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Sample records for background tuberculosis remains

  1. Tuberculosis remains a challenge despite economic growth in Panama.

    PubMed

    Tarajia, M; Goodridge, A

    2014-03-01

    Tuberculosis (TB) is a disease associated with inequality, and wise investment of economic resources is considered critical to its control. Panama has recently secured its status as an upper-middle-income country with robust economic growth. However, the prioritisation of resources for TB control remains a major challenge. In this article, we highlight areas that urgently require action to effectively reduce TB burden to minimal levels. Our conclusions suggest the need for fund allocation and a multidisciplinary approach to ensure prompt laboratory diagnosis, treatment assurance and workforce reinforcement, complemented by applied and operational research, development and innovation.

  2. Genetically susceptible mice remain proportionally more susceptible to tuberculosis after vaccination

    PubMed Central

    Medina, E; North, R J

    1999-01-01

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

  3. Assessing the survival of Mycobacterium tuberculosis in unembalmed and embalmed human remains.

    PubMed

    Correia, J C; Steyl, J L; De Villiers, H C

    2014-04-01

    Anatomy and mortuary technical staff faces an ever existing risk of contracting an infectious disease, such as Mycobacterium tuberculosis (MTB), when exposed to human remains. The transfer and handling of a corpse expels air from the lungs of the diseased and this aerosolizes the bacilli. It is for this reason that personal protective equipment and work space precautions such as ultraviolet germicidal irradiation is a necessity. In this study, the authors explore the viability of MTB before and after embalming. Briefly, lung tissue samples, both apical and hilar, were obtained from 20 cadavers whose death certificate indicated MTB as cause of death. The first sample was taken before embalming and second set 3 weeks after embalming. Tissue was deposited into sterile specimen containers and transported for analysis which included Mycobacterium growth indicator tube cultures and polymerase chain reaction. Results demonstrated that both the apical and the perihilar sample tested positive prior to embalming, 36 days after death. After three weeks post-embalming none tested positive. The results demonstrated that MTB can remain viable after death for up to 36 days. This viability extends beyond the documented cases and highlights the need for precautionary measures and standard operating procedures in accordance with occupational health and safety guidelines.

  4. 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.

  5. 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

  6. Tuberculosis.

    PubMed

    Dheda, Keertan; Barry, Clifton E; Maartens, Gary

    2016-03-19

    Although the worldwide incidence of tuberculosis has been slowly decreasing, the global disease burden remains substantial (∼9 million cases and ∼1·5 million deaths in 2013), and tuberculosis incidence and drug resistance are rising in some parts of the world such as Africa. The modest gains achieved thus far are threatened by high prevalence of HIV, persisting global poverty, and emergence of highly drug-resistant forms of tuberculosis. Tuberculosis is also a major problem in health-care workers in both low-burden and high-burden settings. Although the ideal preventive agent, an effective vaccine, is still some time away, several new diagnostic technologies have emerged, and two new tuberculosis drugs have been licensed after almost 50 years of no tuberculosis drugs being registered. Efforts towards an effective vaccine have been thwarted by poor understanding of what constitutes protective immunity. Although new interventions and investment in control programmes will enable control, eradication will only be possible through substantial reductions in poverty and overcrowding, political will and stability, and containing co-drivers of tuberculosis, such as HIV, smoking, and diabetes.

  7. Tuberculosis.

    PubMed

    Dheda, Keertan; Barry, Clifton E; Maartens, Gary

    2016-03-19

    Although the worldwide incidence of tuberculosis has been slowly decreasing, the global disease burden remains substantial (∼9 million cases and ∼1·5 million deaths in 2013), and tuberculosis incidence and drug resistance are rising in some parts of the world such as Africa. The modest gains achieved thus far are threatened by high prevalence of HIV, persisting global poverty, and emergence of highly drug-resistant forms of tuberculosis. Tuberculosis is also a major problem in health-care workers in both low-burden and high-burden settings. Although the ideal preventive agent, an effective vaccine, is still some time away, several new diagnostic technologies have emerged, and two new tuberculosis drugs have been licensed after almost 50 years of no tuberculosis drugs being registered. Efforts towards an effective vaccine have been thwarted by poor understanding of what constitutes protective immunity. Although new interventions and investment in control programmes will enable control, eradication will only be possible through substantial reductions in poverty and overcrowding, political will and stability, and containing co-drivers of tuberculosis, such as HIV, smoking, and diabetes. PMID:26377143

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

    PubMed

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

    2012-06-01

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

  9. Biomolecular identification of ancient Mycobacterium tuberculosis complex DNA in human remains from Britain and continental Europe.

    PubMed

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

    2014-02-01

    Tuberculosis is known to have afflicted humans throughout history and re-emerged towards the end of the 20th century, to an extent that it was declared a global emergency in 1993. The aim of this study was to apply a rigorous analytical regime to the detection of Mycobacterium tuberculosis complex (MTBC) DNA in 77 bone and tooth samples from 70 individuals from Britain and continental Europe, spanning the 1st-19th centuries AD. We performed the work in dedicated ancient DNA facilities designed to prevent all types of modern contamination, we checked the authenticity of all products obtained by the polymerase chain reaction, and we based our conclusions on up to four replicate experiments for each sample, some carried out in an independent laboratory. We identified 12 samples that, according to our strict criteria, gave definite evidence for the presence of MTBC DNA, and another 22 that we classified as "probable" or "possible." None of the definite samples came from vertebrae displaying lesions associated with TB. Instead, eight were from ribs displaying visceral new bone formation, one was a tooth from a skeleton with rib lesions, one was taken from a skeleton with endocranial lesions, one from an individual with lesions to the sacrum and sacroiliac joint and the last was from an individual with no lesions indicative of TB or possible TB. Our results add to information on the past temporal and geographical distribution of TB and affirm the suitability of ribs for studying ancient TB.

  10. 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.

  11. 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

  12. 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…

  13. Tuberculosis

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Tuberculosis KidsHealth > For Teens > Tuberculosis Print A A A Text Size What's in ... Duration When to Call the Doctor en español Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...

  14. Tuberculosis

    MedlinePlus

    Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs, but they can also damage other parts of the body. TB spreads through the air when a person with ...

  15. [Tuberculosis].

    PubMed

    Iinuma, Y

    2000-11-01

    The incidence of tuberculosis in Japan is the highest among developed countries, with approximately 42,000 new cases reported in 1997, marking the first increase in 38 years. The growing incidence among the elderly and group infections among young adults may be responsible for this increase. Infection with tubercle bacilli(TB) occurs via airborne transmission, which involves dissemination of either airborne droplet nuclei on evaporated droplets that may remain suspended in the air for long periods of time. Microorganisms carried in this manner can be dispersed widely by air currents, therefore, special air handling and ventilation are required to prevent airborne transmission. Patients with infectious TB must be placed in a single room with negative pressure and a ventilation rate of 6 or more air changes per hour. Health care workers must wear an N95 mask when entering the room, and if an incident involving possible TB infection occurs in the hospital, the concerned people should be examined for Tuberculin reaction. Two to 12 weeks after the TB infection has occurred, the tuberculin reaction converts to positive. However, most Japanese people have been vaccinated with BCG, so assessment of the results is difficult. A comparison of the diameter of erythema before and after the potential infection may be the most confirmatory. If latent TB infection is suspected, preventive therapy with isoniazid must be considered. Special biohazard systems in the clinical laboratory and autopsy room have also been proposed to prevent TB dispersal. DOTS(Directly Observed Treatment, Short-course) is useful to prevent the emergence of multi-drug-resistant TB. In some areas of Japan that have low levels of compliance with TB therapy, trials of DOTS have been started. PMID:11132556

  16. Tuberculosis

    MedlinePlus

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

  17. High background rates of positive tuberculosis-specific interferon-γ release assays in a low prevalence region of UK: a surveillance study

    PubMed Central

    2012-01-01

    Background Background rates of latent tuberculosis infection in low prevalence regions of Britain are unknown. These would be valuable data for interpreting positive IGRA results, and guiding cost-benefit analyses. The management of a large outbreak of tuberculosis occurring in a rural district hospital provided an opportunity to determine the background rates and epidemiology of IGRA-positivity amongst unselected hospital patients in a low-prevalence region of U.K. Methods As part of a public health surveillance project we identified 445 individuals exposed to the index cases for clinical assessment and testing by a TB-specific interferon-γ release assay (IGRA): T-Spot.TB. Uniquely, an additional comparator group of 191 age-matched individuals without specific recent exposure, but with a similar age distribution and demographic, were recruited from the same wards where exposure had previously occurred, to undergo assessment by questionnaire and IGRA. Results Rates of IGRA positivity were 8.7% (95%CI, 4.2-13, n=149) amongst unexposed patients, 9.5%(3.0-22, n=21) amongst unexposed staff, 22%(14–29, n=130) amongst exposed patients, 11%(6.1-16, n=142) amongst exposed staff. Amongst the individuals without history of recent exposure to the outbreak, IGRA-positivity was associated with prior TB treatment (OR11, P.04) and corticosteroid use (OR5.9, P.02). Background age-specific prevalences of IGRA-positivity amongst unexposed individuals were: age <40 0%(N/A), age 40–59 15%(12–29), age 60–79 7.0%(1.1-13), age≥80 10%(5.9-19). Conclusions Background rates of IGRA-positivity remain high amongst unselected white-Caucasian hospital inpatients in U.K. These data will aid interpretation of future outbreak studies. As rates peak in the 5th and 6th decade, given an ageing population and increasing iatrogenic immunosuppression, reactivation of LTBI may be a persistent hazard in this population for several decades to come. PMID:23216965

  18. Postmenopausal Tuberculosis Endometritis

    PubMed Central

    Güngördük, Kemal; Ulker, Volkan; Sahbaz, Ahmet; Ark, Cemal; Tekırdag, Alı Ismet

    2007-01-01

    Tuberculosis remains a global health problem, primarily in developing countries with inadequate health services. A significant portion of tuberculosis in these settings is extrapulmonary, including tuberculosis of the genitourinary tract. Patients with genital tuberculosis are usually young women detected during work up for infertility. After menopause, tuberculosis of the endometrium is a rare possibility probably because of the decreased vascularity of the tissues. We present a case of endometrial tuberculosis with postmenopausal vaginal bleeding. PMID:17541465

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

    PubMed Central

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

    2007-01-01

    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 of diabetes as a risk factor for incident pulmonary tuberculosis, using India as an example. Methods We constructed an epidemiological model using data on tuberculosis incidence, diabetes prevalence, population structure, and relative risk of tuberculosis associated with diabetes. We evaluated the contribution made by diabetes to both tuberculosis incidence, and to the difference between tuberculosis incidence in urban and rural areas. Results In India in 2000 there were an estimated 20.7 million adults with diabetes, and 900,000 incident adult cases of pulmonary tuberculosis. Our calculations suggest that diabetes accounts for 14.8% (uncertainty range 7.1% to 23.8%) of pulmonary tuberculosis and 20.2% (8.3% to 41.9%) of smear-positive (i.e. infectious) tuberculosis. We estimate that the increased diabetes prevalence in urban areas is associated with a 15.2% greater smear-positive tuberculosis incidence in urban than rural areas – over a fifth of the estimated total difference. Conclusion Diabetes makes a substantial contribution to the burden of incident tuberculosis in India, and the association is particularly strong for the infectious form of tuberculosis. The current diabetes epidemic may lead to a resurgence of tuberculosis in endemic regions, especially in urban areas. This potentially carries a risk of global spread with serious implications for tuberculosis control and the achievement of the United Nations Millennium Development Goals. PMID:17822539

  20. Tuberculosis caused by RDRio Mycobacterium tuberculosis is not associated with differential clinical features

    PubMed Central

    Barbosa, C. de B.; Lazzarini, L. C. O.; Elias, A. R.; Leung, J. A. M.; Ribeiro, S. B.; da Silva, M. G.; Duarte, R. S.; Suffys, P.; Gomes, H. M.; Kritski, A. L.; Lapa e Silva, J. R.; Ho, J. L.; Boéchat, N.

    2013-01-01

    BACKGROUND We recently described the Mycobacterium tuberculosis RDRio genotype, a clonally derived sublineage within the Latin American–Mediterranean (LAM) family. Genetic diversity of M. tuberculosis likely affects the clinical aspects of tuberculosis (TB). Prospective studies that address this issue are scarce and remain controversial. OBJECTIVE To determine the association of differential clinical features of pulmonary TB with the RDRio M. tuberculosis etiology. METHODS Culture-proven pulmonary TB patients (n = 272) were clinically evaluated, including history, physical examination, chest X-ray and anti-human immunodeficiency virus serology. Isolates were classified as RDRio or non-RDRio M. tuberculosis by multiplex polymerase chain reaction and further spoligotyped. Clinical and M. tuberculosis genotype data were analyzed. RESULTS RDRio M. tuberculosis caused disease in 26.5% (72/270) of all TB cases. The LAM genotype, of which RDRio strains are members, was responsible for 46.0% of the TB cases. Demographic data, major signs and symptoms, radiographic presentation, microbiological features and clinical outcomes were not significantly different among patients with TB caused by RDRio and non-RDRio strains. CONCLUSIONS Disease caused by M. tuberculosis RDRio strains was not clinically distinctive or more severe than disease caused by non-RDRio strains in this series of TB patients. Larger prospective studies specifically designed to disclose differential clinical characteristics of TB caused by specific M. tuberculosis lineages are needed. PMID:22863208

  1. A brief history of tuberculosis in Iran during the 19th and 20th centuries.

    PubMed

    Azizi, Mohammad Hossein; Bahadori, Moslem

    2011-05-01

    The history of tuberculosis as a worldwide fatal illness traces back to antiquity, a well-known disease in ancient civilizations. However, its causative agent remained unidentified until the last decades of the 19th century, when discovered by Robert Koch. In due course, preparation of the BCG vaccine, application of the Mantoux intradermal diagnostic tuberculosis test and administration of proper antituberculosis medications eventually controlled tuberculosis. However, despite these significant advancements tuberculosis remained uneradicated, particularly in developing countries after the emergence of both multidrug-resistant tuberculosis and HIV co-infection. Presented here, is a brief review of the history of tuberculosis in the world as well as its historical background in Iran, mainly during the 19th and 20th centuries.

  2. Peritoneal tuberculosis.

    PubMed

    Guirat, A; Koubaa, M; Mzali, R; Abid, B; Ellouz, S; Affes, N; Ben Jemaa, M; Frikha, F; Ben Amar, M; Beyrouti, M I

    2011-01-01

    The peritoneum is one of the locations outside the most common pulmonary tuberculosis. Peritoneal tuberculosis poses a public health problem in endemic regions of the world. The phenomenon of migration, the increased use of immunosuppressive therapy and the epidemic of AIDS have contributed to a resurgence of this disease in regions where it was previously controlled. The aim of this review is to expose the clinical, biologic end radiologic futures of the peritoneal tuberculosis and to present the methods of diagnosis and treatment. The diagnosis of this disease is difficult and still remains a challenge because of its insidious nature, the variability of presentation and limitations of available diagnostic tests. The disease usually presents a picture of lymphocytic exudative ascites. There are many complementary tests with variable sensitivities and specificities to confirm the diagnosis of peritoneal tuberculosis. Isolation of mycobacteria by culture of ascitic fluid or histological examination of peritoneal biopsy ideally performed by laparoscopy remains the investigation of choice. The role of PCR, ascitic adenosine deaminase, interferon gamma and the radiometric BACTEC system can improve the diagnostic yield. An antituberculous treatment with group 1 of the WHO for 6 months is sufficient in most cases.

  3. Imaging Manifestations of Thoracic Tuberculosis.

    PubMed

    Restrepo, Carlos Santiago; Katre, Rashmi; Mumbower, Amy

    2016-05-01

    Despite significant improvements in the diagnosis and treatment of tuberculosis achieved during the last 3 decades, tuberculosis still remains one of the deadliest communicable diseases worldwide. Tuberculosis is still present in all regions of the world, with a more significant impact in developing countries. This article reviews the most common imaging manifestations of primary and postprimary tuberculosis, their complications, and the critical role of imaging in the diagnosis and follow-up of affected patients.

  4. Tuberculosis and poverty.

    PubMed Central

    Spence, D P; Hotchkiss, J; Williams, C S; Davies, P D

    1993-01-01

    OBJECTIVE--To examine whether the historical link between tuberculosis and poverty still exists. DESIGN--Retrospective study examining the notifications of all forms of tuberculosis by council ward over a six year period and correlating this with four indices of poverty; council housing, free school meals, the Townsend overall deprivation index, and the Jarman index. SETTING--The 33 electoral wards of the city of Liverpool. SUBJECTS--344 residents of Liverpool with tuberculosis. RESULTS--The rate of tuberculosis was correlated with all measures of poverty, the strongest correlation being with the Jarman index (r = 0.73, p < 0.0001). This link was independent of the high rates of tuberculosis seen in ethnic minorities. CONCLUSION--Tuberculosis remains strongly associated with poverty. PMID:8219945

  5. Peritoneal tuberculosis: diagnostic options.

    PubMed Central

    Lal, N; Soto-Wright, V

    1999-01-01

    BACKGROUND: Extrapulmonary tuberculosis has vague symptoms and few signs. It is essential to recognize and diagnose this curable disease prior to performing definitive surgery. Newer tests such as DNA or RNA amplification allow for early diagnosis but have limitations. CASE: We report a case of peritoneal tuberculosis in an immigrant woman. She had vague symptoms of low-grade fever, mild abdominal pain, obstipation, and bloating. Diagnostic laparoscopy was performed to establish the diagnosis. Tuberculosis was confirmed by DNA extraction from the frozen section specimen with subsequent analysis using polymerase chain reaction. CONCLUSION: Peritoneal tuberculosis is a disease that often simulates malignancies. With the increasing prevalence of human immunodeficiency virus in developed countries, tuberculosis is also on the rise and should be considered in the differential diagnosis of a patient with an abdominal/pelvic mass and ascites. PMID:10524670

  6. Ocular tuberculosis: current perspectives

    PubMed Central

    Shakarchi, Faiz I

    2015-01-01

    The World Health Organization currently estimates that nearly two billion people, or one-third of the world’s population, are infected by tuberculosis, and that roughly 10% of the infected people are symptomatic. Tuberculosis affects the lungs in 80% of patients, while in the remaining 20% the disease may affect other organs, including the eye. Uveitis can be seen concurrently with tuberculosis, but a direct association is difficult to prove. Ocular tuberculosis is usually not associated with clinical evidence of pulmonary tuberculosis, as up to 60% of extrapulmonary tuberculosis patients may not have pulmonary disease. The diagnosis of tuberculous uveitis is often problematic and in nearly all reported cases, the diagnosis was only presumptive. Tuberculous uveitis is a great mimicker of various uveitis entities and it can be considered in the differential diagnosis of any type of intraocular inflammation. It is still unknown if ocular manifestations result from a direct mycobacterium infection or hypersensitivity reaction and this is reflected on the management of tuberculous uveitis. Prevalence of tuberculosis as an etiology of uveitis may reach up to 10% in endemic areas. Tuberculous uveitis is a vision-threatening disease that inevitably leads to blindness if not properly diagnosed and treated. The aim of this review is to illustrate the various clinical features and management of presumed tuberculous uveitis. The current review focuses on the diagnostic criteria, significance of tuberculin skin test, and use of systemic corticosteroids in the management of tuberculous uveitis as recommended in recent publications. PMID:26648690

  7. Identification and Genotyping of Mycobacterium tuberculosis Isolated From Water and Soil Samples of a Metropolitan City

    PubMed Central

    Velayati, Ali Akbar; Farnia, Parissa; Mozafari, Mohadese; Malekshahian, Donya; Farahbod, Amir Masoud; Seif, Shima; Rahideh, Snaz

    2015-01-01

    BACKGROUND: The potential role of environmental Mycobacterium tuberculosis in the epidemiology of TB remains unknown. We investigated the transmission of M tuberculosis from humans to the environment and the possible transmission of M tuberculosis from the environment to humans. METHODS: A total of 1,500 samples were collected from three counties of the Tehran, Iran metropolitan area from February 2012 to January 2014. A total of 700 water samples (47%) and 800 soil samples (53%) were collected. Spoligotyping and the mycobacterial interspersed repetitive units-variable number of tandem repeats typing method were performed on DNA extracted from single colonies. Genotypes of M tuberculosis strains isolated from the environment were compared with the genotypes obtained from 55 patients with confirmed pulmonary TB diagnosed during the study period in the same three counties. RESULTS: M tuberculosis was isolated from 11 of 800 soil samples (1%) and 71 of 700 water samples (10%). T family (56 of 82, 68%) followed by Delhi/CAS (11 of 82, 13.4%) were the most frequent M tuberculosis superfamilies in both water and soil samples. Overall, 27.7% of isolates in clusters were related. No related typing patterns were detected between soil, water, and clinical isolates. The most frequent superfamily of M tuberculosis in clinical isolates was Delhi/CAS (142, 30.3%) followed by NEW-1 (127, 27%). The bacilli in contaminated soil (36%) and damp water (8.4%) remained reculturable in some samples up to 9 months. CONCLUSIONS: Although the dominant M tuberculosis superfamilies in soil and water did not correspond to the dominant M tuberculosis family in patients, the presence of circulating genotypes of M tuberculosis in soil and water highlight the risk of transmission. PMID:25340935

  8. Tuberculosis (TB)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis Research The New Challenge for TB Research NIAID ... HIV/AIDS Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis Research Agenda (PDF) TB Research at NIAID Research ...

  9. Tuberculosis (TB)

    MedlinePlus

    ... Skip Content Marketing Share this: Main Content Area Tuberculosis (TB) Overview In developed countries, such as the ... thought to be infected with TB bacteria, Mycobacterium tuberculosis ( Mtb ). TB is a chronic bacterial infection. It ...

  10. [Epidemiology of tuberculosis].

    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.

  11. Bovine Tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  12. Tuberculosis simulating brain tumour.

    PubMed

    Chaudhry, U R; Farooq, M; Rauf, F; Bhatti, S K

    2011-06-30

    The purpose of the study is to highlight the varied presentation of tuberculosis (TB) simulating a brain tumour. Headache and seizures are becoming frequent presenting complaints without any history of tuberculosis. The study comprises 1200 patients of both sexes with ages ranging from ten to sixty years. CT scan and MRI brain control with and without contrast medium were the investigations performed in these cases. In some patients Electroencephalography (EEG), cerebral angiography (DSA) and spectroscopy were also performed. The final diagnosis of tuberculosis was made on the basis of craniotomy, stereotactic and burr hole biopsies with histopathology in most of the cases. Forty per cent of the patients were followed up for eight months. They were put on anti-tuberculosis treatment with symptomatic and anti-epileptic drugs. The incidence was 544 and 757 per 100,000 in Africa and Indo Pakistan respectively. The male to female ratio was 1:1. Tuberculosis, especially with CNS involvement, is not only common in immunosuppressed patients in our setting, but TB has been and remains an important public health problem. TB may involve the CNS either as meningitis or as parenchymal granulomas or abscesses. Patients with brain TB usually present with fever, multiple cranial nerve involvement and occasional behavioural changes. CSF findings remain non specific in most cases. The most common sites are the cerebral hemisphere and basal ganglion in adults and the cerebellum in children. Tuberculosis has unique findings on brain CT and MRI. Cortical and subcortical locations are typical whereas the brain stem is a less common site. Tuberculosis lesions are usually solitary but multiple in 10% to 35% of cases. In spite of all these facts some cases of brain TB still need aggressive neurointervention to reach the final diagnosis of brain TB. Tuberculosis in the CNS may manifest in many different ways. So one should always include tuberculosis in the differential diagnosis in the

  13. Diagnostics for pulmonary tuberculosis

    PubMed Central

    Cudahy, Patrick

    2016-01-01

    Tuberculosis (TB) remains a leading cause of human suffering and mortality despite decades of effective treatment being available. Accurate and timely diagnosis remains an unmet goal. The HIV epidemic has also led to new challenges in the diagnosis of TB. Several new developments in TB diagnostics have the potential to positively influence the global campaign against TB. We aim to review the performance of both established as well as new diagnostics for pulmonary TB in adults, and discuss the ongoing challenges. PMID:27005271

  14. The Epidemic-level Impact of Preventing Nosocomial Transmission of Extensively Drug-Resistant (XDR) Tuberculosis in Rural South African District Hospitals

    PubMed Central

    Andrews, Jason; Poolman, Eric M.; Gandhi, Neel R.; Shah, N. Sarita; Moll, Anthony; Galvani, Alison P.; Friedland, Gerald H.

    2012-01-01

    Background Extensively drug-resistant (XDR) tuberculosis has spread among hospitalized patients in South Africa, but the epidemic-level impact of hospital-based infection control strategies remains unknown. Methods We investigated the effect of administrative, environmental, and personal infection control measures on the epidemic trajectory of XDR tuberculosis in a rural South African community. Assessments were performed with a mathematical model, which incorporated inpatient airborne tuberculosis transmission and community tuberculosis and HIV transmission. Results If no new interventions are introduced, 1,300 cases of XDR tuberculosis are predicted to occur in the area of Tugela Ferry by the end of 2012. Over half of these cases are likely to be nosocomially transmitted. Mask use would avert less than 10% of overall cases, due to long inpatient exposure times and real-world face-seal leakage rates, but could reduce a significant proportion of hospital staff XDR tuberculosis cases. Combining mask use with reduced hospitalization time and a shift to outpatient therapy, however, could prevent nearly one-third of XDR tuberculosis cases. Supplementing this approach with improved ventilation, rapid drug resistance testing, HIV treatment, and tuberculosis isolation facilities could avert 48% of XDR tuberculosis cases (range 34-50%) by the end of 2012. Involuntary detention, however, could result in an unexpected rise in incidence, given limited isolation capacity. Conclusions In the face of rising XDR tuberculosis incidence, prevalence and burden on the health care system, a synergistic combination of available nosocomial infection control strategies may prevent nearly half of XDR tuberculosis cases, even in a resource-limited setting. XDR tuberculosis transmission will continue in the community in spite of such efforts, however, indicating the need to develop parallel community-based programs. PMID:17964351

  15. Relationship Between HIV Coinfection, Interleukin 10 Production, and Mycobacterium tuberculosis in Human Lymph Node Granulomas

    PubMed Central

    Diedrich, Collin R.; O'Hern, Jennifer; Gutierrez, Maximiliano G.; Allie, Nafiesa; Papier, Patricia; Meintjes, Graeme; Coussens, Anna K.; Wainwright, Helen; Wilkinson, Robert J.

    2016-01-01

    Background. Human immunodeficiency virus type 1 (HIV)–infected persons are more susceptible to tuberculosis than HIV–uninfected persons. Low peripheral CD4+ T-cell count is not the sole cause of higher susceptibility, because HIV–infected persons with a high peripheral CD4+ T-cell count and those prescribed successful antiretroviral therapy (ART) remain more prone to active tuberculosis than HIV–uninfected persons. We hypothesized that the increase in susceptibility is caused by the ability of HIV to manipulate Mycobacterium tuberculosis–associated granulomas. Methods. We examined 71 excised cervical lymph nodes (LNs) from persons with HIV and M. tuberculosis coinfection, those with HIV monoinfection, and those with M. tuberculosis monoinfection with a spectrum of peripheral CD4+ T-cell counts and ART statuses. We quantified differences in M. tuberculosis levels, HIV p24 levels, cellular response, and cytokine presence within granulomas. Results. HIV increased M. tuberculosis numbers and reduced CD4+ T-cell counts within granulomas. Peripheral CD4+ T-cell depletion correlated with granulomas that contained fewer CD4+ and CD8+ T cells, less interferon γ, more neutrophils, more interleukin 10 (IL-10), and increased M. tuberculosis numbers. M. tuberculosis numbers correlated positively with IL-10 and interferon α levels and fewer CD4+ and CD8+ T cells. ART reduced IL-10 production. Conclusions. Peripheral CD4+ T-cell depletion correlated with increased M. tuberculosis presence, increased IL-10 production, and other phenotypic changes within granulomas, demonstrating the HIV infection progressively changes these granulomas. PMID:27462092

  16. Tuberculosis (TB): Treatment

    MedlinePlus

    ... Departments & Divisions Home Conditions Tuberculosis Treating Tuberculosis Treating Tuberculosis Make an Appointment Refer a Patient Ask a ... bones is treated longer. NEXT: Preventive Treatment Diagnosing Tuberculosis History of TB Our Specialists Charles L. Daley, ...

  17. Odontoid process pathologic fracture in spinal tuberculosis.

    PubMed

    Ould-Slimane, M; Lenoir, T; Dauzac, C; Breitel, D; Hoffmann, E; Guigui, P; Ilharreborde, B

    2010-02-01

    Craniovertebral junction tuberculosis is a rare lesion in which treatment remains controversial. Options range from conservative treatment to surgery, independently of any associated neurological threat. We here report the first case of pathologic odontoid fracture in a context of spinal tuberculosis, complicated by unusual neurological evolution. The patient presented with non-contiguous multifocal tuberculosis, of which there have previously been only 6 reported cases.

  18. Determination of Urinary Neopterin/Creatinine Ratio to Distinguish Active Tuberculosis from Latent Mycobacterium tuberculosis Infection

    PubMed Central

    Eisenhut, Michael; Hargreaves, Dougal S.; Scott, Anne; Housley, David; Walters, Andrew; Mulla, Rohinton

    2016-01-01

    Background. Biomarkers to distinguish latent from active Mycobacterium (M.) tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (p < 0.01). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (p < 0.01). Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection. PMID:27433370

  19. 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

  20. Disseminated tuberculosis

    MedlinePlus

    Tuberculosis (TB) infection can develop after breathing in droplets sprayed into the air from a cough or sneeze by ... bacterium. The resulting lung infection is called primary TB. The usual site of TB is the lungs ( ...

