, SIT3791, and SIT3800) (n = 32 strains) were created within the present study and 10 were created after a match with an orphan in the database. By using 24-loci MIRU-VNTR-typing on a subset of 110 samples we found a high recent transmission index (RTI) of 33.6%. In conclusion, we present the first unifying framework for both epidemiology and evolutionary analysis of M. tuberculosis in Iraq. PMID:24719873

Mustafa Ali, Ruqaya; Trovato, Alberto; Couvin, David; Al-Thwani, Amina N; Borroni, Emanuele; Dhaer, Fahim H; Rastogi, Nalin; Cirillo, Daniela M

2014-01-01

388

Molecular Epidemiology and Genotyping of Mycobacterium tuberculosis Isolated in Baghdad  

PubMed Central

Tuberculosis (TB) remains a major health problem in Iraq but the strains responsible for the epidemic have been poorly characterized. Our aim was to characterize the TB strains circulating in Bagdad (Iraq). A total of 270 Mycobacterium tuberculosis complex (MTBC) strains isolated between 2010 and 2011 from TB patients attending the Center of Chest and Respiratory diseases in Baghdad were analyzed by Spoligotyping. The analysis indicated that 94.1% of the isolates belong to known genotype clades: CAS 39.6%, ill-defined T clade 29.6%, Manu 7.4%, Haarlem 7%, Ural 4.1%, LAM 3.3%, X 0.7%, LAM7-TUR 0.7%, EAI 0.7%, S 0.7%, and unknown 5.9%. Comparison with the international multimarker database SITVIT2 showed that SIT 309 (CAS1-Delhi) and SIT1144 (T1) were the most common types. In addition, 44 strains were included in SITVIT2 database under 16 new Spoligotype International Types (SITs); of these, 6 SITs (SIT3346, SIT3497, SIT3708, SIT3790, SIT3791, and SIT3800) (n = 32 strains) were created within the present study and 10 were created after a match with an orphan in the database. By using 24-loci MIRU-VNTR-typing on a subset of 110 samples we found a high recent transmission index (RTI) of 33.6%. In conclusion, we present the first unifying framework for both epidemiology and evolutionary analysis of M. tuberculosis in Iraq. PMID:24719873

Mustafa Ali, Ruqaya; Trovato, Alberto; Al-Thwani, Amina N.; Dhaer, Fahim H.; Cirillo, Daniela M.

2014-01-01

389

Structure of phosphoserine aminotransferase from Mycobacterium tuberculosis.  

PubMed

Mycobacterium tuberculosis (Mtb), the causative agent of TB, remains a serious world health problem owing to limitations of the available drugs and the emergence of resistant strains. In this context, key biosynthetic enzymes from Mtb are attractive targets for the development of new therapeutic drugs. Here, the 1.5 Å resolution crystal structure of Mtb phosphoserine aminotransferase (MtbPSAT) in complex with its cofactor, pyridoxal 5'-phosphate (PLP), is reported. MtbPSAT is an essential enzyme in the biosynthesis of serine and in pathways of one-carbon metabolism. The structure shows that although the Mtb enzyme differs substantially in sequence from other PSAT enzymes, its fold is conserved and its PLP-binding site is virtually identical. Structural comparisons suggest that this site remains unchanged throughout the catalytic cycle. On the other hand, PSAT enzymes are obligate dimers in which the two active sites are located in the dimer interface and distinct differences in the MtbPSAT dimer are noted. These impact on the substrate-binding region and access channel and suggest options for the development of selective inhibitors. PMID:22525753

Coulibaly, Fasseli; Lassalle, Edouard; Baker, Heather M; Baker, Edward N

2012-05-01

390

Tuberculosis, bronchiectasis and chronic airflow obstruction.  

