Sample records for background tuberculosis remains

  1. 1453 December 2013 Background: Chronic pain remains a significant challenge

    E-print Network

    Napadow, Vitaly

    1453 December 2013 ABSTRACT Background: Chronic pain remains a significant challenge for modern enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment. Methods: To identify

  2. Old World tuberculosis: Evidence from human remains with a review of current research and future prospects.

    PubMed

    Roberts, Charlotte A

    2015-06-01

    The evidence for TB in archaeological human remains for the Old World is reviewed in published and some unpublished sources. The evidence of Pott's disease was considered specific for TB, with other bone changes, such as rib lesions, as non-specific. Limitations of the data are discussed. Most evidence for TB comes from skeletons from the northern hemisphere, particularly in Europe in the late Medieval period (12(th)-16th centuries AD), but there is early evidence in the Near/Middle East and Egypt. Many parts of Africa, Asia and Australasia have very little or no evidence. aDNA analysis has provided data on species and strains of the Mycobacterium tuberculosis complex organisms affecting people in the past. The extant data suggest the first epidemiological transition (Neolithic agriculture and permanent settlements) led to an increase in TB, with later increases in urban environments of the late Medieval period. A number of causative factors were at play. Future research, particularly using biomolecular analysis, has the potential to further contribute to our understanding of the origin and evolution of TB, thus merging the disciplines of palaeopathology and evolutionary medicine. PMID:25802030

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

    Microsoft Academic Search

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

    Paleogenetic analysis for tuberculosis (TB) was conducted on bone and sediment samples dating from the 17th to 19th centuries from the archeological site of Nossa Senhora do Carmo Church in Rio de Janeiro, Brazil. Forty samples were analyzed, corresponding to 32 individuals from 28 burials, 22 of primary type and 6 of secondary type. The samples were collected following strict

  4. Tuberculosis in Late Neolithic-Early Copper Age human skeletal remains from Hungary.

    PubMed

    Pósa, Annamária; Maixner, Frank; Mende, Balázs Gusztáv; Köhler, Kitti; Osztás, Anett; Sola, Christophe; Dutour, Olivier; Masson, Muriel; Molnár, Erika; Pálfi, György; Zink, Albert

    2015-06-01

    Alsónyék-Bátaszék in Southern Hungary is one of the largest late Neolithic settlements and cemeteries excavated in Central Europe. In total, 2359 burials from the Late Neolithic - Early Copper Age Lengyel culture were found between 2006 and 2009 [1]. Anthropological investigations previously carried out on individuals from this site revealed an interesting paleopathological case of tuberculosis in the form of Pott's disease dated to the early 5(th) millennium BC. In this study, selected specimens from this osteoarcheological series were subjected to paleomicrobiological analysis to establish the presence of MTBC bacteria. As all individuals showing clear osteological signs of TB infection belonged to a single grave group, 38 individuals from this grave group were analysed. The sample included the case of Pott's disease as well as individuals both with and without osseous TB manifestations. The detection of TB DNA in the individual with Pott's disease provided further evidence for the occurrence of TB in Neolithic populations of Europe. Moreover, our molecular analysis indicated that several other individuals of the same grave group were also infected with TB, opening the possibility for further analyses of this unique Neolithic skeletal series. PMID:25857937

  5. Tackling the Remaining Attainment Gap between Students with and without Immigrant Background: An Investigation into the Equivalence of SES Constructs

    ERIC Educational Resources Information Center

    Lenkeit, Jenny; Caro, Daniel H.; Strand, Steve

    2015-01-01

    In England, students with immigrant background exhibit lower educational attainment than those without immigrant background. Family socioeconomic status (SES) helps explain differences in educational attainment, but a gap remains that differs in size for students with different immigrant backgrounds. While the explanatory repertoire for the…

  6. Tuberculosis

    MedlinePLUS

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  7. Tuberculosis

    MedlinePLUS

    ... to address TB and HIV coinfection around the world? The Presidentâ??s U.S. President's Emergency Plan for AIDS ... of those suffering from HIV/AIDS around the world. PEPFARâ??s Global Fund to Fight AIDS, Tuberculosis and ...

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

    E-print Network

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

    2007-09-06

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

  9. Molecular characterisation of Mycobacterium tuberculosis isolates in the First National Survey of Antituberculosis Drug Resistance from Venezuela

    Microsoft Academic Search

    Liselotte Aristimuño; Raimond Armengol; Alberto Cebollada; Mercedes España; Alexis Guilarte; Carmen Lafoz; María A Lezcano; María J Revillo; Carlos Martín; Carmen Ramírez; Nalin Rastogi; Janet Rojas; Albina Vázques de Salas; Christophe Sola; Sofía Samper

    2006-01-01

    BACKGROUND: Molecular typing of Mycobacterium tuberculosis strains has become a valuable tool in the epidemiology of tuberculosis (TB) by allowing detection of outbreaks, tracking of epidemics, identification of genotypes and transmission events among patients who would have remained undetected by conventional contact investigation. This is the first genetic biodiversity study of M. tuberculosis in Venezuela. Thus, we investigated the genetic

  10. Creation of a Clinical Assay for Detection of Mycobacterium Tuberculosis Infection as Well as Rifampin Resistance Using Linear-After-The-Exponential PCR (LATE-PCR)

    Microsoft Academic Search

    Kevin Soares

    2008-01-01

    Background: The World Health Organization reports that in 2006 alone, there were approximately 9.2 million new cases and 1.7 million deaths from tuberculosis (TB). Approximately 98% of these tuberculosis related deaths occur in developing countries (WHO 9). Tuberculosis has beset the human population since recorded history and remains the infectious disease with the highest morbidity and mortality among human civilization

  11. [Tuberculosis epidemiology].

    PubMed

    Mjid, M; Cherif, J; Ben Salah, N; Toujani, S; Ouahchi, Y; Zakhama, H; Louzir, B; Mehiri-Ben Rhouma, N; Beji, M

    2015-01-01

    Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis. It represents, according to World Health Organization (WHO), one of the most leading causes of death worldwide. With nearly 8 million new cases each year and more than 1 million deaths per year, tuberculosis is still a public health problem. Despite of the decrease in incidence, morbidity and mortality remain important partially due to co-infection with human immunodeficiency virus and emergence of resistant bacilli. All WHO regions are not uniformly affected by TB. Africa's region has the highest rates of morbidity and mortality. The epidemiological situation is also worrying in Eastern European countries where the proportion of drug-resistant tuberculosis is increasing. These regional disparities emphasize to develop screening, diagnosis and monitoring to the most vulnerable populations. In this context, the Stop TB program, developed by the WHO and its partner's, aims to reduce the burden of disease in accordance with the global targets set for 2015. PMID:25131367

  12. [Primary and pulmonary tuberculosis].

    PubMed

    Toujani, S; Ben Salah, N; Cherif, J; Mjid, M; Ouahchy, Y; Zakhama, H; Daghfous, J; Beji, M; Mehiri-Ben Rhouma, N; Louzir, B

    2015-01-01

    Tuberculosis is a major public health problem worldwide. Indeed, a third of the world population is infected with Mycobacterium tuberculosis and more than 8 million new cases of tuberculosis each year. Pulmonary tuberculosis is the most common location. Its diagnosis is difficult and often established with a delay causing a spread of infection. The diagnosis of tuberculosis infection is mainly based on immunological tests represented by the tuberculin skin test and detection of gamma interferon, while the diagnosis of pulmonary tuberculosis is suspected on epidemiological context, lasting general and respiratory symptoms, contrasting usually with normal lung examination, and a chest radiography showing suggestive lesions. The radioclinical feature may be atypical in patients with extreme ages and in case of immunodeficiency. Confirmation of tuberculosis is bacteriological. Conventional bacteriological methods remain the reference. Innovative tests using the technique of molecular biology have improved the diagnosis of tuberculosis in terms of sensitivity and especially speed. However, those techniques are of limited use. PMID:25749628

  13. Level of knowledge regarding tuberculosis and stigma among patients suffering from tuberculosis.

    PubMed

    Berisha, M; Zheki, V; Zadzhmi, D; Gashi, S; Hokha, R; Begoli, I

    2009-01-01

    The goal of this study was to determine the degree of the tuberculosis awareness concerning medical aspects of tuberculosis and stigma toward the illness. The main focus was on the supervision of the health educative program effects on the tuberculosis throughout the identification of health needs; to determine demographical aspects associated with the level of knowledge (age, gender, living conditions, level of education etc.); to improve health education program efficacy through identification of health priorities. In the survey 155 tuberculosis patients aged 12-87 years old from different regions of Kosovo (89 females and 66 males) were included; 53.5% of patients were from rural region. Educational background: 11.6% illiterate patients; 39.4% of patients have completed primary and secondary education; 9.7% of patients were highly educated. The special questionnaire was composed and patients were interviewed. The questionnaire consisted of 19 questions. For statistical processing Hi square-test, t-test and linear correlation were used. The investigation showed that level of knowledge regarding tuberculosis was satisfactory. The meaning of direct observational therapy was known to only 51% of patients. In general patients have been informed by the health staff. Stigma was obviously present in Kosovo. More vulnerable were patients without education background and from villages. Key need in global control of tuberculosis remains the adoption of DOTS (directly observed treatment, short course). Health education must be designed depending on target population for achievement of success in fighting and preventing tuberculosis. PMID:19202229

  14. Evaluating the usefulness of the ICT tuberculosis test kit for the diagnosis of tuberculosis

    Microsoft Academic Search

    Chulhun Ludgerus Chang; Eun Yup Lee; Han Chul Son; Soon Kew Park

    2000-01-01

    Background—Early diagnosis of tuberculosis is crucial, especially in Korea, where tuberculosis is endemic.Aims—To evaluate the validity of the ICT tuberculosis test (ICT) in early diagnosis of tuberculosis.Methods—Sixty eight patients with tuberculosis were tested; 37 had no history of previous tuberculosis (patient group 1), and 31 had reactivated tuberculosis (patient group 2). The control groups comprised 77 subjects: 25 healthy adults,

  15. Improving vaccines against tuberculosis

    Microsoft Academic Search

    Warwick J Britton; Umaimainthan Palendira

    2003-01-01

    Tuberculosis remains a major cause of mortality and physical and economic deprivation worldwide. There have been significant recent advances in our understanding of the Mycobacterium tuberculosis genome, mycobacterial genetics and the host determinants of protective immunity. Nevertheless, the challenge is to harness this information to develop a more effective vaccine than BCG, the attenuated strain of Mycobacterium bovis derived by

  16. Is Adipose Tissue a Place for Mycobacterium tuberculosis Persistence?

    E-print Network

    Paris-Sud XI, Université de

    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

  17. Tuberculosis and Pregnancy

    MedlinePLUS

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  18. Tuberculosis in Blacks

    MedlinePLUS

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  19. Global Tuberculosis (TB)

    MedlinePLUS

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  20. Spinal tuberculosis: A review

    PubMed Central

    Garg, Ravindra Kumar; Somvanshi, Dilip Singh

    2011-01-01

    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

  1. Multiple Cytokines Are Released When Blood from Patients with Tuberculosis Is Stimulated with Mycobacterium tuberculosis Antigens

    Microsoft Academic Search

    Kathryn L. Kellar; Jennifer Gehrke; Stephen E. Weis; Aida Mahmutovic-Mayhew; Blachy Davila; Margan J. Zajdowicz; Robin Scarborough; Philip A. LoBue; Alfred A. Lardizabal; Charles L. Daley; Randall R. Reves; John Bernardo; Brandon H. Campbell; William C. Whitworth; Gerald H. Mazurek

    2011-01-01

    BackgroundMycobacterium tuberculosis (Mtb) infection may cause overt disease or remain latent. Interferon gamma release assays (IGRAs) detect Mtb infection, both latent infection and infection manifesting as overt disease, by measuring whole-blood interferon gamma (IFN-?) responses to Mtb antigens such as early secreted antigenic target-6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7. Due to a lack of adequate diagnostic standards

  2. Nocardia Co-Infection in Patients With Pulmonary Tuberculosis

    PubMed Central

    Ekrami, Alireza; Khosravi, Azar Dokht; Samarbaf Zadeh, Ali Reza; Hashemzadeh, Mohammad

    2014-01-01

    Background: Tuberculosis (TB) remains as one of the most serious infectious diseases in the world. Pulmonary tuberculosis can occur with other pulmonary diseases caused by opportunistic organisms such as Nocardia spp. particularly in immunocompromised patients. Therefore, diagnosis of co-infection at the early stage of the disease could be lifesaving. Objectives: The goal of this study was to detect Mycobacterium tuberculosis and Nocardia spp. in sputum specimens in order to assess the concomitant nocardiosis and tuberculosis in patients with suspected pulmonary tuberculosis. Patients and Methods: From March 2011 to April 2012, 189 sputum specimens were obtained from patients who were suspected of having pulmonary tuberculosis. Out of 189 samples, 32 of the samples belonged to hospitalized HIV-infected patients. Samples were examined by Gram and Ziehl-Nelsen staining, culture and PCR methods. Results: From 157 sputum specimens, positive samples by acid fast staining, culture and PCR for M. tuberculosis were reported for 7.6% (12/157), 10.1% (16/157) and 7% (11/157) of samples, respectively. No results were obtained by the described methods for Nocardia spp. Among 32 samples of HIV-infected patients, four (12.5%) had positive results for acid fast staining, culture and PCR detecting M. tuberculosis while only two samples had positive results for Nocardia spp. by PCR and no results were reported by culture, Gram and acid fast staining for this organism. Conclusions: Concurrent pulmonary nocardiosis and tuberculosis is frequent in HIV-infected patients. Rapid and sensitive methods such as PCR are recommended for detection of such co-infections. PMID:25741428

  3. Population Aging and Migrant Workers: Bottlenecks in Tuberculosis Control in Rural China

    PubMed Central

    Lu, Hui; You, Hua; Fan, Hong; Huang, Lifang; Wang, Qungang; Shen, Hongbing; Wang, Jianming

    2014-01-01

    Background Tuberculosis is a serious global health problem. Its paradigms are shifting through time, especially in rapidly developing countries such as China. Health providers in China are at the forefront of the battle against tuberculosis; however, there are few empirical studies on health providers' perspectives on the challenges they face in tuberculosis control at the county level in China. This study was conducted among health providers to explore their experiences with tuberculosis control in order to identify bottlenecks and emerging challenges in controlling tuberculosis in rural China. Methods A qualitative approach was used. Semi-structured, in-depth interviews were conducted with 17 health providers working in various positions within the health system of one rural county (ZJG) of China. Data were analyzed based on thematic content analysis using MAXQDA 10 qualitative data analysis software. Results Health providers reported several problems in tuberculosis control in ZJG county. Migrant workers and the elderly were repeatedly documented as the main obstacles in effective tuberculosis control in the county. At a personal level, doctors showed their frustration with the lack of new drugs for treating tuberculosis patients, and their opinions varied regarding incentives for referring patients. Conclusion The results suggest that several problems still remain for controlling tuberculosis in rural China. Tuberculosis control efforts need to make reaching the most vulnerable populations a priority and encourage local health providers to adopt innovative practices in the local context based on national guidelines to achieve the best results. Considerable changes in China's National Tuberculosis Control Program are needed to tackle these emerging challenges faced by health workers at the county level. PMID:24498440

  4. Unique transcriptome signature of Mycobacterium tuberculosis in pulmonary tuberculosis.

    PubMed

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

    2006-02-01

    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

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

    Microsoft Academic Search

    Gunter Harth; Marcus A. Horwitz

    2003-01-01

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

  6. [Tuberculosis in compromised hosts].

    PubMed

    2003-11-01

    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

  7. Tuberculosis: evidence review for newly arriving immigrants and refugees

    Microsoft Academic Search

    Christina Greenaway; A. Sandoe; Bilkis Vissandjee; Ian Kitai; D. Gruner; W. Wobeser; K. Pottie; E. Ueffing; D. Menzies; K. Schwartzman

    2010-01-01

    Background: The foreign-born population bears a dispro- portionate health burden from tuberculosis, with a rate of active tuberculosis 20 times that of the non-Aboriginal Canadian-born population, and could therefore benefit from tuberculosis screening programs. We reviewed evi- dence to determine the burden of tuberculosis in immigrant populations, to assess the effectiveness of screening and treatment programs for latent tuberculosis infection,

  8. Tuberculosis in Hispanics/Latinos

    MedlinePLUS

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  9. Tuberculosis Information for International Travelers

    MedlinePLUS

    ... the African-American Community Summit Background Slideset Slideset Text version Websites Children Correctional Facilities Table of Contents ... Tuberculosis Laboratory Aggregate Reports Slide Sets Core Curriculum Text- only version Self-Study Modules Module 1 (text ...

  10. Colonic tuberculosis mimicking Crohn's disease: case report

    PubMed Central

    Chatzicostas, Constantinos; Koutroubakis, Ioannis E; Tzardi, Maria; Roussomoustakaki, Maria; Prassopoulos, Panagiotis; Kouroumalis, Elias A

    2002-01-01

    Background Intestinal tuberculosis is a rare disease in western countries, affecting mainly immigrants and immunocompromised patients. Intestinal tuberculosis is a diagnostic challenge, especially when active pulmonary infection is absent. It may mimic many other abdominal diseases. Case presentation Here, we report a case of isolated colonic tuberculosis where the initial diagnostic workup was suggestive of Crohn's disease. Computed tomography findings however, raised the possibility of colonic tuberculosis and the detection of acid-fast bacilli in biopsy specimens confirmed the diagnosis. Conclusions In conclusion, this case highlights the need for awareness of intestinal tuberculosis in the differential diagnosis of chronic intestinal disease PMID:12019037

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

    Microsoft Academic Search

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

    2011-01-01

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

  12. Influenza Virus NS Vectors Expressing the Mycobacterium tuberculosis ESAT-6 Protein Induce CD4+ Th1 Immune Response and Protect Animals against Tuberculosis Challenge

    Microsoft Academic Search

    Sabine Sereinig; Marina Stukova; Natalia Zabolotnyh; Boris Ferko; Christian Kittel; Julia Romanova; Tatiana Vinogradova; Hermann Katinger; Oleg Kiselev; Andrej Egorov

    2006-01-01

    Infection with Mycobacterium tuberculosis remains a major cause of morbidity and mortality all over the world. Since the effectiveness of the only available tuberculosis vaccine, Mycobacterium bovis bacillus Calmette- Guerin (BCG), is suboptimal, there is a strong demand to develop new tuberculosis vaccines. As tuberculosis is an airborne disease, the intranasal route of vaccination might be preferable. Live influenza virus

  13. Colonic Tuberculosis

    Microsoft Academic Search

    EduardoVillanueva Sáenz; PaulinoMartínezHernández Magro; JoséFernandoÁlvarez-Tostado Fernández; MiguelValdés Ovalle

    2002-01-01

    Tubercle bacillus was discovered in 1882 by Robert Koch. With the introduction of chemotherapy for tuberculosis in the 1940s the incidence of this entity decreased. The incidence of the tuberculosis of the colon began to increase at the 1980s with the rise in numbers of patients considered as high risk for this entity, such as HIV-infected individuals, patients with chronic

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

    PubMed Central

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

    2008-01-01

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

  15. Review article Classification of worldwide bovine tuberculosis risk factors

    E-print Network

    Paris-Sud XI, Université de

    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

  16. Forecast analysis of the incidence of tuberculosis in the province of Quebec

    PubMed Central

    2013-01-01

    Background While the overall population prevalence of tuberculosis in Quebec has been declining for many years, tuberculosis is still disproportionately more prevalent among the immigrant and Inuit communities. As such, the aim of this study was to forecast the incidence of tuberculosis in the Province of Quebec over time in order to examine the possible impact of future preventative and treatment programs geared to reducing such disparities. Methods A compartmental differential equation based on a Susceptible Exposed Latent Infectious Recovered (SELIR) model was simulated using the Euler method using Visual Basic for Applications in Excel. Demographic parameters were obtained from census data for the Province of Quebec and the model was fitted to past epidemiological data to extrapolate future values over the period 2015 to 2030. Results The trend of declining tuberculosis rates will continue in the general population, falling by 42% by 2030. The incidence among immigrants will decrease but never vanish, and may increase in the future. Among the Inuit, the incidence is expected to increase, reaching a maximum and then stabilizing, although if re-infection is taken into account it may continue to increase. Tuberculosis among non-indigenous Canadian born persons will continue to decline, with the disease almost eradicated in that group in the mid 21st century. Conclusions While the incidence of tuberculosis in the Province of Quebec is expected to decrease overall, certain populations will remain at risk. PMID:23621907

  17. [Extrapulmonary tuberculosis].

    PubMed

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

    2015-01-01

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

  18. Genetic variation of Mycobacterium tuberculosis circulating in Kharkiv Oblast, Ukraine

    Microsoft Academic Search

    Maya A Dymova; Oleksander O Liashenko; Petro I Poteiko; Valeriy S Krutko; Eugeny A Khrapov; Maxim L Filipenko

    2011-01-01

    Background  A persistent increase of tuberculosis cases has recently been noted in the Ukraine. The reported incidence of drug-resistant\\u000a isolates of M. tuberculosis is growing steadily; however, data on the genetic variation of isolates of M. tuberculosis circulating in northern Ukraine and on the spectrum and frequency of occurrence of mutations determining resistance to the\\u000a principal anti-tuberculosis drugs isoniazid and rifampicin

  19. [Chest tuberculosis imaging].

    PubMed

    Hantous-Zannad, S; Zidi, A; Néji, H; Attia, M; Baccouche, I; Ben Miled-M'rad, K

    2015-01-01

    Tuberculosis is an infectious disease mostly due to Mycobacterium tuberculosis. It is frequent in developing countries and its incidence is rising in developed countries. Lungs are the most involved organs of the chest but other structures can be affected. Imaging is fundamental in the management of the disease. Confirmation of diagnosis can be made only by bacteriologic and/or histologic exams. The first approach of diagnosis is based on clinical symptoms and chest X-ray signs. Radiologic signs depend on patient's age, his immune status and his previous contact with M. tuberculosis. Conventional chest X-ray remains the first-line exam to realize. It can suggest the diagnosis on the appearance and location of the lesions. CT scan is recommended for the positive diagnosis in case of discrepancy between clinical and radiographic signs, as for the diagnosis of parenchymal, vascular, lymph nodes, pleural, parietal or mediastinal complications. It is also essential for the evaluation of parenchyma sequelae. MRI and PET-scan have limited indications. The purpose of this article is to illustrate different radiological forms of chest tuberculosis, its sequelae and complications and to highlight the role of each imaging technique in the patient's management. PMID:24874403

  20. Using statistical methods and genotyping to detect tuberculosis outbreaks

    PubMed Central

    2013-01-01

    Background Early identification of outbreaks remains a key component in continuing to reduce the burden of infectious disease in the United States. Previous studies have applied statistical methods to detect unexpected cases of disease in space or time. The objectives of our study were to assess the ability and timeliness of three spatio-temporal methods to detect known outbreaks of tuberculosis. Methods We used routinely available molecular and surveillance data to retrospectively assess the effectiveness of three statistical methods in detecting tuberculosis outbreaks: county-based log-likelihood ratio, cumulative sums, and a spatial scan statistic. Results Our methods identified 8 of the 9 outbreaks, and 6 outbreaks would have been identified 1–52 months (median = 10 months) before local public health authorities identified them. Assuming no delays in data availability, 46 (59.7%) of the 77 patients in the 9 outbreaks were identified after our statistical methods would have detected the outbreak but before local public health authorities became aware of the problem. Conclusions Statistical methods, when applied retrospectively to routinely collected tuberculosis data, can successfully detect known outbreaks, potentially months before local public health authorities become aware of the problem. The three methods showed similar results; no single method was clearly superior to the other two. Further study to elucidate the performance of these methods in detecting tuberculosis outbreaks will be done in a prospective analysis. PMID:23497235

  1. Multifocal osseous tuberculosis involving hand and feet.

    PubMed

    Amin, Muhammad Umar; Shafique, Mobeen; Mahmood, Rabia; Ali, Liaquat; Nadeem, Ahmed; Anees

    2008-04-01

    A rare case of multifocal cystic tuberculosis of hands and feet is presented in an adolescent female. The presence of multiple lytic areas mimicked secondary metastases and biopsy remained the mainstay for final diagnosis. PMID:18474162

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

    PubMed Central

    2013-01-01

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

  3. Tuberculosis origin: The Neolithic scenario.

    PubMed

    Hershkovitz, Israel; Donoghue, Helen D; Minnikin, David E; May, Hila; Lee, Oona Y-C; Feldman, Michal; Galili, Ehud; Spigelman, Mark; Rothschild, Bruce M; Bar-Gal, Gila Kahila

    2015-06-01

    This paper follows the dramatic changes in scientific research during the last 20 years regarding the relationship between the Mycobacterium tuberculosis complex and its hosts - bovids and/or humans. Once the M. tuberculosis and Mycobacterium bovis genomes were sequenced, it became obvious that the old story of M. bovis evolving into the human pathogen should be reversed, as M. tuberculosis is more ancestral than M. bovis. Nevertheless, the timescale and geographical origin remained an enigma. In the current study human and cattle bone samples were examined for evidence of tuberculosis from the site of Atlit-Yam in the Eastern Mediterranean, dating from 9250 to 8160 (calibrated) years ago. Strict precautions were used to prevent contamination in the DNA analysis, and independent centers used to confirm authenticity of findings. DNA from five M. tuberculosis genetic loci was detected and had characteristics consistent with extant genetic lineages. High performance liquid chromatography was used as an independent method of verification and it directly detected mycolic acid lipid biomarkers, specific for the M. tuberculosis complex. These, together with pathological changes detected in some of the bones, confirm the presence of the disease in the Levantine populations during the Pre-pottery Neolithic C period, more than 8000 years ago. PMID:25726364

  4. [Tuberculosis treatment].

    PubMed

    Ben Amar, J; Dhahri, B; Aouina, H; Azzabi, S; Baccar, M A; El Gharbi, L; Bouacha, H

    2015-01-01

    The aim of this article is to give practicing physicians a practical approach to the treatment of latent and active tuberculosis. Most patients follow TB standard treatment recommended by WHO that depend on category of patient. It is a combination of four essential tuberculosis drugs of the first group: isoniazid, rifampicin, pyrazinamid and ethambutol; in some cases streptomycin can replace ethambutol. This initial phase of intensive treatment is followed by a consolidation phase. Drugs should be administered in the morning on an empty stomach one hour before meals. Treatment of latent tuberculosis (TB) infection is an important component of TB control programs. Preventive treatment can reduce the risk of developing active TB. PMID:25434510

  5. Extensively Drug-Resistant Tuberculosis (XDR TB)

    MedlinePLUS

    ... the African-American Community Summit Background Slideset Slideset Text version Websites Children Correctional Facilities Table of Contents ... Tuberculosis Laboratory Aggregate Reports Slide Sets Core Curriculum Text- only version Self-Study Modules Module 1 (text ...

  6. Tuberculosis and tuberculosis/HIV/AIDS-associated mortality in Africa: the urgent need to expand and invest in routine and research autopsies.

    PubMed

    Mudenda, Victor; Lucas, Sebastian; Shibemba, Aaron; O'Grady, Justin; Bates, Matthew; Kapata, Nathan; Schwank, Samana; Mwaba, Peter; Atun, Rifat; Hoelscher, Michael; Maeurer, Markus; Zumla, Alimuddin

    2012-05-15

    Frequently quoted statistics that tuberculosis and human immunodeficiency virus (HIV)/AIDS are the most important infectious causes of death in high-burden countries are based on clinical records, death certificates, and verbal autopsy studies. Causes of death ascertained through these methods are known to be grossly inaccurate. Most data from Africa on mortality and causes of death currently used by international agencies have come from verbal autopsy studies, which only provide inaccurate estimates of causes of death. Autopsy rates in most sub-Saharan African countries have declined over the years, and actual causes of deaths in the community and in hospitals in most sub-Saharan African countries remain unknown. The quality of cause-specific mortality statistics remains poor. The effect of various interventions to reduce mortality rates can only be evaluated accurately if cause-specific mortality data are available. Autopsy studies could have particular relevance to direct public health interventions, such as vaccination programs or preventive therapy, and could also allow for study of background levels of subclinical tuberculosis disease, Mycobacterium tuberculosis-HIV coinfection, and other infectious and noncommunicable diseases not yet clinically manifest. Autopsies performed soon after death may represent a unique opportunity to understand the pathogenesis of M. tuberculosis and the pathogenesis of early deaths after initiation of antiretroviral therapy. The few autopsies performed so far for research purposes have yielded invaluable information and insights into tuberculosis, HIV/AIDS, and other opportunistic infections. Accurate cause-specific mortality data are essential for prioritization of governmental and donor investments into health services to reduce morbidity and mortality from deadly infectious diseases such as tuberculosis and HIV/AIDS. There is an urgent need for reviving routine and research autopsies in sub-Saharan African countries. PMID:22448024

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

    PubMed Central

    2013-01-01

    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

  8. Urinary tuberculosis

    PubMed Central

    Riddle, P. R.

    1971-01-01

    The present incidence, clinical features and classification of urinary tuberculosis are discussed. Chemotherapy is the mainstay of treatment. The indications for surgical intervention are reviewed and procedures briefly described. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5 PMID:5169185

  9. Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and Th17 Differentiation and Promotes Tuberculosis Pathogenesis.

    PubMed

    Rahman, Md Aejazur; Sobia, Parveen; Dwivedi, Ved Prakash; Bhawsar, Aakansha; Singh, Dhiraj Kumar; Sharma, Pawan; Moodley, Prashini; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

    2015-06-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M. tuberculosis have been identified, its pathogenesis remains incompletely understood. TlyA is a virulence factor in several bacterial infections and is evolutionarily conserved in many Gram-positive bacteria, but its function in M. tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA significantly contributes to the pathogenesis of M. tuberculosis. We show that a TlyA mutant M. tuberculosis strain induces increased IL-12 and reduced IL-1? and IL-10 cytokine responses, which sharply contrasts with the immune responses induced by wild type M. tuberculosis. Furthermore, compared with wild type M. tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to autophagy in macrophages. Consequently, animals infected with the TlyA mutant M. tuberculosis organisms exhibited increased host-protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host evasion factor, thereby contributing to its virulence. PMID:25847237

  10. Prolonged Infectiousness of Tuberculosis Patients in a Directly Observed Therapy Short-Course Program with Standardized Therapy

    PubMed Central

    Fitzwater, Sean P.; Caviedes, Luz; Gilman, Robert H.; Coronel, Jorge; LaChira, Doris; Salazar, Cayo; Saravia, Juan Carlos; Reddy, Krishna; Friedland, Jon S.; Moore, David A. J.

    2015-01-01

    Background Effective tuberculosis control is compromised by a lack of clarity about the timeframe of viable Mycobacterium tuberculosis shedding after treatment initiation under programmatic conditions. This study quantifies time to conversion from smear and culture positivity to negativity in unselected tuberculosis patients receiving standardized therapy in a directly observed therapy short-course (DOTS) program. Methods Longitudinal cohort study following up 93 adults initiating tuberculosis therapy in Lima, Peru. Baseline culture and drug susceptibility tests (DSTs) were performed using the MBBacT, proportion, and microscopic observation drug susceptibility (MODS) methods. Smear microscopy and MODS liquid culture were performed at baseline and weekly for 4 weeks then every other week for 26 weeks. Results Median conversion time from culture positivity to culture negativity of 38.5 days was unaffected by baseline smear status. Patients with fully susceptible tuberculosis had a median time to culture conversion of 37 days; 10% remained culture positive at day 60. Delayed culture conversion was associated with multidrug resistance, regardless of DST method used; non–multidrug resistance as defined by the proportion method and MODS (but not MBBacT) was also associated with delay. Persistent day 60 smear positivity yielded positive and negative predictive values of 67% and 92%, respectively, for detecting multidrug resistance. Conclusions Smear and culture conversion in treated tuberculosis patients takes longer than is conventionally believed, even with fully susceptible disease, and must be accounted for in tuberculosis treatment and prevention programs. Persistent day 60 smear positivity is a poor predictor of multidrug resistance. The industrialized-world convention of universal baseline DST for tuberculosis patients should become the standard of care in multidrug resistance–affected resource-limited settings. PMID:20624064

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

    PubMed Central

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

    2013-01-01

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

  12. Surgical management of renal tuberculosis

    PubMed Central

    Krishnamoorthy, Sriram; Gopalakrishnan, Ganesh

    2008-01-01

    Tuberculosis (TB) is one of the major health problems that our country is facing today. Despite active interventions by our government, control of TB still remains to be achieved. The emergence and exponential growth of the human immunodeficiency virus and drug-resistant strains threaten to further complicate the TB situation in our country. Even in this era of advanced chemotherapy, many lives are lost every day in our country. Tuberculosis of the urinary tract, despite being one of the commonest forms of extra-pulmonary TB, is generally overlooked. Most patients present with vague lower urinary symptoms typical of urinary tract infection. In this article, we shall highlight the various issues related to the surgical management of renal and ureteral tuberculosis. PMID:19468471

  13. Impact of HIV infection on tuberculosis

    PubMed Central

    Zumla, A.; Malon, P.; Henderson, J.; Grange, J.

    2000-01-01

    Tuberculosis is increasing in prevalence in many countries and is now the leading infectious cause of death world wide, being responsible for three million deaths annually. Infection with HIV, likewise increasing in prevalence, has emerged as the most important predisposing factor for developing overt tuberculosis in people co-infected with Mycobacterium tuberculosis. Owing to the widespread geographical overlap of these two infections, it is estimated that in 1999, HIV related tuberculosis will reach one million cases and will cause 30% of the expected 2.5 million AIDS related deaths. Tuberculosis in HIV infected individuals may have unusual clinical features and can cause diagnostic difficulties. Despite the effectiveness of modern short course treatment, the mortality of HIV related tuberculosis during and after treatment remains high, and this may be due to other HIV related infections. The "cursed duet" of infection with both HIV and M tuberculosis is generating a threat to human health of unparalleled proportions which, if not taken seriously by health workers and decision makers, could become totally unmanageable.???Keywords: HIV; AIDS; tuberculosis PMID:10775277

  14. Identification of moaA3 gene in patient isolates of Mycobacterium tuberculosis in Kerala, which is absent in M. tuberculosis H37Rv and H37Ra

    Microsoft Academic Search

    Suma Sarojini; Smitha Soman; Indulakshmi Radhakrishnan; Sathish Mundayoor

    2005-01-01

    BACKGROUND: Tuberculosis is endemic to developing countries like India. Though the whole genome sequences of the type strain M. tuberculosis H37Rv and the clinical strain M. tuberculosis CDC1551 are available, the clinical isolates from India have not been studied extensively at the genome level. This study was carried out in order to have a better understanding of isolates from Kerala,

  15. Risk factors for reactivation of tuberculosis in Manitoba

    PubMed Central

    Johnson, I.L.; Thomson, M.; Manfreda, J.; Hershfield, E.S.

    1985-01-01

    Although rates of reported cases of active tuberculosis have been declining in Manitoba and throughout Canada over the past two decades, the percentage of active cases due to reactivated tuberculosis has remained relatively constant. From 1976 to 1981, 113 cases of reactivated tuberculosis were listed in the Manitoba tuberculosis registry. We found that 36 cases did not meet our criteria for reactivation, primarily because there was no 6-month period of inactivity; another 5 cases could not be verified. In more than half of the remaining 72 the initial episode had occurred before 1960. We also randomly selected from the registry as controls 118 age- and sex-matched cases of nonreactivated tuberculosis. We found that registered Indian status was significantly associated with risk of reactivation, especially when the initial disease had been extensive. Awareness of high-risk groups, earlier diagnosis and adequate treatment are needed to prevent reactivated tuberculosis. PMID:4063933

  16. T-Cell Immunophenotyping Distinguishes Active From Latent Tuberculosis

    PubMed Central

    Pollock, Katrina M.; Whitworth, Hilary S.; Montamat-Sicotte, Damien J.; Grass, Lisa; Cooke, Graham S.; Kapembwa, Moses S.; Kon, Onn M.; Sampson, Robert D.; Taylor, Graham P.; Lalvani, Ajit

    2013-01-01

    Background.?Changes in the phenotype and function of Mycobacterium tuberculosis (M. tuberculosis)-specific CD4+ and CD8+ T-cell subsets in response to stage of infection may allow discrimination between active tuberculosis and latent tuberculosis infection. Methods.?A prospective comparison of M. tuberculosis-specific cellular immunity in subjects with active tuberculosis and latent tuberculosis infection, with and without human immunodeficiency virus (HIV) coinfection. Polychromatic flow cytometry was used to measure CD4+ and CD8+ T-cell subset phenotype and secretion of interferon ? (IFN-?), interleukin 2 (IL-2), and tumor necrosis factor ? (TNF-?). Results.?Frequencies of CD4+ and CD8+ cells secreting IFN-?-only, TNF-?-only and dual IFN-?/TNF-? were greater in active tuberculosis vs latent tuberculosis infection. All M. tuberculosis-specific CD4+ subsets, with the exception of IL-2-only cells, switched from central to effector memory phenotype in active tuberculosis vs latent tuberculosis infection, accompanied by a reduction in IL-7 receptor ? (CD127) expression. The frequency of PPD-specific CD4+ TNF-?-only-secreting T cells with an effector phenotype accurately distinguished active tuberculosis from latent tuberculosis infection with an area under the curve of 0.99, substantially more discriminatory than measurement of function alone. Conclusions.?Combined measurement of T-cell phenotype and function defines a highly discriminatory biomarker of tuberculosis disease activity. Unlocking the diagnostic and monitoring potential of this combined approach now requires validation in large-scale prospective studies. PMID:23966657

  17. Risk Factors for Developing Active Tuberculosis After the Treatment of Latent Tuberculosis in Adults Infected With Human Immunodeficiency Virus

    PubMed Central

    Amoakwa, Kojo; Martinson, Neil A.; Moulton, Lawrence H.; Barnes, Grace L.; Msandiwa, Reginah; Chaisson, Richard E.

    2015-01-01

    Tuberculosis is the leading cause of death among adults infected with human immunodeficiency virus (HIV), and rates of tuberculosis remain high even after preventive therapy. Among 908 HIV-infected adults in a trial of preventive treatment, we found self-reported alcohol consumption, low baseline CD4 count, high baseline viral load, and tuberculin skin test size >15 mm as independent risk factors for incident tuberculosis.

  18. Propellant-remaining modeling

    NASA Technical Reports Server (NTRS)

    Torgovitsky, S.

    1991-01-01

    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.

  19. RAPID TEST FOR SEROLOGICAL DETECTION OF TUBERCULOSIS IN MULTIPLE ANIMAL SPECIES

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    E-print Network

    Demirci, Utkan

    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

  1. Abdominal tuberculosis.

    PubMed Central

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

    1994-01-01

    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

  2. The Mycobacterium tuberculosis Rv2540c DNA sequence encodes a bifunctional chorismate synthase

    Microsoft Academic Search

    Fernanda Ely; José ES Nunes; Evelyn K Schroeder; Jeverson Frazzon; Mário S Palma; Diógenes S Santos; Luiz A Basso

    2008-01-01

    BACKGROUND: The emergence of multi- and extensively-drug resistant Mycobacterium tuberculosis strains has created an urgent need for new agents to treat tuberculosis (TB). The enzymes of shikimate pathway are attractive targets to the development of antitubercular agents because it is essential for M. tuberculosis and is absent from humans. Chorismate synthase (CS) is the seventh enzyme of this route and

  3. 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

  4. Transmission of Mycobacterium tuberculosis between Farmers and Cattle in Central Ethiopia

    PubMed Central

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

    2013-01-01

    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

  5. Diagnosing Tuberculosis With a Novel Support Vector Machine-Based Artificial Immune Recognition System

    PubMed Central

    Saybani, Mahmoud Reza; Shamshirband, Shahaboddin; Golzari Hormozi, Shahram; Wah, Teh Ying; Aghabozorgi, Saeed; Pourhoseingholi, Mohamad Amin; Olariu, Teodora

    2015-01-01

    Background: Tuberculosis (TB) is a major global health problem, which has been ranked as the second leading cause of death from an infectious disease worldwide. Diagnosis based on cultured specimens is the reference standard, however results take weeks to process. Scientists are looking for early detection strategies, which remain the cornerstone of tuberculosis control. Consequently there is a need to develop an expert system that helps medical professionals to accurately and quickly diagnose the disease. Artificial Immune Recognition System (AIRS) has been used successfully for diagnosing various diseases. However, little effort has been undertaken to improve its classification accuracy. Objectives: In order to increase the classification accuracy of AIRS, this study introduces a new hybrid system that incorporates a support vector machine into AIRS for diagnosing tuberculosis. Patients and Methods: Patient epacris reports obtained from the Pasteur laboratory of Iran were used as the benchmark data set, with the sample size of 175 (114 positive samples for TB and 60 samples in the negative group). The strategy of this study was to ensure representativeness, thus it was important to have an adequate number of instances for both TB and non-TB cases. The classification performance was measured through 10-fold cross-validation, Root Mean Squared Error (RMSE), sensitivity and specificity, Youden’s Index, and Area Under the Curve (AUC). Statistical analysis was done using the Waikato Environment for Knowledge Analysis (WEKA), a machine learning program for windows. Results: With an accuracy of 100%, sensitivity of 100%, specificity of 100%, Youden’s Index of 1, Area Under the Curve of 1, and RMSE of 0, the proposed method was able to successfully classify tuberculosis patients. Conclusions: There have been many researches that aimed at diagnosing tuberculosis faster and more accurately. Our results described a model for diagnosing tuberculosis with 100% sensitivity and 100% specificity. This model can be used as an additional tool for experts in medicine to diagnose TBC more accurately and quickly. PMID:26023340

  6. Origin, Spread and Demography of the Mycobacterium tuberculosis Complex

    Microsoft Academic Search

    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

    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

  7. Commercial Serological Antibody Detection Tests for the Diagnosis of Pulmonary Tuberculosis: A Systematic Review

    Microsoft Academic Search

    Karen R Steingart; Megan Henry; Suman Laal; Philip C Hopewell; Andrew Ramsay; Dick Menzies; Jane Cunningham; Karin Weldingh; Madhukar Pai

    2007-01-01

    BackgroundThe global tuberculosis epidemic results in nearly 2 million deaths and 9 million new cases of the disease a year. The vast majority of tuberculosis patients live in developing countries, where the diagnosis of tuberculosis relies on the identification of acid-fast bacilli on unprocessed sputum smears using conventional light microscopy. Microscopy has high specificity in tuberculosis-endemic countries, but modest sensitivity

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

    Microsoft Academic Search

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

    2007-01-01

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

  9. Co-evolution of Mycobacterium tuberculosis and Homo sapiens.

    PubMed

    Brites, Daniela; Gagneux, Sebastien

    2015-03-01

    The causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co-evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter-response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future 'genome-to-genome' studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines. PMID:25703549

  10. Co-evolution of Mycobacterium tuberculosis and Homo sapiens

    PubMed Central

    Brites, Daniela; Gagneux, Sebastien

    2015-01-01

    The causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co-evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter-response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future ‘genome-to-genome’ studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines. PMID:25703549

  11. Clinical presentation of abdominal tuberculosis in HIV seronegative adults

    Microsoft Academic Search

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

    2005-01-01

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

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

    PubMed Central

    2014-01-01

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

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

    Microsoft Academic Search

    Barun Mathema; Karen Shean; Elena Shashkina; Gilla Kaplan

    2004-01-01

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

  14. Play the Tuberculosis Game

    MedlinePLUS

    ... Malaria MRI Nerve Signaling Pavlov's Dog Split Brain Experiments The Cell and its Organelles The Genetic Code ... Life and Work Teachers' Questionnaire Tuberculosis Play Tuberculosis Experiments & Discoveries About the game Discover and experience some ...

  15. Tuberculosis: Medico-Legal Aspects

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Vollrath, Oliver; Lange, Christoph

    2014-01-01

    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

  17. Renal tuberculosis: a case report

    PubMed Central

    TOCCACELI, S.; STELLA, L. PERSICO; DIANA, M.; TACCONE, A.; GIULIANI, G.; DE PAOLA, L.; VALVANO, M.; DE PADUA, C.; DI BIASIO, G.; RANUCCI, C.; ORSI, E.; LA TORRE, F.

    2015-01-01

    Tuberculosis or TB (tubercle bacillus) remains a major public health problem in developing countries. Over the last decades extra-pulmonary locations of the disease have become more frequent due to the increased prevalence of acquired immune deficiency syndrome and the increase number of organ transplants. The urogenital localization represents about 27% of all extra-pulmonary localizations of TB and may be due either to a disseminated infection or to a primitive genitourinary localization. The majority of patients, has pyuria, sometimes with hematuria. The diagnosis of urinary tuberculosis is based on the finding of pyuria in the absence of infection by common bacteria. The initial medical treatment includes isoniazide, rifampicin, pyrazinami-de, ethambutol and streptomycin. This disease should be suspected in patients with unexplained urinary tract infections, especially if immunocompromised and/or coming from endemic areas. PMID:26017107

  18. Tuberculosis: The Connection between TB and HIV (the AIDS Virus)

    MedlinePLUS

    ... the African-American Community Summit Background Slideset Slideset Text version Websites Children Correctional Facilities Table of Contents ... Tuberculosis Laboratory Aggregate Reports Slide Sets Core Curriculum Text- only version Self-Study Modules Module 1 (text ...

  19. [Childhood tuberculosis].

    PubMed

    Hamzaoui, A

    2015-01-01

    Childhood TB is an indication of failing TB control in the community. It allows disease persistence in the population. Mortality and morbidity due to TB is high in children. Moreover, HIV co-infection and multidrug-resistant diseases are as frequent in children as in adults. Infection is more frequent in younger children. Disease risk after primary infection is greatest in infants younger than 2 years. In case of exposure, evidence of infection can be obtained using the tuberculin skin test (TST) or an interferon-gamma assay (IGRA). There is no evidence to support the use of IGRA over TST in young children. TB suspicion should be confirmed whenever possible, using new available tools, particularly in case of pulmonary and lymph node TB. Induced sputum, nasopharyngeal aspiration and fine needle aspiration biopsy provide a rapid and definitive diagnosis of mycobacterial infection in a large proportion of patients. Analysis of paediatric samples revealed higher sensitivity and specificity values of molecular techniques in comparison with the ones originated from adults. Children require higher drugs dosages than adults. Short courses of steroids are associated with TB treatment in case of respiratory distress, bronchoscopic desobstruction is proposed for severe airways involvement and antiretroviral therapy is mandatory in case of HIV infection. Post-exposure prophylaxis in children is a highly effective strategy to reduce the risk of TB disease. The optimal therapy for treatment of latent infection with a presumably multidrug-resistant Mycobacterium tuberculosis strain is currently not known. PMID:24932504

  20. Two-Thirds of Smear-Positive Tuberculosis Cases in the Community Were Undiagnosed in Northwest Ethiopia: Population Based Cross-Sectional Study

    Microsoft Academic Search

    Takele Tadesse; Meaza Demissie; Yemane Berhane; Yigzaw Kebede; Markos Abebe

    2011-01-01

    BackgroundTuberculosis (TB) case detection rate remains low in Ethiopia. One of the underlying reasons is the emphasis on passive case finding strategy which may seriously underestimate the burden of the disease. Estimating the prevalence of smear-positive pulmonary TB through active case finding at population level can help assessing the degree to which passive case detection is successful.Methods and findingsThis is

  1. Evaluation of the Burden of Unsuspected Pulmonary Tuberculosis and CoMorbidity with Non-Communicable Diseases in Sputum Producing Adult Inpatients

    Microsoft Academic Search

    Matthew Bates; Justin O’Grady; Peter Mwaba; Lophina Chilukutu; Judith Mzyece; Busiku Cheelo; Moses Chilufya; Lukundo Mukonda; Maxwell Mumba; John Tembo; Mumba Chomba; Nathan Kapata; Andrea Rachow; Petra Clowes; Markus Maeurer; Michael Hoelscher; Alimuddin Zumla

    2012-01-01

    BackgroundA high burden of tuberculosis (TB) occurs in sub-Saharan African countries and many cases of active TB and drug-resistant TB remain undiagnosed. Tertiary care hospitals provide an opportunity to study TB co-morbidity with non-communicable and other communicable diseases (NCDs\\/CDs). We evaluated the burden of undiagnosed pulmonary TB and multi-drug resistant TB in adult inpatients, regardless of their primary admission diagnosis,

  2. Tuberculosis: evidence review for newly arriving immigrants and refugees

    PubMed Central

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

    2011-01-01

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

  3. [Management of multidrug-resistant tuberculosis].

    PubMed

    Tritar, F; Daghfous, H; Ben Saad, S; Slim-Saidi, L

    2015-01-01

    The emergence of drug-resistant TB in many countries has become a major public health problem and an obstacle to effective tuberculosis control. Multidrug-resistant tuberculosis (MDR-TB), which is most often the result of poor adherence, is a particularly dangerous form of tuberculosis because it is caused by bacilli resistant to at least isoniazid and rifampicin, the two most effective anti-tuberculosis drugs. Techniques for rapid diagnosis of resistance have greatly improved the care of patients by allowing early treatment which remains complex and costly establishment, and requires skills and resources. The treatment is not standardized but it includes in all cases attack phase with five drugs (there must be an injectable agent and a fluoroquinolone that form the basis of the regimen) for eight months and a maintenance phase (without injectable agent) with a total duration of 20 months on average. Surgery may be beneficial as long as the lesions are localized and the patient has a good cardiorespiratory function. Evolution of MDR-TB treated is less favorable than tuberculosis with germ sensitive. The cure rate varies from 60 to 75% for MDR-TB, and drops to 30 to 40% for XDR-TB. Mortality remains high, ranging from 20 to 40% even up to 70-90% in people co-infected with HIV. PMID:25153927

  4. RAPID LATERAL-FLOW FOR BOVINE TUBERCULOSIS

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2013-01-01

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

  6. Completeness and timeliness of tuberculosis case reporting

    Microsoft Academic Search

    Amy B Curtis; Eugene McCray; Matthew McKenna; Ida M Onorato

    2001-01-01

    Background: Tuberculosis (TB) control activities are contingent on the timely identification and reporting of cases to public health authorities to ensure complete assessment and appropriate treatment of contacts and identification of secondary cases. We report the results of a multistate evaluation of completeness and timeliness of reporting of TB cases in the United States during 1993 and 1994.Methods: To determine

  7. [Pharyngeal tuberculosis: Case report].

    PubMed

    Spini, Roxana Gabriela; Bordino, Lucas; Cohen, Daniela; Martins, Andrea; Ramírez, Zaida; González, Norma E

    2015-08-01

    Pharyngeal tuberculosis is a rare extrapulmonary manifestation. In Argentina, the number of cases of tuberculosis reported in children under 19 years in 2012 was 1752. Only 12.15% had extrapulmonary manifestation. A case of a 17 year old girl with pharyngeal tuberculosis is reported. The patient presented intermittent fever and swallowing pain for 6 months, without response to conventional antibiotic treatment. Chest X-ray showedbilateral micronodular infiltrate, so hospitalization was decided to study and treat. The sputum examination for acid-fast resistant bacilli was positive and treatment with four antituberculous drugs was started, with good evolution and disappearance of symptoms. Diagnostic confirmation with the isolation of Mycobacterium tuberculosis in sputum culture was obtained. The main symptoms of pharyngeal tuberculosis are sore throat and difficulty in swallowing of long evolution. It is important to consider tuberculosis as differential diagnosis in patients with chronic pharyngitis unresponsive to conventional treatment. PMID:26172025

  8. Mycobacterium tuberculosis effectors interfering host apoptosis signaling.

    PubMed

    Liu, Minqiang; Li, Wu; Xiang, Xiaohong; Xie, Jianping

    2015-07-01

    Tuberculosis remains a serious human public health concern. The coevolution between its pathogen Mycobacterium tuberculosis and human host complicated the way to prevent and cure TB. Apoptosis plays subtle role in this interaction. The pathogen endeavors to manipulate the apoptosis via diverse effectors targeting key signaling nodes. In this paper, we summarized the effectors pathogen used to subvert the apoptosis, such as LpqH, ESAT-6/CFP-10, LAMs. The interplay between different forms of cell deaths, such as apoptosis, autophagy, necrosis, is also discussed with a focus on the modes of action of effectors, and implications for better TB control. PMID:25840680

  9. Abdominal Tuberculosis: A Diagnostic Dilemma

    PubMed Central

    Saxena, Manoj; Ahmad, Faiyaz; Kumar, Ashutosh; Dutta, Shyamoli

    2015-01-01

    Background Abdominal tuberculosis (TB) is the sixth most common form of extra-pulmonary site of infection after lymphatic, genitourinary, bone and joint, miliary and meningeal TB with a rising incidence in recent years. TB can affect any part of the gastro-intestinal (GI) tract including anus, peritoneum and hepato-biliary system. The clinical manifestations of abdominal tuberculosis are non-specific and mimic various GI disorders and cause delay in diagnosis and management. Aim To evaluate the various clinical, radiological and microbiological findings of abdominal tuberculosis and to define the role of histopathological examination in establishing the diagnosis in resource poor settings and to analyze the compliance and response to anti-tubercular treatment. Materials and Methods A five year retrospective study (January 2010 to December 2014) was done in a tertiary teaching hospital in Northern India and all the cases diagnosed as abdominal tuberculosis during the study period, were included. The relevant clinical informations, laboratory results, microbiological and radiological investigations were recorded. Histopathological examination of all the resected / excised specimens was done and Ziehl-Neelsen (ZN) staining to detect the tubercular bacilli and Periodic acid-Schiff (PAS) stain to rule out fungal infection was done in all the cases. Results Out of 48 cases with abdominal tuberculosis, the average age of presentation was 27.4 years with a slight male predominance (Male:Female=1.4:1). Abdominal pain (100%) was the most common presenting symptom followed by anorexia (98%), fever (88%) and intestinal obstruction (88%). The ileum was the most common site of involvement. All the 45 resected / excised tissue specimens (34 cases of intestinal resection and 11 cases of intesinal, omental and lymph nodes biopsies) showed epithelioid granulomas along with necrosis (in 38 cases) and Langhans giant cells (in 42 cases). Acid Fast Bacilli (AFB) positivity was seen in 5 tissue specimens only. All patients were put on anti-tubercular treatment and majority showed good response to therapy. Conclusion Abdominal tuberculosis should be considered as a differential diagnosis in patients with vague GI symptoms. Study of histopathological findings can aid in the diagnosis in the settings where advanced molecular methods of diagnosis are not available, leading to early diagnosis and management.