  1. [Tuberculosis and human rights].

    PubMed

    Nagai, Hideaki; Inagaki, Tomokazu; Toyoda, Emiko; Kawabe, Yoshiko; Fujiwara, Keiko; Masuyama, Hidenori; Takahashi, Shigeru

    2005-01-01

    . Discontinued hospitalization in tuberculosis patient: Yoshiko KAWABE (National Hospital Organization Tokyo National Hospital) We investigated the background of tuberculosis patients who entered our hospital in 11 years from 1993 to 2003 and discontinued hospitalization. Out of 4,126 cases 76 cases (1.8 %) discontinued hospitalization. We classify three groups. One is self discharged group who leaved hospital without permission. Second is obligatory discharged group who were displaced for some trouble. Third is transferred group who were transferred to another hospital including mental hospital that have ward for tuberculosis. Major reasons were drinking during hospitalization, violence, roam because of dementia and major backgrounds were repeatedly noncompliant patients, homeless people, and suffering from senile dementia. We concluded we need some legal intervention for few cases who cannot continue hospitalization. 3. Tuberculosis control policy and human rights in public health center: Keiko FUJIWARA (Infection Diseases Control Division, Public Health Bureau, City of Yokohama) It is required for a success of the tuberculosis control policy to consider human rights. Patients' human rights should be respected, and surrounding people's human rights should also be respected. We sometimes see a tuberculosis patient who cannot continue tuberculosis treatment. A society as a whole has to share the recognition of tuberculosis as a social illness. The completion of tuberculosis treatment is not only the benefit of individual, but also it is very important as social defense. When we revise the tuberculosis control policy, we should think about both protecting a society from tuberculosis and protecting tuberculosis patients' human rights and obtain national consensus. 4. The mandatory TB control policy in the US: Hidenori MASUYAMA (Shibuya Dispensary, Japan Anti-TB Association) The mandatory TB control policy in the US was discussed. If the mandatory health policy would be applied

  2. Tuberculosis and aging: a global health problem.

    PubMed

    Rajagopalan, S

    2001-10-01

    Despite the World Health Organization's declaration that the spread of tuberculosis is a global emergency and despite the implementation of strong tuberculosis-control initiatives, this highly infectious disease continues to affect all vulnerable populations, including the elderly population (age > or =65 years). Tuberculosis in aging adults remains a clinical and epidemiological challenge. Atypical clinical manifestations of tuberculosis in older persons can result in delay in diagnosis and initiation of treatment; thus, unfortunately, higher rates of morbidity and mortality from this treatable infection can occur. Underlying illnesses, age-related diminution in immune function, the increased frequency of adverse drug reactions, and institutionalization can complicate the overall clinical approach to tuberculosis in elderly patients; maintenance of a high index of suspicion for tuberculosis in this vulnerable population is, thus, undoubtedly justifiable.

  3. 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

  4. Immune Responses of HIV-1 Tat Transgenic Mice to Mycobacterium Tuberculosis W-Beijing SA161

    PubMed Central

    Honda, Jennifer R; Shang, Shaobin; Shanley, Crystal A; Caraway, Megan L; Henao-Tamayo, Marcela; Chan, Edward D; Basaraba, Randall J; Orme, Ian M; Ordway, Diane J; Flores, Sonia C

    2011-01-01

    Background: Mycobacterium tuberculosis remains among the leading causes of death from an infectious agent in the world and exacerbates disease caused by the human immunodeficiency virus (HIV). HIV infected individuals are prone to lung infections by a variety of microbial pathogens, including M. tuberculosis. While the destruction of the adaptive immune response by HIV is well understood, the actual pathogenesis of tuberculosis in co-infected individuals remains unclear. Tat is an HIV protein essential for efficient viral gene transcription, is secreted from infected cells, and is known to influence a variety of host inflammatory responses. We hypothesize Tat contributes to pathophysiological changes in the lung microenvironment, resulting in impaired host immune responses to infection by M. tuberculosis. Results: Herein, we show transgenic mice that express Tat by lung alveolar cells are more susceptible than non-transgenic control littermates to a low-dose aerosol infection of M. tuberculosis W-Beijing SA161. Survival assays demonstrate accelerated mortality rates of the Tat transgenic mice compared to non-transgenics. Tat transgenic mice also showed poorly organized lung granulomata-like lesions. Analysis of the host immune response using quantitative RT-PCR, flow cytometry for surface markers, and intracellular cytokine staining showed increased expression of pro-inflammatory cytokines in the lungs, increased numbers of cells expressing ICAM1, increased numbers of CD4+CD25+Foxp3+ T regulatory cells, and IL-4 producing CD4+ T cells in the Tat transgenics compared to infected non-tg mice. Conclusions: Our data show quantitative differences in the inflammatory response to the SA161 clinical isolate of M. tuberculosis W-Beijing between Tat transgenic and non-transgenic mice, suggesting Tat contributes to the pathogenesis of tuberculosis. PMID:22046211

  5. 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.

  6. Tuberculosis Infection and Latent Tuberculosis

    PubMed Central

    2016-01-01

    Active tuberculosis (TB) has a greater burden of TB bacilli than latent TB and acts as an infection source for contacts. Latent tuberculosis infection (LTBI) is the state in which humans are infected with Mycobacterium tuberculosis without any clinical symptoms, radiological abnormality, or microbiological evidence. TB is transmissible by respiratory droplet nucleus of 1–5 µm in diameter, containing 1–10 TB bacilli. TB transmission is affected by the strength of the infectious source, infectiousness of TB bacilli, immunoresistance of the host, environmental stresses, and biosocial factors. Infection controls to reduce TB transmission consist of managerial activities, administrative control, engineering control, environmental control, and personal protective equipment provision. However, diagnosis and treatment for LTBI as a national TB control program is an important strategy on the precondition that active TB is not missed. Therefore, more concrete evidences for LTBI management based on clinical and public perspectives are needed. PMID:27790271

  7. [Tuberculosis in Iceland. 1976].

    PubMed

    Sigurdsson, Sigurdur

    2005-01-01

    ray examination was made in all cases where tuberculin examination had not been made or was incomplete. The negative reactors were not X rayed. The tuberculin tests were percutaneous, cutaneous and intracutaneous. The X ray examination during the first years was performed by means of fluoroscopy and roentgenograms were made in all doubtful cases. In 1945 when the survey of the capital city of Reykjavík was made and comprised a total of 43,595 persons photoroentgenograms were made. After 1948 only this method together with tuberculin testing was used in all the larger towns in the country. During the period 1940-1945 such surveys were carried out in 12 medical districts, or parts thereof and included 58,837 persons or 47 percent of the entire population. The attendance in these surveys ranged from 89.3 percent to 100 percent of those considered able to attend. In the capital city, Reykjavík, the attendance was 99.32 percent. The course and prevalence of tuberculosis in Iceland from 1911 to 1970 are traced on the basis of tuberculosis reporting registers, mortality records which were ordered by law in 1911, tuberculin surveys and post mortem examinations. The deficiencies of these sources are pointed out. Since 1939 the morbidity rates are accurate. The number of reported cases of tuberculosis increases steadily up to the year 1935, when 1.6 percent of the population is reported to have active tuberculosis at the end of that year. Thereafter it begins to decline gradually the first years but abruptly in 1939, then without doubt because of the revision of the tuberculosis legislation and more exact reporting regulations. After that year the fall is almost constant with rather small fluctuations as regards new cases, relapses and total number of reported cases remaining on register at the end of each year. In 1950 the new cases are down to 1.6 per thousand and at the end of the year the rate for those remaining on register is 6.9 per thousand. In the year 1954 there is

  8. Tuberculosis: General Information

    MedlinePlus

    TB Elimination Tuberculosis: General Information What is TB? Tuberculosis (TB) is a disease caused by germs that are spread from person ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination CS227840_A What Does a Positive Test ...

  9. Global Tuberculosis Report 2015

    MedlinePlus

    ... Feed Youtube Twitter Facebook Google + iTunes Play Store Tuberculosis (TB) Menu Tuberculosis The End TB Strategy Areas ... data News, events and features About us Global tuberculosis report 2015 This is the twentieth global report ...

  10. Tuberculosis: New Aspects of an Old Disease

    PubMed Central

    Jordao, Luisa; Vieira, Otilia V.

    2011-01-01

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

  11. 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-1β 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.

  12. Nutritional supplements for people being treated for active tuberculosis

    PubMed Central

    Grobler, Liesl; Nagpal, Sukrti; Sudarsanam, Thambu D; Sinclair, David

    2016-01-01

    Background Tuberculosis and malnutrition are linked in a complex relationship. Tuberculosis may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there is no evidence-based nutritional guidance for adults and children being treated for tuberculosis. Objectives To assess the effects of oral nutritional supplements in people being treated with antituberculous drug therapy for active tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2016), MEDLINE (from 1946 to 4 February 2016), EMBASE (from 1980 to 4 February 2016), LILACS (from 1982 to 4 February 2016), the metaRegister of Controlled Trials (mRCT), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the Indian Journal of Tuberculosis up to 4 February 2016, and checked the reference lists of all included studies. Selection criteria Randomized controlled trials that compared any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. The primary outcomes of interest were all-cause death, and cure at six and 12 months. Data collection and analysis Two review authors independently selected trials for inclusion, and extracted data and assessed the risk of bias in the included trials. We presented the results as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). Where appropriate, we pooled data from trials with similar interventions and outcomes. We assessed the quality of the evidence using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Main results Thirty-five trials

  13. Nutritional supplements for people being treated for active tuberculosis

    PubMed Central

    Grobler, Liesl; Nagpal, Sukrti; Sudarsanam, Thambu D; Sinclair, David

    2016-01-01

    Background Tuberculosis and malnutrition are linked in a complex relationship. Tuberculosis may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there is no evidence-based nutritional guidance for adults and children being treated for tuberculosis. Objectives To assess the effects of oral nutritional supplements in people being treated with antituberculous drug therapy for active tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 1, 2016), MEDLINE (from 1946 to 4 February 2016), EMBASE (from 1980 to 4 February 2016), LILACS (from 1982 to 4 February 2016), the metaRegister of Controlled Trials (mRCT), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the Indian Journal of Tuberculosis up to 4 February 2016, and checked the reference lists of all included studies. Selection criteria Randomized controlled trials that compared any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. The primary outcomes of interest were all-cause death, and cure at six and 12 months. Data collection and analysis Two review authors independently selected trials for inclusion, and extracted data and assessed the risk of bias in the included trials. We presented the results as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CIs). Where appropriate, we pooled data from trials with similar interventions and outcomes. We assessed the quality of the evidence using the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Main results Thirty-five trials

  14. Tuberculosis (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Tuberculosis KidsHealth > For Parents > Tuberculosis Print A A A Text Size What's in ... When to You Call the Doctor en español Tuberculosis Tuberculosis (popularly known as "TB") is a disease ...

  15. Role of Mycobacterium tuberculosis pknD in the Pathogenesis of central nervous system tuberculosis

    PubMed Central

    2012-01-01

    Background Central nervous system disease is the most serious form of tuberculosis, and is associated with high mortality and severe neurological sequelae. Though recent clinical reports suggest an association of distinct Mycobacterium tuberculosis strains with central nervous system disease, the microbial virulence factors required have not been described previously. Results We screened 398 unique M. tuberculosis mutants in guinea pigs to identify genes required for central nervous system tuberculosis. We found M. tuberculosis pknD (Rv0931c) to be required for central nervous system disease. These findings were central nervous system tissue-specific and were not observed in lung tissues. We demonstrated that pknD is required for invasion of brain endothelia (primary components of the blood-brain barrier protecting the central nervous system), but not macrophages, lung epithelia, or other endothelia. M. tuberculosis pknD encodes a "eukaryotic-like" serine-threonine protein kinase, with a predicted intracellular kinase and an extracellular (sensor) domain. Using confocal microscopy and flow cytometry we demonstrated that the M. tuberculosis PknD sensor is sufficient to trigger invasion of brain endothelia, a process which was neutralized by specific antiserum. Conclusions Our findings demonstrate a novel in vivo role for M. tuberculosis pknD and represent an important mechanism for bacterial invasion and virulence in central nervous system tuberculosis, a devastating and understudied disease primarily affecting young children. PMID:22243650

  16. 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

  17. Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

    PubMed Central

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

    2008-01-01

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

  18. Edaxadiene: A New Bioactive Diterpene from Mycobacterium tuberculosis

    PubMed Central

    2009-01-01

    Mycobacterium tuberculosis remains a widespread and devastating human pathogen. Presented here is the characterization of an atypical class I diterpene cyclase from M. tuberculosis that catalyzes an unusual cyclization reaction in converting the known M. tuberculosis metabolite halimadienyl diphosphate to a further cyclized novel diterpene, which we have termed edaxadiene, as it directly inhibits maturation of the phagosomal compartment in which the bacterium is taken up during infection. PMID:19583202

  19. Cancer-specific incidence rates of tuberculosis

    PubMed Central

    Seo, Gi Hyeon; Kim, Min Jae; Seo, Soyoung; Hwang, Boram; Lee, Eugene; Yun, Yujin; Choi, Minsun; Kim, Moonsuk; Kim, Jin Won; Kim, Eu Suk; Kim, Hong Bin; Song, Kyoung-Ho

    2016-01-01

    Abstract Population-based studies of the incidence of tuberculosis in cancer patients according to the type of cancer are limited. We investigated the cancer-specific incidence of tuberculosis in a nationwide population-based cohort in a country with an intermediate burden of tuberculosis. We used mandatory National Health Insurance claims data to construct a cancer cohort of adults (aged 20–99 years) with newly diagnosed malignancies other than lung cancer, from January 2008 to December 2012. Patients who developed tuberculosis in this period were identified in the cancer cohort and the general population. Standardized incidence ratios (SIRs) of tuberculosis in the cancer cohort according to type of cancer and time after cancer diagnosis were calculated by comparing the observed incidence rates with those inferred from the age- and gender-specific incidence rates in the general population. A total of 855,382 cancer patients and 1589,876 person-years (py) were observed. A total of 5745 patients developed tuberculosis; the mean incidence rate was 361.3 per 100,000 py, and the SIR was 2.22 (95% confidence interval [CI], 2.17–2.27). The incidence rate was highest for hematologic malignancy and lowest for thyroid cancer. It was also highest as 650.1 per 100,000 py, with SIR of 3.70 (CI, 3.57–3.83) for the first 6 months after diagnosis of malignancy and then declined. However, it still remained higher than that of the general population after 24 months (SIR = 1.43, CI, 1.36–1.51). The incidence of tuberculosis increases after diagnosis in patients with malignancies. The risk of tuberculosis differs according to the type of cancer and remains elevated even 24 months after cancer diagnosis. Tuberculosis should be considered an important comorbidity in patients with malignancies. PMID:27661041

  20. Clinical Evaluation of Tuberculosis Viability Microscopy for Assessing Treatment Response

    PubMed Central

    Datta, Sumona; Sherman, Jonathan M.; Bravard, Marjory A.; Valencia, Teresa; Gilman, Robert H.; Evans, Carlton A.

    2015-01-01

    Background. It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis. Methods. To assess treatment response, sputum samples (n = 124) from unselected patients (n = 35) with sputum microscopy–positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate. Results. Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (rS = 0.85; P < .0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P < .001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P = .4) or quantitative culture (P = .6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P < .001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P = .6). Conclusions. Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy

  1. Gr1intCD11b+ Myeloid-Derived Suppressor Cells in Mycobacterium tuberculosis Infection

    PubMed Central

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

    2013-01-01

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

  2. [Tuberculosis: actual problems with diagnosis and treatment].

    PubMed

    Korzeniewska-Koseła, Maria

    2016-01-01

    Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex. It remains health problem also in developed countries. Most common form of tuberculosis is pulmonary disease but other sites of the body can be affected (extrapulmonary TB). As TB incidence falls, the probability of developing active diseases in people infected with M. tuberculosis is higher among imunocompromised people and in people from risk groups. People who present with unexplained cough lasting two or more weeks or with findings suggestive of tuberculosis on chest radiographs should be evaluated for tuberculosis. For patients suspected of having pulmonary or extrapulmonary tuberculosis specimens from the sites of involvement should be obtained for microbiological tests. Bronchoscopy and BAL should be performed in patients that do not produce sputum and with negative sputum smears. Ct scan may also play an important role in the evaluation of patients suspected of having TB but with negative sputum smears. The standard therapy for TB should consist of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol in the initial phase and of isoniazid and rifampicin given for 4 months (the continuation phase). PMID:27421129

  3. Multidrug-Resistant Tuberculosis in Admitted Patients at a Tertiary Referral Hospital of Bangladesh

    PubMed Central

    Banu, Sayera; Mahmud, Asif Mujtaba; Rahman, Md. Toufiq; Hossain, Arman; Uddin, Mohammad Khaja Mafij; Ahmed, Tahmeed; Khatun, Razia; Akhanda, Wahiduzzaman; Brosch, Roland

    2012-01-01

    Background This study was set out to investigate the magnitude, patterns and molecular characterization of drug-resistant Mycobacterium tuberculosis strains at a tertiary referral hospital in Bangladesh. Methods Pulmonary tuberculosis (TB) patients admitted at National Institute of Diseases of the Chest and Hospital from February 2002 to September 2005 with or without previous history of TB and/or other complications were randomly interviewed. Among 265 participants enrolled, M. tuberculosis isolates from 189 patients were finally tested for susceptibility to rifampicin (RMP), isoniazid (INH), ethambutol (ETM) and streptomycin (STM). Genotyping of M. tuberculosis was done using deletion analysis and spoligotyping. Results Eighty-eight percent (n = 167) of the patients had history of previous anti-TB treatment while the remaining 12% were new TB cases. Of the 189 isolates, 9% were fully susceptible to the first line anti-TB drugs and 73.5% were multi-drug resistant TB. Other susceptibility results showed 79.4%, 77.2%, 76.7% and 78.8% resistance to INH, RMP, ETM and STM respectively. Multi-drug resistance was significantly higher among the 130 (78%) patients with previous history of anti-tuberculosis treatment (95% confidence interval, p = 0.001). Among the 189 analyzed isolates, 69% were classified as “modern” M. tuberculosis strains (i.e. TbD1- strains, lacking the M. tuberculosis-deletion region TbD1), whereas the remaining 31% were found to belong to the “ancestal” TbD1+ M. tuberculosis lineages. One hundred and five different spoligotype patterns were identified in which 16 clusters contained 100 strains and 89 strains had unique pattern. Strains with a spoligotype characteristic for the “Beijing” cluster were predominant (19%) and most of these strains (75%) were multi-drug resistant (MDR). Conclusions A high level of drug resistance observed among the re-treatment patients poses a threat of transmission of resistant strains to susceptible

  4. Challenges in tuberculosis management in Peru and England.

    PubMed

    Ivany, Elena; Boulton, Jacqueline

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

  5. Challenges in tuberculosis management in Peru and England.

    PubMed

    Ivany, Elena; Boulton, Jacqueline

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

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

    PubMed Central

    Queipo-Ortuño, María Isabel; Colmenero, Juan D.; Bermudez, Pilar; Bravo, María José; Morata, Pilar

    2009-01-01

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

  7. Tuberculosis update: will good news become bad news?

    PubMed

    Efferen, L S

    1997-03-01

    Recent efforts to reestablish control of tuberculosis have resulted in some success. However, deaths from tuberculosis continue to increase worldwide. Molecular techniques have dominated investigators' efforts to improve diagnostic methods and therapeutic options. Unfortunately, no significant advances in the development of new drugs have occurred. Ongoing attempts to develop more effective vaccines hold some preliminary promise, but delineation of the protective antigens on Mycobacterium tuberculosis and the development of a vaccine for use in humans is considered decades away from clinical use. The lack of political commitment worldwide and the potential loss of support nationally remain major obstacles to the establishment of effective and long-lasting tuberculosis control.

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

    PubMed Central

    2013-01-01

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

  9. Tuberculosis and Pregnancy

    MedlinePlus

    ... Contacts of Persons with Infectious TB Epidemiology of Pediatric Tuberculosis in the United States Targeted Tuberculosis Testing ... and unknown risks of second-line antituberculosis drugs. Breastfeeding Breastfeeding should not be discouraged for women being ...

  10. Isolated perianal tuberculosis.

    PubMed

    Akgun, E; Tekin, F; Ersin, S; Osmanoglu, H

    2005-03-01

    Perianal tuberculosis, without the presence of any previous or active pulmonary infection, is extremely rare. A case of isolated perianal tuberculosis without gastrointestinal or pulmonary spread will be discussed here with an evaluation of the clinical features. PMID:15813425

  11. Tuberculosis and Diabetes

    MedlinePlus

    TUBERCULOSIS www.who.int/tb & DIABETES THE DUAL EPIDEMIC OF TB AND DIABETES DEADLY LINKAGES  People with ... higher risk of progressing from latent to active tuberculosis.  Diabetes triples a person’s risk of developing TB. ...

  12. Virulence factors of the Mycobacterium tuberculosis complex

    PubMed Central

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

    2013-01-01

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

  13. 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

  14. Tuberculosis diagnostics: Challenges and opportunities.

    PubMed

    Nema, Vijay

    2012-07-01

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

  15. Differential influence of nutrient-starved Mycobacterium tuberculosis on adaptive immunity results in progressive tuberculosis disease and pathology.

    PubMed

    Dietrich, Jes; Roy, Sugata; Rosenkrands, Ida; Lindenstrøm, Thomas; Filskov, Jonathan; Rasmussen, Erik Michael; Cassidy, Joseph; Andersen, Peter

    2015-12-01

    When infected with Mycobacterium tuberculosis, most individuals will remain clinically healthy but latently infected. Latent infection has been proposed to partially involve M. tuberculosis in a nonreplicating stage, which therefore represents an M. tuberculosis phenotype that the immune system most likely will encounter during latency. It is therefore relevant to examine how this particular nonreplicating form of M. tuberculosis interacts with the host immune system. To study this, we first induced a state of nonreplication through prolonged nutrient starvation of M. tuberculosis in vitro. This resulted in nonreplicating persistence even after prolonged culture in phosphate-buffered saline. Infection with either exponentially growing M. tuberculosis or nutrient-starved M. tuberculosis resulted in similar lung CFU levels in the first phase of the infection. However, between week 3 and 6 postinfection, there was a very pronounced increase in bacterial levels and associated lung pathology in nutrient-starved-M. tuberculosis-infected mice. This was associated with a shift from CD4 T cells that coexpressed gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) or IFN-γ, TNF-α, and interleukin-2 to T cells that only expressed IFN-γ. Thus, nonreplicating M. tuberculosis induced through nutrient starvation promotes a bacterial form that is genetically identical to exponentially growing M. tuberculosis yet characterized by a differential impact on the immune system that may be involved in undermining host antimycobacterial immunity and facilitate increased pathology and transmission. PMID:26416911

  16. Global and Regional Burden of Isoniazid-Resistant Tuberculosis

    PubMed Central

    Yuen, Courtney M.; Jenkins, Helen E.; Rodriguez, Carly A.; Keshavjee, Salmaan

    2015-01-01

    BACKGROUND: Isoniazid has been the backbone of tuberculosis chemotherapy for 6 decades. Resistance to isoniazid threatens the efficacy of treatment of tuberculosis disease and infection. To inform policies around treatment of tuberculosis disease and infection in children, we sought to estimate both the proportion of child tuberculosis cases with isoniazid resistance and the number of incident isoniazid-resistant tuberculosis cases in children, by region. METHODS: We determined the relationship between rates of isoniazid resistance among child cases and among treatment-naive adult cases through a systematic literature review. We applied this relationship to regional isoniazid resistance estimates to estimate proportions of childhood tuberculosis cases with isoniazid resistance. We applied these proportions to childhood tuberculosis incidence estimates to estimate numbers of children with isoniazid-resistant tuberculosis. RESULTS: We estimated 12.1% (95% confidence interval [CI] 9.8% to 14.8%) of all children with tuberculosis had isoniazid-resistant disease, representing 120 872 (95% CI 96 628 to 149 059) incident cases of isoniazid-resistant tuberculosis in children in 2010. The majority of these occurred in the Western Pacific and Southeast Asia regions; the European region had the highest proportion of child tuberculosis cases with isoniazid resistance, 26.1% (95% CI: 20.0% to 33.6%). CONCLUSIONS: The burden of isoniazid-resistant tuberculosis in children is substantial, and risk varies considerably by setting. The large number of child cases signals extensive ongoing transmission from adults with isoniazid-resistant tuberculosis. The risk of isoniazid resistance must be considered when evaluating treatment options for children with disease or latent infection to avoid inadequate treatment and consequent poor outcomes. PMID:26034243

  17. Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis.

    PubMed

    Coppola, Mariateresa; van den Eeden, Susan J F; Wilson, Louis; Franken, Kees L M C; Ottenhoff, Tom H M; Geluk, Annemieke

    2015-09-01

    Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive, and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study investigated an SLP derived from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed by "dormant" M. tuberculosis and well recognized by T cells from latently M. tuberculosis-infected individuals. In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon-positive/tumor necrosis factor-positive (IFN-γ(+)/TNF(+)) and IFN-γ(+) CD4(+) T cells and Rv1733c-specific antibodies and led to a significant reduction in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was observed both in a pre- and in a post-M. tuberculosis challenge setting. Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy of BCG, demonstrating the potential of M. tuberculosis latency antigens to improve BCG efficacy. These data suggest a promising role for M. tuberculosis latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic and in a postinfection setting.

  18. Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis

    PubMed Central

    Coppola, Mariateresa; van den Eeden, Susan J. F.; Wilson, Louis; Franken, Kees L. M. C.; Ottenhoff, Tom H. M.

    2015-01-01

    Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. Mycobacterium bovis BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive, and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis latency antigens. Synthetic long peptides (SLPs) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study investigated an SLP derived from Rv1733c, a major M. tuberculosis latency antigen which is highly expressed by “dormant” M. tuberculosis and well recognized by T cells from latently M. tuberculosis-infected individuals. In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administered to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited gamma interferon-positive/tumor necrosis factor-positive (IFN-γ+/TNF+) and IFN-γ+ CD4+ T cells and Rv1733c-specific antibodies and led to a significant reduction in the bacterial load in the lungs of M. tuberculosis-challenged mice. This was observed both in a pre- and in a post-M. tuberculosis challenge setting. Moreover, Rv1733c SLP immunization significantly boosted the protective efficacy of BCG, demonstrating the potential of M. tuberculosis latency antigens to improve BCG efficacy. These data suggest a promising role for M. tuberculosis latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic and in a postinfection setting. PMID:26202436

  19. Cutaneous tuberculosis in children.

    PubMed

    Sethuraman, Gomathy; Ramesh, Venkatesh

    2013-01-01

    Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis that accounts for 1% to 2% of cases. Childhood skin tuberculosis represents 18% to 82% of all cutaneous tuberculosis cases. Scrofuloderma and lupus vulgaris are the two most common clinical forms in children. An increase in the number of tuberculids, especially lichen scrofulosorum, has been observed in the last several years. Cutaneous tuberculosis in children can be severe and have a protracted course. Multiplicity of lesions and multifocal disseminated involvement in scrofuloderma and lupus vulgaris is common. Scrofuloderma progressing to gummatous lesions (scrofulous gumma) is mostly described in children. Morbidities and deformities are more severe in children.

  20. 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

  1. Tuberculosis: medico-legal aspects.

    PubMed

    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

  2. [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.

  3. [Semeiotics of abdominal tuberculosis].

    PubMed

    Guseĭnov, G K; Ramazanova, A M; Guseĭnov, A G

    1984-01-01

    Examination of 119 patients with abdominal tuberculosis permitted the description of the characteristic semiotics of the illness. Today the patients with abdominal tuberculosis are mainly women of child-bearing age with a long-term tuberculosis catamnesis and intoxication, with a history of tuberculosis of different sites, those suffering from tuberculosis or its sequels at present (64%), those with pains (94%), discomfort or swelling of the abdomen (79%), malfunction of the gastrointestinal tract (65%), weight loss (86%), malnutrition (72%), anemia (63%), not infrequently with inflammatory induration (43%) or ascites in the abdominal cavity (39%). In addition to this characteristic semiotics, the patients with abdominal tuberculosis may demonstrate the most different and unexpected symptoms up to acute abdomen (23%). To make differential diagnosis of abdominal tuberculosis, one has often to resort to diagnostic laparotomy, laparoscopy, Koch's test and to trial therapy.

  4. Abdominal Tuberculosis May Masquerade Many Diseases

    PubMed Central

    Sinhasan, Sankappa P.; Puranik, Rekha B.; Kulkarni, Mohan H.