PubMed

Both tuberculosis and bronchiectasis carry a significant burden worldwide in terms of morbidity and mortality, as well as financial, especially in the developing world. Epidemiological data for tuberculosis are now more readily available since the World Health Organisation declared it 'a global emergency' in 1993. The global prevalence of bronchiectasis, a recognized sequel of tuberculosis, is unknown, but is by no means insignificant. The pathophysiology of chronic airflow obstruction in both of these diseases is poorly understood, but it is associated with an accelerated rate of loss in pulmonary function. This article examines the global burden of tuberculosis and bronchiectasis, and focuses on the interrelation with chronic airflow obstruction. PMID:20409028

Jordan, Toni S; Spencer, Elspeth M; Davies, Peter

2010-05-01

391

Neurons Are Host Cells for Mycobacterium tuberculosis  

PubMed Central

Mycobacterium tuberculosis infection of the central nervous system is thought to be initiated once the bacilli have breached the blood brain barrier and are phagocytosed, primarily by microglial cells. In this study, the interactions of M. tuberculosis with neurons in vitro and in vivo were investigated. The data obtained demonstrate that neurons can act as host cells for M. tuberculosis. M. tuberculosis bacilli were internalized by murine neuronal cultured cells in a time-dependent manner after exposure, with superior uptake by HT22 cells compared to Neuro-2a cells (17.7% versus 9.8%). Internalization of M. tuberculosis bacilli by human SK-N-SH cultured neurons suggested the clinical relevance of the findings. Moreover, primary murine hippocampus-derived neuronal cultures could similarly internalize M. tuberculosis. Internalized M. tuberculosis bacilli represented a productive infection with retention of bacterial viability and replicative potential, increasing 2- to 4-fold within 48 h. M. tuberculosis bacillus infection of neurons was confirmed in vivo in the brains of C57BL/6 mice after intracerebral challenge. This study, therefore, demonstrates neurons as potential new target cells for M. tuberculosis within the central nervous system. PMID:24566619

Randall, Philippa J.; Hsu, Nai-Jen; Lang, Dirk; Cooper, Susan; Sebesho, Boipelo; Allie, Nasiema; Keeton, Roanne; Francisco, Ngiambudulu M.; Salie, Sumayah; Labuschagne, Antoinette; Quesniaux, Valerie; Ryffel, Bernhard; Kellaway, Lauriston

2014-01-01

392

[Development of a serological test for tuberculosis].  

PubMed

Antigens secreted by M. tuberculosis in the culture medium and antigens obtained from sonicated M. tuberculosis were characterized, at the laboratory of Tropical Hygiene of the Royal Tropical Institute and the division of Pulmonary Medicine at the Academic Medical Centre, in order to explore which antigens could be valuable in the development of a serological test for tuberculosis. Using murine monoclonal antibodies in immunoblot, a pattern of protein bands distinct from that of the corresponding M. tuberculosis sonicate was found in the culture medium. The major protein bands of the culture medium, of 24 and 12 kD, and the major protein band of 16 kD in sonicate were purified. These antigens were tested in ELISA with sera from 20 patients with tuberculosis, diagnosed by a positive culture of M. tuberculosis, and from 21 control subjects. The ELISA results obtained with these 3 antigens were combined and the mean value obtained in the control group plus 2 times the standard deviation was chosen as the cut-off level. Sixteen of the 20 patients with tuberculosis had antibodies against 1 of the purified antigens, while none of the control subjects had. By combining the results, obtained with these 3 antigens, 17 of the 20 patients with tuberculosis were positive in this serological test and none of the control subjects. The 24, 12 and 16 kD antigens may be valuable for the development of a serological test for tuberculosis. PMID:1900580

Verbon, A; Kuijper, S; Jansen, H M; Speelman, P; Kolk, A H

1991-01-26

393

Rare Association of Severe Cryptococcal and Tuberculosis in Central Nervous System in a case of Sarcoidosis.  

PubMed

Sarcoidosis is a multisystem noncaseating granulomatous disease with a propensity for lung, eye, and skin which recently have been proposed that mycobacterium tuberculosis may contribute in its pathogenesis, and rarely involves central nervous system (CNS). Despite CD4+ lymphocytopenia, sarcoidosis by itself does not increase risk of opportunistic infections other than cryptococcosis. Nonetheless, simultaneous association of CNS cryptococcosis and tuberculosis infection remains extremely rare event in immunocompetent states, and has not been reported in sarcoidosis yet. We here presented such a case in a 42 years old man, a known case of sarcoidosis with diagnostic and therapeutic difficulties were encountered in a fourteen-month-long hospitalization period. PMID:25250282

Siroos, Bahaadin; Ahmadinejad, Zahra; Tabaeizadeh, Mohamad; Hedayat Yaghoobi, Mojtaba; Torabi, Alireza; Ghaffarpour, Majid

2014-01-01

394

Pyoderma gangrenosum with an underlying ulcerative colitis associated with bone tuberculosis  