  10. Imaging in tuberculosis.

    PubMed

    Skoura, Evangelia; Zumla, Alimuddin; Bomanji, Jamshed

    2015-03-01

    Early diagnosis of tuberculosis (TB) is necessary for effective treatment. In primary pulmonary TB, chest radiography remains the mainstay for the diagnosis of parenchymal disease, while computed tomography (CT) is more sensitive in detecting lymphadenopathy. In post-primary pulmonary TB, CT is the method of choice to reveal early bronchogenic spread. Concerning characterization of the infection as active or not, CT is more sensitive than radiography, and (18)F-fluorodeoxyglucose positron emission tomography/CT ((18)F-FDG PET/CT) has yielded promising results that need further confirmation. The diagnosis of extrapulmonary TB sometimes remains difficult. Magnetic resonance imaging (MRI) is the preferred modality in the diagnosis and assessment of tuberculous spondylitis, while (18)F-FDG PET shows superior image resolution compared with single-photon-emitting tracers. MRI is considered superior to CT for the detection and assessment of central nervous system TB. Concerning abdominal TB, lymph nodes are best evaluated on CT, and there is no evidence that MRI offers added advantages in diagnosing hepatobiliary disease. As metabolic changes precede morphological ones, the application of (18)F-FDG PET/CT will likely play a major role in the assessment of the response to anti-TB treatment. PMID:25809762

  11. Tuberculosis in Children

    PubMed Central

    Esposito, Susanna; Tagliabue, Claudia; Bosis, Samantha

    2013-01-01

    Tuberculosis (TB) in children is a neglected aspect of the TB epidemic despite it constituting 20% or more of all TB cases in many countries with high TB incidence. Childhood TB is a direct consequence of adult TB but remains overshadowed by adult TB because it is usually smear-negative. Infants and young children are more likely to develop life-threatening forms of TB than older children and adults due to their immature immune systems. Therefore, prompt diagnoses are extremely important although difficult since clinical and radiological signs of TB can be non-specific and variable in children. Despite undeniable advances in identifying definite, probable, or possible TB markers, pediatricians still face many problems when diagnosing TB diagnosis. Moreover, curing TB can be difficult when treatment is delayed and when multi-drug resistant (MDR) pathogens are the cause of the disease. In these cases, the prognosis in children is particularly poor because MDR-TB treatment and treatment duration remain unclear. New studies of diagnostic tests and optimal treatment in children are urgently needed with the final goal of developing an effective anti-TB vaccine. PMID:24363879

  12. [Tuberculosis, the old fellow].

    PubMed

    Tresselt, Christiane; Hösli, Irene

    2008-12-01

    There are many issues concerning tuberculosis during pregnancy. In our case report we discuss a 24-year-old Portuguese woman with unclear weight loss and non-specific symptoms such as fatigue and nausea during pregnancy. After diagnostic work up a pulmonary tuberculosis was diagnosed close to delivery. The treatment and outcome of tuberculosis during pregnancy and the question of breastfeeding after delivery are discussed. PMID:19048529

  13. Automated Tuberculosis Detection

    Microsoft Academic Search

    George Hripcsak; Charles A Knirsch; Nilesh L Jain; Ariel Pablos-Mendez

    1997-01-01

    ObjectiveTo measure the accuracy of automated tuberculosis case detection.SettingAn inner-city medical center.InterventionAn electronic medical record and a clinical event monitor with a natural language processor were used to detect tuberculosis cases according to Centers for Disease Control criteria.MeasurementCases identified by the automated system were compared to the local health department's tuberculosis registry, and positive predictive value and sensitivity were calculated.ResultsThe

  14. CT of parenchymal and bronchial tuberculosis

    Microsoft Academic Search

    C. Beigelman; D. Sellami; M. Brauner

    2000-01-01

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

  15. TUBERCULOSIS COMO ENFERMEDAD OCUPACIONAL

    PubMed Central

    Mendoza-Ticona, Alberto

    2014-01-01

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

  16. Characterization of the genetic diversity of Mycobacterium tuberculosis in São Paulo city, Brazil

    PubMed Central

    2011-01-01

    Background Tuberculosis is a major health problem in São Paulo, Brazil, which is the most populous and one of the most cosmopolitan cities in South America. To characterize the genetic diversity of Mycobacterium tuberculosis in the population of this city, the genotyping techniques of spoligotyping and MIRU were applied to 93 isolates collected in two consecutive years from 93 different tuberculosis patients residing in São Paulo city and attending the Clemente Ferreira Institute (the reference clinic for the treatment of tuberculosis). Findings Spoligotyping generated 53 different spoligotype patterns. Fifty-one isolates (54.8%) were grouped into 13 spoligotyping clusters. Seventy- two strains (77.4%) showed spoligotypes described in the international databases (SpolDB4, SITVIT), and 21 (22.6%) showed unidentified patterns. The most frequent spoligotype families were Latin American Mediterranean (LAM) (26 isolates), followed by the T family (24 isolates) and Haarlem (H) (11 isolates), which together accounted for 65.4% of all the isolates. These three families represent the major genotypes found in Africa, Central America, South America and Europe. Six Spoligo-International-types (designated SITs by the database) comprised 51.8% (37/72) of all the identified spoligotypes (SIT53, SIT50, SIT42, SIT60, SIT17 and SIT1). Other SITs found in this study indicated the great genetic diversity of M. tuberculosis, reflecting the remarkable ethnic diversity of São Paulo city inhabitants. The MIRU technique was more discriminatory and did not identify any genetic clusters with 100% similarity among the 93 isolates. The allelic analysis showed that MIRU loci 26, 40, 23 and 10 were the most discriminatory. When MIRU and spoligotyping techniques were combined, all isolates grouped in the 13 spoligotyping clusters were separated. Conclusions Our data indicated the genomic stability of over 50% of spoligotypes identified in São Paulo and the great genetic diversity of M. tuberculosis isolates in the remaining SITs, reflecting the large ethnic mix of the São Paulo city inhabitants. The results also indicated that in this city, M. tuberculosis isolates acquired drug resistance independently of genotype and that resistance was more dependent on the selective pressure of treatment failure and the environmental circumstances of patients. PMID:21801364

  17. Incidence, Clinical Features and Impact on AntiTuberculosis Treatment of AntiTuberculosis Drug Induced Liver Injury (ATLI) in China

    Microsoft Academic Search

    Penghui Shang; Yinyin Xia; Feiying Liu; Xiaomeng Wang; Yanli Yuan; Daiyu Hu; Dehua Tu; Yixin Chen; Peiyuan Deng; Shiming Cheng; Lin Zhou; Yu Ma; Lizhen Zhu; Weiwei Gao; Hongyuan Wang; Dafang Chen; Li Yang; Pingping He; Shanshan Wu; Shaowen Tang; Xiaozhen Lv; Zheng Shu; Yuan Zhang; Zhirong Yang; Yan Chen; Na Li; Feng Sun; Xiaoting Li; Yingjian He; Paul Garner; Siyan Zhan

    2011-01-01

    BackgroundAnti-tuberculosis drug induced liver injury (ATLI) is emerging as a significant threat to tuberculosis control in China, though limited data is available about the burden of ATLI at population level. This study aimed to estimate the incidence of ATLI, to better understand its clinical features, and to evaluate its impact on anti-tuberculosis (TB) treatment in China.Methodology\\/Principal FindingsIn a population-based prospective

  18. Comprehensive Tuberculosis Testing for the Dermatologist

    PubMed Central

    Jordan, Laura

    2015-01-01

    Tuberculosis remains a noteworthy disease worldwide, rendering detection of latent tuberculosis of great importance. As healthcare workers, dermatologists should be aware of the available testing options and how they compare. In general, the tuberculin skin test has been around longer and, thus, there have been more studies performed on its sensitivity and specificity compared to interferon gamma release assays, which are newer to the market. The tuberculin skin test requires more office visits, takes longer to obtain results, is subject to healthcare worker bias, and can cause a booster phenomenon; whereas, interferon gamma release assays have a higher cost and less data available on their use in children under five years old. Both the tuberculin skin test and interferon gamma release assays fail to differentiate between recent and remote infections, have a low predictive value for active tuberculosis, and a lower sensitivity in people living with human immunodeficiency virus/acquired immunodeficiency syndrome. PMID:26060517

  19. Deprivation, immigration and tuberculosis incidence in Naples, 1996-2000.

    PubMed

    Ponticiello, Antonio; Sturkenboom, Miriam C J M; Simonetti, Andrea; Ortolani, Rosanna; Malerba, Mario; Sanduzzi, Alessandro

    2005-01-01

    Most of the tuberculosis cases in Campania occur in Naples, the biggest city in the South of Italy with the highest unemployment and immigration rates. However, the occurrence of tuberculosis differs between the different neighbourhoods and it is not known whether these differences are associated with poverty or with immigration. We describe tuberculosis incidence and its association with socio-economic status and immigration in the city of Naples during the period 1996-2000. The basic design was an ecological study, correlating the incidence of tuberculosis which was calculated on the basis of notified tuberculosis cases to census data on immigration and socio-economic deprivation per neighbourhood. Immigrants had a high risk for tuberculosis (RR=34 for Africans) but the incidence of TB varied largely by districts and seemed independent of immigration. All socioeconomic factors increased the incidence of TB significantly. In a multivariate Poisson regression analysis only the rate of unemployment (p=0.02) and the population density (p=0.002) remained independently associated with tuberculosis incidence. In this study we showed that deprivation explained differences in tuberculosis incidence in Naples to a greater extent than immigration. PMID:16151887

  20. Tuberculosis among American Indians of the contiguous United States.

    PubMed Central

    Rieder, H L

    1989-01-01

    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

  1. Paleopathology of Human Tuberculosis and the Potential Role of Climate

    PubMed Central

    Nerlich, Andreas G.; Lösch, Sandra

    2009-01-01

    Both origin and evolution of tuberculosis and its pathogens (Mycobacterium tuberculosis complex) are not fully understood. The paleopathological investigation of human remains offers a unique insight into the molecular evolution and spread including correlative data of the environment. The molecular analysis of material from Egypt (3000–500 BC), Sudan (200–600 AD), Hungary (600–1700 AD), Latvia (1200–1600 AD), and South Germany (1400–1800 AD) urprisingly revealed constantly high frequencies of tuberculosis in all different time periods excluding significant environmental influence on tuberculosis spread. The typing of various mycobacteria strains provides evidence for ancestral M. tuberculosis strains in Pre- to early Egyptian dynastic material (3500–2650 BC), while typical M. africanum signatures were detected in a Middle Kingdom tomb (2050–1650 BC). Samples from the New Kingdom to Late Period (1500–500 BC) indicated modern M. tuberculosis strains. No evidence was seen for M. bovis in Egyptian material while M. bovis signatures were first identified in Siberian biomaterial dating 2000 years before present. These results contraindicates the theory that M. tuberculosis evolved from M. bovis during early domestication in the region of the “Fertile Crescent,” but supports the scenario that M. tuberculosis probably derived from an ancestral progenitor strain. The environmental influence of this evolutionary scenario deserves continuing intense evaluation. PMID:19360109

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

    PubMed Central

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

    2014-01-01

    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

  3. Association of Pulmonary Tuberculosis and Diabetes in Mexico: Analysis of the National Tuberculosis Registry 2000–2012

    PubMed Central

    Delgado-Sánchez, Guadalupe; García-García, Lourdes; Castellanos-Joya, Martín; Cruz-Hervert, Pablo; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Hernández, Andrés; Ortega-Baeza, Victor Manuel; Montero-Campos, Rogelio; Sulca, José Antonio; Martínez-Olivares, Ma. de Lourdes; Mongua-Rodríguez, Norma; Baez-Saldaña, Renata; González-Roldán, Jesús Felipe; López-Gatell, Hugo; Ponce-de-León, Alfredo; Sifuentes-Osornio, José; Jiménez-Corona, María Eugenia

    2015-01-01

    Background Tuberculosis (TB) remains a public health problem in Mexico while the incidence of diabetes mellitus type 2 (DM) has increased rapidly in recent years. Objective To describe the trends of incidence rates of pulmonary TB associated with DM and not associated with DM and to compare the results of treatment outcomes in patients with and without DM. Materials and Methods We analysed the National Tuberculosis Registry from 2000 to 2012 including patients with pulmonary TB among individuals older than 20 years of age. The association between DM and treatment failure was analysed using logistic regression, accounting for clustering due to regional distribution. Results In Mexico from 2000 to 2012, the incidence rates of pulmonary TB associated to DM increased by 82.64%, (p <0.001) in contrast to rates of pulmonary TB rate without DM, which decreased by 26.77%, (p <0.001). Patients with a prior diagnosis of DM had a greater likelihood of failing treatment (adjusted odds ratio, 1.34 (1.11–1.61) p <0.002) compared with patients who did not have DM. There was statistical evidence of interaction between DM and sex. The odds of treatment failure were increased in both sexes. Conclusion Our data suggest that the growing DM epidemic has an impact on the rates of pulmonary TB. In addition, patients who suffer from both diseases have a greater probability of treatment failure. PMID:26075393

  4. Tuberculosis terpene targets.

    PubMed

    Oldfield, Eric

    2015-04-23

    In this issue, Young, Moody, and colleagues report the discovery of an isomer of the Mycobacterium tuberculosis (Mtb) virulence factor 1-tuberculosinyl adenosine, N(6)-tuberculosinyl adenosine, in mice infected with tuberculosis. These Mtb-derived terpene compounds may serve as sensitive and specific biomarkers of infection. PMID:25910241

  5. Tuberculosis of the oesophagus

    Microsoft Academic Search

    A. R. Fahmy; R. Guindi; A. Farid

    1969-01-01

    A case of primary tuberculosis of the oesophagus is presented; the patient was successfully treated by oesophagectomy. The condition, being rare, has stimulated the authors to review the literature concerning primary and secondary oesophageal tuberculosis. The history, modes of infection, the pathology, clinical picture, diagnosis, investigations, and methods of treatment are discussed. In contradistinction to the secondary disease, which is

  6. Evaluation of an immunochromatographic test for discrimination between Mycobacterium tuberculosis complex & non tuberculous mycobacteria in clinical isolates from extra-pulmonary tuberculosis

    PubMed Central

    Maurya, Anand Kumar; Nag, Vijaya Lakshmi; Kant, Surya; Kushwaha, Ram Aawadh Singh; Kumar, Manoj; Mishra, Vikas; Rahman, W.; Dhole, Tapan N.

    2012-01-01

    Background & objectives: Accurate diagnosis of tuberculosis (TB) is crucial to facilitate early treatment of the patients, and to reduce its spread. Clinical presentation of Mycobacterium tuberculosis complex (MTBC) and non tuberculous mycobacteria (NTM) may or may not be the same, but the treatment regimen is always different for both the infections. Differentiation between MTBC and NTM by routine laboratory methods is time consuming and cumbersome. This study was aimed to evaluate an immunochromatographic test (ICT), based on mouse monoclonal anti-MPT64, for simple and rapid discrimination between MTBC and NTM in clinical isolates from extra-pulmonary tuberculosis cases. Methods: A total of 800 clinical samples were collected from patients suspected to have extra-pulmonary tuberculosis. Preliminary diagnosis has been done by direct Ziehl–Neelsen (ZN) staining followed by culture in BACTEC system. A total of 150 clinical isolates, which were found positive in BD 460 TB system during September 2009 to September 2010 were selected for the screening by ICT test. p-nitro-?-acetylamino- ?-hydroxy propiophenone (NAP) test was performed for differentiation of MTBC and NTM. M. tuberculosis complex was further confirmed by IS6110 PCR of BACTEC culture positive isolates, this served as the reference method for MTBC identification and comparative evaluation of the ICT kit. Results: Of the 150 BACTEC culture positive isolates tested by ICT kit, 101 (67.3%) were found positive for MTBC and remaining 49 (32.7%) were considered as NTM. These results were further confirmed by IS6110 PCR that served as the reference method for detection of MTBC. H37Rv reference strain was taken as a control for ICT test and IS6110 PCR. The reference strain showed the presence of MPT64 antigen band in the ICT test. Similar bands were formed in 101 of 102 MTBC isolates tested, proving 99.1 per cent sensitivity and no bands were detected in 48 (100%) NTM isolates tested, proving 100 per cent specificity of the ICT kit. Interpretation & conclusions: Our findings show that ICT test can be used on direct culture positive specimens. It does not require any special equipment, is simple and less time consuming. It can easily discriminate between MTBC and NTM and thus can help in appropriate management of tuberculosis. PMID:22825610

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

    PubMed Central

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

    2014-01-01

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

  8. Is Mycobacterium tuberculosis stressed out? A critical assessment of the genetic evidence.

    PubMed

    Stallings, Christina L; Glickman, Michael S

    2010-12-01

    Mycobacterium tuberculosis is an obligate human intracellular pathogen which remains a major killer worldwide. A remarkable feature of M. tuberculosis infection is the ability of the pathogen to persist within the host for decades despite an impressive onslaught of stresses. In this review we seek to outline the host-inflicted stresses experienced by M. tuberculosis, the bacterial strategies used to withstand these stresses, and how this information should guide our efforts to combat this global pathogen. PMID:20691805

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

    PubMed Central

    2010-01-01

    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

  10. The production of consumption: addressing the impact of mineral mining on tuberculosis in southern Africa

    PubMed Central

    Basu, Sanjay; Stuckler, David; Gonsalves, Gregg; Lurie, Mark

    2009-01-01

    Background Miners in southern Africa experience incident rates of tuberculosis up to ten times greater than the general population. Migration to and from mines may be amplifying tuberculosis epidemics in the general population. Discussion Migration to and from mineral mines contributes to HIV risks and associated tuberculosis incidence. Health and safety conditions within mines also promote the risk of silicosis (a tuberculosis risk factor) and transmission of tuberculosis bacilli in close quarters. In the context of migration, current tuberculosis prevention and treatment strategies often fail to provide sufficient continuity of care to ensure appropriate tuberculosis detection and treatment. Reports from Lesotho and South Africa suggest that miners pose transmission risks to other household or community members as they travel home undetected or inadequately treated, particularly with drug-resistant forms of tuberculosis. Reducing risky exposures on the mines, enhancing the continuity of primary care services, and improving the enforcement of occupational health codes may mitigate the harmful association between mineral mining activities and tuberculosis incidence among affected communities. Summary Tuberculosis incidence appears to be amplified by mineral mining operations in southern Africa. A number of immediately-available measures to improve continuity of care for miners, change recruitment and compensation practices, and reduce the primary risk of infection may critically mitigate the negative association between mineral mining and tuberculosis. PMID:19785769

  11. Tuberculosis and subsequent risk of lung cancer in Xuanwei, China

    PubMed Central

    Engels, Eric A.; Shen, Min; Chapman, Robert S.; Pfeiffer, Ruth M.; Yu, Ying-Ying; He, Xingzhou; Lan, Qing

    2008-01-01

    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 2459 (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 1000 person-years). The association was especially pronounced in the first five 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. PMID:19058197

  12. Tuberculosis after renal transplantation.

    PubMed

    Kaaroud, H; Beji, S; Boubaker, K; Abderrahim, E; Ben Hamida, F; Ben Abdallah, T; El Younsi, F; Ben Moussa, F; Kheder, A

    2007-05-01

    Tuberculosis (TB) remains a major public health problem in our country. Its diagnosis in immunodeficient patients is difficult. In this retrospective study, we analyzed the prevalence, clinical presentation, and outcome of TB after renal transplantation (RT) in our Tunisian team's experience. Among 359 renal transplant recipients, 9 (2.5%) developed TB at 49.6 months (range, 3-156 months) after RT. There were 7 men and 2 women of mean age 37.8 years (range, 15-53 years). The organs involved included lymph nodes in 1 case; lung in 5 cases; genitourinary system in 1 case; rachis in 1 case; pleural in 1 case; and both pulmonary and urinary systems in 1 case. The diagnosis was bacteriologic in 6 cases; histologic in 1 case; and 2 patients had a high index of suspicion. All patients were treated with a combination of rifampicin, isoniazide, pyrazinamide, and ethambutal. Recurrence of TB infection was noted in 3 cases with multiple localizations: lymph node, muscle abscess, meningitis, genitourinary system, rachis, and lung. Two patients died. In conclusion, among renal transplant patients, extrapulmonary involvement and recurrence of TB were frequent. PMID:17524877

  13. Longitudinal Assessment of an ELISPOT Test for Mycobacterium tuberculosis Infection

    Microsoft Academic Search

    Philip C. Hill; Roger H. Brookes; Annette Fox; Dolly Jackson-Sillah; David J. Jeffries; Moses D. Lugos; Simon A. Donkor; Ifedayo M. Adetifa; Bouke C. de Jong; Alex M. Aiken; Richard A. Adegbola; Keith P. McAdam

    2007-01-01

    BackgroundVery little longitudinal information is available regarding the performance of T cell-based tests for Mycobacterium tuberculosis infection. To address this deficiency, we conducted a longitudinal assessment of the enzyme-linked immunosorbent spot test (ELISPOT) test in comparison to the standard tuberculin skin test (TST).Methods and FindingsIn tuberculosis (TB) contacts we repeated ELISPOT tests 3 mo (n = 341) and 18 mo

  14. Improving bacteriological diagnosis of tuberculosis.

    PubMed

    Wattal, Chand

    2002-11-01

    This review is to summarize recent developments in the field of mycobacteriology since the diagnosis of tuberculosis remains elusive in spite of our best efforts and great scientific advances. Progress has been made in further improving upon the age old, time tested traditional techniques like microscopy (Auramine-Rhodamine Fluorescent staining and peptide nucleic acids), culture and sensitivity techniques (solid, liquid, radiometric, and non-radiometric systems) that still remain as the gold standard for its diagnosis. Development of rapid methods [(high performance liquid chromatography, thin layer chromatography, RNA sequencing and polymerase chain reaction (PCR), nucleic acid sequence based amplification assay (NASBA), Transcription mediated assay (TMA) and Ligase chain reaction (LCR)] have paved the way for its rapid detection and treatment. It is interesting to see the role of molecular assays appearing more often in literature now. The molecular amplification systems (PCR, NASBA, TMA, LCR) besides identifying Mycobacterium tuberculosis (MTB) as well as non-tuberculous mycobacteria (NTM), directly from the sample can also identify Rifampin (rpoB gene)/Isoniazide (katG gene) resistant strain. Molecular assays have been found useful particularly in smear positive sputum with high sensitivity and specificity whereas variable sensitivity for sputum negative and extra pulmonary specimens has been observed. Representative specimen and its quality affect the performance of these assays. Emphasis should given to proper collection and transportation of the representative specimen for appropriate evaluation. PMID:12501920

  15. Detection of Antibodies Against 6, 16 and 38 kDa Antigens of Mycobacterium tuberculosis as a Rapid Test for Diagnosis of Tuberculosis

    PubMed Central

    Tabarsi, Payam; Sabour, Hojat; Dehghani, Shokoufeh; Marjani, Majid; Shamaei, Masoud; Jabbari, Ali; Amiri, Majid Valiollahpour; Velayati, Ali Akbar

    2011-01-01

    Background Serological assays for diagnosis of tuberculosis (TB) are very attractive because they are inexpensive, non invasive and simple. Present study was conducted to evaluate the tuberculosis rapid test device in Iran. Materials and Methods The tuberculosis rapid test device based on detection of IgM, IgA and IgG antibodies against 6, 16 and 38-kDa antigens of Mycobacterium tuberculosis via chromatography was used in 96 cases of pulmonary and extra pulmonary TB. Fifty four patients with conditions other than TB were selected as the control group. Tuberculin skin test (TST) was performed in two groups. None of the patients were immunodeficient. All of them were evaluated in terms of presence of BCG scar. Results Tuberculosis rapid test was positive in 75 cases (78.1%) and 15 controls (27.8%). This difference was statistically significant (P-value < 0.001). TST was positive in 66 patients (68.8%) with tuberculosis and 10 (18.5%) controls with no statistically significant difference (P-value = 0.065). Sensitivity, specificity, positive and negative predictive values of the tuberculosis rapid test for diagnosis of tuberculosis were 78.1%, 72.2%, 83.3% and 65%, respectively. These parameters for TST were 31.3%, 81.5%, 75%, and 40%, respectively. Conclusion Tuberculosis rapid test has better sensitivity than TST and may be helpful in diagnosis of tuberculosis as a complementary test or in epidemiological investigations. PMID:25191383

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

    Microsoft Academic Search

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

    2009-01-01

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

  17. Expanding the epidemiologic profile: risk factors for active tuberculosis in people immigrating to Ontario

    Microsoft Academic Search

    Wendy L. Wobeser; Lilian Yuan; Monika Naus; Paul Corey; Jeff Edelson; Neil Heywood; D. Linn Holness

    Background: Many people immigrating to Canada come from countries with a high burden of tuberculosis. The aim of this study was to develop a detailed epi- demiologic profile of foreign-born people with tuberculosis living in Ontario. Methods: In this population-based case-control study, cases of tuberculosis diag- nosed in 1994-1995 were identified from the database of the Ontario Re- portable Disease

  18. The Effect of Tuberculosis on Mortality in HIV Positive People: A Meta-Analysis

    Microsoft Academic Search

    Masja Straetemans; Ana L. Bierrenbach; Nico Nagelkerke; Philippe Glaziou; Marieke J. van der Werf; Madhukar Pai

    2010-01-01

    BackgroundTuberculosis is a leading cause of death in people living with HIV (PLWH). We conducted a meta analysis to assess the effect of tuberculosis on mortality in people living with HIV.MethodsMeta-analysis of cohort studies assessing the effect of tuberculosis on mortality in PLWH. To identify eligible studies we systematically searched electronic databases (until December 2008), performed manual searches of citations

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

    Microsoft Academic Search

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

    2010-01-01

    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

  20. The Forest behind the Tree: Phylogenetic Exploration of a Dominant Mycobacterium tuberculosis Strain Lineage from a High Tuberculosis Burden Country

    Microsoft Academic Search

    Maranibia Cardoso Oelemann; Harrison M. Gomes; Eve Willery; Lia Possuelo; Karla Valéria Batista Lima; Caroline Allix-Béguec; Camille Locht; Yves-Olivier L. Goguet de La Salmonière; Maria Cristina Gutierrez; Philip Suffys; Philip Supply; Herman Tse

    2011-01-01

    BackgroundGenotyping of Mycobacterium tuberculosis isolates is a powerful tool for epidemiological control of tuberculosis (TB) and phylogenetic exploration of the pathogen. Standardized PCR-based typing, based on 15 to 24 mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) loci combined with spoligotyping, has been shown to have adequate resolution power for tracing TB transmission and to be useful for predicting

  1. Comparison of Xpert MTB/RIF Assay and the Conventional Sputum Microscopy in Detecting Mycobacterium tuberculosis in Northern Thailand

    PubMed Central

    Pinyopornpanish, Kanokwan; Chaiwarith, Romanee; Pantip, Chansom; Keawvichit, Rassamee; Wongworapat, Kanlaya; Khamnoi, Phadungkiat; Supparatpinyo, Khuanchai; Sirisanthana, Thira

    2015-01-01

    Background. Despite low sensitivity in detection of Mycobacterium tuberculosis, sputum acid-fast smear remains the main diagnostic method. This study aimed to compare the diagnostic performance of Xpert MTB/RIF assay versus conventional sputum acid-fast smear. Materials and Methods. A cross-sectional study was conducted at Chiang Mai University Hospital, Thailand. Patients who were ?15 years old and had clinically suspected pulmonary tuberculosis were included. Results. 109 specimens from 57 patients were included. Using MGIT sputum culture as a reference standard, the sensitivity (SEN) and specificity (SPEC) for Xpert were 95.3% (95% CI, 84.2%, 99.4%) and 86.4% (95% CI, 75.7%, 93.6%). The SEN and SPEC for sputum acid-fast smear were 60.5% (95% CI, 44.4%, 75.0%) and 98.5% (95% CI, 91.8%, 100%). Xpert had significantly higher sensitivity (p value < 0.001) and lower specificity (p value = 0.022) than sputum acid-fast smear. Among 43 culture-proven M. tuberculosis specimens, sensitivity of Xpert was 100% (95% CI, 86.7%, 100%) in acid-fast positive smears (n = 26) and 88.2% (95% CI, 63.5%, 98.5%) in acid-fast negative smears (n = 17). Conclusions. The good sensitivity and specificity of Xpert assay in detecting M. tuberculosis from sputum specimens may help in early diagnosis and treatment of pulmonary tuberculosis, particularly among patients who had acid-fast negative sputum smear.

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

    PubMed Central

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

    2014-01-01

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

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

    Microsoft Academic Search

    Neema Jamshidi; Bernhard Ø Palsson

    2007-01-01

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

  4. Novel human recombinant antibodies against Mycobacterium tuberculosis antigen 85B

    PubMed Central

    2014-01-01

    Background Tuberculosis is the leading cause of death due to bacterial infections worldwide, mainly caused by Mycobacterium tuberculosis. The antigen 85 complex comprises a set of major secreted proteins of M. tuberculosis, which are potential biomarkers for diagnostic. Results In this work, the first human single chain fragment variable (scFv) antibodies specific for the tuberculosis biomarker 85 B were selected by phage display from naïve antibody gene libraries (HAL7/8). Produced as scFv-Fc in mammalian cells, these antibodies were further characterized and analysed for specificity and applicability in different tuberculosis antigen detection assays. Sandwich detection of recombinant 85 B was successful in enzyme linked immunosorbent assay (ELISA), lateral flow immunoassay and immunoblot. Whereas detection of M. tuberculosis cell extracts and culture filtrates was only possible in direct ELISA and immunoblot assays. It was found that the conformation of 85 B, depending on sample treatment, influenced antigen detection. Conclusions Recombinant antibodies, selected by phage display, may be applicable for 85 B detection in various assays. These antibodies are candidates for the development of future point of care tuberculosis diagnostic kits. Using 85 B as a biomarker, the antigen conformation influenced by sample treatment is important. PMID:25033887

  5. Center for Treatment and Research on AIDS, Malaria, Tuberculosis and Other Epidemics

    E-print Network

    Klein, Ophir

    1 TRAC Plus Center for Treatment and Research on AIDS, Malaria, Tuberculosis and Other Epidemics-up of international resources has required rapid responses in planning and targeting prevention and treatment programs to achieve similar purposes remains. The Center for Treatment and Research on HIV/AIDS, Malaria, Tuberculosis

  6. Breast lump, a rare presentation of costochondral junction tuberculosis: a case report

    Microsoft Academic Search

    Sanjay Jain; Adesh Shrivastava; Dinesh Chandra

    2009-01-01

    The diagnosis of musculoskeletal tuberculosis remains a challenge for clinicians and requires a high index of suspicion. The combination of indolent onset of symptom and signs with histological or cytological features and compatible radiography findings, strongly suggest the diagnosis. Prompt diagnosis and treatment are important to prevent serious bone and joint destruction. Tuberculosis involving ribs and presenting with breast mass

  7. The impact of badger removal on the control of tuberculosis in cattle herds in Ireland

    Microsoft Academic Search

    J. M. Griffin; D. H. Williams; G. E. Kelly; T. A. Clegg; I. O’Boyle; J. D. Collins; S. J. More

    2005-01-01

    In Ireland, the herd prevalence of bovine tuberculosis has remained stable for several decades, and in common with several other countries, progress towards eradication has stalled. There is evidence in support of the potential role of infected badgers (Meles meles, a protected species) in bovine tuberculosis in Ireland and Britain. However, this evidence on its own has not been sufficient

  8. Diversity of Mycobacterium tuberculosis isolates from new pulmonary tuberculosis cases in Addis Ababa, Ethiopia.

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  10. Indoleamides are active against drug-resistant Mycobacterium tuberculosis

    PubMed Central

    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.

    2014-01-01

    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 anti-mycobacterial 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

  11. Tuberculosis endometrial polyp.

    PubMed

    Seror, Julien; Faivre, Erika; Prevot, Sophie; Deffieux, Xavier

    2013-01-01

    Tuberculosis can cause infertility when it infects the genital tract (e.g., endometritis). A 31-year-old woman (origin: Algeria) was referred to our academic gynecological institute for unexplained primary infertility. The patient presented with no complaint. Hysteroscopy showed a 10?mm sized endometrial polyp. The polyp was removed. Pathology showed lymphocytic and plasmacytic chronic inflammatory modification, granulomatous modification, and gigantocellular modification,which lead to the diagnosis of tuberculosis. No acid fast organism was seen on Ziehl-Neelsen staining. A chest thorax X-ray revealed no sign of pulmonary tuberculosis. The patient underwent antituberculosis therapy during one year. Posttreatment hysteroscopy revealed no abnormality. This is the first reported case of endometrial tuberculosis diagnosed following removal of a polyp with classical benign appearance. PMID:23607011

  12. Tuberculosis Endometrial Polyp

    PubMed Central

    Seror, Julien; Faivre, Erika; Prevot, Sophie; Deffieux, Xavier

    2013-01-01

    Tuberculosis can cause infertility when it infects the genital tract (e.g., endometritis). A 31-year-old woman (origin: Algeria) was referred to our academic gynecological institute for unexplained primary infertility. The patient presented with no complaint. Hysteroscopy showed a 10?mm sized endometrial polyp. The polyp was removed. Pathology showed lymphocytic and plasmacytic chronic inflammatory modification, granulomatous modification, and gigantocellular modification,which lead to the diagnosis of tuberculosis. No acid fast organism was seen on Ziehl-Neelsen staining. A chest thorax X-ray revealed no sign of pulmonary tuberculosis. The patient underwent antituberculosis therapy during one year. Posttreatment hysteroscopy revealed no abnormality. This is the first reported case of endometrial tuberculosis diagnosed following removal of a polyp with classical benign appearance. PMID:23607011

  13. Multifocal tuberculosis verrucosa cutis.

    PubMed

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

    2015-01-01

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

  14. [The new tools of microbiological diagnosis of tuberculosis].

    PubMed

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

    2014-12-01

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

  15. Esophageal tuberculosis mimicking malignancy.

    PubMed

    Geusens, E; Verschakelen, J A; Flamaing, J; Bogaert, J; Ponette, E; Decramer, M; Baert, A L

    1996-01-01

    A case of pulmonary and esophageal tuberculosis in an 82-year-old female is presented. Esophageal tuberculosis is very rarely seen in Europe and the United States, but the disease is still endemic in India. The major differential diagnosis is esophageal malignancy. Findings that can suggest the diagnosis are tracheo-esophageal fistula formation, enlarged, centrally necrotizing lymph nodes, and a micronodular lung pattern. PMID:8797957

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

    Microsoft Academic Search

    Jianming Wang; Hongbing Shen

    2009-01-01

    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

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

    Microsoft Academic Search

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

    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

  18. Self-paced learning stations for tuberculosis respirator training: Report of a pilot program

    Microsoft Academic Search

    Victoria A. Lieb; Wesley P. Kozinn; Pamela Baxter

    1996-01-01

    Background: In response to the Centers for Disease Control and Prevention's recently issued “Guidelines for Preventing the Transmission of Mycobacterium Tuberculosis in Health-Care Facilities, 1994,” during May 1994 we implemented and evaluated a pilot tuberculosis respirator training program that used four self-directed learning stations, through which participants proceeded at their own pace. Employee tuberculin skin testing was included in the

  19. Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases

    Microsoft Academic Search

    Alexander M Aiken; Philip C Hill; Annette Fox; Keith PWJ McAdam; Dolly Jackson-Sillah; Moses D Lugos; Simon A Donkor; Richard A Adegbola; Roger H Brookes

    2006-01-01

    BACKGROUND: New tools are required to improve tuberculosis (TB) diagnosis and treatment, including enhanced ability to compare new treatment strategies. The ELISPOT assay uses Mycobacterium tuberculosis-specific antigens to produce a precise quantitative readout of the immune response to pathogen. We hypothesized that TB patients in The Gambia would have reduced ELISPOT counts after successful treatment. METHODS: We recruited Gambian adults

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

    Microsoft Academic Search

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

    2009-01-01

    BACKGROUND: Tuberculosis is a growing international health concern. It is the biggest killer among the infectious diseases in the world today. Early detection of drug resistance allows starting of an appropriate treatment. Resistance to drugs is due to particular genomic mutations in specific genes of Mycobacterium tuberculosis(MTB). The aim of this study was to identify the presence of Isoniazid (INH)

  1. High genetic diversity among Mycobacterium tuberculosis complex strains from Sierra Leone

    Microsoft Academic Search

    Susanne Homolka; Erik Post; Barbara Oberhauser; Abu Garawani George; Lars Westman; Foday Dafae; Sabine Rüsch-Gerdes; Stefan Niemann

    2008-01-01

    BACKGROUND: Among tuberculosis (TB) high incidence regions, Sub-Saharan Africa is particularly affected with approx. 1.6 million new cases every year. Besides this dramatic situation, data on the diversity of Mycobacterium tuberculosis complex (MTBC) strains causing this epidemic in this area are only sparsely available. Here we analyzed the population structure of strains from Sierra Leone with a special focus on

  2. Genomic Diversity among Drug Sensitive and Multidrug Resistant Isolates of Mycobacterium tuberculosis with Identical DNA Fingerprints

    Microsoft Academic Search

    Stefan Niemann; Claudio U. Köser; Sebastien Gagneux; Claudia Plinke; Susanne Homolka; Helen Bignell; Richard J. Carter; R. Keira Cheetham; Anthony Cox; Niall A. Gormley; Paula Kokko-Gonzales; Lisa J. Murray; Roberto Rigatti; Vincent P. Smith; Felix P. M. Arends; Helen S. Cox; Geoff Smith; John A. C. Archer; Niyaz Ahmed

    2009-01-01

    BackgroundMycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB), is characterized by low sequence diversity making this bacterium one of the classical examples of a genetically monomorphic pathogen. Because of this limited DNA sequence variation, routine genotyping of clinical MTBC isolates for epidemiological purposes relies on highly discriminatory DNA fingerprinting methods based on mobile and repetitive genetic elements. According

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

    Microsoft Academic Search

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

    2009-01-01

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

  4. Identification and characterization of Mycobacterium tuberculosis antigens in urine of patients with active pulmonary tuberculosis: an innovative and alternative approach of antigen discovery of useful microbial molecules

    PubMed Central

    Kashino, S S; Pollock, N; Napolitano, D R; Rodrigues, V; Campos-Neto, A

    2008-01-01

    Despite the clear need to control tuberculosis, the diagnosis and prevention of this serious disease are poorly developed and have remained fundamentally unchanged for more than 50 years. Here, we introduce an innovative approach to directly identify Mycobacterium tuberculosis antigens produced in vivo in humans with tuberculosis. We combined reversed phase high performance liquid chromatography and mass spectrometry and categorize four distinct M. tuberculosis proteins produced presumably in lung lesions and excreted in the urine of patients with pulmonary tuberculosis. The genes (MT_1721, MT_1694, MT_2462 and MT_3444) coding for these proteins were cloned and the recombinant molecules were produced in Escherichia coli. The proteins were recognized by immunoglobulin G antibodies from tuberculosis patients but not from non-diseased subjects. In addition, the recombinant proteins were recognized strongly by peripheral blood mononuclear cells from healthy purified protein derivative of tuberculin-positive individuals and to a lesser extent from patients with tuberculosis. These molecules are the only proteins reported to date that are derived directly from bodily fluids of tuberculosis patients, therefore are interesting candidate antigens for the development of vaccine and/or antigen detection assay for accurate diagnosis of active tuberculosis. PMID:18460016

  5. Multiple Cytokines Are Released When Blood from Patients with Tuberculosis Is Stimulated with Mycobacterium tuberculosis Antigens

    PubMed Central

    Kellar, Kathryn L.; Gehrke, Jennifer; Weis, Stephen E.; Mahmutovic-Mayhew, Aida; Davila, Blachy; Zajdowicz, Margan J.; Scarborough, Robin; LoBue, Philip A.; Lardizabal, Alfred A.; Daley, Charles L.; Reves, Randall R.; Bernardo, John; Campbell, Brandon H.; Whitworth, William C.; Mazurek, Gerald H.

    2011-01-01

    Background Mycobacterium tuberculosis (Mtb) infection may cause overt disease or remain latent. Interferon gamma release assays (IGRAs) detect Mtb infection, both latent infection and infection manifesting as overt disease, by measuring whole-blood interferon gamma (IFN-?) responses to Mtb antigens such as early secreted antigenic target-6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7. Due to a lack of adequate diagnostic standards for confirming latent Mtb infection, IGRA sensitivity for detecting Mtb infection has been estimated using patients with culture-confirmed tuberculosis (CCTB) for whom recovery of Mtb confirms the infection. In this study, cytokines in addition to IFN-? were assessed for potential to provide robust measures of Mtb infection. Methods Cytokine responses to ESAT-6, CFP-10, TB7.7, or combinations of these Mtb antigens, for patients with CCTB were compared with responses for subjects at low risk for Mtb infection (controls). Three different multiplexed immunoassays were used to measure concentrations of 9 to 20 different cytokines. Responses were calculated by subtracting background cytokine concentrations from cytokine concentrations in plasma from blood stimulated with Mtb antigens. Results Two assays demonstrated that ESAT-6, CFP-10, ESAT-6+CFP-10, and ESAT-6+CFP-10+TB7.7 stimulated the release of significantly greater amounts of IFN-?, IL-2, IL-8, MCP-1 and MIP-1? for CCTB patients than for controls. Responses to combination antigens were, or tended to be, greater than responses to individual antigens. A third assay, using whole blood stimulation with ESAT-6+CFP-10+TB7.7, revealed significantly greater IFN-?, IL-2, IL-6, IL-8, IP-10, MCP-1, MIP-1?, and TNF-? responses among patients compared with controls. One CCTB patient with a falsely negative IFN-? response had elevated responses with other cytokines. Conclusions Multiple cytokines are released when whole blood from patients with CCTB is stimulated with Mtb antigens. Measurement of multiple cytokine responses may improve diagnostic sensitivity for Mtb infection compared with assessment of IFN-? alone. PMID:22132075

  6. Global Incidence of Multidrug?Resistant Tuberculosis

    Microsoft Academic Search

    Matteo Zignol; Abigail Wright; Paul Nunn; Christopher Dye

    2006-01-01

    Background. The global number of incident cases of multidrug-resistant (MDR) tuberculosis (TB) in 2000 was estimated to be 272,906 (95% confidence interval (CI), 184,948-414,295). For accurate planning of TB control programs, this estimate and others have been revised using data from additional countries and by including in the model previously treated TB cases, which had not been accounted for in

  7. The Seasonality of Tuberculosis, Sunlight, Vitamin D, and Household Crowding

    PubMed Central

    Wingfield, Tom; Schumacher, Samuel G.; Sandhu, Gurjinder; Tovar, Marco A.; Zevallos, Karine; Baldwin, Matthew R.; Montoya, Rosario; Ramos, Eric S.; Jongkaewwattana, Chulanee; Lewis, James J.; Gilman, Robert H.; Friedland, Jon S.; Evans, Carlton A.

    2014-01-01

    Background.?Unlike other respiratory infections, tuberculosis diagnoses increase in summer. We performed an ecological analysis of this paradoxical seasonality in a Peruvian shantytown over 4 years. Methods.?Tuberculosis symptom-onset and diagnosis dates were recorded for 852 patients. Their tuberculosis-exposed cohabitants were tested for tuberculosis infection with the tuberculin skin test (n = 1389) and QuantiFERON assay (n = 576) and vitamin D concentrations (n = 195) quantified from randomly selected cohabitants. Crowding was calculated for all tuberculosis-affected households and daily sunlight records obtained. Results.?Fifty-seven percent of vitamin D measurements revealed deficiency (<50 nmol/L). Risk of deficiency was increased 2.0-fold by female sex (P < .001) and 1.4-fold by winter (P < .05). During the weeks following peak crowding and trough sunlight, there was a midwinter peak in vitamin D deficiency (P < .02). Peak vitamin D deficiency was followed 6 weeks later by a late-winter peak in tuberculin skin test positivity and 12 weeks after that by an early-summer peak in QuantiFERON positivity (both P < .04). Twelve weeks after peak QuantiFERON positivity, there was a midsummer peak in tuberculosis symptom onset (P < .05) followed after 3 weeks by a late-summer peak in tuberculosis diagnoses (P < .001). Conclusions.?The intervals from midwinter peak crowding and trough sunlight to sequential peaks in vitamin D deficiency, tuberculosis infection, symptom onset, and diagnosis may explain the enigmatic late-summer peak in tuberculosis. PMID:24596279

  8. New tuberculosis drugs in development.

    PubMed

    Laughon, Barbara E

    2007-01-01

    Over the past 50 years, no new drug classes have been introduced to treat tuberculosis. Tuberculosis (TB) kills nearly two million people a year mainly in the poorest communities in the developing world. It afflicts millions more. About one third of the world's population is silently infected with TB that may erupt into disease with increased age or suppression of the immune system. Nearly nine million new active cases develop every year. The World Health Organization (WHO) declared the disease a global emergency as long ago as 1993. Although huge efforts in public health control have reduced the disease burden within most established market economies, in Africa and Asia the epidemic continues to accelerate, particularly fueled by the HIV epidemic. Furthermore, resistance to the standard drugs isoniazid and rifampicin is increasing worldwide. Since the 1990s, mycobacteria have emerged with resistance patterns rendering all currently available antibiotics ineffectual. The pharmaceutical industry has mostly abandoned TB drug development due to perceived non-profitable consumer market and the diminishing number of companies engaged in anti-infective research. The public sector and infectious disease researchers have responded to advance fundamental science and to create new chemical entities as early drug candidates. With support from research funding agencies, philanthropic donors, and the STOP-TB Partnership, new chemical tools and new approaches to effectively implement TB control programs are evolving. Advanced preclinical development and strategies for Phase III clinical trials remain gap areas that will require additional engagement from all sectors. PMID:17346192

  9. Mycobacterium tuberculosis: Success through dormancy

    PubMed Central

    Gengenbacher, Martin; Kaufmann, Stefan H. E.

    2012-01-01

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

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

    PubMed Central

    2014-01-01

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

  11. Direct molecular detection of Mycobacterium tuberculosis complex from clinical samples – An adjunct to cultural method of laboratory diagnosis of tuberculosis

    PubMed Central

    Alli, Oyebode A. T.; Ogbolu, Olusoga D.; Alaka, Olubunmi O.