    2011-01-01

    Background/Aim: Intestinal tuberculosis needs to be considered in the differential diagnosis when patients with intestinal pathology are encountered. Tuberculosis can mimic other disease entities like, ischemic enteritis, inflammatory bowel diseases, malignancies, intussusception etc., clinically as well as morphologically in resected intestinal specimens. We aimed to study the various clinical presentations leading to intestinal resection, with identification of different etiological factors by histopathological examination; and to illustrate, discuss and describe the various histopathological features of the lesions in these resected intestinal specimens with clinicopathological correlation. Materials and Methods: We studied 100 cases of resected intestinal specimens received during September 2002 to December 2003. We totally encountered 22 request forms with clinical suspicion of ileoceocal tuberculosis. Results: Abdominal tenderness and mass in ileoceocal region were noted in all cases. In many instances, the cases were operated for acute/subacute intestinal obstruction. Clinical and intra-operative diagnoses of tubercular enteritis, in many instances, were finally diagnosed histopathologically as ischemic enteritis (nine cases), chronic nonspecific enteritis (four cases), adenocarcinoma of the caecum, Crohn’s disease, intussusception (each one case), and correctly as intestinal tuberculosis in only six cases. Conclusion: Tuberculosis can mimic various disease entities, clinically and sometimes morphologically. Vice versa is also true. An increased awareness of intestinal tuberculosis coupled with varied clinical presentations, nonspecific signs and symptoms, difficulties in diagnostic methods and need of early and specific treatment should improve the outcome for patients with this disease. PMID:21372347

  5. Interferon-Gamma Improves Macrophages Function against M. tuberculosis in Multidrug-Resistant Tuberculosis Patients.

    PubMed

    Khan, Taj Ali; Mazhar, Humaira; Saleha, Shamim; Tipu, Hamid Nawaz; Muhammad, Niaz; Abbas, Muhammad Nasser

    2016-01-01

    Background. Mycobacterium tuberculosis (M. tuberculosis) that causes tuberculosis (TB) kills millions of infected people annually especially multidrug-resistant tuberculosis (MDR-TB). On infection, macrophages recognize the mycobacteria by toll-like receptor (TLR) followed by phagocytosis and control of mycobacteria. In addition, macrophages also secrete IL-12 to induce IFN-γ production by T, which, in turn, increases the phagocytosis and oxidative burst. Individuals with defects in innate or adaptive immunity exhibit increased susceptibility to M. tuberculosis. Understanding these immunologic mechanisms will help in TB control. We aimed to investigate the immunopathologic mechanisms in MDR-TB and role of recombinant human interferon-gamma (rhIFN-γ). Study Design and Methods. Monocyte-derived macrophages (MDMs) were generated from peripheral blood mononuclear cells of MDR-TB patients and healthy subjects and were investigated for immunologic response by ELISA and flow cytometry. Results. Different functional and molecular anomalies were observed in macrophages. In addition, a defective immune response to M. tuberculosis from the patient's MDMs was characterized, which in turn improved by pretreatment with rhIFN-γ. Conclusion. This work highlights the fact that rhIFN-γ improves macrophages function against M. tuberculosis and treatment of patients with poor responsiveness to TB therapy may be needed in future to include IFN-γ as adjuvant therapy after the full characterization of pathological and molecular mechanisms in these and in other more multidrug-resistant TB patients. PMID:27478636

  6. Interferon-Gamma Improves Macrophages Function against M. tuberculosis in Multidrug-Resistant Tuberculosis Patients

    PubMed Central

    Mazhar, Humaira; Muhammad, Niaz; Abbas, Muhammad Nasser

    2016-01-01

    Background. Mycobacterium tuberculosis (M. tuberculosis) that causes tuberculosis (TB) kills millions of infected people annually especially multidrug-resistant tuberculosis (MDR-TB). On infection, macrophages recognize the mycobacteria by toll-like receptor (TLR) followed by phagocytosis and control of mycobacteria. In addition, macrophages also secrete IL-12 to induce IFN-γ production by T, which, in turn, increases the phagocytosis and oxidative burst. Individuals with defects in innate or adaptive immunity exhibit increased susceptibility to M. tuberculosis. Understanding these immunologic mechanisms will help in TB control. We aimed to investigate the immunopathologic mechanisms in MDR-TB and role of recombinant human interferon-gamma (rhIFN-γ). Study Design and Methods. Monocyte-derived macrophages (MDMs) were generated from peripheral blood mononuclear cells of MDR-TB patients and healthy subjects and were investigated for immunologic response by ELISA and flow cytometry. Results. Different functional and molecular anomalies were observed in macrophages. In addition, a defective immune response to M. tuberculosis from the patient's MDMs was characterized, which in turn improved by pretreatment with rhIFN-γ. Conclusion. This work highlights the fact that rhIFN-γ improves macrophages function against M. tuberculosis and treatment of patients with poor responsiveness to TB therapy may be needed in future to include IFN-γ as adjuvant therapy after the full characterization of pathological and molecular mechanisms in these and in other more multidrug-resistant TB patients. PMID:27478636

  7. Multispacer Sequence Typing for Mycobacterium tuberculosis Genotyping

    PubMed Central

    Djelouadji, Zoheira; Arnold, Catherine; Gharbia, Saheer; Raoult, Didier; Drancourt, Michel

    2008-01-01

    Background Genotyping methods developed to survey the transmission dynamics of Mycobacterium tuberculosis currently rely on the interpretation of restriction and amplification profiles. Multispacer sequence typing (MST) genotyping is based on the sequencing of several intergenic regions selected after complete genome sequence analysis. It has been applied to various pathogens, but not to M. tuberculosis. Methods and Findings In M. tuberculosis, the MST approach yielded eight variable intergenic spacers which included four previously described variable number tandem repeat loci, one single nucleotide polymorphism locus and three newly evaluated spacers. Spacer sequence stability was evaluated by serial subculture. The eight spacers were sequenced in a collection of 101 M. tuberculosis strains from five phylogeographical lineages, and yielded 29 genetic events including 13 tandem repeat number variations (44.82%), 11 single nucleotide mutations (37.93%) and 5 deletions (17.24%). These 29 genetic events yielded 32 spacer alleles or spacer-types (ST) with an index of discrimination of 0.95. The distribution of M. tuberculosis isolates into ST profiles correlated with their assignment into phylogeographical lineages. Blind comparison of a further 93 M. tuberculosis strains by MST and restriction fragment length polymorphism-IS6110 fingerprinting and mycobacterial interspersed repetitive units typing, yielded an index of discrimination of 0.961 and 0.992, respectively. MST yielded 41 different profiles delineating 16 related groups and proved to be more discriminatory than IS6110-based typing for isolates containing <8 IS6110 copies (P<0.0003). MST was successfully applied to 7/10 clinical specimens exhibiting a Cts ≤ 42 cycles in internal transcribed spacer-real time PCR. Conclusions These results support MST as an alternative, sequencing-based method for genotyping low IS6110 copy-number M. tuberculosis strains. The M. tuberculosis MST database is freely available

  8. Tuberculosis as an Etiological Factor in Liver Abscess in Adults

    PubMed Central

    Dey, Jaideep; Venugopal, Shwetha; Mirdha, Bijay Ranjan

    2016-01-01

    Background. Tuberculosis of the liver without active pulmonary or miliary tuberculosis is considered as an uncommon diagnosis. The aim of the present study was to determine the etiological role of tuberculosis in adult patients presenting with features of liver abscess. Methods. A total of 40 patients with liver abscess were included in the study. The liver abscess aspirate was subjected to microscopy, culture, and polymerase chain reaction to determine the role of tuberculosis as an etiological factor in liver abscess. Results. Of the 40 patients enrolled, 25% (10/40) were diagnosed with having tubercular liver abscess. In a total of 40 specimens, 2.5% (1/40) were positive for acid fast bacilli by Ziehl-Neelsen method, while 10% (4/40) were positive for M. tuberculosis by culture using BACTEC 460 and the yield increased to 25% (10/40) by polymerase chain reaction for M. tuberculosis. Conclusion. 25% of the patients presenting with liver abscess had tubercular etiology without features of active pulmonary or miliary tuberculosis. Liver can act as the primary site of involvement in the absence of activity elsewhere in the body. Tuberculosis should be considered as an important differential diagnosis of liver abscess irrespective of evidence of active tuberculosis elsewhere in the body. PMID:27595021

  9. Tuberculosis as an Etiological Factor in Liver Abscess in Adults.

    PubMed

    Dey, Jaideep; Gautam, Hitender; Venugopal, Shwetha; Porwal, Chhavi; Mirdha, Bijay Ranjan; Gupta, Naresh; Singh, Urvashi B

    2016-01-01

    Background. Tuberculosis of the liver without active pulmonary or miliary tuberculosis is considered as an uncommon diagnosis. The aim of the present study was to determine the etiological role of tuberculosis in adult patients presenting with features of liver abscess. Methods. A total of 40 patients with liver abscess were included in the study. The liver abscess aspirate was subjected to microscopy, culture, and polymerase chain reaction to determine the role of tuberculosis as an etiological factor in liver abscess. Results. Of the 40 patients enrolled, 25% (10/40) were diagnosed with having tubercular liver abscess. In a total of 40 specimens, 2.5% (1/40) were positive for acid fast bacilli by Ziehl-Neelsen method, while 10% (4/40) were positive for M. tuberculosis by culture using BACTEC 460 and the yield increased to 25% (10/40) by polymerase chain reaction for M. tuberculosis. Conclusion. 25% of the patients presenting with liver abscess had tubercular etiology without features of active pulmonary or miliary tuberculosis. Liver can act as the primary site of involvement in the absence of activity elsewhere in the body. Tuberculosis should be considered as an important differential diagnosis of liver abscess irrespective of evidence of active tuberculosis elsewhere in the body. PMID:27595021

  10. Natural History of Tuberculosis: Duration and Fatality of Untreated Pulmonary Tuberculosis in HIV Negative Patients: A Systematic Review

    PubMed Central

    Tiemersma, Edine W.; van der Werf, Marieke J.; Borgdorff, Martien W.; Williams, Brian G.; Nagelkerke, Nico J. D.

    2011-01-01

    Background The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. Methodology and Principal Findings To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Conclusions Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory. PMID:21483732

  11. Tuberculosis in the lung (image)

    MedlinePlus

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

  12. Tuberculosis Facts - Testing for TB

    MedlinePlus

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

  13. Tuberculosis Facts - Exposure to TB

    MedlinePlus

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

  14. Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel.

    PubMed

    Gupta, Amita; Mathad, Jyoti S; Abdel-Rahman, Susan M; Albano, Jessica D; Botgros, Radu; Brown, Vikki; Browning, Renee S; Dawson, Liza; Dooley, Kelly E; Gnanashanmugam, Devasena; Grinsztejn, Beatriz; Hernandez-Diaz, Sonia; Jean-Philippe, Patrick; Kim, Peter; Lyerly, Anne D; Mirochnick, Mark; Mofenson, Lynne M; Montepiedra, Grace; Piper, Jeanna; Sahin, Leyla; Savic, Radojka; Smith, Betsy; Spiegel, Hans; Swaminathan, Soumya; Watts, D Heather; White, Amina

    2016-03-15

    Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population. PMID:26658057

  15. [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.

  16. Assessment of linezolid efficacy, safety and tolerability in the treatment of tuberculosis: A retrospective case review.

    PubMed

    Tse-Chang, Alena; Kunimoto, Dennis; Der, Evelina; Ahmed, Rabia

    2013-01-01

    Linezolid is a potentially effective drug for the treatment of patients with drug-resistant tuberculosis. Among 13 patients treated for tuberculosis with linezolid in the present study, nine had treatment success and four remain on treatment. Adverse effects occurred in 11 (85%) patients, of whom three discontinued treatment because of adverse effects. The present study adds to the growing evidence supporting the efficacy of linezolid for tuberculosis, although treatment remains complicated by adverse effects.

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

    PubMed Central

    2012-01-01

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

  18. [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

  19. High Tuberculosis Prevalence in a South African Prison: The Need for Routine Tuberculosis Screening

    PubMed Central

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

    2014-01-01

    Background Tuberculosis is a major health concern in prisons, particularly where HIV prevalence is high. Our objective was to determine the undiagnosed pulmonary tuberculosis (“undiagnosed tuberculosis”) prevalence in a representative sample of prisoners in a South African prison. In addition we investigated risk factors for undiagnosed tuberculosis, to explore if screening strategies could be targeted to high risk groups, and, the performance of screening tools for tuberculosis. Methods and Findings In this cross-sectional survey, male prisoners were screened for tuberculosis using symptoms, chest radiograph (CXR) and two spot sputum specimens for microscopy and culture. Anonymised HIV antibody testing was performed on urine specimens. The sensitivity, specificity and predictive values of symptoms and investigations were calculated, using Mycobacterium tuberculosis isolated on sputum culture as the gold standard. From September 2009 to October 2010, 1046 male prisoners were offered enrolment to the study. A total of 981 (93.8%) consented (median age was 32 years; interquartile range [IQR] 27–37 years) and were screened for tuberculosis. Among 968 not taking tuberculosis treatment and with sputum culture results, 34 (3.5%; 95% confidence interval [CI] 2.4–4.9%) were culture positive for Mycobacterium tuberculosis. HIV prevalence was 25.3% (242/957; 95% CI 22.6–28.2%). Positive HIV status (adjusted odds ratio [aOR] 2.0; 95% CI 1.0–4.2) and being an ex-smoker (aOR 2.6; 95% CI 1.2–5.9) were independently associated with undiagnosed tuberculosis. Compared to the gold standard of positive sputum culture, cough of any duration had a sensitivity of 35.3% and specificity of 79.6%. CXR was the most sensitive single screening modality (sensitivity 70.6%, specificity 92.2%). Adding CXR to cough of any duration gave a tool with sensitivity of 79.4% and specificity of 73.8%. Conclusions Undiagnosed tuberculosis and HIV prevalence was high in this prison

  20. 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

  1. Isolated Optic Disc Tuberculosis

    PubMed Central

    Mansour, Ahmad M.; Tabbara, Khalid F.; Tabbarah, Zuhair

    2015-01-01

    We present a healthy male subject who developed progressive visual loss in the left eye initially diagnosed as optic neuritis. Upon suspicion of infectious etiology, testing was positive for tuberculosis. There were no signs or symptoms of active systemic tuberculosis infection. The patient responded swiftly to antimycobacterial therapy with return of vision and resolution of disc swelling. Positive purified protein derivative skin test, negative chest radiograph, negative systemic workup, negative workup for other causes of unilateral optic neuritis and quick response to mycobacterial therapy reaffirm the entity of isolated optic disc tuberculosis similar to isolated choroidal tuberculosis without systemic manifestation. PMID:26483675

  2. Autophagy in Tuberculosis

    PubMed Central

    Deretic, Vojo

    2014-01-01

    Autophagy as an immune mechanism controls inflammation and acts as a cell-autonomous defense against intracellular microbes including Mycobacterium tuberculosis. An equally significant role of autophagy is its anti-inflammatory and tissue-sparing function. This combination of antimicrobial and anti-inflammatory actions prevents active disease in animal models. In human populations, genetic links between autophagy, inflammatory bowel disease, and susceptibility to tuberculosis provide further support to these combined roles of autophagy. The autophagic control of M. tuberculosis and prevention of progressive disease provide novel insights into physiological and immune control of tuberculosis. It also offers host-based therapeutic opportunities because autophagy can be pharmacologically modulated. PMID:25167980

  3. The Socioeconomic Factors and the Indigenous Component of Tuberculosis in Amazonas

    PubMed Central

    2016-01-01

    Despite the availability of tuberculosis prevention and control services throughout Amazonas, high rates of morbidity and mortality from tuberculosis remain in the region. Knowledge of the social determinants of tuberculosis in Amazonas is important for the establishment of public policies and the planning of effective preventive and control measures for the disease. To analyze the relationship of the spatial distribution of the incidence of tuberculosis in municipalities and regions of Amazonas to the socioeconomic factors and indigenous tuberculosis component, from 2007 to 2013. An ecological study was conducted based on secondary data from the epidemiological surveillance of tuberculosis. A linear regression model was used to analyze the relationship of the annual incidence of tuberculosis to the socioeconomic factors, performance indicators of health services, and indigenous tuberculosis component. The distribution of the incidence of tuberculosis in the municipalities of Amazonas was positively associated with the Gini index and the population attributable fraction of tuberculosis in the indigenous peoples, but negatively associated with the proportion of the poor and the unemployment rate. The spatial distribution of tuberculosis in the different regions of Amazonas was heterogeneous and closely related with the socioeconomic factors and indigenous component of tuberculosis. PMID:27362428

  4. The Socioeconomic Factors and the Indigenous Component of Tuberculosis in Amazonas.

    PubMed

    Castro, Daniel Barros de; Pinto, Rosemary Costa; Albuquerque, Bernardino Cláudio de; Sadahiro, Megumi; Braga, José Ueleres

    2016-01-01

    Despite the availability of tuberculosis prevention and control services throughout Amazonas, high rates of morbidity and mortality from tuberculosis remain in the region. Knowledge of the social determinants of tuberculosis in Amazonas is important for the establishment of public policies and the planning of effective preventive and control measures for the disease. To analyze the relationship of the spatial distribution of the incidence of tuberculosis in municipalities and regions of Amazonas to the socioeconomic factors and indigenous tuberculosis component, from 2007 to 2013. An ecological study was conducted based on secondary data from the epidemiological surveillance of tuberculosis. A linear regression model was used to analyze the relationship of the annual incidence of tuberculosis to the socioeconomic factors, performance indicators of health services, and indigenous tuberculosis component. The distribution of the incidence of tuberculosis in the municipalities of Amazonas was positively associated with the Gini index and the population attributable fraction of tuberculosis in the indigenous peoples, but negatively associated with the proportion of the poor and the unemployment rate. The spatial distribution of tuberculosis in the different regions of Amazonas was heterogeneous and closely related with the socioeconomic factors and indigenous component of tuberculosis. PMID:27362428

  5. Prevalence and annual risk of tuberculosis infection in Edirne, Turkey.

    PubMed

    Yorulmaz, F; Cağlar, T; Erel, C; Ozaydin, M

    2002-01-01

    Tuberculosis is still an important problem in developing countries. A total of 3,774 students from primary schools in Edirne, Turkey were included in this study in order to determine the annual infection risk for the year 1994. Five tuberculin units of purified protein derivative were applied using a Mantoux test and evaluated. The mean induration diameter was 14.6 mm. A total of 51.6% of the students were found to be sensitive to tuberculin. The annual infection risk of tuberculosis was found to be 1.51%, lower than that found in 1987. Other studies from Turkey have reported lower values than ours. We did not diagnose any cases of tuberculosis. We revealed that the annual infection risk among primary schoolchildren in Edirne is close to the average for Turkey and thus tuberculosis is still a serious risk for these children. Tuberculosis remains an important public health problem in Turkey and is partially attributable to socioeconomic difficulties.

  6. Community Coauthoring: Whose Voice Remains?

    ERIC Educational Resources Information Center

    Larson, Joanne; Webster, Stephanie; Hopper, Mindy

    2011-01-01

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

  7. Content and Access Remain Key

    ERIC Educational Resources Information Center

    Johnson, Linda B.

    2007-01-01

    It is impossible to review the year's outstanding government publication landscape without acknowledging that change remains paramount. Just as striking, however, is that these changes go hand in hand with some familiar constants. Within this shifting environment, there are the consistency and dependability of government information itself,…

  8. 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

  9. Craniocervical junction tuberculosis: Usual pathology at an unusual site

    PubMed Central

    Nayak, Biswaranjan; Patnaik, Sanjeev; Sahoo, Prafulla Kumar; Biswal, Debabrata

    2015-01-01

    Background: Tuberculosis (TB) of the craniocervical junction is rare even where the condition is endemic. It poses problems in both diagnosis and management if not managed in time it may cause life-threatening complications. Case Description: An 18-year-old male patient presented with pain in the nape of the neck since 12 months duration which was not improving with medication. After magnetic resonance imaging of cervical spine, he was diagnosed as craniocervical junction TB. We did a transoral decompression of abscess with biopsy along with posterior decompression of cord and occipitocervical fusion. Biopsy of pathological material came as TB. He was advised for anti-tubercular therapy for 18 months. Conclusion: Although craniocervical junction TB is a rare disease, the outcome of treatment is good. Antituberculous drug therapy remains the mainstay of treatment after confirming the diagnosis. The surgical management options include transoral decompression with or without posterior fusion, depending upon the presence and persistence of atlantoaxial instability. PMID:26229730

  10. Paleopathology of human tuberculosis and the potential role of climate.

    PubMed

    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

  11. 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

  12. Immunological aspects of pulmonary tuberculosis in children.

    PubMed

    Lagrange, P H; Wargnier, A

    1995-01-01

    In recent years new information has been collected about the immunological responses to pathogenic mycobacteria. More information on cellular and molecular responses of cells in murine and human tuberculosis has been produced and T cells' role in the production of selected cytokines has been clarified. Studies in mice have provided insight into the phases of the T cell response to virulent M. tuberculosis, the role of various T cell subsets, and the repertoire of antigens recognized by these cells. However, despite this new information, some of which has been confirmed in humans, large gaps remain in our knowledge about the immune response to this infection, particularly concerning cellular or molecular mechanisms involved in acquired protection. Even if some extrapolations from adult data can be made, large gaps in our knowledge exist on the potential immune defects in young infants who are prone to develop tuberculosis soon after infection.

  13. 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

  14. [Spinal tuberculosis or bone metastases? Case report].

    PubMed

    Dima-Cozma, Corina; Mitu, F; Rezuş, Elena; Arhire, Oana; Petcu, I; Grigoraş, C; Banu, Claudia; Cozma, S

    2010-01-01

    Tuberculosis remains one of the most important infectious disease worldwide and skeletal form has an incidence between 3% and 10%, depending on geographic area. The thoracolumbar junction is the most commonly involved in vertebral tuberculosis; some radiologic features are specifics, but other could be indistinguishable from that of lymphoma or metastases. We discuss the case of a 80-year-old man presented with a 2-month history of thoracolumbar pain, fatigability and fever. The vertebral radiography showed narrowing of the intervertebral disc space between T1 and T12, adjacent irregularity, erosion and lisis of vertebres, features visibles also on computed tomography. After the exclusion of the other causes of osteolisis, we started a standard regimen of tuberculostatic treatment and after one month of treatment the symptoms of patient improved noticeably. Other problems of diagnostic and treatment modalities of spinal tuberculosis are discussed. PMID:20509287

  15. Clinical value of the measurement of Mycobacterium tuberculosis specific antibody in pulmonary tuberculosis.

    PubMed Central

    Bothamley, G H; Rudd, R; Festenstein, F; Ivanyi, J

    1992-01-01

    BACKGROUND: A serological test that could help to diagnose tuberculosis, especially smear negative disease, would contribute to patient management. METHODS: Levels of antibody to distinct antigens of Mycobacterium tuberculosis were assessed for their value in the diagnosis and management of pulmonary tuberculosis. Serum was taken from 52 patients who were smear positive, from 27 patients who were smear negative but with evidence of active tuberculosis (sputum culture positive in 16, response to antituberculosis chemotherapy in 11), from 11 patients with old healed tuberculosis (pre-antibiotic era), and from 39 healthy subjects vaccinated with BCG. RESULTS: In smear positive tuberculosis an enzyme linked immunosorbent assay using a single 38 kDa antigen gave a diagnostic sensitivity of 80% with a 100% specificity. In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95%. Recurrent and extensive radiographic disease with a poor prognosis was associated with high anti-38 kDa and low anti-14 kDa antibody levels in patients with active disease. Patients with less pulmonary cavitation had high anti-19 kDa titres. Bacteriological relapse during treatment was indicated by a rise in anti-14 kDa (TB68 epitope) antibodies. Four patients with non-tuberculous mycobacterial infection showed no anti-38 kDa antibody. CONCLUSION: Antigen or epitope specific serology may help in the diagnosis, assessment of prognosis, and monitoring of chemotherapy in patients with pulmonary tuberculosis. PMID:1585290

  16. [Multifocal tuberculosis in immunocompetent patients].

    PubMed

    Rezgui, Amel; Fredj, Fatma Ben; Mzabi, Anis; Karmani, Monia; Laouani, Chadia

    2016-01-01

    Multifocal tuberculosis is defined as the presence of lesions affecting at least two extrapulmonary sites, with or without pulmonary involvement. This retrospective study of 10 cases aims to investigate the clinical and evolutionary characteristics of multifocal tuberculosis. It included 41 cases with tuberculosis collected between 1999 and 2013. Ten patients had multifocal tuberculosis (24%): 9 women and 1 man, the average age was 50 years (30-68 years). Our patients were correctly BCG vaccinated. The evaluation of immunodepression was negative in all patients. 7 cases had lymph node tuberculosis, 3 cases digestive tuberculosis, 2 cases pericardial tuberculosis, 2 cases osteoarticular tuberculosis, 1 case brain tuberculosis, 2 cases urinary tuberculosis, 4 cases urogenital tuberculosis, 1 case adrenal tuberculosis, 1 case cutaneous and 1 case muscle tuberculosis. All patients received anti-tuberculosis treatment for a mean duration of 10 months, with good evolution. Multifocal tuberculosis is difficult to diagnose. It can affect immunocompetent patients but often has good prognosis. Anti-tuberculosis therapy must be initiated as soon as possible to avoid sequelae. PMID:27583077

  17. Combating Tuberculosis Infection: A Forbidding Challenge

    PubMed Central

    Rawal, Tejal; Butani, Shital

    2016-01-01

    After 50 years drought, several drugs are looming from the pipeline to combat tuberculosis. They will serve as a boon to the field that has been burdened with primitive, inadequate treatments and drug-resistant bacterial strains. From the decades, due to lack of interest and resources, the field has suffered a lot. Learning from the flaws, scientists have renovated their approaches to the finding of new antitubercular drugs. The first line drugs take about six months or more for the entire treatment. The second line remedy for resistant-tuberculosis requires daily injections which carry severe side effects. Drug resistance remains a constant menace because patients stop the medication once they start feeling better. So new drugs are required to be explored which are effective against tuberculosis especially drug resistant tuberculosis. These drugs need to work well with other drugs as well as with antivirals used for the treatment of human immunodeficiency virus. It is also very important to be considered that the treatments need to be cheap, as tuberculosis primarily affects people more in the developing countries. Further, new drugs must cure the disease in short span of time than the current six to nine month regimen. Recently a few new and potent drugs such as bedaquiline, delamanid, teixobactin have been evolved which may serve as a nice step forward, with a better outcome. Teixobactin, a new antibiotic has been found to have promising action against resistant strains, is also under consideration. PMID:27168676

  18. Pyrimidine salvage pathway in Mycobacterium tuberculosis.

    PubMed

    Villela, A D; Sánchez-Quitian, Z A; Ducati, R G; Santos, D S; Basso, L A

    2011-01-01

    The causative agent of tuberculosis (TB), Mycobacterium tuberculosis, infects one-third of the world population. TB remains the leading cause of mortality due to a single bacterial pathogen. The worldwide increase in incidence of M. tuberculosis has been attributed to the high proliferation rates of multi and extensively drug-resistant strains, and to co-infection with the human immunodeficiency virus. There is thus a continuous requirement for studies on mycobacterial metabolism to identify promising targets for the development of new agents to combat TB. Singular characteristics of this pathogen, such as functional and structural features of enzymes involved in fundamental metabolic pathways, can be evaluated to identify possible targets for drug development. Enzymes involved in the pyrimidine salvage pathway might be attractive targets for rational drug design against TB, since this pathway is vital for all bacterial cells, and is composed of enzymes considerably different from those present in humans. Moreover, the enzymes of the pyrimidine salvage pathway might have an important role in the mycobacterial latent state, since M. tuberculosis has to recycle bases and/or nucleosides to survive in the hostile environment imposed by the host. The present review describes the enzymes of M. tuberculosis pyrimidine salvage pathway as attractive targets for the development of new antimycobacterial agents. Enzyme functional and structural data have been included to provide a broader knowledge on which to base the search for compounds with selective biological activity.

  19. "Tuberculosis Case Management" Training.

    ERIC Educational Resources Information Center

    Knebel, Elisa; Kolodner, Jennifer

    2001-01-01

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

  20. Tuberculosis in Somalia.

    PubMed

    Turpie, I D

    2008-05-01

    This is a description of a tuberculosis treatment programme in a country at war where security and the absence of order pose problems to health care delivery. It is also a description of an epidemic of tuberculosis where treatment and diagnosis are difficult and the methods used have changed little in many years. More international pressure is needed.

  1. Pulmonary Paragonimiasis Mimicking Tuberculosis.

    PubMed

    Prasad, Kj; Basu, Arup; Khana, Shilpi; Wattal, Chand

    2015-08-01

    Paragonimiasis is a disease which is frequently misdiagnosed as pulmonary tuberculosis. In the areas where people eat crab/crayfish this disease should be considered in the differential diagnosis to avoid antituberculosis treatment for a non-tubercular condition. We are reporting a case of pulmonary paragonimiasis who had been treated for tuberculosis. PMID:27604443

  2. Seasonality of Tuberculosis

    PubMed Central

    Fares, Auda

    2011-01-01

    Objectives: This study was designed to review previous studies and analyse the current knowledge and controversies related to seasonal variability of tuberculosis (TB) to examine whether TB has an annual seasonal pattern. Study Design and Methods: Systematic review of peer reviewed studies identified through literature searches using online databases belonging to PubMed and the Cochrane library with key words “Tuberculosis, Seasonal influence” and “Tuberculosis, Seasonal variation”. The search was restricted to articles published in English. The references of the identified papers for further relevant publications were also reviewed. Results: Twelve studies conducted between the period 1971 and 2006 from 11 countries/regions around the world (South Western Cameroon, South Africa, India, Hong Kong, Japan, Kuwait, Spain, UK, Ireland, Russia, and Mongolia) were reviewed. A seasonal pattern of tuberculosis with a mostly predominant peak is seen during the spring and summer seasons in all of the countries (except South Western Cameroon and Russia). Conclusions: The observation of seasonality leads to assume that the risk of transmission of M. tuberculosis does appear to be the greatest during winter months. Vitamin D level variability, indoor activities, seasonal change in immune function, and delays in the diagnosis and treatment of tuberculosis are potential stimuli of seasonal tuberculosis disease. Additionally, seasonal variation in food availability and food intake, age, and sex are important factors which can play a role in the tuberculosis notification variability. Prospective studies regarding this topic and other related subjects are highly recommended. PMID:21572609

  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: a re-emerging problem for health care workers.