PubMed Central

Pyoderma gangrenosum is a rare noninfective neutrophilic dermatosis, characterized by progressive painful ulceration. It is frequently associated with systemic disorders like inflammatory bowel disease, rheumatoid arthritis and myeloproliferative diseases. However, its association with infectious diseases in particular with tuberculosis is extremely rare. Diagnosis is based on the history of an underlying disease, a typical clinical presentation, histopathology and exclusion of other diseases leading to ulcerations of similar appearance. Immunosuppression with corticosteroids remains the mainstay of treatment. We report a case of a 49-year-old male with long-standing ulcerative colitis, associated with tuberculosis of hip, who presented with nonhealing ulcers over the lower extremity. PMID:23440150

Patvekar, Milind A.; Virmani, Neha C.

2013-01-01

395

Rare Association of Severe Cryptococcal and Tuberculosis in Central Nervous System in a case of Sarcoidosis  

PubMed Central

Sarcoidosis is a multisystem noncaseating granulomatous disease with a propensity for lung, eye, and skin which recently have been proposed that mycobacterium tuberculosis may contribute in its pathogenesis, and rarely involves central nervous system (CNS). Despite CD4+ lymphocytopenia, sarcoidosis by itself does not increase risk of opportunistic infections other than cryptococcosis. Nonetheless, simultaneous association of CNS cryptococcosis and tuberculosis infection remains extremely rare event in immunocompetent states, and has not been reported in sarcoidosis yet. We here presented such a case in a 42 years old man, a known case of sarcoidosis with diagnostic and therapeutic difficulties were encountered in a fourteen-month-long hospitalization period.

Siroos, Bahaadin; Ahmadinejad, Zahra; Tabaeizadeh, Mohamad; Hedayat Yaghoobi, Mojtaba; Torabi, Alireza; Ghaffarpour, Majid

2014-01-01

396

The postcranial remains of the Régourdou 1 Neandertal: the shoulder and arm remains  

Microsoft Academic Search

The Régourdou 1 partial skeleton, of a young adult of indeterminate sex from the initial last glacial of southwestern France, preserves both clavicles, humeri, radii and ulnae, with these bones for the right side lacking only the ulnar olecranon and styloid process. These shoulder and arm remains are similar to those of other European and Near Eastern late archaic humans

Bernard Vandermeersch; Erik Trinkaus

1995-01-01

397

Annual Risk of Tuberculosis Infection in Hellenic Air Force Recruits  

PubMed Central

Background: The annual risk of Tuberculosis infection (ARTI) is a key indicator in epidemiology, of the extent of transmission in a community. There have been several suggested methods in order to evaluate the prevalence of Tuberculosis infection using tuberculin skin data. This survey estimates the ARTI in young Hellenic air force recruits. The effect of BCG vaccination has also been investigated. Materials and Methods: During the period November 2006-November 2007 tuberculin skin tests were conducted to estimate the prevalence of mycobacterium tuberculosis infection and also to determine the ARTI. Tuberculin PPD-RT 23, dose 2 IU was used in 7.492 Greek air force military recruits with a mean age of 23.57 years. All recruits were examined for previous bacill Calmette-Guérin vaccination through BCG scar. A vast number of personal, epidemiological significance, data of the participants was collected. Results: The ARTI was 0.2%, in those who were not previously BCG vaccinated; this was derived from a tuberculin skin test cut-off point of 10 mm. There were not any statistically significant differences, neither between urban and rural population concerning the positivity of the tuberculin skin test, nor among the population in recent contact with immigrants from high-incidence countries. Conclusion: The estimated ARTI among non BCG vaccinated young Greek men is 0.2%. PMID:24459536

Garyfalia, Vlachou; Irini, Gerogianni; Vasilios, Skoufaras; Konstantinos, Gourgoulianis