    2011-01-01

    Background: Tuberculosis, a communicable disease with significant morbidity and mortality, is the leading cause of death in the world from bacterial infectious disease. Because of its public health importance, there is need for rapid and definitive method of detecting the causative organism. Several approaches have been attempted, but the molecular methods, especially Polymerase Chain Reaction assays are the most promising for rapid detection of Mycobacterium tuberculosis complex from clinical samples. Aim: This study was aimed at using Polymerase Chain Reaction for detection of Mycobacterium tuberculosis complex from clinical samples using universal sample processing methodology. Subjects and Methods: Two hundred clinical samples sent to Tuberculosis laboratories in Ibadan and Osogbo, Nigeria, were enrolled in this study. The samples were processed by universal sample processing methodology for PCR; smear microscopy was carried out on sputum samples by Ziehl Nelseen staining technique; and cultured on Middlebrook agar medium containing oleic acid albumin dextrose complex supplement after decontamination of samples. Results: Ninety six (48%) samples were detected positive for M. tuberculosis complex by polymerase chain reaction using the combination of boiling and vortexing and microscopy detected 72 (36%) samples positive for acid fast bacilli. Using culture method as gold standard, it was found that polymerase chain reaction assay was more sensitive (75.5%) and specific (94.8%) than microscopy (sensitivity of 48.5% and specificity of 85.7%) in detecting M. tuberculosis complex from clinical samples. There was significant difference in detecting M. tuberculosis from clinical samples when compared to microscopy (p<0.05). Conclusion: The study recommends that direct molecular detection of M. tuberculosis complex is sensitive and specific and polymerase chain reaction method should be used as an adjunct to other methods of laboratory diagnosis of tuberculosis. PMID:22540099

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

    PubMed Central

    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

    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

  13. Unusual Clinical Presentation of Thoracic Tuberculosis: The Need for a Better Knowledge of Illness

    PubMed Central

    Manca, Sandra; Fois, Alessandro Giuseppe; Santoru, Luigi; Trisolini, Rocco; Polo, Maria Francesca; Ostera, Salvatore; Patelli, Marco; Pirina, Pietro

    2015-01-01

    Patient: Male, 73 Final Diagnosis: Bronchoesophageal fistula in endobronchial tuberculosis and mediastinal lymphadenopathy Symptoms: Nonproductive cough • weight loss Medication: Isoniazid • rifampin • pyrazinamide • ethambutol Clinical Procedure: Laser treatment Specialty: Pulmonology Objective: Unusual clinical course Background: Pulmonary tuberculosis (TB), a highly contagious infectious disease, is a significant public health problem all over the world and remains an important cause of preventable death in the adult population. Endobronchial TB is an unusual form of thoracic TB that may be complicated by tracheobronchial stenosis, and bronchoesophageal fistula formation is a very rare complication. Tubercular lymphadenitis can also lead to fistula formation through a process of caseum necrosis and opening of a fistula between the bronchus and oesophagus. Case Report: We report an uncommon case of thoracic TB in an immunocompetent 73-year-old Caucasian man who presented several problems: bronchoesophageal fistula, endobronchial TB, and mediastinal lymphadenopathy in the absence of contemporary parenchymal consolidation. Furthermore, he presented a normal chest radiograph and mostly unclear and non-specific symptoms at onset. Conclusions: We emphasize the need for a better knowledge of this illness and awareness that it may have an unusual presentation. In these cases, diagnosis and proper treatment can be delayed, with severe complications for the patient. Pulmonary TB remains a real diagnostic challenge: a normal chest radiograph and nonspecific symptoms do not allow us to exclude this persistent infectious disease. PMID:25907152

  14. Demographic and microbial characteristics of extrapulmonary tuberculosis cases diagnosed in Malatya, Turkey, 2001-2007

    PubMed Central

    2011-01-01

    Background Extrapulmonary tuberculosis (EPTB) has an increasing rate in Turkey. The reason remains largely unknown. A better understanding of the demographic and microbial characteristics of EPTB in the Turkish population would extend the knowledgebase of EPTB and allow us to develop better strategies to control tuberculosis (TB). Methods We retrospectively evaluated clinical and laboratory data of 397 bacteriologically-confirmed TB cases diagnosed during an eight year-period using by chi-square analysis and multivariate logistic regression model. Results Of the 397 study patients, 103 (25.9%) had EPTB and 294 (74.1%) had pulmonary tuberculosis (PTB). The most commonly seen two types of EPTB were genitourinary TB (27.2%) and meningeal TB (19.4%). TB in bone/joints, pleural cavity, lymph nodes, skin, and peritoneal cavity occurred at a frequency ranging from 9.7% to 10.7%. The age distribution was significantly different (P < 0.01) between PTB and EPTB, with patients older than 45 years tending to have an increased risk of EPTB. Furthermore, the distribution of different types of EPTB differed significantly among age groups (P = 0.03). Meningeal and bone and/or joint TB were more commonly observed among the male patients, while lymphatic, genitourinary, and peritoneal TB cases were more frequently seen among females. Unique strain infection was statistically significantly associated with EPTB (OR: 2.82, 95% CI [1.59, 5.00]) Conclusions EPTB accounted for a significant proportion of TB cases in Malatya, Turkey between 2001 and 2007. The current study has provided an insight into the dynamics of EPTB in Malatya, Turkey. However, the risk factors for having EPTB in Malatya, Turkey remain to be assessed in future studies using population-based or randomly selected sample. PMID:21385458

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

    PubMed Central

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

    2014-01-01

    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

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

    Microsoft Academic Search

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

    2006-01-01

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

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

    PubMed Central

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

    2014-01-01

    Background: Tuberculosis (TB) remains a serious public health problem worldwide. The emergence of drug resistance and multidrug resistance (MDR) has become the main threat to TB treatment and control programs. Rapid detection is critical for the effective treatment of patients. In recent times, a new method using the colorimetric indicator resazurin has been proposed for drug susceptibility of Mycobacterium tuberculosis. Materials and Methods: In this study, the resazurin reduction assay was adapted to screw cap tubes. Using the Resazurin Tube Method (RTM), a total of 100 clinical isolates were tested against Rifampicin (RIF) and Isoniazide (INH). By visual reading, the minimum inhibitory concentrations (MICs) were obtained after eight days. The results obtained were compared with the gold standard proportion method. Results: Excellent results were obtained for RTM with a sensitivity of 100% for both RIF and INH, with a specificity of 98.7 and 95.3%, respectively. Kappa is the measure of agreement between the RTM and proportion method (PM) for RIF and INH, which was found to be 0.972 and 0.935 for RIF and INH, respectively. Conclusion: The RTM appears to be a reliable method for the rapid and simultaneous detection of MDR-TB and drug susceptibility testing (DST) of M. tuberculosis. It is simple, inexpensive, and with no biohazard risk involved. PMID:25538453

  18. Promising drugs against tuberculosis.

    PubMed

    de Souza, Marcus Vinícius Nora

    2006-01-01

    Tuberculosis (TB) is an important public health problem worldwide due to AIDS epidemic, the advent of multidrug resistant strains (MDR) and the lack of new drugs in the market. TB is responsible for almost 3 millions deaths each year. According to WHO (World Health Organization), which declared tuberculosis a global health emergency in 1993, tuberculosis, without a coordinated control effort, will infect an estimated 1 billion people by 2020, killing 70 million. In spite of this problem, there is a lack of development of new TB drugs. For example, it has been nearly 35 years since the introduction of a new class of compounds for the treatment of TB. Thus, there is an urgent need for new drugs to fight against this disease. Considering that, this review aims promising drug candidates that are in development against TB. PMID:18221132

  19. Spoligotyping and Mycobacterium tuberculosis.

    PubMed

    Gori, Andrea; Bandera, Alessandra; Marchetti, Giulia; Degli Esposti, Anna; Catozzi, Lidia; Nardi, Gian Piero; Gazzola, Lidia; Ferrario, Giulio; van Embden, Jan D A; van Soolingen, Dick; Moroni, Mauro; Franzetti, Fabio

    2005-08-01

    We evaluated the clinical usefulness of spoligotyping, a polymerase chain reaction-based method for simultaneous detection and typing of Mycobacterium tuberculosis strains, with acid-fast bacilli-positive slides from clinical specimens or mycobacterial cultures. Overall sensitivity and specificity were 97% and 95% for the detection of M. tuberculosis and 98% and 96% when used with clinical specimens. Laboratory turnaround time of spoligotyping was less than that for culture identification by a median of 20 days. In comparison with IS6110-based restriction fragment length polymorphism typing, spoligotyping overestimated the number of isolates with identical DNA fingerprints by approximately 50%, but showed a 100% negative predictive value. Spoligotyping resulted in the modification of ongoing antimycobacterial treatment in 40 cases and appropriate therapy in the absence of cultures in 11 cases. The rapidity of this method in detection and typing could make it useful in the management of tuberculosis in a clinical setting. PMID:16102314

  20. A novel murine cytomegalovirus vaccine vector protects against Mycobacterium tuberculosis.

    PubMed

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

    2014-09-01

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

  1. Genetic Basis of Virulence Attenuation Revealed by Comparative Genomic Analysis of Mycobacterium tuberculosis Strain H37Ra versus H37Rv

    Microsoft Academic Search

    Huajun Zheng; Liangdong Lu; Bofei Wang; Shiying Pu; Xianglin Zhang; Genfeng Zhu; Wanliang Shi; Lu Zhang; Honghai Wang; Shengyue Wang; Guoping Zhao; Ying Zhang; Dana Davis

    2008-01-01

    Tuberculosis, caused by Mycobacterium tuberculosis, remains a leading infectious disease despite the availability of chemotherapy and BCG vaccine. The commonly used avirulent M. tuberculosis strain H37Ra was derived from virulent strain H37 in 1935 but the basis of virulence attenuation has remained obscure despite numerous studies. We determined the complete genomic sequence of H37Ra ATCC25177 and compared that with its

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

    PubMed

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

    2014-03-01

    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

  3. Tuberculosis case finding based on symptom screening among immigrants, refugees and asylum seekers in Rome

    PubMed Central

    2013-01-01

    Background In Italy the proportion of cases of tuberculosis in persons originating from high-prevalence countries has been increasing in the last decade. We designed a study to assess adherence to and yield of a tuberculosis screening programme based on symptom screening conducted at primary care centres for regular and irregular immigrants and refugees/asylum seekers. Methods Presence of symptoms suggestive of active tuberculosis was investigated by verbal screening in migrants presenting for any medical condition to 3 free primary care centres in the province of Rome. Individuals reporting at least one symptom were referred to a tuberculosis clinic for diagnostic workup. Results Among 2142 migrants enrolled, 254 (11.9%) reported at least one symptom suggestive of active tuberculosis and 176 were referred to the tuberculosis clinic. Of them, 80 (45.4%) did not present for diagnostic evaluation. Tuberculosis was diagnosed in 7 individuals representing 0.33% of those screened and 7.3% of those evaluated for tuberculosis. Conclusion The overall yield of this intervention was in the range reported for other tuberculosis screening programmes for migrants, although we recorded an unsatisfactory adherence to diagnostic workup. Possible advantages of this intervention include low cost and reduced burden of medical procedures for the screened population. Further evaluation of this approach appears to be warranted. PMID:24053349

  4. Control and prevention of tuberculosis in the United Kingdom: Code of Practice 2000

    PubMed Central

    Joint, T

    2000-01-01

    BACKGROUND—The guidelines on control and prevention of tuberculosis in the United Kingdom have been reviewed and updated.?METHODS—A subcommittee was appointed by the Joint Tuberculosis Committee (JTC) of the British Thoracic Society to revise the guidelines published in 1994 by the JTC, including representatives of the Royal College of Nursing, Public Health Medicine Environmental Group, and Medical Society for Study of Venereal Diseases. In preparing the revised guidelines the authors took account of new published evidence and graded the strength of evidence for their recommendations. The guidelines have been approved by the JTC and the Standards of Care Committee of the British Thoracic Society.?RECOMMENDATIONS—Tuberculosis services in each district should have staffing and resources to fulfil both the control and prevention recommendations in this document and to ensure adequate treatment monitoring. Notification of tuberculosis is required for surveillance and to initiate contact tracing (where appropriate). The following areas are discussed and recommendations made where appropriate: (1) public health law in relation to tuberculosis; (2) the organisational requirements for tuberculosis services; (3) measures for control of tuberculosis in hospitals, including segregation of patients; (4) the requirements for health care worker protection, including HIV infected health care workers; (5) measures for control of tuberculosis in prisons; (6) protection for other groups with potential exposure to tuberculosis; (7) awareness of the high rates of tuberculosis in the homeless together with local plans for detection and action; (8) detailed advice on contact tracing; (9) contact tracing required for close contacts of bovine tuberculosis; (10) management of tuberculosis in schools; (11) screening of new immigrants and how this should be performed; (12) outbreak contingency investigation; and (13) BCG vaccination and the management of positive reactors found in the schools programme.?? PMID:11050256

  5. Post-treatment change in Mycobacterium tuberculosis antigen-stimulated tumor necrosis factor-alpha release in patients with active tuberculosis

    PubMed Central

    Kim, Chang Ho; Yoo, Seung Soo; Lee, Shin Yup; Cha, Seung Ick; Park, Jae Yong

    2015-01-01

    Background Monitoring tuberculosis (TB) treatment response remains challenging due to lack of reliable laboratory markers. In recent years, increased efforts have been exerted toward development of new biomarkers reflecting treatment response appropriately. While performance of interferon-gamma release assays (IGRAs) to monitor anti-TB treatment has been extensively evaluated, there is no data about post-treatment changes in Mycobacterium tuberculosis (MTB) antigen-stimulated tumor necrosis factor-alpha (TNF-?) release in active TB patients. Herein, we explored whether the MTB antigen-stimulated TNF-? release would be useful for monitoring responses to anti-TB treatment. Methods We compared unstimulated (TNF-?Nil), MTB antigen-stimulated (TNF-?Ag), and MTB antigen-stimulated minus unstimulated TNF-? levels (TNF-?Ag-Nil) in supernatants from QuantiFERON-TB Gold In-Tube tests before and after treatment in 16 active TB patients, 25 latent TB infection (LTBI) subjects, and 10 healthy controls (HC). Results TNF-?Ag and TNF-?Ag-Nil levels decreased significantly after treatment in patients with active TB. In addition, TNF-?Nil, TNF-?Ag, and TNF-?Ag-Nil levels were significantly higher in untreated active TB patients compared to LTBI subjects and HC. Conclusions This finding cautiously suggests that MTB Ag-stimulated TNF-? response may be a potential adjunctive marker for monitoring treatment response in active TB patients.

  6. Mycobacterium tuberculosis evades host immunity by recruiting mesenchymal stem cells.

    PubMed

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

    2010-12-14

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

  7. Novel and Improved Technologies for Tuberculosis Diagnosis: Progress and Challenges

    Microsoft Academic Search

    Madhukar Pai; Jessica Minion; Hojoon Sohn; Alice Zwerling; Mark D. Perkins

    2009-01-01

    Despite substantial success in implementing standardized care and improving rates of cure in recent years, the global burden of tuberculosis (TB) remains enormous. Lack of rapid and accu- rate diagnosis and case detection are major obstacles to TB control. TB diagnosis, even today, continues to rely heavily on tools such as direct smear microscopy, solid culture, chest radiog- raphy, and

  8. Cattle movements and bovine tuberculosis in Great Britain

    Microsoft Academic Search

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

    2005-01-01

    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

  9. [New era in molecular epidemiology of tuberculosis in Japan].

    PubMed

    Takashima, Tetsuya; Iwamoto, Tomotada

    2006-11-01

    Molecular epidemiology of tuberculosis (TB) is a science to study TB transmission dynamics and to enhance our understanding of the epidemiology of TB by utilizing molecular typing methods as an adjunct to classical epidemiological approach. Before the era of molecular epidemiology, it was quite difficult to ascertain the source of the infections since M. tuberculosis is spread by air-borne droplets of respiratory secretions expelled by an infectious person to a susceptible host and it can remain latent as an asymptomatic infection for years. Now a day, our understanding of TB transmission dynamics has been refined by genotyping of M. tuberculosis strains. The methods of molecular epidemiology, especially IS6110 RFLP of M. tuberculosis, were first introduced to outbreak investigations and then gradually been expanded its application to population-based study in Japan. IS6110 RFLP is obviously a powerful tool for strain differentiation of M. tuberculosis but its labor-intensiveness limits the achievable throughput and makes it less useful for long-term prospective studies. Recently, apart from IS6110 RFLP, DNA amplification-based method, i.e., variable number of tandem repeats (VNTR) has appeared as a substitute for or adjunct to the IS6110 RFLP. In this symposium, we have invited four opinion leaders in molecular epidemiology of TB from different fields: Mycobacterium reference center, basic science, clinical practice, and public health practice. We, as the chairpersons of this symposium, hope that this symposium would trigger the development of molecular epidemiological network of TB in Japan. 1. Achievement and problem of molecular epidemiologic study with IS6110-RFLP analyses of tuberculosis in Okinawa: Shinji MAEDA (Mycobacterium Reference Center, The Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association) The long-term RFLP analyses of tuberculosis in Okinawa showed that endemic M. tuberculosis might be present. This is one of the achievements of our project study. On the other hand, for more effective examination of contact persons, information of molecular epidemiology should be used actively. Therefore because the analysis report needs to be sent back quickly, the PCR-based VNTR method should substitute for the RFLP analysis. 2. Basic knowledge and application of Variable Numbers of Tandem Repeats: Kei NISHIMORI (Department of epidemiology, National Institute of Animal Health) Genomic loci of Variable Numbers of Tandem Repeats (VNTR loci) in Mycobacterium tuberculosis complex and Mycobacterium avium, the history of analysis of VNTR loci, the hypothetical mechanisms of increase or decrease of number of repeats, the structures of the loci, and the necessity of standardizing the VNTR typing were introduced. 3. Clinical application of VNTR: Tomoshige MATSUMOTO, and Hiromi ANO (Department of Clinical Research and Development, Osaka Prefectural Hospital Organization Osaka Prefectural Medical Center for Respiratory and Allergic Diseases) Tuberculosis genotyping was first introduced to outbreak investigations and population-based studies. The advent of Variable Numbers of Tandem Repeats (VNTR) can be applied to clinical fields of not only Mycobacterium tuberculosis but also of Mycobacterium avium. In Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, clinical application of VNTR was first introduced in Japan to determine whether Mycobacterium tuberculosis or avium disease was caused by reactivation or reinfection when relapsed. We showed some examples about usefulness of the clinical application of VNTR. 4. Molecular epidemiology of tuberculosis to improve TB prevention and control activities: Tomotada IWAMOTO (Department of microbiology, Kobe Institute of Health), Riyo FUJIYAMA, Noriko TANAKA, Yasuto KAWAKAMI (Kobe City Public Health Center), Chika SHIRAI (Hyogo-ku Health and Welfare Department, Kobe) M. tuberculosis isolates in Kobe have been characterized as: a) Beijing family strains are highly prevalent (77%), b) two major MIRU profiles in Beijing family were found, one is global

  10. 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.

  11. Genetic vaccination against tuberculosis

    Microsoft Academic Search

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

    1997-01-01

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

  12. [Tuberculosis: a forgotten challenge].

    PubMed

    Martins, P; Machado, A; Alves, A D; Valente, P; Dias, P G

    1997-01-01

    Tuberculosis continues to be a serious problem in public health even thought eh causative bacillus was discovered over 100 years ago. The authors present a clinical case that illustrates the current concern regarding the disease. The case concerns a child of emigrant parents, who are drug addicts and whose illness has not been fully ascertained. The child was hospitalised at three and an half months with fever, malnutrition, opisthotonos and hepatosplenomegaly. After the diagnosis of disseminated tuberculosis affecting the central nervous system, treatment was started with five antituberculosis drugs and with corticosteroids. Respiration improved favourably, but after 19 days the patient suffered a partial tonic-clonic seizure. Subsequently, hydrocephalus was observed and a shunt was applied. Bacteriological examination of the gastric aspirate showed a strain of Mycobacterium tuberculosis resistant to isoniazid and streptomycin. In the eight month of therapeutics, three antituberculosis drugs were still being administered, the shunt was still present and the patient showed a severe psychomotor retardation. The child belonged to a risk group and presented a serious form of tuberculosis with multidrug-resistance, illustrating that this group of children is particularly vulnerable and reflect transmission of this illness among adults. PMID:9341047

  13. [Surgery for thoracic tuberculosis].

    PubMed

    Kilani, T; Boudaya, M S; Zribi, H; Ouerghi, S; Marghli, A; Mestiri, T; Mezni, F

    2015-01-01

    Tuberculosis is mainly a medical disease. Surgery has been the unique therapeutic tool for a long time before the advent of specific antituberculous drugs, and the role of surgery was then confined to the treatment of the sequelae of tuberculosis and their complications. The resurgence of tuberculosis and the emergence of multidrug-resistant TB combined to immunosuppressed patients represent a new challenge for tuberculosis surgery. Surgery may be indicated for a diagnostic purpose in patients with pulmonary, pleural, mediastinal or thoracic wall involvement, or with a therapeutic purpose (drainage, resection, residual cavity obliteration). Modern imaging techniques and the advent of video-assisted thoracic surgery allowed a new approach of this pathology; the majority of diagnostic interventions and selected cases requiring lung resection can be performed through a mini-invasive approach. Patients proposed for aggressive surgery may be treated with the best results thanks to a good evaluation of the thoracic lesions, of the patients' nutritional, infectious and general status combined with a good coordination between the specialized medical team for an optimal preparation to surgery. PMID:24894967

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

    Microsoft Academic Search

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

    2005-01-01

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. Drugs in development for tuberculosis.

    PubMed

    Ginsberg, Ann M

    2010-12-01

    Tuberculosis (TB) drug research and development efforts have resurged in the past 10 years to meet urgent medical needs, but enormous challenges remain. These urgent needs are largely driven by the current long and arduous multidrug regimens, which have significant safety, tolerability and compliance issues; rising and disturbing rates of multidrug- and extensively drug-resistant TB; the existence of approximately 2 billion individuals already latently infected with Mycobacterium tuberculosis, the causative pathogen of TB; and a global TB-HIV co-epidemic. Stakeholders in TB drug development are moving to enable and streamline development and registration of novel, multidrug treatment regimens, comprised of multiple new chemical entities with novel mechanisms of action that do not demonstrate cross-resistance to current first- and second-line TB drugs. Ideally, these new regimens will ultimately provide a short, simple treatment suitable for essentially all TB patients, whether sensitive or resistant to the current anti-TB agents, whether HIV-positive or -negative, and irrespective of patient age. This article reviews the challenges faced by those trying to develop these novel regimens and the key agents currently in clinical testing for TB; the latter are organized for discussion into three categories: (i) novel drugs (TMC207, SQ109, sudoterb [LL3858]); (ii) present first-line TB drugs being re-evaluated to optimize their efficacy (rifampicin, rifapentine); and (iii) currently licensed drugs for other indications and 'next-generation' compounds of the same chemical class being repurposed for TB (gatifloxacin and moxifloxacin; linezolid, PNU100480 and AZD5847; metronidazole, OPC-67683 and PA-824). PMID:21080738

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

    PubMed Central

    2013-01-01

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

  18. New diagnostics for tuberculosis: fulfilling patient needs first

    Microsoft Academic Search

    Jean-François Lemaire; Martina Casenghi

    2010-01-01

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

  19. Death by aortoesophageal fistula due to disseminated tuberculosis: a case study

    PubMed Central

    Na, Joo-Young; Kim, Youn-Shin; Choi, Yoo-Duk; Kim, Hyung-Seok; Park, Jong-Tae

    2015-01-01

    Tuberculosis remains a serious public health problem worldwide, especially in Korea. Although tuberculosis is generally considered a non-fatal chronic disease, deaths have occurred. In this case study, a 68-year-old man was admitted to the hospital with dyspepsia, vomiting, and abdominal pain. Nine hours later, he suffered severe hematemesis and died despite cardiopulmonary resuscitation. A medico-legal autopsy was performed and an external examination revealed no external injuries. However, an internal examination revealed an aortoesophageal fistula and a large amount of blood in the stomach. A histologic examination confirmed tuberculous mediastinitis with disseminated tuberculosis involving multiple organs, including the heart, lungs, liver, kidneys, and spleen. Both an aortoesophageal fistula and sudden death due to tuberculosis infection are rare. This paper reports the case of a fatal aortoesophageal fistula associated with disseminated tuberculosis.

  20. What steps do we need to take to improve diagnosis of tuberculosis in children?

    PubMed

    Venturini, Elisabetta; Remaschi, Giulia; Berti, Elettra; Montagnani, Carlotta; Galli, Luisa; de Martino, Maurizio; Chiappini, Elena

    2015-07-01

    Tuberculosis still represents a big global public health challenge. The diagnosis of tuberculosis and the differentiation between active and latent tuberculosis remain difficult, particularly in childhood, because of the lack of a gold standard test for diagnosis. In the last decade, novel diagnostic assays have been developed. Among immunologic tests, new assays based on the measurement of different cytokines released by specific T cells in response to Mycobacterium tuberculosis antigens, other than INF-?, have been investigated. Promising results rely on nucleic acid amplification techniques, also able to detect drugs resistance. Innovative research fields studied the modifications of CD27 expression in T cells as well as different host gene expression in response to M. tuberculosis. Further studies are needed to assess the diagnostic value and the accuracy of these new assays. PMID:25938981

  1. Antibiotics. Targeting DnaN for tuberculosis therapy using novel griselimycins.

    PubMed

    Kling, Angela; Lukat, Peer; Almeida, Deepak V; Bauer, Armin; Fontaine, Evelyne; Sordello, Sylvie; Zaburannyi, Nestor; Herrmann, Jennifer; Wenzel, Silke C; König, Claudia; Ammerman, Nicole C; Barrio, María Belén; Borchers, Kai; Bordon-Pallier, Florence; Brönstrup, Mark; Courtemanche, Gilles; Gerlitz, Martin; Geslin, Michel; Hammann, Peter; Heinz, Dirk W; Hoffmann, Holger; Klieber, Sylvie; Kohlmann, Markus; Kurz, Michael; Lair, Christine; Matter, Hans; Nuermberger, Eric; Tyagi, Sandeep; Fraisse, Laurent; Grosset, Jacques H; Lagrange, Sophie; Müller, Rolf

    2015-06-01

    The discovery of Streptomyces-produced streptomycin founded the age of tuberculosis therapy. Despite the subsequent development of a curative regimen for this disease, tuberculosis remains a worldwide problem, and the emergence of multidrug-resistant Mycobacterium tuberculosis has prioritized the need for new drugs. Here we show that new optimized derivatives from Streptomyces-derived griselimycin are highly active against M. tuberculosis, both in vitro and in vivo, by inhibiting the DNA polymerase sliding clamp DnaN. We discovered that resistance to griselimycins, occurring at very low frequency, is associated with amplification of a chromosomal segment containing dnaN, as well as the ori site. Our results demonstrate that griselimycins have high translational potential for tuberculosis treatment, validate DnaN as an antimicrobial target, and capture the process of antibiotic pressure-induced gene amplification. PMID:26045430

  2. Does M. tuberculosis genomic diversity explain disease diversity?

    PubMed Central

    Coscolla, Mireilla; Gagneux, Sebastien

    2010-01-01

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

  3. Performance of the Genotype® MTBDRPlus assay in the diagnosis of tuberculosis and drug resistance in Samara, Russian Federation

    Microsoft Academic Search

    Vladyslav Nikolayevskyy; Yanina Balabanova; Tatyana Simak; Nadezhda Malomanova; Ivan Fedorin; Francis Drobniewski

    2009-01-01

    BACKGROUND: Russia is a high tuberculosis (TB) burden country with a high prevalence of multidrug resistant tuberculosis (MDRTB). Molecular assays for detection of MDRTB on clinical specimens are not widely available in Russia. RESULTS: We performed an evaluation of the GenoType® MTBDRplus assay (HAIN Lifescience GmbH, Germany) on a total of 168 sputum specimens from individual patients at a public

  4. Arginine Adjunctive Therapy in Active Tuberculosis

    PubMed Central

    Shafaat, Omid; Sofian, Masoomeh; Kahbazi, Manijeh

    2015-01-01

    Background. Dietary supplementation has been used as a mechanism to augment the immune system. Adjunctive therapy with L-arginine has the potential to improve outcomes in active tuberculosis. Methods. In a randomized clinical trial 63 participants with smear-positive pulmonary tuberculosis in Markazi Province of Iran were given arginine or placebo for 4 weeks in addition to conventional chemotherapy. The final treatment success, sputum conversion, weight gain, and clinical symptoms after one and two months were considered as primary outcomes and secondary outcomes were ESR, CRP, and Hg. Data were collected and analyzed with SPSS software (ver. 18). Results. Arginine supplementation reduced constitutional symptoms (P = 0.032) in patients with smear-positive TB at the end of the first month of treatment. Arginine treated patients had significantly increased BMI at the end of the first and second months of treatment (P = 0.032 and P = 0.04) and a reduced CRP at the end of the first month of treatment (P = 0.03) versus placebo group. Conclusion. Arginine is useful as an adjunctive therapy in patients with active tuberculosis, in which the effects are more likely mediated by the increased production of nitric oxide and improved constitutional symptoms and weight gain. This trial is registered with Clinical Trials Registry of Iran: IRCT201211179855N2. PMID:25734013

  5. Pyrazinamide-Monoresistant Mycobacterium tuberculosis in the United States

    PubMed Central

    Hannan, Margaret M.; Desmond, Edward P.; Morlock, Glenn P.; Mazurek, Gerald H.; Crawford, Jack T.

    2001-01-01

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

  6. High-throughput screen of essential gene modules in Mycobacterium tuberculosis: a bibliometric approach

    PubMed Central

    2013-01-01

    Background Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). The annotation of functional genome and signaling network in M. tuberculosis are still not systematic. Essential gene modules are a collection of functionally related essential genes in the same signaling or metabolic pathway. The determination of essential genes and essential gene modules at genomic level may be important for better understanding of the physiology and pathology of M. tuberculosis, and also helpful for the development of drugs against this pathogen. The establishment of genomic operon database (DOOR) and the annotation of gene pathways have felicitated the genomic analysis of the essential gene modules of M. tuberculosis. Method Bibliometric approach has been used to perform a High-throughput screen for essential genes of M. tuberculosis strain H37Rv. Ant colony algorithm were used to identify the essential genes in other M. tuberculosis reference strains. Essential gene modules were analyzed by operon database DOOR. The pathways of essential genes were assessed by Biocarta, KEGG, NCI-PID, HumanCyc and Reactome. The function prediction of essential genes was analyzed by Pfam. Results A total approximately 700 essential genes were identified in M. tuberculosis genome. 40% of operons are consisted of two or more essential genes. The essential genes were distributed in 92 pathways in M. tuberculosis. In function prediction, 61.79% of essential genes were categorized into virulence, intermediary metabolism/respiration,cell wall related and lipid metabolism, which are fundamental functions that exist in most bacteria species. Conclusion We have identified the essential genes of M. tuberculosis using bibliometric approach at genomic level. The essential gene modules were further identified and analyzed. PMID:23687949

  7. Household contact investigation for tuberculosis in Vietnam: study protocol for a cluster randomized controlled trial

    PubMed Central

    2013-01-01

    Background Tuberculosis is an infectious disease that continues to cause considerable morbidity and mortality globally. Only 65% of patients worldwide are currently diagnosed. Contact investigation is a strategy that aims to increase case detection and reduce transmission of tuberculosis, yet there is little evidence to show its effectiveness. Methods/Design We will conduct a cluster randomized controlled trial of contact investigation within the national tuberculosis control program of Vietnam. Household contacts of patients with smear-positive pulmonary tuberculosis will be invited to attend district tuberculosis units for symptom screening, examination, and chest radiography on four occasions over a two-year period. The primary endpoint is clinically confirmed tuberculosis among contacts during the 24 months of follow-up, ascertained using capture-recapture analysis. Microbiologically proven tuberculosis and treatment completion rates among contacts diagnosed with tuberculosis will be secondary endpoints. The incremental cost-effectiveness ratio will be estimated. The study will have 80% power to detect a 50% increase in the primary endpoint in the active intervention arm compared with the control arm. The study will include 8,829 contacts in each of the active screening and control groups, within 70 districts in 8 provinces in Vietnam, in both rural and urban settings. Discussion The effectiveness of contact investigation as a tool for improved tuberculosis case finding has not been established. This cluster randomized trial will provide valuable operational information for national tuberculosis programs in high-prevalence countries, in order to select the most cost-effective strategies to improve tuberculosis case detection. Trial registration The ACT2 study has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000600044). PMID:24138766

  8. Advances in Mycobacterium tuberculosis therapeutics discovery utlizing structural biology

    PubMed Central

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

    2013-01-01

    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

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

    PubMed Central

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

    2014-01-01

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

  10. Epidemiological basis of tuberculosis eradication in an advanced country

    PubMed Central

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

    1959-01-01

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

  11. Survival mechanisms of pathogenic Mycobacterium tuberculosis H37Rv.

    PubMed

    Meena, Laxman S; Rajni

    2010-06-01

    Mycobacterium tuberculosis H(37)Rv is a highly successful pathogen and its success fully relies on its ability to utilize macrophages for its replication and, more importantly, the macrophage should remain viable to host the Mycobacterium. Despite the fact that these phagocytes are usually very effective in internalizing and clearing most of the bacteria, M. tuberculosis H(37)Rv has evolved a number of very effective survival strategies, including: (a) the inhibition of phagosome-lysosome fusion; (b) the inhibition of phagosome acidification; (c) the recruitment and retention of tryptophan-aspartate containing coat protein on phagosomes to prevent their delivery to lysosomes; and (d) the expression of members of the host-induced repetitive glycine-rich protein family of proteins. However, the mechanisms by which M. tuberculosis H(37)Rv enters the host cell, circumvents host defenses and spreads to neighboring cell are not completely understood. Therefore, a better understanding of host-pathogen interaction is essential if the global tuberculosis pandemic is ever to be controlled. This review addresses some of the pathogenic strategies of the M. tuberculosis H(37)Rv that aids in its survival and pathogenicity. PMID:20553485

  12. Spoligotyping of Mycobacterium tuberculosis complex isolates using hydrogel oligonucleotide microarrays.

    PubMed

    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

    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

  13. Tuberculosis of spine

    PubMed Central

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

    2010-01-01

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

  14. 21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  15. 21 CFR 866.3370 - Mycobacterium tuberculosis immunofluorescent reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  16. Tuberculosis in children.

    PubMed

    Marais, Ben J

    2014-10-01

    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

  17. System-level strategies for studying the metabolism of Mycobacterium tuberculosis

    PubMed Central

    Beste, Dany J. V.

    2010-01-01

    Despite decades of research many aspects of the biology of Mycobacterium tuberculosis remain unclear and this is reflected in the antiquated tools available to treat and prevent tuberculosis and consequently this disease remains a serious public health problem. Important discoveries linking M. tuberculosis's metabolism and pathogenesis have renewed interest in this area of research. Previous experimental studies were limited to the analysis of individual genes or enzymes whereas recent advances in computational systems biology and high throughput experimental technologies now allow metabolism to be studied on a genome scale. Here we discuss the progress being made in applying system level approaches to studying the metabolism of this important pathogen. The information from these studies will fundamentally change our approach to tuberculosis research and lead to new targets for therapeutic drugs and vaccines. PMID:20938502

  18. Diabetes and immunity to tuberculosis

    PubMed Central

    Martinez, Nuria; Kornfeld, Hardy

    2014-01-01

    Summary The dual burden of tuberculosis and diabetes has attracted much attention in the past decade as diabetes prevalence has increased dramatically in countries already afflicted with a high burden of tuberculosis. The confluence of these two major diseases presents a serious threat to global public health; at the same time it also presents an opportunity to learn more about the key elements of human immunity to tuberculosis that may be relevant to the general population. Some effects of diabetes on innate and adaptive immunity which are potentially relevant to tuberculosis defense have been identified, but have yet to be verified in humans and are unlikely to fully explain the interaction of these two disease states. This review provides an update on the clinical and epidemiological features of tuberculosis in the diabetic population and relates them to recent advances in understanding the mechanistic basis of tuberculosis susceptibility and other complications of diabetes. Issues that merit further investigation, such as geographic host and pathogen differences in the diabetes/tuberculosis interaction, the role of hyperglycemia-induced epigenetic reprogramming in immune dysfunction and the impact of diabetes on lung injury and fibrosis caused by tuberculosis, are highlighted in this review. PMID:24448841

  19. Computed tomography of intracranial tuberculosis

    Microsoft Academic Search

    J. R. Jinkins

    1991-01-01

    The many clinico-radiological manifestations of intracranial tuberculosis have been well documented; however, few long-term retrospective serial studies of large series of patients on therapy have been reported utilizing computed imaging. The computed tomographic appearance, sequential periodic evolution, and final outcome of all patients with cranial tuberculosis seen at this institution in a period of ten years have been evaluated. A

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

    Microsoft Academic Search

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

    2003-01-01

    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

  1. Protein targets for structure-based anti- Mycobacterium tuberculosis drug discovery

    Microsoft Academic Search

    Zhiyong Lou; Xiaoxue Zhang

    2010-01-01

    Mycobacterium tuberculosis, which belongs to the genus Mycobacterium, is the pathogenic agent for most tuberculosis (TB). As TB remains one of the most rampant infectious diseases, causing morbidity\\u000a and death with emergence of multi-drug-resistant and extensively-drug-resistant forms, it is urgent to identify new drugs\\u000a with novel targets to ensure future therapeutic success. In this regards, the structural genomics of M.

  2. A Critical Role for CD8 T Cells in a Nonhuman Primate Model of Tuberculosis

    Microsoft Academic Search

    Crystal Y. Chen; Dan Huang; Richard C. Wang; Ling Shen; Gucheng Zeng; Shuyun Yao; Yun Shen; Lisa Halliday; Jeff Fortman; Milton McAllister; Jim Estep; Robert Hunt; Daphne Vasconcelos; George Du; Steven A. Porcelli; Michelle H. Larsen; William R. Jacobs; Barton F. Haynes; Norman L. Letvin; Zheng W. Chen

    2009-01-01

    The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell–mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the specificity and functions of CD8 T cells, such as the expression

  3. DAHP synthase from Mycobacterium tuberculosis H37Rv: cloning, expression, and purification of functional enzyme

    Microsoft Academic Search

    Caroline Rizzi; Jeverson Frazzon; Fernanda Ely; Patrícia G. Weber; Isabel O. da Fonseca; Michelle Gallas; Jaim S. Oliveira; Maria A. Mendes; Bibiana M. de Souza; Mário S. Palma; Diógenes S. Santos; Luiz A. Basso

    2005-01-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality due to a bacterial pathogen. According to the 2004 Global TB Control Report of the World Health Organization, there are 300,000 new cases per year of multi-drug resistant strains (MDR-TB), defined as resistant to isoniazid and rifampicin, and 79% of MDR-TB cases are now “super strains,” resistant to

  4. Thyroid Tuberculosis in Southeastern Turkey: Is This the Resurgence of a Stubborn Disease?

    Microsoft Academic Search

    Nilgun Sogutcu; Zulfu Arikanoglu; Sule Bakir; Abdullah Ulku; Yusuf Yagmur

    Background  While tuberculosis (TB) has been found in many parts of the body, involvement of the thyroid gland is rare. In this study\\u000a we describe the clinicopathological characteristics of seven patients with primary thyroid tuberculosis (TTB).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  This report is a retrospective case study of seven patients with thyroid tuberculosis who were treated surgically in our clinic\\u000a between 2004 and 2010. Data

  5. Immune Thrombocytopenia in Tuberculosis: Causal or Coincidental?

    PubMed Central

    Srividya, Gopalakrishnan; Nikhila, Gopalakrishna Pillai Syamala; Kaushik, Adusumilli Venkatakrishna; Jayachandran, Kuppusamy

    2014-01-01

    Immune thrombocytopenia is a relatively rare hematological manifestation in tuberculosis. We report two cases of immune thrombocytopemia, one in sputum positive pulmonary tuberculosis and the other in miliary tuberculosis. Antituberculous drugs and immunosuppressive therapy corrected the thrombocytopenia in both patients. Our case reports stress that tuberculosis should be considered during the evaluation of immune thrombocytopenia, and also highlights the safety of immunosuppressive therapy during active tuberculosis along with antituberculous drugs. PMID:25191056

  6. Deciphering sulfoglycolipids of Mycobacterium tuberculosis.

    PubMed

    Layre, Emilie; Paepe, Diane Cala-De; Larrouy-Maumus, Gérald; Vaubourgeix, Julien; Mundayoor, Sathish; Lindner, Buko; Puzo, Germain; Gilleron, Martine

    2011-06-01

    For 4 decades, in vivo and in vitro studies have suggested that sulfoglycolipids (SGLs) play a role in the virulence or pathogenesis of the tubercle bacilli. However, the SGL structure and biosynthesis pathway remain only partially elucidated. Using the modern tools of structural analysis, including MALDI-time-of-flight MS, MS/MS, and two-dimensional NMR, we reevaluated the structure of the different SGL acyl (di-, tri-, and tetra-acylated) forms of the reference strain Mycobacterium tuberculosis H37Rv, as well as those produced by the mmpL8 knockout strains previously described to intracellularly accumulate di-acylated SGL. We report here the identification of new acyl forms: di-acylated SGL esterified by simple fatty acids only, as well as mono-acylated SGL bearing a hydroxyphthioceranoic acid, which were characterized in the wild-type strain. In a clinical strain, a complete family of mono-acylated SGLs was characterized in high abundance for the first time. For the mmpL8 mutant, SGLs were found to be esterified i) by an oxophthioceranoic acid, never observed so far, and ii) at nonconventional positions in the case of the unexpected tri-acylated forms. Our results further confirm the requirement of MmpL8 for the complete assembly of the tetra-acylated forms of SGL and also provide, by the discovery of new intermediates, insights in terms of the possible SGL biosynthetic pathways. PMID:21482713

  7. Tuberculosis and Crohn's Disease Revisited.

    PubMed

    Onal, Ibrahim Koral; Kekilli, Murat; Tanoglu, Alpaslan; Erdal, Harun; Ibis, Mehmet; Arhan, Mehmet

    2015-06-01

    Crohn's Disease (CD) and Intestinal Tuberculosis (ITB) share confusingly similar clinical, endoscopic, radiological and pathological manifestations. There is no simple test for differentiating ITB from CD. Although there are a number of sensitive and specific parameters for distinguishing between CD and ITB, the differential diagnosis still remains challenging and both clinical suspicion and appropriate clinical and laboratory studies are required to establish the diagnosis. Correct diagnosis is crucial because the therapy strategies of the two diseases are dramatically different. Treatment of ITB with immunosuppressive agents would lead to worsening of the patients' condition. Likewise, unnecessary antituberculosis therapy would delay the treatment of CD. Another important consideration is the risk of reactivation TB in patients with inflammatory bowel diseases which has been significantly increased following the widespread use of anti-Tumor Necrosis Factor Alpha (TNF-?) therapy. The majority of reactivation cases are extrapulmonary or disseminated TB. And it is widely recommended that patients with IBD who are to receive TNF inhibitor therapy should be screened for evidence of latent TB. This paper mainly reviews current literature on differential diagnosis between CD and ITB, and summarizes strategies to reduce the TB risk among candidates for TNF antagonist therapy in this specific patient population. PMID:26100999

  8. Comparison of membrane proteins of Mycobacterium tuberculosis H37Rv and H37Ra strains

    Microsoft Academic Search

    Hiwa Målen; Gustavo A De Souza; Sharad Pathak; Tina Søfteland; Harald G Wiker

    2011-01-01

    BACKGROUND: The potential causes for variation in virulence between distinct M. tuberculosis strains are still not fully known. However, differences in protein expression are probably an important factor. In this study we used a label-free quantitative proteomic approach to estimate differences in protein abundance between two closely related M. tuberculosis strains; the virulent H37Rv strain and its attenuated counterpart H37Ra.

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

    Microsoft Academic Search

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

    2011-01-01

    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

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

    Microsoft Academic Search

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

    2006-01-01

    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

  11. Tuberculin skin testing underestimates a high prevalence of latent tuberculosis infection in hemodialysis patients

    Microsoft Academic Search

    Martina Sester; Urban Sester; Peter Clauer; Gunnar Heine; Ulrich Mack; Thomas Moll; Gerhard W. Sybrecht; Ajit Lalvani; Hans Köhler

    2004-01-01

    Tuberculin skin testing underestimates a high prevalence of latent tuberculosis infection in hemodialysis patients.BackgroundIdentification of latent Mycobacterium tuberculosis infection in hemodialysis patients is hampered by reduced sensitivity of the established tuberculin skin test. We investigated whether in vitro quantitation of purified protein derivative (PPD)–specific T cells using a rapid 6-hour assay may represent an alternative approach for detecting latent infection.MethodsOne

  12. MPT 64 Antigen detection for Rapid confirmation of M.tuberculosis isolates

    Microsoft Academic Search

    Vijay GS Kumar; Tejashree A Urs; Rajani R Ranganath

    2011-01-01

    Background  A new rapid Immunochromatographic test kit(SD MPT64TB Ag Kit) for detection of MPT 64 Antigen in M. tuberculosis isolates using mouse monoclonal MPT 64 Antibody developed by SD Bioline, South Korea was evaluated for rapid identification\\u000a of M. tuberculosis isolates. We also assessed the sensitivity, specificity and predictive values of this kit. The test kit has an excellent\\u000a sensitivity, specificity,

  13. Highly structured genetic diversity of the Mycobacterium tuberculosis population in

    E-print Network

    Choisy, Marc

    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

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

    PubMed Central

    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

    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

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

    Microsoft Academic Search

    Dermot Maher

    2010-01-01

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

  16. Redox biology of Mycobacterium tuberculosis H37Rv: protein-protein interaction between GlgB and WhiB1 involves exchange of thiol-disulfide

    Microsoft Academic Search

    Saurabh Garg; Richa Bajpai; KV Radha Kishan; Pushpa Agrawal

    2009-01-01

    BACKGROUND: Mycobacterium tuberculosis, an intracellular pathogen encounters redox stress throughout its life inside the host. In order to protect itself from the redox onslaughts of host immune system, M. tuberculosis appears to have developed accessory thioredoxin-like proteins which are represented by ORFs encoding WhiB-like proteins. We have earlier reported that WhiB1\\/Rv3219 is a thioredoxin like protein of M. tuberculosis and

  17. Minor contribution of mutations at iniA codon 501 and embC-embA intergenic region in ethambutol-resistant clinical Mycobacterium tuberculosis isolates in Kuwait

    Microsoft Academic Search

    Al-Anoud Jaber; Suhail Ahmad; Eiman Mokaddas

    2009-01-01

    BACKGROUND: Ethambutol (EMB) is a first-line drug for the treatment of tuberculosis (TB). Resistance to EMB in Mycobacterium tuberculosis isolates is mediated by mutations in several genes involved in arabinan synthesis notably three emb (arabinosyl transferase) and iniA (isoniazid-inducible) genes. Most epidemiologically unrelated EMB-resistant M. tuberculosis strains contain mutations at embB codons 306, 406 and 497, embC-embA intergenic region (IGR)

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

    PubMed Central

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

    2014-01-01

    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

  19. Increase in the Number of Tuberculosis Cases Treated following Tuberculin Skin Testing in First-Year Schoolchildren in Madagascar

    PubMed Central

    Ratovoson, Rila; Raharimanga, Voamalala; Rakotosamimanana, Niaina; Ravaloson, B.; Ratsitorahina, Maherisosa; Randremanana, Rindra; Ramarokoto, Herimanana; Rajatonirina, Soatiana; Rasolofo, Voahangy; Richard, Vincent

    2014-01-01

    Background Tuberculosis continues to cause unacceptably high levels of disease and death worldwide. Active preventive strategies are required to improve tuberculosis control and to increase the number of cases treated in developing countries. The aim of this study was to evaluate the utility of the tuberculin skin test (TST) in first-year schoolchildren as a means of increasing the number of tuberculosis cases detected through the screening of close contacts. Methods All members of the households of 90 schoolchildren assigned to three groups on the basis of TST category (?5 mm, [5–15)mm, ?15 mm) were screened for sputum smear-positive pulmonary tuberculosis. The percentage detection of tuberculosis in close contacts was compared between TST categories. Results We identified 433 close contacts of the 90 schoolchildren, who were then evaluated for tuberculosis. We identified 11 cases of pulmonary tuberculosis among the close contacts (7 already on treatment and 4 previously undiagnosed): 0 in TST category ?5 mm, 3 in TST category [5–15) mm and 8 in TST category ?15 mm). This approach increased the detection of tuberculosis cases by a factor of 1.6 in first-year schoolchildren of the TST ?5 mm group. Conclusion TST in first-year schoolchildren is a potentially effective method for improving the detection of tuberculosis in close contacts. PMID:24743554

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

    PubMed

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

    2014-01-01

    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

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

    PubMed Central

    2014-01-01

    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

  2. Energy Metabolism and Drug Efflux in Mycobacterium tuberculosis

    PubMed Central

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

    2014-01-01

    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

  3. Tuberculosis: Past, Present and Future

    PubMed Central

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

    1979-01-01

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

  4. Concomitant acromioclavicular and miliary tuberculosis

    PubMed Central

    Agathangelidis, Filon; Boutsiadis, Achilleas; Fouka, Evangelia; Karataglis, Dimitrios

    2013-01-01

    A 48-year-old man was being treated unsuccessfully for miliary tuberculosis for 5?months until he presented with acromioclavicular joint swelling. Imaging of the shoulder revealed destruction of the acromioclavicular joint and the patient was brought to the operating theatre and underwent the excision of the distal end of the clavicle, synovectomy and drainage of the abscess. Surgery was followed by prompt clinical, functional and radiological improvement. Histopathology confirmed the diagnosis of acromioclavicular tuberculosis. Resistance to appropriate antituberculous treatment in patients with miliary tuberculosis can sometimes be a result of undiagnosed extrapulmonary site of infection. PMID:23813516

  5. Exosomes carrying mycobacterial antigens can protect mice against an M. tuberculosis Infection

    PubMed Central

    Cheng, Yong; Schorey, Jeffery S.

    2014-01-01

    Summary 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

  6. Identification of proteins from Mycobacterium tuberculosis missing in attenuated Mycobacterium bovis BCG strains.

    PubMed

    Mattow, J; Jungblut, P R; Schaible, U E; Mollenkopf, H J; Lamer, S; Zimny-Arndt, U; Hagens, K; Müller, E C; Kaufmann, S H

    2001-08-01

    A proteome approach, combining high-resolution two-dimensional electrophoresis (2-DE) with mass spectrometry, was used to compare the cellular protein composition of two virulent strains of Mycobacterium tuberculosis with two attenuated strains of Mycobacterium bovis Bacillus Calmette-Guerin (BCG), in order to identify unique proteins of these strains. Emphasis was given to the identification of M. tuberculosis specific proteins, because we consider these proteins to represent putative virulence factors and interesting candidates for vaccination and diagnosis of tuberculosis. The genome of M. tuberculosis strain H37Rv comprises nearly 4000 predicted open reading frames. In contrast, the separation of proteins from whole mycobacterial cells by 2-DE resulted in silver-stained patterns comprising about 1800 distinct protein spots. Amongst these, 96 spots were exclusively detected either in the virulent (56 spots) or in the attenuated (40 spots) mycobacterial strains. Fifty-three of these spots were analyzed by mass spectrometry, of which 41 were identified, including 32 M. tuberculosis specific spots. Twelve M. tuberculosis specific spots were identified as proteins, encoded by genes previously reported to be deleted in M. bovis BCG. The remaining 20 spots unique for M. tuberculosis were identified as proteins encoded by genes that are not known to be missing in M. bovis BCG. PMID:11565788

  7. Stable association between strains of Mycobacterium tuberculosis and their human host populations

    PubMed Central

    Hirsh, Aaron E.; Tsolaki, Anthony G.; DeRiemer, Kathryn; Feldman, Marcus W.; Small, Peter M.

    2004-01-01

    Mycobacterium tuberculosis is an important human pathogen in virtually every part of the world. Here we investigate whether distinct strains of M. tuberculosis infect different human populations and whether associations between host and pathogen populations are stable despite global traffic and the convergence of diverse strains of the pathogen in cosmopolitan urban centers. The recent global movement and transmission history of 100 M. tuberculosis isolates was inferred from a molecular epidemiologic study of tuberculosis that spans 12 years. Genetic relationships among these isolates were deduced from the distribution of large genomic deletions, which were identified by DNA microarray and confirmed by PCR and sequence analysis. Phylogenetic analysis of these deletions indicates that they are unique event polymorphisms and that horizontal gene transfer is extremely rare in M. tuberculosis. In conjunction with the epidemiological data, phylogenies reveal three large phylogeographic regions. A host's region of origin is predictive of the strain of tuberculosis he or she carries, and this association remains strong even when transmission takes place in a cosmopolitan urban center outside of the region of origin. Approximate dating of the time since divergence of East Asian and Philippine clades of M. tuberculosis suggests that these lineages diverged centuries ago. Thus, associations between host and pathogen populations appear to be highly stable. PMID:15041743

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

    PubMed Central

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

    2013-01-01

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

  9. New vaccines against tuberculosis.

    PubMed

    Mark Doherty, T

    2004-07-01

    In September 2000, recognizing the effect of communicable diseases as obstacles to development in poorer countries, the European Commission assembled a special round table on 'accelerated action targeted at major communicable diseases within the context of poverty reduction'. The three major communicable diseases discussed were tuberculosis (TB), malaria and HIV. One outcome of this discussion was a workshop examining issues related to the fight against TB in Africa, which took place in Gorée, Sénégal, in May 2001. The timing was propitious, as new vaccines for TB (recombinant MVA and BCG, and adjuvanated recombinant fusion proteins or peptide constructs), are just beginning to enter human clinical trials. All but the last of these have shown promise in animal models, up to and including non-human primates, and all are strongly immunogenic and apparently safe. Humans trials for safety and efficacy are thus the logical next step. This review summarizes recent advances in tuberculosis vaccine development, with a special emphasis on issues raised at the Gorée meeting about testing and deploying new generation vaccines in TB-endemic areas such as Africa. PMID:15228493

  10. Educating workers about tuberculosis.

    PubMed

    Watson, L H; Rosen, J D

    1994-01-01

    At a state penitentiary, workers are told that the communicable disease unit is a safe environment in which to work due to the negative air pressure in the isolation rooms and the improved ventilation system. However, nobody is trained to monitor the system or understands the role of negative air pressure, and isolation room doors are occasionally left open. As a result, workers are reluctant to work in the unit. At a soup kitchen, workers refuse to serve people with HIV due to fear of tuberculosis transmission. They have heard that people infected with HIV are likely to have TB and, therefore, to protect themselves, they feel the soup kitchen should not serve people with HIV. In a large, urban social service agency, workers buy masks and begin wearing them to work when they hear a coworker has tuberculosis. Pictures of them in the newspaper instigate a string of similar actions in other agencies. Emergency room workers in a city hospital have been told they are not at increased risk of contracting TB, because they do not have prolonged contact with infectious patients. However, when they discover that several coworkers tested positive on PPD screening tests, they go to their union demanding action. PMID:7878495

  11. Mycobacterium tuberculosis arabinomannan–protein conjugates protect against tuberculosis

    Microsoft Academic Search

    Beston Hamasur; Melles Haile; Andrzej Pawlowski; Ulf Schröder; Ann Williams; Graham Hatch; Graham Hall; Philip Marsh; Gunilla Källenius; Stefan B. Svenson

    2003-01-01

    Lipoarabinomannan (LAM) is a major structural surface component of mycobacteria. Arabinomannan (AM) oligosaccharides derived from LAM of Mycobacterium tuberculosis H37Rv were isolated and covalently conjugated to tetanus toxoid (TT) or to short-term culture filtrate proteins (antigen 85B (Ag85B) or a 75kDa protein) from M. tuberculosis strain Harlingen. The different AM oligosaccharide (AMOs)–protein conjugate vaccine candidates proved to be highly immunogenic,

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

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

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

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

    PubMed Central

    Cruz-Hervert, Luis Pablo; García-García, Lourdes; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Cano-Arellano, Bulmaro; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Báez-Saldaña, Renata; Téllez-Vázquez, Norma; Nava-Mercado, Ariadna; Juárez-Sandino, Luis; Delgado-Sánchez, Guadalupe; Fuentes-Leyra, César Alejandro; Montero-Campos, Rogelio; Martínez-Gamboa, Rosa Areli; Small, Peter M.; Sifuentes-Osornio, José; Ponce-de-León, Alfredo

    2012-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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

  15. [Treatment of extrapulmonary tuberculosis and complicated forms of pulmonary tuberculosis].