    PubMed

    Bagg, J

    1996-05-25

    The current upward trend in the incidence of tuberculosis, particularly in the USA, and the problems of treating multiply drug resistant strains of Mycobacterium tuberculosis have caused a resurgence of interest in this infection. This review describes the microbiology, routes of transmission and epidemiology of Mycobacterium tuberculosis infections. The emergence and problems of treating multiply drug resistant strains are outlined. The significant potential for occupationally acquired infection among health care workers is discussed, together with a summary of the available infection control measures currently being examined. The true level of occupational risk to dental personnel remains uncertain.

  5. 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

  6. The examination of skeletal remains.

    PubMed

    Knight, B

    1985-01-01

    In summary, unless the more sophisticated methods listed in the references are repeated and more success obtained with a series of bone samples of known date, no physico-chemical or morphological techniques have yet been devised that will determine date independently of environmental deterioration. The only exception is the radiocarbon estimation in bones of greater antiquity than those of medico-legal interest. The best mentor in the examination of skeletal remains is experience. Unfortunately, the majority of samples brought to the medical examiner remain of unknown provenance, and this prevents the doctor from checking his expertise against the true facts of identity and dating. The main point to bear in mind is that the tendency toward overinterpretation and dogmatic opinion should be avoided where the available data do not merit such a degree of certainty. There is no advantage in offering unfounded opinions to the investigators, since this might merely mislead them and perhaps cause them to exclude a class of possible identities because the doctor has unwisely told them to look only within a certain bracket of date and identifiable factors. As in any branch of forensic medicine, it is dangerous to speculate where the facts cannot firmly support the opinion.

  7. Procalcitonin as a Diagnostic and Prognostic Factor for Tuberculosis Meningitis

    PubMed Central

    Kim, Jinseung; Kim, Si Eun; Park, Bong Soo; Shin, Kyong Jin; Ha, Sam Yeol; Park, JinSe; Kim, Sung Eun

    2016-01-01

    Background and Purpose We investigated the potential role of serum procalcitonin in differentiating tuberculosis meningitis from bacterial and viral meningitis, and in predicting the prognosis of tuberculosis meningitis. Methods This was a retrospective study of 26 patients with tuberculosis meningitis. In addition, 70 patients with bacterial meningitis and 49 patients with viral meningitis were included as the disease control groups for comparison. The serum procalcitonin level was measured in all patients at admission. Differences in demographic and laboratory data, including the procalcitonin level, were analyzed among the three groups. In addition, we analyzed the predictive factors for a prognosis of tuberculosis meningitis using the Glasgow Coma Scale (GCS) at discharge, and the correlation between the level of procalcitonin and the GCS score at discharge. Results Multiple logistic regression analysis showed that a low level of procalcitonin (≤1.27 ng/mL) independently distinguished tuberculosis meningitis from bacterial meningitis. The sensitivity and specificity for distinguishing tuberculosis meningitis from bacterial meningitis were 96.2% and 62.9%, respectively. However, the level of procalcitonin in patients with tuberculosis meningitis did not differ significantly from that in patients with viral meningitis. In patients with tuberculosis meningitis, a high level of procalcitonin (>0.4 ng/mL) was a predictor of a poor prognosis, and the level of procalcitonin was negatively correlated with the GCS score at discharge (r=-0.437, p=0.026). Conclusions We found that serum procalcitonin is a useful marker for differentiating tuberculosis meningitis from bacterial meningitis and is also valuable for predicting the prognosis of tuberculosis meningitis. PMID:27165424

  8. Tuberculosis in complex emergencies.

    PubMed

    Coninx, Rudi

    2007-08-01

    This paper describes the key factors and remaining challenges for tuberculosis (TB) control programmes in complex emergencies. A complex emergency is "a humanitarian crisis in a country, region or society where there is total or considerable breakdown of authority resulting from internal or external conflict and which requires an international response that goes beyond the mandate or capacity of any single agency and/or the ongoing United Nations country programme." Some 200 million people are believed to live in countries affected by complex emergencies; almost all of these are developing countries that also bear the main burden of TB. The effects of complex emergencies impact on TB control programmes, interfering with the goals of identifying and curing TB patients and possibly leading to the emergence of MDR-TB. There are many detailed descriptions of aid interventions during complex emergencies; yet TB control programmes are absent from most of these reports. If TB is neglected, it may quickly result in increased morbidity and mortality, as was demonstrated in Bosnia and Herzegovina and in Somalia. TB is a major disease in complex emergencies and requires an appropriate public health response. While there is no manual to cover complex emergencies, the interagency manual for TB control in refugee and displaced populations provides valuable guidance. These programmes contribute to the body of evidence needed to compile such a manual, and should ensure that the experiences of TB control in complex emergencies lead to the establishment of evidence-based programmes. PMID:17768523

  9. 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

  10. Optimization of recombinant Mycobacterium tuberculosis RNA polymerase expression and purification.

    PubMed

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

    2014-07-01

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

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

    SciTech Connect

    Engels, E.A.; Shen, M.; Chapman, R.S.; Pfeiffer, R.M.; Yu, Y.Y.; He, X.Z.; Lan, Q.

    2009-03-15

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

  12. A tuberculosis nationwide prevalence survey in Gambia, 2012

    PubMed Central

    Kendall, Lindsay; Bashorun, Adedapo; Linda, Christopher; Omoleke, Semeeh; Jeffries, David; Maane, Rahmatulai; Alorse, Beatrice Dei; Alorse, William Dei; Okoi, Catherine Bi; Mlaga, Kodjovi D; Kinteh, Ma Ansu; Donkor, Simon; de Jong, Bouke C; Antonio, Martin; d’Alessandro, Umberto

    2016-01-01

    Abstract Objective To estimate the population prevalence of active pulmonary tuberculosis in Gambia. Methods Between December 2011 and January 2013, people aged ≥ 15 years participating in a nationwide, multistage cluster survey were screened for active pulmonary tuberculosis with chest radiography and for tuberculosis symptoms. For diagnostic confirmation, sputum samples were collected from those whose screening were positive and subjected to fluorescence microscopy and liquid tuberculosis cultures. Multiple imputation and inverse probability weighting were used to estimate tuberculosis prevalence. Findings Of 100 678 people enumerated, 55 832 were eligible to participate and 43 100 (77.2%) of those participated. A majority of participants (42 942; 99.6%) were successfully screened for symptoms and by chest X-ray. Only 5948 (13.8%) were eligible for sputum examination, yielding 43 bacteriologically confirmed, 28 definite smear-positive and six probable smear-positive tuberculosis cases. Chest X-ray identified more tuberculosis cases (58/69) than did symptoms alone (43/71). The estimated prevalence of smear-positive and bacteriologically confirmed pulmonary tuberculosis were 90 (95% confidence interval, CI: 53–127) and 212 (95% CI: 152–272) per 100 000 population, respectively. Tuberculosis prevalence was higher in males (333; 95% CI: 233–433) and in the 35–54 year age group (355; 95% CI: 219–490). Conclusion The burden of tuberculosis remains high in Gambia but lower than earlier estimates of 490 per 100 000 population in 2010. Less than half of all cases would have been identified based on smear microscopy results alone. Successful control efforts will require interventions targeting men, increased access to radiography and more accurate, rapid diagnostic tests. PMID:27274595

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

    PubMed Central

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

    2014-01-01

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

  14. Tuberculosis epidemiology and selection in an autochthonous Siberian population from the 16th-19th century.

    PubMed

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

    2014-01-01

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

  15. New tuberculosis diagnostics and rollout.

    PubMed

    McNerney, Ruth; Cunningham, Jane; Hepple, Pamela; Zumla, Alimuddin

    2015-03-01

    Early detection and effective treatment are crucial for tuberculosis control, but global case detection rates remain low. The diagnosis of paediatric and extrapulmonary disease is problematic and there are, as yet, no rapid screening tests to assist active case finding in the community. Progress has been made in clinic-based detection tools with the introduction of Xpert MTB/RIF, a nucleic acid amplification test that combines sample processing and analysis in a single instrument to provide a diagnostic result and detection of resistance to rifampicin in under 2h. Enthusiasm for Xpert MTB/RIF has been high and global rollout has been facilitated by donor agencies. However, concerns remain about access and sustainability due to the high cost and infrastructure requirements. Although more sensitive than smear microscopy, early studies suggest the impact of the new test on case detection rates and patient survival has been limited. Alternative technologies are being developed, including non-sputum-based tests to assist the detection of extrapulmonary disease. Evaluation studies are needed to provide evidence of the impact of the new technologies on patient outcomes. This will enable appropriate placement of new diagnostic products in the healthcare system to support the control and eventual eradication of tuberculosis disease.

  16. [Treatment of tuberculosis].

    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.

  17. Hyperferritinemia in pulmonary tuberculosis.

    PubMed

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

    2013-07-01

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

  18. Treatment of Tuberculosis. A Historical Perspective.

    PubMed

    Murray, John F; Schraufnagel, Dean E; Hopewell, Philip C

    2015-12-01

    Of all achievements in medicine, the successful treatment of tuberculosis has had one of the greatest impacts on society. Tuberculosis was a leading cause of disease and a mortal enemy of humanity for millennia. The first step in finding a cure was the discovery of the cause of tuberculosis by Robert Koch in 1882. The sanatorium movement that began shortly afterward in Europe, and soon spread to the United States, brought attention to the plight of afflicted persons, and catalyzed public health action. The antituberculosis benefit of streptomycin was announced in 1945, although application was limited by the rapid development of resistance. para-Aminosalicylic acid, also discovered in 1945, when combined with streptomycin was found to greatly reduce the occurrence of drug resistance. In 1952, isoniazid opened the modern era of treatment; it was inexpensive, well tolerated, and safe. In the early 1960s, ethambutol was shown to be effective and better tolerated than para-aminosalicylic acid, which it replaced. In the 1970s, rifampin found its place as a keystone in the therapy of tuberculosis. The use of rifampin enabled the course of treatment to be reduced to nine months. Incorporation of pyrazinamide into the first-line regimen led to a further reduction of treatment duration to six months. Treatment of multiple drug-resistant tuberculosis remains a difficult problem requiring lengthy treatment with toxic drugs. However, shortened regimens show promise, and two new drugs, bedaquiline and delamanid, have demonstrated effectiveness in preliminary studies and are being used for extensively drug-resistant tuberculosis.

  19. Stigma against Tuberculosis Patients in Addis Ababa, Ethiopia

    PubMed Central

    Tadesse, Sebsibe

    2016-01-01

    Background Stigma attached to tuberculosis contributes to the limited effectiveness of current TB control approaches. However, there is a dearth of studies that explore the causes of stigma attached to tuberculosis and its effects on patients and tuberculosiscontrol programs in Ethiopia. Methods An institution-based qualitative study was conducted at St. Peter Tuberculosis Specialized Hospital in Addis Ababa, Ethiopia from July to August, 2015. Ten in-depth interviews and 6 key-informant interviews were carried out among tuberculosis patients and healthcare workers, respectively.The Open Code computer software package was used to analyze the data thematically. Results The study revealed that fear of infection and inappropriate health education messages by media were the main causes of tuberculosis stigma. The patients experienced isolation within their family and community, separation, and financial crisis. The stigma attached to tuberculosis may contribute to delayed healthcare seeking, poor treatment adherence, and poor prognosis. Conclusion Interventions thatreduce the stigma attached to tuberculosis should target on areas, such as creating community awareness, patient counseling on problem-solving and emotional skills, preparing culturally sensitive and scientifically sound media messages, providing financial support for the patients, and enhancing the qualities of the healthcare workers, such as empathy, concern, respect for the patient and cultural sensitivity. PMID:27054714

  20. Smoking increases the risk of relapse after successful tuberculosis treatment

    PubMed Central

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

    2008-01-01

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

  1. Silicon photonics: some remaining challenges

    NASA Astrophysics Data System (ADS)

    Reed, G. T.; Topley, R.; Khokhar, A. Z.; Thompson, D. J.; Stanković, S.; Reynolds, S.; Chen, X.; Soper, N.; Mitchell, C. J.; Hu, Y.; Shen, L.; Martinez-Jimenez, G.; Healy, N.; Mailis, S.; Peacock, A. C.; Nedeljkovic, M.; Gardes, F. Y.; Soler Penades, J.; Alonso-Ramos, C.; Ortega-Monux, A.; Wanguemert-Perez, G.; Molina-Fernandez, I.; Cheben, P.; Mashanovich, G. Z.

    2016-03-01

    This paper discusses some of the remaining challenges for silicon photonics, and how we at Southampton University have approached some of them. Despite phenomenal advances in the field of Silicon Photonics, there are a number of areas that still require development. For short to medium reach applications, there is a need to improve the power consumption of photonic circuits such that inter-chip, and perhaps intra-chip applications are viable. This means that yet smaller devices are required as well as thermally stable devices, and multiple wavelength channels. In turn this demands smaller, more efficient modulators, athermal circuits, and improved wavelength division multiplexers. The debate continues as to whether on-chip lasers are necessary for all applications, but an efficient low cost laser would benefit many applications. Multi-layer photonics offers the possibility of increasing the complexity and effectiveness of a given area of chip real estate, but it is a demanding challenge. Low cost packaging (in particular, passive alignment of fibre to waveguide), and effective wafer scale testing strategies, are also essential for mass market applications. Whilst solutions to these challenges would enhance most applications, a derivative technology is emerging, that of Mid Infra-Red (MIR) silicon photonics. This field will build on existing developments, but will require key enhancements to facilitate functionality at longer wavelengths. In common with mainstream silicon photonics, significant developments have been made, but there is still much left to do. Here we summarise some of our recent work towards wafer scale testing, passive alignment, multiplexing, and MIR silicon photonics technology.

  2. Evolution of Mycobacterium tuberculosis.

    PubMed

    Behr, Marcel A

    2013-01-01

    Genomic studies have provided a refined understanding of the genetic diversity within the Mycobacterium genus, and more specifically within Mycobacterium tuberculosis. These results have informed a new perspective on the macro- and micro-evolution of the tubercle bacillus. In the first step, a M. kansasii-like opportunistic pathogen acquired new genes, through horizontal gene transfer, that enabled it to better exploit an intracellular niche and ultimately evolve into a professional pathogen. In the second step, different subspecies and strains of the M. tuberculosis complex emerged through mutation and deletion of unnecessary DNA. Understanding the differences between M. tuberculosis and related less pathogenic mycobacteria is expected to reveal key bacterial virulence mechanisms and provide opportunities to understand host resistance to mycobacterial infection. Understanding differences within the M. tuberculosis complex and the evolutionary forces shaping these differences is important for investigating the basis of its success as both a symbiont and a pathogen.

  3. Update on cutaneous tuberculosis*

    PubMed Central

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

    2014-01-01

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

  4. Tuberculosis Data and Statistics

    MedlinePlus

    ... Organization Chart Advisory Groups Federal TB Task Force Data and Statistics Language: English Español (Spanish) Recommend on ... United States publication. PDF [6 MB] Interactive TB Data Tool Online Tuberculosis Information System (OTIS) OTIS is ...

  5. Tuberculosis Diagnostics in 2015: Landscape, Priorities, Needs, and Prospects

    PubMed Central

    Pai, Madhukar; Schito, Marco

    2015-01-01

    In 2015, tuberculosis remains a major global health problem, and drug-resistant tuberculosis is a growing threat. Although tuberculosis diagnosis in many countries is still reliant on older tools, new diagnostics are changing the landscape. Stimulated, in part, by the success and roll out of Xpert MTB/RIF, there is now considerable interest in new technologies. The landscape looks promising, with a robust pipeline of new tools, particularly molecular diagnostics, and well over 50 companies actively engaged in product development. However, new diagnostics are yet to reach scale, and there needs to be greater convergence between diagnostics development and development of shorter-duration tuberculosis drug regimens. Another concern is the relative absence of non–sputum-based diagnostics in the pipeline for children and of biomarker tests for triage, cure, and progression of latent Mycobacterium tuberculosis infection. Several initiatives, described in this supplement, have been launched to further stimulate product development and policy, including assessment of needs and priorities, development of target product profiles, compilation of data on resistance-associated mutations, and assessment of market size and potential for new diagnostics. Advocacy is needed to increase funding for tuberculosis research and development, and governments in high-burden countries must invest more in tuberculosis control to meet post-2015 targets for care, control, and prevention. PMID:25765103

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

    PubMed Central

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

    2013-01-01

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

  7. Tuberculosis in children.

    PubMed

    Marais, Ben J; Schaaf, H Simon

    2014-09-01

    Many clinicians regard tuberculosis as an adult pulmonary disease, but tuberculosis (TB) is a major cause of disease, both pulmonary and extrapulmonary, and death in young children from TB-endemic countries, especially in areas affected by poverty, social disruption, and human immunodeficiency virus (HIV) infection. This article reviews the disease burden and the natural history of disease in children with TB. It also provides guidance regarding the diagnosis, treatment, and prevention of TB in children. PMID:25037105

  8. Nanoparticle delivery of anti-tuberculosis chemotherapy as a potential mediator against drug-resistant tuberculosis.

    PubMed

    Smith, Jonathan Paul

    2011-12-01

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

  9. Prevalence and characterization of opportunistic candidal infections among patients with pulmonary tuberculosis

    PubMed Central

    Astekar, Madhusudan; Bhatiya, Priyanka Sharma; Sowmya, GV

    2016-01-01

    Background: Although Candida albicans remains the most common cause of human candidiasis, the frequency of infection attributed to other members of the genus is also increasing. Hence, the present study was carried out to know the prevalence of opportunistic candidal infection in tuberculosis, and if positive, the species of Candida that is most commonly associated. Materials and Methods: The present study comprised sixty pulmonary tuberculosis patients who were divided into (1) fresh or untreated group, (2A) chronic or treated group having no complications and (2B) having complications, comprising twenty patients each, respectively. The collected sputum samples were initially stained with Ziehl–Neelsen stain for confirmation of presence of tubercle Bacilli. Primary isolation was done on Sabouraud Dextrose Agar (SDA). The candidal colonies were confirmed microscopically for the presence of pseudohyphae. Further speciation of the positive candidal samples was carried out using ChromAgar. Result: The total fungal prevalence among 60 patients with pulmonary tuberculosis on SDA was 33 (55%) Candida and 3 (5%) Aspergillus. The prevalence of different candidal species on ChromAgar showed C. albicans as the predominant one, followed by Candida tropicalis and Candida krusei. Freshly diagnosed or untreated group was less commonly associated with pulmonary mycoses than chronic or treated group. The prevalence of Candida had increased with treatment, duration and age, and it was more in males than females. Conclusion: The present study confirms the phenomenon of opportunistic candidal infections in pulmonary tuberculosis patients. Rapid and reliable identification of Candida species is essential as they differ in their virulence and sensitivity to antifungal drugs.

  10. Functional characterization of two members of histidine phosphatase superfamily in Mycobacterium tuberculosis

    PubMed Central

    2013-01-01

    Background Functional characterization of genes in important pathogenic bacteria such as Mycobacterium tuberculosis is imperative. Rv2135c, which was originally annotated as conserved hypothetical, has been found to be associated with membrane protein fractions of H37Rv strain. The gene appears to contain histidine phosphatase motif common to both cofactor-dependent phosphoglycerate mutases and acid phosphatases in the histidine phosphatase superfamily. The functions of many of the members of this superfamily are annotated based only on similarity to known proteins using automatic annotation systems, which can be erroneous. In addition, the motif at the N-terminal of Rv2135c is ‘RHA’ unlike ‘RHG’ found in most members of histidine phosphatase superfamily. These necessitate the need for its experimental characterization. The crystal structure of Rv0489, another member of the histidine phosphatase superfamily in M. tuberculosis, has been previously reported. However, its biochemical characteristics remain unknown. In this study, Rv2135c and Rv0489 from M. tuberculosis were cloned and expressed in Escherichia coli with 6 histidine residues tagged at the C terminal. Results Characterization of the purified recombinant proteins revealed that Rv0489 possesses phosphoglycerate mutase activity while Rv2135c does not. However Rv2135c has an acid phosphatase activity with optimal pH of 5.8. Kinetic parameters of Rv2135c and Rv0489 are studied, confirming that Rv0489 is a cofactor dependent phosphoglycerate mutase of M. tuberculosis. Additional characterization showed that Rv2135c exists as a tetramer while Rv0489 as a dimer in solution. Conclusion Most of the proteins orthologous to Rv2135c in other bacteria are annotated as phosphoglycerate mutases or hypothetical proteins. It is possible that they are actually phosphatases. Experimental characterization of a sufficiently large number of bacterial histidine phosphatases will increase the accuracy of the automatic

  11. Prevalence and characterization of opportunistic candidal infections among patients with pulmonary tuberculosis

    PubMed Central

    Astekar, Madhusudan; Bhatiya, Priyanka Sharma; Sowmya, GV

    2016-01-01

    Background: Although Candida albicans remains the most common cause of human candidiasis, the frequency of infection attributed to other members of the genus is also increasing. Hence, the present study was carried out to know the prevalence of opportunistic candidal infection in tuberculosis, and if positive, the species of Candida that is most commonly associated. Materials and Methods: The present study comprised sixty pulmonary tuberculosis patients who were divided into (1) fresh or untreated group, (2A) chronic or treated group having no complications and (2B) having complications, comprising twenty patients each, respectively. The collected sputum samples were initially stained with Ziehl–Neelsen stain for confirmation of presence of tubercle Bacilli. Primary isolation was done on Sabouraud Dextrose Agar (SDA). The candidal colonies were confirmed microscopically for the presence of pseudohyphae. Further speciation of the positive candidal samples was carried out using ChromAgar. Result: The total fungal prevalence among 60 patients with pulmonary tuberculosis on SDA was 33 (55%) Candida and 3 (5%) Aspergillus. The prevalence of different candidal species on ChromAgar showed C. albicans as the predominant one, followed by Candida tropicalis and Candida krusei. Freshly diagnosed or untreated group was less commonly associated with pulmonary mycoses than chronic or treated group. The prevalence of Candida had increased with treatment, duration and age, and it was more in males than females. Conclusion: The present study confirms the phenomenon of opportunistic candidal infections in pulmonary tuberculosis patients. Rapid and reliable identification of Candida species is essential as they differ in their virulence and sensitivity to antifungal drugs. PMID:27601806

  12. Pulmonary Tuberculosis Diagnosis: Where We Are?

    PubMed Central

    Leylabadlo, Hamed Ebrahimzadeh; Yousefi, Mehdi; Aghazadeh, Mohammad; Asgharzadeh, Mohammad

    2016-01-01

    In recent years, in spite of medical advancement, tuberculosis (TB) remains a worldwide health problem. Although many laboratory methods have been developed to expedite the diagnosis of TB, delays in diagnosis remain a major problem in the clinical practice. Because of the slow growth rate of the causative agent Mycobacterium tuberculosis, isolation, identification, and drug susceptibility testing of this organism and other clinically important mycobacteria can take several weeks or longer. During the past several years, many methods have been developed for direct detection, species identification, and drug susceptibility testing of TB. A good understanding of the effectiveness and practical limitations of these methods is important to improve diagnosis. This review summarizes the currently-used advances in nonmolecular and molecular diagnostics. PMID:27433173

  13. 53. INTERIOR VIEW LOOKING NORTH NORTHEAST SHOWING THE REMAINS OF ...

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

    53. INTERIOR VIEW LOOKING NORTH NORTHEAST SHOWING THE REMAINS OF A WOODEN SETTLING BOX IN THE BACKGROUND RIGHT. AMALGAMATING PANS IN THE FOREGROUND. - Standard Gold Mill, East of Bodie Creek, Northeast of Bodie, Bodie, Mono County, CA

  14. 7. VIEW OF VESSEL FROM PORT BON, SHOWING REMAINS OF ...

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

    7. VIEW OF VESSEL FROM PORT BON, SHOWING REMAINS OF MAIN CABIN. AFT CABIN STILL STANDS ON STERN IN BACKGROUND - Motorized Sailing Vessel "Fox", Beached on East Bank ofBayou Lafourche, Larose, Lafourche Parish, LA

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

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

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

  16. Diagnosis of Pulmonary Tuberculosis in Children: Assessment of the 2012 National Institutes of Health Expert Consensus Criteria

    PubMed Central

    Zar, Heather J.; Workman, Lesley J.; Little, Francesca; Nicol, Mark P.

    2015-01-01

    Background. The 2012 National Institutes of Health (NIH) consensus criteria for standardized diagnostic categories of pulmonary tuberculosis in children have not been validated. We aimed to assess the NIH diagnostic criteria in children with culture-confirmed pulmonary tuberculosis and those in whom tuberculosis has been excluded. Methods. We performed a retrospective analysis of consecutive children hospitalized with suspected pulmonary tuberculosis in Cape Town, South Africa, who were enrolled in a diagnostic study. Children were categorized as definite tuberculosis (culture positive), probable tuberculosis (chest radiograph consistent), possible tuberculosis (chest radiograph inconsistent), or not tuberculosis (improved without tuberculosis treatment). We applied the NIH diagnostic categories to the cohort and evaluated their performance specifically in children with definite tuberculosis and not tuberculosis. Results. Four hundred sixty-four children (median age, 25.1 months [interquartile range, 13.5–61.5 months]) were included; 96 (20.7%) were HIV infected. Of these, 165 (35.6%) were definite tuberculosis, and 299 (64.4%) were not tuberculosis. If strict NIH symptom criteria were applied, 100 (21.6%) were unclassifiable including 21 (21.0%) with definite pulmonary tuberculosis, as they did not meet the NIH criteria due to short duration of symptoms; 71 (71%) had cough <14 days, 48 (48%) had recent weight loss, and 39 (39%) had fever <7 days. Of 364 classifiable children, there was moderate agreement (κ = 0.48) with 100% agreement for definite tuberculosis and moderate agreement for not tuberculosis (220 [60.4%] vs 89 [24.5%]). Conclusions. Entry criteria for diagnostic studies should not be restrictive. Data from this analysis have informed revision of the NIH definitions. PMID:26409280

  17. Trends of spinal tuberculosis research (1994–2015)

    PubMed Central

    Wang, Yiran; Wang, Qijin; Zhu, Rongbo; Yang, Changwei; Chen, Ziqiang; Bai, Yushu; Li, Ming; Zhai, Xiao

    2016-01-01

    Abstract Background: Spinal tuberculosis is the most common form of skeletal tuberculosis. However, there were limited data to evaluate the trend of spinal tuberculosis research. This study aims to investigate the trend of spinal tuberculosis research and compare the contribution of research from different countries and authors. Methods: Spinal tuberculosis-related publications from 1994 to 2015 were retrieved from the Web of Science database. Excel 2013, GraphPad Prism 5, and VOSviewer software were used to analyze the search results for number of publications, cited frequency, H-index, and country contributions. Results: A total of 1558 papers were identified and were cited 16,152 times as of January 25, 2016. The United States accounted for 15.1% of the articles, 22.3% of the citations, and the highest H-index (33). China ranked third in total number of articles, fifth in citation frequency (815), and ranked seventh in H-index (13). The journal Spine (IF 2.297) had the highest number of publications. The author Jain A.K. has published the most papers in this field (20). The article titled “Tuberculosis of the spine: Controversies and a new challenge” was the most popular article and cited a total of 1138 times. The keyword “disease” was mentioned the most for 118 times and the word “bone fusion” was the latest hotspot by 2015. Conclusion: Literature growth in spinal tuberculosis is slowly expanding. Although publications from China are increasing, the quality of the articles still requires improvements. Meanwhile, the United States continues to be the largest contributor in the field of spinal tuberculosis. According to our bibliometric study, bone fusion may be an emerging topic within spinal tuberculosis research and is something that should be closely observed. PMID:27661044

  18. Recent advances in the diagnosis of childhood tuberculosis

    PubMed Central

    Marais, Ben J; Pai, Madhukar

    2007-01-01

    Children account for a major proportion of the global tuberculosis disease burden, especially in endemic areas. However, the accurate diagnosis of childhood tuberculosis remains a major challenge. This review provides an overview of the most important recent advances in the diagnosis of intrathoracic childhood tuberculosis: (1) symptom‐based approaches, including symptom‐based screening of exposed children and symptom‐based diagnosis of active disease; (2) novel immune‐based approaches, including T cell assays and novel antigen‐based tests; and (3) bacteriological and molecular methods that are more rapid and/or less expensive than conventional culture techniques for tuberculosis diagnosis and/or drug‐resistance testing. Recent advances have improved our ability to diagnose latent infection and active tuberculosis in children, but establishing a diagnosis of either latent infection or active disease in HIV‐infected children remains a major challenge, particularly in high‐burden settings. Although improved access to diagnosis and treatment is essential, ultimately the burden of childhood tuberculosis is determined by the level of epidemic control achieved in a particular community. Several recent initiatives, in particular the United Nations Millennium Developmental Goals, deal with the problem of poverty and disease in a holistic fashion, but global political commitment is required to support these key initiatives. PMID:17449528

  19. Tuberculosis: Getting Healthy, Staying Healthy

    MedlinePlus

    Tuberculosis Getting Healthy, Staying Healthy U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases Tuberculosis Getting Healthy, Staying Healthy U.S. DEPARTMENT OF HEALTH ...