2013-01-01

398

Anti Tuberculosis Drug Resistance in West of Iran  

PubMed Central

Background and Objective: Mycobacterium tuberculosis has developed resistance to antituberculosis drugs and becoming a major and alarming public health problem in worldwide. This study was aimed to determine antituberculosis drug resistance rate and to identify multidrug resistant tuberculosis (MDR-TB) in West of Iran. Materials and Methods: Of 130 samples were included between December 2011 and July 2012 in the study from that 112 cases were M. tuberculosis. The proportional method was carried out according to the Clinical and Laboratory Standards Institute on Lowenstein-Jensen against isoniazid, rifampicin, streptomycin, ethambutol, pyrazinamide, para aminosalicylic acid, ethionamide, cycloserine (CYC). The microdilution method was carried out using 7H9 broth with 96 well-plates. Results: From 112 isolates, resistance was observed to isoniazid 18 (16.07%), rifampicin 16 (14.28%), streptomycin 25 (22.32%), ethambutol 15 (13.39%), pyrazinamide 27 (24.10%), para aminosalicylic acid 19 (16.96%), CYC 4 (3.57%), and ethionamide 14 (12.5%) cases. 16 isolates were MDR. Conclusion: The high prevalence of MDR-TB in our study is assumed to be due to recent transmission of drug-resistant strains. Overall, the rate of drug resistance in our study was high, which is in line with findings of some high-burden countries. Hence that early case detection, rapid drug susceptibility testing, and effective anti-TB treatment is necessary.

Mohajeri, Parviz; Norozi, Baharak; Atashi, Sara; Farahani, Abbas

2014-01-01

399

Looking for Cosmic Neutrino Background  

NASA Astrophysics Data System (ADS)

Since the discovery of neutrino oscillation in atmospheric neutrinos by the Super-Kamiokande experiment in 1998, study of neutrinos has been one of exciting fields in high-energy physics. All the mixing angles were measured. Quests for 1) measurements of the remaining parameters, the lightest neutrino mass, the CP violating phase(s), and the sign of mass splitting between the mass eigenstates m3 and m1, and 2) better measurements to determine whether the mixing angle theta23 is less than pi/4, are in progress in a well-controlled manner. Determining the nature of neutrinos, whether they are Dirac or Majorana particles is also in progress with continuous improvement. On the other hand, although the ideas of detecting cosmic neutrino background have been discussed since 1960s, there has not been a serious concerted effort to achieve this goal. One of the reasons is that it is extremely difficult to detect such low energy neutrinos from the Big Bang. While there has been tremendous accumulation of information on Cosmic Microwave Background since its discovery in 1965, there is no direct evidence for Cosmic Neutrino Background. The importance of detecting Cosmic Neutrino Background is that, although detailed studies of Big Bang Nucleosynthesis and Cosmic Microwave Background give information of the early Universe at ~a few minutes old and ~300 k years old, respectively, observation of Cosmic Neutrino Background allows us to study the early Universe at ˜ 1 sec old. This article reviews progress made in the past 50 years on detection methods of Cosmic Neutrino Background.

Yanagisawa, Chiaki

2014-06-01

400

Pancreatic and peripancreatic tuberculosis presenting as hypoechoic mass and malignancy diagnosed by ultrasound-guided fine-needle aspiration cytology  

PubMed Central

Background: Pancreatic and peripancreatic tuberculosis is an extremely uncommon disease, presenting as hypoechoic mass on ultrasonography and imaging mimicking malignancy. Consequently, it represents a diagnostic challenge. Aims: To study 14 unusual cases of pancreatic and peripancreatic tuberculosis undergoing ultrasound-/endoscopic-guided fine-needle aspiration cytology (FNAC) in the 5-year period from 2006 to 2010. Materials and Methods: Endoscopic-guided FNAC was done in two cases, while ultrasound-guided FNAC was performed in 12 cases using 22-G needles via a percutaneous transabdominal approach. The aspirated material was quickly smeared onto glass slides, air dried, and wet fixed in 95% ethyl alcohol for subsequent Papanicolaou staining. Results: All pancreatic and peripancreatic tuberculosis cases showed solid-cystic pancreatic mass. Smears showed epithelioid cell granulomas, multinucleated giant cells, mixed inflammatory cells and histiocytes against a necrotic background. The common anatomic locations were the head, peripancreatic, tail and body of the pancreas. Conclusions: Ultrasound-/endoscopic-guided FNAC is a safe, reliable and cost-effective method for preoperative diagnosis of pancreatic and peripancreatic tuberculosis. Clinical symptoms and accurate diagnostic approach by ultrasound-/endoscopic-guided FNAC of pancreatic and peripancreatic tuberculosis is needed to avoid performing redundant laparotomy. Despite its rarity, pancreatic and peripancreatic tuberculosis should be considered for differential diagnosis of pancreatic and peripancreatic cystic mass in endemic developing countries. PMID:23833404