    PubMed

    2008-09-01

    Tuberculosis is one of the most important health problems worldwide. In developed countries there is an increased number of cases due to different reasons. The most likely determinant cause is from immigrants coming from high endemic areas. This phenomenon is a direct cause of the increase in extrapulmonary and complicated pulmonary forms of tuberculosis. There are only a few controlled clinical trials evaluating therapies for extrapulmonary tuberculosis. Consequently, documented evidence is scarce, particularly in paediatrics. The majority of therapeutic recommendations are based on series of cases or expert opinions, with a lack of uniformity provided by the different consensus of the main scientific societies. The main objective of this fourth consensus by the Tuberculosis Study Group of the Spanish Society of Paediatric Infectious Diseases (Sociedad Española de Infectología Pediátrica, SEIP) is to perform a thorough revision of the data obtained from scientific literature, in order to establish recommendations for the treatment of extrapulmonary tuberculosis and complicated forms of pulmonary tuberculosis, adapted to the characteristics and drugs available in Spain. PMID:18775275

  16. A conformal Bayesian network for classification of Mycobacterium tuberculosis complex lineages

    PubMed Central

    2010-01-01

    Background We present a novel conformal Bayesian network (CBN) to classify strains of Mycobacterium tuberculosis Complex (MTBC) into six major genetic lineages based on two high-throuput biomarkers: mycobacterial interspersed repetitive units (MIRU) and spacer oligonucleotide typing (spoligotyping). MTBC is the causative agent of tuberculosis (TB), which remains one of the leading causes of disease and morbidity world-wide. DNA fingerprinting methods such as MIRU and spoligotyping are key components in the control and tracking of modern TB. Results CBN is designed to exploit background knowledge about MTBC biomarkers. It can be trained on large historical TB databases of various subsets of MTBC biomarkers. During TB control efforts not all biomarkers may be available. So, CBN is designed to predict the major lineage of isolates genotyped by any combination of the PCR-based typing methods: spoligotyping and MIRU typing. CBN achieves high accuracy on three large MTBC collections consisting of over 34,737 isolates genotyped by different combinations of spoligotypes, 12 loci of MIRU, and 24 loci of MIRU. CBN captures distinct MIRU and spoligotype signatures associated with each lineage, explaining its excellent performance. Visualization of MIRU and spoligotype signatures yields insight into both how the model works and the genetic diversity of MTBC. Conclusions CBN conforms to the available PCR-based biological markers and achieves high performance in identifying major lineages of MTBC. The method can be readily extended as new biomarkers are introduced for TB tracking and control. An online tool (http://www.cs.rpi.edu/~bennek/tbinsight/tblineage) makes the CBN model available for TB control and research efforts. PMID:20438651

  17. SUBFOSSIL REMAINS OF Camptocercus lilljeborgii (ANOMOPODA, CHYDORIDAE)

    Microsoft Academic Search

    Kaarina Sarmaja-Korjonen

    Subfossil remains of Camptocercus lilljeborgii were abundant in the sediments of a core taken from a presently paludi- fied shore of Lake Väike Juusa, southern Estonia. This made it possible to identify and describe the subfossil remains of the taxon, especially headshields and shells. The remains resemble those of Camptocercus rectirostris but differ in details that make the identification easy.

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

    PubMed

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

    2014-12-01

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

  19. A mobile health approach to tuberculosis contact tracing in resource-limited settings.

    PubMed

    Ha, Yoonhee P; Littman-Quinn, Ryan; Antwi, Cynthia; Seropola, Gorewang; Green, Rebecca S; Tesfalul, Martha A; Ho-Foster, Ari; Luberti, Anthony A; Holmes, John H; Steenhoff, Andrew P; Kovarik, Carrie L

    2013-01-01

    Tuberculosis remains a leading cause of morbidity and mortality worldwide. In 2011, there were 8.7 million new cases and 1.4 million deaths from the disease, with >95% of these deaths taking place in low- and middle-income countries [1]. Contact tracing prevents the spread of tuberculosis by identifying and screening a case's contacts and referring symptomatic individuals to health care providers. Traditionally, contact tracing has been conducted with paper forms, which can lead to considerable inefficiencies in data collection, storage, and retrieval. These inefficiencies are problematic as tuberculosis can continue to spread if disruption of disease transmission is delayed. Mobile health approaches to tuberculosis contact tracing remain largely unaddressed and limited to management and monitoring of multidrug-resistant tuberculosis [2].To address these limitations, a mobile health application that digitizes and automates contact tracing was developed. This poster presents work currently underway to evaluate this new approach in Botswana, which has the tenth highest incidence rate of tuberculosis in the world [3]. Operational considerations for implementing a mobile health approach to contact tracing in resource-limited settings are also presented. PMID:23920962

  20. Molecular epidemiology of tuberculosis in the Tula area, Central Russia, before the introduction of the Directly Observed Therapy Strategy.

    PubMed

    Dubiley, S; Ignatova, A; Mukhina, T; Nizova, A; Blagodatskikh, S; Stepanshina, V; Shemyakin, I

    2010-09-01

    Tuberculosis remains a major public health concern in Russia and worldwide. Given the great geographical, ethnic, and socio-economic heterogeneities between Russian regions, epidemiological data cannot be generalized from a regional to a country-wide level. We present data on the epidemiology of tuberculosis in Central Russia. We report a high level of resistance to major antitubercular drugs in both new and previously treated patients in the region. The level of drug resistance in new cases was almost twice as high as the estimated average national level. The Mycobacterium tuberculosis strains that circulated in the region were predominantly represented by LAM-RUS and Beijing genotypes. These two lineages were strongly associated with drug resistance and clustering. Using molecular epidemiology techniques, we showed a high interpenetration by M. tuberculosis strains between the prison and civilian populations. A limited number of identical strains were responsible for the majority of drug-resistant tuberculosis cases in both settings. PMID:19886904

  1. Tuberculosis care: an evaluability study

    PubMed Central

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

    2014-01-01

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

  2. Tuberculosis presenting as epitrochlear lymphadenitis.

    PubMed

    Crum, Nancy F

    2003-01-01

    Epitrochlear lymphadenitis is an uncommon presentation of extrapulmonary tuberculosis in an immunocompetent host. This case report describes the third case in the literature and provides a review of the literature. PMID:14723371

  3. Molecular patterns of multidrug resistance of Mycobacterium tuberculosis in Georgia

    PubMed Central

    Shubladze, N.; Tadumadze, N.; Bablishvili, N.

    2014-01-01

    Background Tuberculosis (TB) infections caused by multidrug-resistant Mycobacterium tuberculosis (MDR MTB) remain a significant public health concern worldwide. Georgia has a high prevalence of MDR MTB. The genetic mechanisms underlying the emergence of MDR MTB strains in this region are poorly understood and need to be determined for developing better strategies for TB control. This study investigated the frequency of major drug resistance mutations across rpoB, katG and inhA loci of Georgian MDR MTB strains and explored differences between new and previously treated patients. A total of 634 MTB strains were examined for which an MDR phenotype had been previously determined by the proportions method. The GenoType®MTBDRplus system was applied to screen the strains for the presence of rpoB (S531L, H526D, H526Y, and D516V), katG (S315T) and inhA promoter region (C15T and T8C) mutations. The target loci were amplified by PCR and then hybridized with the respective site-specific and wild type (control) probes. Results Out of the 634 isolates tested considered by phenotypic testing to be resistant to RIF and INH, this resistance was confirmed by the GenoType®MTBDRplus assay in 575 (90.7%) isolates. RIF resistance was seen in 589 (92.9%) and INH resistance was seen in 584 (92.1%); 67.2% and 84.3% of MDR strains harbored respectively rpoB S531L and katG S315T mutations (generally known as having low or no fitness cost in MTB). The inhA C15T mutation was detected in 22.6% of the strains, whereas rpoB H526D, rpoB H526Y, rpoB D516V and inhA T8C were revealed at a markedly lower frequency (?5.2%). The specific mutations responsible for the RIF resistance of 110 isolates (17.4%) could not be detected as no corresponding mutant probe was indicated in the assay. There was no specific association of the presence of mutations with the gender/age groups. All types of prevailing mutations had higher levels in new cases. A great majority of the Georgian MDR MTB strains have a strong preference for the drug resistance mutations carrying no or low fitness cost. Thus, it can be suggested that MDR MTB strains with such mutations will continue to arise in Georgia at a high frequency even in the absence of antibiotic pressure. PMID:24904758

  4. Tuberculosis in the Inuit Community of Quebec, Canada

    Microsoft Academic Search

    Dao Nguyen; Jean-Francois Proulx; Jennifer Westley; Louise Thibert; Serge Dery; Marcel A. Behr

    2003-01-01

    In low-incidence countries targeting tuberculosis (TB) elimination, TB remains a problem of a few high-risk groups. In Canada, Aborigi- nals, and particularly the Arctic Inuit communities, have witnessed dramatic decreases in TB during the 1960s to 1970s, but rates re- main at least 10 to 20 times higher than the national average. We are describing the results of an integrated

  5. Mediastinal Lymphadenopathy: Melioidosis Mimicking Tuberculosis

    PubMed Central

    Chan, Hiang Ping; Yip, Hwee Seng

    2015-01-01

    Melioidosis has protean manifestations and often mimics other disease processes. We present a case of a gentleman presenting with chronic cough whose initial radiographic findings of a cavitatory lung lesion and mediastinal lymphadenopathy were suggestive of tuberculosis. This case highlights the important role that bronchoscopy and endobronchial ultrasound can play in the diagnosis of melioidosis in patients presenting with mediastinal lymphadenopathy whose initial microbiological findings from sputum are negative for tuberculosis.

  6. Mediastinal Lymphadenopathy: Melioidosis Mimicking Tuberculosis.

    PubMed

    Chan, Hiang Ping; Yip, Hwee Seng

    2015-06-01

    Melioidosis has protean manifestations and often mimics other disease processes. We present a case of a gentleman presenting with chronic cough whose initial radiographic findings of a cavitatory lung lesion and mediastinal lymphadenopathy were suggestive of tuberculosis. This case highlights the important role that bronchoscopy and endobronchial ultrasound can play in the diagnosis of melioidosis in patients presenting with mediastinal lymphadenopathy whose initial microbiological findings from sputum are negative for tuberculosis. PMID:26060421

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

    Microsoft Academic Search

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

    2010-01-01

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

  8. Isoniazid’s Bactericidal Activity Ceases because of the Emergence of Resistance, Not Depletion of Mycobacterium tuberculosis in the Log Phase of Growth

    Microsoft Academic Search

    Tawanda Gumbo; Arnold Louie; Weiguo Liu; David Brown

    2007-01-01

    Background. It is believed that the cessation of isoniazid's early bactericidal activity during the initial phase of antituberculosis therapy is due to the depletion of Mycobacterium tuberculosis in the exponential phase of growth. We examined the veracity of this cornerstone belief. Methods. We used an in vitro infection model in which M. tuberculosis was exposed to isoniazid concentration- time profiles

  9. Use of the GenoType® MTBDRplus assay to assess drug resistance of Mycobacterium tuberculosis isolates from patients in rural Uganda

    Microsoft Academic Search

    Joel Bazira; Benon B Asiimwe; Moses L Joloba; Fred Bwanga; Mecky I Matee

    2010-01-01

    BACKGROUND: Drug resistance levels and patterns among Mycobacterium tuberculosis isolates from newly diagnosed and previously treated tuberculosis patients in Mbarara Uganda were investigated. METHODS: We enrolled, consecutively, all newly diagnosed and previously treated smear-positive TB patients aged ? 18 years. Isolates were tested for drug resistance against rifampicin (RIF) and isoniazid (INH) using the Genotype® MDRTBplus assay and results were

  10. First insights into the genetic diversity of Mycobacterium tuberculosis isolates from HIV-infected Mexican patients and mutations causing multidrug resistance

    Microsoft Academic Search

    Rocio Lopez-Alvarez; Claudia Badillo-Lopez; Jorge F Cerna-Cortes; Ivan Castillo-Ramirez; Sandra Rivera-Gutierrez; Addy C Helguera-Repetto; Diana Aguilar; Rogelio Hernandez-Pando; Sofia Samper; Jorge A Gonzalez-y-Merchand

    2010-01-01

    BACKGROUND: The prevalence of infections with Mycobacterium tuberculosis (MTb) and nontuberculous mycobacteria (NTM) species in HIV-infected patients in Mexico is unknown. The aims of this study were to determine the frequency of MTb and NTM species in HIV-infected patients from Mexico City, to evaluate the genotypic diversity of the Mycobacterium tuberculosis complex strains, to determine their drug resistance profiles by

  11. Immunodiagnosis of tuberculosis: An update.

    PubMed

    Bhatia, A S; Kumar, Satish; Harinath, B C

    2003-07-01

    Tuberculosis is still a major health problem in most developing countries and its incidence is rising in many developed countries. This resurgence has been attributed to the HIV epidemic and TB has been declared as a global health emergency by WHO in 1993. The diagnosis of tuberculosis mainly depends upon initial clinical suspicion and radiographic findings with subsequent bacteriological confirmation by sputum smear examination and culture. Lack of sensitivity in smear examination, non specificity of radiological findings, extended tum around time ofMycobacterium tuberculosis culture and difficulties in diagnosing paucibacillary, childhood and extrapulmonary tuberculosis has necessitated to explore the utility of immunodiagnosis of tuberculosis as a convenient and cost effective test to supplement clinical information for definite diagnosis. Many commercial tests are available in the market for diagnosis of TB. Most of these tests are based on the detection of IgG, IgA and IgM antibodies to specific mycobacterial antigen or mixture of antigens. Indigenous immunoassay systems have explored excretory-secretory ES-31 mycobacterial antigen for immunodiagnosis of TB. Many a time there is lack of consistent elevation in all the three Ig classes in active infection thus making it more important to determine the ideal antibody isotype assay for reliable diagnosis of tuberculosis and to save the costs of the patient for unnecessary investigations. PMID:23105384

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

    PubMed Central

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

    2012-01-01

    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

  13. Enhanced Specialized Transduction Using Recombineering in Mycobacterium tuberculosis

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

    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

    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

  15. Bovine tuberculosis in Canadian wildlife: an updated history.

    PubMed

    Wobeser, Gary

    2009-11-01

    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

  16. Understanding Rifampicin Resistance in Tuberculosis through a Computational Approach

    PubMed Central

    Jena, Lingaraja

    2014-01-01

    The disease tuberculosis, caused by Mycobacterium tuberculosis (MTB), remains a major cause of morbidity and mortality in developing countries. The evolution of drug-resistant tuberculosis causes a foremost threat to global health. Most drug-resistant MTB clinical strains are showing resistance to isoniazid and rifampicin (RIF), the frontline anti-tuberculosis drugs. Mutation in rpoB, the beta subunit of DNA-directed RNA polymerase of MTB, is reported to be a major cause of RIF resistance. Amongst mutations in the well-defined 81-base-pair central region of the rpoB gene, mutation at codon 450 (S450L) and 445 (H445Y) is mainly associated with RIF resistance. In this study, we modeled two resistant mutants of rpoB (S450L and H445Y) using Modeller9v10 and performed a docking analysis with RIF using AutoDock4.2 and compared the docking results of these mutants with the wild-type rpoB. The docking results revealed that RIF more effectively inhibited the wild-type rpoB with low binding energy than rpoB mutants. The rpoB mutants interacted with RIF with positive binding energy, revealing the incapableness of RIF inhibition and thus showing resistance. Subsequently, this was verified by molecular dynamics simulations. This in silico evidence may help us understand RIF resistance in rpoB mutant strains. PMID:25705170

  17. Bovine tuberculosis in Canadian wildlife: An updated history

    PubMed Central

    Wobeser, Gary

    2009-01-01

    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

  18. The Diagnostic Accuracy of Urine Lipoarabinomannan Test for Tuberculosis Screening in a South African Correctional Facility

    PubMed Central

    Hanifa, Yasmeen; Telisinghe, Lilanganee; Fielding, Katherine L.; Malden, Justin L.; Churchyard, Gavin J.; Grant, Alison D.; Charalambous, Salome

    2015-01-01

    Background We evaluated the diagnostic accuracy of the urine lipoarabinomannan (LAM) antigen detection assay (Clearview TB-ELISA) to screen for tuberculosis in a South African correctional facility. Methods Between September 2009 and October 2010, male offenders were screened for tuberculosis (symptoms, chest radiograph, two spot sputum specimens for microscopy and culture), and urine tested for LAM. Sensitivity, specificity and predictive values of LAM were calculated using definite and probable tuberculosis combined as our gold standard. Findings 33/871 (3.8%) participants (26% HIV-positive) had tuberculosis. Amongst HIV-positive vs. HIV-negative offenders the sensitivity and specificity of LAM was 7.1% vs. 0% and 98.5% vs. 99.8% respectively. Conclusion Urine LAM ELISA has inadequate sensitivity for TB screening in this population. PMID:26010840

  19. Utility of MPT64 Antigen Detection for Rapid Confirmation of Mycobacterium tuberculosis Complex

    PubMed Central

    Arora, Jyoti; Kumar, Gavish; Verma, Ajoy Kumar; Bhalla, Manpreet; Sarin, Rohit; Myneedu, Vithal Prasad

    2015-01-01

    Background: Rapid differentiation of the Mycobacterium tuberculosis complex (MTBC) and mycobacteria other than tuberculosis (MOTT) is crucial to facilitate early and effective treatment of the patients. Clinical presentation of MTBC and MOTT is not always very clear and routine conventional methods are time consuming. Materials and Methods: In the present study, the MPT64 protein detection-based immunochomatographic test (SD Bioline Kit, Standard Diagnostics, Inc., Korea) was compared with the conventional biochemical method. Results: The sensitivity, specificity, positive predictive, and negative predictive values of the SD AgMPT64 kit were found to be 100, 96.4, 98.72, and 100%, respectively. Conclusions: Our results have demonstrated that the SD bioline kit is a rapid, reliable method and it can be used in the Revised National Tuberculosis Control Program (RNTCP) of India, for the appropriate management of tuberculosis.

  20. Challenges of Loss to Follow-up in Tuberculosis Research

    Microsoft Academic Search

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

    2012-01-01

    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

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

    PubMed Central

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

    2012-01-01

    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

  2. Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998

    PubMed Central

    Joint, T

    1998-01-01

    BACKGROUND—The guidelines on chemotherapy and management of tuberculosis in the United Kingdom have been reviewed and updated.?METHODS—A subcommittee was appointed by the Joint Tuberculosis Committee (JTC) of the British Thoracic Society to revise the guidelines published in 1990 by the JTC. In preparing the revised guidelines the authors took account of new published evidence and graded the strength of evidence for their recommendations. The guidelines have been approved by the JTC and the Standards of Care Committee of the British Thoracic Society.?RECOMMENDATIONS—(1) Patients with tuberculosis should be notified. (2) In view of the rising incidence of drug resistance, bacteriological confirmation and drug susceptibility testing should be sought whenever possible. (3) A six month short course regimen, with four drugs in the initial phase, should be used for all forms of tuberculosis, except meningitis, in both adults and children. (4) The fourth drug (ethambutol) in the initial phase can be omitted in certain circumstances. (5) Treatment of all patients should be supervised by physicians with full training in the management of tuberculosis and with direct working access to tuberculosis nurse specialists or health visitors. (6) Advice is given on (a) management in special situations and patient groups, (b) drug interactions, and special precautions and pretreatment screening, (c) chemoprophylaxis for different groups, and (d) the management of single and multiple drug resistance. (7) Advice is given on follow up after treatment and the organisational framework for tuberculosis services. (8) The role of directly observed therapy is discussed. (9) The management of multidrug resistant tuberculosis is explained in outline: such patients should be managed by physicians with special experience and in close liaison with the Mycobacterium Reference Units, and in hospitals with appropriate isolation facilities. (10) Infection control and segregation for such patients and for patients with dual infection with human immunodeficiency virus (HIV) and tuberculosis are covered in an appendix.?? PMID:9797751

  3. Human tuberculosis predates domestication in ancient Syria.

    PubMed

    Baker, Oussama; Lee, Oona Y-C; Wu, Houdini H T; Besra, Gurdyal S; Minnikin, David E; Llewellyn, Gareth; Williams, Christopher M; Maixner, Frank; O'Sullivan, Niall; Zink, Albert; Chamel, Bérénice; Khawam, Rima; Coqueugniot, Eric; Helmer, Daniel; Le Mort, Françoise; Perrin, Pascale; Gourichon, Lionel; Dutailly, Bruno; Pálfi, György; Coqueugniot, Hélène; Dutour, Olivier

    2015-06-01

    The question of pre-neolithic tuberculosis is still open in paleopathological perspective. One of the major interests is to explore what type of infection could have existed around the early stage of animal domestication. Paleopathological lesions evoking skeletal TB were observed on five human skeletons coming from two PPNB sites in Syria, which belongs to the geographical cradle of agriculture. These sites represent respectively pre-domestication phase (Dja'de el Mughara, Northern Syria, 8800-8300 BCE cal.) and early domestication phase (Tell Aswad, Southern Syria, 8200-7600 BCE cal.). MicroCT scan analyses were performed on two specimens (one per site) and revealed microscopic changes in favor of TB infection. Detection of lipid biomarkers is positive for two specimens (one per site). Initial molecular analysis further indicates the presence of TB in one individual from Dja'de. Interestingly, no morphological evidence of TB was observed on animal remains of wild and newly domesticated species, discovered in these sites. These observations strongly suggest the presence of human tuberculosis before domestication and at its early stages. PMID:25819157

  4. Macrophages in Tuberculosis: Friend or Foe

    PubMed Central

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

    2013-01-01

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

  5. Diagnosis and Treatment of Extrapulmonary Tuberculosis

    PubMed Central

    2015-01-01

    Extrapulmonary tuberculosis (EPTB) constitutes about 20% of all cases of tuberculosis (TB) in Korea. Diagnosing EPTB remains challenging because clinical samples obtained from relatively inaccessible sites may be paucibacillary, thus decreasing the sensitivity of diagnostic tests. Whenever practical, every effort should be made to obtain appropriate specimens for both mycobacteriologic and histopathologic examinations. The measurement of biochemical markers in TB-affected serosal fluids (adenosine deaminase or gamma interferon) and molecular biology techniques such as polymerase chain reaction may be useful adjuncts in the diagnosis of EPTB. Although the disease usually responds to standard anti-TB drug therapy, the ideal regimen and duration of treatment have not yet been established. A paradoxical response frequently occurs during anti-TB therapy. It should be distinguished from other causes of clinical deterioration. Surgery is required mainly to obtain valid diagnostic specimens and to manage complications. Because smear microscopy or culture is not available to monitor patients with EPTB, clinical monitoring is the usual way to assess the response to treatment. PMID:25861336

  6. Phospholipase C in Beijing strains of Mycobacterium tuberculosis

    PubMed Central

    Mirsamadi, ES; Farnia, P; Jahani Sherafat, S; Esfahani, M; Faramarzi, N

    2010-01-01

    Background and Objectives Phospholipase of Mycobacterium tuberculosis plays an important role in pathogenesis through breaking up phospholipids and production of diacylglycerol. In this study, we examined the Beijing strains of Mycobacterium tuberculosis isolated from Iranian patients for the genes encoding this enzyme. Materials and Methods DNA extraction was performed using CTAB (cetyltrimethylammonium bromide) from positive culture specimens in tuberculosis patients. PCR was then used to amplify the plcA, plcB, plcC genes of Beijing strain, and non-Beijing strains were identified by spoligotyping. Results Of 200 specimens, 19 (9.5%) were Beijing strain and 181 (90.5%) were non-Beijing strains. The results of PCR for Beijing strains were as follows: 16 strains (84.2%) were positive for plcA, 17 (89.4%) were positive for plcB and 17 (89.4%) were positive for plcC genes. The standard strain (H37RV) was used as control. Conclusion The majority of Beijing strains have phospholipase C genes which can contribute to their pathogenesis but we need complementary studies to confirm the role of phospholipase C in pathogenecity of Mycobacterium tuberculosis. PMID:22347572

  7. INHIBITOR STUDIES ON MYCOBACTERIUM TUBERCULOSIS MALATE SYNTHASE 

    E-print Network

    Owen, Joshua

    2008-08-03

    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...

  8. A case of isolated splenic tuberculosis

    PubMed Central

    Basa, Johanna V.; Singh, Lilly; Jaoude, Wassim Abi; Sugiyama, Gainosuke

    2014-01-01

    There are few cases of isolated splenic tuberculosis reported in the literature internationally, and nearly none from western medical centers. The incidence of tuberculosis has declined in the United States since the 1950s, with 11,585 reported cases in 2009, 21% of which were exclusively extrapulmonary. Splenic tuberculosis occurs mostly as part of miliary tuberculosis in immunocompromised patients. Isolated splenic tuberculosis is extremely rare, particularly in the immunocompetent patient. Patients susceptible to acquiring splenic tuberculosis usually have one of the following risk factors: immunosuppression, preceding pyogenic infections, splenic abnormalities, prior trauma to the spleen, sickle cell disease and other hemopathies, and in the immunocompetent patient another body site infected by M. tuberculosis. In this report we present the case of a young immunocompetent male with no other significant past medical history with isolated splenic tuberculosis. PMID:25667987

  9. Abdominal tuberculosis mimicking Crohn’s disease’s exacerbation: A clinical, diagnostic and surgical dilemma. A case report

    PubMed Central

    Papis, Davide; Branchi, Vittorio; Gomez, Luis; Herrerias, Fernando; Vilardell, Felip; Gonzalez, Marta; Olsina, Jorge J

    2014-01-01

    Introduction Tuberculosis in Europe is a health public problem, which has increased constantly over the last few decades. The most common clinical manifestation of tuberculosis is pulmonary. The diagnosis of extrapulmonary tuberculosis can be challenging and clinical manifestations of gastrointestinal tuberculosis are unspecific and can mimic other pathologies. Presentation of case A young Chinese man, who had recently been diagnosed with Crohn’s disease, was admitted to the emergency room of our hospital with a one-month history of diffuse abdominal pain and weight loss. The patient initially presented with epigastric pain, which had been constantly increasing over the last 48 h. Other symptoms included diarrhea, nausea, and fever. The patient was then admitted with the diagnosis of Crohn’s disease exacerbation, and a treatment with corticosteroids, azathioprine, mesalazine, adalimumab, and antibiotic therapy was started. The symptoms were due to an initially misdiagnosed case of abdominal tuberculosis. Discussion Intestinal tuberculosis is mainly localized at the ileocecal level in 85% of patients. Medical therapy is the treatment of choice and surgery is not required if it is diagnosed at an early stage.? Conclusion The diagnosis of abdominal tuberculosis still remains a challenge for both internists and surgeons. Before starting a therapy with adalimumab, every patient should be tested for latent tuberculosis infection. PMID:25528041

  10. Smoking and tuberculosis among silicotic patients.

    PubMed

    Leung, C C; Yew, W W; Law, W S; Tam, C M; Leung, M; Chung, Y W; Cheung, K W; Chan, K W; Fu, F

    2007-04-01

    The aim of the present study was to investigate the relationship between smoking and tuberculosis (TB) among high-risk silicotic patients in Hong Kong. A cohort of 435 silicotic patients tuberculin tested from 1995-2002 was prospectively followed-up until the end of 2005. Baseline characteristics were analysed with respect to positive tuberculin reaction (> or =10 mm) at baseline and subsequent development of TB. Smoking, alcohol use and body mass index were independent predictors of positive tuberculin reaction at baseline in multiple logistic regression analysis. Total cigarette pack-yrs did not demonstrate any significant effect. The annual incidences of TB were 1,841, 2,294 and 4,181 per 100,000 for never-, ex- and current smokers, respectively. On Cox proportional hazard analysis, current smokers have a significantly higher risk of TB than other silicotic patients (adjusted hazard ratio (95% confidence interval (CI)): 1.96 (1.14-3.35)) after controlling for age, alcohol use, tuberculin status, treatment for latent TB infection and other relevant background/disease factors. A significant dose-response relationship was also observed with the daily number of cigarettes currently smoked. Smoking cessation may reduce 32.4% (95% CI: 6.5-54.0) of the risk. Smoking increases the risk of both tuberculosis infection and subsequent development of the disease among silicotic patients. PMID:17182648

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2014-01-01

    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

  13. Ghost Remains After Black Hole Eruption

    NASA Astrophysics Data System (ADS)

    2009-05-01

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

  14. Where do those remains come from?

    PubMed

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

    2014-10-14

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

  15. Knowledge, Health Seeking Behavior and Perceived Stigma towards Tuberculosis among Tuberculosis Suspects in a Rural Community in Southwest Ethiopia

    Microsoft Academic Search

    Gemeda Abebe; Amare Deribew; Ludwig Apers; Kifle Woldemichael; Jaffer Shiffa; Markos Tesfaye; Alemseged Abdissa; Fetene Deribie; Chali Jira; Mesele Bezabih; Abraham Aseffa; Luc Duchateau; Robert Colebunders

    2010-01-01

    BackgroundPerceived stigma and lack of awareness could contribute to the late presentation and low detection rate of tuberculosis (TB). We conducted a study in rural southwest Ethiopia among TB suspects to assess knowledge about and stigma towards TB and their health seeking behavior.MethodsA community based cross sectional survey was conducted from February to March 2009 in the Gilgel Gibe field

  16. An Update on Global Tuberculosis (TB)

    PubMed Central

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

    2013-01-01

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

  17. Oropharyngeal tuberculosis causing severe odynophagia and dysphagia

    Microsoft Academic Search

    Rahmet Caylan; Kemalettin Aydin

    2002-01-01

    Oropharyngeal tuberculosis is a rare disease and is usually secondary to laryngeal involvement in pulmonary tuberculosis.\\u000a The major symptom in such patients is sore throat. Here, we report a case of tuberculosis of the posterior oropharyngeal wall\\u000a without laryngeal involvement and causing severe dysphagia and odynophagia without esophageal or mediastinal involvement.\\u000a The unusual presentation of extrapulmonary tuberculosis is emphasized, and

  18. Miliary tuberculosis and adult respiratory distress syndrome

    Microsoft Academic Search

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

    1987-01-01

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

  19. Rapid diagnosis of pulmonary tuberculosis

    PubMed Central

    Sarmiento, José Mauricio Hernández; Restrepo, Natalia Builes; Mejía, Gloria Isabel; Zapata, Elsa; Restrepo, Mary Alejandra; Robledo, Jaime

    2014-01-01

    Introduction World Health Organization had estimated 9.4 million tuberculosis cases on 2009, with 1.7 million of deaths as consequence of treatment and diagnosis failures. Improving diagnostic methods for the rapid and timely detection of tuberculosis patients is critical to control the disease. The aim of this study was evaluating the accuracy of the cord factor detection on the solid medium Middlebrook 7H11 thin layer agar compared to the Lowenstein Jensen medium for the rapid tuberculosis diagnosis. Methods Patients with suspected tuberculosis were enrolled and their sputum samples were processed for direct smear and culture on Lowenstein Jensen and BACTEC MGIT 960, from which positive tubes were subcultured on Middlebrook 7H11 thin layer agar. Statistical analysis was performed comparing culture results from Lowenstein Jensen and the thin layer agar, and their corresponding average times for detecting Mycobacterium tuberculosis. The performance of cord factor detection was evaluated determining its sensitivity, specificity, positive and negative predictive value. Results 111 out of 260 patients were positive for M. tuberculosis by Lowenstein Jensen medium with an average time ± standard deviation for its detection of 22.3 ± 8.5 days. 115 patients were positive by the MGIT system identifying the cord factor by the Middlebrook 7H11 thin layer agar which average time ± standard deviation was 5.5 ± 2.6 days. Conclusion The cord factor detection by Middlebrook 7H11 thin layer agar allows early and accurate tuberculosis diagnosis during an average time of 5 days, making this rapid diagnosis particularly important in patients with negative sputum smear. PMID:25419279

  20. Humus composition of peat land plant remains

    Microsoft Academic Search

    Renzô Kondô

    1974-01-01

    Plant remains of peat collected in Hokkaido were examined with regard to humus compositions by means similar to those used by Kumadaet al. The examined samples of plant remains covered 34 species, 24 genera, and 19 families. The results were as follows:(1) HT, HE, and PQ varied considerably with the samples over a fairly large range, implying their relationships with

  1. Novel technologies: A weapon against tuberculosis

    PubMed Central

    Hari, B.N. Vedha; Chitra, Karuna Priya; Bhimavarapu, Ramadevi; Karunakaran, Prabhu; Muthukrishnan, N.; Rani, B. Samyuktha

    2010-01-01

    Tuberculosis (TB) is a leading chronic bacterial infection. Despite potentially curative pharmacotherapies being available for over 50 years, the length of the treatment and the pill burden can hamper patient lifestyle. Low compliance and adherence to administration schedules remain the main reasons for therapeutic failure and contribute to the development of multidrug-resistant strains. The design of novel antibiotics attempts to overcome drug resistance, to shorten the treatment course, and to reduce drug interactions. In this framework, nanotechnology appears as one of the promising approaches for the development of more effective medicines. The present review thoroughly overviews the development of novel microparticulate, encapsulation, and various other carrier-based drug delivery systems for incorporating the principal anti-TB agents. Drug delivery systems have been designed that either target the site of TB or reduce the dosing frequency with the aim of improving patient healthcare. PMID:21189901

  2. [New diagnosis methods of tuberculosis].

    PubMed

    Slim-Saidi, L; Mehiri-Zeghal, E; Ghariani, A; Tritar, F

    2015-01-01

    Bacteriological diagnosis of tuberculosis has benefited in recent years from many technological advances to improve rapidity and sensitivity of the techniques. Thus, new LED fluorescence microscopes are in the process of replacing the optical microscopes and the Ziehl-Neelsen technique, making the examination more precise, faster and easier. The manual and automatic liquid culture has improved Lowenstein-Jensen culture and helped shorten antibiotic sensitivity test, allowing appropriate management of patients. The development and standardization of molecular biology methods led to the rapid detection and identification of mycobacterium directly in clinical samples but also of resistance genes for early diagnosis of MDR-TB and dealing with them quickly. However, the performance of these techniques does not sufficiently cover the diagnosis of smear-negative tuberculosis, extrapulmonary forms, children- and immune-compromised tuberculosis where sensitivity is limited. The diagnosis of latent tuberculosis is reinforced by the in vitro release testing of gamma interferon overcoming the lack of specificity of the tuberculin skin test. Despite considerable progress, more amelioration is still needed to improve these techniques in order to extend them to the paucibacillary tuberculosis and to facilitate their access to low-resource countries. PMID:25754128

  3. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    PubMed Central

    Saif, Muhammad Wasif

    2014-01-01

    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

  4. Pancreatic tuberculosis or autoimmune pancreatitis.

    PubMed

    Salahuddin, Ayesha; Saif, Muhammad Wasif

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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

  6. Clinical presentation of abdominal tuberculosis in HIV seronegative adults

    PubMed Central

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

    2005-01-01

    Background The accurate diagnosis of abdominal tuberculosis usually takes a long time and requires a high index of suspicion in clinic practice. Eighty-eight immune-competent patients with abdominal tuberculosis were grouped according to symptoms at presentation and followed prospectively in order to investigate the effect of symptomatic presentation on clinical diagnosis and prognosis. Methods Based upon the clinical presentation, the patients were divided into groups such as non-specific abdominal pain & less prominent in bowel habit, ascites, alteration in bowel habit, acute abdomen and others. Demographic, clinical and laboratory features, coexistence of pulmonary tuberculosis, diagnostic procedures, definitive diagnostic tests, need for surgical therapy, and response to treatment were assessed in each group. Results According to clinical presentation, five groups were constituted as non-specific abdominal pain (n = 24), ascites (n = 24), bowel habit alteration (n = 22), acute abdomen (n = 9) and others (n = 9). Patients presenting with acute abdomen had significantly higher white blood cell counts (p = 0.002) and abnormalities in abdominal plain radiographs (p = 0.014). Patients presenting with alteration in bowel habit were younger (p = 0.048). The frequency of colonoscopic abnormalities (7.5%), and need for therapeutic surgery (12.5%) were lower in patients with ascites, (p = 0.04) and (p = 0.001), respectively. There was no difference in gender, disease duration, diagnostic modalities, response to treatment, period to initial response, and mortality between groups (p > 0.05). Gastrointestinal tract alone was the most frequently involved part (38.5%), and this was associated with acid-fast bacteria in the sputum (p = 0.003). Conclusion Gastrointestinal tract involvement is frequent in patients with active pulmonary tuberculosis. Although different clinical presentations of patients with abdominal tuberculosis determine diagnostic work up and need for therapeutic surgery, evidence based diagnosis and consequences of the disease does not change. PMID:15969744

  7. Multidrug-resistant tuberculosis in children: evidence from global surveillance.

    PubMed

    Zignol, Matteo; Sismanidis, Charalambos; Falzon, Dennis; Glaziou, Philippe; Dara, Masoud; Floyd, Katherine

    2013-09-01

    Multidrug-resistant tuberculosis (MDR-TB) can affect persons of any age, but it remains unknown whether children are more or less likely than adults to have MDR-TB. Representative drug resistance surveillance data reported to the World Health Organization between 1994 and 2011 were analysed to test the association between MDR-TB and age group (children aged <15 years versus adults aged ? 15 years), using odds ratios derived by logistic regression with robust standard errors. Of 85 countries with data from nationwide surveys or surveillance systems, 35 reported at least one paediatric MDR-TB case. Aggregated data on age and drug susceptibility testing for 323 046 tuberculosis cases notified in these 35 countries were analysed. Odds ratios for MDR-TB in children compared to adults varied widely between countries. In Germany, Namibia, South Africa, the UK and the USA, MDR-TB was positively associated with age <15 years. In the remaining countries no association was established. Despite the limitations intrinsic to the use of surveillance data and to the challenges of diagnosing childhood tuberculosis, our analysis suggests that proportions of MDR-TB in children and adults are similar in many settings. Of particular concern is the association found between age <15 years and MDR-TB in southern African countries with high HIV prevalence. PMID:23222872

  8. Complete republication: Epidemiology of tuberculosis in the EU/EEA in 2010 – Monitoring the progress towards tuberculosis elimination

    PubMed Central

    Hollo, V.; Huitric, E.; Ködmön, C.

    2012-01-01

    The 2012 combined tuberculosis (TB) surveillance and monitoring report for the European Union and European Economic Area identifies a mean annual decline in TB notification rate by 4.4% from 2006 to 2010. Culture confirmation for new pulmonary cases and drug susceptibility testing have increased to 65.6% and 70.8%, but remain under their targets of 80% and 100%, respectively. Reporting of treatment outcome and coinfection with human immunodeficiency virus also remain suboptimal. Strengthened control practices are needed to allow progress towards TB elimination. PMID:24265912

  9. [Choroidal tuberculosis: reports of 3 cases].

    PubMed

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

    2009-01-01

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

  10. Membrane Type 1 Matrix Metalloproteinase Regulates Monocyte Migration and Collagen Destruction in Tuberculosis.

    PubMed

    Sathyamoorthy, Tarangini; Tezera, Liku B; Walker, Naomi F; Brilha, Sara; Saraiva, Luisa; Mauri, Francesco A; Wilkinson, Robert J; Friedland, Jon S; Elkington, Paul T

    2015-08-01

    Tuberculosis (TB) remains a global pandemic and drug resistance is rising. Multicellular granuloma formation is the pathological hallmark of Mycobacterium tuberculosis infection. The membrane type 1 matrix metalloproteinase (MT1-MMP or MMP-14) is a collagenase that is key in leukocyte migration and collagen destruction. In patients with TB, induced sputum MT1-MMP mRNA levels were increased 5.1-fold compared with matched controls and correlated positively with extent of lung infiltration on chest radiographs (r = 0.483; p < 0.05). M. tuberculosis infection of primary human monocytes increased MT1-MMP surface expression 31.7-fold and gene expression 24.5-fold. M. tuberculosis-infected monocytes degraded collagen matrix in an MT1-MMP-dependent manner, and MT1-MMP neutralization decreased collagen degradation by 73%. In human TB granulomas, MT1-MMP immunoreactivity was observed in macrophages throughout the granuloma. Monocyte-monocyte networks caused a 17.5-fold increase in MT1-MMP surface expression dependent on p38 MAPK and G protein-coupled receptor-dependent signaling. Monocytes migrating toward agarose beads impregnated with conditioned media from M. tuberculosis-infected monocytes expressed MT1-MMP. Neutralization of MT1-MMP activity decreased this M. tuberculosis network-dependent monocyte migration by 44%. Taken together, we demonstrate that MT1-MMP is central to two key elements of TB pathogenesis, causing collagen degradation and regulating monocyte migration. PMID:26091717

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Correa, Andre F.; Bailão, Alexandre M.; Bastos, Izabela M. D.; Orme, Ian M.; Soares, Célia M. A.; Kipnis, Andre

    2014-01-01

    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

  14. Membrane Type 1 Matrix Metalloproteinase Regulates Monocyte Migration and Collagen Destruction in Tuberculosis

    PubMed Central

    Sathyamoorthy, Tarangini; Tezera, Liku B.; Walker, Naomi F.; Brilha, Sara; Saraiva, Luisa; Mauri, Francesco A.; Wilkinson, Robert J.; Friedland, Jon S.

    2015-01-01

    Tuberculosis (TB) remains a global pandemic and drug resistance is rising. Multicellular granuloma formation is the pathological hallmark of Mycobacterium tuberculosis infection. The membrane type 1 matrix metalloproteinase (MT1-MMP or MMP-14) is a collagenase that is key in leukocyte migration and collagen destruction. In patients with TB, induced sputum MT1-MMP mRNA levels were increased 5.1-fold compared with matched controls and correlated positively with extent of lung infiltration on chest radiographs (r = 0.483; p < 0.05). M. tuberculosis infection of primary human monocytes increased MT1-MMP surface expression 31.7-fold and gene expression 24.5-fold. M. tuberculosis–infected monocytes degraded collagen matrix in an MT1-MMP–dependent manner, and MT1-MMP neutralization decreased collagen degradation by 73%. In human TB granulomas, MT1-MMP immunoreactivity was observed in macrophages throughout the granuloma. Monocyte–monocyte networks caused a 17.5-fold increase in MT1-MMP surface expression dependent on p38 MAPK and G protein–coupled receptor-dependent signaling. Monocytes migrating toward agarose beads impregnated with conditioned media from M. tuberculosis–infected monocytes expressed MT1-MMP. Neutralization of MT1-MMP activity decreased this M. tuberculosis network–dependent monocyte migration by 44%. Taken together, we demonstrate that MT1-MMP is central to two key elements of TB pathogenesis, causing collagen degradation and regulating monocyte migration. PMID:26091717

  15. 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

    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

    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

  16. Tracheobronchial Tuberculosis Without Lung Involvement

    PubMed Central

    Campos, Jeronimo; Ernst, Glenda; Borsini, Eduardo; Garcia, Artemio; Blasco, Miguel; Bosio, Martin; Salvado, Alejandro

    2015-01-01

    Endotracheal tuberculosis (ETTB) is an infrequent form of tuberculosis whose major feature is the infection of the tracheobronchial tree by Mycobacterium tuberculosis. This case presents a 73-year-old man admitted to our hospital with fatigue, weakness, dry cough and weight loss. His chest X-ray was normal but the high resolution computed tomography (HRCT) showed normal parenchyma images with mediastinal and hilar lymphadenopathy. There was inflammation of the tracheal wall and infiltrates in pavement epithelium; however, the tracheal biopsy for acid-fast bacilli was negative. He was finally diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the lymph nodes. Four drugs were prescribed and symptoms improved. EBUS-TBNA contributed to prompt diagnosis. The patient was treated and evolved without complications, such as tracheal stenosis. PMID:26124914

  17. Tracheobronchial Tuberculosis Without Lung Involvement.

    PubMed

    Campos, Jeronimo; Ernst, Glenda; Borsini, Eduardo; Garcia, Artemio; Blasco, Miguel; Bosio, Martin; Salvado, Alejandro

    2015-08-01

    Endotracheal tuberculosis (ETTB) is an infrequent form of tuberculosis whose major feature is the infection of the tracheobronchial tree by Mycobacterium tuberculosis. This case presents a 73-year-old man admitted to our hospital with fatigue, weakness, dry cough and weight loss. His chest X-ray was normal but the high resolution computed tomography (HRCT) showed normal parenchyma images with mediastinal and hilar lymphadenopathy. There was inflammation of the tracheal wall and infiltrates in pavement epithelium; however, the tracheal biopsy for acid-fast bacilli was negative. He was finally diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of the lymph nodes. Four drugs were prescribed and symptoms improved. EBUS-TBNA contributed to prompt diagnosis. The patient was treated and evolved without complications, such as tracheal stenosis. PMID:26124914

  18. Risk analysis and bovine tuberculosis, a re-emerging zoonosis.

    PubMed

    Etter, Eric; Donado, Pilar; Jori, Ferran; Caron, Alexandre; Goutard, Flavie; Roger, François

    2006-10-01

    The widespread of immunodeficiency with AIDS, the consequence of poverty on sanitary protection and information at both individual and state levels lead control of tuberculosis (TB) to be one of the priorities of World Health Organization programs. The impact of bovine tuberculosis (BTB) on humans is poorly documented. However, BTB remains a major problem for livestock in developing countries particularly in Africa and wildlife is responsible for the failure of TB eradication programs. In Africa, the consumption of raw milk and raw meat, and the development of bushmeat consumption as a cheap source of proteins, represent one of the principal routes for human contaminations with BTB. The exploration of these different pathways using tools as participatory epidemiology allows the risk analysis of the impact of BTB on human health in Africa. This analysis represents a management support and decision tool in the study and the control of zoonotic BTB. PMID:17135495

  19. Transcription factor regulatory network for early lung immune response to tuberculosis in mice.

    PubMed

    Yaqubi, Moein; Mohammadnia, Abdulshakour; Fallahi, Hossein

    2015-08-01

    Numerous transcription factors (TFs) have been suggested to have a role in Mycobacterium tuberculosis infection; however, the TFs involved in the early immune response of lung cells remains to be fully elucidated. The present study aimed to identify TFs which may have a role in the early immune response to tuberculosis and the gene regulatory networks in which they are involved. Gene expression data obtained from microarray analysis of the early lung immune response to tuberculosis (Gene Expression Omnibus; accession no. GSE23014) was integrated with data for TF binding sites and protein?protein interactions in order to construct a TF regulatory network. The role of TFs in protein complexes, active modules, topology of the network and regulation of immune processes were investigated. The results demonstrated that the constructed gene regulatory network harbored 1,270 differentially expressed (DE) genes with 4,070 regulatory and protein?protein interactions. In addition, it was revealed that 17 DE TFs were involved in the positive regulation of numerous immunological and biological processes, including T cell activation, T cell proliferation and tuberculosis?associated gene expression, in the constructed regulatory network. Signal transducer and activator of transcription 4, interferon regulatory factor 8, spleen focus-forming virus proviral integration 1, enhancer of zeste homolog 2 and kruppel?like factor 4 were predicted to be the primary TFs regulating the DE genes during early lung infection by M. tuberculosis, as determined through various analyses of the gene regulatory network. In conclusion, the present study identified novel TFs involved in the early response to M. tuberculosis infection, which may enhance current understanding of the molecular mechanism underlying tuberculosis infection and introduced potential targets for novel tuberculosis therapies. PMID:25955085

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

    PubMed Central

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

    2014-01-01

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

  1. Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

    PubMed Central

    Sable, Suraj B.; Cheruvu, Mani; Nandakumar, Subhadra; Sharma, Sunita; Bandyopadhyay, Kakali; Kellar, Kathryn L.; Posey, James E.; Plikaytis, Bonnie B.; Amara, Rama Rao; Shinnick, Thomas M.

    2011-01-01

    Background The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis. Methods and Principal Findings In this study, a comparison of intranasal (i.n.) and subcutaneous (s.c.) vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860) was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study. Conclusion and Significance Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis. PMID:21799939

  2. Targeting the chromosome partitioning protein ParA in tuberculosis drug discovery

    PubMed Central

    Nisa, Shahista; Blokpoel, Marian C. J.; Robertson, Brian D.; Tyndall, Joel D. A.; Lun, Shichun; Bishai, William R.; O'Toole, Ronan

    2010-01-01

    Objective To identify inhibitors of the essential chromosome partitioning protein ParA that are active against Mycobacterium tuberculosis. Methods Antisense expression of the parA orthologue MSMEG_6939 was induced on the Mycobacterium smegmatis background. Screening of synthetic chemical libraries was performed to identify compounds with higher anti-mycobacterial activity in the presence of parA antisense. Differentially active compounds were validated for specific inhibition of purified ParA protein from M. tuberculosis (Rv3918c). ParA inhibitors were then characterized for their activity towards M. tuberculosis in vitro. Results Under a number of culture conditions, parA antisense expression in M. smegmatis resulted in reduced growth. This effect on growth provided a basis for the detection of compounds that increased susceptibility to expression of parA antisense. Two compounds identified from library screening, phenoxybenzamine and octoclothepin, also inhibited the in vitro ATPase activity of ParA from M. tuberculosis. Structural in silico analyses predict that phenoxybenzamine and octoclothepin undergo interactions compatible with the active site of ParA. Octoclothepin exhibited significant bacteriostatic activity towards M. tuberculosis. Conclusions Our data support the use of whole-cell differential antisense screens for the discovery of inhibitors of specific anti-tubercular drug targets. Using this approach, we have identified an inhibitor of purified ParA and whole cells of M. tuberculosis. PMID:20810423

  3. The Factors Associated with Tuberculosis Recurrence in the Northwest and West of Iran

    PubMed Central

    SAHEBI, Leyla; ANSARIN, Khalil; Maryam, SEYYEDI; MONFAREDAN, Amir; SABBGH JADID, Hamed

    2014-01-01

    Background: Identifying the factors associated with the recurrence of Mycobacterium tuberculosis (MTB) can help in tuberculosis disease prevention and reducing the burden on the health care system. This study was designed to identify the factors associated with recurrence in MTB patients in five border provinces of Iran. Methods: In a cross-sectional study (2010 to 2012), clinical, economic, and social factors associated with the recurrence of tuberculosis were evaluated. The data were collected by a questionnaire and survey of medical records. Simple and multiple logistic regression analyses were performed using SPSS V.18. Results: A total of 300 patients with an average age of 51.9 years (SD 24.2) were randomly selected. Overall, 7.2% of the patients were diagnosed with a recurrence of tuberculosis. Sixty-four percent (n = 151) of the patients were in a low-income class. The migration from a village to a city (OR = 8.4) and weight loss (OR = 1.5) were significantly associated with an increased chance of recurrence. Conclusion: In this study, the selected provinces of Iran had moderate rates of tuberculosis recurrence in comparison to global reports. Further studies on the relationship of both weight loss and the immigration from a village to a city with tuberculosis recurrence are necessary. PMID:25897280

  4. Mycobacterium tuberculosis Rv0679c protein sequences involved in host-cell infection: Potential TB vaccine candidate antigen

    Microsoft Academic Search

    Diana P Cifuentes; Marisol Ocampo; Hernando Curtidor; Magnolia Vanegas; Martha Forero; Manuel E Patarroyo; Manuel A Patarroyo

    2010-01-01

    BACKGROUND: To date, the function of many hypothetical membrane proteins of Mycobacterium tuberculosis is still unknown and their involvement in pathogen-host interactions has not been yet clearly defined. In this study, the biological activity of peptides derived from the hypothetical membrane protein Rv0679c of M. tuberculosis and their involvement in pathogen-host interactions was assessed. Transcription of the Rv0679c gene was

  5. Secreted Mycobacterium tuberculosis Rv3654c and Rv3655c Proteins Participate in the Suppression of Macrophage Apoptosis

    Microsoft Academic Search

    Lia Danelishvili; Yoshitaka Yamazaki; Jeannie Selker; Luiz E. Bermudez; Delia Goletti

    2010-01-01

    BackgroundInhibition of macrophage apoptosis by Mycobacterium tuberculosis has been proposed as one of the virulence mechanisms whereby the pathogen avoids the host defense. The mechanisms by which M. tuberculosis H37Rv strain suppress apoptosis and escapes human macrophage killing was investigated.Methodology\\/Principal FindingsThe screening of a transposon mutant bank identified several mutants, which, in contrast to the wild-type bacterium, had impaired ability

  6. Validation of the GenoType® MTBDRplus assay for diagnosis of multidrug resistant tuberculosis in South Vietnam

    Microsoft Academic Search

    Mai NT Huyen; Edine W Tiemersma; Nguyen TN Lan; Frank GJ Cobelens; Nguyen H Dung; Dinh N Sy; Tran N Buu; Kristin Kremer; Pham T Hang; Maxine Caws; Richard O'Brien; Dick van Soolingen

    2010-01-01

    BACKGROUND: To control multidrug resistant tuberculosis (MDR-TB), the drug susceptibility profile is needed to guide therapy. Classical drug susceptibility testing (DST) may take up to 2 to 4 months. The GenoType® MTBDRplus test is a commercially available line-probe assay that rapidly detects Mycobacterium tuberculosis (MTB) complex, as well as the most common mutations associated with rifampin and isoniazid resistance. We

  7. 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

    Shin, Sonya S.

    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, ...