  20. [Intestinal tuberculosis--cause of acute surgical abdomen].

    PubMed

    Ciurea, M; Ion, D; Ionescu, S; Tica, M R

    2001-01-01

    Tuberculosis, in its various forms, remains an important cause of morbidity and mortality in developing countries in immunodeficitary patients. The indicatives of epidemiology of tuberculosis show that Romania presents a fresh outbreak of the disease in the last few years. The purpose of this paper is to present from the various forms of extrapulmonary tuberculosis, the intestinal tipe which have a high incidence. The authors describe theirs preliminary experience of intraoperative small and large bowel emergencies resections in a short period (1 year) of three young patients (between 30 and 40 years old) with history of pulmonary tuberculosis. The pathology was complex (bowel obstructions, peritonitis) and so were the surgical operations (resections, devirations). The patients showed short and long term good results.

  1. Issues Related to the Updated 2014 Korean Guidelines for Tuberculosis.

    PubMed

    Park, Jae Seuk

    2016-01-01

    Tuberculosis (TB) remains a major public health problem in South Korea. The Joint Committee for the Development of Korean Guidelines for Tuberculosis published the Korean Guidelines for Tuberculosis in 2011 to provide evidence-based practical recommendations to health care workers caring for patients with TB in South Korea. After reviewing recent national and international scientific data on TB, the committee updated the Korean guidelines for TB in 2014. This article presents some practical issues related to the 2014 updated guidelines: namely use of the Mycobacterium tuberculosis - polymerase chain reaction assay and the Xpert MTB/RIF assay in the diagnosis of TB, as well as medical treatment for patients with multidrug-resistant TB.

  2. Low-Density Granulocytes Are Elevated in Mycobacterial Infection and Associated with the Severity of Tuberculosis.

    PubMed

    Deng, Yating; Ye, Jianqing; Luo, Qing; Huang, Zhikun; Peng, Yiping; Xiong, Guoliang; Guo, Yang; Jiang, Hong; Li, Junming

    2016-01-01

    Tuberculosis remains a global health problem caused by infection with Mycobacterium tuberculosis. Numerous studies have established a close correlation between the development of tuberculosis and the roles of neutrophils. Recently, a distinct population of CD15+ granulocytes was found to be present in the peripheral blood mononuclear cell (PBMC) fraction in humans. This population of granulocytes, termed low-density granulocytes (LDGs), was reported to be elevated and associated with disease activity or severity in a number of different conditions including SLE, asthma and HIV infection. However, both the frequency and clinical significance of LDGs associated with tuberculosis are unclear. Here we determined LDG levels and made comparisons between subjects with active pulmonary tuberculosis (PTB) and healthy controls, between PTB patients with mild-to-moderate disease and patients with advanced disease, and among PTB patients following anti-tuberculous therapy of varying durations. The direct correlation between M. tuberculosis infection and LDG levels was confirmed by in vitro infection of whole peripheral blood and isolated granulocytes with mycobacteria. Our results demonstrated that PBMCs in PTB patients contained significantly elevated percentages of LDGs compared with control subjects. LDGs in tuberculosis expressed higher levels of activation markers compared to normal-density granulocytes (NDGs). M. tuberculosis induced the generation of LDGs in both whole blood and isolated NDGs from control subjects, which suggests that LDGs associated with M. tuberculosis infection are likely to originate from in situ activation. Furthermore, our results revealed that the frequency of LDGs is associated with the severity of tuberculosis. PMID:27073889

  3. Mycobacterium tuberculosis: Manipulator of Protective Immunity

    PubMed Central

    Korb, Vanessa C.; Chuturgoon, Anil A.; Moodley, Devapregasan

    2016-01-01

    Mycobacterium tuberculosis (MTB) is one of the most successful pathogens in human history and remains a global health challenge. MTB has evolved a plethora of strategies to evade the immune response sufficiently to survive within the macrophage in a bacterial-immunological equilibrium, yet causes sufficient immunopathology to facilitate its transmission. This review highlights MTB as the driver of disease pathogenesis and presents evidence of the mechanisms by which MTB manipulates the protective immune response into a pathological productive infection. PMID:26927066

  4. [Pulmonary manifestations of tuberculosis in children].

    PubMed

    Olivier, C

    1997-12-01

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

  5. Urogenital tuberculosis: definition and classification

    PubMed Central

    2014-01-01

    Objectives To improve the approach to the diagnosis and management of urogenital tuberculosis (UGTB), we need clear and unique classification. UGTB remains an important problem, especially in developing countries, but it is often an overlooked disease. As with any other infection, UGTB should be cured by antibacterial therapy, but because of late diagnosis it may often require surgery. Methods Scientific literature dedicated to this problem was critically analyzed and juxtaposed with the author’s own more than 30 years’ experience in tuberculosis urology. Results The conception, terms and definition were consolidated into one system; classification stage by stage as well as complications are presented. Classification of any disease includes dispersion on forms and stages and exact definitions for each stage. Clinical features and symptoms significantly vary between different forms and stages of UGTB. A simple diagnostic algorithm was constructed. Conclusions UGTB is multivariant disease and a standard unified approach to it is impossible. Clear definition as well as unique classification are necessary for real estimation of epidemiology and the optimization of therapy. The term ‘UGTB’ has insufficient information in order to estimate therapy, surgery and prognosis, or to evaluate the epidemiology. PMID:25745561

  6. Tuberculosis vaccines: hopes and hurdles.

    PubMed

    Ahsan, Mohamed J; Garg, Shiv K; Vashistha, Bharat; Sharma, Piush

    2013-10-01

    Tuberculosis (TB) remains as one of the most serious public health problems worldwide. It is one of the main causes of death in poor and developing countries, especially in sub-Saharan Africa, where it may be associated with the human immunodeficiency virus (HIV). It has been estimated that one third of the world population is infected by Mycobacterium tuberculosis (Mtb), and there were about 8.7 million new TB cases, and about 1.4 million yearly deaths due to TB in 2011. DOTS is the currently used drug therapy in TB but there is non-compliance which results in emergence of resistance. Bacille Calmette Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the only licensed TB vaccine, but not recommended in HIV-infected infants. There are 14 vaccine candidates that have entered clinical trials and over 35 candidates in discovery and preclinical development. Mycobacterium indicus pranii [Mw; MIP] and M. vaccae are in phase III clinical trial and the Drug Controller of India licensed MIP for human use in India.

  7. [Tuberculosis in children in Romania].

    PubMed

    Didilescu, Cristian; Cioran, Nicoleta; Chiotan, Domnica; Popescu, Gilda

    2013-01-01

    According to the World Health Organization and Stop TB Partnership, tuberculosis among children often remains undiagnosed, the main reported causes being lack of access to health services or because health professionals unrecognizing the signs and symptoms of tuberculosis in this age group. In Romania, consistent with TB endemic levels, the overall incidence progressively decreased from 142.2%ooo in 2002 to 82.8%ooo in 2011, incidence of TB in children 0-14 years dropped steadily from 47.2 %ooo (1784 cases) in the same "peak year"2002 to 23.6% ooo (766 cases) in 2011. The distribution of TB disease in children by counties shows variations between these, the explanations may be related both to differences in offer of the bacilli between different areas (prevalence of pulmonary patients smear and/or culture positive) and by deficiencies in the detection of cases and lack of rigor in diagnosis (variation in the incidence of TB in 0-14 years from 2.S%ooo in Sălaj county up to 53.2%ooo in Maramures county in 2011). The number of serious cases of TB in children (meningoencephalitis, miliary, cavitary) still maintains a constant high annual rate (65 cases in 2011), which demonstrates the severity of endemic TB in our country. Prompt assurance of TB diagnostic and also the accurate management of TB treatment constitute the guarantee of the decrease of this disease, goal applies to all age groups.

  8. Pulmonary Disease due to Mycobacterium tuberculosis in a Horse: Zoonotic Concerns and Limitations of Antemortem Testing.

    PubMed

    Lyashchenko, Konstantin P; Greenwald, Rena; Esfandiari, Javan; Lecu, Alexis; Waters, W Ray; Posthaus, Horst; Bodmer, Thomas; Janssens, Jean-Paul; Aloisio, Fabio; Graubner, Claudia; Grosclaude, Eléonore; Piersigilli, Alessandra; Schiller, Irene

    2012-01-01

    A case of pulmonary tuberculosis caused by Mycobacterium tuberculosis was diagnosed in a horse. Clinical evaluation performed prior to euthanasia did not suggest tuberculosis, but postmortem examination provided pathological and bacteriological evidence of mycobacteriosis. In the lungs, multiple tuberculoid granulomas communicating with the bronchiolar lumen, pleural effusion, and a granulomatous lymphadenitis involving mediastinal and tracheobronchial lymph nodes were found. Serologic response to M. tuberculosis antigens was detected in the infected horse, but not in the group of 42 potentially exposed animals (18 horses, 14 alpacas, 6 donkeys, and 4 dogs) which showed no signs of disease. Diagnosis of tuberculosis in live horses remains extremely difficult. Four of 20 animal handlers at the farm were positive for tuberculous infection upon follow-up testing by interferon-gamma release assay, indicating a possibility of interspecies transmission of M. tuberculosis. PMID:22567544

  9. Local ischemia and increased expression of vascular endothelial growth factor following ocular dissemination of Mycobacterium tuberculosis.

    PubMed

    Thayil, Seema M; Albini, Thomas A; Nazari, Hossein; Moshfeghi, Andrew A; Parel, Jean-Marie A; Rao, Narsing A; Karakousis, Petros C

    2011-01-01

    The pathogenesis of intraocular tuberculosis remains poorly understood partly due to the lack of adequate animal models that accurately simulate human disease. Using a recently developed model of ocular tuberculosis following aerosol infection of guinea pigs with Mycobacterium tuberculosis, we studied the microbiological, histological, and clinical features of intraocular tuberculosis infection. Viable tubercle bacilli were cultivated from all eyes by Day 56 after aerosol delivery of ∼200 bacilli to guinea pig lungs. Choroidal tuberculous granulomas showed reduced oxygen tension, as evidenced by staining with the hypoxia-specific probe pimonidazole, and expression of vascular endothelial growth factor (VEGF) was detected in the retinal pigment epithelium (RPE) and photoreceptors. Fundoscopic examination of M. tuberculosis-infected guinea pig eyes revealed altered vascular architecture and chorioretinal hemorrhage by Day 56 after infection. This model may be useful in further elucidating the pathogenesis of ocular tuberculosis, as well as in developing tools for diagnosis and assessment of antituberculosis treatment responses in the eye.

  10. Tuberculosis among Children in Alaska.

    ERIC Educational Resources Information Center

    Gessner, Bradford D.

    1997-01-01

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

  11. Childhood Tuberculosis, Still with Us...

    ERIC Educational Resources Information Center

    Chaulet, Pierre; And Others

    1992-01-01

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

  12. Tuberculosis: A Problem for Lifeguards?

    ERIC Educational Resources Information Center

    Skaros, Susan

    1996-01-01

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

  13. Tuberculosis-resistant transgenic cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Tuberculosis is a devastating disease that affects humans and many animal species. In humans, tuberculosis (TB) is mainly caused by Mycobacterium tuberculosis, while most cases in cattle are caused by Mycobacterium bovis. However, Mb can also cause, albeit rarely, human TB. In this issue, Wu et al. ...

  14. [Clinical diagnosis of HIV infection in patients with acute surgical diseases of the abdominal cavity organs and pulmonary tuberculosis].

    PubMed

    Nguen, V Kh; Stroganov, P V; Geshelin, S A

    2011-09-01

    The results of treatment of 81 patients, suffering tuberculosis and operated in emergency for an acute surgical diseases of the abdominal cavity organs, are adduced, in 29 of them--nonspecific diseases of nontuberculosis genesis were diagnosed. In 52 patients the indication for emergency operation performance were complications of abdominal tuberculosis (perforation of the tuberculosis ulcers of small intestine--in 37, the tuberculosis mesadenitis--in 15), of them in 34--pulmonary tuberculosis was in inactive phase, that's why the HIV presence was supposed. In 26 patients the diagnosis was confirmed, basing on serologic analysis data. The presence of intraabdominal catastrophe, caused by abdominal tuberculosis complications on inactive pulmonary tuberculosis background witnesses with 85.3% probability the HIV-infectioning of the patient.

  15. Decline in Tuberculosis among Mexico-Born Persons in the United States, 2000–2010

    PubMed Central

    Baker, Brian J.; Jeffries, Carla D.; Moonan, Patrick K.

    2016-01-01

    Background In 2010, Mexico was the most common (22.9%) country of origin for foreign-born persons with tuberculosis in the United States, and overall trends in tuberculosis morbidity are substantially influenced by the Mexico-born population. Objectives To determine the risk of tuberculosis disease among Mexico-born persons living in the United States. Methods Using data from the U.S. National Tuberculosis Surveillance System and the American Community Survey, we examined tuberculosis case counts and case rates stratified by years since entry into the United States and geographic proximity to the United States–Mexico border. We calculated trends in case rates over time measured by average annual percent change. Results The total tuberculosis case count (−14.5%) and annual tuberculosis case rate (average annual percent change −5.1%) declined among Mexico-born persons. Among those diagnosed with tuberculosis less than 1 year since entry into the United States (newly arrived persons), there was a decrease in tuberculosis cases (−60.4%), no change in tuberculosis case rate (average annual percent change of 0.0%), and a decrease in population (−60.7%). Among those living in the United States for more than 5 years (non-recently arrived persons), there was an increase in tuberculosis cases (+3.4%), a decrease in tuberculosis case rate (average annual percent change of −4.9%), and an increase in population (+62.7%). In 2010, 66.7% of Mexico-born cases were among non–recently arrived persons, compared with 51.1% in 2000. Although border states reported the highest proportions (>15%) of tuberculosis cases that were Mexico-born, the highest Mexico-born–specific tuberculosis case rates (>20/100,000 population) were in states in the eastern and southeastern regions of the United States. Conclusions The decline in tuberculosis morbidity among Mexico-born persons may be attributed to fewer newly arrived persons from Mexico and lower tuberculosis case rates among

  16. The Human Antibody Response to the Surface of Mycobacterium tuberculosis

    PubMed Central

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

    2014-01-01

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

  17. Molecular diagnostics in tuberculosis.

    PubMed

    Cheng, V C C; Yew, W W; Yuen, K Y

    2005-11-01

    Molecular diagnostics in tuberculosis has enabled rapid detection of Mycobacterium tuberculosis complex in clinical specimens, identification of mycobacterial species, detection of drug resistance, and typing for epidemiological investigation. In the laboratory diagnosis of tuberculosis, the nucleic acid amplification (NAA) test is rapid and specific but not as sensitive as culture of mycobacteria. The primary determinant of successful NAA testing for tuberculosis depends on the shedding of mycobacterial DNA in secretions from caseating granulomas and its dissemination into sterile body fluids or tissue biopsies. In multibacillary diseases with a high mycobacterial load, a positive Ziehl-Neelsen smear with a positive NAA test is diagnostic of active tuberculosis, whereas a positive Ziehl-Neelsen smear with a negative NAA test in the absence of inhibitors would indicate nontuberculous mycobacterial disease. The role of the NAA test is more important in paucibacillary diseases with low mycobacterial loads. The presence of polymerase chain reaction (PCR) inhibitors, however, especially in extrapulmonary specimens, may produce false-negative results. Although this problem can be overcome to some extent by extra extraction steps, the additional processing invariably leads to the loss of mycobacterial DNA. To circumvent this problem, a brief culture augmentation step is carried out before the NAA test is performed, which can enhance the mycobacterial load while concomitantly diluting inhibitors, thereby maintaining the sensitivity of the test without excessively increasing turnaround time.

  18. 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

  19. Molecular Epidemiology of Mycobacterium tuberculosis Isolates in 100 Patients With Tuberculosis Using Pulsed Field Gel Electrophoresis

    PubMed Central

    Pooideh, Mohammad; Jabbarzadeh, Ismail; Ranjbar, Reza; Saifi, Mahnaz

    2015-01-01

    Background: Tuberculosis (TB) is a widespread infectious disease. Today, TB has created a public health crisis in the world. Genotyping of Mycobacterium tuberculosis isolates is useful for surveying the dynamics of TB infection, identifying new outbreaks, and preventing the disease. Different molecular methods for clustering of M. tuberculosis isolates have been used. Objectives: During a one year study of genotyping, 100 M. tuberculosis isolates from patients referred to Pasteur Institute of Iran were collected and their genotyping was accomplished using pulsed field gel electrophoresis (PFGE) method. Materials and Methods: Identification of all M. tuberculosis isolates was accomplished using standard biochemical and species-specific polymerase chain reaction (PCR) methods. Antibiotic susceptibility tests were performed using proportional method. After preparing PFGE plaques for each isolate of M. tuberculosis, XbaI restriction enzyme was applied for genome digestion. Finally, the digested DNA fragments were separated on 1% agarose gel and analyzed with GelCompar II software. Results: Genotyping of the studied isolates in comparison with the molecular weight marker revealed two common types; pulsotype A with 71 isolates and one multidrug resistant mycobacterium (MDR) case, and pulsotype B including 29 isolates and three MDR cases. No correlation between the antibiotypes and pulsotypes was observed. Conclusions: Molecular epidemiology studies of infectious diseases have been useful when bacterial isolates have been clustered in a period of time and in different geographical regions with variable antibiotic resistance patterns. In spite of high geographical differences and different antibiotic resistant patterns, low genetic diversity among the studied TB isolates may refer to the low rate of mutations in XbaI restriction sites in the mycobacterial genome. We also identified three MDR isolates in low-incidence pulsotype B, which could be disseminated and is highly

  20. Inhibiting Mycobacterium tuberculosis within and without.

    PubMed

    Cole, Stewart T

    2016-11-01

    Tuberculosis remains a scourge of global health with shrinking treatment options due to the spread of drug-resistant strains of Mycobacterium tuberculosis Intensive efforts have been made in the past 15 years to find leads for drug development so that better, more potent drugs inhibiting new targets could be produced and thus shorten treatment duration. Initial attempts focused on repurposing drugs that had been developed for other therapeutic areas but these agents did not meet their goals in clinical trials. Attempts to find new lead compounds employing target-based screens were unsuccessful as the leads were inactive against M. tuberculosis Greater success was achieved using phenotypic screening against live tubercle bacilli and this gave rise to the drugs bedaquiline, pretomanid and delamanid, currently in phase III trials. Subsequent phenotypic screens also uncovered new leads and targets but several of these targets proved to be promiscuous and inhibited by a variety of seemingly unrelated pharmacophores. This setback sparked an interest in alternative screening approaches that mimic the disease state more accurately. Foremost among these were cell-based screens, often involving macrophages, as these should reflect the bacterium's niche in the host more faithfully. A major advantage of this approach is its ability to uncover functions that are central to infection but not necessarily required for growth in vitro For instance, inhibition of virulence functions mediated by the ESX-1 secretion system severely attenuates intracellular M. tuberculosis, preventing intercellular spread and ultimately limiting tissue damage. Cell-based screens have highlighted the druggability of energy production via the electron transport chain and cholesterol metabolism. Here, I review the scientific progress and the pipeline, but warn against over-optimism due to the lack of industrial commitment for tuberculosis drug development and other socio-economic factors.This article is

  1. [Tuberculosis pulmonum--"threaten us of epidemic"?].

    PubMed

    Chyczewska, Elzbieta

    2008-01-01

    Tuberculosis (TB) remains a deadly infectious disease affecting millions of people worldwide with 95% of cases and 98% of deaths occuring in developing countries (9 milion new cases, 1 million deaths annually) vs.WHO. Tuberculosis is on the increase in developed countries, because of AIDS, the use of immunosuppresive drugs which depress the host defence mechanism, decreased socioeconomic conditions, as well as increased immigration of persons from areas of high endemicity. The major reason for this increase was because of rapid rise in cases from sub-Saharan Africa (due to AIDS) nad Russia. Incidense of tuberculosis in Poland 2007--the number of notified cases was 8014. Pulmonary cases represented 92.7% of total all TB cases and 628 cases of extrapulmonary TB. Chidren TB cases represented 0.9% (74 cases) of all cases notified in Poland. The incidence of tuberculosis increases with age from 1.1 in children do 41.2 among 65 and older. The incidence of men (31.5) was two times higher than in women--14.5 per 100 000 respectivly. There were 716 deaths due to pulmonary TB and 23 from extrapulmonary TB. Multidrug resistance (MDR) of Mycobacterium tuberculosis is a major therapeutic problem, in the world, with a high mortality and occurs mainly in HIV-infected patients. The WHO estimates that around 50 million people are infected with MDR-TB! WHO suggest that a greater investment in the establishment treatment strategy of DOTS (Directly Observed Treatment Short-course) into all posible regions. PMID:22320031

  2. [Tuberculosis and immigration].

    PubMed

    Salas-Coronas, Joaquín; Rogado-González, M Cruz; Lozano-Serrano, Ana Belén; Cabezas-Fernández, M Teresa

    2016-04-01

    The incidence of tuberculosis worldwide is declining. However, in Western countries this decline is slower due to the impact of immigration. Tuberculosis in the immigrant population is related to health status in the country of origin and with overcrowding and poverty conditions in the host country. Immigrants with tuberculosis are younger, have a higher prevalence of extrapulmonary forms, greater proportion of drug resistance and higher treatment default rates than those of natives. New molecular techniques not only reduce diagnostic delay time but also allow the rapid identification of resistances and improve knowledge of transmission patterns. It is necessary to implement measures to improve treatment compliance in this population group like facilitating access to health card, the use of fixed-dose combination drugs, the participation of cultural mediators and community health workers and gratuity of drugs. PMID:26851978

  3. Tuberculosis of the oesophagus

    PubMed Central

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

    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 terminal, primary tuberculosis of the oesophagus is a curable disease with a fairly good prognosis. The case report shows that the surgeon should pay careful attention to the site of the anastomosis; otherwise post-operative stricture can develop. Even this responds well to dilatations and the patient can regain normal health. PMID:5821628

  4. [Urogenital tuberculosis. Diagnostic aspects].

    PubMed

    Bennani, S; Hafiani, M; Debbagh, A; el Mrini, M; Benjelloun, S

    1995-01-01

    Urogenital tuberculosis still represents a major urologic problem in the northern part of Africa, and it is a serious disease because its diagnosis is usually late. Furthermore, the affection is frequently bilateral, which may cause the renal failure. 86 cases of urogenital tuberculosis have been reviewed. Our patients were young adults (average age: 34 year old). Cystitis is the most frequent sign (74%), hematuria, lumbar pain, genital signs and nephrologic signs are not rare. Urine was negative in 46 patients, and amicrobial leucocyturia was present in 24 cases. Diagnosis relies on a range of signs, especially intravenous pyelography that has an important place. Endoscopic biopsy did confirm the diagnosis of tuberculosis in 12 patients. Generally, definitive diagnosis was based on the histologic study of the operative specimen. PMID:8558041

  5. The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome

    PubMed Central

    Cadena, Anthony M.; Fortune, Sarah M.

    2016-01-01

    ABSTRACT Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease. PMID:27048801

  6. The Importance of First Impressions: Early Events in Mycobacterium tuberculosis Infection Influence Outcome.

    PubMed

    Cadena, Anthony M; Flynn, JoAnne L; Fortune, Sarah M

    2016-01-01

    Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease.

  7. 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

  8. Immune parameters differentiating active from latent tuberculosis infection in humans.

    PubMed

    Lee, Ji Yeon; Jung, Young Won; Jeong, Ina; Joh, Joon-Sung; Sim, Soo Yeon; Choi, Boram; Jee, Hyeon-Gun; Lim, Dong-Gyun

    2015-12-01

    Tuberculosis remains a highly prevalent infectious disease worldwide. Identification of the immune parameters that differentiate active disease from latent infection will facilitate the development of efficient control measures as well as new diagnostic modalities for tuberculosis. Here, we investigated the cytokine production profiles of monocytes and CD4(+) T lymphocytes upon encountering mycobacterial antigens. In addition, cytokines and lipid mediators with immune-modulating activities were examined in plasma samples ex vivo. Comparison of these parameters in active tuberculosis patients and healthy subjects with latent infection revealed that, active tuberculosis was associated with diminished Th1-type cytokine secretion from CD4(+) T cells and less augmented inflammatory cytokine secretion from monocytes induced by IFN-γ than that in latent tuberculosis infection. In addition, a higher plasma concentration of lipoxin A4 and lower ratio of prostaglandin E2 to lipoxin A4 were observed in active cases than in latent infections. These findings have implications for preparing new therapeutic strategies and for differential diagnosis of the two types of tuberculosis infection.

  9. Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines.

    PubMed

    Schito, Marco; Migliori, Giovanni Battista; Fletcher, Helen A; McNerney, Ruth; Centis, Rosella; D'Ambrosio, Lia; Bates, Matthew; Kibiki, Gibson; Kapata, Nathan; Corrah, Tumena; Bomanji, Jamshed; Vilaplana, Cris; Johnson, Daniel; Mwaba, Peter; Maeurer, Markus; Zumla, Alimuddin

    2015-10-15

    Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid-based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required.

  10. Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines

    PubMed Central

    Schito, Marco; Migliori, Giovanni Battista; Fletcher, Helen A.; McNerney, Ruth; Centis, Rosella; D'Ambrosio, Lia; Bates, Matthew; Kibiki, Gibson; Kapata, Nathan; Corrah, Tumena; Bomanji, Jamshed; Vilaplana, Cris; Johnson, Daniel; Mwaba, Peter; Maeurer, Markus; Zumla, Alimuddin

    2015-01-01

    Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid–based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required. PMID:26409271

  11. Ruxolitinib Associated Tuberculosis Presenting as a Neck Lump.

    PubMed

    Shamil, Eamon; Cunningham, David; Wong, Billy L K; Jani, Piyush

    2015-01-01

    Tuberculosis is an opportunistic infection with protean clinical manifestations. We describe a case of Ruxolitinib induced miliary tuberculosis presenting as a neck lump. A 78-year-old female presented with a two-month history of right-sided neck lump associated with fever, night sweats, and significant weight loss. She had a past medical history that included myelofibrosis, being treated with Ruxolitinib. Examination demonstrated 4 × 4 cm right-sided cervical lymphadenopathy. A chest radiograph showed extensive shadowing in both lungs. CT scan demonstrated perilymphatic nodes in addition to the cervical mass. An ultrasound-guided biopsy of a cervical lymph node demonstrated confirmed Mycobacterium tuberculosis infection. It was hypothesized that use of Ruxolitinib through its selective inhibition of Janus-activated kinases 1 and 2 resulted in immunosuppression and miliary tuberculosis in this patient. The medication was stopped and a 12-month regime of antituberculosis therapy commenced. She remained well at one-year follow-up with resolution of lung involvement. Clinicians should consider tuberculosis as a differential diagnosis for patients presenting with a neck lump, particularly in those taking immunosuppressant medication such as Ruxolitinib. A multidisciplinary approach is needed to promptly treat the tuberculosis and consider discontinuation of Ruxolitinib. PMID:26788384

  12. The Singapore Tuberculosis Elimination Programme: the first five years.

    PubMed Central

    Chee, Cynthia B. E.; James, Lyn

    2003-01-01

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

  13. Tuberculosis diagnosis: primary health care or emergency medical services?

    PubMed Central

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

    2013-01-01

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

  14. Integrating Social Contact and Environmental Data in Evaluating Tuberculosis Transmission in a South African Township

    PubMed Central

    Andrews, Jason R.; Morrow, Carl; Walensky, Rochelle P.; Wood, Robin

    2014-01-01

    Background. Population models of tuberculosis transmission have not accounted for social contact structure and the role of the environment in which tuberculosis is transmitted. Methods. We utilized extensions to the Wells–Riley model of tuberculosis transmission, using exhaled carbon dioxide as a tracer gas, to describe transmission patterns in an endemic community. Drawing upon social interaction data and carbon dioxide measurements from a South African township, we created an age-structured model of tuberculosis transmission in households, public transit, schools, and workplaces. We fit the model to local data on latent tuberculosis prevalence by age. Results. Most tuberculosis infections (84%) were estimated to occur outside of one's own household. Fifty percent of infections among young adults (ages 15–19) occurred in schools, due to high contact rates and poor ventilation. Despite lower numbers of contacts in workplaces, assortative mixing among adults with high rates of smear-positive tuberculosis contributed to transmission in this environment. Households and public transit were important sites of transmission between age groups. Conclusions. Consistent with molecular epidemiologic estimates, a minority of tuberculosis transmission was estimated to occur within households, which may limit the impact of contact investigations. Further work is needed to investigate the role of schools in tuberculosis transmission. PMID:24610874

  15. Counting Children with Tuberculosis: Why Numbers Matter

    PubMed Central

    Seddon, James A; Jenkins, Helen E; Liu, Li; Cohen, Ted; Black, Robert E; Becerra, Mercedes C.; Graham, Stephen M; Sismanidis, Charalambos; Dodd, Peter J

    2016-01-01

    Summary In the last five years, childhood tuberculosis (TB) has received increasing attention from international organisations, national tuberculosis programmes, and academics. For the first time, a number of different groups are developing techniques to estimate the burden of childhood TB. We review the challenges in diagnosing TB in children and the reasons cases in children can go unreported. We discuss the importance of an accurate understanding of burden for identifying problems in programme delivery, targeting interventions, monitoring trends, setting targets, allocating resources appropriately and providing strong advocacy. We briefly review the estimates produced by new analytical methods, outline the reasons for recent improvements in our understanding, and potential future directions. We conclude that while innovation, collaboration and better data have improved our understanding of childhood TB burden, it remains substantially incomplete. PMID:26564535

  16. 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

  17. Comparative analyses of the proteins from Mycobacterium tuberculosis and human genomes: Identification of potential tuberculosis drug targets.