Rao, R. N.; Pandey, Rakesh; Rana, Manoj Kumar; Rai, Praveer; Gupta, Archna

2013-01-01

401

Subcellular Localization of the Intracellular Survival-Enhancing Eis Protein of Mycobacterium tuberculosis  

PubMed Central

Mycobacterium tuberculosis is a facultative intracellular pathogen that has evolved the ability to survive and multiply within human macrophages. It is not clear how M. tuberculosis avoids the destructive action of macrophages, but this ability is fundamental in the pathogenicity of tuberculosis. A gene previously identified in M. tuberculosis, designated eis, was found to enhance intracellular survival of Mycobacterium smegmatis in the human macrophage-like cell line U-937 (J. Wei et al., J. Bacteriol. 182:377–384, 2000). When eis was introduced into M. smegmatis on a multicopy vector, sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed the appearance of a unique 42-kDa protein band corresponding to the predicted molecular weight of the eis gene product. This band was electroeluted from the gel with a purity of >90% and subjected to N-terminal amino acid sequencing, which demonstrated that the 42-kDa band was indeed the protein product of eis. The Eis protein produced by M. tuberculosis H37Ra had an identical N-terminal amino acid sequence. A synthetic polypeptide corresponding to a carboxyl-terminal region of the deduced eis protein sequence was used to generate affinity-purified rabbit polyclonal antibodies that reacted with the 42-kDa protein in Western blot analysis. Hydropathy profile analysis showed the Eis protein to be predominantly hydrophilic with a potential hydrophobic amino terminus. Phase separation of M. tuberculosis H37Ra lysates by the nonionic detergent Triton X-114 revealed the Eis protein in both the aqueous and detergent phases. After fractionation of M. tuberculosis by differential centrifugation, Eis protein appeared mainly in the cytoplasmic fraction but also in the membrane, cell wall, and culture supernatant fractions as well. Forty percent of the sera from pulmonary tuberculosis patients tested for anti-Eis antibody gave positive reactions in Western blot analysis. Although the function of Eis remains unknown, evidence presented here suggests it associates with the cell surface and is released into the culture medium. It is produced during human tuberculosis infection and therefore may be an important M. tuberculosis immunogen. PMID:11401966

Dahl, John L.; Wei, Jun; Moulder, James W.; Laal, Suman; Friedman, Richard L.

2001-01-01

402

Keto-mycolic acid-dependent pellicle formation confers tolerance to drug-sensitive Mycobacterium tuberculosis.  

PubMed

ABSTRACT The chronic nature of tuberculosis (TB), its requirement of long duration of treatment, its ability to evade immune intervention, and its propensity to relapse after drug treatment is discontinued are reminiscent of other chronic, biofilm-associated bacterial diseases. Historically, Mycobacterium tuberculosis was grown as a pellicle, a biofilm-like structure, at the liquid-air interface in a variety of synthetic media. Notably, the most widely administered human vaccine, BCG, is grown as a pellicle for vaccine production. However, the molecular requirements for this growth remain ill defined. Here, we demonstrate that keto-mycolic acids (keto-MA) are essential for pellicle growth, and mutants lacking in or depleted of this MA species are unable to form a pellicle. We investigated the role of the pellicle biofilm in the reduction of antibiotic sensitivity known as drug tolerance using the pellicle-defective ?mmaA4 mutant strain. We discovered that the ?mmaA4 mutant, which is both pellicle defective and highly sensitive to rifampicin (RIF) under planktonic growth, when incorporated within the wild-type pellicle biofilm, was protected from the bactericidal activity of RIF. The observation that growth within the M. tuberculosis pellicle biofilm can confer drug tolerance to a drug-hypersensitive strain suggests that identifying molecular requirements for pellicle growth could lead to development of novel interventions against mycobacterial infections. Our findings also suggest that a class of drugs that can disrupt M. tuberculosis biofilm formation, when used in conjunction with conventional antibiotics, has the potential to overcome drug tolerance. IMPORTANCE Two of the most important questions in tuberculosis (TB) research are (i) how does Mycobacterium tuberculosis persist in the human host for decades in the face of an active immune response and (ii) why does it take six months and four drugs to treat uncomplicated TB. Both these aspects of M. tuberculosis biology are reminiscent of infections caused by organisms capable of forming biofilms. M. tuberculosis is capable of growing as a biofilm-like structure called the pellicle. In this study, we demonstrate that a specific cell wall component, keto-mycolic acid, is essential for pellicle growth. We also demonstrate that a strain of M. tuberculosis that is both drug sensitive and pellicle defective exhibits commensal behavior and becomes drug tolerant by becoming part of a heterogeneous pellicle, a characteristic of multispecies biofilms. These observations could have important implications for identifying novel pathways for M. tuberculosis drug tolerance and the design of new modalities to rapidly treat TB. PMID:23653446