  8. Interferon-Gamma Release Assay Performance in Pulmonary and Extrapulmonary Tuberculosis

    PubMed Central

    Feng, Yun; Diao, Ni; Shao, Lingyun; Wu, Jing; Zhang, Shu; Jin, Jialin; Wang, Feifei; Weng, Xinhua; Zhang, Ying; Zhang, Wenhong

    2012-01-01

    Background The diagnosis of tuberculosis remains difficult. This study aimed to assess performance of interferon-gamma release assay (IGRA) in diagnosis of active tuberculosis (ATB) with pulmonary and extrapulmonary involvements, and to determine the diagnostic role of IGRA (T-SPOT.TB) and tuberculin skin test (TST) in BCG-vaccinated population. Methods and Findings Two hundred twenty-six ATB suspects were recruited and examined with T-SPOT.TB. Among them, fifty-two and seventy-six subjects were simultaneously tested by TST with 5TU or 1TU of purified protein derivative (PPD). The sensitivity of T-SPOT.TB was 94.7% (71/75), comparable in pulmonary and extrapulmonary disease groups (95.6% vs. 93.3%, P>0.05), while the specificity was 84.10% (90/107) but differed in two groups (69.2% vs. 88.9%, P?=?0.02). Compared to T-SPOT.TB, TST with 5TU-PPD showed less sensitivity (92.3% vs. 56.4%) and specificity (84.6% vs. 61.5%) (both P<0.01); the sensitivity of TST with 1TU-PPD was 27.8%, and despite its specificity identical to T-SPOT.TB (both 82.8%) positive predictive value (PPV) was only 33.3%. By combining T-SPOT.TB with TST (1TU), the specificity rose to 95%, but the PPV stayed unchanged. Conclusions IGRA could function as a powerful immunodiagnostic test to explore pulmonary and extrapulmonary TB, while TST failed to play a reliable or auxiliary role in identifying TB disease and infection in the BCG-vaccinated population. PMID:22427859

  9. Adherence with isoniazid for prevention of tuberculosis among HIV-infected adults in South Africa

    PubMed Central

    Szakacs, Tom A; Wilson, Douglas; Cameron, D William; Clark, Michael; Kocheleff, Paul; Muller, F James; McCarthy, Anne E

    2006-01-01

    Background Tuberculosis (TB) is the most common opportunistic infection in HIV-infected adults in developing countries. Isoniazid (INH) is recommended for treatment of latent TB infection, however non-adherence is common. The purpose of this study was to apply in-house prepared isoniazid (INH) urine test strips in a clinical setting, and identify predictors of positive test results in an adherence questionnaire in HIV-infected adults taking INH for prevention of TB. Methods Cross-sectional study of adherence using a questionnaire and urine test strips for detection of INH metabolites at two hospitals in Pietermaritzburg, South Africa. Participants were aged at least 18 years, HIV positive, and receiving INH for prevention of tuberculosis disease. Univariate and multivariate analyses are used to identify factors relevant to adherence. Results 301 consecutive patients were recruited. 28% of participants had negative urine tests. 32 (37.2%, 95% CI25.4, 45.0) of the 86 patients who received INH from peripheral pharmacies said the pharmacy had run out of INH at some time, compared with central hospital pharmacies (p = 0.0001). In univariate analysis, a negative test was associated with self-reported missed INH doses (p = 0.043). Each 12-hour increment since last reported dose increased the likelihood of a negative test by 34% (p = 0.0007). Belief in INH safety was associated with a positive test (p = 0.021). In multivariate analysis, patients who believed INH is important for prevention of TB disease were more likely to be negative (p = 0.0086). Conclusion Adequate drug availability at peripheral pharmacies remains an important intervention for TB prevention. Key questions may identify potentially non-adherent patients. In-house prepared urine tests strips are an effective and cheap method of objectively assessing INH adherence, and could be used an important tool in TB control programs. PMID:16772037

  10. Higher Rate of Tuberculosis in Second Generation Migrants Compared to Native Residents in a Metropolitan Setting in Western Europe

    PubMed Central

    Marx, Florian M.; Fiebig, Lena; Hauer, Barbara; Brodhun, Bonita; Glaser-Paschke, Gisela; Haas, Walter

    2015-01-01

    Background In Western Europe, migrants constitute an important risk group for tuberculosis, but little is known about successive generations of migrants. We aimed to characterize migration among tuberculosis cases in Berlin and to estimate annual rates of tuberculosis in two subsequent migrant generations. We hypothesized that second generation migrants born in Germany are at higher risk of tuberculosis compared to native (non-migrant) residents. Methods A prospective cross-sectional study was conducted. All tuberculosis cases reported to health authorities in Berlin between 11/2010 and 10/2011 were eligible. Interviews were conducted using a structured questionnaire including demographic data, migration history of patients and their parents, and language use. Tuberculosis rates were estimated using 2011 census data. Results Of 314 tuberculosis cases reported, 154 (49.0%) participated. Of these, 81 (52.6%) were first-, 14 (9.1%) were second generation migrants, and 59 (38.3%) were native residents. The tuberculosis rate per 100,000 individuals was 28.3 (95CI: 24.0–32.6) in first-, 10.2 (95%CI: 6.1–16.6) in second generation migrants, and 4.6 (95%CI: 3.7–5.6) in native residents. When combining information from the standard notification variables country of birth and citizenship, the sensitivity to detect second generation migration was 28.6%. Conclusions There is a higher rate of tuberculosis among second generation migrants compared to native residents in Berlin. This may be explained by presumably frequent contact and transmission within migrant populations. Second generation migration is insufficiently captured by the surveillance variables country of birth and citizenship. Surveillance systems in Western Europe should allow for quantifying the tuberculosis burden in this important risk group. PMID:26061733

  11. Improving Outcomes for Multidrug-Resistant Tuberculosis: Aggressive Regimens Prevent Treatment Failure and Death

    PubMed Central

    Velásquez, Gustavo E.; Becerra, Mercedes C.; Gelmanova, Irina Y.; Pasechnikov, Alexander D.; Yedilbayev, Askar; Shin, Sonya S.; Andreev, Yevgeny G.; Yanova, Galina; Atwood, Sidney S.; Mitnick, Carole D.; Franke, Molly F.; Rich, Michael L.; Keshavjee, Salmaan

    2014-01-01

    Background.?Evidence is sparse regarding the optimal construction of regimens to treat multidrug-resistant (MDR) tuberculosis disease due to strains of Mycobacterium tuberculosis resistant to at least both isoniazid and rifampin. Given the low potency of many second-line antituberculous drugs, we hypothesized that an aggressive regimen of at least 5 likely effective drugs during the intensive phase, including a fluoroquinolone and a parenteral agent, would be associated with a reduced risk of death or treatment failure. Methods.?We conducted a retrospective cohort study of patients initiating MDR tuberculosis treatment between 2000 and 2004 in Tomsk, Russian Federation. We used a multivariate Cox proportional hazards model to assess whether monthly exposure to an aggressive regimen was associated with the risk of death or treatment failure. Results.?Six hundred fourteen individuals with confirmed MDR tuberculosis were eligible for analysis. On multivariable analysis that adjusted for extensively drug-resistant (XDR) tuberculosis—MDR tuberculosis isolates resistant to fluoroquinolones and parenteral agents—we found that monthly exposure to an aggressive regimen was significantly associated with a lower risk of death or treatment failure (hazard ratio, 0.52 [95% confidence interval, .29–.94]; P = .030). Conclusions.?Receipt of an aggressive treatment regimen was a robust predictor of decreased risk of death or failure during MDR tuberculosis treatment. These findings further support the use of this regimen definition as the benchmark for the standard of care of MDR tuberculosis patients and should be used as the basis for evaluating novel therapies. PMID:24729493

  12. Rapid Detection of Mycobacterium tuberculosis in Sputum Samples by Cepheid Xpert Assay: A Clinical Study

    PubMed Central

    Jindal, Neerja; Bansal, Renu; Arora, Shilpa

    2015-01-01

    Background and Objective Tuberculosis (TB) is one of the commonest opportunistic infection and the leading cause of death in HIV patients in developing countries. HIV infection is a well recognised risk factor for both activation of initial infection and reactivation of latent infection. This study was done to find out the co-prevalence and the trend of HIV infection among tuberculosis patients and to determine the prevalence of MDR Tuberculosis in HIV positive patients using Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, United States). Materials and Methods The sputum samples are received from five districts of Punjab. Sputum samples of the patients with symptoms suggestive of pulmonary tuberculosis including both new cases and on treatment are received from the various district and civil hospitals of five districts. Sputum specimen was processed for TB detection by Cartridge Based Nucleic Acid Amplification testing (CB-NAAT) using Xpert MTB/RiF assay technology. Results The study period is from October 2013 to September 2014. A total of 907 patients with symptoms suggestive of pulmonary tuberculosis including both new cases and on treatment. Out of these patients 733 were reported MTB detected. Out of these 907 patients 29 were reported HIV positive and out of 733 patients 19(2.5%) were reported positive for (HIV +TUBERCULOSIS). Of these 19 cases 16(84.21%) cases were sensitive to rifampicin (RIF) and 3(15.78%) cases were showing resistance to rifampicin (RIF) Drug. Conclusion Co-existence of HIV and tuberculosis is high and there is high Prevalence of MDR tuberculosis in HIV patients.

  13. Tuberculosis Disease Diagnosis Using Artificial Immune Recognition System

    PubMed Central

    Shamshirband, Shahaboddin; Hessam, Somayeh; Javidnia, Hossein; Amiribesheli, Mohsen; Vahdat, Shaghayegh; Petkovi?, Dalibor; Gani, Abdullah; Kiah, Miss Laiha Mat

    2014-01-01

    Background: There is a high risk of tuberculosis (TB) disease diagnosis among conventional methods. Objectives:This study is aimed at diagnosing TB using hybrid machine learning approaches. Materials and Methods: Patient epicrisis reports obtained from the Pasteur Laboratory in the north of Iran were used. All 175 samples have twenty features. The features are classified based on incorporating a fuzzy logic controller and artificial immune recognition system. The features are normalized through a fuzzy rule based on a labeling system. The labeled features are categorized into normal and tuberculosis classes using the Artificial Immune Recognition Algorithm. Results:Overall, the highest classification accuracy reached was for the 0.8 learning rate (?) values. The artificial immune recognition system (AIRS) classification approaches using fuzzy logic also yielded better diagnosis results in terms of detection accuracy compared to other empirical methods. Classification accuracy was 99.14%, sensitivity 87.00%, and specificity 86.12%. PMID:24688316

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

    PubMed Central

    Raman, Karthik; Yeturu, Kalidas; Chandra, Nagasuma

    2008-01-01

    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, perhaps because standard methodologies to identify such targets in a high-throughput fashion do not really exist. With different kinds of 'omics' data that are now available, computational approaches can be powerful means of obtaining short-lists of possible targets for further experimental validation. Results We report a comprehensive in silico target identification pipeline, targetTB, for Mycobacterium tuberculosis. The pipeline incorporates a network analysis of the protein-protein interactome, a flux balance analysis of the reactome, experimentally derived phenotype essentiality data, sequence analyses and a structural assessment of targetability, using novel algorithms recently developed by us. Using flux balance analysis and network analysis, proteins critical for survival of M. tuberculosis are first identified, followed by comparative genomics with the host, finally incorporating a novel structural analysis of the binding sites to assess the feasibility of a protein as a target. Further analyses include correlation with expression data and non-similarity to gut flora proteins as well as 'anti-targets' in the host, leading to the identification of 451 high-confidence targets. Through phylogenetic profiling against 228 pathogen genomes, shortlisted targets have been further explored to identify broad-spectrum antibiotic targets, while also identifying those specific to tuberculosis. Targets that address mycobacterial persistence and drug resistance mechanisms are also analysed. Conclusion The pipeline developed provides rational schema for drug target identification that are likely to have high rates of success, which is expected to save enormous amounts of money, resources and time in the drug discovery process. A thorough comparison with previously suggested targets in the literature demonstrates the usefulness of the integrated approach used in our study, highlighting the importance of systems-level analyses in particular. The method has the potential to be used as a general strategy for target identification and validation and hence significantly impact most drug discovery programmes. PMID:19099550

  15. Association between vitamin D insufficiency and tuberculosis in a vietnamese population

    PubMed Central

    2010-01-01

    Background Recent in vitro evidence suggests a link between vitamin D status and the risk of tuberculosis (TB). This study sought to examine the association between vitamin D status, parathyroid hormone (PTH) and the risk of TB in a Vietnamese population. Methods The study was designed as a matched case-control study, which involved 166 TB patients (113 men and 53 women), who were age-and-sex matched with 219 controls (113 men and 106 women). The average age of men and women was 49 and 50, respectively. TB was diagnosed by the presence of acid-fast bacilli on smears from sputum, and the isolation of M. tuberculosis. All patients were hospitalized for treatment in a TB specialist hospital. Controls were randomly drawn from the general community within the Ho Chi Minh, Vietnam. 25-hydroxyvitamin D [25(OH)D] and PTH was measured prior to treatment by an electrochemiluminescence immunoassay (ECLIA) on a Roche Elecsys. A serum level of 25(OH)D below 30 ng/mL was deemed to be vitamin D insufficient. Results The prevalence of vitamin D insufficiency was 35.4% in men with TB and 19.5% in controls (P = 0.01). In women, there were no significant differences in serum 25(OH)D and serum PTH levels between TB patients and controls. The prevalence of vitamin D insufficiency in women with TB (45.3%) was not significantly different from those without TB (47.6%; P = 0.91). However, in both genders, serum calcium levels in TB patients were significantly lower than in non-TB individuals. Smoking (odds ratio [OR] 1.25; 95% confidence interval [CI] 1.10 - 14.7), reduced 25(OH)D (OR per standard deviation [SD]: 1.14; 95% CI 1.07 - 10.7) and increased PTH (OR per SD 1.13; 95% CI 1.05 - 10.4) were independently associated with increased risk of TB in men. Conclusion These results suggest that vitamin D insufficiency was a risk factor for tuberculosis in men, but not in women. However, it remains to be established whether the association is a causal relationship. PMID:20973965

  16. Bacterial Genetic Signatures of Human Social Phenomena among M. tuberculosis from an Aboriginal Canadian Population

    PubMed Central

    Pepperell, Caitlin; Hoeppner, Vernon H.; Lipatov, Mikhail; Wobeser, Wendy; Schoolnik, Gary K.; Feldman, Marcus W.

    2010-01-01

    Despite a widespread global distribution and highly variable disease phenotype, there is little DNA sequence diversity among isolates of Mycobacterium tuberculosis. In addition, many regional population genetic surveys have revealed a stereotypical structure in which a single clone, lineage, or clade makes up the majority of the population. It is often assumed that dominant clones are highly adapted, that is, the overall structure of M. tuberculosis populations is the result of positive selection. In order to test this assumption, we analyzed genetic data from extant populations of bacteria circulating in Aboriginal communities in Saskatchewan, Canada. Demographic parameters of the bacterial population were estimated from archival epidemiological data collected over ?130 years since the onset of epidemic tuberculosis in the host communities. Bacterial genetic data were tested against neutral theory expectations and the local evolutionary history of M. tuberculosis investigated by phylogenetic analysis. Our findings are not consistent with positive selection on the bacterial population. Instead, we uncovered founder effects persisting over decades and barriers to gene flow within the bacterial population. Simulation experiments suggested that a combination of these neutral influences could result in the stereotypical structure of M. tuberculosis populations. Some aspects of population structure were suggestive of background selection, and data were on the whole consistent with combined effects of population bottlenecks, subdivision, and background selection. Neutral phenomena, namely, bottlenecks and partitions within populations, are prominent influences on the evolution of M. tuberculosis and likely contribute to restricted genetic diversity observed within this species. Given these influences, a complex evolutionary model will be required to define the relative fitness of different M. tuberculosis lineages and, ultimately, to uncover the genetic basis for its success as a pathogen. PMID:19861642

  17. Bacterial genetic signatures of human social phenomena among M. tuberculosis from an Aboriginal Canadian population.

    PubMed

    Pepperell, Caitlin; Hoeppner, Vernon H; Lipatov, Mikhail; Wobeser, Wendy; Schoolnik, Gary K; Feldman, Marcus W

    2010-02-01

    Despite a widespread global distribution and highly variable disease phenotype, there is little DNA sequence diversity among isolates of Mycobacterium tuberculosis. In addition, many regional population genetic surveys have revealed a stereotypical structure in which a single clone, lineage, or clade makes up the majority of the population. It is often assumed that dominant clones are highly adapted, that is, the overall structure of M. tuberculosis populations is the result of positive selection. In order to test this assumption, we analyzed genetic data from extant populations of bacteria circulating in Aboriginal communities in Saskatchewan, Canada. Demographic parameters of the bacterial population were estimated from archival epidemiological data collected over approximately 130 years since the onset of epidemic tuberculosis in the host communities. Bacterial genetic data were tested against neutral theory expectations and the local evolutionary history of M. tuberculosis investigated by phylogenetic analysis. Our findings are not consistent with positive selection on the bacterial population. Instead, we uncovered founder effects persisting over decades and barriers to gene flow within the bacterial population. Simulation experiments suggested that a combination of these neutral influences could result in the stereotypical structure of M. tuberculosis populations. Some aspects of population structure were suggestive of background selection, and data were on the whole consistent with combined effects of population bottlenecks, subdivision, and background selection. Neutral phenomena, namely, bottlenecks and partitions within populations, are prominent influences on the evolution of M. tuberculosis and likely contribute to restricted genetic diversity observed within this species. Given these influences, a complex evolutionary model will be required to define the relative fitness of different M. tuberculosis lineages and, ultimately, to uncover the genetic basis for its success as a pathogen. PMID:19861642

  18. Time to Culture Conversion and Regimen Composition in Multidrug-Resistant Tuberculosis Treatment

    PubMed Central

    Tierney, Dylan B.; Franke, Molly F.; Becerra, Mercedes C.; Alcántara Virú, Félix A.; Bonilla, César A.; Sánchez, Epifanio; Guerra, Dalia; Muñoz, Maribel; Llaro, Karim; Palacios, Eda; Mestanza, Lorena; Hurtado, Rocío M.; Furin, Jennifer J.; Shin, Sonya; Mitnick, Carole D.

    2014-01-01

    Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs. PMID:25238411

  19. Truman State University Student Health Center Tuberculosis Screening Form

    E-print Network

    Gering, Jon C.

    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

  20. Primary isolation of Mycobacterium tuberculosis on blood agar during the diagnostic process for cat scratch disease

    Microsoft Academic Search

    M. Arvand; M. E. A. Mielke; T. Regnath; H. Hahn; T. Weinke

    1998-01-01

    We here present a case of necrotizing lymphadenitis from which we isolated Mycobacreriunr tuberculosis on blood agar within 13 days during the diagnostic process for cat scratch disease. A 82-year-old woman was admitted with a 4-month history of enlarged right supraclavicular lymph nodes. Ultrasonography revealed three enlarged, partially suppurated nodes. An incision biopsy was performed and yielded pus which remained

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

    Microsoft Academic Search

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

    2008-01-01

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

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

    Microsoft Academic Search

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

    2007-01-01

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

  3. Background Dirty Paper Coding Codeword Binning Code construction Lossless Watermarking Remaining problems Information Hiding

    E-print Network

    Regalia, Phillip A.

    or transmission, information hiding is trivial: Replace select bits imperceptibly. Cover signal TOP SECRET message Hiding algorithm Modified signal Extraction algorithm TOP SECRET Recovered message Clear channel If cover is trivial: Replace select bits imperceptibly. Cover signal TOP SECRET message Hiding algorithm Modified

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

    PubMed

    Velayati, Ali Akbar; Farnia, Parissa; Mozafari, Mohadese; Sheikholeslami, Maryam Fatemeh; Karahrudi, Mona Afraei; Tabarsi, Payam; Hoffner, Sven

    2014-01-01

    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

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

    PubMed Central

    Velayati, Ali Akbar; Farnia, Parissa; Mozafari, Mohadese; Sheikholeslami, Maryam Fatemeh; Karahrudi, Mona Afraei; Tabarsi, Payam; Hoffner, Sven

    2014-01-01

    We determined the prevalence of rifampin-monoresistant tuberculosis (RMR-TB) in Iran. Because development of RMR-TB is not common, we also identified the major risk factors associated with RMR-TB reported from different provinces of Iran. Data for 3,020 TB patients who remained or became smear positive after two, four, six, and nine months of standard first-line chemotherapy were retrospectively analyzed. Of 3,020 patients, 1,242 patients (41.1%) were culture and DNA positive for Mycobacterium tuberculosis. Of these patients, 73 (7.4%) patients had monoresistant isolates to rifampin, which was significantly higher than that for multidrug-resistant TB (5.8%). The average rate of RMR-TB in the studied population ranged from 5% to 10%. Classical investigation showed that 33.6% of patients had either a previous or family history of TB. Molecular epidemiology methods (i.e., spoligotyping and Mycobacterium intespersed repetitive unit–variable number tandem repeat), defined transmission link in three clusters (13%). These results outline the urgent need for a comprehensive plan for detection and treatment of RMR-TB cases. PMID:24189362

  6. Epidemiological Characterization of Drug Resistance among Mycobacterium tuberculosis Isolated from Patients in Northeast of Iran during 2012-2013

    PubMed Central

    Tavanaee Sani, Ashraf; Shakiba, Abolfazl; Bahrami Taghanaki, Hamid Reza; Ayati Fard, Seiedeh Fatemeh; Ghazvini, Kiarash

    2015-01-01

    Introduction. Tuberculosis is still one of the most important health problems in developing countries and increasing drug resistance is the main concern for its treatment. This study was designed to characterize the drug resistant Mycobacterium tuberculosis isolated from patients suffering from pulmonary tuberculosis in northeast of Iran. Method. In this cross-sectional study during 2012-2013, drug susceptibility testing was performed on Mycobacterium tuberculosis isolated in northeast of Iran using proportional method. Epidemiological data concerning these strains were also analyzed. Results. Among 125 studied isolates, 25 mycobacteria (20%) were diagnosed as nontuberculosis mycobacteria. Among the remaining 100 Mycobacterium tuberculosis isolates, the resistance rates were 7%, 7%, 3%, and 9% against isoniazid, rifampin, ethambutol, and streptomycin, respectively. Four isolates were resistant against both isoniazid and rifampin (MDR tuberculosis). The highest resistance rate was observed among 15–45-year-old patients. The MDR tuberculosis was much more prevalent among those who had previous history of treatment. Conclusion. Considering these findings, DOTS strategy should be emphasized and promptly used in order to prevent further resistance. Regarding the high rate of nontuberculosis mycobacteria, it is recommended that confirmatory tests were performed before any therapeutic decision. PMID:26064950

  7. Facing multi-drug resistant tuberculosis.

    PubMed

    Sotgiu, Giovanni; Migliori, Giovanni Battista

    2015-06-01

    Multi-drug resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis strains resistant to at least two of the most effective anti-tuberculosis drugs (i.e., isoniazid and rifampicin). Therapeutic regimens based on second- and third-line anti-tuberculosis medicines showed poor efficacy, safety, and tolerability profiles. It was estimated that in 2012 the multi-drug resistant tuberculosis incidence ranged from 300,000 to 600,000 cases, mainly diagnosed in the Eastern European and Central Asian countries. The highest proportion of cases is among individuals previously exposed to anti-tuberculosis drugs. Three main conditions can favour the emergence and spread of multi-drug resistant tuberculosis: the poor implementation of the DOTS strategy, the shortage or the poor quality of the anti-tuberculosis drugs, and the poor therapeutic adherence of the patients to the prescribed regimens. Consultation with tuberculosis experts (e.g., consilium) is crucial to tailor the best anti-tuberculosis therapy. New therapeutic options are necessary: bedaquiline and delamanid seem promising drugs; in particular, during the development phase they demonstrated a protective effect against the emergence of further resistances towards the backbone drugs. In the recent past, other antibiotics have been administered off-label: the most relevant efficacy, safety, and tolerability profile was proved in linezolid-, meropenem/clavulanate-, cotrimoxazole-containing regimens. New research and development activities are needed in the diagnostic, therapeutic, preventive fields. PMID:24792579

  8. Incidence, etiopathogenesis and pathological aspects of genitourinary tuberculosis in India: A journey revisited

    PubMed Central

    Das, Prasenjit; Ahuja, Arvind; Gupta, Siddhartha Datta

    2008-01-01

    Background: Tuberculosis is one of the major health problems in India. Genitourinary tuberculosis comprises 20% of all extrapulmonary tuberculosis, and is the most common extrapulmonary system to be affected by this disease. The recent surge in the incidence of HIV-infected patients in India has further ignited the fury. Though the members of the Mycobacterium species are well identified, the incidence could not be controlled due to its complex etiopathogenesis and genetic background. Pathological Spectrum: The spectrum of pathological changes of genitourinary tuberculosis is wide, which varies from normal morphology to markedly scarred kidney, bladder, and epididymis with autocystectomy. A thorough knowledge is required to prevent the end-stage complications. The sequel can be detrimental for the patient's physical, behavioral, psychological, and financial health. Diagnostic Dilemmas: Though culture and polymerase chain reaction are available for the detection of tuberculosis, the sensitivity and specificity varies widely and one should be aware. Conclusions: A thorough knowledge of epidemiology, immunopathogenesis, spectrum of the disease and the possible sequels, will help better and effective management of the disease. PMID:19468469

  9. Childhood tuberculosis in general practice.

    PubMed

    Kumar, Prawin; Kumar, Amber; Lodha, Rakesh; Kabra, S K

    2015-04-01

    Tuberculosis (TB) in children is a common cause of morbidity. Diagnosis is difficult because of paucibacillary nature of illness and difficulty in obtaining appropriate samples. Children presenting with poor weight gain, fever with or without cough for more than two weeks or contact with an adult in family with pulmonary tuberculosis should be investigated for TB. In all suspected cases of tuberculosis initial investigations include radiograph of chest (CXR) and Mantoux test. If CXR is suggestive of TB, an ambulatory gastric aspirate and induced sputum for acid fast bacilli (AFB) smear may be carried out in two days. Children with AFB positive or abnormal CXR with positive Mantoux test should be started on Antitubercular therapy (ATT). Rest of the patients require more investigations and should be referred to a specialist. All children with newly diagnosed tuberculosis should be treated with 6 mo of ATT (two months with 4 drugs, followed by four months with 2 drugs). Children on ATT should be monitored for improvement in symptoms and weight gain along with side effects of medications. CXR should be done after completion of treatment. PMID:25280927

  10. Screening of tuberculosis before biologics.

    PubMed

    Mrozek, N; Pereira, B; Soubrier, M; Gourdon, F; Laurichesse, H

    2012-01-01

    Using anti-TNF has significantly improved the management of chronic inflammatory rheumatism. However, there is clear evidence that this treatment increases the risk of reactivating tuberculosis. The intradermal tuberculin skin test (ITT) and interferon-?-release assays (IGRAs) are currently used to detect latent tuberculosis infection. The results of ITT are difficult to analyze in patients vaccinated with Bacille Calmette-Guérin (BCG) and because of variation in test administration and reading. Numerous authors have compared the sensitivity and specificity of IGRA and ITT, including in two recent meta-analyses and one literature review. These authors, however, compared different populations with different ITT positive thresholds (5, 10, and 15mm). We performed a meta-analysis of studies in which the threshold was 15mm, the recommended level in France. The sensitivity of QuantiFERON, T-spot, and ITT was 79% (IC 76%-83%), 84% (IC 75%-95%), and 69% (IC 65%-73%), respectively. In France, it is recommended to detect latent tuberculosis infection on the basis of history taking, physical examination, 5-unit ITT, and lung X-ray. This screening leads to treating 20%-30% of patients, with considerable adverse-effects. Because of the sensitivity and specificity of IGRAs, it is no longer justified to systematically perform TST for detection of tuberculosis before initiating anti-TNF treatment. PMID:21907513

  11. Tuberculosis: clinical manifestations and outcomes.

    PubMed

    Nissapatorn, V; Kuppusamy, I; Anuar, A Khairul; Quek, K F; Latt, H M

    2003-01-01

    A total of 290 HIV/AIDS patients were recruited into this retrospective study, which was carried out at the National Tuberculosis Center (NTBC), Kuala Lumpur. The age range was 18 to 75 years with a mean age of 36.10 (SD +/- 7.44) years. Males outnumbered females by a ratio of 31:1. In this study, the majority of patients were male (96.9%), Malay (47.2%), single (66.9%), unemployed (81%), and smoked (61.4%). The main risk marker identified was injecting drug use (74.5%). The most common clinical manifestations were cough, fever, sputum, lymphadenopathy, and chest infiltrations. More than half of the patients (85.9%) were diagnosed with localized tuberculosis (pulmonary) and the others (14.1%) had extra-pulmonary or disseminated tuberculosis. At the time of this study, the majority of the patients (16.9%) had CD4 cell counts of less than 200 cell/mm3, with a median of 221 cell/mm3. Clinical outcomes demonstrated that among those who survived, 11.0% and 20.7% of the patients had completed treatment either > or = 6 or > or = 9 months, respectively, whereas 54.8% of patients were lost to follow-up, including 0.7% for MDR-TB. Diagnostic criteria for tuberculosis in this study were mainly clinical symptoms/signs and chest x-ray findings (31.0%). PMID:19238668

  12. IL-12R?1 Deficiency in Two of Fifty Children with Severe Tuberculosis from Iran, Morocco, and Turkey

    PubMed Central

    Bustamante, Jacinta; Feinberg, Jacqueline; Samarina, Arina; Grant, Audrey V.; Janniere, Lucile; El Hafidi, Naima; Hassani, Amal; Nolan, Daniel; Najib, Jilali; Camcioglu, Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Tanir, Gonul; Aytekin, Caner; Keser, Melike; Somer, Ayper; Aksu, Guside; Kutukculer, Necil; Mansouri, Davood; Mahdaviani, Alireza; Mamishi, Setareh; Alcais, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

    2011-01-01

    Background and Objectives In the last decade, autosomal recessive IL-12R?1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from Morocco, Spain, and Turkey, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12R?1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. Methods and Principal Findings We searched for IL12RB1 mutations in a series of 50 children from Iran, Morocco, and Turkey. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from Iran and another from Morocco, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12R?1 deficiency. Despite the small sample studied, our findings suggest that IL-12R?1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. Significance This finding may have important medical implications, as recombinant IFN-? is an effective treatment for mycobacterial infections in IL-12R?1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity. PMID:21533230

  13. Coal remains a hot commodity for Australia

    SciTech Connect

    Bram, L.

    2006-02-15

    Based largely on analyses by the Australian Bureau of Agricultural and Resource Economics in late 2005 and early 2006, the article looks at the recent and near future export market for Australian coal. Demand in Asia is growing; European demand remains steady. Developments existing and new mines in Queensland are summarised in the article. 3 tabs.

  14. Juveniles' Motivations for Remaining in Prostitution

    ERIC Educational Resources Information Center

    Hwang, Shu-Ling; Bedford, Olwen

    2004-01-01

    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…

  15. Essential Qualities of Math Teaching Remain Unknown

    ERIC Educational Resources Information Center

    Cavanagh, Sean

    2008-01-01

    According to a new federal report, the qualities of an effective mathematics teacher remain frustratingly elusive. The report of the National Mathematics Advisory Panel does not show what college math content and coursework are most essential for teachers. While the report offered numerous conclusions about math curriculum, cognition, and…

  16. The case for fencing remains intact.

    PubMed

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

    2013-11-01

    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

  17. REMAINING ISSUES OVER HAZARDOUS WASTE THERMAL DESTRUCTION

    EPA Science Inventory

    Since 1980, the U.S. Environmental Protection Agency (EPA) has conducted extensive research to assess the performance of hazardous waste thermal destruction processes. Some members of the scientific and the environmental action community remain concerned about the long-term safet...

  18. Odor analysis of decomposing buried human remains

    SciTech Connect

    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

    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.

  19. Russian questions remain after space station review

    NASA Technical Reports Server (NTRS)

    Asker, James R.

    1994-01-01

    Following the project's first major design review, some unresolved technical issues, mainly centered on details of how to integrate Russian hardware into the U.S./international space station, remain. No 'show stoppers' were found in the review. Specific open technical issues are discussed in this article.

  20. Predicting the remaining service life of concrete

    SciTech Connect

    Clifton, J.F.

    1991-11-01

    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.

  1. Function and Potentials of M. tuberculosis Epitopes

    PubMed Central

    Ivanyi, Juraj

    2014-01-01

    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

  2. Salvage therapy for multidrug-resistant tuberculosis.

    PubMed

    Seung, K J; Becerra, M C; Atwood, S S; Alcántara, F; Bonilla, C A; Mitnick, C D

    2014-05-01

    Treatment of multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis resistant to both isoniazid and rifampicin, is challenging under the best of circumstances, and particularly in resource-limited settings. For patients who remain persistently sputum-culture-positive despite therapy with second-line TB drugs, treatment options are limited, especially if disease is too advanced for resective surgery. Salvage therapy refers to the design of a regimen combining new and previously used drugs in a final effort to attain sputum conversion before declaring treatment to have failed. We retrospectively evaluated the outcomes of salvage therapy in 213 Peruvian patients. Salvage regimens included a median of two new drugs (range 1-6) and nine (range 5-13) total (new plus previously used) drugs. The most frequently used new drug was moxifloxacin, followed by capreomycin, amoxicillin-clavulanate, kanamycin and clarithromycin. Culture conversion occurred in 65 (30.5%) patients. Salvage regimens that included moxifloxacin were significantly more likely to be followed by culture conversion (OR 2.2; p 0.02). Later-generation fluoroquinolones such as moxifloxacin should be used in salvage therapy but also in the initial treatment of MDR-TB, if the best clinical strategy is to use the most effective drugs when the patient has the best chance for cure. New TB drugs are most likely to be initially used in salvage patients, in conditions similar to those described here. Close bacteriological monitoring of these patients will be essential, as useful information about the best way to use these new drugs can be gained from analysis of salvage therapy cohorts. PMID:23991934

  3. Mannosylated Lipoarabinomannan in serum as a biomarker candidate for subclinical bovine tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Early and unambiguous detection of bovine tuberculosis (bTB), a significant disease of cattle worldwide, is necessary to control the spread of infection to other animals and humans. Current testing strategies are laborious, time consuming and heavily reliant on host responses that do n...

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

    Microsoft Academic Search

    Hsien-Ho Lin; Majid Ezzati; Megan Murray

    2007-01-01

    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

  5. A Dynamic Analysis of Tuberculosis Dissemination to Improve Control and Surveillance

    Microsoft Academic Search

    Rita M. Zorzenon Dos Santos; Ana Amador; Wayner V. de Souza; Maria Fatima P. M. de Albuquerque; Silvina Ponce Dawson; Antonio Ruffino-Netto; Carlos R. Zárate-Bladés; Celio L. Silva; Robert J. Wilkinson

    2010-01-01

    BackgroundDetailed analysis of the dynamic interactions among biological, environmental, social, and economic factors that favour the spread of certain diseases is extremely useful for designing effective control strategies. Diseases like tuberculosis that kills somebody every 15 seconds in the world, require methods that take into account the disease dynamics to design truly efficient control and surveillance strategies. The usual and

  6. Cutaneous Tuberculosis of the Penis and Sexual Transmission of Tuberculosis Confirmed by Molecular Typing

    Microsoft Academic Search

    Malcolm Yates; C. Conlon; I. Byren

    2001-01-01

    A case of culture-positive primary cutaneous Mycobacterium tuberculosis infection of the penis was diagnosed in a male patient; 1 year later, endometrial tuberculosis was diagnosed in the patient's wife. These organisms were confirmed to be indistinguishable by use of molecular techniques. Extrapulmonary tuberculosis is a relatively uncommon condition in the developed world. It is occasionally associated with other serious underlying

  7. [Increased IL-4 production in response to virulent Mycobacterium tuberculosis in tuberculosis patients with advanced disease].

    PubMed

    Ordway, Diane J; Martins, Marta S; Costa, Leonor M; Freire, Mónica S; Arroz, Maria J; Dockrell, Hazel M; Ventura, Fernando A

    2005-01-01

    The study was designed to compare immune responses to Mycobacterium tuberculosis bacilli and antigens in healthy Portuguese subjects and pulmonary tuberculosis patients (TB), and to correlate immune status with clinical severity of tuberculosis disease. PBMC were cultured and stimulated with live and killed M. tuberculosis H37Rv and purified protein derivative (PPD) and lymphoproliferation and production of IFN-gamma and IL-5/IL-4 by these cultures were evaluated by the use of ELISA and multi-parameter flow cytometry. PBMC from 30 tuberculosis patients demonstrated significantly reduced amounts of proliferation and IFN-gamma when stimulated with live M. tuberculosis compared the control group. Of 15 tuberculosis patients tested for intracellular IL-4 following stimulation with M. tuberculosis, 7 showed greatly increased IL-4 production in CD8+ and gammadelta+ T cells. Tuberculosis patients demonstrated an increase of intracellular IL-4 after PBMC were stimulated with live M. tuberculosis in the CD4+ phenotype, but more notably in CD8+ and gammadelta TCR+ subsets. Increased production of IL-4 in tuberculosis patients was primarily in individuals with advanced involvement of lung parenchymal with high bacterial loads in sputum. These results suggest that an alteration in type 1 and type 2 cytokine balance can occur in patients with tuberculosis at an advanced clinical stage of disease. PMID:16202332

  8. Diabetes mellitus and tuberculosis in countries with high tuberculosis burdens: individual

    E-print Network

    Cohen, Ted

    Diabetes mellitus and tuberculosis in countries with high tuberculosis burdens: individual risks of type 2 diabetes as an individual-level risk factor for tuberculosis (TB), though evi- dence from the poor, in whom diabetes may be less common. We assessed the relationship between individual-level risk

  9. Pyoderma gangrenosum with an underlying ulcerative colitis associated with bone tuberculosis

    PubMed Central

    Patvekar, Milind A.; Virmani, Neha C.

    2013-01-01

    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

  10. Fatal congenital tuberculosis due to a Beijing strain in a premature neonate.

    PubMed

    Abalain, M L; Petsaris, O; Héry-Arnaud, G; Marcorelles, P; Couturaud, F; Dobrzynski, M; Payan, C; Gutierrez, C

    2010-06-01

    Congenital tuberculosis (TB) remains a rare disease but is fatal if untreated. Early detection is difficult because of the non-specific nature of the symptoms in TB during pregnancy and infancy. This report summarizes a case of congenital TB in a very premature infant, born at 25 weeks gestation. Miliary TB was diagnosed in the mother when the neonate was 20 days old. Antituberculous therapy allowed a rapid improvement in the mother. The infant died at 27 days old. A Beijing genotype strain of Mycobacterium tuberculosis was isolated both in the mother, from pulmonary and urine specimens, and in the infant, from peritoneal fluid. PMID:20203217

  11. Treatment of advanced ovarian carcinoma coexistent with peritoneal tuberculosis

    PubMed Central

    NAGASHIMA, AIKO; MATSUMOTO, YOSHINARI; OHSAWA, MASAHIKO; SUMI, TOSHIYUKI

    2013-01-01

    Primary ovarian carcinoma is often chemosensitive. Therefore, aggressive treatment is recommended for patients with ovarian carcinoma. Peritoneal tuberculosis is rare and may present with symptoms similar to those of advanced ovarian carcinoma. To the best of our knowledge, this is the first report of a case of primary advanced ovarian carcinoma coexistent with peritoneal tuberculosis. The patient had undergone three courses of neoadjuvant chemotherapy with tri-weekly paclitaxel and carboplatin (TC), followed by total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and pelvic and para-aortic lymphadenectomy. The postoperative pathological examination confirmed the diagnosis of ovarian serous papillary adenocarcinoma coexistent with peritoneal tuberculosis. The patient was started on antituberculous chemotherapy, followed 2 weeks later by four courses of antitumor chemotherapy with weekly TC. The plasma concentration of paclitaxel was measured after the first administration of TC. We considered that rifampicin may enhance the metabolism of paclitaxel, causing the plasma concentration of paclitaxel to decrease. Therefore, rifampicin administration was discontinued on days 1, 8 and 15. The patient completed the antitumor and antituberculous chemotherapy and has remained alive and recurrence-free for 5-years. Although rifampicin may enhance the metabolism of paclitaxel, we suggest that it may be possible to administer concurrent antituberculous and antitumor chemotherapy under close observation. PMID:24649297

  12. Treatment of advanced ovarian carcinoma coexistent with peritoneal tuberculosis.

    PubMed

    Nagashima, Aiko; Matsumoto, Yoshinari; Ohsawa, Masahiko; Sumi, Toshiyuki

    2013-11-01

    Primary ovarian carcinoma is often chemosensitive. Therefore, aggressive treatment is recommended for patients with ovarian carcinoma. Peritoneal tuberculosis is rare and may present with symptoms similar to those of advanced ovarian carcinoma. To the best of our knowledge, this is the first report of a case of primary advanced ovarian carcinoma coexistent with peritoneal tuberculosis. The patient had undergone three courses of neoadjuvant chemotherapy with tri-weekly paclitaxel and carboplatin (TC), followed by total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and pelvic and para-aortic lymphadenectomy. The postoperative pathological examination confirmed the diagnosis of ovarian serous papillary adenocarcinoma coexistent with peritoneal tuberculosis. The patient was started on antituberculous chemotherapy, followed 2 weeks later by four courses of antitumor chemotherapy with weekly TC. The plasma concentration of paclitaxel was measured after the first administration of TC. We considered that rifampicin may enhance the metabolism of paclitaxel, causing the plasma concentration of paclitaxel to decrease. Therefore, rifampicin administration was discontinued on days 1, 8 and 15. The patient completed the antitumor and antituberculous chemotherapy and has remained alive and recurrence-free for 5-years. Although rifampicin may enhance the metabolism of paclitaxel, we suggest that it may be possible to administer concurrent antituberculous and antitumor chemotherapy under close observation. PMID:24649297

  13. Genotyping of ancient Mycobacterium tuberculosis strains reveals historic genetic diversity

    PubMed Central

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

    2014-01-01

    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

  14. Remaining Questions about Clinical Variola Major

    PubMed Central

    2011-01-01

    After the recent summary of World Health Organization–authorized research on smallpox, several clinical issues remain. This policy review addresses whether early hemorrhagic smallpox is disseminated intravascular coagulation and speculates about the cause of the high mortality rate among pregnant women and whether ocular smallpox is partly the result of trachoma or vitamin A deficiency. The joint destruction common in children with smallpox might be prevented by antiviral drugs, but intraarticular infusion of antiviral drugs is unprecedented. Development of highly effective antiviral drugs against smallpox raises the issue of whether postexposure vaccination can be performed without interference by an antiviral drug. Clinicians should consider whether patients with smallpox should be admitted to general hospitals. Although an adequate supply of second-generation smallpox vaccine exists in the United States, its use is unclear. Finally, political and ethical forces suggest that destruction of the remaining stocks of live smallpox virus is now appropriate. PMID:21470458

  15. Mycobacterium tuberculosis 6-kDa Early Secreted Antigenic Target (ESAT-6) protein downregulates Lipopolysaccharide induced c-myc expression by modulating the Extracellular Signal Regulated Kinases 1\\/2

    Microsoft Academic Search

    Niladri Ganguly; Pham H Giang; Sandip K Basu; Fayaz Ahmad Mir; Imran Siddiqui; Pawan Sharma

    2007-01-01

    BACKGROUND: Mycobacterium tuberculosis (Mtb) causes death of 2–3 million people every year. The persistence of the pathogenic mycobacteria inside the macrophage occurs through modulation of host cell signaling which allows them, unlike the other non-pathogenic species, to survive inside the host. The secretory proteins of M. tuberculosis have gained attention in recent years both as vaccine candidates and diagnostic tools;

  16. Pulmonary Tuberculoma and Miliary Tuberculosis in Silicosis

    PubMed Central

    Verma, Sanjeev Kumar; Karmakar, Saurabh

    2013-01-01

    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

  17. Association between neuromyelitis optica and tuberculosis in a Chinese population

    PubMed Central

    2014-01-01

    Background A number of reports have described the presence of tuberculosis (TB) in neuromyelitis optica (NMO) patients. However, a definite association between the two conditions has not been conclusively demonstrated. Methods To investigate the association between NMO and TB in a Chinese population, we performed a retrospective review of hospital records of NMO patients, control patients and tuberculosis meningitis (TBM) patients from January 1, 1995 to December 31, 2011. Results The frequency of preceding/simultaneous active pulmonary TB (PTB) was not significantly different between NMO patients (1.1%) and control groups (2.3% in myasthenia gravis, 1.1% in polymyositis or dermatomyositis, zero in idiopathic facial palsy and viral meningitis/meningoencephalitis). NMO cases differed from TBM cases in terms of demographics, course (recurrent or monophasic), cerebrospinal fluid analysis and magnetic resonance images. Two TBM patients shared partial clinical features with NMO (one of the TBM patients had a longitudinal extensive spinal cord lesion involving the holocord, and the other had optic neuritis before anti-tuberculosis treatment). NMO antibodies were only detected in NMO patients and not in TBM patients with myelitis or optic neuritis. Conclusions We could not confirm previous suggestions of the association between PTB and NMO. Direct infection of the central nervous system by TB may mimic NMO in some respects, but whether NMO-like symptoms that develop during the course of TB should be considered and diagnosed as NMO is open to discussion. PMID:24555792

  18. A New Approach for Pyrazinamide Susceptibility Testing in Mycobacterium tuberculosis

    PubMed Central

    Loli, Sebastian; Gilman, Robert H.; Gutierrez, Andrés; Fuentes, Patricia; Cotrina, Milagros; Kirwan, Daniela; Sheen, Patricia

    2012-01-01

    Background: Pyrazinamide (PZA) is an important drug in the treatment of tuberculosis. Microbiological methods of PZA susceptibility testing are controversial and have low reproducibility. After conversion of PZA into pyrazinoic acid (POA) by the bacterial pyrazinamidase enzyme, the drug is expelled from the bacteria by an efflux pump. Objective: To evaluate the rate of POA extrusion from Mycobacterium tuberculosis as a parameter to detect PZA resistance. Methods: The rate of POA extrusion and PZA susceptibility determined by BACTEC 460 were measured for 34 strains in a previous study. PZA resistance was modeled in a logistic regression with the pyrazinoic efflux rate. Result: POA efflux rate predicted PZA resistance with 70.83%–92.85% sensitivity and 100% specificity compared with BACTEC 460. Conclusion: POA efflux rate could be a useful tool for predicting PZA resistance in M. tuberculosis. Further exploration of this approach may lead to the development of new tools for diagnosing PZA resistance, which may be of public health importance. PMID:22372927

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

    PubMed

    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

    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

  20. Spectrum of tuberculosis in patients with HIV infection in British Columbia: report of 40 cases.

    PubMed Central

    Korzeniewska-Kosela, M; FitzGerald, J M; Vedal, S; Allen, E A; Schechter, M T; Lawson, L; Phillips, P; Black, W; Montaner, J S

    1992-01-01

    OBJECTIVE: To review the clinical features, treatment and outcome of all known cases of tuberculosis in patients with human immunodeficiency virus (HIV) infection in British Columbia between 1984 and 1990. DESIGN: Retrospective case review. SETTING: Provincial tuberculosis registry and university-affiliated HIV clinic. PATIENTS: All people with HIV infection in whom active tuberculosis was diagnosed during the study period. RESULTS: All 40 patients identified were men; their mean age was 38 years. Of the subjects 30 (75%) were homosexual, 6 (15%) were homosexual and used intravenous drugs, 2 (5%) just used intravenous drugs, and 1 (2%) had had heterosexual contact with prostitutes; for the remaining subject the risk factor for HIV infection was not established. In all cases cultures of specimens from 15 body sources yielded Mycobacterium tuberculosis. Thirty-five of the patients had acquired immunodeficiency syndrome (AIDS), and five had HIV infection uncomplicated except for tuberculosis. In 28 (70%) of the cases no AIDS-defining disease had previously been diagnosed, and in 23 (58%) extrapulmonary tuberculosis represented the AIDS-defining disease. Symptoms at presentation included weight loss (in 80% of the cases), fever (in 75%), cough (in 70%) and night sweats (in 55%). The mean CD4 lymphocyte count was 0.2 x 10(9)/L (in 15 cases). Tuberculin skin test results were positive in 8 of 16 cases. The most striking radiologic finding was intrathoracic adenopathy. All except one of the 36 patients who received appropriate treatment responded favourably at first. Adverse reactions necessitating changes in treatment occurred in 12 (33%) of the cases. Relapse occurred after completion of therapy in two cases (one at 3 weeks and the other at 9 months after treatment was stopped). Tuberculosis was the cause of death in five cases. CONCLUSIONS: Tuberculosis in people with HIV infection commonly presents as extrapulmonary disease and precedes or coincides with other AIDS-defining opportunistic infections. In most cases tuberculosis is the AIDS-defining disease. Even though radiologic findings are often unusual physicians should suspect tuberculosis. A careful examination for evidence of disease at multiple sites should be done. The duration and choice of therapy must be adequate to avoid relapse. PMID:1596841

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

    PubMed Central

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

    2001-01-01

    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

  2. T cells and adaptive immunity to Mycobacterium tuberculosis in humans.

    PubMed

    Jasenosky, Luke D; Scriba, Thomas J; Hanekom, Willem A; Goldfeld, Anne E

    2015-03-01

    The adaptive immune response mediated by T cells is critical for control of Mycobacterium tuberculosis (M. tuberculosis) infection in humans. However, the M. tuberculosis antigens and host T-cell responses that are required for an effective adaptive immune response to M. tuberculosis infection are yet to be defined. Here, we review recent findings on CD4(+) and CD8(+) T-cell responses to M. tuberculosis infection and examine the roles of distinct M. tuberculosis-specific T-cell subsets in control of de novo and latent M. tuberculosis infection, and in the evolution of T-cell immunity to M. tuberculosis in response to tuberculosis treatment. In addition, we discuss recent studies that elucidate aspects of M. tuberculosis-specific adaptive immunity during human immunodeficiency virus co-infection and summarize recent findings from vaccine trials that provide insight into effective adaptive immune responses to M. tuberculosis infection. PMID:25703553

  3. [Intestinal tuberculosis: Easier overlooked than diagnosed].