    PubMed

    Sridhar, Settu; Dash, Pallabini; Guruprasad, Kunchur

    2016-03-15

    Tuberculosis, one of the major infectious diseases affecting human beings is caused by the bacillus Mycobacterium tuberculosis. Increased resistance to known drugs commonly used for the treatment of tuberculosis has created an urgent need to identify new targets for validation and to develop drugs. In this study, we have used various bioinformatics tools, to compare the protein sequences from twenty-three M. tuberculosis genome strains along with the known human protein sequences, in order to identify the 'conserved' M. tuberculosis proteins absent in human. Further, based on the analysis of protein interaction networks, we selected one-hundred and forty proteins that were predicted as potential M. tuberculosis drug targets and prioritized according to the ranking of 'clusters' of interacting proteins. Comparison of the predicted 140 TB targets with literature indicated that 46 of them were previously reported, thereby increasing the confidence in our predictions of the remaining 94 targets too. The analyses of the structures and functions corresponding to the predicted potential TB drug targets indicated a diverse range of proteins that included ten 'druggable' targets with some of the known drugs. PMID:26762852

  18. Comparative analyses of the proteins from Mycobacterium tuberculosis and human genomes: Identification of potential tuberculosis drug targets.

    PubMed

    Sridhar, Settu; Dash, Pallabini; Guruprasad, Kunchur

    2016-03-15

    Tuberculosis, one of the major infectious diseases affecting human beings is caused by the bacillus Mycobacterium tuberculosis. Increased resistance to known drugs commonly used for the treatment of tuberculosis has created an urgent need to identify new targets for validation and to develop drugs. In this study, we have used various bioinformatics tools, to compare the protein sequences from twenty-three M. tuberculosis genome strains along with the known human protein sequences, in order to identify the 'conserved' M. tuberculosis proteins absent in human. Further, based on the analysis of protein interaction networks, we selected one-hundred and forty proteins that were predicted as potential M. tuberculosis drug targets and prioritized according to the ranking of 'clusters' of interacting proteins. Comparison of the predicted 140 TB targets with literature indicated that 46 of them were previously reported, thereby increasing the confidence in our predictions of the remaining 94 targets too. The analyses of the structures and functions corresponding to the predicted potential TB drug targets indicated a diverse range of proteins that included ten 'druggable' targets with some of the known drugs.

  19. Tuberculosis Facts - TB and HIV/AIDS

    MedlinePlus

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

  20. [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.

  1. Cousin Lizzie's tuberculosis tent.

    PubMed

    Haddy, Richard I; Haddy, Theresa B

    2007-12-01

    Before the discovery of antibiotics as a cure for tuberculosis in the 1940s, open-air therapy was the standard treatment for the disease. This article describes how families and health care institutions used tents, shacks, balconies, and verandas to expose loved ones and patients to the cold, pure air that was believed to help them fight tubercle bacillus. PMID:18196779

  2. Transcriptional Adaptation of Drug-tolerant Mycobacterium tuberculosis During Treatment of Human Tuberculosis

    PubMed Central

    Walter, Nicholas D.; Dolganov, Gregory M.; Garcia, Benjamin J.; Worodria, William; Andama, Alfred; Musisi, Emmanuel; Ayakaka, Irene; Van, Tran T.; Voskuil, Martin I.; de Jong, Bouke C.; Davidson, Rebecca M.; Fingerlin, Tasha E.; Kechris, Katerina; Palmer, Claire; Nahid, Payam; Daley, Charles L.; Geraci, Mark; Huang, Laurence; Cattamanchi, Adithya; Strong, Michael; Schoolnik, Gary K.; Davis, John Lucian

    2015-01-01

    Background. Treatment initiation rapidly kills most drug-susceptible Mycobacterium tuberculosis, but a bacterial subpopulation tolerates prolonged drug exposure. We evaluated drug-tolerant bacilli in human sputum by comparing messenger RNA (mRNA) expression of drug-tolerant bacilli that survive the early bactericidal phase with treatment-naive bacilli. Methods. M. tuberculosis gene expression was quantified via reverse-transcription polymerase chain reaction in serial sputa from 17 Ugandans treated for drug-susceptible pulmonary tuberculosis. Results. Within 4 days, bacterial mRNA abundance declined >98%, indicating rapid killing. Thereafter, the rate of decline slowed >94%, indicating drug tolerance. After 14 days, 16S ribosomal RNA transcripts/genome declined 96%, indicating slow growth. Drug-tolerant bacilli displayed marked downregulation of genes associated with growth, metabolism, and lipid synthesis and upregulation in stress responses and key regulatory categories—including stress-associated sigma factors, transcription factors, and toxin-antitoxin genes. Drug efflux pumps were upregulated. The isoniazid stress signature was induced by initial drug exposure, then disappeared after 4 days. Conclusions. Transcriptional patterns suggest that drug-tolerant bacilli in sputum are in a slow-growing, metabolically and synthetically downregulated state. Absence of the isoniazid stress signature in drug-tolerant bacilli indicates that physiological state influences drug responsiveness in vivo. These results identify novel drug targets that should aid in development of novel shorter tuberculosis treatment regimens. PMID:25762787

  3. Pulmonary tuberculosis presenting with oral aphthae

    PubMed Central

    Bayraktar, Kevser; Gürer, Gülcan

    2015-01-01

    Tuberculosis is caused by the Mycobacterium tuberculosis bacterium. Tuberculosis primarily affects the lungs. Patients mainly complain of cough, sputum, night sweating, weight loss, and fever. However, there may be cases of atypical presentations. Although aphthous mouth ulcers are mostly present in the oral cavity in primary tuberculosis patients, our literature search showed only one case report of pulmonary tuberculosis with oral aphthae. Here we report a case of a patient with pulmonary tuberculosis admitted to the hospital with the complaint of oral aphthae.

  4. Tuberculosis masquerading as oral malignancy

    PubMed Central

    Kannan, S.; Thakkar, Purvi; Dcruz, Anil K.

    2011-01-01

    Tuberculosis of the oral cavity is a rare condition. A 55-year-old labourer was referred as a case of oral cancer for further management. The patient had no systemic symptoms. Biopsy of the lesion revealed caseating granulomatous inflammation. Chest X-ray and sputum revealed evidence of asymptomatic pulmonary tuberculosis. The purpose of this paper is to sensitize clinicians to consider oral tuberculosis as a differential diagnosis in patients with an Non-healing oral cavity ulcer. PMID:22557791

  5. National survey of notifications of tuberculosis in England and Wales in 1988. Medical Research Council Cardiothoracic Epidemiology Group.

    PubMed Central

    1992-01-01

    BACKGROUND: A survey was undertaken to determine the distribution of tuberculosis in England and Wales and, by comparison with the findings of similar surveys in 1978-9 and 1983, to study trends in the incidence of the disease by ethnic group over the decade. METHODS: The survey included all cases of tuberculosis in England and Wales newly notified to the medical officers for environmental health during the six months from 2 January to 1 July 1988. Notification rates were calculated from population estimates from the 1988 Labour Force Survey. RESULTS: Clinical details were obtained from the clinician for 2149 (99.4%) of the 2163 newly notified and previously untreated patients. Over 90% were either white (53%) or of Indian, Pakistani, or Bangladeshi ethnic origin (39%). The notification rate in the white population was 4.7/100,000/year, a decline of 7.2% per year since 1978. The rate was 134.6/100,000/year in the population of Indian ethnic origin, and 100.5/100,000/year in that of Pakistani or Bangladeshi ethnic origin, a decline of 6% a year since 1978 for the two groups combined (standardised for age, country of birth, and length of time in the UK). In all ethnic groups rates of disease were much higher in the elderly than in the young. Bacteriological results were available in 1161 (80%) of the 1443 pulmonary cases. In 939 (81%) Mycobacterium tuberculosis was cultured; 614 cases (53%) also had positive smears, of which 424 (69%) were from white patients. CONCLUSIONS: Notification rates for tuberculosis in England and Wales declined over the decade, but major differences remained between ethnic groups. Images PMID:1481174

  6. 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

  7. Evaluation of the effect of Pulicaria gnaphalodes and Perovskia abrotanoides essential oil extracts against Mycobacterium tuberculosis strains

    PubMed Central

    Hozoorbakhsh, Fereshte; Esfahani, Bahram Nasr; Moghim, Sharareh; Asghari, Gholamreza

    2016-01-01

    Background: Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB), which remains one of the major public health problems in the world. The increasing incidence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) worldwide highlights the urgent need to search for alternative antimycobacterial agents. More and more people in developing countries utilize traditional medicine for their major primary health care needs. It has been determined that the medicinal plants Pulicaria gnaphalodes and Perovskia abrotanoides possess strong antibacterial effect. Materials and Methods: In this study, the antimycobacterial effects of P. gnaphalodes and P. abrotanoides essential oil on MTB were examined. Essential oil was prepared from P. gnaphalodes aerial parts and P. abrotanoides flower. The effects of six different concentrations (20 μg/ml, 40 μg/ml, 80 μg/ml, 160 μg/ml, 320 μg/ml, and 640 μg/ml) were examined against sensitive isolates of MTB and MTB H37Rv (ATCC 27294). Results: The results showed that P. gnaphalodes and P. abrotanoides essential oil extracts have strong inhibitory effects on MTB. This activity for P. gnaphalodes was observed from very low (4%) to good (70.9%) effect; meanwhile, this activity for P. abrotanoides was observed from very low (4%) to strong (86%) effect. Conclusion: The mean of inhibition percentage for P. gnaphalodes and P. abrotanoides in 640 μg/ml was 58.1% and 76.2%, respectively. So, P. abrotanoides plant is more effective against MTB than P. gnaphalodes. Identification of the effective fraction against MTB is a further step to be studied. PMID:27195252

  8. Epidemiology of tuberculosis in Europe.

    PubMed

    Rieder, H L

    1995-09-01

    The risk of exposure to tuberculosis depends upon the incidence of infectious cases, the duration of their infectiousness, and the number of personal interactions an infectious case accomplishes per unit of time. The risk of infection, given exposure, depends on the density of infectious particles in the ambient air x duration of exposure to that air. The risk of infection has rapidly declined in Europe for decades by 10% or more annually, resulting in a shift of the infected to the oldest generation. Thus, with the passage of time, cohorts are increasingly replaced by successive cohorts with less and less infection. The risk of progression from infection to tuberculosis depends largely on the cellular immune system's capability to prevent tubercle bacilli from multiplication. The three most important risk factors for the progression from subclinical infection to tuberculosis include: human immunodeficiency virus (HIV) infection, recency of infection, and fibrotic residuals from earlier tuberculosis. The number of tuberculosis cases has rapidly decreased during this century, accompanied by an upward shift in the median age of patients. In recent years, tuberculosis among immigrants has gained in significance and is likely to continue to do so, while HIV infection has limited impact on the tuberculosis epidemic in Europe. The risk of dying from tuberculosis is determined by form and site of disease, and patient's and doctor's delay. The number of deaths caused by tuberculosis in Europe is rapidly decreasing.

  9. Data for action: collection and use of local data to end tuberculosis.

    PubMed

    Theron, Grant; Jenkins, Helen E; Cobelens, Frank; Abubakar, Ibrahim; Khan, Aamir J; Cohen, Ted; Dowdy, David W

    2015-12-01

    Accelerating progress in the fight against tuberculosis will require a drastic shift from a strategy focused on control to one focused on elimination. Successful disease elimination campaigns are characterised by locally tailored responses that are informed by appropriate data. To develop such a response to tuberculosis, we suggest a three-step process that includes improved collection and use of existing programmatic data, collection of additional data (eg, geographic information, drug resistance, and risk factors) to inform tailored responses, and targeted collection of novel data (eg, sequencing data, targeted surveys, and contact investigations) to improve understanding of tuberculosis transmission dynamics. Development of a locally targeted response for tuberculosis will require substantial investment to reconfigure existing systems, coupled with additional empirical data to evaluate the effectiveness of specific approaches. Without adoption of an elimination strategy that uses local data to target hotspots of transmission, ambitious targets to end tuberculosis will almost certainly remain unmet.

  10. 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.

  11. Translating the Tuberculosis Research Agenda: Much Accomplished, but Much More to Be Done.

    PubMed

    Schito, Marco; Maeurer, Markus; Kim, Peter; Hanna, Debra; Zumla, Alimuddin

    2015-10-15

    Despite the availability of effective diagnostics and curative treatment regimens for tuberculosis, millions of people die each year of this disease. The steady global increase in the number of tuberculosis cases caused by multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis are of major concern, especially in light of the thin tuberculosis drug pipeline. New tuberculosis drugs are undergoing clinical evaluation, and renewed hope comes from fresh approaches to improve treatment outcomes using a range of adjunct host-directed cellular and repurposed drug therapies. Current efforts in developing second-generation and new rapid point-of-care diagnostic assays take advantage of recent genetic and molecular advances. Slow progress in the development of prophylactic and therapeutic vaccines requires increased funding for basic as well as translational research. Although major challenges remain, these can be overcome by cementing our resolve, raising advocacy, bolstering global funder investments, and leveraging more effective collaborations through equitable public-private partnerships.

  12. Data for action: collection and use of local data to end tuberculosis.

    PubMed

    Theron, Grant; Jenkins, Helen E; Cobelens, Frank; Abubakar, Ibrahim; Khan, Aamir J; Cohen, Ted; Dowdy, David W

    2015-12-01

    Accelerating progress in the fight against tuberculosis will require a drastic shift from a strategy focused on control to one focused on elimination. Successful disease elimination campaigns are characterised by locally tailored responses that are informed by appropriate data. To develop such a response to tuberculosis, we suggest a three-step process that includes improved collection and use of existing programmatic data, collection of additional data (eg, geographic information, drug resistance, and risk factors) to inform tailored responses, and targeted collection of novel data (eg, sequencing data, targeted surveys, and contact investigations) to improve understanding of tuberculosis transmission dynamics. Development of a locally targeted response for tuberculosis will require substantial investment to reconfigure existing systems, coupled with additional empirical data to evaluate the effectiveness of specific approaches. Without adoption of an elimination strategy that uses local data to target hotspots of transmission, ambitious targets to end tuberculosis will almost certainly remain unmet. PMID:26515676

  13. 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-γ, 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.

  14. Mycobacterium tuberculosis Complex and HIV Co-Infection among Extrapulmonary Tuberculosis Suspected Cases at the University of Gondar Hospital, Northwestern Ethiopia

    PubMed Central

    Fanosie, Alemu; Gelaw, Baye; Tessema, Belay; Tesfay, Wogahta; Admasu, Aschalew; Yitayew, Gashaw

    2016-01-01

    Background Extrapulmonary Tuberculosis (EPTB) and Human Immunodeficiency Virus (HIV) infection are interrelated as a result of immune depression. The aim of this study was to determine the prevalence of Mycobacterium tuberculosis complex isolates and the burden of HIV co-infection among EPTB suspected patients. Method An institution based cross-sectional study was conducted among EPTB suspected patients at the University of Gondar Hospital. Socio-demographic characteristics and other clinical data were collected using a pretested questionnaire. GeneXpert MTB/RIF assay was performed to diagnosis Mycobacterium tuberculosis complex and Rifampicin resistance. All samples were also investigated by cytology and culture. The HIV statuses of all patients were screened initially by KHB, and all positive cases were further re-tested by STAT-pack. Data was analyzed using SPSS version 20 computer software and a P-value of < 0.05 was taken as statistically significant. Results A total of 141 extrapulmonary suspected patients were enrolled in this study. The overall prevalence of culture confirmed extrapulmonary tuberculosis infection was 29.8%, but the GeneXpert result showed a 26.2% prevalence of Mycobacterium tuberculosis complex infection. The 78.4% prevalence of extrapulmonary tuberculosis infection was found to be higher among the adult population. The prevalence of HIV infection among EPTB suspected patients was 14.1%, while it was 32.4% among GeneXpert-confirmed extrapulmonary TB cases (12/37). Tuberculosis lymphadenitis was the predominant (78.4%) type of EPTB infection followed by tuberculosis cold abscess (10.7%). Adult hood, previous history of contact with known pulmonary tuberculosis patients, and HIV co-infection showed a statistically significant association with extrapulmonary tuberculosis infection (P<0.013). Conclusion The prevalence of culture confirmed-EPTB infection was high, and a higher EPTB-HIV co-infection was also observed. PMID:26950547

  15. Salmonella spondylodiscitis of the thoracic vertebrae mimicking spine tuberculosis.

    PubMed

    Muhamad Effendi, Ferdhany; Ibrahim, Mohd Ikraam; Mohd Miswan, Mohd Fairudz

    2016-01-01

    Extraintestinal Salmonella infection involving the thoracic spine is very rare. It commonly presents with non-specific chronic back pain and can occur with no gastrointestinal manifestation. Blood test results and imaging findings are often indistinguishable from more common chronic spine infections such as spine tuberculosis. Culture studies remain the key to establishing a definitive diagnosis and subsequently successful treatment. We report a case in which a patient presented with symptoms and signs suggestive of spine tuberculosis, yet the culture examination revealed otherwise. PMID:27381996

  16. 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

  17. 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

  18. An Unconventional Hexacoordinated Flavohemoglobin from Mycobacterium tuberculosis*

    PubMed Central

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

    2012-01-01

    Being an obligate aerobe, Mycobacterium tuberculosis faces a number of energetic challenges when it encounters hypoxia and environmental stress during intracellular infection. Consequently, it has evolved innovative strategies to cope with these unfavorable conditions. Here, we report a novel flavohemoglobin (MtbFHb) from M. tuberculosis that exhibits unique features within its heme and reductase domains distinct from conventional FHbs, including the absence of the characteristic hydrogen bonding interactions within the proximal heme pocket and mutations in the FAD and NADH binding regions of the reductase domain. In contrast to conventional FHbs, it has a hexacoordinate low-spin heme with a proximal histidine ligand lacking imidazolate character and a distal heme pocket with a relatively low electrostatic potential. Additionally, MtbFHb carries a new FAD binding site in its reductase domain similar to that of d-lactate dehydrogenase (d-LDH). When overexpressed in Escherichia coli or Mycobacterium smegmatis, MtbFHb remained associated with the cell membrane and exhibited d-lactate:phenazine methosulfate reductase activity and oxidized d-lactate into pyruvate by converting the heme iron from Fe3+ to Fe2+ in a FAD-dependent manner, indicating electron transfer from d-lactate to the heme via FAD cofactor. Under oxidative stress, MtbFHb-expressing cells exhibited growth advantage with reduced levels of lipid peroxidation. Given the fact that d-lactate is a byproduct of lipid peroxidation and that M. tuberculosis lacks the gene encoding d-LDH, we propose that the novel d-lactate metabolizing activity of MtbFHb uniquely equips M. tuberculosis to balance the stress level by protecting the cell membrane from oxidative damage via cycling between the Fe3+/Fe2+ redox states. PMID:22437825

  19. 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

  20. Tuberculosis control learning games.

    PubMed

    Smith, I

    1993-07-01

    In teaching health workers about tuberculosis (TB) control we frequently concentrate on the technological aspects, such as diagnosis, treatment and recording. Health workers also need to understand the sociological aspects of TB control, particularly those that influence the likelihood of diagnosis and cure. Two games are presented that help health workers comprehend the reasons why TB patients often delay in presenting for diagnosis, and why they then frequently default from treatment. PMID:8356734

  1. Genitourinary Presentation of Tuberculosis

    PubMed Central

    Yuan, Jerry

    2015-01-01

    Tuberculosis (TB) is less common in developed countries; however, the incidence of TB—especially resistant strains—is on the rise worldwide. Cases of TB manifesting as urologic complications are rare in the United States. Urologists should be aware of this potential manifestation, especially in patients who have recently immigrated to the United States or have traveled abroad for prolonged periods. Two cases are presented here to illustrate this entity. PMID:27222648

  2. Challenges in childhood tuberculosis.

    PubMed

    Swaminathan, S; Ramachandran, G

    2015-09-01

    While tuberculosis (TB) typically causes respiratory disease in adults, the spectrum of disease is different in children, ranging from paucibacillary lymphadenitis or limited intrathoracic disease to severe disseminated disease. Diagnosing pediatric TB and monitoring treatment response is challenging, as collecting respiratory specimens is difficult in children and disease may be extrapulmonary. While basic principles of treatment are similar to adults, developmental differences in pharmacokinetics and pharmacodynamics require that drug dosages in children be adjusted for body weight and age.

  3. Initial Presentations Predict Mortality in Pulmonary Tuberculosis Patients - A Prospective Observational Study

    PubMed Central

    Feng, Jia-Yih; Su, Wei-Juin; Chiu, Yu-Chi; Huang, Shiang-Fen; Lin, Yung-Yang; Huang, Ruay-Ming; Lin, Ching-Hsiung; Hwang, Jhi-Jhu; Lee, Jen-Jyh; Yu, Ming-Chih; Yu, Kwok-Woon; Lee, Yu-Chin

    2011-01-01

    Background Despite effective anti-TB treatments, tuberculosis remains a serious threat to public health and is associated with high mortality. Old age and multiple co-morbidities are known risk factors for death. The association of clinical presentations with mortality in pulmonary tuberculosis patients remains an issue of controversy. Methods This prospective observational study enrolled newly diagnosed, culture-proven pulmonary tuberculosis patients from five medical centers and one regional hospital, which were referral hospitals of TB patients. Radiographic findings and clinical symptoms were determined at the time of diagnosis. Patients who died for any reason during the course of anti-TB treatment were defined as mortality cases and death that occurred within 30 days of initiating treatment was defined as early mortality. Clinical factors associated with overall mortality and early mortality were investigated. Results A total of 992 patients were enrolled and 195 (19.7%) died. Nearly one-third (62/195, 31.8%) of the deaths occurred before or within 30 days of treatment initiation. Older age (RR = 1.04, 95%CI: 1.03–1.05), malignancy (RR = 2.42, 95%CI: 1.77–3.31), renal insufficiency (RR = 1.77, 95%CI: 1.12–2.80), presence of chronic cough (RR = 0.63, 95%CI: 0.47–0.84), fever (RR = 1.45, 95%CI: 1.09–1.94), and anorexia (RR = 1.49, 95%CI: 1.07–2.06) were independently associated with overall mortality. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients present with fever (p<0.001), anorexia (p = 0.005), and without chronic cough (p<0.001). Among patients of mortality, those with respiratory symptoms of chronic cough (RR = 0.56, 95%CI: 0.33–0.98) and dyspnea (HR = 0.51, 95%CI: 0.27–0.98) were less likely to experience early mortality. The radiological features were comparable between survivors and non-survivors. Conclusions In addition to demographic characteristics, clinical

  4. Cancer-specific incidence rates of tuberculosis: A 5-year nationwide population-based study in a country with an intermediate tuberculosis burden.

    PubMed

    Seo, Gi Hyeon; Kim, Min Jae; Seo, Soyoung; Hwang, Boram; Lee, Eugene; Yun, Yujin; Choi, Minsun; Kim, Moonsuk; Kim, Jin Won; Kim, Eu Suk; Kim, Hong Bin; Song, Kyoung-Ho

    2016-09-01

    Population-based studies of the incidence of tuberculosis in cancer patients according to the type of cancer are limited. We investigated the cancer-specific incidence of tuberculosis in a nationwide population-based cohort in a country with an intermediate burden of tuberculosis.We used mandatory National Health Insurance claims data to construct a cancer cohort of adults (aged 20-99 years) with newly diagnosed malignancies other than lung cancer, from January 2008 to December 2012. Patients who developed tuberculosis in this period were identified in the cancer cohort and the general population. Standardized incidence ratios (SIRs) of tuberculosis in the cancer cohort according to type of cancer and time after cancer diagnosis were calculated by comparing the observed incidence rates with those inferred from the age- and gender-specific incidence rates in the general population.A total of 855,382 cancer patients and 1589,876 person-years (py) were observed. A total of 5745 patients developed tuberculosis; the mean incidence rate was 361.3 per 100,000 py, and the SIR was 2.22 (95% confidence interval [CI], 2.17-2.27). The incidence rate was highest for hematologic malignancy and lowest for thyroid cancer. It was also highest as 650.1 per 100,000 py, with SIR of 3.70 (CI, 3.57-3.83) for the first 6 months after diagnosis of malignancy and then declined. However, it still remained higher than that of the general population after 24 months (SIR = 1.43, CI, 1.36-1.51).The incidence of tuberculosis increases after diagnosis in patients with malignancies. The risk of tuberculosis differs according to the type of cancer and remains elevated even 24 months after cancer diagnosis. Tuberculosis should be considered an important comorbidity in patients with malignancies. PMID:27661041

  5. Cancer-specific incidence rates of tuberculosis: A 5-year nationwide population-based study in a country with an intermediate tuberculosis burden.

    PubMed

    Seo, Gi Hyeon; Kim, Min Jae; Seo, Soyoung; Hwang, Boram; Lee, Eugene; Yun, Yujin; Choi, Minsun; Kim, Moonsuk; Kim, Jin Won; Kim, Eu Suk; Kim, Hong Bin; Song, Kyoung-Ho

    2016-09-01

    Population-based studies of the incidence of tuberculosis in cancer patients according to the type of cancer are limited. We investigated the cancer-specific incidence of tuberculosis in a nationwide population-based cohort in a country with an intermediate burden of tuberculosis.We used mandatory National Health Insurance claims data to construct a cancer cohort of adults (aged 20-99 years) with newly diagnosed malignancies other than lung cancer, from January 2008 to December 2012. Patients who developed tuberculosis in this period were identified in the cancer cohort and the general population. Standardized incidence ratios (SIRs) of tuberculosis in the cancer cohort according to type of cancer and time after cancer diagnosis were calculated by comparing the observed incidence rates with those inferred from the age- and gender-specific incidence rates in the general population.A total of 855,382 cancer patients and 1589,876 person-years (py) were observed. A total of 5745 patients developed tuberculosis; the mean incidence rate was 361.3 per 100,000 py, and the SIR was 2.22 (95% confidence interval [CI], 2.17-2.27). The incidence rate was highest for hematologic malignancy and lowest for thyroid cancer. It was also highest as 650.1 per 100,000 py, with SIR of 3.70 (CI, 3.57-3.83) for the first 6 months after diagnosis of malignancy and then declined. However, it still remained higher than that of the general population after 24 months (SIR = 1.43, CI, 1.36-1.51).The incidence of tuberculosis increases after diagnosis in patients with malignancies. The risk of tuberculosis differs according to the type of cancer and remains elevated even 24 months after cancer diagnosis. Tuberculosis should be considered an important comorbidity in patients with malignancies.

  6. Pathology of bovine tuberculosis.

    PubMed

    Domingo, M; Vidal, E; Marco, A

    2014-10-01

    Bovine tuberculosis (bTB) is a chronic granulomatous caseous-necrotising inflammatory process that mainly affects the lungs and their draining lymph nodes (Ln.). The pathological changes associated with bTB infection reflect the interplay between the host defence mechanisms and the mycobacterial virulence factors and the balance between the immunologic protective responses and the damaging inflammatory processes. Inhalation is the most common infection route and causes lesions of the nasopharynx and lower respiratory tract, including its associated lymph nodes. The initial infection (primary complex) may be followed by chronic (post-primary) tuberculosis or may be generalised. Goat tuberculosis often produces liquefactive necrosis and caverns, similarly to human TB. The assessment of the severity of TB lesions is crucial for vaccine trials. Semi-quantitative gross lesion scoring systems have been developed for cattle, but imaging technology has allowed the development of more standardised, objective, and quantitative methods, such as multi-detector computed tomography (MDCT), which provides quantitative measures of lesion volume. PMID:24731532

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

    PubMed Central

    2014-01-01

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

  8. Effects of smoking and solid-fuel use on COPD, lung cancer, and tuberculosis in China: a time-based, multiple risk factor, modelling study

    PubMed Central

    Lin, Hsien-Ho; Murray, Megan; Cohen, Ted; Colijn, Caroline; Ezzati, Majid

    2009-01-01

    Summary Background Chronic obstructive pulmonary disease (COPD), lung cancer, and tuberculosis are three leading causes of death in China, where prevalences of smoking and solid-fuel use are also high. We aimed to predict the effects of risk-factor trends on COPD, lung cancer, and tuberculosis. Methods We used representative data sources to estimate past trends in smoking and household solid-fuel use and to construct a range of future scenarios. We obtained the aetiological effects of risk factors on diseases from meta-analyses of epidemiological studies and from large studies in China. We modelled future COPD and lung cancer mortality and tuberculosis incidence, taking into account the accumulation of hazardous effects of risk factors on COPD and lung cancer over time, and dependency of the risk of tuberculosis infection on the prevalence of disease. We quantified the sensitivity of our results to methods and data choices. Findings If smoking and solid-fuel use remain at current levels between 2003 and 2033, 65 million deaths from COPD and 18 million deaths from lung cancer are predicted in China; 82% of COPD deaths and 75% of lung cancer deaths will be attributable to the combined effects of smoking and solid-fuel use. Complete gradual cessation of smoking and solid-fuel use by 2033 could avoid 26 million deaths from COPD and 6·3 million deaths from lung cancer; interventions of intermediate magnitude would reduce deaths by 6−31% (COPD) and 8−26% (lung cancer). Complete cessation of smoking and solid-fuel use by 2033 would reduce the projected annual tuberculosis incidence in 2033 by 14−52% if 80% DOTS coverage is sustained, 27−62% if 50% coverage is sustained, or 33−71% if 20% coverage is sustained. Interpretation Reducing smoking and solid-fuel use can substantially lower predictions of COPD and lung cancer burden and would contribute to effective tuberculosis control in China. Funding International Union Against Tuberculosis and Lung Disease. PMID

  9. Genetic diversity of Mycobacterium tuberculosis isolates from central India

    PubMed Central

    Desikan, Prabha; Chauhan, D.S.; Sharma, Pragya; Panwalkar, Nikita; Chourey, Manju; Patidar, Mohan Lal; Yadav, Priyanka; Chandrasekaran, V.; Ohri, B.S.