Sambandan, Dhinakaran; Dao, Dee N; Weinrick, Brian C; Vilchèze, Catherine; Gurcha, Sudagar S; Ojha, Anil; Kremer, Laurent; Besra, Gurdyal S; Hatfull, Graham F; Jacobs, William R

2013-01-01

403

Intracellular activity of tedizolid phosphate and ACH-702 versus Mycobacterium tuberculosis infected macrophages  

PubMed Central

Background Due to the emergency of multidrug-resistant strains of Mycobacterium tuberculosis, is necessary the evaluation of new compounds. Findings Tedizolid, a novel oxazolidinone, and ACH-702, a new isothiazoloquinolone, were tested against M. tuberculosis infected THP-1 macrophages. These two compounds significantly decreased the number of intracellular mycobacteria at 0.25X, 1X, 4X and 16X the MIC value. The drugs were tested either in nanoparticules or in free solution. Conclusion Tedizolid and ACH-702 have a good intracellular killing activity comparable to that of rifampin or moxifloxacin. PMID:24708819

2014-01-01

404

Genotypic Diversity Analysis of Mycobacterium tuberculosis Strains Collected from Beijing in 2009, Using Spoligotyping and VNTR Typing  

PubMed Central

Background Tuberculosis (TB) is a serious problem in China. While there have been some studies on the nationwide genotyping of Mycobacterium tuberculosis (M. tuberculosis), there has been little detailed research in Beijing, the capital of China, which has a huge population. Here, M. tuberculosis clinical strains collected in Beijing during 2009 were genotyped by classical methods. Methodology/Principal Findings Our aim was to analyze the genetic diversity of M. tuberculosis strains within the Beijing metropolitan area. We characterized these strains using two standard methods, spoligotyping (n?=?1585) and variable number of tandem repeat (VNTR) typing (n?=?1053). We found that the most prominent genotype was Beijing family genotype. Other genotypes included the MANU, T and H families etc. Spoligotyping resulted in 137 type patterns, included 101 unclustered strains and 1484 strains clustered into 36 clusters. In VNTR typing analysis, we selected 12-locus (QUB-11b, MIRU10, Mtub21, MIRU 23, MIRU39, MIRU16, MIRU40, MIRU31, Mtub24, Mtub04, MIRU20, and QUB-4156c) and named it 12-locus (BJ) VNTR. VNTR resulted in 869 type patterns, included 796 unclustered strains and 257 strains clustered into 73 clusters. It has almost equal discriminatory power to the 24-locus VNTR. Conclusions/Significance Our study provides a detailed characterization of the genotypic diversity of M. tuberculosis in Beijing. Combining spoligotyping and VNTR typing to study the genotyping of M. tuberculosis gave superior results than when these techniques were used separately. Our results indicated that Beijing family strains were still the most prevalent M. tuberculosis in Beijing. Moreover, VNTR typing analyzing of M. tuberculosis strains in Beijing was successfully accomplished using 12-locus (BJ) VNTR. This method used for strains genotyping from the Beijing metropolitan area was comparable. This study will not only provide TB researchers with valuable information for related studies, but also provides guidance for the prevention and control of TB in Beijing.

Liu, Yi; Tian, Miao; Wang, Xueke; Wei, Rongrong; Xing, Qing; Ma, Tizhuang; Jiang, Xiaoying; Li, Wensheng; Zhang, Zhiguo; Xue, Yu; Zhang, Xuxia; Wang, Wei; Wang, Tao; Hong, Feng; Zhang, Junjie; Wang, Sumin; Li, Chuanyou

2014-01-01

405

Characteristics of patients with drug resistant and drug sensitive tuberculosis in East London between 1984 and 1992.  