    PubMed

    Göke, M N; Leppert, A; Flemming, P; Soudah, B; Bange, F C; Bleck, J S; Widjaja, A; Högemann, B; Mellmann, J; Ockenga, J; Schedel, I; Gebel, M; Manns, M P

    2001-12-01

    Intestinal tuberculosis: Easier overlooked than diagnosed. The medical history of two Asian immigrants suffering from intestinal tuberculosis demonstrates the difficulties in finding the correct diagnosis. Intestinal tuberculosis resembles Crohn's disease with regard to clinical symptoms, macroscopic and microscopic intestinal findings. Sonographic, radiologic, endoscopic, and histological examinations facilitate distinguishing both entities. Diagnosis of intestinal tuberculosis is made by identification of the causative microorganism in tissue specimens. As this may be difficult and time-consuming, a therapeutic trial with anti-tuberculous agents may be warranted. PMID:11753786

  4. Skin tuberculosis in children: learning from India.

    PubMed

    Sethuraman, Gomathy; Ramesh, V; Ramam, M; Sharma, Vinod K

    2008-04-01

    Cutaneous tuberculosis in children is a major health problem in India. It accounts for about 1.5% of all the cases of extrapulmonary tuberculosis. Scrofuloderma and lupus vulgaris are the two most common forms of tuberculosis. However, the trend in the pattern of cutaneous tuberculosis is changing, as the tuberculid, lichen scrofulosorum, has become more common in recent years. Overall, the clinical patterns are comparable with adults. However, children can have widespread and severe involvement because many unusual and uncommon patterns are known to occur in children. Underlying systemic involvement is more common in children, compared with adults. PMID:18346559

  5. Isolated hepatosplenic tuberculosis: a rare presentation.

    PubMed

    Hasan, Roumina; Kumar, Sandeep; Mathew, Mary; Kadavigere, Rajagopal

    2015-01-01

    Tuberculosis caused by Mycobacterium tuberculosis presents a major health challenge in endemic countries and spares no organ in the human body. This infection is a mimicker of various disease processes such as metastasis, lymphoproliferative diseases, and other granulomatous conditions such as sarcoidosis and fungal infections. The most challenging and important differential is metastasis, especially in the disseminated form of tuberculosis. We present a histopathologically proven case of isolated hepatosplenic tuberculosis that was provisionally diagnosed as lymphoma due to its unusual, restricted involvement of the liver and spleen. PMID:26153294

  6. Immunogenic potential of latency associated antigens against Mycobacterium tuberculosis.

    PubMed

    Singh, Swati; Saraav, Iti; Sharma, Sadhna

    2014-02-01

    Tuberculosis remains a great health threat to the world among infectious diseases particularly with the advent of human immunodeficiency virus and emergence of drug resistant strains. In the light of the inconsistent efficacy imparted by the only currently available pre-exposure vaccine bacillus Calmette-Guerin BCG, the development of an improved TB vaccine is a very high international research priority. Vaccine candidates currently in clinical trials are also pre-exposure vaccines that aim to prevent active tuberculosis during an individual's lifetime. According to World Health Organization approximately a third of the world's population is latently infected with Mycobacterium tuberculosis. Dormancy or latency of Mycobacteria is associated with the formation of granuloma with poorly perfused interior leading to expression of genes which help them survive in this hostile environment. A group of about 50 genes belonging to the DosR regulon also known as latency antigens are expressed by Mycobacteria when they are persisting in the immuno-competent host. An understanding of the immunological effects produced by products of these latency induced genes may help in making a more potent vaccine. Incorporation of latency antigens into improved (live or subunit) vaccines may enhance the impact of these vaccines in which BCG priming can be followed by multisubunit protein boosting. These vaccines could act as post exposure vaccines for containment and prevention of latent TB activation. This heterologous boosting of BCG-primed immunity will be able to stimulate the known immune correlates of protective immunity against M. tuberculosis i.e. TH1 cells (CD4(+) and CD8(+) T cells) mediated immune responses with cytokines such as IFN-? and TNF-?? In our review we have analysed and compared the immunogenic potential of various latency-associated antigens of the DosR regulon in line with the current strategy of developing a recombinant post exposure booster vaccine. PMID:24300592

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

    PubMed Central

    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

    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. PMID:25237849

  8. Vitamin D Receptor Gene Polymorphisms on the Risk of Tuberculosis, a Meta-Analysis of 29 Case-Control Studies

    PubMed Central

    Chen, Cheng; Liu, Qiao; Zhu, Limei; Yang, Haitao; Lu, Wei

    2013-01-01

    The relationship of four potentially functional polymorphisms of the vitamin D receptor (VDR) gene, ApaI, BsmI, FokI and TaqI , with tuberculosis susceptibility were considered. The aim of this meta-analysis was to explore the association between the four polymorphisms and tuberculosis risk in different ethnic backgrounds. Eligible case-control studies that were catalogued before April 1st 2013 were enrolled, and the heterogeneity between the studies was evaluated using a ?2 based Q-test. Fixed and random effect models were built to evaluate the association of the four polymorphisms with the risk of tuberculosis, and the association between the four polymorphisms and tuberculosis was expressed as the odds ratio (OR) and 95% confidence interval (CI). Finally, twenty nine qualified studies were enrolled for this meta-analysis that included 6179 tuberculosis cases and 6585 healthy controls. The variant homozygote genotype of the FokI polymorphism was associated with a significantly increased risk of tuberculosis when compared to the heterozygote and wild type homozygote genotypes in the Chinese population (ff vs. Ff+FF: ORrecessive=1.97, 95%CI: 1.32-2.93, Pbonferroni=0.0032; heterogeneity test: ?2=0.24, P=0.62). For European subjects, the homozygote and heterozygote genotypes of the BsmI polymorphism were associated with a significantly decreased risk of tuberculosis when compared to the wild type homozygote (bb+Bb vs. BB: ORdominant=0.41, 95%CI, 0.22-0.76, Pbonferroni=0.02; heterogeneity test: ?2=2.59, P=0.11). Based on the above results, we conclude that variants of the VDR gene that are homozygous for the FokI polymorphism might be more susceptible to tuberculosis in Chinese. Furthermore, larger sample studies are warranted to confirm the protective effects of BsmI variants on tuberculosis in the Europeans. PMID:24349552

  9. Evaluation of the radiological sequelae after treatment completion in new cases of pulmonary, pleural, and mediastinal tuberculosis

    PubMed Central

    Menon, Balakrishnan; Nima, Gaki; Dogra, Vikas; Jha, Santosh

    2015-01-01

    Background: Residual radiological lesions may persist even after successful treatment of tuberculosis. There is insufficient data as to the nature and magnitude of these opacities in the treated cases of tuberculosis. Aims and Objectives: This study evaluates the nature and magnitude of residual radiological opacities and of complete radiological resolution in new successfully treated cases of tuberculosis. Design: Four hundred and forty one new cases of pulmonary, pleural or mediastinal tuberculosis were radiologically evaluated by chest x-ray, PA view, at the start and end of a successful treatment, which was as per the World Health Organization (WHO), Revised National Tuberculosis Control Program (RNTCP), and Directly Observed Treatment, Short-Course (DOTS) guidelines. Patients with a previous history of tuberculosis or other lung conditions, treatment failure, retreatment cases, and multidrug tuberculosis (MDR-TB) cases were excluded. Results: Residual x-ray lesions were seen in 178 cases of tuberculosis (40.36%). Complete radiological resolution was seen in 263 cases (59.64%). Of the residual lesions, 67.4% were parenchymal were parenchymal in nature, 23.59% were pleural lesions and 8.99% were mediastinal lesions. Out of the 126 sputum-positive cases, 70% (n = 88)had residual lesions on chest x-ray whereas of the 315 sputum-negative cases 28.5%, (n = 99) had radiological residual lesions. Conclusion: Residual radiological opacities are seen in a large proportion of treated cases of tuberculosis (40%). Pulmonary lesions show more residual lesions (67%) than pleural (23%) and mediastinal lesions (9%). PMID:25983409

  10. Evaluation of anti-A60 antigen IgG enzyme-linked immunosorbent assay for serodiagnosis of pulmonary tuberculosis

    PubMed Central

    Bukhary, Zakeya Abdulbaqi

    2007-01-01

    BACKGROUND: Problems in the diagnosis of tuberculosis using smear and culture techniques have necessitated the exploration of the utility of serodiagnosis to support clinical suspicion of tuberculosis. Anti-A60 antigen IgG enzyme-linked immunosorbent assay (ELISA) was evaluated as a tool for the diagnosis of active pulmonary tuberculosis. MATERIALS AND METHODS: ELISA was used for the detection of immunoglobulin G (IgG) against A60 antigen in parallel with other familiar diagnostic methods in 70 patients with pulmonary tuberculosis (Group_I) along with 70 controls showing evidence of latent tuberculosis infection (Group II). RESULTS: ELISA results were positive in 63 (90%) patients in Group_I compared to three (4%) controls in Group_II. Group_I patients had significantly higher titers of IgG (mean = 750.79 ± 115.87 U/ml against the A60 antigen as compared to Group II controls (mean = 206.67 ± 20.81 U/ml (P < 0.0001). The overall sensitivity and specificity obtained using ELISA were 90 and 95.7% respectively in active pulmonary tuberculosis. Ziehl-Nielsen (Z-N) stains for acid-fast bacilli were positive in 60 (85.7%) patients. In 48 (68.6%) patients, M. tuberculosis grew on both Lowenstein-Jensen (L-J) medium and BACTEC MGIT 960 liquid medium with mean detection times of 45 and 8 days respectively. Tuberculin skin test was positive in 38 (54.3%) patients. Chest X-ray results were consistent with the diagnosis of pulmonary tuberculosis in 53 (75.7%) patients. CONCLUSION: Anti-A60 IgG ELISA results were significantly positive and associated with elevated antibody titers in pulmonary tuberculosis as compared to latent mycobacterium infection. The high diagnostic performance of the test makes it a useful, simple and rapid supporting tool to validate clinical suspicion of active pulmonary disease. PMID:19727345

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

    PubMed Central

    2014-01-01

    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

  12. Smoking and 2-month culture conversion during anti-tuberculosis treatment

    PubMed Central

    Maciel, E. L.; Brioschi, A. P.; Peres, R. L.; Guidoni, L. M.; Ribeiro, F. K.; Hadad, D. J.; Vinhas, S. A.; Zandonade, E.; Palaci, M.; Dietze, R.; Johnson, J. L.

    2013-01-01

    SUMMARY OBJECTIVE To investigate risk factors for delayed sputum culture conversion to negative during anti-tuberculosis treatment, with an emphasis on smoking. DESIGN Nested case-control study of adults with non-cavitary, culture-confirmed pulmonary tuberculosis (TB) participating in an anti-tuberculosis treatment trial in Brazil. A case of delayed culture conversion was a patient who remained culture-positive after 2 months of treatment. Odds ratios with 95% confidence intervals were calculated. RESULTS Fifty-three cases and 240 control patients were analyzed. Smokers had three-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.007) than non-smokers, while smokers and ex-smokers who smoked >20 cigarettes a day had two-fold greater odds of remaining culture-positive after 2 months of treatment (P = 0.045). CONCLUSION Cigarette smoking adversely affects culture conversion during anti-tuberculosis treatment. Support for smoking cessation should be considered to improve outcomes in TB control programs. PMID:23317958

  13. Characteristics of tuberculosis patients at intake in Cambodia, two provinces in China, and Viet Nam

    PubMed Central

    2011-01-01

    Background The tuberculosis register is a critical data source for the information system of national tuberculosis control programs. From the information in the tuberculosis case register, it is possible to extend the standard analysis of age and sex characteristics among sputum smear-positive cases to all tuberculosis case categories. National tuberculosis programs might utilize such information to identify problems related to referral and access to diagnosis and treatment. Objectives Based on the electronic database we created, our objectives were to provide a detailed description of age and sex characteristics of tuberculosis patients at registration and to provide a comparison of age-specific sex characteristics among incident and prevalent sputum smear-positive cases. Methods A representative sample of tuberculosis case registers from 1 January 2003 to 31 December 2005 was selected in Cambodia, two provinces in China and Viet Nam. Age and sex characteristics of cases in the three separate prevalence surveys in the three jurisdictions (Cambodia: year 2002; China: year 2000; and Viet Nam: year 2006-2007) were obtained for comparison. Results A total 37,635 patients had been registered during the period in the selected units in the three countries. Cases were more frequently male in all three countries with 53%, 71%, and 69% in Cambodia, China, and Viet Nam, respectively. The ratios of the female-to-male odds in the notification system to that in the prevalence survey in smear-positive cases in Cambodia, China and Viet Nam were 2.1, 0.9, and 1.8, respectively. Because of the small proportion of extrapulmonary tuberculosis registered in China, we limited the analysis on age and sex distribution for extrapulmonary cases to Cambodia and Viet Nam. The proportion with extrapulmonary tuberculosis among all cases was 18.5% in Cambodia and 15.7% in Viet Nam, decreasing in frequency with increasing age. Conclusions Characteristics of patients greatly differed between countries and between patient categories. In Cambodia and Viet Nam, efforts should be made for improved case-finding of sputum smear-positive tuberculosis among males. PMID:21605382

  14. Transmission of Multidrug-Resistant and Drug-Susceptible Tuberculosis within Households: A Prospective Cohort Study

    PubMed Central

    Grandjean, Louis; Gilman, Robert H.; Martin, Laura; Soto, Esther; Castro, Beatriz; Lopez, Sonia; Coronel, Jorge; Castillo, Edith; Alarcon, Valentina; Lopez, Virginia; San Miguel, Angela; Quispe, Neyda; Asencios, Luis; Dye, Christopher; Moore, David A. J.

    2015-01-01

    Background The “fitness” of an infectious pathogen is defined as the ability of the pathogen to survive, reproduce, be transmitted, and cause disease. The fitness of multidrug-resistant tuberculosis (MDRTB) relative to drug-susceptible tuberculosis is cited as one of the most important determinants of MDRTB spread and epidemic size. To estimate the relative fitness of drug-resistant tuberculosis cases, we compared the incidence of tuberculosis disease among the household contacts of MDRTB index patients to that among the contacts of drug-susceptible index patients. Methods and Findings This 3-y (2010–2013) prospective cohort household follow-up study in South Lima and Callao, Peru, measured the incidence of tuberculosis disease among 1,055 household contacts of 213 MDRTB index cases and 2,362 household contacts of 487 drug-susceptible index cases. A total of 35/1,055 (3.3%) household contacts of 213 MDRTB index cases developed tuberculosis disease, while 114/2,362 (4.8%) household contacts of 487 drug-susceptible index patients developed tuberculosis disease. The total follow-up time for drug-susceptible tuberculosis contacts was 2,620 person-years, while the total follow-up time for MDRTB contacts was 1,425 person-years. Using multivariate Cox regression to adjust for confounding variables including contact HIV status, contact age, socio-economic status, and index case sputum smear grade, the hazard ratio for tuberculosis disease among MDRTB household contacts was found to be half that for drug-susceptible contacts (hazard ratio 0.56, 95% CI 0.34–0.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting. Conclusions The low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult. PMID:26103620

  15. Transgenic carrot expressing fusion protein comprising M. tuberculosis antigens induces immune response in mice.

    PubMed

    Permyakova, Natalia V; Zagorskaya, Alla A; Belavin, Pavel A; Uvarova, Elena A; Nosareva, Olesya V; Nesterov, Andrey E; Novikovskaya, Anna A; Zav'yalov, Evgeniy L; Moshkin, Mikhail P; Deineko, Elena V

    2015-01-01

    Tuberculosis remains one of the major infectious diseases, which continues to pose a major global health problem. Transgenic plants may serve as bioreactors to produce heterologous proteins including antibodies, antigens, and hormones. In the present study, a genetic construct has been designed that comprises the Mycobacterium tuberculosis genes cfp10, esat6 and dIFN gene, which encode deltaferon, a recombinant analog of the human ?-interferon designed for expression in plant tissues. This construct was transferred to the carrot (Daucus carota L.) genome by Agrobacterium-mediated transformation. This study demonstrates that the fusion protein CFP10-ESAT6-dIFN is synthesized in the transgenic carrot storage roots. The protein is able to induce both humoral and cell-mediated immune responses in laboratory animals (mice) when administered either orally or by injection. It should be emphasized that M. tuberculosis antigens contained in the fusion protein have no cytotoxic effect on peripheral blood mononuclear cells. PMID:25949997

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

    PubMed

    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

    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

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

    PubMed Central

    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

    2013-01-01

    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

  18. BTLA exhibits immune memory for ?? T cells in patients with active pulmonary tuberculosis

    PubMed Central

    Zeng, Jin-Cheng; Lin, Dong-Zi; Yi, Lai-Long; Liu, Gan-Bin; Zhang, Hui; Wang, Wan-Dang; Zhang, Jun-Ai; Wu, Xian-Jing; Xiang, Wen-Yu; Kong, Bin; Chen, Zheng W; Wang, Cong-Yi; Xu, Jun-Fa

    2014-01-01

    Despite past extensive studies, the role of B and T lymphocyte attenuator (BTLA) in ?? T cells in patients with active pulmonary tuberculosis (ATB) remains poorly understood. Here we demonstrate that BTLA expression on ?? T cells is decreased in patients with M. tuberculosis (Mtb) infection. Particularly, BTLA expression levels are likely critical for ?? T cells to manifest and maintain an active central memory phenotype with high capacity for secretion of IFN-? and perforin, which are important for immune memory against TB infection. BTLAhigh ?? T cells also exhibited higher capacity in response to Mtb peptide stimulation. In contrast to the role of BTLA played for negative regulation of immune responses, our data in the current studies suggest that BTLA expression on ?? T cells is likely associated with protective immune memory against Mtb infection in the setting of patients with active pulmonary tuberculosis. This previous unappreciated role for BTLA may have implications for prevention and treatment of patients with Mtb infection. PMID:25360214

  19. Peritoneal tuberculosis due to multidrug-resistant Mycobacterium tuberculosis.

    PubMed

    Esposito, Susanna; Bosis, Samantha; Canazza, Lorena; Tenconi, Rossana; Torricelli, Maurizio; Principi, Nicola

    2013-04-01

    The emergence of drug-resistant Mycobacterium tuberculosis has been widely reported throughout the world, but there are very few data regarding children. We describe the case of a 14-year-old Peruvian adolescent who had been living in Italy since the age of 8 years and was diagnosed as having peritoneal tuberculosis (TB). While she was receiving first-line anti-TB therapy, she developed pyrazinamide-associated thrombocytopenia and cultures revealed a multidrug-resistant strain of Mycobacterium tuberculosis. Pyrazinamide, rifampicin and isoniazid were replaced by moxifloxacin, which was continued for 9 months together with ethambutol. The patient recovered without experiencing any drug-related adverse event or the recurrence of TB in the following year. In conclusion, this case illustrates some of the problems that can arise when multidrug-resistant TB has to be treated in children and adolescents, and also highlights the fact that further studies are needed to clarify which drugs should be used and for how long. PMID:23679177

  20. Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG.

    PubMed Central

    Pithie, A D; Rahelu, M; Kumararatne, D S; Drysdale, P; Gaston, J S; Iles, P B; Innes, J A; Ellis, C J

    1992-01-01

    BACKGROUND: Macrophage activation by cytokines provides only a partial explanation of antimycobacterial immunity in man. Because cytolytic T lymphocytes have been shown to contribute to immunity in animal models of intracellular infection, the generation of mycobacterial antigen specific cytotoxic T cells was examined in the peripheral blood of patients with tuberculosis. METHODS: Subjects comprised 36 patients with active tuberculosis (18 newly diagnosed) and 32 healthy volunteers, of whom 25 had had BCG vaccination and seven were Mantoux negative. The ability of purified protein derivative (PPD) stimulated peripheral blood lymphocytes to lyse autologous, mycobacterial antigen bearing macrophages was examined by using a chromium 51 release assay. RESULTS: PPD stimulated lymphocytes from normal, Mantoux positive, BCG vaccinated subjects produced high levels of PPD specific cytolysis, whereas lymphocytes from unvaccinated, uninfected subjects caused little or no cytolysis. The generation of cytolytic T lymphocytes by patients with tuberculosis was related to their clinical state. Those with cavitating pulmonary disease or lymph node tuberculosis generated PPD specific lymphocytes with cytotoxic ability similar to that of those from Mantoux positive control subjects, whereas lymphocytes from patients with non-cavitating pulmonary infiltrates showed poor antigen specific cytolysis. After seven days of stimulation with PPD in vitro, lymphoblasts contained both CD4+ and CD8+ cells. Mycobacterial antigen specific cytolysis was restricted to the CD4+ cell population and was blocked by monoclonal antibodies directed against major histocompatibility class II (MHC) antigens. CONCLUSION: CD4+ cytolytic T cells can lyse autologous macrophages presenting mycobacterial antigen and were found in patients with cavitating pulmonary tuberculosis or tuberculous lymphadenitis and in normal, Mantoux positive control subjects. The ability to generate these T cell responses seems to be a marker for response to mycobacteria and may contribute to tissue damage in tuberculosis. These responses do not provide protective immunity against Mycobacterium tuberculosis but may help in disease localisation. Images PMID:1440463

  1. [The factors related to the stagnation in the decline of tuberculosis incidence in Japan].

    PubMed

    Ohmori, M

    1993-09-01

    The mortality from tuberculosis in Japan had extremely decreased from the end of the 1940's to the beginning of the 1950's, due to the end of chaos after World War II and also due to the introduction of antituberculosis drugs. The rapid decline of mortality usually leads to the reduction in the infection risk of tuberculosis in the general population. Such a drastic change in the history of tuberculosis have been dividing general population into two groups, i.e. those who were born during the rapid spread of infection with tubercle bacilli and others who were born after. With the passage of time, the limiting age between those two groups reached 40-50 years old as of 1980. The elderly people who were infected with tubercle bacilli in the remote past, have a high risk of development of tuberculosis by endogenous breakdown. In addition, the population of the aged in Japan has been expanding very fast as compared to that in European countries. Owing to such a change of historical and demographical background, the proportion of the elderly cases developed to tuberculosis have increased considerably and it played a major role in a small decrease of tuberculosis incidence rates since 1980. On the other hand, a generation gap on the prevalence of tuberculosis infection caused the recent smallest reduction rate of incidence among young adults. As the majority of young people have not been infected with tubercle bacilli, since 1980, the micro-epidemic among adolescent and young adults have been reported often.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8230961

  2. Surveillance data analysis of Revised National Tuberculosis Control Program of Kangra, Himachal Pradesh

    PubMed Central

    Gupta, Surender Nikhil; Gupta, Naveen; Gupta, Shivani

    2013-01-01

    Background: The annual risk of tuberculosis infection is 1.9% in Himachal Pradesh against a national average of 1%. Revised national tuberculosis control program (RNTCP) in Kangra was introduced in October, 1998. We analyzed the 5-year (2001-2005) RNTCP secondary data from Kangra to evaluate the performance of the program. Materials and Methods: We collected data from all the five tuberculosis units the district. We calculated the following indicators-case detection rate, tuberculosis cases by category-new smear positive (or smear negative but seriously ill) defaulters, relapses and failures, extra-pulmonary, and new smear negative cases. We compared the results with Himachal Pradesh and India. We employed the standardized program indicators-sputum positivity, cure, death, failure and default rates. Results: Extra pulmonary cases ranged in between 56% and 73%, normal being 15-20%. The highest category-1 varies from 42% to 48%. New smear positive case detection rates (78-90%) and cure rates (88-91%) were the highest as compared to figures of the state and country. Failure rate was maximum in Kangra Tuberculosis Units (TU)-6.5% and the default rate was 7.2% in TU Palampur. The tuberculosis cases have fallen down from 6,462/100, 000 in 1999 to 2,195/100, 000 in 2005 following the introduction of RNTCP in 1999. Age specific (15-55 years) and sex-wise males were more affected than the females (59-64%). Conclusions: Continue investment in the program to sustain progress achieved. Investigate the cause of high proportion of extra-pulmonary tuberculosis. Investigate Kangra TU unit with a high default rate. PMID:24479092

  3. Tuberculosis control and research strategies for the 1990s: memorandum from a WHO meeting.

    PubMed

    1992-01-01

    Tuberculosis is the largest cause of death from a single infectious agent in the world, killing nearly 3 million people every year. This death toll represents 25% of avoidable adult deaths in developing countries. It imposes a heavy burden on the 8 million new individuals who contract the disease each year, and on their households; morbidity and mortality are concentrated in young adults. The association of tuberculosis and HIV infection will significantly exacerbate the situation in developed and developing countries, making the need for action all the more pressing. Effective control measures are available. Broad action is therefore warranted and should be aimed at introducing the effective strategies on as wide a scale as possible to reach the targets of 70% case detection and 85% cure of smear-positive patients, by the year 2000. Research is needed to implement these strategies throughout the world and to ensure that effective tools will remain available for controlling tuberculosis despite emerging problems such as resistance to the major drugs currently available. To make a real impact on the tuberculosis problem, a focused global programme must be created, under the leadership of WHO, to bring tuberculosis to the world's attention, to mobilize support on a major scale, and to provide direct guidance and support to national programmes. PMID:1568278

  4. Outcomes of HIV-infected Patients Treated for Recurrent Tuberculosis with the Standard Retreatment Regimen

    PubMed Central

    McGreevy, Jolion; Juste, Marc Antoine Jean; Severe, Patrice; Collins, Sean; Koenig, Serena; Pape, Jean William; Fitzgerald, Daniel W

    2013-01-01

    SETTING AIDS and tuberculosis center in Port-au-Prince, Haiti. OBJECTIVE To measure the effectiveness of tuberculosis retreatment with the standard regimen (2HRZES/1HRZE/5HRE) in HIV-infected adults. DESIGN Cohort study. RESULTS Of 1,318 HIV-infected patients with access to antiretroviral therapy following World Health Organization guidelines, 56 were diagnosed with recurrent pulmonary tuberculosis and retreated with the standard regimen. Ten patients (18%) died during retreatment, 3 patients (5%) defaulted, and 2 patients (4%) failed. Forty-one patients (73%) had a good retreatment outcome (cure, treatment completed). Of these, 8 patients (20%) died during follow-up, 5 patients (12%) were lost, and 5 patients (12%) had a second recurrence of tuberculosis. Only 26 (46%) of the 56 patients remained alive, in-care, and TB-free after a median of 36 months follow-up. CONCLUSION HIV-infected patients treated for recurrent tuberculosis with the standard retreatment regimen have a high mortality and poor long-term outcomes. PMID:22507948

  5. ESX-1-induced apoptosis is involved in cell-to-cell spread of Mycobacterium tuberculosis.

    PubMed

    Aguilo, J I; Alonso, H; Uranga, S; Marinova, D; Arbués, A; de Martino, A; Anel, A; Monzon, M; Badiola, J; Pardo, J; Brosch, Roland; Martin, Carlos

    2013-12-01

    Apoptosis modulation is a procedure amply utilized by intracellular pathogens to favour the outcome of the infection. Nevertheless, the role of apoptosis during infection with Mycobacterium tuberculosis, the causative agent of human tuberculosis, is subject of an intense debate and still remains unclear. In this work, we describe that apoptosis induction in host cells is clearly restricted to virulent M. tuberculosis strains, and is associated with the capacity of the mycobacteria to secrete the 6 kDa early secreted antigenic target ESAT-6 bothunder in vitro and in vivo conditions. Remarkably, only apoptosis-inducing strains are able to propagate infection into new cells, suggesting that apoptosis is used by M. tuberculosis as a colonization mechanism. Finally, we demonstrate that in vitro modulation of apoptosis affects mycobacterial cell-to-cell spread capacity, establishing an unambiguous relationship between apoptosis and propagation of M. tuberculosis. Our data further indicate that BCG and MTBVAC vaccines are inefficient in inducing apoptosis and colonizing new cells, correlating with the strong attenuation profile of these strains previously observed in vitro and in vivo. PMID:23848406

  6. Expression of apoptosis-related genes in an Ethiopian cohort study correlates with tuberculosis clinical status.

    PubMed

    Abebe, Markos; Doherty, T Mark; Wassie, Liya; Aseffa, Abraham; Bobosha, Kidist; Demissie, Abebech; Zewdie, Martha; Engers, Howard; Andersen, Peter; Kim, Louise; Huggett, Jim; Rook, Graham; Yamuah, Lawrence K; Zumla, Alimuddin

    2010-01-01

    Mycobacterium tuberculosis remains one of the world's deadliest pathogens in part because of its ability to persist in the face of an active immune response. It has been suggested that apoptosis of infected macrophages is one way in which the host deals with intracellular pathogens and that M. tuberculosis can inhibit this process. To assess the relevance of this process for human disease, we compared the expression of multiple genes involved in the activation of the extrinsic ("death receptor initiated") pathway of apoptosis in 29 tuberculosis patients, 70 tuberculosis contacts and 27 community controls from Ethiopia. We found that there is a strong upregulation of genes for factors that promote apoptosis in PBMC from individuals with active disease, including TNF-alpha and its receptors, Fas and FasL and pro-Caspase 8. The anti-apoptotic factor FLIP, however, was also upregulated. A possible explanation for this dichotomy was given by fractionation of PBMC using CD14, which suggests that macrophage/monocytes may regulate several key molecules differently from non-monocytic cells (especially TNF-alpha and its receptors, a finding confirmed by protein ELISA) potentially reducing the sensitivity to apoptotic death of monocyte/macrophages--the primary host cell for M. tuberculosis. This may represent an important survival strategy for the pathogen. PMID:19877018

  7. Copper Homeostasis in Mycobacterium tuberculosis

    PubMed Central

    Shi, Xiaoshan; Darwin, K. Heran

    2015-01-01

    Copper (Cu) is a trace element essential for the growth and development of almost all organisms, including bacteria. However, Cu overload in most systems is toxic. Studies show Cu accumulates in macrophage phagosomes infected with bacteria, suggesting Cu provides an innate immune mechanism to combat invading pathogens. To counteract the host-supplied Cu, increasing evidence suggests that bacteria have evolved Cu resistance mechanisms to facilitate their pathogenesis. In particular, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has evolved multiple pathways to respond to Cu. Here, we summarize what is currently known about Cu homeostasis in Mtb and discuss potential sources of Cu encountered by this and other pathogens in a mammalian host. PMID:25614981

  8. Pharmacotherapy for multidrug resistant tuberculosis

    PubMed Central

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

    2012-01-01

    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

  9. Copper homeostasis in Mycobacterium tuberculosis.

    PubMed

    Shi, Xiaoshan; Darwin, K Heran

    2015-06-10

    Copper (Cu) is a trace element essential for the growth and development of almost all organisms, including bacteria. However, Cu overload in most systems is toxic. Studies show Cu accumulates in macrophage phagosomes infected with bacteria, suggesting Cu provides an innate immune mechanism to combat invading pathogens. To counteract the host-supplied Cu, increasing evidence suggests that bacteria have evolved Cu resistance mechanisms to facilitate their pathogenesis. In particular, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has evolved multiple pathways to respond to Cu. Here, we summarize what is currently known about Cu homeostasis in Mtb and discuss potential sources of Cu encountered by this and other pathogens in a mammalian host. PMID:25614981

  10. Immunohistochemical diagnosis of abdominal and lymph node tuberculosis by detecting Mycobacterium tuberculosis complex specific antigen MPT64

    PubMed Central

    Purohit, Manju R; Mustafa, Tehmina; Wiker, Harald G; Mørkve, Odd; Sviland, Lisbet

    2007-01-01

    Background The aim of this study was to evaluate the diagnostic potential of immunohistochemistry using an antibody to the secreted mycobacterial antigen MPT64, in abdominal and lymph node tuberculosis. Methods We used formalin-fixed histologically diagnosed abdominal tuberculosis (n = 33) and cervical tuberculous lymphadenitis (n = 120) biopsies. These were investigated using a combination of Ziehl-Neelsen method, culture, immunohistochemistry with an antibody to MPT64, a specific antigen for Mycobacterium tuberculosis complex organisms. Abdominal and cervical lymph node biopsies from non-mycobacterial diseases (n = 50) were similarly tested as negative controls. Immunohistochemistry with commercially available anti-BCG and nested PCR for IS6110 were done for comparison. Nested PCR was positive in 86.3% cases and the results of all the tests were compared using nested PCR as the gold standard. Results In lymph node biopsies, immunohistochemistry with anti-MPT64 was positive in 96 (80%) cases and 4 (12.5%) controls and with anti-BCG 92 (76.6%), and 9 (28%) respectively. The results for cases and controls in abdominal biopsies were 25 (75.7%) and 2 (11.1%) for anti-MPT64 and 25 (75.7%) and 4 (22%) for anti-BCG. The overall sensitivity, specificity, positive and negative predictive values of immunohistochemistry with anti-MPT64 was 92%, 97%, 98%, and 85%, respectively while the corresponding values for anti-BCG were 88%, 85%, 92%, and 78%. Conclusion Immunohistochemistry using anti-MPT64 is a simple and sensitive technique for establishing an early and specific diagnosis of M. tuberculosis infection and one that can easily be incorporated into routine histopathology laboratories. PMID:17894882

  11. Impaired M. tuberculosis Antigen-Specific IFN-? Response without IL-17 Enhancement in Patients with Severe Cavitary Pulmonary Tuberculosis

    PubMed Central

    Fan, Lin; Xiao, Heping; Mai, Guangliang; Su, Bo; Ernst, Joel; Hu, Zhongyi

    2015-01-01

    Background Th1 cells play an essential role in immune protection against tuberculosis. Th17 cells might be involved with immune pathology in active human tuberculosis (TB). The balance between Th1 and Th17 cells in patients with cavitary tuberculosis needs to be clarified which might help understanding the immunological basis of pathologic pathogenesis in TB. Method Initially treated pulmonary TB (PTB) patients with or without cavities were recruited before chemotherapy. We isolated peripheral blood mononuclear cells, stimulated with phytohemagglutinin (PHA), PPD, or ESAT-6 antigens, and assayed supernatant IFN-? and IL-17 by ELISA after 24 or 72 hours incubation, respectively. Cells were also stained with antibodies to CD3, CD4, CD8, IFN-? or IL-17 and the proportion of stained cells was measured by flow cytometry. Results We found wide variation of IFN-? response in active PTB patients, but less subject-to-subject variation of IL-17 was observed as we previously reported. There were no significant differences in IFN-? and IL-17 between cavitary and non-cavitary PTB; however, we found decreased IFN-? secretion in severe cavitary PTB compared to mild lesion non-cavitary PTB (p < 0.05). We also found a decrease in the proportion of CD3+CD4+ T cells in the blood of severe cavitary PTB patients (p < 0.05). Conclusions IL-17 seemed to have no association with the formation of cavities in active PTB from the study of PBMC. Impaired IFN-? without IL-17 enhancement occurs in peripheral blood during severe cavitary PTB. Our results demonstrate that M. tuberculosis antigen-specific Th1 response is decreased when PTB lesions develop to severe cavities. PMID:26018190

  12. The Forest behind the Tree: Phylogenetic Exploration of a Dominant Mycobacterium tuberculosis Strain Lineage from a High Tuberculosis Burden Country

    PubMed Central

    Cardoso Oelemann, Maranibia; Gomes, Harrison M.; Willery, Eve; Possuelo, Lia; Batista Lima, Karla Valéria; Allix-Béguec, Caroline; Locht, Camille; Goguet de la Salmonière, Yves-Olivier L.; Gutierrez, Maria Cristina; Suffys, Philip; Supply, Philip

    2011-01-01

    Background Genotyping of Mycobacterium tuberculosis isolates is a powerful tool for epidemiological control of tuberculosis (TB) and phylogenetic exploration of the pathogen. Standardized PCR-based typing, based on 15 to 24 mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) loci combined with spoligotyping, has been shown to have adequate resolution power for tracing TB transmission and to be useful for predicting diverse strain lineages in European settings. Its informative value needs to be tested in high TB-burden countries, where the use of genotyping is often complicated by dominance of geographically specific, genetically homogeneous strain lineages. Methodology/Principal Findings We tested this genotyping system for molecular epidemiological analysis of 369 M. tuberculosis isolates from 3 regions of Brazil, a high TB-burden country. Deligotyping, targeting 43 large sequence polymorphisms (LSPs), and the MIRU-VNTRplus identification database were used to assess phylogenetic predictions. High congruence between the different typing results consistently revealed the countrywide supremacy of the Latin-American-Mediterranean (LAM) lineage, comprised of three main branches. In addition to an already known RDRio branch, at least one other branch characterized by a phylogenetically informative LAM3 spoligo-signature seems to be globally distributed beyond Brazil. Nevertheless, by distinguishing 321 genotypes in this strain population, combined MIRU-VNTR typing and spoligotyping demonstrated the presence of multiple distinct clones. The use of 15 to 24 loci discriminated 21 to 25% more strains within the LAM lineage, compared to a restricted lineage-specific locus set suggested to be used after SNP analysis. Noteworthy, 23 of the 28 molecular clusters identified were exclusively composed of patient isolates from a same region, consistent with expected patterns of mostly local TB transmission. Conclusions/Significance Standard MIRU-VNTR typing combined with spoligotyping can reveal epidemiologically meaningful clonal diversity behind a dominant M. tuberculosis strain lineage in a high TB-burden country and is useful to explore international phylogenetical ramifications. PMID:21464915

  13. The genetics of Mycobacterium tuberculosis

    Microsoft Academic Search

    S. Vijaya

    1998-01-01

    Gene manipulation inMycobacterium tuberculosis has been slow in coming of age owing to the inherent difficulties associated with working on this aerosol-transmitted pathogen,\\u000a in addition to the paucity of molecular tools such as plasmids and transposons. One of the early approaches to overcome these\\u000a difficulties was the development of phasmids, which combined the properties of phages and plasmids and allowed

  14. Primary tuberculosis of the clavicle.

    PubMed

    Prakash, Jatin; Aggarwal, Shilpi; Mehtani, Anil

    2014-10-01

    Tuberculosis of the clavicle is a rare lesion, accounting for less than 1% of all osteoarticular tuberculosis. The lesion has been described in a few case reports. The lesion can have a varied presentation, ranging from dull, aching pain to bony swelling and a draining sinus. The rarity of the lesion, its nonspecific symptoms, and its striking resemblance to common cystic conditions such as bone tumors and metabolic conditions such as rickets make diagnosis difficult. The authors describe a series of 17 patients with primary tuberculosis of the clavicle. Radiographs and magnetic resonance images were obtained for all patients, and a preliminary diagnosis was made on the basis of clinical features and the results of erythrocyte sedimentation rate, C-reactive protein, and Mantoux tests. Erythrocyte sedimentation rate was uniformly elevated. Radiographs showed diffused thickening and honeycombing, eccentric expansile lytic lesions with surrounding osteopenia, or sequestration not unlike pyogenic infection. Magnetic resonance imaging is useful for determining the extent of the lesion and soft tissue involvement. The radiological and laboratory findings provided complementary information. The diagnosis was confirmed on biopsy material that was analyzed with histopathology, pus culture and sensitivities, gram stain, acid-fast stain, and cultures on Löwenstein-Jensen medium. Patients were treated with multidrug antitubercular chemotherapy for 18 months and were assessed on pre- and posttreatment radiology, erythrocyte sedimentation rate, and University of California, Los Angeles (UCLA) shoulder rating scale. The results of conservative management of tubercular osteomyelitis were uniformly good, and all patients recovered well. PMID:25275974

  15. Epidemiological basis of tuberculosis eradication

    PubMed Central

    Horwitz, Ole; Wilbek, Erik; Erickson, Pennifer A.

    1969-01-01

    The introduction of chemotherapy dramatically changed the epidemiology of tuberculosis as the risk of infection was thereby nearly eliminated. The present paper illustrates the risk of disease under these conditions. A large and representative segment of the Danish population, a total of over 626 000 persons aged 15-44 years, was examined by a standardized technique in 1950-52 and has now been followed for 12 years. It has been possible by means of simple parameters such as infection and vaccination status, X-ray lesion and age to divide the population into groups with widely different incidence rates. The time trend in disease rates among vaccinated persons and natural reactors suggests that post-primary tuberculosis is of great significance in the present tuberculosis situation. Three-quarters of all cases stem from the natural reactors. It would have been of great practical significance to identify high-risk groups which yielded a great part of the patients. This was not possible since the majority of cases developed among reactors whose distinctive feature was that they were infected at time of examination. PMID:5309087

  16. Tuberculosis in Pregnancy: A Review

    PubMed Central

    Loto, Olabisi M.; Awowole, Ibraheem

    2012-01-01

    Tuberculosis (TB) was declared a public health emergency by WHO in 2005. The disease is a significant contributor to maternal mortality and is among the three leading causes of death among women aged 15–45 years in high burden areas. The exact incidence of tuberculosis in pregnancy, though not readily available, is expected to be as high as in the general population. Diagnosis of tuberculosis in pregnancy may be challenging, as the symptoms may initially be ascribed to the pregnancy, and the normal weight gain in pregnancy may temporarily mask the associated weight loss. Obstetric complications of TB include spontaneous abortion, small for date uterus, preterm labour, low birth weight, and increased neonatal mortality. Congenital TB though rare, is associated with high perinatal mortality. Rifampicin, INH and Ethambutol are the first line drugs while Pyrazinamide use in pregnancy is gaining popularity. Isoniazid preventive therapy is a WHO innovation aimed at reducing the infection in HIV positive pregnant women. Babies born to this mother should be commenced on INH prophylaxis for six months, after which they are vaccinated with BCG if they test negative. Successful control of TB demands improved living conditions, public enlightenment, primary prevention of HIV/AIDS and BCG vaccination. PMID:22132339

  17. Investigations of late archaic coprolites: pollen and macrofossil remains from Hinds Cave (41VV456), Val Verde County, Texas 

    E-print Network

    Edwards, Sherrian Kay

    1990-01-01

    , continued CHAPTER III. MICROFOSSILS RECOVERED Pollen Page 34 History 34 Present Study Economic Pollen 36 39 Background Pollen 52 Unknown Pollen Grains 56 Parasites 56 IV. MACROFOSSILS RECOVERED Animal Remains 60 Plant Remains 85...

  18. How can immunology contribute to the control of tuberculosis?

    Microsoft Academic Search

    Stefan H. E. Kaufmann

    2001-01-01

    Tuberculosis poses a significant threat to mankind. Multidrug-resistant strains are on the rise, and Mycobacterium tuberculosis infection is often associated with human immunodeficiency virus infection. Satisfactory control of tuberculosis can only be achieved using a highly efficacious vaccine. Tuberculosis is particularly challenging for the immune system. The intracellular location of the pathogen shields it from antibodies, and a variety of

  19. Multidrug-Resistant Mycobacterium tuberculosis: Molecular Perspectives

    Microsoft Academic Search

    Ashok Rattan; Awdhesh Kalia; Nishat Ahmad

    1998-01-01

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

  20. Local epidemic history as a predictor of tuberculosis incidence in Saskatchewan Aboriginal communities

    PubMed Central

    Pepperell, Caitlin; Chang, Alicia H; Wobeser, Wendy; Parsonnet, Julie; Hoeppner, Vernon H.

    2012-01-01

    SUMMARY Background Average tuberculosis (TB) incidence rates are high in Canadian Aboriginal communities, but there is significant variability within this group. Objective To determine whether local history of post-contact TB epidemics is predictive of contemporary epidemiology among Aboriginal communities in Saskatchewan, Canada. Methods TB incidence, age-specific morbidity patterns, and rates of clustering of TB genotypes from 1986 to 2004 were compared between two groups of communities: Group 1, in which post-contact epidemics of TB were established around 1870, and Group 2, in which they were delayed until after 1920. Concomitant effects of socioeconomic and geographic variables were explored with multivariate models. Results Group 2 communities were characterized by higher annual incidence of TB (median 431/100 000 versus 38/100 000). In multivariate models that included socioeconomic and geographic variables, historical grouping remained a significant independent predictor of community incidence of TB. Clustering of TB genotypes was associated with Group 2 (OR 8.7, 95%CI 3.3–22.7) and age 10–34y (OR 2.5, 95%CI 1.1–5.7). Conclusions TB transmission dynamics can vary significantly as a function of a population’s historical experience with TB. Populations at different stages along the epidemic trajectory may be amenable to different types of interventions. PMID:21682962

  1. Adverse Outcomes after Non-Chest Surgeries in Patients with Pulmonary Tuberculosis: A Nationwide Study

    PubMed Central

    Lin, Chao-Shun; Yeh, Chun-Chieh; Chung, Chi-Li; Hung, Chih-Jen; Chen, Ta-Liang

    2015-01-01

    Background The association between pulmonary tuberculosis (TB) and postoperative outcomes remains unknown. This study investigated outcomes following non-chest surgeries in patients with previous pulmonary TB. Methods Using Taiwan’s National Health Insurance Research Database, we analyzed 6911 patients (aged ? 20 years) with preoperative diagnosis of pulmonary TB and 6911 propensity score-matched controls receiving non-chest surgeries in 2008–2010. Postoperative outcomes were compared between patients with or without pulmonary TB by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the multivariate logistic regressions. Results Surgical patients with pulmonary TB had a significantly higher postoperative complication rates than controls, including septicemia, pneumonia, acute renal failure, deep wound infection, overall complications, and 30-day postoperative mortality (OR 1.41; 95% CI 1.07–1.86). The ORs of patients with low-income status were as high as 2.27 (95% CI 1.03–5.03). Preoperative use of TB drugs and TB-related medical expenditure also associated with higher postoperative mortality among surgical patients with pulmonary TB. Conclusions Surgical patients with pulmonary TB have significantly increased risks of postoperative complications and mortality after non-chest surgeries. This study suggests the need to improve postoperative care for surgical patients with pulmonary TB. PMID:26172153

  2. Barriers and Delays in Tuberculosis Diagnosis and Treatment Services: Does Gender Matter?

    PubMed Central

    Yang, Wei-Teng; Gounder, Celine R.; Akande, Tokunbo; De Neve, Jan-Walter; McIntire, Katherine N.; Chandrasekhar, Aditya; de Lima Pereira, Alan; Gummadi, Naveen; Samanta, Santanu; Gupta, Amita

    2014-01-01

    Background. Tuberculosis (TB) remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52%) and delays (42%), 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus 0%) than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men. PMID:24876956

  3. Tuberculosis among migrant populations in the European Union and the European Economic Area

    PubMed Central

    Tillmann, Taavi; Sandgren, Andreas; Williams, Gemma; Rechel, Bernd; Ingleby, David; Noori, Teymur; Mladovsky, Philipa; McKee, Martin

    2015-01-01

    Background: Although tuberculosis (TB) incidence has been decreasing in the European Union/European Economic Area (EU/EEA) in the last decades, specific subgroups of the population, such as migrants, remain at high risk of TB. This study is based on the report ‘Key Infectious Diseases in Migrant Populations in the EU/EEA’ commissioned by The European Centre for Disease Prevention and Control. Methods: We collected, critically appraised and summarized the available evidence on the TB burden in migrants in the EU/EEA. Data were collected through: (i) a comprehensive literature review; (ii) analysis of data from The European Surveillance System (TESSy) and (iii) evidence provided by TB experts during an infectious disease workshop in 2012. Results: In 2010, of the 73 996 TB cases notified in the EU/EEA, 25% were of foreign origin. The overall decrease of TB cases observed in recent years has not been reflected in migrant populations. Foreign-born people with TB exhibit different socioeconomic and clinical characteristics than native sufferers. Conclusion: This is one of the first studies to use multiple data sources, including the largest available European database on infectious disease notifications, to assess the burden and provide a comprehensive description and analysis of specific TB features in migrants in the EU/EEA. Strengthened information about health determinants and factors for migrants’ vulnerability is needed to plan, implement and evaluate targeted TB care and control interventions for migrants in the EU/EEA. PMID:25500265

  4. Molecular Epidemiology of Tuberculosis in Kaohsiung City Located at Southern Taiwan, 2000-2008

    PubMed Central

    Chen, Yih-Yuan; Chang, Jia-Ru; Kuo, Shu-Chen; Tseng, Fan-Chen; Huang, Wei-Chen; Huang, Tsi-Shu; Chen, Yao-Shen; Chiueh, Tzong-Shi; Sun, Jun-Ren; Su, Ih-Jen; Dou, Horng-Yunn

    2015-01-01

    Background We present the first comprehensive analysis of Mycobacterium tuberculosis (MTB) isolates circulating in southern Taiwan. In this 9-year population-based study, the TB situation in the Kaohsiung region was characterized by genotypic analysis of 421 MTB isolates. Methods All 421 isolates of MTB were analyzed by spoligotyping and MIRU-VNTR typing. Drug-resistance patterns were also analyzed. Results The percentage of EAI (East African-Indian) strains increased across sampling years (2000–2008) in southern Taiwan, whereas the proportion of Beijing lineages remained unchanged. Clustering was more frequent with EAI genotype infections (odds ratio = 3.6, p<0.0001) when compared to Beijing genotypes. Notably, MTB resistance to streptomycin (STR) had significantly increased over time, but resistance to other antibiotics, including multidrug resistance, had not. Three major genes (gidB, rpsL and rrs) implicated in STR resistance were sequenced and specific mutations identified. Conclusions This study revealed that EAI strains were highly transmissible and that STR resistance has increased between 2000 and 2008 in Kaohsiung, Taiwan. PMID:25629610

  5. Space Weathering of Asteroids: Issues Remain

    NASA Astrophysics Data System (ADS)

    Chapman, C. R.

    2003-05-01

    After decades of debate, consensus now exists that asteroid reflectance spectra are affected by space weathering. Based on a recent consensus [1] about the physical processes that space weather the Moon, we can realistically hypothesize about the causes of asteroidal space weathering and about how the processes might be manifested on different types of asteroids. But issues and questions remain. While vapor deposition on grains dominates lunar space weathering, for asteroids the relative vapor production by solar wind sputtering versus micrometeorite impact (or even other processes masked on the Moon) remains uncertain. Particularly troublesome are the different styles of space weathering on Ida and Eros; these otherwise similarly sized SIV asteroids differ mainly in being either in the belt or in near-Earth space, but how does that affect space weathering so dramatically? A vital issue is the timescale for space weathering to be manifested, or to mature, under various conditions (e.g. in or out of the belt, for different taxonomic types, or for different sizes). An extraordinary discovery may finally help provide an answer. Nesvorny et al. [2,3] have discovered how to date the creation of specific asteroids (i.e. in a catastrophic collisional break-up) with a robust precision of several percent, competitive with meteoritic age-dating techniques except that we know which specific asteroids the dates pertain to. The Karin cluster, within the S-type Koronis family, formed 5.8 +/-0.2 Myr ago. This age is of the order of estimates of space-weathering/regolith-evolution timescales. Spectral studies of Karin cluster members, and members of other dated families, may determine the absolute rates of space weathering processes. That in turn can elucidate the physical processes and permit better extrapolation to other asteroids. References: [1] B. Hapke (2001) J. Geophys. Res. 106, 10039-10073; [2] D. Nesvorny et al. (2002) Nature 417, 720-722; [3] D. Nesvorny et al. (2003) Astrophys. J. 591, 486-497.

  6. Rifampicin Resistance in Tuberculosis Outbreak, London, England

    PubMed Central

    Claxton, Alleyna P.; Shorten, Robert J.; McHugh, Timothy D.; Gillespie, Stephen H.

    2005-01-01

    Mycobacterium tuberculosis isolates cultured from 6 patients associated with an isoniazid-resistant M. tuberculosis outbreak acquired rifampicin resistance. The rpoB gene sequence showed that resistance was associated with rare mutations in each isolate. Three isolates had a mutation outside the rifampicin resistance–determining region. PMID:15963290

  7. Extra-pulmonary tuberculosis in children

    PubMed Central

    Maltezou, H; Spyridis, P; Kafetzis, D

    2000-01-01

    METHODS—The clinical and epidemiological features of 102 children with extra-pulmonary tuberculosis, diagnosed between 1982 and 1998at P & A Kyriakou Children's Hospital were reviewed.?RESULTS—During the past decade, a 50% increase of admissions for extra-pulmonary tuberculosis was observed. The source of infection was disclosed in 48 patients. Diagnoses included superficial lymphadenitis (n = 48), pleural effusion (n = 27), meningitis (n = 16), skeletal tuberculosis (n = 5), miliary tuberculosis (n = 3), abdominal tuberculosis (n = 2), and pericarditis (n = 1). Miliary tuberculosis developed in infants, lymphadenitis and meningitis in preschool children, and pleural effusion and skeletal tuberculosis in older children. None of the patients with extra-pulmonary tuberculosis died; however, six patients with meningitis developed permanent neurological deficits. In these patients, antituberculous treatment was introduced at a median of six days following admission as compared with one day in patients with no complications. Poverty, immigration, and limited access to medical services were common among patients with meningitis.?? PMID:10999874

  8. Multidrug-Resistant Mycobacterium tuberculosis, Southwestern Colombia

    PubMed Central

    Nieto, Luisa Maria; Rozo, Juan C.; Forero, Liliana; van Soolingen, Dick

    2011-01-01

    Using spoligotyping, we identified 13 genotypes and 17 orphan types among 160 Mycobacterium tuberculosis isolates from patients in Valle del Cauca, Colombia. The Beijing genotype represented 15.6% of the isolates and was correlated with multidrug-resistant tuberculosis, female sex of the patients, and residence in Buenaventura and may represent a new public health threat. PMID:21762581

  9. Remaining life assessment of superheater and reheater tubes: Final report

    SciTech Connect

    Paterson, S.R.; Rettig, T.W.