    2016-01-01

    Background & objectives: There is a paucity of data available on genetic biodiversity of Mycobacterium tuberculosis isolates from central India. The present study was carried out on isolates of M. tuberculosis cultured from diagnostic clinical samples of patients from Bhopal, central India, using spoligotyping as a method of molecular typing. Methods: DNA was extracted from 340 isolates of M. tuberculosis from culture, confirmed as M. tuberculosis by molecular and biochemical methods and subjected to spoligotyping. The results were compared with the international SITVIT2 database. Results: Sixty five different spoligo international type (SIT) patterns were observed. A total of 239 (70.3%) isolates could be clustered into 25 SITs. The Central Asian (CAS) and East African Indian (EAI) families were found to be the two major circulating families in this region. SIT26/CAS1_DEL was identified as the most predominant type, followed by SIT11/EAI3_IND and SIT288/CAS2. Forty (11.8%) unique (non-clustered) and 61 (17.9%) orphan isolates were identified in the study. There was no significant association of clustering with clinical and demographic characteristics of patients. Interpretation & conclusions: Well established SITs were found to be predominant in our study. SIT26/CAS1_DEL was the most predominant type. However, the occurrence of a substantial number of orphan isolates may indicate the presence of active spatial and temporal evolutionary dynamics within the isolates of M. tuberculosis. PMID:27377505

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

    PubMed

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

    2012-05-19

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

  11. Pathogen-derived biomarkers for active tuberculosis diagnosis.

    PubMed

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

    2014-01-01

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

  12. 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

  13. Tuberculosis in an indigenous young white south Wales population.

    PubMed

    Lowe, G L; Temple, J M F; Lyons, M; Bruce, K; White, J P

    2002-12-01

    Concerns about tuberculosis in young people in two linked deprived non-metropolitan communities triggered an investigation into local disease incidence and control measures. A pragmatic case-finding exercise, epidemiological enquiry and DNA genotyping were carried out to establish incidence and connections between cases over a five-year period. Of the 91 cases identified, 88 were from the white indigenous population. Approximately one third of cases were aged under thirty. Eight disease clusters were identified. Epidemiological investigation found spurious links between these, and DNA genotyping was necessary to clarify links. Seven cases and several contacts had been in prisons throughout the United Kingdom. Index cases under thirty generated more contacts, more contacts needing prophylaxis and more secondary cases than older patients. The workload resulting from tuberculosis control in younger cases was considerable. Tuberculosis remains an important problem in this population. PMID:12564254

  14. Mycobacterium tuberculosis infection in a HIV-positive patient.

    PubMed

    Montales, Maria Theresa; Beebe, Alexandria; Chaudhury, Arun; Patil, Naveen

    2015-01-01

    Mycobacterium tuberculosis (MTB) and human immunodeficiency virus (HIV) coinfection remains a global public health challenge. We report a 40 year old African American male who is a known HIV-positive patient, non-compliant with his antiretrovirals and developed pulmonary tuberculosis. His chief complaints were chronic cough, fever, night sweats and undocumented weight loss. He had a prior positive T-SPOT-TB test; however, chest radiograph and sputum smear examination revealed normal results. PCR-based GeneXPERT MTB/RIF assay was ordered and confirmed MTB infection. The sputum cultures grew MTB and sensitivities showed susceptibility to all primary anti-tuberculosis medications. A delay in diagnosis and initiation of MTB therapy, in the setting of HIV or AIDS, may result in rapid disease progression and worse clinical outcome. PMID:26744689

  15. Economic challenges associated with tuberculosis diagnostic development.

    PubMed

    Hanrahan, Colleen F; Shah, Maunank

    2014-08-01

    Tuberculosis remains a global health crisis in part due to underdiagnosis. Technological innovations are needed to improve diagnostic test accuracy and reduce the reliance on expensive laboratory infrastructure. However, there are significant economic challenges impeding the development and implementation of new diagnostics. The aim of this piece is to examine the current state of TB diagnostics, outline the unmet needs for new tests, and detail the economic challenges associated with development of new tests from the perspective of developers, policy makers and implementers. PMID:24766367

  16. Economic challenges associated with tuberculosis diagnostic development

    PubMed Central

    Hanrahan, Colleen F.; Shah, Maunank

    2015-01-01

    Tuberculosis remains a global health crisis in part due to underdiagnosis. Technological innovations are needed to improve diagnostic test accuracy and reduce the reliance on expensive laboratory infrastructure. However, there are significant economic challenges impeding the development and implementation of new diagnostics. The aim of this piece is to examine the current state of TB diagnostics, outline the unmet needs for new tests, and detail the economic challenges associated with development of new tests from the perspective of developers, policy makers and implementers. PMID:24766367

  17. Tuberculosis endometritis presenting as a leiomyoma.

    PubMed

    Shirazi, Mahboobeh; Shahbazi, Fatemeh; Pirzadeh, Leila; Mohammadi, Seyed Rahim; Ghaffari, Parisa; Eftekhar, Tahereh

    2015-01-01

    Genitourinary tuberculosis is a common extrapulmonary manifestation of tuberculosis. Taking into consideration that genitourinary tuberculosis may be associated with a diversity of presentations, its diagnoses may be difficult. A young woman with an initial presumptive diagnosis of a uterine leiomyoma presented with abdominal pain and a pelvic mass that after further investigations, she was diagnosed with genital tuberculosis. PMID:25780530

  18. Tuberculosis Endometritis Presenting as A Leiomyoma

    PubMed Central

    Shirazi, Mahboobeh; Shahbazi, Fatemeh; Pirzadeh, Leila; Mohammadi, Seyed Rahim; Ghaffari, Parisa; Eftekhar, Tahereh

    2015-01-01

    Genitourinary tuberculosis is a common extrapulmonary manifestation of tuberculosis. Taking into consideration that genitourinary tuberculosis may be associated with a diversity of presentations, its diagnoses may be difficult. A young woman with an initial presumptive diagnosis of a uterine leiomyoma presented with abdominal pain and a pelvic mass that after further investigations, she was diagnosed with genital tuberculosis. PMID:25780530

  19. Noninvasive Test for Tuberculosis Detection among Primates

    PubMed Central

    Mugisha, Lawrence; Shoyama, Fernanda Miyagaki; O’Malley, Melanie J.; Flynn, JoAnne L.; Asiimwe, Benon; Travis, Dominic A.; Singer, Randall S.; Sreevatsan, Srinand

    2015-01-01

    Traditional testing methods have limited epidemiologic studies of tuberculosis among free-living primates. PCR amplification of insertion element IS6110 of Mycobacterium tuberculosis from fecal samples was evaluated as a noninvasive screening test for tuberculosis in primates. Active tuberculosis was detected among inoculated macaques and naturally exposed chimpanzees, demonstrating the utility of this test. PMID:25695329

  20. Social and cultural factors in the successful control of tuberculosis.

    PubMed Central

    Rubel, A J; Garro, L C

    1992-01-01

    The burden of tuberculosis on the public health is staggering. Worldwide, annual incidence of new cases is estimated to be about 8 million. Almost 3 million deaths occur yearly. Early case identification and adherence to treatment regimens are the remaining barriers to successful control. In many nations, however, fewer than half those with active disease receive a diagnosis, and fewer than half those beginning treatment complete it. The twin problems of delay in seeking treatment and abandonment of a prescribed regimen derive from complex factors. People's confusion as to the implications of the tuberculosis symptoms, costs of transportation to clinic services, the social stigma that attaches to tuberculosis, the high cost of medication, organizational problems in providing adequate followup services, and patients' perception of clinic facilities as inhospitable all contribute to the complexity. Sociocultural factors are emphasized in this report because hitherto they have not been adequately explored. Salient among those sociocultural factors is the health culture of the patients. That is, the understanding and information people have from family, friends, and neighbors as to the nature of a health problem, its cause, and its implications. A knowledge of the health culture of their patients has become a critical tool if tuberculosis control programs are to be successful. Several anthropological procedures are recommended to help uncover the health culture of people served by tuberculosis clinics. PMID:1454974

  1. Resistance to cellular autophagy by Mycobacterium tuberculosis Beijing strains.

    PubMed

    Haque, Md Fazlul; Boonhok, Rachasak; Prammananan, Therdsak; Chaiprasert, Angkana; Utaisincharoen, Pongsak; Sattabongkot, Jetsumon; Palittapongarnpim, Prasit; Ponpuak, Marisa

    2015-10-01

    Autophagy represents a key pathway in innate immune defense to restrict Mycobacterium tuberculosis growth inside host macrophages. Induction of autophagy has been shown to promote mycobacterial phagosome acidification and acquisition of lysosomal hydrolases, resulting in the elimination of intracellular M. tuberculosis reference strains such as H37Rv. The notorious Beijing genotype has been previously shown to be hyper-virulent and associated with increased survival in host cells and a high mortality rate in animal models, but the underlying mechanism that renders this family to have such advantages remains unclear. We hypothesize that autophagic control against M. tuberculosis Beijing strains may be altered. Here, we discovered that the Beijing strains can resist autophagic killing by host cells compared with that of the reference strain H37Rv and a strain belonging to the East African Indian genotype. Moreover, we have determined a possible underlying mechanism and found that the greater ability to evade autophagic elimination possessed by the Beijing strains stems from their higher capacity to inhibit autophagolysosome biogenesis upon autophagy induction. In summary, a previously unrecognized ability of the M. tuberculosis Beijing strains to evade host autophagy was identified, which may have important implications for tuberculosis treatment, especially in regions prevalent by the Beijing genotype. PMID:26160686

  2. 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

  3. 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

  4. TUBERCULOSIS AND LUNG CANCER.

    PubMed

    Tamura, Atsuhisa

    2016-01-01

    The occurrence of pulmonary tuberculosis (PTB) and lung cancer as comorbidities has been extensively discussed in many studies. In the past, it was well known that lung cancer is a specific epidemiological successor of PTB and that lung cancer often develops in scars caused by PTB. In recent years, the relevance of the two diseases has drawn attention in terms of the close epidemiological connection and chronic inflammation-associated carcinogenesis. In Japanese case series studies, most lung cancer patients with tuberculous sequelae received supportive care alone in the past, but more recently, the use of aggressive lung cancer treatment is increasing. Many studies on PTB and lung cancer as comorbidities have revealed that active PTB is noted in 2-5% of lung cancer cases, whereas lung cancer is noted in 1-2% of active PTB cases. In such instances of comorbidity, many active PTB cases showed Type II (non-extensively cavitary disease) and Spread 2-3 (intermediate-extensive diseases) on chest X-rays, but standard anti-tuberculosis treatment easily eradicates negative conversion of sputum culture for M. tuberculosis; lung cancer cases were often stage III- IV and squamous cell carcinoma predominant, and the administration of aggressive treatment for lung cancer is increasing. The major clinical problems associated with PTB and lung cancer as comorbidities include delay in diagnosis (doctor's delay) and therapeutic limitations. The former involves two factors of radiographic interpretation: the principles of parsimony (Occam's razor) and visual search; the latter involves three factors of lung cancer treatment: infectivity of M.tuberculosis, anatomical limitation due to lung damage by tuberculosis, and drug-drug interactions between rifampicin and anti-cancer drugs, especially molecularly targeted drugs. The comorbidity of these two diseases is an important health-related issue in Japan. In the treatment of PTB, the possibility of concurrent lung cancer should be kept

  5. Tuberculosis, Fiji, 2002-2013.

    PubMed

    Pezzoli, Lorenzo; Gounder, Shakti; Tamani, Talatoka; Daulako, Mary Raori; Underwood, Frank; Mainawalala, Sakiusa; Nawadra-Taylor, Vasiti; Rafai, Eric; Gillini, Laura

    2016-03-01

    During 2002-2013, a total of 1,890 tuberculosis cases were recorded in Fiji. Notification rates per 100,000 population increased from 17.4 cases in 2002 to 28.4 in 2013. Older persons were most affected, but tuberculosis also increased sharply in persons 25-44 years of age.

  6. Tuberculosis, Fiji, 2002–2013

    PubMed Central

    Gounder, Shakti; Tamani, Talatoka; Daulako, Mary Raori; Underwood, Frank; Mainawalala, Sakiusa; Nawadra-Taylor, Vasiti; Rafai, Eric; Gillini, Laura

    2016-01-01

    During 2002–2013, a total of 1,890 tuberculosis cases were recorded in Fiji. Notification rates per 100,000 population increased from 17.4 cases in 2002 to 28.4 in 2013. Older persons were most affected, but tuberculosis also increased sharply in persons 25–44 years of age. PMID:26890215

  7. Microdissection approaches in tuberculosis research

    PubMed Central

    Hudock, Teresa A.; Lackner, Andrew A.; Kaushal, Deepak

    2015-01-01

    Mycobacterium tuberculosis, a globally significant pathogen, results in active or latent tuberculosis. The granuloma is the characteristic lesion that offers insight into host-pathogen interactions in these distinct states. Microdissection provides a way to isolate and consequently investigate specific tissue sections. We review various techniques available and in use. PMID:25164280

  8. Protection by novel vaccine candidates, Mycobacterium tuberculosis ΔmosR and ΔechA7, against challenge with a Mycobacterium tuberculosis Beijing strain

    PubMed Central

    Marcus, Sarah A.; Steinberg, Howard; Talaat, Adel M.

    2015-01-01

    Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), infects over two billion people, claiming around 1.5 million lives annually. The only vaccine approved for clinical use against this disease is the Bacillus Calmette-Guérin (BCG) vaccine. Unfortunately, BCG has limited efficacy against the adult, pulmonary form of tuberculosis. This vaccine was developed from M. bovis with antigen expression and host specificity that differ from M. tuberculosis. To address these problems, we have designed two novel, live attenuated vaccine (LAV) candidates on an M. tuberculosis background: ΔmosR and ΔechA7. These targeted genes are important to M. tuberculosis pathogenicity during infection. To examine the efficacy of these strains, C57BL/6 mice were vaccinated subcutaneously with either LAV, BCG, or PBS. Both LAV strains persisted up to 16 weeks in the spleens or lungs of vaccinated mice, while eliciting minimal pathology prior to challenge. Following challenge with a selected, high virulence M. tuberculosis Beijing strain, protection was notably greater for both groups of LAV vaccinated animals as compared to BCG at both 30 and 60 days post-challenge. Additionally, vaccination with either ΔmosR or ΔechA7 elicited an immune response similar to BCG. Although these strains require further development to meet safety standards, this first evidence of protection by these two new, live attenuated vaccine candidates shows promise. PMID:26363381

  9. Profiling the Proteome of Mycobacterium tuberculosis during Dormancy and Reactivation*

    PubMed Central

    Gopinath, Vipin; Raghunandanan, Sajith; Gomez, Roshna Lawrence; Jose, Leny; Surendran, Arun; Ramachandran, Ranjit; Pushparajan, Akhil Raj; Mundayoor, Sathish; Jaleel, Abdul; Kumar, Ramakrishnan Ajay

    2015-01-01

    Tuberculosis, caused by Mycobacterium tuberculosis, still remains a major global health problem. The main obstacle in eradicating this disease is the ability of this pathogen to remain dormant in macrophages, and then reactivate later under immuno-compromised conditions. The physiology of hypoxic nonreplicating M. tuberculosis is well-studied using many in vitro dormancy models. However, the physiological changes that take place during the shift from dormancy to aerobic growth (reactivation) have rarely been subjected to a detailed investigation. In this study, we developed an in vitro reactivation system by re-aerating the virulent laboratory strain of M. tuberculosis that was made dormant employing Wayne's dormancy model, and compared the proteome profiles of dormant and reactivated bacteria using label-free one-dimensional LC/MS/MS analysis. The proteome of dormant bacteria was analyzed at nonreplicating persistent stage 1 (NRP1) and stage 2 (NRP2), whereas that of reactivated bacteria was analyzed at 6 and 24 h post re-aeration. Proteome of normoxially grown bacteria served as the reference. In total, 1871 proteins comprising 47% of the M. tuberculosis proteome were identified, and many of them were observed to be expressed differentially or uniquely during dormancy and reactivation. The number of proteins detected at different stages of dormancy (764 at NRP1, 691 at NRP2) and reactivation (768 at R6 and 983 at R24) was very low compared with that of the control (1663). The number of unique proteins identified during normoxia, NRP1, NRP2, R6, and R24 were 597, 66, 56, 73, and 94, respectively. We analyzed various biological functions during these conditions. Fluctuation in the relative quantities of proteins involved in energy metabolism during dormancy and reactivation was the most significant observation we made in this study. Proteins that are up-regulated or uniquely expressed during reactivation from dormancy offer to be attractive targets for therapeutic

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

    PubMed Central

    2011-01-01

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

  11. Non-human sources of Mycobacterium tuberculosis.

    PubMed

    Ghodbane, Ramzi; Drancourt, Michel

    2013-11-01

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

  12. Transformative tools for tackling tuberculosis.

    PubMed

    Gardiner, Jennifer L; Karp, Christopher L

    2015-10-19

    The world is in need of more effective approaches to controlling tuberculosis. The development of improved control strategies has been hampered by deficiencies in the tools available for detecting Mycobacterium tuberculosis and defining the dynamic consequences of the interaction of M. tuberculosis with its human host. Key needs include a highly sensitive, specific nonsputum diagnostic; biomarkers predictive of responses to therapy; correlates of risk for disease development; and host response-independent markers of M. tuberculosis infection. Tools able to sensitively detect and quantify total body M. tuberculosis burden might well be transformative across many needed use cases. Here, we review the current state of the field, paying particular attention to needed changes in experimental paradigms that would facilitate the discovery, validation, and development of such tools.

  13. Student Pharmacists as Tuberculosis Screeners.

    PubMed

    McKennon, Skye A; Arnold, Jennifer

    2016-03-25

    Objective. To develop, implement, and evaluate a targeted educational module on tuberculosis screening with second-year professional pharmacy students that improves their knowledge, skills, and attitudes regarding tuberculosis screening. Design. A tuberculosis-screening educational module was developed in collaboration with the Washington State Pharmacy Association and Department of Health and incorporated in a core student pharmacist class. Students completed online didactic training and a live practicum, each lasting 90 minutes. Assessment. Students were assessed using a pre/postdidactic assessment, live practicum tuberculin skin testing (TST) administration and evaluation assessment, and postprogram written reflection. Student pre/postknowledge assessment scores improved in all areas except in documentation. Conclusion. The tuberculosis screening educational module significantly improved student knowledge, skills, and attitudes regarding tuberculosis screening. PMID:27073277

  14. Student Pharmacists as Tuberculosis Screeners

    PubMed Central

    Arnold, Jennifer

    2016-01-01

    Objective. To develop, implement, and evaluate a targeted educational module on tuberculosis screening with second-year professional pharmacy students that improves their knowledge, skills, and attitudes regarding tuberculosis screening. Design. A tuberculosis-screening educational module was developed in collaboration with the Washington State Pharmacy Association and Department of Health and incorporated in a core student pharmacist class. Students completed online didactic training and a live practicum, each lasting 90 minutes. Assessment. Students were assessed using a pre/postdidactic assessment, live practicum tuberculin skin testing (TST) administration and evaluation assessment, and postprogram written reflection. Student pre/postknowledge assessment scores improved in all areas except in documentation. Conclusion. The tuberculosis screening educational module significantly improved student knowledge, skills, and attitudes regarding tuberculosis screening. PMID:27073277

  15. Transformative tools for tackling tuberculosis

    PubMed Central

    2015-01-01

    The world is in need of more effective approaches to controlling tuberculosis. The development of improved control strategies has been hampered by deficiencies in the tools available for detecting Mycobacterium tuberculosis and defining the dynamic consequences of the interaction of M. tuberculosis with its human host. Key needs include a highly sensitive, specific nonsputum diagnostic; biomarkers predictive of responses to therapy; correlates of risk for disease development; and host response–independent markers of M. tuberculosis infection. Tools able to sensitively detect and quantify total body M. tuberculosis burden might well be transformative across many needed use cases. Here, we review the current state of the field, paying particular attention to needed changes in experimental paradigms that would facilitate the discovery, validation, and development of such tools. PMID:26458772

  16. Tuberculosis incidence among contacts of active pulmonary tuberculosis

    PubMed Central

    Cailleaux-Cezar, M.; de A. Melo, D.; Xavier, G. M.; de Salles, C. L. G.; de Mello, F. C. Q.; Ruffino-Netto, A.; Golub, J. E.; Efron, A.; Chaisson, R. E.; Conde, M. B.

    2013-01-01

    SUMMARY BACKGROUND Treatment of latent tuberculosis (TB) infection (LTBI) in Brazil is recommended only in the case of contacts of pulmonary smear-positive TB patients aged ≤15 years with a tuberculin skin test (TST) ≥10 mm and no previous bacille Calmette-Guérin (BCG) vaccination or with a TST ≥15 mm regardless of previous BCG vaccination. OBJECTIVE To evaluate the 2-year incidence and predictors of TB among contacts who did not meet the Brazilian criteria for LTBI treatment. DESIGN Retrospective cohort study. Contacts aged between 12 and 15 years and those aged >15 years who did not meet the Brazilian criteria for LTBI treatment were enrolled in the study. RESULTS TB incidence was 3.2% (22/667), with an estimated TB rate of 1649 per 100 000 population. Risk of TB was greater among the 349 contacts with TST ≥5 mm (5.4%) compared to the 318 contacts with TST < 5 mm (0.9%; RR 6.04, 95%CI 1.7–20.6). CONCLUSION The high incidence of TB among contacts who did not meet the Brazilian criteria for LTBI treatment strongly suggests that these criteria should be reviewed. Furthermore, even among BCG-vaccinated contacts, TST induration ≥5 mm was the only variable that predicted the development of TB disease within 2 years. PMID:19146746

  17. Where do those remains come from?

    PubMed

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

    2014-12-01

    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

  18. A Blueprint to Address Research Gaps in the Development of Biomarkers for Pediatric Tuberculosis.

    PubMed

    Nicol, Mark Patrick; Gnanashanmugam, Devasena; Browning, Renee; Click, Eleanor S; Cuevas, Luis E; Detjen, Anne; Graham, Steve M; Levin, Michael; Makhene, Mamodikoe; Nahid, Payam; Perez-Velez, Carlos M; Reither, Klaus; Song, Rinn; Spiegel, Hans M L; Worrell, Carol; Zar, Heather J; Walzl, Gerhard

    2015-10-15

    Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area.

  19. 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

  20. Tuberculosis notifications in Australia, 2011.

    PubMed

    Bareja, Christina; Waring, Justin; Stapledon, Richard; Toms, Cindy; Douglas, Paul

    2014-12-31

    The National Notifiable Diseases Surveillance System received 1,385 tuberculosis (TB) notifications in 2011, representing a rate of 6.2 cases per 100,000 population. While Australia has maintained a rate of 5 to 6 cases per 100,000 for TB since the mid-1980s, there has been a steady increase in incidence over the past decade. In 2011, Australia's overseas-born population continued to represent the majority of TB notifications (88%) with a notification rate of 20.2 per 100,000. The incidence of TB in the Australian-born Indigenous population has fluctuated over the last decade and showed no clear trend; however, in 2011 the notification rate was 4.9 per 100,000, which is a notable decrease from the 7.5 per 100,000 recorded in 2010. The incidence of TB in the Australian-born non-Indigenous population has continued to remain low at 0.9 per 100,000. Australia continued to record only a small number of multi-drug-resistant TB (MDR-TB) cases nationally (n=25), all of which were identified in the overseas-born population. To ensure that Australia can retain its low TB rate and work toward reducing rates further, it is essential that Australia maintains good centralised national TB reporting to monitor trends and identify at-risk populations, and continues to contribute to global TB control initiatives.

  1. Host genomics and control of tuberculosis infection.

    PubMed

    Cobat, A; Orlova, M; Barrera, L F; Schurr, E

    2013-01-01

    Tuberculosis (TB), caused by the human pathogenic bacterium Mycobacterium tuberculosis, poses a major global health problem. The tubercle bacillus is transmitted from person to person by aerosol, but only a proportion of those in contact with infectious aerosol particles will become infected. If infection occurs, less than 10% of those infected will develop clinical signs of TB, while the majority will develop latent TB infection (LTBI). The identification and treatment of LTBI persons is a major aspect of TB control, especially in low-incidence, highly developed nations. In the absence of a gold standard test for latent TB, infection is inferred with the help of either the in vivo tuberculin skin test or in vitro interferon gamma release assays of anti-mycobacterial immunity. Recent work has observed high heritability of these immune assays indicating the critical role of the host genetic background on the establishment of infection and latency. Additional genetic studies have identified the host genetic background as an important covariate for the proper interpretation of the results obtained from LTBI assays. Taken together, these data suggest TB surveillance and control can likely be improved by including host genetic information into the interpretation of these widely used assays.

  2. [Tuberculosis in Asia].

    PubMed

    2002-10-01

    1. Philippines: The development, expansion and maintenance of pilot area activities: Cristina B. Giango (Technical Division, Cebu Provincial Health Office, the Philippines) In 1994, the Department of Health developed the new NTP policies based on WHO recommendations and started a pilot project in Cebu Province in collaboration with the Japan International Cooperation Agency. To test its feasibility and effectiveness, the new NTP policies were pre-tested in one city and one Rural Health Unit. The test showed a high rate of three sputum collection (90%), high positive rate (10%), and high cure rate (80%). Before the new guidelines were introduced, the new policy was briefed, a baseline survey of the facility was conducted, equipment was provided, and intensive training was given. Recording/Reporting forms and procedures were also developed to ensure accurate reporting. Supervision, an important activity to ensure effective performance, was institutionalized. Laboratory services were strengthened, and a quality-control system was introduced in 1995 to ensure the quality of the laboratory services. With the implementation of DOTS strategy, barangay health workers were trained as treatment partners. In partnership with the private sector, the TB Diagnostic Committee was organized to deliberate and assess sputum negative but X-ray positive cases. The implementation of the new NTP guidelines in Cebe Province has reached a satisfactory level, the cure rate and positive rate have increased, and laboratory services have improved. Because of its successful implementation, the new NTP guidelines are now being used nationwide. 2. Nepal: The DOTS Strategy in the area with hard geographic situation: Dirgh Singh Bam (National Tuberculosis Center, Nepal) Three groups of factors characterize the population of Nepal: 1) Socio-cultural factors, e.g. migration, poverty, language; 2) Environmental factors, e.g. geography and climate; and 3) Political factors, prisoners and refugee

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

    PubMed Central

    2014-01-01

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

  4. 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

  5. Fish mycobacteriosis (Tuberculosis)

    USGS Publications Warehouse

    Parisot, T.J.; Wood, J.W.

    1959-01-01

    The etiologic agent for the bacterial disease, "fish tuberculosis" (more correctly "mycobacteriosis"), was first observed in carp in 189& from a pond in France. Subsequently similar agents have been isolated from or observed in fish in fresh water, salt water, and brackish water, in fish in aquaria, hatcheries, and natural habitat~ (wild populations of fish). The disease has been recognized as an important infection among hatchery reared salmonid fishes on the West Coast of the United States, and in aquarium fishes such as the neon tetra, the Siamese fighting fish, and in salt water fish held in zoological displays.

  6. Contemporary mediastinal tuberculosis.

    PubMed Central

    Bloomberg, T J; Dow, C J

    1980-01-01

    Mediastinal lymphadenopathy is a prominent feature of adult tuberculosis in immigrant groups in the United Kingdom. Chest radiography of 95 tuberculous immigrants showed mediastinal gland enlargement in 29 cases, whereas none of the 42 Europeans showed this feature. An analysis has been made of the distribution of the disease in all groups together with a more detailed evaluation of mediastinal involvement in the immigrants. Pericardial effusions were seen in eight patients together with the following three unusual complications: (1) broncho-oesophageal fistula; (2) bronchial erosion; (3) superior mediastinal obstruction. Images PMID:7434292

  7. Primary tuberculosis of palate.

    PubMed

    Chen, Ihk; Jamal, S; Pua, K C

    2015-01-01

    Primary tuberculosis (TB) of the hard palate is very rare. A 74-year-old man was presented with 6-month history of dysphagia along with an irregular mass in the hard and soft palate. Magnetic resonance imaging (MRI) revealed thickened and increased signal intensity within hard and soft palate. Tissue biopsy showed focal caseating granulomatous-like lesion and the histochemical staining using Ziehl-Neelsen stain for acid-fast bacilli was positive. Positive histochemical studies provided evidences that the hard palate mass was most likely due to TB. Thus, the patient was started on antituberculous therapy.