PubMed Central

BACKGROUND--The aim of this study was to investigate retrospectively factors associated with drug resistant tuberculosis at the London Chest Hospital. METHODS--The microbiology results for patients with tuberculosis at the hospital for the period 1984-92 were reviewed, together with case notes and chest radiographs of all patients with drug resistant tuberculosis and of 101 patients with drug sensitive tuberculosis notified during the same period as a control group. RESULTS--Culture positive pulmonary tuberculosis occurred in 292 patients. Drug resistant strains were isolated from 20 patients (6.8%). Ten of the 292 (3.4%) had strains resistant to a single drug and nine (3.1%) had resistance to more than one first line drug. One patient had strains resistant to isoniazid and capreomycin. Strains resistant to more than one drug were all resistant to isoniazid and rifampicin. In five patients these strains were also resistant to pyrazinamide and in two they were resistant to streptomycin. Single drug resistant strains were resistant to isoniazid (nine patients) or streptomycin (one patient). Among the risk factors studied previous treatment for tuberculosis was the most significant association with drug resistant tuberculosis (7/9) for patients with resistance to more than one drug; 5/11 for single drug resistance compared with 6/101 patients in the drug sensitive group (odds ratio 22.8). Other risk factors were bilateral disease at presentation (odds ratio 8.5), and disease at a young age (odds ratio 1.03). CONCLUSIONS--Previous treatment for tuberculosis and bilateral disease at presentation were found to be more commonly associated with cases of drug resistant than with drug sensitive tuberculosis. PMID:8091328

al Jarad, N.; Parastatides, S.; Paul, E. A.; Sheldon, C. D.; Gaya, H.; Rudd, R. M.; Empey, D. W.

1994-01-01

406

BALToma masquerading as pulmonary tuberculosis.  

PubMed

A 53-year-old man with a significant smoking history presented with chronic cough, exertional breathlessness, intermittent fever, weight loss and anorexia. A review of his past medical records revealed he was diagnosed to have sputum smear-positive pulmonary tuberculosis 5?years earlier, for which he had received multiple courses of incomplete antitubercular therapy. This time, though he was primarily suspected to have active pulmonary tuberculosis, lack of microbiological evidence and further investigations including histopathological evaluation of lung lesions confirmed a diagnosis of Marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALToma/BALToma). The patient was managed with radical radiation therapy to which he responded well. PMID:25398919

Magazine, Rahul; Shahul, Hameed Aboobackar; Monappa, Vidya; Chogtu, Bharti

2014-01-01

407

Pharmacotherapy for multidrug resistant tuberculosis.  

PubMed

The current global concern in the treatment of tuberculosis (TB) is the emergence of resistance to the two most potent drugs namely, isoniazid and rifampicin. Emergence of multidrug resistance tuberculosis (MDR-TB) is now a health problem faced by most of the developing countries as well as developed countries across the globe. MDR-TB is a man-made disease that is caused by improper treatment, inadequate drug supplies, and poor patient supervision. HIV infection and AIDS have been implicated as important cause for this. The review of a published literature suggests that the most powerful predictor of treatment of MDR-TB is a history of treatment of TB. Although the treatment is efficacious, there are also a number of adverse effects caused by drugs used in the treatment of MDR-TB. PMID:22629081

Chhabra, Naveen; Aseri, M L; Dixit, Ramakant; Gaur, S

2012-04-01

408

Pharmacotherapy for multidrug resistant tuberculosis  

PubMed Central

The current global concern in the treatment of tuberculosis (TB) is the emergence of resistance to the two most potent drugs namely, isoniazid and rifampicin. Emergence of multidrug resistance tuberculosis (MDR-TB) is now a health problem faced by most of the developing countries as well as developed countries across the globe. MDR-TB is a man-made disease that is caused by improper treatment, inadequate drug supplies, and poor patient supervision. HIV infection and AIDS have been implicated as important cause for this. The review of a published literature suggests that the most powerful predictor of treatment of MDR-TB is a history of treatment of TB. Although the treatment is efficacious, there are also a number of adverse effects caused by drugs used in the treatment of MDR-TB. PMID:22629081

Chhabra, Naveen; Aseri, M. L.; Dixit, Ramakant; Gaur, S.

2012-01-01

409

Drug tolerance in Mycobacterium tuberculosis.  