    1988-05-01

    The purpose of this project was to provide a validated procedure in the form of a computer code and users guide for predicting the remaining useful life of Type SA213-T22 superheater and reheater tubes. The procedure was to be based on steamside oxide scale measurements, tube geometry measurements, and other readily available operating parameters. To achieve this objective, six tasks were performed. These were: (1) acquisition and compilation of oxide growth information for 2/1/4/Cr--1Mo steel, (2) acquisition and examination of Type SA213-T22 superheater and reheater tubes taken out of service after considerable service exposure or after the tube ruptured, (3) empirical development of a creep damage accumulation procedure which is accurate for nonsteady state temperature and stress histories, (4) measurement of the steamside scale thickening and fireside wastage rates in tubes removed from service, (5) integration of the foregoing tasks into damage counting algorithms and casting these into a user-friendly computer code, and (6) comparison of the remaining life predictions made using the developed computer code with well characterized tube failures and with postexposure stress rupture test results obtained from a nonruptured service degraded tube. A user-oriented computer code for predicting the remaining life of superheater and reheater tubes using easily measured tube characteristics and readily available operational data were developed. This report provides the technical basis and background for this computer code. 60 figs., 11

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

    PubMed Central

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

    2013-01-01

    SUMMARY Tuberculosis remains a major threat as drug resistance continues to increase. Pulmonary tuberculosis in adults is responsible for 80% of clinical cases and nearly 100% of transmission of infection. Unfortunately, since we have no animal models of adult type pulmonary tuberculosis, the most important type of disease remains largely out of reach of modern science and many fundamental questions remain unanswered. This paper reviews research dating back to the 1950’s providing compelling evidence that cord factor (trehalose 6,6? dimycolate [TDM]) is essential for understanding tuberculosis. However, the original papers by Bloch and Noll were too far ahead of their time to have immediate impact. We can now recognize that the physical and biologic properties of cord factor are unprecedented in science, especially its ability to switch between two sets of biologic activities with changes in conformation. While TDM remains on organisms, it protects them from killing within macrophages, reduces antibiotic effectiveness and inhibits the stimulation of protective immune responses. If it comes off organisms and associates with lipid, TDM becomes a driver of tissue damage and necrosis. Studies emanating from cord factor research have produced (1) a rationale for improving vaccines, (2) an approach to new drugs that overcome natural resistance to antibiotics, (3) models of caseating granulomas that reproduce multiple manifestations of human tuberculosis. (4) evidence that TDM is a key T cell antigen in destructive lesions of tuberculosis, and (5) a new understanding of the pathology and pathogenesis of postprimary tuberculosis that can guide more informative studies of long standing mysteries of tuberculosis. PMID:20006299

  11. Molecular clues of a microepidemy among homeless tuberculosis patients in Budapest due to a new and local Mycobacterium tuberculosis clade

    Microsoft Academic Search

    Csaba Ködmön; Stefan Niemann; M. Cristina Gutierrez; Christophe Sola; Nalin Rastogi; Judit Lukács; Ákos Somoskövi

    2007-01-01

    In Budapest, the capital of Hungary, one of the most important tuberculosis related risk factor is homelessness. The aim of this retrospective study was the genetic characterization of Mycobacterium tuberculosis strains isolated from 66 homeless tuberculosis patients by spoligotyping and mycobacterial interspersed repetitive unit (MIRU) typing. The study identified a local microepidemy in the district with the highest tuberculosis incidence

  12. Evaluation of the Semiautomated Abbott LCx Mycobacterium tuberculosis Assay for Direct Detection of Mycobacterium tuberculosis in Respiratory Specimens

    Microsoft Academic Search

    VICENTE AUSINA; FREDY GAMBOA; ELENA GAZAPO; JOAN LONCA; LURDES MATAS; JOAN R. MANZANO; CARLOS RODRIGO; PERE J. CARDONA; EDUARDO PADILLA

    Five hundred twenty processed respiratory specimens from 326 patients received for the diagnosis of tuberculosis or other mycobacterial infections were tested by means of the LCx Mycobacterium tuberculosis Assay from Abbott Laboratories, which uses ligase chain reaction technology for the direct detection of M. tuberculosis complex in respiratory specimens. The results of the LCx M. tuberculosis Assay were compared with

  13. Cough and the transmission of tuberculosis.

    PubMed

    Turner, Richard D; Bothamley, Graham H

    2015-05-01

    Cough is a predominant feature of respiratory infection and, in tuberculosis, is of prime importance for transmitting infection. Tuberculosis is transmitted by the air, yet the process by which bacilli are aerosolized has received little attention. Features of cough may account for differences in transmission rates from source cases of pulmonary disease. We review the literature on the mechanisms and characteristics of cough in tuberculosis in the context of the dissemination of infection. Coughing is probably more important than other respiratory maneuvers, and characteristics of mucus may have an important role but data are scarce. Direct mechanisms of cough in tuberculosis are unknown, as are temporal and other patterns that correlate with the release of viable airborne bacilli. Other than antituberculous chemotherapy and masks, there are few methods of modulating cough in tuberculosis. This is an increasingly important area for research. PMID:25387581

  14. Tonsillar Tuberculosis: A Forgotten Clinical Entity

    PubMed Central

    Das, Anirban; Das, Sibes K.; Pandit, Sudipta; Basuthakur, Sumitra

    2015-01-01

    Tuberculosis of tonsils is an extremely rare variety of extra-pulmonary tuberculosis which frequently simulates the tonsillar malignancy, especially in elderly individuals. Secondary form is more common than primary one, and in present day, contact with the infected sputum or saliva in a case of sputum smear positive pulmonary tuberculosis is the main source of the disease. Chronic or recurrent tonsillitis with enlarged tonsils and sore throat is the main clinical presentation. As it is very difficult to differentiate it from tonsillar malignancy on clinical ground, histopathological examination of the tissue is must for the diagnosis of tonsillar TB. Antitubercular therapy is adequate for its successful resolution. Here, we report a primary form of tonsillar tuberculosis in a 76-year-old male, in whom, no pulmonary tuberculosis was documented. PMID:25811002

  15. Miliary tuberculosis and adult respiratory distress syndrome.

    PubMed

    Piqueras, A R; Marruecos, L; Artigas, A; Rodriguez, C

    1987-01-01

    Although, miliary tuberculosis is an unusual cause of severe acute respiratory failure, we describe nine patients with miliary tuberculosis who developed adult respiratory distress syndrome. This complication occurred in seven patients despite treatment with antituberculous drugs. In two patients who developed the syndrome, miliary tuberculosis was diagnosed only at postmortem. The presence of pulmonary hypertension in all cases and disseminated intravascular coagulation in seven cases suggests a possible pathophysiologic relationship with severe pulmonary vascular damage. The high mortality rate (88.8%) was associated with nonpulmonary organ system failure. Miliary tuberculosis should be considered in patients with adult respiratory distress syndrome of unknown etiology, and simple diagnostic procedures such as sputum, bronchial brushing, and gastric examination should be followed by invasive diagnostic procedures to confirm this etiology. Since untreated miliary tuberculosis is usually fatal, early recognition of this disease is of great importance, and specific therapy may play a lifesaving role. PMID:3584648

  16. Epidemiological models of Mycobacterium tuberculosis complex infections

    PubMed Central

    Ozcaglar, Cagri; Shabbeer, Amina; Vandenberg, Scott L.; Yener, Bülent; Bennett, Kristin P.

    2012-01-01

    The resurgence of tuberculosis in the 1990s and the emergence of drug-resistant tuberculosis in the first decade of the 21st century increased the importance of epidemiological models for the disease. Due to slow progression of tuberculosis, the transmission dynamics and its long-term effects can often be better observed and predicted using simulations of epidemiological models. This study provides a review of earlier study on modeling different aspects of tuberculosis dynamics. The models simulate tuberculosis transmission dynamics, treatment, drug resistance, control strategies for increasing compliance to treatment, HIV/TB co-infection, and patient groups. The models are based on various mathematical systems, such as systems of ordinary differential equations, simulation models, and Markov Chain Monte Carlo methods. The inferences from the models are justified by case studies and statistical analysis of TB patient datasets. PMID:22387570

  17. A New Vaccine against Tuberculosis Affords Greater Survival after Challenge than the Current Vaccine in the Guinea Pig Model of Pulmonary Tuberculosis

    Microsoft Academic Search

    Marcus A. Horwitz; Gunter Harth

    2003-01-01

    Tuberculosis (TB) remains an enormous global health problem, and a new vaccine against TB more potent than the current inadequate vaccine, Mycobacterium bovis BCG, is urgently needed. We describe a recombinant BCG vaccine (rBCG30) expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuber- culosis, the primary causative agent of TB, that affords greater survival after challenge than parental

  18. Is Tuberculosis Treatment Really Free in China? A Study Comparing Two Areas with Different Management Models

    PubMed Central

    Zhang, Simin; Peng, Xianzhen; Zheng, Xianzhi; Xu, Guisheng; Wang, Min; Wang, Jianming; Lu, Hui

    2015-01-01

    Objective China has implemented a free-service policy for tuberculosis. However, patients still have to pay a substantial proportion of their annual income for treatment of this disease. This study describes the economic burden on patients with tuberculosis; identifies related factors by comparing two areas with different management models; and provides policy recommendation for tuberculosis control reform in China. Methods There are three tuberculosis management models in China: the tuberculosis dispensary model, specialist model and integrated model. We selected Zhangjiagang (ZJG) and Taixing (TX) as the study sites, which correspond to areas implementing the integrated model and dispensary model, respectively. Patients diagnosed and treated for tuberculosis since January 2010 were recruited as study subjects. A total of 590 patients (316 patients from ZJG and 274 patients from TX) were interviewed with a response rate of 81%. The economic burden attributed to tuberculosis, including direct costs and indirect costs, was estimated and compared between the two study sites. The Mann-Whitney U Test was used to compare the cost differences between the two groups. Potential factors related to the total out-of-pocket costs were analyzed based on a step-by-step multivariate linear regression model after the logarithmic transformation of the costs. Results The average (median, interquartile range) total cost was 18793.33 (9965, 3200-24400) CNY for patients in ZJG, which was significantly higher than for patients in TX (mean: 6598.33, median: 2263, interquartile range: 983–6688) (Z = 10.42, P < 0.001). After excluding expenses covered by health insurance, the average out-of-pocket costs were 14304.4 CNY in ZJG and 5639.2 CNY in TX. Based on the multivariable linear regression analysis, factors related to the total out-of-pocket costs were study site, age, number of clinical visits, residence, diagnosis delay, hospitalization, intake of liver protective drugs and use of the second-line drugs. Conclusion Under the current “free of diagnosis and treatment” policy, the financial burden remains heavy on tuberculosis patients. Policy makers need to consider appropriate steps to lessen the burden of out-of-pocket costs for tuberculosis patients in China and how best to improve service delivery for poor patients. PMID:25993411

  19. Pentacyclic Nitrofurans with In Vivo Efficacy and Activity against Nonreplicating Mycobacterium tuberculosis

    PubMed Central

    Scherman, Michael S.; Woolhiser, Lisa K.; Madhura, Dora B.; Maddox, Marcus M.; Singh, Aman P.; Lee, Robin B.; Hurdle, Julian G.; McNeil, Michael R.; Lenaerts, Anne J.; Meibohm, Bernd; Lee, Richard E.

    2014-01-01

    The reductively activated nitroaromatic class of antimicrobials, which include nitroimidazole and the more metabolically labile nitrofuran antitubercular agents, have demonstrated some potential for development as therapeutics against dormant TB bacilli. In previous studies, the pharmacokinetic properties of nitrofuranyl isoxazolines were improved by incorporation of the outer ring elements of the antitubercular nitroimidazole OPC-67683. This successfully increased stability of the resulting pentacyclic nitrofuran lead compound Lee1106 (referred to herein as 9a). In the current study, we report the synthesis and antimicrobial properties of 9a and panel of 9a analogs, which were developed to increase oral bioavailability. These hybrid nitrofurans remained potent inhibitors of Mycobacterium tuberculosis with favorable selectivity indices (>150) and a narrow spectrum of activity. In vivo, the pentacyclic nitrofuran compounds showed long half-lives and high volumes of distribution. Based on pharmacokinetic testing and lack of toxicity in vivo, 9a remained the series lead. 9a exerted a lengthy post antibiotic effect and was highly active against nonreplicating M. tuberculosis grown under hypoxia. 9a showed a low potential for cross resistance to current antitubercular agents, and a mechanism of activation distinct from pre-clinical tuberculosis candidates PA-824 and OPC-67683. Together these studies show that 9a is a nanomolar inhibitor of actively growing as well as nonreplicating M. tuberculosis. PMID:24505329

  20. Treatment of Drug Susceptible Pulmonary Tuberculosis

    PubMed Central

    Shin, Hong-Joon

    2015-01-01

    Tuberculosis (TB) remains a major global health problem, and the incidence of TB cases has not significantly decreased over the past decade in Korea. The standard short course regimen is highly effective against TB, but requires multiple TB-specific drugs and a long treatment duration. Recent studies using late-generation fluoroquinolones and/or high-dose rifapentine-containing regimens to shorten the duration of TB treatment showed negative results. Extending the treatment duration may be considered in patients with cavitation on the initial chest radiograph and positivity in sputum culture at 2 months of treatment for preventing TB relapse. Current evidence does not support the use of fixed-dose combinations compared to separate drugs for the purpose of improving treatment outcomes. All patients receiving TB treatment should be monitored regularly for response to therapy, facilitation of treatment completion, and management of adverse drug reactions. Mild adverse effects can be managed with symptomatic therapy and changing the timing of the drug administration, but severe adverse effects require a discontinuation of the offending drugs. PMID:26175767

  1. Deciphering sulfoglycolipids of Mycobacterium tuberculosis[S

    PubMed Central

    Layre, Emilie; Cala-De Paepe, Diane; Larrouy-Maumus, Gérald; Vaubourgeix, Julien; Mundayoor, Sathish; Lindner, Buko; Puzo, Germain; Gilleron, Martine

    2011-01-01

    For 4 decades, in vivo and in vitro studies have suggested that sulfoglycolipids (SGLs) play a role in the virulence or pathogenesis of the tubercle bacilli. However, the SGL structure and biosynthesis pathway remain only partially elucidated. Using the modern tools of structural analysis, including MALDI-time-of-flight MS, MS/MS, and two-dimensional NMR, we reevaluated the structure of the different SGL acyl (di-, tri-, and tetra-acylated) forms of the reference strain Mycobacterium tuberculosis H37Rv, as well as those produced by the mmpL8 knockout strains previously described to intracellularly accumulate di-acylated SGL. We report here the identification of new acyl forms: di-acylated SGL esterified by simple fatty acids only, as well as mono-acylated SGL bearing a hydroxyphthioceranoic acid, which were characterized in the wild-type strain. In a clinical strain, a complete family of mono-acylated SGLs was characterized in high abundance for the first time. For the mmpL8 mutant, SGLs were found to be esterified i) by an oxophthioceranoic acid, never observed so far, and ii) at nonconventional positions in the case of the unexpected tri-acylated forms. Our results further confirm the requirement of MmpL8 for the complete assembly of the tetra-acylated forms of SGL and also provide, by the discovery of new intermediates, insights in terms of the possible SGL biosynthetic pathways. PMID:21482713

  2. A Common Mechanism of Inhibition of the Mycobacterium tuberculosis Mycolic Acid Biosynthetic Pathway by Isoxyl and Thiacetazone*

    PubMed Central

    Grzegorzewicz, Anna E.; Korduláková, Jana; Jones, Victoria; Born, Sarah E. M.; Belardinelli, Juan M.; Vaquié, Adrien; Gundi, Vijay A. K. B.; Madacki, Jan; Slama, Nawel; Laval, Françoise; Vaubourgeix, Julien; Crew, Rebecca M.; Gicquel, Brigitte; Daffé, Mamadou; Morbidoni, Hector R.; Brennan, Patrick J.; Quémard, Annaik; McNeil, Michael R.; Jackson, Mary

    2012-01-01

    Isoxyl (ISO) and thiacetazone (TAC), two prodrugs once used in the clinical treatment of tuberculosis, have long been thought to abolish Mycobacterium tuberculosis (M. tuberculosis) growth through the inhibition of mycolic acid biosynthesis, but their respective targets in this pathway have remained elusive. Here we show that treating M. tuberculosis with ISO or TAC results in both cases in the accumulation of 3-hydroxy C18, C20, and C22 fatty acids, suggestive of an inhibition of the dehydratase step of the fatty-acid synthase type II elongation cycle. Consistently, overexpression of the essential hadABC genes encoding the (3R)-hydroxyacyl-acyl carrier protein dehydratases resulted in more than a 16- and 80-fold increase in the resistance of M. tuberculosis to ISO and TAC, respectively. A missense mutation in the hadA gene of spontaneous ISO- and TAC-resistant mutants was sufficient to confer upon M. tuberculosis high level resistance to both drugs. Other mutations found in hypersusceptible or resistant M. tuberculosis and Mycobacterium kansasii isolates mapped to hadC. Mutations affecting the non-essential mycolic acid methyltransferases MmaA4 and MmaA2 were also found in M. tuberculosis spontaneous ISO- and TAC-resistant mutants. That MmaA4, at least, participates in the activation of the two prodrugs as proposed earlier is not supported by our biochemical evidence. Instead and in light of the known interactions of both MmaA4 and MmaA2 with HadAB and HadBC, we propose that mutations affecting these enzymes may impact the binding of ISO and TAC to the dehydratases. PMID:23002234

  3. Mycobacterium tuberculosis-Induced Polarization of Human Macrophage Orchestrates the Formation and Development of Tuberculous Granulomas In Vitro

    PubMed Central

    Guo, Yang; Chen, Jie; Xiong, Guoliang; Peng, Yiping; Ye, Jianqing; Li, Junming

    2015-01-01

    The tuberculous granuloma is an elaborately organized structure and one of the main histological hallmarks of tuberculosis. Macrophages, which are important immunologic effector and antigen-presenting cells, are the main cell type found in the tuberculous granuloma and have high plasticity. Macrophage polarization during bacterial infection has been elucidated in numerous recent studies; however, macrophage polarization during tuberculous granuloma formation and development has rarely been reported. It remains to be clarified whether differences in the activation status of macrophages affect granuloma formation. In this study, the variation in macrophage polarization during the formation and development of tuberculous granulomas was investigated in both sections of lung tissues from tuberculosis patients and an in vitro tuberculous granuloma model. The roles of macrophage polarization in this process were also investigated. Mycobacterium tuberculosis (M. tuberculosis) infection was found to induce monocyte-derived macrophage polarization. In the in vitro tuberculous granuloma model, macrophage transformation from M1 to M2 was observed over time following M. tuberculosis infection. M2 macrophages were found to predominate in both necrotic and non-necrotic granulomas from tuberculosis patients, while both M1 and M2 polarized macrophages were found in the non-granulomatous lung tissues. Furthermore, it was found that M1 macrophages promote granuloma formation and macrophage bactericidal activity in vitro, while M2 macrophages inhibit these effects. The findings of this study provide insights into the mechanism by which M. tuberculosis circumvents the host immune system as well as a theoretical foundation for the development of novel tuberculosis therapies based on reprogramming macrophage polarization. PMID:26091535

  4. [Commemorative lecture of receiving Imamura Memorial Prize. NK cell in pulmonary tuberculosis from basic and clinical point of view].

    PubMed

    Yoneda, T

    1996-11-01

    Although natural killer (NK) cells, which lyse certain tumors in vitro, have been shown to provide early defense mechanism against cancer growth and viral infection, possible role in the host defense against pulmonary tuberculosis remains undefined. A series of my studies have recently provided several evidence supporting the involvement of NK cells in the immunopathology of pulmonary tuberculosis. NK cell activity in patients with active pulmonary tuberculosis was significantly augmented compared with that in age-, sex- matched healthy controls, which suggests NK cells are activated in vivo in pulmonary tuberculosis. Lung NK cells from BCG-infected mice also are shown to be activated. Asialo GM 1 was demonstrated to be a novel surface marker of mice NK cells, which inhibited activation of NK cells by interferon. Chronic intractable tuberculosis was classified with a combination of NK cell activity and delayed-type hypersensitivity reaction to 2, 4-dinitrochrolbenzene. Subgroup defined with high NK cell activity and normal delayed-type hypersensitivity was characterized with moderate radiographical lesions and stable clinical course, suggesting the immune-spectrum classification was associated with clinical manifestations. Malnutrition has been suggested to be a risk factor associated with the development and reactivation of pulmonary tuberculosis. NK cell activity was significantly correlated with visceral proteins. IL-2 producing capability was significantly decreased in patients with serum albumin less than 3.5 g/dl. More recently, I established an in vitro system evaluating quantitative capability for intracellular killing by human monocytes, in which monocyte phagocytize Mycobacterium tuberculosis and subsequently inhibit intracellular replication of the organisms by adding some cytokines or cells. Purified NK cells by using discontinuous gradient centrifugation and magnetic separation technique were added to M. tuberculosis-infected monocytes monolayer. Purified NK cells inhibit intracellular replication within monocytes in dose response manner. PMID:8958676

  5. Risk factors for pulmonary tuberculosis in Croatia: a matched case–control study

    PubMed Central

    2013-01-01

    Background Mycobacterium tuberculosis is a necessary, but not sufficient, cause of tuberculosis. A number of studies have addressed the issue of risk factors for tuberculosis development. Croatia is a European country with an incidence rate of 14/100 000 which is slowly decreasing. The aim of this study is to evaluate the potential demographic, socioeconomic, behavioural and biological risk factors for tuberculosis in Croatia in comparison to other high-income, low-incidence European countries. Methods A total of 300 tuberculosis patients were matched for age, sex and county of residence to 300 controls randomly selected from general practitioners’ registers. They were interviewed and their medical records were evaluated for variables broadly described as potential risk factors. Results In multiple logistic regression, the following factors were significant: parents born in a particular neighbouring county (Bosnia and Herzegovina) (OR?=?3.90, 95% CI 2.01-7.58), the lowest level of education (OR?=?3.44, 95% CI 1.39-8.50), poor household equipment (OR?=?4.72, 95% CI 1.51-14.76), unemployment (OR?=?2.69, 95% CI 1.18-6.16), contact with tuberculosis (OR?=?2.19, 95% CI 1.27-3.77), former (OR?=?2.27, 95% CI 1.19-4.33) and current smoking habits (OR?=?2.35, 95% CI 1.27-4.36), diabetes (OR?=?2.38, 95% CI 1.05-5.38), a malignant disease (OR?=?5.79, 95% CI 1.49-22.42), being underweight in the previous year (OR?=?13.57, 95% CI 1.21-152.38). Conclusion In our study, the identified risk groups for tuberculosis reflect a complex interaction between socioeconomic conditions, lifestyle and non-communicable diseases. Interventions focused on poverty will undoubtedly be useful, but not sufficient. Tuberculosis control would benefit from a combination of broad public health activities aimed at the prevention and control of risky lifestyles and non-communicable diseases, interventions outside the health sector, and efforts to constantly improve the Croatian national tuberculosis programme. PMID:24144113

  6. Critical reflections on evidence, ethics and effectiveness in the management of tuberculosis: public health and global perspectives

    PubMed Central

    Verma, Geetika; Upshur, Ross EG; Rea, Elizabeth; Benatar, Solomon R

    2004-01-01

    Background Tuberculosis is a major cause of morbidity and mortality globally. Recent scholarly attention to public health ethics provides an opportunity to analyze several ethical issues raised by the global tuberculosis pandemic. Discussion Recently articulated frameworks for public health ethics emphasize the importance of effectiveness in the justification of public health action. This paper critically reviews the relationship between these frameworks and the published evidence of effectiveness of tuberculosis interventions, with a specific focus on the controversies engendered by the endorsement of programs of service delivery that emphasize direct observation of therapy. The role of global economic inequities in perpetuating the tuberculosis pandemic is also discussed. Summary Tuberculosis is a complex but well understood disease that raises important ethical challenges for emerging frameworks in public health ethics. The exact role of effectiveness as a criterion for judging the ethics of interventions needs greater discussion and analysis. Emerging frameworks are silent about the economic conditions contributing to the global burden of illness associated with tuberculosis and this requires remediation. PMID:15113419

  7. Genetic determination of the effect of post-translational modification on the innate immune response to the 19 kDa lipoprotein of Mycobacterium tuberculosis

    Microsoft Academic Search

    Katalin A Wilkinson; Sandra M Newton; Graham R Stewart; Adrian R Martineau; Janisha Patel; Susan M Sullivan; Jean-Louis Herrmann; Olivier Neyrolles; Douglas B Young; Robert J Wilkinson

    2009-01-01

    BACKGROUND: The 19 kDa lipoprotein of Mycobacterium tuberculosis (MTB) is an important target of the innate immune response. To investigate the effect of post-translation modification of this protein on innate recognition in the context of the whole bacillus, we derived a recombinant M. tuberculosis H37Rv that lacked the 19 kDa gene (?19) and complemented this strain by reintroduction of the

  8. The Effects of HIV on the Sensitivity of a Whole Blood IFN-gamma Release Assay in Zambian Adults with Active Tuberculosis

    Microsoft Academic Search

    Edward Raby; Maureen Moyo; Akash Devendra; Joseph Banda; Petra de Haas; Helen Ayles; Peter Godfrey-Faussett; Madhukar Pai

    2008-01-01

    BackgroundInterferon gamma release assays (IGRA) are replacing the tuberculin skin test (TST) as a diagnostic tool for Mycobacterium tuberculosis infection. However research into the test's performance in the high HIV-TB burden setting is scarce. This study aimed to define the sensitivity of an IGRA, QuantiFERON-TB® Gold In-Tube (QGIT), in adult Zambian patients with active smear-positive tuberculosis. Secondary outcomes focussed on

  9. Theory-Informed Interventions to Improve the Quality of Tuberculosis Evaluation at Ugandan Health Centers: A Quasi-Experimental Study

    PubMed Central

    Haguma, Priscilla; Ochom, Emmanuel; Ayakaka, Irene; Mugabe, Frank; Miller, Cecily; Vittinghoff, Eric; Davis, J. Lucian; Handley, Margaret A.; Cattamanchi, Adithya

    2015-01-01

    Background Tuberculosis (TB) remains under-diagnosed in many countries, in part due to poor evaluation practices at health facilities. Theory-informed strategies are needed to improve implementation of TB evaluation guidelines. We aimed to evaluate the impact of performance feedback and same-day smear microscopy on the quality of TB evaluation at 6 health centers in rural Uganda. Methods We tested components of a multi-faceted intervention to improve adherence to the International Standards for Tuberculosis Care (ISTC): performance feedback and same-day smear microscopy. The strategies were selected based on a qualitative assessment guided by the Theory of Planned Behavior and the PRECEDE model. We collected patient data 6 months before and after the introduction of each intervention component, and compared ISTC adherence in the pre- and post-intervention periods for adults with cough ? 2 weeks’ duration. Results The performance feedback evaluation included 1,446 adults; 838 (58%) were evaluated during the pre-intervention period and 608 (42%) during the post-intervention period. Performance feedback resulted in a 15% (95%CI +10% to +20%, p<0.001) increase in the proportion of patients receiving ISTC-adherent care. The same-day microscopy evaluation included 1,950 adults; 907 (47%) were evaluated during the pre-intervention period and 1,043 (53%) during the post-intervention period. Same-day microscopy was associated with a 14% (95%CI +10% to +18%, p<0.001) increase in the proportion of patients receiving ISTC-adherent care. Conclusions Performance feedback and same-day microscopy should be considered along with ISTC training as part of a multi-faceted intervention to improve the quality of TB evaluation in other high TB burden countries. PMID:26172948

  10. Insight to the Epidemiology and Risk Factors of Extrapulmonary Tuberculosis in Tianjin, China during 2006-2011

    PubMed Central

    Wang, Xiaoqing; Yang, Zhenhua; Fu, Yanyong; Zhang, Guoqin; Wang, Xu; Zhang, Yuhua; Wang, Xiexiu

    2014-01-01

    Background The proportion of extrapulmonary tuberculosis (EPTB) among all the reported tuberculosis (TB) cases has increased in different populations. Despite the large burden of TB in China, the epidemiology of EPTB in China remains largely understudied and the risk factors for having EPTB diagnosis in China have not been identified. Methods To gain insight to EPTB epidemiology in China, we analyzed TB surveillance data collected in Tianjin, China, during 2006 to 2011. The frequency of EPTB among all TB cases and within different socio-demographic groups of the study patients aged 15 years and older was determined for EPTB in general and by specific types. The distribution of socio-demographic characteristics was compared between pulmonary TB (PTB) group and EPTB group by chi-square test. Crude and multiple logistic regression-derived adjusted odds ratios (aOR) and 95% confidence intervals (CI) were determined to assess the associations between having EPTB diagnosis and each individual explanatory variable in question. Results About one-tenth (1,512/14,561) of the patients investigated in this study had EPTB. Of these 1,512 EPTB cases, about two thirds were pleural TB. Significant difference in age, occupation, and urbanity of residence were found between PTB and EPTB groups (p<0.05). Patients with EPTB diagnosis were more likely to be 65 years or older (aOR?=?1.22, 95% CI: 1.02, 1.46), to be retired (aOR?=?1.37, 95% CI: 1.08, 1.75), and to live in urban areas (aOR?=?1 38, 95% CI: 1.22, 1.55). Conclusions The findings of this study extends the knowledgebase of EPTB epidemiology in developing countries and highlight the need for improved EPTB detection in China, especially in subpopulations with high risk for EPTB or having limited access to medical facilities with adequate capacity for EPTB diagnosis. PMID:25494360

  11. Inherited and acquired immunodeficiencies underlying tuberculosis in childhood.

    PubMed

    Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; El Azbaoui, Safaa; Agader, Aomar; Hassani, Amal; El Hafidi, Naima; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

    2015-03-01

    Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-? immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

  12. Screening ancient tuberculosis with qPCR: challenges and opportunities.

    PubMed

    Harkins, Kelly M; Buikstra, Jane E; Campbell, Tessa; Bos, Kirsten I; Johnson, Eric D; Krause, Johannes; Stone, Anne C

    2015-01-19

    The field of ancient DNA (aDNA) has rapidly accelerated in recent years as a result of new methods in next-generation sequencing, library preparation and targeted enrichment. Such research is restricted, however, by the highly variable DNA preservation within different tissues, especially when isolating ancient pathogens from human remains. Identifying positive candidate samples via quantitative PCR (qPCR) for downstream procedures can reduce reagent costs, increase capture efficiency and maximize the number of sequencing reads of the target. This study uses four qPCR assays designed to target regions within the Mycobacterium tuberculosis complex (MTBC) to examine 133 human skeletal samples from a wide geographical and temporal range, identified by the presence of skeletal lesions typical of chronic disseminated tuberculosis. Given the inherent challenges working with ancient mycobacteria, strict criteria must be used and primer/probe design continually re-evaluated as new data from bacteria become available. Seven samples tested positive for multiple MTBC loci, supporting them as strong candidates for downstream analyses. Using strict and conservative criteria, qPCR remains a fast and effective screening tool when compared with screening by more expensive sequencing and enrichment technologies. PMID:25487341

  13. Detection of IgG and IgA against the mycobacterial antigen A60 in patients with extrapulmonary tuberculosis

    PubMed Central

    Alifano, M.; De Pascalis, R.; Sofia, M.; Faraone, S.; Del Pezzo, M.; Covelli, I.

    1998-01-01

    BACKGROUND—Diagnosis of extrapulmonary tuberculosis is often difficult to establish using standard methods. Serological techniques based on detection of antibodies against mycobacterial antigen A60 have shown good sensitivity and specificity in pulmonary tuberculosis. The present study was undertaken to define the diagnostic accuracy of testing for IgG and IgA against A60 in extrapulmonary tuberculosis.?METHODS—One hundred and ninety eight subjects were studied: 42 patients with extrapulmonary tuberculosis confirmed by microbiology and/or histology, 24 subjects with healed pulmonary or extrapulmonary tuberculosis, 44 patients with a defined non-tuberculous disease, and 88 healthy volunteers (44 PPD negative and 44 PPD positive). Detection of IgG and IgA against A60 antigen was carried out by enzyme-linked immunosorbent assay. Cut off values were determined by receiver operating characteristic curves.?RESULTS—Sensitivity of the IgG test was 73.8% in extrapulmonary tuberculosis, while the specificity was 96.1%. The IgA test showed a sensitivity of 69.0% with a specificity of 93.6%. Combination of the IgG and IgA tests showed a sensitivity of 80.9% and a specificity of 92.3%. Patients with extrapulmonary tuberculosis showed significantly higher titres of both IgG and IgA against A60 than other groups.?CONCLUSIONS—Anti-A60 IgG or IgA tests are characterised by good sensitivity and specificity. The combined use of both tests allows an increase in diagnostic accuracy of extrapulmonary tuberculosis.?? PMID:9708230

  14. The Association between Mycobacterium Tuberculosis Genotype and Drug Resistance in Peru

    PubMed Central

    Grandjean, Louis; Iwamoto, Tomotada; Lithgow, Anna; Gilman, Robert H; Arikawa, Kentaro; Nakanishi, Noriko; Martin, Laura; Castillo, Edith; Alarcon, Valentina; Coronel, Jorge; Solano, Walter; Aminian, Minoo; Guezala, Claudia; Rastogi, Nalin; Couvin, David; Sheen, Patricia; Zimic, Mirko; Moore, David AJ

    2015-01-01

    Background The comparison of Mycobacterium tuberculosis bacterial genotypes with phenotypic, demographic, geospatial and clinical data improves our understanding of how strain lineage influences the development of drug-resistance and the spread of tuberculosis. Methods To investigate the association of Mycobacterium tuberculosis bacterial genotype with drug-resistance. Drug susceptibility testing together with genotyping using both 15-loci MIRU-typing and spoligotyping, was performed on 2,139 culture positive isolates, each from a different patient in Lima, Peru. Demographic, geospatial and socio-economic data were collected using questionnaires, global positioning equipment and the latest national census. Results The Latin American Mediterranean (LAM) clade (OR 2.4, p<0.001) was significantly associated with drug-resistance and alone accounted for more than half of all drug resistance in the region. Previously treated patients, prisoners and genetically clustered cases were also significantly associated with drug-resistance (OR's 2.5, 2.4 and 1.8, p<0.001, p<0.05, p<0.001 respectively). Conclusions Tuberculosis disease caused by the LAM clade was more likely to be drug resistant independent of important clinical, genetic and socio-economic confounding factors. Explanations for this include; the preferential co-evolution of LAM strains in a Latin American population, a LAM strain bacterial genetic background that favors drug-resistance or the "founder effect" from pre-existing LAM strains disproportionately exposed to drugs. PMID:25984723

  15. Is it better to be rich in a poor area or poor in a rich area? A multilevel analysis of a case–control study of social determinants of tuberculosis

    PubMed Central

    de Alencar Ximenes, Ricardo Arraes; de Fátima Pessoa Militão de Albuquerque, Maria; Souza, Wayner V; Montarroyos, Ulisses R; Diniz, George T N; Luna, Carlos F; Rodrigues, Laura C

    2009-01-01

    Background Tuberculosis is known to have socio-economic determinants at individual and at area levels, but it is not known whether they are independent, whether they interact and their relative contributions to the burden of tuberculosis. Methods A case–control study was conducted in Recife, Brazil, to investigate individual and area social determinants of tuberculosis, to explore the relationship between determinants at the two levels and to calculate their relative contribution to the burden of tuberculosis. It included 1452 cases of tuberculosis diagnosed by the tuberculosis services and 5808 controls selected at random from questionnaires completed for the demographic census. Exhaustive information on social factors was collected from cases, using the questionnaire used in the census. Socio-economic information for areas was downloaded from the census. Multilevel logistic regression investigated individual and area effects. Results There was a marked and independent influence of social variables on the risk of tuberculosis, both at individual and area levels. At individual level, being aged ?20, being male, being illiterate, not working in the previous 7 days and possessing few goods, all increased the risk of tuberculosis. At area level, living in an area with many illiterate people and where few households own a computer also increased this risk; individual and area levels did not appear to interact. Twice as many cases were attributable to social variables at individual level than at area level. Conclusions Although individual characteristics are the main contributor to the risk of tuberculosis, contextual characteristics make a substantial independent contribution. PMID:19656772

  16. Post-exposure rate of tuberculosis infection among health care workers measured with tuberculin skin test conversion after unprotected exposure to patients with pulmonary tuberculosis: 6-year experience in an Italian teaching hospital

    PubMed Central

    2014-01-01

    Background This study assesses the risk of LTBI at our Hospital among HCWs who have been exposed to TB patients with a delayed diagnosis and respiratory protection measures were not implemented. Methods All HCWs exposed to a patient with cultural confirmed pulmonary TB and respiratory protection measures were not implemented were included. Data on TST results performed in the past (defined as T0) were recorded. TST was performed twice: first, immediately after exposure to an index patient (T1) and three months later (T2). The period of time between T0 and T1 was used to calculate he annual rate of tuberculosis infection (ARTI), while le period of time between T1 and T2 was used to calculate the post exposure annual rate of tuberculosis infection (PEARTI). Results Fourteen index patients were admitted; sputum smear was positive in 7 (58.3%), 4 (28.6%) were non-Italian born patients. 388 HCWs were exposed to index patients, a median of 27 (12-39) HCW per each index patient. One hundred eighty (46.4%) HCWs received BCG in the past. One hundred twenty two HCWs (31%) were TST positive at a previous routine screening and not evaluated in this subset. Among the remaining 255 HCWs with negative TST test in the past, TST at T1 was positive in 11 (4.3%). ARTI was 1.6 (95% CI 0.9-2.9) per 100 PY. TST at T2 was positive in 9 (3.7%) HCWs, that were TST negative at T1. PEARTI was 26 (95% CI 13.6-50) per 100 PY. At univariate analysis, older age was associated with post exposure latent tuberculosis infection (HR 1.12; 95% CI 1.03-1.22, p=0.01). Conclusions PEARTI was considerably higher among HCWs exposed to index patients than ARTI. These data underscore the overwhelming importance of performing a rapid diagnosis, as well as implementing adequate respiratory protection measures when TB is suspected. PMID:24919953

  17. Mycobacterium tuberculosis ecology in Venezuela: epidemiologic correlates of common spoligotypes and a large clonal cluster defined by MIRU-VNTR-24

    PubMed Central

    2009-01-01

    Background Tuberculosis remains an endemic public health problem, but the ecology of the TB strains prevalent, and their transmission, can vary by country and by region. We sought to investigate the prevalence of Mycobacterium tuberculosis strains in different regions of Venezuela. A previous study identified the most prevalent strains in Venezuela but did not show geographical distribution nor identify clonal genotypes. To better understand local strain ecology, we used spoligotyping to analyze 1298 M. tuberculosis strains isolated in Venezuela from 1997 to 2006, predominantly from two large urban centers and two geographically distinct indigenous areas, and then studied a subgroup with MIRU-VNTR 24 loci. Results The distribution of spoligotype families is similar to that previously reported for Venezuela and other South American countries: LAM 53%, T 10%, Haarlem 5%, S 1.9%, X 1.2%, Beijing 0.4%, and EAI 0.2%. The six most common shared types (SIT's 17, 93, 605, 42, 53, 20) accounted for 49% of the isolates and were the most common in almost all regions, but only a minority were clustered by MIRU-VNTR 24. One exception was the third most frequent overall, SIT 605, which is the most common spoligotype in the state of Carabobo but infrequent in other regions. MIRU-VNTR homogeneity suggests it is a clonal group of strains and was named the "Carabobo" genotype. Epidemiologic comparisons showed that patients with SIT 17 were younger and more likely to have had specimens positive for Acid Fast Bacilli on microscopy, and patients with SIT 53 were older and more commonly smear negative. Female TB patients tended to be younger than male patients. Patients from the high incidence, indigenous population in Delta Amacuro state were younger and had a nearly equal male:female distribution. Conclusion Six SIT's cause nearly half of the cases of tuberculosis in Venezuela and dominate in nearly all regions. Strains with SIT 17, the most common pattern overall may be more actively transmitted and SIT 53 strains may be less virulent and associated with reactivation of past infections in older patients. In contrast to other common spoligotypes, strains with SIT 605 form a clonal group centered in the state of Carabobo. PMID:19660112

  18. Effect of a publicly funded tuberculosis service on the diagnosis of tuberculosis at a teaching hospital.

    PubMed

    Bass, J B; Hawkins, E L

    1984-03-01

    The speed and accuracy of diagnosis of tuberculosis on general medical teaching services were retrospectively compared to that on a designated publicly funded tuberculosis service and to recent discouraging reports in the literature. The diagnosis was confirmed in all patients on the designated service and in 78.8% of patients not on the designated service within one week. No patient was discharged undiagnosed. Acid-fast smears done by the hospital laboratory showed a sensitivity of 82.5% and a specificity of 98.4%. Radiologic reports indicated the presence of tuberculosis or cavities in 85% of chest x-ray films in patients with pulmonary disease. These results may indicate that a publicly funded tuberculosis service, by providing emphasis on tuberculosis, allows more rapid and accurate diagnosis of tuberculosis in all patients. The impact of such training on future health care delivery should be recognized when decisions regarding allocation of public funds are made. PMID:6422562

  19. Simultaneous occurrence of multiple types of cutaneous tuberculosis (TVC and PNT) with internal organ tuberculosis (PTB).

    PubMed

    Miah, M A; Chowdhury, U A; Ahmed, N; Shafique, M; Islam, N

    2007-01-01

    A 40 years old male patient of poor socioeconomic condition presented with a well circumscribed rough surfaced and fissured, verrucous plaque on left axilla and a similar lesion on right foot- which were clinically diagnosed as tuberculosis verrucosa cutis. He also had necrotic papular eruption with varioliform scarring in some lesions on upper back clinically diagnosed as papulonecrotic tuberculid. He had fever and cough and mild weight loss suspicious of pulmonary tuberculosis. On investigation ESR was raised, mild anaemia was present, MT was strongly positive, chest x-ray was suggestive of tuberculosis. So, he was diagnosed as a case of simultaneous occurrence of tuberculosis verrucosa cutis (TVC) with papulonecrotic tuberculid (PNT) with pulmonary tuberculosis (PTB). Standard anti tuberculosis chemotherapy already started to offer cure of all lesions. PMID:17344792

  20. Novel Adjunctive Therapies for the Treatment of Tuberculosis

    PubMed Central

    Ordonez, A.A.; Maiga, M.; Gupta, S.; Weinstein, E.A.; Bishai, W.R.; Jain, S.K.

    2015-01-01

    Despite significant efforts to control tuberculosis (TB), the disease remains a major global threat, with an estimated 8.6 million new cases and 1.3 million deaths in 2012 alone. Significant treatment challenges include HIV co-infection, the dramatic rise of multidrug-resistant TB and the vast reservoir of latently infected individuals, who will develop active disease years after the initial infection. The long duration of chemotherapy also remains a major barrier to effective large scale treatment of TB. Significant advances are being made in the development of shorter and effective TB drug regimens and there is growing evidence that host-directed and “non-antimicrobial” pathogen-directed therapies, could serve as novel approaches to enhance TB treatments. This review highlights the rationale for using these therapies and summarizes some of the progress in this field. PMID:24236454

  1. Mycobacterium tuberculosis Serine/Threonine Protein Kinases

    PubMed Central

    PRISIC, SLADJANA; HUSSON, ROBERT N.

    2014-01-01

    The Mycobacterium tuberculosis genome encodes 11 serine/threonine protein kinases (STPKs). A similar number of two-component systems are also present, indicating that these two signal transduction mechanisms are both important in the adaptation of this bacterial pathogen to its environment. The M. tuberculosis phosphoproteome includes hundreds of Ser- and Thr-phosphorylated proteins that participate in all aspects of M. tuberculosis biology, supporting a critical role for the STPKs in regulating M. tuberculosis physiology. Nine of the STPKs are receptor type kinases, with an extracytoplasmic sensor domain and an intracellular kinase domain, indicating that these kinases transduce external signals. Two other STPKs are cytoplasmic and have regulatory domains that sense changes within the cell. Structural analysis of some of the STPKs has led to advances in our understanding of the mechanisms by which these STPKs are activated and regulated. Functional analysis has provided insights into the effects of phosphorylation on the activity of several proteins, but for most phosphoproteins the role of phosphorylation in regulating function is unknown. Major future challenges include characterizing the functional effects of phosphorylation for this large number of phosphoproteins, identifying the cognate STPKs for these phosphoproteins, and determining the signals that the STPKs sense. Ultimately, combining these STPK-regulated processes into larger, integrated regulatory networks will provide deeper insight into M. tuberculosis adaptive mechanisms that contribute to tuberculosis pathogenesis. Finally, the STPKs offer attractive targets for inhibitor development that may lead to new therapies for drug-susceptible and drug-resistant tuberculosis. PMID:25429354

  2. Genetic engineering of Mycobacterium tuberculosis: a review.

    PubMed

    Lamrabet, Otmane; Drancourt, Michel

    2012-09-01

    Genetic engineering has been used for decades to mutate and delete genes in the Mycobacterium tuberculosis genome with the translational goal of producing attenuated mutants with conserved susceptibility to antituberculous antibiotics. The development of plasmids and mycobacteriophages that can transfer DNA into the M. tuberculosis chromosome has effectively overcome M. tuberculosis slow growth rate and the capsule and mycolic acid wall, which limit DNA uptake. The use of genetic engineering techniques has shed light on many aspects of pathogenesis mechanisms, including cellular growth, mycolic acid biosynthesis, metabolism, drug resistance and virulence. Moreover, such research gave clues to the development of new vaccines or new drugs for routine clinical practice. The use of genetic engineering tools is mainly based on the underlying concept that altering or reducing the M. tuberculosis genome could decrease its virulence. A contrario, recent post-genomic analyses indicated that reduced bacterial genomes are often associated with increased bacterial virulence and that M. tuberculosis acquired genes by lateral genetic exchange during its evolution. Therefore, ancestors utilizing genetic engineering to add genes to the M. tuberculosis genome may lead to new vaccines and the availability of M. tuberculosis isolates with increased susceptibility to antituberculous antibiotics. PMID:22789498

  3. HIV Infection Disrupts the Sympatric Host–Pathogen Relationship in Human Tuberculosis

    PubMed Central

    Fenner, Lukas; Egger, Matthias; Bodmer, Thomas; Furrer, Hansjakob; Ballif, Marie; Battegay, Manuel; Helbling, Peter; Fehr, Jan; Gsponer, Thomas; Rieder, Hans L.; Zwahlen, Marcel; Hoffmann, Matthias; Bernasconi, Enos; Cavassini, Matthias; Calmy, Alexandra; Dolina, Marisa; Frei, Reno; Janssens, Jean-Paul; Borrell, Sonia; Stucki, David; Schrenzel, Jacques; Böttger, Erik C.; Gagneux, Sebastien

    2013-01-01

    The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host. To test this hypothesis, we performed a nine-year nation-wide molecular-epidemiological study of HIV–infected and HIV–negative patients with tuberculosis (TB) between 2000 and 2008 in Switzerland. We analyzed 518 TB patients of whom 112 (21.6%) were HIV–infected and 233 (45.0%) were born in Europe. We found that among European-born TB patients, recent transmission was more likely to occur in sympatric compared to allopatric host–pathogen combinations (adjusted odds ratio [OR] 7.5, 95% confidence interval [95% CI] 1.21–infinity, p?=?0.03). HIV infection was significantly associated with TB caused by an allopatric (as opposed to sympatric) M. tuberculosis lineage (OR 7.0, 95% CI 2.5–19.1, p<0.0001). This association remained when adjusting for frequent travelling, contact with foreigners, age, sex, and country of birth (adjusted OR 5.6, 95% CI 1.5–20.8, p?=?0.01). Moreover, it became stronger with greater immunosuppression as defined by CD4 T-cell depletion and was not the result of increased social mixing in HIV–infected patients. Our observation was replicated in a second independent panel of 440 M. tuberculosis strains collected during a population-based study in the Canton of Bern between 1991 and 2011. In summary, these findings support a model for TB in which the stable relationship between the human host and its locally adapted M. tuberculosis is disrupted by HIV infection. PMID:23505379

  4. Mycobacterium tuberculosis mammalian cell entry operon ( mce) homologs in Mycobacterium other than tuberculosis (MOTT)

    Microsoft Academic Search

    Yoseph Haile; Dominique A. Caugant; Gunnar Bjune; Harald G. Wiker

    2002-01-01

    The cloned mammalian cell entry gene mce1a from Mycobacterium tuberculosis confers to non-pathogenic Escherichia coli the ability to invade and survive inside macrophages and HeLa cells. The aim of this work was to search for and characterize homologs of the four M. tuberculosis mammalian cell entry operons (mce1, mce2, mce3 and mce4) in mycobacteria other than tuberculosis (MOTT). The dot-blot

  5. Early Deaths During Tuberculosis Treatment Are Associated With Depressed Innate Responses, Bacterial Infection, and Tuberculosis Progression

    PubMed Central

    Peter K. Banda, N.; White, Sarah A.; Kampmann, Beate; Kumwenda, Jean; Heyderman, Robert S.; Pirmohamed, Munir; Squire, S. Bertel

    2011-01-01

    Up to 14% of Malawian adults die during the intensive phase of tuberculosis treatment. In a prospective cohort of 199 Malawian adults with microbiologically confirmed pulmonary tuberculosis, clinical and laboratory parameters were compared between those who died or deteriorated with those who had an uneventful recovery. Baseline tumor necrosis factor alpha responses to stimulation with heat-killed Mycobacterium tuberculosis and lipopolysaccharide were reduced among the 22 patients with poor outcome (P = .017). Low body mass index (P = .002) and elevated respiratory rate (P = .01) at tuberculosis diagnosis independently predicted poor outcome. Validation of a clinical score identifying high-risk individuals is warranted, together with further investigation of immunological derangements. PMID:21742833

  6. Excess Mortality Associated with Influenza among Tuberculosis Deaths in South Africa, 1999–2009

    PubMed Central

    Walaza, Sibongile; Cohen, Cheryl; Nanoo, Ananta; Cohen, Adam L.; McAnerney, Johanna; von Mollendorf, Claire; Moyes, Jocelyn; Tempia, Stefano

    2015-01-01

    Background Published data on the interaction between influenza and pulmonary tuberculosis (PTB) are limited. We aimed to estimate the influenza-associated mortality among individuals with PTB in South Africa from 1999–2009. Methods We modelled the excess influenza-associated mortality by applying Poisson regression models to monthly PTB and non-tuberculosis respiratory deaths, using laboratory-confirmed influenza as a covariate. Results PTB deaths increased each winter, coinciding with influenza virus circulation. Among individuals of any age, mean annual influenza-associated PTB mortality rate was 164/100,000 person-years (n = 439). The rate of non-tuberculosis respiratory deaths was 27/100,000 (n = 1125) for HIV-infected and 5/100,000 (n = 2367) for HIV-uninfected individuals of all ages. Among individuals aged <65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-infected (relative risk (RR): 5.2; 95% CI: 4.6–5.9) and HIV-uninfected individuals (RR: 61.0; CI: 41.4–91.0). Among individuals aged ?65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-uninfected individuals (RR: 13.0; 95% CI: 12.0–14.0). Conclusion We observed an increased risk of influenza-associated mortality in persons with PTB compared to non-tuberculosis respiratory deaths. If confirmed in other settings, our findings may support recommendations for active inclusion of patients with TB for influenza vaccination and empiric influenza anti-viral treatment of patients with TB during influenza epidemics. PMID:26076197

  7. Polymerase chain reaction targeting insertion sequence for the diagnosis of extrapulmonary tuberculosis

    PubMed Central

    Makeshkumar, V.; Madhavan, Radha; Narayanan, Sujatha

    2014-01-01

    Background & objectives: Diagnosis of extrapulmonary tuberculosis (EPTB) is difficult using conventional diagnostic methods. This study was conducted to evaluate the use of polymerase chain reaction (PCR) in diagnosis of definitive and probable extrapulmonary tuberculosis patients, and to assess the performance of insertion sequence (IS) 6110 based PCR assay as compared to conventional culture by Lowenstein-Jensen (LJ) method for the diagnosis of EPTB. Methods: A total of 178 non repeated clinical specimens were collected from clinically suspected extrapulmonary tuberculosis patients. The specimens included 59 ascitic fluid, 54 pleural fluid, 25 cerebrospinal fluid (CSF), 12 fine needle aspiration (FNA), 8 urine, 7 pus, 6 synovial fluid, 2 skin tissue, one pericardial fluid, one liver abscess, one pancreatic cyst fluid, one omental biopsy and one semen sample. All these clinical samples were subjected to Ziehl-Neelsen staining (ZN) for acid fast bacilli (AFB) and culture on LJ medium. PCR was performed by targeting 123bp fragment of insertion sequence IS6110 of Mycobacterium tuberculosis (MTB). Results: Of the 178 specimens, 10 (5.61%) were ZN smear positive for AFB, six (3.37%) were L-J culture positive from 10 AFB smear positive cases and 48 (26.96%) were PCR IS 6110 positive for M. tuberculosis. Interpretation & conclusions: PCR using IS6110 primer was able to pick up more EPTB patients compared to conventional L-J culture method for detection of M. tuberculosis. False positive PCR IS6110 in three CSF samples may be due to latent TB infection which was limitation in this study. PMID:24604051

  8. Genitourinary tuberculosis: an atypical clinical presentation.

    PubMed

    Lim, Pei Shan; Atan, Ixora Kamisan; Naidu, Aruku

    2012-01-01

    Genitourinary tuberculosis is one of the common forms of extrapulmonary tuberculosis. We report a case of atypical genitourinary tuberculosis: massive uterovaginal prolapse with cervical lesion mimicking cervical carcinoma. This particular case highlights the problem of healthcare in most of the developing countries. Lack of patient education, awareness, and access to a healthcare system resulted in a complicated situation. In an endemic area or in an immunocompromised individual, a higher index of suspicion would allow early recognition and treatment institution to minimise its late consequences as well as spreading of the disease. Though anti-TB is the mainstay of treatment, surgical intervention might be needed in selected cases. PMID:23320216

  9. Knowledge of diabetes mellitus in tuberculosis amongst healthcare workers in Nigeria

    PubMed Central

    Ogbera, Okeoghene Anthonia; Adeyeye, Olufunke; Odeniyi, Ifedayo Adeola; Adeleye, Olufunmilayo

    2013-01-01

    Background: There is a World Diabetes Foundation funded research on detection of diabetes mellitus (DM) in tuberculosis (TB) which is currently being carried out in 56 TB centers in Lagos State Nigeria and against this background, we decided to evaluate the knowledge of DM and (TB) amongst the health workers from these facilities. Materials and Methods: We employed the use of self-administered questionnaires comprising questions to determine participant's knowledge on risk factors, clinical presentation and complications of DM, diagnosis, management of DM, and presentation and management of TB. We documented and also compared responses that differed in a statistically significant manner amongst the various cadres of health worker and the three tiers of healthcare facilities. Results: A total of 263 health care workers responded, out of which medical doctors constituted 72 (27.4%) while nurses and other categories of health care workers constituted 191 (72.6%). All the respondents knew that TB is a communicable disease and a large majority– 86% knew that DM is a chronic disorder that as of now has no cure. One hundred and eighty one (71%) respondents gave a correct response of a fasting plasma glucose level of 9mmol/L, which is in the range for diagnosis of DM. About a third-90-of the health workers, however, stated that DM may be diagnosed solely on clinical symptoms of DM. However, 104 (46%) of the Study participants stated that urine may be employed for objectively diagnosing DM. All respondents had hitherto not had patients with TB who had been routinely screened for DM. There was insufficient knowledge on the non-pharmacological management with over half of the respondents, irrespective ofstatus, maintained that all persons diagnosed with DM should be made to lose weight and carbohydrate should make up less than 30% of the component of their meals. Conclusion: There remains largely inadequate knowledge on diagnosing and non-pharmacological management of DM among the health workers in our TB facilities. PMID:23961490

  10. The Burden of MDR/XDR Tuberculosis in Coastal Plains Population of China

    PubMed Central

    Yang, Xiujun; Yuan, Yanli; Pang, Yu; Wang, Bo; Bai, Yunlong; Wang, Yanhua; Yu, Baozhu; Zhang, Zhiying; Fan, Ming; Zhao, Yanlin

    2015-01-01

    Background We conducted a first baseline survey in Jilin Province of China to determine the proportion of drug-resistant tuberculosis (TB), and to analyze risk factors associated with the emergence of drug-resistance. Methodology/Principal Findings Thirty counties in Jilin Province were randomly selected as survey sites using a stratified cluster sampling method. People enrolled in the survey were new and re-treated, smear-positive pulmonary TB patients newly enrolled in local TB control and prevention institutions during the survey period. Sputum samples were collected, and the susceptibility of bacterial strains to anti-TB drugs was analyzed by proportion method. Based on the survey results, we estimated the number of drug-resistant TB patients and analyzed the risk factors associated with the emergence of drug resistance. Of 1,174 new TB patients and 597 re-treated TB patients, 8.6% and 23.2% were multi-drug resistant (MDR)-TB patients, respectively. Approximately 12% of MDR-TB patients were extensively drug-resistant. We estimate that approximately 1,290 new MDR-TB cases develop in Jilin Province every year. Of these, 810 cases would be new patients, and 480 cases would involve re-treated patients. Risk factors associated with MDR-TB include employment status, educational background, and income level. Conclusions/Significance Jilin Province remains one of the highest-burden areas in China for drug-resistant TB. The higher number of MDR-TB among new cases suggested that the transmission of drug-resistant strains in Jilin is an urgent problem in the MDR-TB control and prevention system of Jilin Province. Improving the treatment compliance of TB patients and the quality of medical care in public health institutions is urgently needed. PMID:25689373

  11. Detection of Buried Human Remains Using Bioreporter Fluorescence

    SciTech Connect

    Vass, A. Dr.; Singleton, G. B.