PubMed

Although Mycobacterium tuberculosis is eradicated rapidly during therapy in some patients with pulmonary tuberculosis, it can persist for many months in others. This study examined the relationship between mycobacterial drug tolerance (delayed killing in vitro), persistence, and relapse. It was performed with 39 fully drug-susceptible isolates from a prospective trial of standard short-course antituberculous therapy with sputum smear-positive, human immunodeficiency virus-uninfected subjects with pulmonary tuberculosis in Brazil and Uganda. The rate of killing in vitro was determined by monitoring the growth index (GI) in BACTEC 12B medium after addition of drug to established cultures and was measured as the number of days required for 99% sterilization. Drugs differed significantly in bactericidal activity, in the following order from greatest to least, rifampin > isoniazid-ethambutol > ethambutol (P < 0.001). Isolates from subjects who had relapses (n = 2) or in whom persistence was prolonged (n = 1) were significantly more tolerant of isoniazid-ethambutol and rifampin than isolates from other subjects (P < 0.01). More generally, the duration of persistence during therapy was predicted by strain tolerance to isoniazid and rifampin (P = 0.012 and 0.026, respectively). Tolerance to isoniazid-ethambutol and tolerance to rifampin were highly correlated (P < 0.001). Tolerant isolates did not differ from others with respect to the MIC of isoniazid; the rate of killing of a tolerant isolate by isoniazid-ethambutol was not increased at higher drug concentrations. These observations suggest that tolerance may not be due to drug-specific mechanisms. Tolerance was of the phenotypic type, although increased tolerance appeared to emerge after prolonged drug exposure in vivo. This study suggests that drug tolerance may be an important determinant of the outcome of therapy for tuberculosis. PMID:10543735

Wallis, R S; Patil, S; Cheon, S H; Edmonds, K; Phillips, M; Perkins, M D; Joloba, M; Namale, A; Johnson, J L; Teixeira, L; Dietze, R; Siddiqi, S; Mugerwa, R D; Eisenach, K; Ellner, J J

1999-11-01

410

Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans.  

PubMed

Tuberculosis caused 20% of all human deaths in the Western world between the seventeenth and nineteenth centuries and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. We analyzed the whole genomes of 259 M. tuberculosis complex (MTBC) strains and used this data set to characterize global diversity and to reconstruct the evolutionary history of this pathogen. Coalescent analyses indicate that MTBC emerged about 70,000 years ago, accompanied migrations of anatomically modern humans out of Africa and expanded as a consequence of increases in human population density during the Neolithic period. This long coevolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low and high host densities. PMID:23995134

Comas, Iñaki; Coscolla, Mireia; Luo, Tao; Borrell, Sonia; Holt, Kathryn E; Kato-Maeda, Midori; Parkhill, Julian; Malla, Bijaya; Berg, Stefan; Thwaites, Guy; Yeboah-Manu, Dorothy; Bothamley, Graham; Mei, Jian; Wei, Lanhai; Bentley, Stephen; Harris, Simon R; Niemann, Stefan; Diel, Roland; Aseffa, Abraham; Gao, Qian; Young, Douglas; Gagneux, Sebastien

2013-10-01

411

Out-of-Africa migration and Neolithic co-expansion of Mycobacterium tuberculosis with modern humans  

PubMed Central

Tuberculosis caused 20% of all human deaths in the Western world between the 17th and 19th centuries, and remains a cause of high mortality in developing countries. In analogy to other crowd diseases, the origin of human tuberculosis has been associated with the Neolithic Demographic Transition, but recent studies point to a much earlier origin. Here we used 259 whole-genome sequences to reconstruct the evolutionary history of the Mycobacterium tuberculosis complex (MTBC). Coalescent analyses indicate that MTBC emerged about 70 thousand years ago, accompanied migrations of anatomically modern humans out of Africa, and expanded as a consequence of increases in human population density during the Neolithic. This long co-evolutionary history is consistent with MTBC displaying characteristics indicative of adaptation to both low- and high host densities. PMID:23995134

Comas, Inaki; Coscolla, Mireia; Luo, Tao; Borrell, Sonia; Holt, Kathryn E.; Kato-Maeda, Midori; Parkhill, Julian; Malla, Bijaya; Berg, Stefan; Thwaites, Guy; Yeboah-Manu, Dorothy; Bothamley, Graham; Mei, Jian; Wei, Lanhai; Bentley, Stephen; Harris, Simon R.; Niem