    2001-10-01

    The search for buried human remains is a difficult, laborious and time-consuming task for law enforcement agencies. This study was conducted as a proof of principle demonstration to test the concept of using bioreporter microorganisms as a means to cover large areas in such a search. These bioreporter microorganisms are affected by a particular component of decaying organic matter that is distinct from decaying vegetation. The diamino compounds cadaverine and putrescine were selected as target compounds for the proof-of-principle investigation, and a search for microorganisms and genes that are responsive to either of these compounds was conducted. One recombinant clone was singled out for characterization based on its response to putrescine. The study results show that small concentrations of putrescine increased expression from this bioreporter construct. Although the level of increase was small (making it difficult to distinguish the signal from background), the results demonstrate the principle that bioreporters can be used to detect compounds resulting from decaying human remains and suggest that a wider search for target compounds should be conducted.

  12. New drugs in resistant tuberculosis.

    PubMed

    Rao, Nisar Ahmed

    2007-05-01

    The World Health Organization estimates that up to 50 million persons worldwide may be infected with drug resistant strains of TB. The fatality rate of MDR-TB is 20-80%. Drug resistant tuberculosis cases are on the rise in Pakistan. The reasons for this menace are multiple including improper prescription, compliance and over the counter sale of anti-TB drugs. The treatment cost of drug-resistant TB is high, both to the individual patient and society. This article is written to create awareness about the available second line drugs and those in the pipeline. Considering the fact that resistant tuberculosis is difficult to manage, it is suggested that these drugs should only be used after consultation with a physician experienced in the treatment of drug resistant TB. The most frequent mistake made by treating physicians is addition of one drug in the failing regimen. At present, 27 potential anti-TB drugs are at various stages of development. The aim is that by 2010 at least one of these molecules completes the journey and should come in the market. PMID:17571483

  13. Perspectives on tuberculosis in pregnancy.

    PubMed

    Bates, Matthew; Ahmed, Yusuf; Kapata, Nathan; Maeurer, Markus; Mwaba, Peter; Zumla, Alimuddin

    2015-03-01

    Tuberculosis (TB) has been recognized as an important cause of morbidity and mortality in pregnancy for nearly a century, but research and efforts to roll out comprehensive TB screening and treatment in high-risk populations such as those with a high prevalence of HIV or other diseases of poverty, have lagged behind similar efforts to address HIV infection in pregnancy and the prevention of mother-to-child-transmission. Immunological changes during pregnancy make the activation of latent TB infection or de novo infection more likely than among non-pregnant women. TB treatment in pregnancy poses several problems that have been under-researched, such as contraindications to anti-TB and anti-HIV drugs and potential risks to the neonate, which are particularly important with respect to second-line TB treatment. Whilst congenital TB is thought to be rare, data from high HIV burden settings suggest this is not the case. There is a need for more studies screening for TB in neonates and observing outcomes, and testing preventative or curative actions. National tuberculosis control programmes (NTPs) should work with antenatal and national HIV programmes in high-burden populations to provide screening at antenatal clinics, or to establish functioning systems whereby pregnant women at high risk can drop in to routine NTP screening stations. PMID:25809768

  14. Primary sinonasal tuberculosis confined to the unilateral maxillary sinus

    PubMed Central

    Kim, Kyung Yeon; Bae, Jung Ho; Park, Jee Soo; Lee, Seung-Sin

    2014-01-01

    Extrapulmonary tuberculosis is not rare and occurs mainly in the head and neck region. Cervical tuberculous lymphadenopathy is the most common form of extrapulmonary tuberculosis. Sinonasal tuberculosis is known to occur very rarely due to the protective functions of sinonasal mucosa. Although some signs of sinonasal tuberculosis may be present, such as associated facial abscesses, the symptoms and signs are usually nonspecific. Clinical suspicion is important for timely diagnosis and proper management of sinonasal tuberculosis due to its rarity and nonspecific clinical presentation. We report a case of tuberculosis confined to the unilateral maxillary sinus that was first misdiagnosed as recurrent rhinosinusitis after endoscopic sinus surgery. PMID:24551309

  15. An unusual case of prostate tuberculosis: a case report

    PubMed Central

    Abdulsalam, Ahmad Jasem; Abdulsalam, Mohammad Adel

    2015-01-01

    Introduction Tuberculosis of the prostate is a rare complication of miliary tuberculosis. Case presentation We report a 32-year-old Iranian male diagnosed with a case of miliary tuberculosis affecting the prostate. The patient was admitted to the hospital with convulsions. Computerized tomography increased the clinical suspicion of miliary tuberculosis extending to the prostate where a trans-rectal urethral biopsy was obtained. The biopsy revealed multiple necrotizing granulomata suggestive of tuberculosis. Conclusion A strong clinical suspicion and availability of sophisticated tests with confirmation by biopsy, polymerase chain reaction, and culture are needed in order to avoid misdiagnosis of complicated miliary tuberculosis cases. PMID:25999770

  16. Different screening strategies (single or dual) for the diagnosis of suspected latent tuberculosis: a cost effectiveness analysis

    Microsoft Academic Search

    Anil Pooran; Helen Booth; Robert F Miller; Geoff Scott; Motasim Badri; Jim F Huggett; Graham Rook; Alimuddin Zumla; Keertan Dheda

    2010-01-01

    BACKGROUND: Previous health economic studies recommend either a dual screening strategy [tuberculin skin test (TST) followed by interferon-?-release assay (IGRA)] or a single one [IGRA only] for latent tuberculosis infection (LTBI), the former largely based on claims that it is more cost-effective. We sought to examine that conclusion through the use of a model that accounts for the additional costs

  17. Evaluation of Ethanol Extracted Surface Antigens of Mycobacterium bovis for Diagnosis of Bovine Tuberculosis in Livestock Cattle and Wild Deer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Bovine tuberculosis (TB), caused by Mycobacterium bovis, is a zoonotic disease resulting in chronic granulomatous lymphadenitis, particularly in the lungs and lung-associated lymph nodes. Although bovine TB has been nearly eradicated in many developed countries, the disease persists pri...

  18. Financing and cost-effectiveness analysis of public-private partnerships: provision of tuberculosis treatment in South Africa

    Microsoft Academic Search

    Edina Sinanovic; Lilani Kumaranayake

    2006-01-01

    BACKGROUND: Public-private partnerships (PPP) could be effective in scaling up services. We estimated cost and cost-effectiveness of different PPP arrangements in the provision of tuberculosis (TB) treatment, and the financing required for the different models from the perspective of the provincial TB programme, provider, and the patient. METHODS: Two different models of TB provider partnerships are evaluated, relative to sole

  19. Quality assessment of an interferon-gamma release assay for tuberculosis infection in a resource-limited setting

    Microsoft Academic Search

    Nguyen TL Hang; Naoki Ishizuka; Naoto Keicho; Le T Hong; Do B Tam; Vu TX Thu; Ikumi Matsushita; Nobuyuki Harada; Kazue Higuchi; Shinsaku Sakurada; Luu T Lien

    2009-01-01

    BACKGROUND: When a test for diagnosis of infectious diseases is introduced in a resource-limited setting, monitoring quality is a major concern. An optimized design of experiment and statistical models are required for this assessment. METHODS: Interferon-gamma release assay to detect tuberculosis (TB) infection from whole blood was tested in Hanoi, Viet Nam. Balanced incomplete block design (BIBD) was planned and

  20. 9 CFR 311.2 - Tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...When a tuberculosis lesion is found in any muscle or intermuscular tissue, or bone, or joint, or abdominal organ (excluding...or in any lymph node as a result of draining a muscle, bone, joint, or abdominal organ (excluding...

  1. Tuberculosis of the ear, a professional disease?

    PubMed

    Sens, Patrícia Maria; Almeida, Clemente I R; Valle, Lupércio O do; Costa, Luís H C; Angeli, Miguel L S

    2008-01-01

    Tuberculosis is a rare cause of chronic suppurative otitis media and mastoiditis; the predisposing factors of this association, however, are not commonly described. There has been an alarming increase in the incidence of tuberculosis in Brazil, including tuberculous otitis media. These patients typically present multiple perforations of the tympanic membrane, an ear discharge, and progressive hearing loss. This diagnosis should be taken into account in patients that do not respond to routine therapy for fungal external otitis or bacterial otitis media. In this retrospective study, the authors describe four cases of patients with tuberculous otitis media. This sample consisted of two physicians, a chemical engineer and an underage child in whose family there were cases of active tuberculosis. Predisposing factors for tuberculous otitis were contact with family members that had tuberculosis, professional contact with patients and exposure to pathogenic microorganisms in airways. PMID:18852993

  2. Implementing Tuberculosis Control in Papua New Guinea: A Clash of Culture and Science?

    Microsoft Academic Search

    Kindin Ongugo; John Hall; John Attia

    2011-01-01

    Tuberculosis (TB) remains a major health problem in Papua New Guinea (PNG) and the Directly Observed Treatment Short course\\u000a (DOTS) strategy has been adopted as a framework for controlling the disease. We review here the local and cultural factors\\u000a in PNG that act as barriers to implementing each component of the DOTS program. Political Will is needed to tackle the

  3. hp calculators HP 50g Remaining Loan Balance

    E-print Network

    Vetter, Frederick J.

    hp calculators HP 50g Remaining Loan Balance The FINANCE menu Remaining Balances Practice solving loan remaining balance problems #12;hp calculators HP 50g Remaining Loan Balance hp calculators - 2 - HP 50g Remaining Loan Balance The FINANCE menu The Finance solver is accessed from the WHITE shifted

  4. Functional Genetic Diversity among Mycobacterium tuberculosis Complex Clinical Isolates: Delineation of Conserved Core and Lineage-Specific Transcriptomes during Intracellular Survival

    PubMed Central

    Homolka, Susanne; Niemann, Stefan; Russell, David G.; Rohde, Kyle H.

    2010-01-01

    Tuberculosis exerts a tremendous burden on global health, with ?9 million new infections and ?2 million deaths annually. The Mycobacterium tuberculosis complex (MTC) was initially regarded as a highly homogeneous population; however, recent data suggest the causative agents of tuberculosis are more genetically and functionally diverse than appreciated previously. The impact of this natural variation on the virulence and clinical manifestations of the pathogen remains largely unknown. This report examines the effect of genetic diversity among MTC clinical isolates on global gene expression and survival within macrophages. We discovered lineage-specific transcription patterns in vitro and distinct intracellular growth profiles associated with specific responses to host-derived environmental cues. Strain comparisons also facilitated delineation of a core intracellular transcriptome, including genes with highly conserved regulation across the global panel of clinical isolates. This study affords new insights into the genetic information that M. tuberculosis has conserved under selective pressure during its long-term interactions with its human host. PMID:20628579

  5. Tuberculosis: Pathogenesis, immune response, and host genetics

    Microsoft Academic Search

    A. Apt; T. K. Kondratieva

    2008-01-01

    Tuberculosis is a chronic infectious disease that predominantly affects the lungs. The hallmark of tuberculosis infection\\u000a is the formation of granulomas in the vicinity of infectious foci. Tuberculous granulomas are highly organized bodies with\\u000a a complex cell composition and well-orchestrated biochemical pathways. Granuloma development plays a dual role. The process\\u000a restricts the infection dissemination and forms a battlefield for protective

  6. Recent progress in bacterial vaccines: Tuberculosis

    Microsoft Academic Search

    Keith P. W. J. McAdam

    1997-01-01

    Bacille Calmette-Guérin (BCG) is the most widely used vaccine worldwide. However, its efficacy varies from 80% to zero among studies. Meta-analysis of all the published prospective trials and case-control studies indicates approximately 50% efficacy against all forms of tuberculosis, but it is even more effective against the invasive forms of the disease, meningitis and miliary tuberculosis. Geographic latitude accounts for

  7. [Management of tuberculosis during pregnancy and puerperium].

    PubMed

    Toyota, Emiko; Minoura, Shigeki; Miyazawa, Hirofumi

    2002-11-01

    We reported 22 cases with tuberculosis in pregnancy and puerperium, who were treated in our hospital from 1993 to 2001. Nine out of 22 cases were foreign women and the onset of tuberculosis was not clear and the diagnosis tended to be delayed in most cases. In the reports from industrial countries, most of those patients are foreign bone and the delay in diagnosis is common because symptoms are apt to be mixed up those for pregnancy and puerperium. In 10 of 22 cases, extrapulmonary lesions were noted. Most of our cases were treated with INH, RFP and EB, and in some severer cases PZA was added. WHO and BTS recommend standard therapy with PZA but ATS recommends INH, RFP and EB without PZA. Generally SM is contraindicated because of adverse effect of hearing loss for all pregnant periods, and the data for PZA and other second line drugs are insufficient. Our cases and their neonates showed normal course and no malformation nor congenital tuberculosis. 2 cases could not keep adherence for drugs and 2 babies got active tuberculosis. Precaution for infection is one of most important problem to deal with cases with tuberculosis during pregnancy and postpartum in the hospital. If she is still infectious on delivery, we should consider prevention for transmission and manage her in isolated manner. CDC recommends not to treat for latent tuberculosis during pregnancy because of high frequency of hepatic damage due to INH. It is the best way to check and treat latent tuberculosis before gestation if she is at high risk with tuberculosis. PMID:12494507

  8. TUBERCULOSIS: A RESURGENT DISEASE IN IMMUNOSUPPRESSED PATIENTS

    Microsoft Academic Search

    V Nissapatorn; I Kuppusamy; FP Josephine; I Jamaiah; M Rohela; A Khairul Anuar

    A total of 136 patients, 67 HIV, 69 diabetes mellitus (DM) with or without (±) end-stage renal disease (ESRD), were registered for tuberculosis treatment at the National Tuberculosis Center (NTBC) from May to December, 2003. Ages ranged from 21-78 years (median 57.7 years) in TB\\/DM patients, and 21-62 (mean 37.6 ± 8.3 years) in TB\\/HIV patients. TB was significantly found

  9. [A rare cause of anosmia: nasosinusal tuberculosis].

    PubMed

    Hemmaoui, B; Fejjal, N; Errami, N; Temsamani, H; Benchafai, I; Jahidi, A; Benariba, F

    2014-10-01

    We report the case of a 46-year-old-woman who presented with anosmia and nasal obstruction. Primary nasal tuberculosis was discovered. Primary nasal tuberculosis is very rare. Women are more touched than men. Symptomatology is often unilateral with nasal obstruction, anterior rhinorrhea or epistaxis. Diagnosis relies on the anatomopathologic and bacteriological examinations. The treatment is mainly medical based on antituberculosis drugs. In the light of this case report, a review of the literature was made. PMID:24878190

  10. Vegetarian diet as a risk factor for tuberculosis in immigrant south London Asians.

    PubMed Central

    Strachan, D. P.; Powell, K. J.; Thaker, A.; Millard, F. J.; Maxwell, J. D.

    1995-01-01

    BACKGROUND--In a previous retrospective study of tuberculosis in south London among Asian immigrants from the Indian subcontinent Hindu Asians were found to have a significantly increased risk for tuberculosis compared with Muslims. This finding has been further investigated by examining the role of socioeconomic and lifestyle variables, including diet, as risk factors for tuberculosis in Asian immigrants from the Indian subcontinent resident in south London. METHODS--Using a case-control study technique Asian immigrants from the Indian subcontinent diagnosed with tuberculosis during the past 10 years and two Asian control groups (community and outpatient clinic controls) from the Indian subcontinent were investigated. Cases and community controls were approached by letter. A structured questionnaire concerning a range of demographic, migration, socioeconomic, dietary, and health topics was administered by a single trained interviewer to subjects (56 cases and 100 controls) who agreed to participate. RESULTS--The results confirmed earlier findings that Hindu Asians had an increased risk of tuberculosis compared with Muslims. However, further analysis revealed that religion had no independent influence after adjustment for vegetarianism (common among Hindu Asians). Unadjusted odds ratios for tuberculosis among vegetarians were 2.7 (95% CI 1.1 to 6.4) using community controls, and 4.3 (95% CI 1.8 to 10.4) using clinic controls. There was a trend of increasing risk of tuberculosis with decreasing frequency of meat or fish consumption. Lactovegetarians had an 8.5 fold risk (95% CI 1.6 to 45.4) compared with daily meat/fish eaters. Adjustment for a range of other socioeconomic, migration, and lifestyle variables made little difference to the relative risks derived using either community or clinic controls. CONCLUSIONS--These results indicate that a vegetarian diet is an independent risk factor for tuberculosis in immigrant Asians. The mechanism is unexplained. However, vitamin D deficiency, common among vegetarian Asians in south London, is known to affect immunological competence. Decreased immunocompetence associated with a vegetarian diet might result in increased mycobacterial reactivation among Asians from the Indian subcontinent. PMID:7701458

  11. A systematic review of missed opportunities for improving tuberculosis and HIV/AIDS control in Sub-saharan Africa: what is still missed by health experts?

    PubMed

    Keugoung, Basile; Fouelifack, Florent Ymele; Fotsing, Richard; Macq, Jean; Meli, Jean; Criel, Bart

    2014-01-01

    In sub-Saharan Africa, HIV/AIDS and tuberculosis are major public health problems. In 2010, 64% of the 34 million of people infected with HIV were reported to be living in sub-Saharan Africa. Only 41% of eligible HIV-positive people had access to antiretroviral therapy (ART). Regarding tuberculosis, in 2010, the region had 12% of the world's population but reported 26% of the 8.8 million incident cases and 254000 tuberculosis-related deaths. This paper aims to review missed opportunities for improving HIV/AIDS and tuberculosis prevention and care. We conducted a systematic review in PubMed using the terms 'missed'(Title) AND 'opportunities'(Title). We included systematic review and original research articles done in sub-Saharan Africa on missed opportunities in HIV/AIDS and/or tuberculosis care. Missed opportunities for improving HIV/AIDS and/or tuberculosis care can be classified into five categories: i) patient and community; ii) health professional; iii) health facility; iv) local health system; and v) vertical programme (HIV/AIDS and/or tuberculosis control programmes). None of the reviewed studies identified any missed opportunities related to health system strengthening. Opportunities that are missed hamper tuberculosis and/or HIV/AIDS care in sub-Saharan Africa where health systems remain weak. What is still missing in the analysis of health experts is the acknowledgement that opportunities that are missed to strengthen health systems also undermine tuberculosis and HIV/AIDS prevention and care. Studying why these opportunities are missed will help to understand the rationales behind the missed opportunities, and customize adequate strategies to seize them and for effective diseases control. PMID:25478041

  12. Congenital tuberculosis: presentation of a rare case.

    PubMed

    ?en, Velat; Selimo?lu ?en, Hadice; Aktar, Fesih; Uluca, Ünal; Karabel, Müsemma; Fuat Gürkan, Mehmet

    2015-04-01

    Congenital tuberculosis is a rare disease with a high mortality rate. Congenital tuberculosis is considered the result of mother-to-child transmission from the placenta to the fetus, through the ingestion of the amniotic fluid, or via transplacental transmission through the umbilical vein. Given the non-specific clinical signs of tuberculosis, it is usually difficult to diagnose it. The case of a 48-day-old male infant hospitalized due to weight loss, fever, cough, hemoptysis, and respiratory distress for the past 20 days, is presented. In this period, he had received broad spectrum antibiotics but with no improvement. A chest x-ray showed the presence of consolidation and a cavitary lesion in the upper and middle left lung fields. Mycobacterium tuberculosis was detected by polymerase chain reaction in a bronchoalveolar lavage specimen. Congenital tuberculosis was diagnosed based on this finding; hence, a tuberculostatic regimen was started accordingly. The patient died 13 days after treatment initiation. Congenital tuberculosis should be considered in infants with weight loss, fever, cough, hemoptysis and respiratory distress. PMID:25727833

  13. [Immigration and tuberculosis. Five year experience].

    PubMed

    Rifes, Graça; Villar, Miguel

    2003-01-01

    Immigrants are a tuberculosis risk group. In Portugal, in 2000, they had an incidence rate 3.6 times higher than the global incidence, and were native, predominantly, from Angola and Cabo Verde. Being the Chest Disease Center of Venda Nova located in a residential area with a great number of immigrants, most of them living in slums, we decided to evaluate the tuberculosis cases in this group, between 1996/2000, comparing the data obtained with some data of the tuberculosis cases in the non-immigrants. Immigrants with tuberculosis corresponded to 24.5% of all cases, 71.4% male, 93.9% black and mostly native from Cabo Verde and Angola. 73% lived in Portugal for more than 5 years, 86.7% were new cases and 13.3% relapses. 174 were pulmonary forms, 70.7% of which were D+ and 81% confirmed (against 75% in the non-immigrants). Of the 91 drug susceptibility tests done in the pulmonary forms, 9.9% revealed multidrug resistance, against 5% in the non-immigrants. Twenty six point six percent had AIDS against 18% in the non-immigrants. Some conclusions: important percentage of immigrants with tuberculosis in the Chest Disease Center of Venda Nova; immigrants have a higher confirmation rate of pulmonary tuberculosis, more multidrug resistance and AIDS cases. PMID:14685630

  14. Gamma delta T cell responses associated with the development of tuberculosis in health care workers.

    PubMed

    Ordway, Diane J; Pinto, Luisa; Costa, Leonor; Martins, Marta; Leandro, Clara; Viveiros, Miguel; Amaral, Leonard; Arroz, Maria J; Ventura, Fernando A; Dockrell, Hazel M

    2005-03-01

    This study evaluated T cell immune responses to purified protein derivative (PPD) and Mycobacterium tuberculosis (Mtb) in health care workers who remained free of active tuberculosis (HCWs w/o TB), health care workers who went on to develop active TB (HCWs w/TB), non-health care workers who were TB free (Non-HCWs) and tuberculosis patients presenting with minimal (Min TB) or advanced (Adv TB) disease. Peripheral blood mononuclear cells (PBMC) were stimulated with Mtb and PPD and the expression of T cell activation markers CD25+ and HLA-DR+, intracellular IL-4 and IFN-gamma production and cytotoxic responses were evaluated. PBMC from HCWs who developed TB showed decreased percentages of cells expressing CD8+CD25+ in comparison to HCWs who remained healthy. HCWs who developed TB showed increased gammadelta TCR+ cell cytotoxicity and decreased CD3+gammadelta TCR- cell cytotoxicity in comparison to HCWs who remained healthy. PBMC from TB patients with advanced disease showed decreased percentages of CD25+CD4+ and CD25+CD8+ T cells that were associated with increased IL-4 production in CD8+ and gammadelta TCR+ phenotypes, in comparison with TB patients presenting minimal disease. TB patients with advanced disease showed increased gammadelta TCR+ cytotoxicity and reduced CD3+gammadelta TCR- cell cytotoxicity. Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of gammadelta TCR+ cells which did not prevent TB. PMID:15708307

  15. Skeletal Lesions in Human Tuberculosis May Sometimes Heal: An Aid to Palaeopathological Diagnoses

    PubMed Central

    Holloway, Kara L.; Link, Karl; Rühli, Frank; Henneberg, Maciej

    2013-01-01

    In three to five percent of active cases of tuberculosis, skeletal lesions develop. Typically, these occur on the vertebrae and are destructive in nature. In this paper, we examined cases of skeletal tuberculosis from a skeletal collection (Galler Collection) with focus on the manifestation of bony changes due to tuberculosis in various body regions in association with antibiotic introduction. This skeletal collection was created in 1925–1977 by a pathologist at the University Hospital in Zürich, Ernst Galler. It includes the remains of 2426 individuals with documented clinical histories as well as autopsies. It contained 29 cases of skeletal tuberculosis lesions. We observed natural healing of vertebral lesions through several processes including fusion of vertebrae, bone deposition and fusion of posterior elements. In these cases, we observed a higher frequency and proportion of bone deposition and fusion of posterior vertebral elements where pharmacological agents were used. There were also four cases of artificial healing through surgically induced posterior spinal fusion. With the introduction of pharmaceutical treatments, the number of individuals with multiple tuberculous foci decreased from 80% to 25% when compared to individuals who did not receive any drug therapy. Investigation of comorbidities showed that pneumonia, pleuritis and being underweight were consistently present, even with pharmaceutical treatment. Our results have applications in palaeopathological diagnoses where healing and consequent bone deposition may complicate differential diagnoses. PMID:23638146

  16. Myeloid Sirtuin 2 Expression Does Not Impact Long-Term Mycobacterium tuberculosis Control

    PubMed Central

    Moreira-Teixeira, Lúcia; Sousa, Jeremy; Torrado, Egídio; Silvestre, Ricardo; Castro, António Gil; Saraiva, Margarida; Pais, Teresa F.

    2015-01-01

    Sirtuins (Sirts) regulate several cellular mechanisms through deacetylation of several transcription factors and enzymes. Recently, Sirt2 was shown to prevent the development of inflammatory processes and its expression favors acute Listeria monocytogenes infection. The impact of this molecule in the context of chronic infections remains unknown. We found that specific Sirt2 deletion in the myeloid lineage transiently increased Mycobacterium tuberculosis load in the lungs and liver of conditional mice. Sirt2 did not affect long-term infection since no significant differences were observed in the bacterial burden at days 60 and 120 post-infection. The initial increase in M. tuberculosis growth was not due to differences in inflammatory cell infiltrates in the lung, myeloid or CD4+ T cells. The transcription levels of IFN-?, IL-17, TNF, IL-6 and NOS2 were also not affected in the lungs by Sirt2-myeloid specific deletion. Overall, our results demonstrate that Sirt2 expression has a transitory effect in M. tuberculosis infection. Thus, modulation of Sirt2 activity in vivo is not expected to affect chronic infection with M. tuberculosis. PMID:26135889

  17. [A case of gallbladder tuberculosis diagnosed by positive tuberculosis-polymerase chain reaction].

    PubMed

    Ryu, Mi Jin; Jeon, Tae Joo; Park, Ji Young; Choi, Yena; Baek, Seung Suk; Sinn, Dong Hyun; Oh, Tae Hoon; Kim, Jung Yeon

    2014-01-25

    Gallbladder tuberculosis is an extremely rare disease that is rarely reported in the literature. Arriving at the correct diagnosis of gallbladder tuberculosis is difficult, and it is usually made by histopathologic examination after cholecystectomy. However, due to the low sensitivity of acid-fast stain and culture result, diagnosing gallbladder tuberculosis is still demanding even after tissue acquisition. To overcome this problem, tuberculosis-polymerase chain reaction (TB-PCR) is performed on the resected specimen, which has high sensitivity and specificity. A 70-year-old female who had previously undergone total gastrectomy for advanced gastric cancer was admitted with right upper quadrant pain. Abdominal ultrasonography and computed tomography revealed acute cholecystitis without gallstones or sludge. She underwent cholecystectomy and the histopathologic finding of the specimen showed chronic active cholecystitis without gallstones or sludge. Because she was suspected to have pulmonary tuberculosis, TB-PCR was also performed on the resected gallbladder. TB-PCR showed positive reaction for Mycobacterium tuberculosis and we could diagnose it as gallbladder tuberculosis. Herein, we present a case of gallbladder tuberculosis diagnosed by TB-PCR from resected gallbladder. PMID:24463290

  18. Vaccine approaches for bovine tuberculosis: Correlates of protection and relevance to human tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tuberculosis (TB), primarily due to Mycobacterium tuberculosis in humans and Mycobacterium bovis in cattle, is a classic model of the One Health Concept. M. bovis Bacillus Calmette Guerin (BCG) was first proven effective in cattle prior to use in humans. Recent experimental trials with cattle have d...

  19. DNA Vaccination against Tuberculosis: Expression of a Ubiquitin-Conjugated Tuberculosis Protein Enhances Antimycobacterial Immunity

    Microsoft Academic Search

    GIOVANNI DELOGU; ANGELA HOWARD; FRANK M. COLLINS; SHELDON L. MORRIS

    2000-01-01

    Genetic immunization is a promising new technology for developing vaccines against tuberculosis that are more effective. In the present study, we evaluated the effects of intracellular turnover of antigens expressed by DNA vaccines on the immune response induced by these vaccines in a mouse model of pulmonary tuberculosis. The mycobacterial culture filtrate protein MPT64 was expressed as a chimeric protein

  20. Profiling Antibodies to Mycobacterium tuberculosis by Multiplex Microbead Suspension Arrays for Serodiagnosis of Tuberculosis

    Microsoft Academic Search

    Imran H. Khan; Resmi Ravindran; JoAnn Yee; Melanie Ziman; David M. Lewinsohn; Marila L. Gennaro; JoAnne L. Flynn; Celia W. Goulding; Kathryn DeRiemer; Nickolas W. Lerche; Paul A. Luciw

    2008-01-01

    Received 29 August 2007\\/Returned for modification 20 September 2007\\/Accepted 26 November 2007 Tuberculosis (TB) is a serious global disease. The fatality rate attributed to TB is among the highest of infectious diseases, with approximately 2 million deaths occurring per year worldwide. Identification of individuals infected with Mycobacterium tuberculosis and screening of their immediate contacts is crucial for controlling the spread

  1. The immune response to bovine tuberculosis: Correlates of protection and relevance to human tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tuberculosis (TB), primarily due to Mycobacterium tuberculosis in humans and Mycobacterium bovis in cattle, is a classic model for demonstration of the One Health Concept. Early studies with cattle were instrumental in the development of the use of Koch’s tuberculin as an in vivo measure of cell-med...

  2. Mycobacterium tuberculosis strains of the Beijing genotype are rarely observed in tuberculosis patients in South America

    Microsoft Academic Search

    Viviana Ritacco; Beatriz López; Patricia I Cafrune; Lucilaine Ferrazoli; Philip N Suffys; Norma Candia; Lucy Vásquez; Teresa Realpe; Jorge Fernández; Karla V Lima; Jeannete Zurita; Jaime Robledo; Maria L Rossetti; Afranio L Kritski; Maria A Telles; Juan C Palomino; Herre Heersma; Dick van Soolingen; Kristin Kremer; Lucía Barrera

    2008-01-01

    The frequency of the Beijing genotype of Mycobacterium tuberculosis as a cause of tuberculosis (TB) in South America was determined by analyzing genotypes of strains isolated from patients that had been diagnosed with the disease between 1997 and 2003 in seven countries of the subcontinent. In total, 19 of the 1,202 (1.6%) TB cases carried Beijing isolates, including 11 of

  3. Molecular Epidemiology and Clinical Characteristics of Drug-Resistant Mycobacterium tuberculosis in a Tuberculosis Referral Hospital in China

    PubMed Central

    Zhao, Yanlin; Li, Hong Min; Li, Bing Xi; Hu, Yong Liang; Woo, Patrick C. Y.; Liu, Cui Hua

    2014-01-01

    Background Despite the large number of drug-resistant tuberculosis (TB) cases in China, few studies have comprehensively analyzed the drug resistance-associated gene mutations and genotypes in relation to the clinical characteristics of M. tuberculosis (Mtb) isolates. Methodology/Principal Findings We thus analyzed the phenotypic and genotypic drug resistance profiles of 115 Mtb clinical isolates recovered from a tuberculosis referral hospital in Beijing, China. We also performed genotyping by 28 loci MIRU-VNTR analysis. Socio-demographic and clinical data were retrieved from medical records and analyzed. In total, 78 types of mutations (including 42 previously reported and 36 newly identified ones) were identified in 115 Mtb clinical isolates. There was significant correlation between phenotypic and genotypic drug resistance rates for first-line anti-TB drugs (P<0.001). Genotyping revealed 101 MIRU-VNTR types, with 20 isolates (17.4%) being clustered and 95 isolates (82.6%) having unique genotypes. Higher proportion of re-treatment cases was observed among patients with clustered isolates than those with unique MIRU-VNTR genotypes (75.0% vs. 41.1%). Moreover, clinical epidemiological links were identified among patients infected by Mtb strains belonging to the same clusters, suggesting a potential of transmission among patients. Conclusions/Significance Our study provided information on novel potential drug resistance-associated mutations in Mtb. In addition, the genotyping data from our study suggested that enforcement of the implementation of genotyping in diagnostic routines would provide important information for better monitor and control of TB transmission. PMID:25302501

  4. Evaluation of six different DNA extraction methods for detection of Mycobacterium tuberculosis by means of PCR-IS6110: preliminary study

    PubMed Central

    2013-01-01

    Background Developments in molecular detection and strain differentiation of members of Mycobacterium tuberculosis complex have proved to be useful. The DNA extraction method influences the amplification efficiency, causing interference on the sensitivity and respective inhibitors. The aim of this study was to standardize a simple and fast DNA extraction method, providing DNA amplification by IS6110-PCR effectively free from undue interferences. Findings The efficiency of the six different protocols tested in M. tuberculosis cultures has varied from 75% to 92.5%. This preliminary study evaluating the IS6110 PCR sensitivity and specificity was developed in DNA extracted from microscope slides, and achieved 100% of efficiency. Conclusions DNA extraction by Chelex?+?NP-40 method from both, cultures of M. tuberculosis and smear slides, resulted in good quantity of interference free DNA, especially in samples with low concentrations of genetic material; therefore, such technique may be used for the molecular diagnosis of tuberculosis. PMID:24373461

  5. Feasibility, acceptability, and cost of tuberculosis testing by whole-blood interferon-gamma assay

    Microsoft Academic Search

    Puneet Kumar Dewan; Jennifer Grinsdale; Sally Liska; Ernest Wong; Robert Fallstad; L Masae Kawamura

    2006-01-01

    BACKGROUND: The whole-blood interferon-gamma release assay (IGRA) is recommended in some settings as an alternative to the tuberculin skin test (TST). Outcomes from field implementation of the IGRA for routine tuberculosis (TB) testing have not been reported. We evaluated feasibility, acceptability, and costs after 1.5 years of IGRA use in San Francisco under routine program conditions. METHODS: Patients seen at

  6. Ligand Specificity of Group I Biotin Protein Ligase of Mycobacterium tuberculosis

    Microsoft Academic Search

    Sudha Purushothaman; Garima Gupta; Richa Srivastava; Vasanthakumar Ganga Ramu; Avadhesha Surolia

    2008-01-01

    Background: Fatty acids are indispensable constituents of mycolic acids that impart toughness & permeability barrier to the cell envelope of M. tuberculosis. Biotin is an essential co-factor for acetyl-CoA carboxylase (ACC) the enzyme involved in the synthesis of malonyl-CoA, a committed precursor, needed for fatty acid synthesis. Biotin carboxyl carrier protein (BCCP) provides the co-factor for catalytic activity of ACC.

  7. Ligand Specificity of Group I Biotin Protein Ligase of Mycobacterium tuberculosis

    Microsoft Academic Search

    Sudha Purushothaman; Garima Gupta; Richa Srivastava; Vasanthakumar Ganga Ramu; Avadhesha Surolia; Edathara Abraham

    2008-01-01

    BackgroundFatty acids are indispensable constituents of mycolic acids that impart toughness & permeability barrier to the cell envelope of M. tuberculosis. Biotin is an essential co-factor for acetyl-CoA carboxylase (ACC) the enzyme involved in the synthesis of malonyl-CoA, a committed precursor, needed for fatty acid synthesis. Biotin carboxyl carrier protein (BCCP) provides the co-factor for catalytic activity of ACC.Methodology\\/Principal FindingsBPL\\/BirA

  8. Targeted BCG Vaccination Against Severe Tuberculosis in Low-prevalence Settings Epidemiologic and Economic Assessment

    Microsoft Academic Search

    Hester Korthals Altes; Frederika Dijkstra; Anna Lugnèr; Frank Cobelens; Jacco Wallinga

    2009-01-01

    Background: BCG vaccine protects against the severe forms of tuberculosis (TB) in children. Several low-prevalence countries are reviewing their policy, usually shifting from universal vaccination to vaccination of infants in high-risk groups only. We combined an epidemiologic analysis with a cost-effectiveness analysis to evaluate the cost-effectiveness of targeted strategies. Methods: We fitted a static model to the data to estimate

  9. Outcome of pulmonary tuberculosis treatment in the tertiary care setting — Toronto 1992\\/93

    Microsoft Academic Search

    Wendy Wobeser; Lilian Yuan; Monika Naus; Charles K. N. Chan; Jeffrey D. Edelson; Donald E. Low; Irving E. Salit; Andrew E. Simor

    Background: Completion of treatment of active cases of tuberculosis (TB) is the most important priority of TB control programs. This study was carried out to as- sess treatment completion for active cases of pulmonary TB in Toronto. Methods: Consecutive cases of culture-proven pulmonary TB were obtained from the microbiology laboratories of 5 university-affiliated tertiary care centres in Toronto in 1992\\/93.

  10. In vitro and in vivo Activities of a New Lead Compound I2906 against Mycobacterium tuberculosis

    Microsoft Academic Search

    Jingning Lu; Jun Yue; Jing Wu; Rusong Luo; Zhidong Hu; Jianrong Li; Yun Bai; Zhijiao Tang; Qiaoyang Xian; Xuelian Zhang; Honghai Wang

    2010-01-01

    Background: Due to the long duration of treatment and the emergence of multidrug-resistant strains, new antitubercular agents are urgently needed. I2906, as a novel lead, was screened and tested for efficacy in vitro and in vivo. Methods:To determine the efficacy of I2906,the minimum inhibitory concentrations against Mycobacterium tuberculosis and cytotoxicity were tested, and its in vivo activities were assessed by

  11. Redox homeostasis in mycobacteria: the key to tuberculosis control?

    PubMed Central

    Kumar, Ashwani; Farhana, Aisha; Guidry, Loni; Saini, Vikram; Hondalus, Mary; Steyn, Adrie J.C.

    2011-01-01

    Mycobacterium tuberculosis (Mtb) is a metabolically flexible pathogen that has the extraordinary ability to sense and adapt to the continuously changing host environment experienced during decades of persistent infection. Mtb is continually exposed to endogenous reactive oxygen species (ROS) as part of normal aerobic respiration, as well as exogenous ROS and reactive nitrogen species (RNS) generated by the host immune system in response to infection. The magnitude of tuberculosis (TB) disease is further amplified by exposure to xenobiotics from the environment such as cigarette smoke and air pollution, causing disruption of the intracellular prooxidant–antioxidant balance. Both oxidative and reductive stresses induce redox cascades that alter Mtb signal transduction, DNA and RNA synthesis, protein synthesis and antimycobacterial drug resistance. As reviewed in this article, Mtb has evolved specific mechanisms to protect itself against endogenously produced oxidants, as well as defend against host and environmental oxidants and reductants found specifically within the microenvironments of the lung. Maintaining an appropriate redox balance is critical to the clinical outcome because several antimycobacterial prodrugs are only effective upon bioreductive activation. Proper homeostasis of oxido-reductive systems is essential for Mtb survival, persistence and subsequent reactivation. The progress and remaining deficiencies in understanding Mtb redox homeostasis are also discussed. PMID:22172201

  12. Identification of potential biomarkers of disease progression in bovine tuberculosis.

    PubMed

    Blanco, Federico Carlos; Bigi, Fabiana; Soria, Marcelo Abel

    2014-08-15

    Bovine tuberculosis (bTB) remains an important animal and zoonotic disease in many countries. The diagnosis of bTB is based on tuberculin skin test and IFN-? release assays (IGRA). Positive animals are separated from the herd and sacrificed. The cost of this procedure is difficult to afford for developing countries with high prevalence of bTB; therefore, the improvement of diagnostic methods and the identification of animals in different stages of the disease will be helpful to control the infection. To identify biomarkers that can discriminate between tuberculin positive cattle with and without tuberculosis lesions (ML+ and ML-, respectively), we assessed a group of immunological parameters with three different classification methods: lineal discriminant analysis (LDA), quadratic discriminant analysis (QDA) and K nearest neighbors (k-nn). For this purpose, we used data from 30 experimentally infected cattle. All the classifiers (LDA, QDA and k-nn) selected IL-2 and IL-17 as the most discriminatory variables. The best classification method was LDA using IL-17 and IL-2 as predictors. The addition of IL-10 to LDA improves the performance of the classifier to discriminate ML-individuals (93.3% vs. 86.7%). Thus, the expression of IL-17, IL-2 and, in some cases, IL-10 would serve as an additional tool to study disease progression in herds with a history of bTB. PMID:24856732

  13. Controlled-release approaches towards the chemotherapy of tuberculosis

    PubMed Central

    Saifullah, Bullo; Hussein, Mohd Zobir B; Al Ali, Samer Hasan Hussein

    2012-01-01

    Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis, is notorious for its lethality to humans. Despite technological advances, the tubercle bacillus continues to threaten humans. According to the World Health Organization’s 2011 global report on TB, 8.8 million cases of TB were reported in 2010, with a loss of 1.7 million human lives. As drug-susceptible TB requires long-term treatment of between 6 and 9 months, patient noncompliance remains the most important reason for treatment failure. For multidrug-resistant TB, patients must take second-line anti-TB drugs for 18–24 months and many adverse effects are associated with these drugs. Drug-delivery systems (DDSs) seem to be the most promising option for advancement in the treatment of TB. DDSs reduce the adverse effects of drugs and their dosing frequency as well as shorten the treatment period, and hence improve patient compliance. Further advantages of these systems are that they target the disease area, release the drugs in a sustained manner, and are biocompatible. In addition, targeted delivery systems may be useful in dealing with extensively drug-resistant TB because many side effects are associated with the drugs used to cure the disease. In this paper, we discuss the DDSs developed for the targeted and slow delivery of anti-TB drugs and their possible advantages and disadvantages. PMID:23091386

  14. Tuberculosis drug discovery in the post-post-genomic era

    PubMed Central

    Lechartier, Benoit; Rybniker, Jan; Zumla, Alimuddin; Cole, Stewart T

    2014-01-01

    The expectation that genomics would result in new therapeutic interventions for infectious diseases remains unfulfilled. In the post-genomic era, the decade immediately following the availability of the genome sequence of Mycobacterium tuberculosis, tuberculosis (TB) drug discovery relied heavily on the target-based approach but this proved unsuccessful leading to a return to whole cell screening. Genomics underpinned screening by providing knowledge and many enabling technologies, most importantly whole genome resequencing to find resistance mutations and targets, and this resulted in a selection of leads and new TB drug candidates that are reviewed here. Unexpectedly, many new targets were found to be ‘promiscuous’ as they were inhibited by a variety of different compounds. In the post-post-genomics era, more advanced technologies have been implemented and these include high-content screening, screening for inhibitors of latency, the use of conditional knock-down mutants for validated targets and siRNA screens. In addition, immunomodulation and pharmacological manipulation of host functions are being explored in an attempt to widen our therapeutic options. PMID:24401837

  15. Tuberculosis in Mexico and the USA, Comparison of Trends Over Time 1990-2010

    PubMed Central

    Mendoza-Damián, Fabiola; Garduño-Alanís, Adriana; Ayón-Garibaldo, Salvador

    2015-01-01

    Background The aim was to compare tuberculosis trends in Mexico and United States and to evaluate Mexican diagnostic methods and contact investigation. Methods Retrospective comparative study of tuberculosis cases and incidence rates between both countries (1990-2010). Diagnostic methods and contact investigations were also evaluated for Mexico. Estimates were obtained from official websites. Results In Mexico, no clear trend was found over time for cases. Pulmonary (PTB) and all forms of tuberculosis (AFTB) incidence decreased 2.0% annually. There was a negative correlation between the mean contacts examined per case and AFTB incidence (r2=-0.44, p=0.01) with a 33% reduction in AFTB incidence. In United States, PTB and AFTB cases have been decreasing 6.0% and 5.6% annually, respectively. The incidence decreased 7.3% and 6.8%, respectively. Conclusion The incidence of tuberculosis in Mexico is decreasing slightly over time at 2% annually. In the United States, cases and incidence rates have been decreasing at a higher rate (5% to 7% annually). The inverse association between number of contacts examined per state and incidence rates in Mexico underscore the importance of reinforcing and improving contact investigations with the likely translation of a decrease of TB incidence at a higher rate.

  16. Patients’ Experience of Tuberculosis Treatment Using Directly Observed Treatment, Short-Course (DOTS): A Qualitative Study

    PubMed Central

    Behzadifar, Masoud; Mirzaei, Masoud; Behzadifar, Meysam; Keshavarzi, Abouzar; Behzadifar, Maryam; Saran, Maryam

    2015-01-01

    Background: Despite effective diagnosis and treatment, prevalence of tuberculosis (TB) is still growing. The directly observed treatment, short-course (DOTS) strategy to treat TB was introduced by the World Health Organization more than a decade ago. Little is known about patients’ experience of TB treatment, according to DOTS, in Iran. Objectives: This study aimed to understand the patients’ experience of tuberculosis treatment according to DOTS in Iran. Patients and Methods: This study is a qualitative study, using content analysis to examine patients’ experience of TB treatment and to understand their compliance during DOTS. In this study, a semi-structured interview with open questions was answered by 40 patients, who had a diagnosis of pulmonary and extrapulmonary tuberculosis, and improved during the course of their treatment. The method of sampling was purposive sample and the interview process lasted until data saturation. Results: Data analysis resulted in the extraction of six themes, which reflect the experiences of the study participants. The themes are: 1) individual factors; 2) change of the attitudes and beliefs of patients on TB treatment; 3) support terms of patients with tuberculosis; 4) the role of health care professionals; 5) social factors and 6) the financial burden. Conclusions: Successful completion of TB treatment requires an effective partnership between the patient and health care professionals, and a harmony between the cultural context, attitude of the patient, family support and health literacy. Future health policies should address these issues to improve patients’ adherence to DOTS. PMID:26023334

  17. Identification and survival studies of Mycobacterium tuberculosis within Laboratory-Fermented bovine milk

    PubMed Central

    2014-01-01

    Background Mycobacterium tuberculosis and Mycobacterium bovis are the classic agents causing tuberculosis (TB) in humans and animals respectively. Transmission of tuberculous bacteria to humans usually occurs by inhalation of aerosols containing droplets of tubercle bacilli or via consumption of contaminated foods and drinks, primarily milk. The practice of milk pooling, including from cows with TB of the udder, further exacerbates the situation by rendering the whole milk supply infective. The simultaneous presence of indigenous lactic acid bacteria (LAB) in Mycobacterium-contaminated milk is believed to confer protective effect when the milk is adequately fermented. This study assessed the effect of LAB on the viability of mycobacteria in inherently contaminated pool of raw milk during fermentation as a function of time. Findings Growth was obtained in the pooled raw milk culture, and identified to be M. tuberculosis. This M. tuberculosis growth was undetectable in the milk culture by day 7 as assessed by plating serial dilutions of the milk culture for up to 14 days. Conclusions Some LAB species appear to show inhibitory effect on tubercle bacilli. If proven by more rigorous, controlled experimental results regarding such effect, selected LAB (with proven safety and efficacy) may have potential applications as anti-mycobacterial agents. PMID:24666844

  18. Tuberculosis vaccine types and timings.

    PubMed

    Orme, Ian M

    2015-03-01

    Traditionally, the design of new vaccines directed against Mycobacterium tuberculosis, the most successful bacterial pathogen on the planet, has focused on prophylactic candidates that would be given to individuals while they are still young. It is becoming more apparent, however, that there are several types of vaccine candidates now under development that could be used under various conditions. Thus, in addition to prophylactic vaccines, such as recombinant Mycobacterium bovis BCG or BCG-boosting vaccines, other applications include vaccines that could prevent infection, vaccines that could be given in emergency situations as postexposure vaccines, vaccines that could be used to facilitate chemotherapy, and vaccines that could be used to reduce or prevent relapse and reactivation disease. These approaches are discussed here, including the type of immunity we are trying to specifically target, as well as the limitations of these approaches. PMID:25540272

  19. Spinal Tuberculosis: Diagnosis and Management

    PubMed Central

    Rasouli, Mohammad R.; Mirkoohi, Maryam; Vaccaro, Alexander R.; Yarandi, Kourosh Karimi

    2012-01-01

    The spinal column is involved in less than 1% of all cases of tuberculosis (TB). Spinal TB is a very dangerous type of skeletal TB as it can be associated with neurologic deficit due to compression of adjacent neural structures and significant spinal deformity. Therefore, early diagnosis and management of spinal TB has special importance in preventing these serious complications. In order to extract current trends in diagnosis and medical or surgical treatment of spinal TB we performed a narrative review with analysis of all the articles available for us which were published between 1990 and 2011. Althoug h the development of more accurate imaging modalities such as magnetic resonance imaging and advanced surgical techniques have made the early diagnosis and management of spinal TB much easier, these are still very challenging topics. In this review we aim to discuss the diagnosis and management of spinal TB based on studies with acceptable design, clearly explained results and justifiable conclusions. PMID:23275816

  20. Environmental infection control of tuberculosis.

    PubMed

    Nardell, Edward A

    2003-12-01

    Current infection control guidelines for tuberculosis focus first on administrative interventions to promptly identify and isolate a known or suspected infectious case. Environmental control measures come next, and finally personal respiratory protection is recommended as a final strategy to prevent transmission. However, both environmental controls and the use of personal respiratory protection are also focused on known or suspected cases, and certain high-risk procedures. There is little focus on general medical areas where unsuspected cases are believed to transmit their infection before they become suspected cases. This review makes the case for increased attention to such areas as general medical wards, clinics, and waiting areas. Administrative controls are needed to improve detection and to reduce the possibility of transmission to high-risk groups. Improved air disinfection through general ventilation, filtration, and ultraviolet germicidal irradiation are needed as ways to address this overlooked source of transmission. PMID:14679478