  8. The Effectiveness and Safety of Fluoroquinolone-Containing Regimen as a First-Line Treatment for Drug-Sensitive Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Lee, Hyun Woo; Lee, Jung Kyu; Kim, Eunyoung; Yim, Jae-Joon; Lee, Chang-Hoon

    2016-01-01

    Background Fluoroquinolone is recommended as a pivotal antituberculous agent for treating multi-drug-resistant pulmonary tuberculosis. However, its effectiveness as first-line treatment remains controversial. The present study was conducted to validate the fluoroquinolone-containing regimen for drug-sensitive pulmonary tuberculosis. Methods We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials until June 5, 2015. Randomized controlled trials (RCTs) that compared antituberculous regimens containing fluoroquinolone with the standard regimen were included. Results Eleven RCTs that included 6,334 patients were selected. Fluoroquinolone-containing regimens had a higher rate of sputum culture conversion at 2 months of treatment (M-H fixed odds ratio [OR], 1.36; 95% confidence interval [CI], 1.20–1.54). However, the outcomes were less favorable (M-H fixed OR, 0.69; 95% CI, 0.59–0.82) and the associated total adverse events were more frequent (M-H fixed OR, 1.84; 95% CI, 1.46–2.31) in the fluoroquinolone-containing regimen group, without a significant heterogeneity according to treatment duration. Treatment with the fluoroquinolone-containing regimen for 4 months showed a higher relapse rate. Conclusions Despite a higher culture conversion rate at 2 months of treatment, the fluoroquinolone-containing regimen had limitations, including less favorable outcomes and more adverse events, as the first-line therapy for drug-sensitive pulmonary tuberculosis. PMID:27455053

  9. Tuberculosis in the AIDS era.

    PubMed Central

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

    1995-01-01

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

  10. Experience with pulmonary resection for extensively drug-resistant tuberculosis.

    PubMed

    Shiraishi, Yuji; Katsuragi, Naoya; Kita, Hidefumi; Toishi, Masayuki; Onda, Takahito

    2008-12-01

    Extensively drug-resistant tuberculosis is becoming a global threat. It is a relatively new phenomenon, and its optimal management remains undetermined. We report our experience in using pulmonary resection for treating patients with this disease. Records were reviewed of 54 consecutive patients undergoing a pulmonary resection for multidrug-resistant tuberculosis at Fukujuji Hospital between 2000 and 2006. These patients were identified using the definition approved by the World Health Organization Global Task Force on extensively drug-resistant tuberculosis in October 2006. Five (9%) patients (3 men and 2 women) aged 31-60 years met the definition. None of the patients was HIV-positive. Although the best available multidrug regimens were initiated, no patient could achieve sputum conversion. Adjuvant resectional surgery was considered because the patients had localized disease. Procedures performed included pneumonectomy (2) and upper lobectomy (3). There was no operative mortality or morbidity. All patients attained sputum-negative status after the operation, and they were maintained on multidrug regimens for 12-25 months postoperatively. All patients remained free from disease at the time of follow-up. Pulmonary resection under cover of state-of-the-art chemotherapy is safe and effective for patients with localized extensively drug-resistant tuberculosis.

  11. Changing trends in childhood tuberculosis.

    PubMed

    Mukherjee, Aparna; Lodha, Rakesh; Kabra, S K

    2011-03-01

    Several changes have been observed in the epidemiology, clinical manifestations, diagnostic modalities and treatment of tuberculosis. Emergence of HIV epidemic and drug resistance have posed significant challenges. With increase in the number of diseased adults and spread of HIV infection, the infection rates in children are likely to increase. It is estimated that in developing countries, the annual risk of tuberculosis infection in children is 2.5%. Nearly 8-20% of the deaths caused by tuberculosis occur in children. Extra pulmonary tuberculosis has increased over last two decades. HIV infected children are at an increased risk of tuberculosis, particularly disseminated disease. In last two decades, drug resistant tuberculosis has increased gradually with emergence of MDR and XDR-TB. The rate of drug resistance to any drug varied from 20% to 80% in different geographic regions. Significant changes have occurred in TB diagnostics. Various diagnostic techniques such as fluorescence LED microscopy, improved culture techniques, antigen detection, nucleic acid amplification, line probe assays and IGRAs have been developed and evaluated to improve diagnosis of childhood tuberculosis. Serodiagnosis is an attractive investigation but till date none of the tests have desirable sensitivity and specificity. Tests based on nucleic acid amplification are a promising advance but relatively less experience in children, need for technical expertise and high cost are limiting factors for their use in children with tuberculosis. Short-course chemotherapy for childhood tuberculosis is well established. Directly observed treatment strategy (DOTS) have shown encouraging result. DOTS plus strategy has been introduced for MDR TB. PMID:21161446

  12. New Regimens to Prevent Tuberculosis in Adults with HIV Infection

    PubMed Central

    Martinson, Neil A.; Barnes, Grace L.; Moulton, Lawrence H.; Msandiwa, Reginah; Hausler, Harry; Ram, Malathi; McIntyre, James A.; Gray, Glenda E.; Chaisson, Richard E.

    2012-01-01

    BACKGROUND Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus (HIV) is efficacious, but few patients around the world receive such treatment. We evaluated three new regimens for latent tuberculosis that may be more potent and durable than standard isoniazid treatment. METHODS We randomly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6 months (control group). The primary end point was tuberculosis-free survival. RESULTS The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter. Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine–isoniazid group, 2.9 per 100 person-years in the rifampin–isoniazid group, and 2.7 per 100 person-years in the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the control group (P>0.05 for all comparisons). Serious adverse reactions were more common in the continuous-isoniazid group (18.4 per 100 person-years) than in the other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance. CONCLUSIONS On the basis of the expected rates of tuberculosis in this population of HIV-infected adults, all secondary prophylactic regimens were effective. Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid. PMID:21732833

  13. Toys Remain Viral Playground for 24 Hours

    MedlinePlus

    ... a toy's surface at typical indoor temperatures and humidity levels. Specifically, they tested the ability of so- ... East Respiratory Syndrome (MERS). At 60 percent relative humidity, 1 percent of the virus remained infectious on ...

  14. Immunometabolism in Tuberculosis

    PubMed Central

    Shi, Lanbo; Eugenin, Eliseo A.; Subbian, Selvakumar

    2016-01-01

    Immunometabolism, the study of the relationship between bioenergetic pathways and specific functions of immune cells, has recently gained increasing appreciation. In response to infection, activation of the host innate and adaptive immune cells is accompanied by a switch in the bioenergetic pathway from oxidative phosphorylation to glycolysis, a metabolic remodeling known as the Warburg effect, which is required for the production of antimicrobial and pro-inflammatory effector molecules. In this review, we summarize the current understanding of the Warburg effect and discuss its association with the expression of host immune responses in tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb). We also discuss potential mechanisms underlying the Warburg effect with a focus on the expression and regulation of hypoxia-inducible factor 1 alpha (HIF-1α), the regulatory subunit of HIF-1, a major transcription regulator involved in cellular stress adaptation processes, including energy metabolism and antimicrobial responses. We also propose a novel hypothesis that Mtb perturbs the Warburg effect of immune cells to facilitate its survival and persistence in the host. A better understanding of the dynamics of metabolic states of immune cells and their specific functions during TB pathogenesis can lead to the development of immunotherapies capable of promoting Mtb clearance and reducing Mtb persistence and the emergence of drug resistant strains. PMID:27148269

  15. [Microbiological diagnosis of tuberculosis].

    PubMed

    Allerberger, F; Fille, M; Streif, W; Luef, G; Schmutzhard, E; Dierich, M P

    1994-01-01

    The increased incidence of tuberculosis as well as the availability of new diagnostic testing methods clearly have various implications for the routine microbiology laboratory: samples must be sent to the microbiology lab for testing immediately after being taken and microscopically investigated the same day. In other countries, difficult to treat, multi-resistant Mycobacterium tuberculosis strains have occurred. Thus decisive hygienic measures must be taken early on in cases of highly infectious patients (i.e. patients with microscopically positive sputum). Liquid media (MB Check Roche, Bactec) as well as Löwenstein Jensen media must be inoculated in the lab. Liquid media allow both faster detection of certain atypical mycobacteria and increased accuracy. Classification of culturally established agents through commercial genetic probes (AccuProbe Mycobacterien) or with high pressure liquid chromatography is possible within hours when acid-fast rods are present. Time consuming identification by determination of biochemical and culture morphological characteristics should be reserved for reference labs. Today, rapid tests like analysis of tuberculostearic acid or polymerase chain reaction are already useful for special questions like ruling out tuberculous meningitis. In most cases, however, these rapid tests cannot replace identification of microbes with culture techniques. PMID:7941601

  16. Immunometabolism in Tuberculosis.

    PubMed

    Shi, Lanbo; Eugenin, Eliseo A; Subbian, Selvakumar

    2016-01-01

    Immunometabolism, the study of the relationship between bioenergetic pathways and specific functions of immune cells, has recently gained increasing appreciation. In response to infection, activation of the host innate and adaptive immune cells is accompanied by a switch in the bioenergetic pathway from oxidative phosphorylation to glycolysis, a metabolic remodeling known as the Warburg effect, which is required for the production of antimicrobial and pro-inflammatory effector molecules. In this review, we summarize the current understanding of the Warburg effect and discuss its association with the expression of host immune responses in tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb). We also discuss potential mechanisms underlying the Warburg effect with a focus on the expression and regulation of hypoxia-inducible factor 1 alpha (HIF-1α), the regulatory subunit of HIF-1, a major transcription regulator involved in cellular stress adaptation processes, including energy metabolism and antimicrobial responses. We also propose a novel hypothesis that Mtb perturbs the Warburg effect of immune cells to facilitate its survival and persistence in the host. A better understanding of the dynamics of metabolic states of immune cells and their specific functions during TB pathogenesis can lead to the development of immunotherapies capable of promoting Mtb clearance and reducing Mtb persistence and the emergence of drug resistant strains. PMID:27148269

  17. Cellular therapy in tuberculosis.

    PubMed

    Parida, Shreemanta K; Madansein, Rajhmun; Singh, Nalini; Padayatchi, Nesri; Master, Iqbal; Naidu, Kantharuben; Zumla, Alimuddin; Maeurer, Markus

    2015-03-01

    Cellular therapy now offer promise of potential adjunct therapeutic options for treatment of drug-resistant tuberculosis (TB). We review here the role of Mesenchymal stromal cells, (MSCs), as well as other immune effector cells in the therapy of infectious diseases with a focus on TB. MSCs represent a population of tissue-resident non-hematopoietic adult progenitor cells which home into injured tissues increase the proliferative potential of broncho-alveolar stem cells and restore lung epithelium. MSCs have been shown to be immune-modulatory and anti-inflammatory mediated via cell-cell contacts as well as soluble factors. We discuss the functional profile of MSCs and their potential use for adjunct cellular therapy of multi-drug resistant TB, with the aim of limiting tissue damage, and to convert unproductive inflammatory responses into effective anti-pathogen directed immune responses. Adjunct cellular therapy could potentially offer salvage therapy options for patients with drug-resistant TB, increase clinically relevant anti-M.tuberculosis directed immune responses and possibly shorten the duration of anti-TB therapy. PMID:25809753

  18. 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

  19. Molecular Epidemiology of Mycobacterium tuberculosis among South African Gold Miners

    PubMed Central

    Lewis, James J.; Connors, Jeremy; Chihota, Violet N.; Shashkina, Elena; van der Meulen, Minty; Graviss, Edward A.; Ha, Ngan P.; Kreiswirth, Barry N.; Grant, Alison D.; Fielding, Katherine L.; Dorman, Susan E.; Churchyard, Gavin J.

    2015-01-01

    Rationale: HIV-associated tuberculosis remains a major health problem among the gold-mining workforce in South Africa. We postulate that high levels of recent transmission, indicated by strain clustering, are fueling the tuberculosis epidemic among gold miners. Objectives: To combine molecular and epidemiologic data to describe Mycobacterium tuberculosis genetic diversity, estimate levels of transmission, and examine risk factors for clustering. Methods: We conducted a cross-sectional study of culture-positive M. tuberculosis isolates in 15 gold mine shafts across three provinces in South Africa. All isolates were subject IS6110-based restriction fragment length polymorphisms, and we performed spoligotyping analysis and combined it with basic demographic and clinical information. Measurements and Main Results: Of the 1,602 M. tuberculosis patient isolates, 1,240 (78%) had genotyping data available for analysis. A highly diverse bacillary population was identified, comprising a total of 730 discrete genotypes. Four genotypic families (Latin American Mediterranean spoligotype family; W-Beijing; AH or X; and T1–T4) accounted for over 50% of all strains. Overall, 45% (560/1,240) of strains were genotypically clustered. The minimum estimate for recent transmission (n − 1 method) was 32% (range, 27–34%). There were no individual-level risk factors for clustering, apart from borderline evidence for being non–South African and having self-reported HIV infection. Conclusions: The high M. tuberculosis genetic diversity and lack of risk factors for clustering are indicative of a universal risk for disease among gold miners and likely mixing with nonmining populations. Our results underscore the urgent need to intensify interventions to interrupt transmission across the entire gold-mining workforce in South Africa. PMID:25419914

  20. [Risk groups for tuberculosis in Chile].

    PubMed

    Herrera, Tania

    2015-02-01

    Tuberculosis (TB) remains a major global and national problem. In Chile the incidence rate has remained at 13 per 100,000 inhabitants for several years without tendency to the expected decline that would allow their elimination by 2020. As a low prevalence country, TB cases have been concentrated in risk groups, reaching 33% in 2013, and this proportion increases as younger people are analyzed. The main risk groups in Chile are HIV co-infection, foreigners and population of prisons. By 2013, the proportion of cases for these three groups was 8.7%, 8.4% and 3.9% respectively, and these percentages vary significantly when regional situation is analyzed. In addition, many of these patients have more than one risk factor, demons-rating the existence of clusters more vulnerable to TB.

  1. [Risk groups for tuberculosis in Chile].

    PubMed

    Herrera, Tania

    2015-02-01

    Tuberculosis (TB) remains a major global and national problem. In Chile the incidence rate has remained at 13 per 100,000 inhabitants for several years without tendency to the expected decline that would allow their elimination by 2020. As a low prevalence country, TB cases have been concentrated in risk groups, reaching 33% in 2013, and this proportion increases as younger people are analyzed. The main risk groups in Chile are HIV co-infection, foreigners and population of prisons. By 2013, the proportion of cases for these three groups was 8.7%, 8.4% and 3.9% respectively, and these percentages vary significantly when regional situation is analyzed. In addition, many of these patients have more than one risk factor, demons-rating the existence of clusters more vulnerable to TB. PMID:25860037

  2. Advances in Diagnostic Assays for Tuberculosis.

    PubMed

    Lawn, Stephen D

    2015-08-07

    Approximately one-third of the global burden of tuberculosis (TB) remains undiagnosed each year and the vast majority of cases of multidrug-resistant TB remain undetected. Many countries still place heavy reliance on outdated technologies that are blunt and ineffective tools for controlling this epidemic. However, during the past 10 years, there has been substantial progress within the TB diagnostics developmental pipeline. Old technologies have been reviewed and improved and new technologies have been developed and evaluated and are now being implemented. This review summarizes these developments and describes the currently available diagnostic tools. Consideration is given to the requirements of future diagnostic tests and how these should be evaluated not only with regard to their diagnostic accuracy and operational feasibility, but ultimately in terms of whether they impact clinical outcomes cost effectively, especially for those most in need.

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

    PubMed Central

    2013-01-01

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

  4. [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.

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

    PubMed Central

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

    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 constructed, consisting of 849 unique reactions and 739 metabolites, and involving 726 genes. The model was calibrated by growing Mycobacterium bovis bacille Calmette Guérin in continuous culture and steady-state growth parameters were measured. Flux balance analysis was used to calculate substrate consumption rates, which were shown to correspond closely to experimentally determined values. Predictions of gene essentiality were also made by flux balance analysis simulation and were compared with global mutagenesis data for M. tuberculosis grown in vitro. A prediction accuracy of 78% was achieved. Known drug targets were predicted to be essential by the model. The model demonstrated a potential role for the enzyme isocitrate lyase during the slow growth of mycobacteria, and this hypothesis was experimentally verified. An interactive web-based version of the model is available. Conclusion The GSMN-TB model successfully simulated many of the growth properties of M. tuberculosis. The model provides a means to examine the metabolic flexibility of bacteria and predict the phenotype of mutants, and it highlights previously unexplored features of M. tuberculosis metabolism. PMID:17521419

  6. Tuberculosis associates with both airflow obstruction and low lung function: BOLD results

    PubMed Central

    Amaral, André F. S.; Coton, Sonia; Kato, Bernet; Tan, Wan C.; Studnicka, Michael; Janson, Christer; Gislason, Thorarinn; Mannino, David; Bateman, Eric D.; Buist, Sonia; Burney, Peter G. J.

    2015-01-01

    Background In small studies and cases series, a history of tuberculosis has been associated with both airflow obstruction, which is characteristic of chronic obstructive pulmonary disease, and restrictive patterns on spirometry. Objective To assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults. Methods The study was performed in adults, aged 40 and above, who took part in the multicentre cross-sectional, general population-based, Burden of Obstructive Lung Disease study, had provided acceptable post-bronchodilator spirometry measurements and information on a history of tuberculosis. The associations between a history of tuberculosis and airflow obstruction and spirometric restriction were assessed within each participating centre, and estimates combined using meta-analysis. These estimates were stratified by high and low/middle income countries, according to gross national income. Results A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio = 2.51, 95% confidence interval 1.83-3.42) and spirometric restriction (adjusted odds ratio = 2.13, 95% confidence interval 1.42-3.19). Conclusion A history of tuberculosis was associated with both airflow obstruction and spirometric restriction, and should be considered as a potentially important cause of obstructive disease and low lung function, particularly where tuberculosis is common. PMID:26113680

  7. 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

  8. Use of PCR in routine diagnosis of treated and untreated pulmonary tuberculosis.

    PubMed Central

    Yuen, K Y; Chan, K S; Chan, C M; Ho, B S; Dai, L K; Chau, P Y; Ng, M H

    1993-01-01

    AIMS--To assess the routine use of a polymerase chain reaction (PCR) assay for the direct detection of Mycobacterium tuberculosis in expectorated sputum specimens. METHODS--A pair of primers (20-mer) were designed to amplify the 38 kilodalton protein of M tuberculosis. The specificity of the assay was evaluated in 31 M tuberculosis strains, 15 atypical mycobacterium species, and several commensal bacteria of the upper respiratory tract. The assay was subsequently applied to 519 sputum specimens from 85 inpatients of a chest hospital in Hong Kong. RESULTS--An amplified product of 239 base pairs was found in all M tuberculosis strains, standard strains of M bovis, and M africanum but not in the other bacterial strains tested. For the 51 patients with pulmonary radiographic lesions, the diagnosis of pulmonary tuberculosis was subsequently confirmed by both culture and PCR in 41 of them. Five patients who were treated before admission were positive by PCR alone. All but one patient in the control group (patients with acute exacerbation of chronic obstructive airway diseases) or those with atypical mycobacterial diseases were PCR negative. The PCR remained positive after four weeks of anti-tuberculosis treatment in 29 patients, 16 of whom had become culture negative. CONCLUSION--This PCR assay is a useful technique for the diagnosis of untreated and recently treated cases of pulmonary tuberculosis. Images PMID:8496388

  9. A rare location of sacral tuberculosis: A report of three cases

    PubMed Central

    Lazrak, Faiza; Abourazzak, Fatima Ezzahra; Elouzzani, Fatima Ezzahra; Benzagmout, Mohammed; Harzy, Taoufik

    2014-01-01

    Tuberculosis remains one of the most common infectious diseases in the world. Vertebral tuberculosis is the commonest form of bone and joint tuberculosis; however, isolated sacral tuberculosis is rare. This atypical presentation may lead to a delay in diagnosis and treatment. We report three cases of sacral tuberculosis diagnosed in young women, aged 30, 23, and 35 years old, respectively. Lombosciatic pain was the main symptom in all cases. All patients had a biological assessment, plain radiographs, and CT scan. However, magnetic resonance imaging was done in only two cases. All patients underwent surgical sacral biopsy, and the diagnosis of tuberculosis was confirmed by histology in all cases. The evolution was satisfactory with the adjunction of antituberculous chemotherapy in all cases. Spinal tuberculosis should be the first and foremost differential diagnosis in the presence of atypical clinical and radiological features of a sacral lesion, particularly in developing countries. Early diagnosis and treatment could prevent or minimize the neurological morbidity in such cases. PMID:27708880

  10. Pathway Analyses Identify Novel Variants in the WNT Signaling Pathway Associated with Tuberculosis in Chinese Population

    PubMed Central

    Hu, Xuejiao; Zhou, Juan; Chen, Xuerong; Zhou, Yanhong; Song, Xingbo; Cai, Bei; Zhang, Jingya; Lu, Xiaojun; Ying, Binwu

    2016-01-01

    Tuberculosis remains a global public health problem, and its immunopathogenesis is still poorly understood. In this study, 25 single nucleotide polymorphisms (SNPs) in the WNT pathway were evaluated in relation to tuberculosis risk in a Chinese Han discovery set, and 6 candidate susceptible SNPs were further validated in a Chinese Tibetan cohort. Luciferase reporter assay, RT-qPCR and Western blot were used to assess the functionality of the important WNT polymorphisms. Five polymorphisms were associated with tuberculosis susceptibility after Bonferroni correction: SFRP1 rs4736958, CTNNB1 rs9859392, rs9870255 and rs3864004 showed decreased tuberculosis risk; SFRP1 rs7832767 was related to an increased risk (OR = 1.81, 95% CI = 1.30–2.52, p = 0.010). Patients with TT genotype of rs4736958 and rs7832767 correlated with higher CRP concentrations (p = 0.003, <0.001, respectively). Functional assays revealed that mutant alleles of rs9859392 (G), rs9870255 (C) and rs3864004 (A) were associated with significantly decreased transcriptional activity, lower CTNNB1 mRNA expression and p-β-catenin level, which were consistent with their effects of decreasing TB risk. Our results provide evidences that WNT pathway polymorphisms influence tuberculosis susceptibility and host immune response to Mycobacterium tuberculosis, suggesting that these variations may serve as novel markers for identifying the risk of developing tuberculosis. PMID:27334567

  11. 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.

  12. Isolated tuberculosis of the coccyx.

    PubMed

    Kumar, A; Varshney, M K; Trikha, V; Khan, S A

    2006-10-01

    Vertebral disease constitutes approximately 50% of all skeletal tuberculosis. We describe a patient who developed a discharging sinus at the tip of the coccyx. Extensive examination revealed isolated tuberculosis of the coccyx. Although rare, the condition should be suspected in patients presenting with a chronic sinus in the sacrococcygeal area and a lytic lesion in the coccyx on CT or MRI, particularly in the developing world.

  13. Occupational risk factors for developing tuberculosis.

    PubMed

    Rosenman, K D; Hall, N

    1996-08-01

    We sought to assess whether there is an increased risk of tuberculosis among individuals who work in certain industries or occupations. A case-referent study of 149 male tuberculosis (TB) patients reported to the New Jersey Health Department from 1985 to 1987 and 290 referents was performed. Standardized interviews were conducted via the telephone or in person. Increased risk of TB was highest in heavy drinkers (OR = 3.33, 95% CL 1.99-5.59) and those who had a history of living with someone who had a history of TB (OR = 10.92, 95% CL 4.92-24.22). Occupations and industries associated with elevated risk for TB included: four silica-using industries-quarrying (OR = 3.96, 95% CL 0.36-44.02), pottery and related products (OR = 1.99, 95% CL 0.49-8.06), nonmetallic mineral and stone products (OR = 4.00, 95% CL 0.72-22.10), and ship and boat building and repair (OR = 1.84, 95% CL 0.76-4.43); hospitals (OR = 2.10, 95% CL 1.08-4.10); light truck drivers (OR = 2.49, 95% CL 1.30-4.77); agriculture (OR = 2.31, 95% CL 0.82-6.50); eating and drinking establishments (OR = 2.83, 95% CL 1.11-7.20); and janitors/cleaners (OR = 2.00, 95% CL 0.63-6.31). Except for janitors/cleaners, these elevated odds ratios remained for the above occupations/industries after controlling for alcohol or a history of having lived with someone with tuberculosis. Limitations of the study include a poor response rate (38%) and the exclusion of women from the study. PMID:8844044

  14. Occupational risk factors for developing tuberculosis.

    PubMed

    Rosenman, K D; Hall, N

    1996-08-01

    We sought to assess whether there is an increased risk of tuberculosis among individuals who work in certain industries or occupations. A case-referent study of 149 male tuberculosis (TB) patients reported to the New Jersey Health Department from 1985 to 1987 and 290 referents was performed. Standardized interviews were conducted via the telephone or in person. Increased risk of TB was highest in heavy drinkers (OR = 3.33, 95% CL 1.99-5.59) and those who had a history of living with someone who had a history of TB (OR = 10.92, 95% CL 4.92-24.22). Occupations and industries associated with elevated risk for TB included: four silica-using industries-quarrying (OR = 3.96, 95% CL 0.36-44.02), pottery and related products (OR = 1.99, 95% CL 0.49-8.06), nonmetallic mineral and stone products (OR = 4.00, 95% CL 0.72-22.10), and ship and boat building and repair (OR = 1.84, 95% CL 0.76-4.43); hospitals (OR = 2.10, 95% CL 1.08-4.10); light truck drivers (OR = 2.49, 95% CL 1.30-4.77); agriculture (OR = 2.31, 95% CL 0.82-6.50); eating and drinking establishments (OR = 2.83, 95% CL 1.11-7.20); and janitors/cleaners (OR = 2.00, 95% CL 0.63-6.31). Except for janitors/cleaners, these elevated odds ratios remained for the above occupations/industries after controlling for alcohol or a history of having lived with someone with tuberculosis. Limitations of the study include a poor response rate (38%) and the exclusion of women from the study.

  15. Identification of infant skeletal remains: case report.

    PubMed

    Yoshino, M; Miyasaka, S; Sato, H; Miyake, B; Seta, S

    1989-12-01

    Three cases of infant skeletal remains were described from the view point of personal identification. The age was exactly estimated from union of ossification centers, dental calcification and eruption. While, the sex estimation was not highly reliable, because sex differences had not clearly appeared in infant skeletons, and it was rather difficult in some cases. In infant skeletal remains, age estimation is especially important to help personal identification. The most recent photograph of a presumed person should be used for personal identification by superimposition technique since the size and proportion of infant skull constantly change as a result of its development.

  16. Engaging communities in tuberculosis research.

    PubMed

    Boulanger, Renaud F; Seidel, Stephanie; Lessem, Erica; Pyne-Mercier, Lee; Williams, Sharon D; Mingote, Laia Ruiz; Scott, Cherise; Chou, Alicia Y; Lavery, James V

    2013-06-01

    According to a growing consensus among biomedical researchers, community engagement can improve the ethics and outcomes of clinical trials. Although successful efforts to develop community engagement practices in HIV/AIDS research have been reported, little attention has been given to engagement with the community in tuberculosis research. This article aims to draw attention to some existing community engagement initiatives in tuberculosis research and to resources that might help tuberculosis researchers to establish and implement community engagement programmes for their trials. One of these resources-the good participatory practice guidelines for tuberculosis drug trials-offers a conceptual framework and practical guidance for community engagement in tuberculosis research. To build momentum and to improve community engagement, lessons need to be shared, and formal assessment strategies for community engagement initiatives need to be developed. To build successfully on the promising activities described in this personal view, research funders and sponsors should show leadership in allocation of resources for the implementation and assessment of community engagement programmes in tuberculosis trials.

  17. Pre-multidrug-resistant Mycobacterium tuberculosis Beijing strain associated with disseminated tuberculosis in a pet dog.

    PubMed

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

    2014-01-01

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

  18. Asymmetric cell division in Mycobacterium tuberculosis and its unique features.

    PubMed

    Vijay, Srinivasan; Nagaraja, Mukkayyan; Sebastian, Jees; Ajitkumar, Parthasarathi

    2014-03-01

    Recently, several reports showed that about 80 % of mid-log phase Mycobacterium smegmatis, Mycobacterium marinum, and Mycobacterium bovis BCG cells divide symmetrically with 5-10 % deviation in the septum position from the median. However, the mode of cell division of the pathogenic mycobacterial species, Mycobacterium tuberculosis, remained unclear. Therefore, in the present study, using electron microscopy, fluorescence microscopy of septum- and nucleoid-stained live and fixed cells, and live cell time-lapse imaging, we show the occurrence of asymmetric cell division with unusually deviated septum/constriction in 20 % of the 15 % septating M. tuberculosis cells in the mid-log phase population. The remaining 80 % of the 15 % septating cells divided symmetrically but with 2-5 % deviation in the septum/constriction position, as reported for M. smegmatis, M. marinum, and M. bovis BCG cells. Both the long and the short portions of the asymmetrically dividing M. tuberculosis cells with unusually deviated septum contained nucleoids, thereby generating viable short and long cells from each asymmetric division. M. tuberculosis short cells were acid fast positive and, like the long cells, further readily underwent growth and division to generate micro-colony, thereby showing that they were neither mini cells, spores nor dormant forms of mycobacteria. The freshly diagnosed pulmonary tuberculosis patients' sputum samples, which are known for the prevalence of oxidative stress conditions, also contained short cells at the same proportion as that in the mid-log phase population. The probable physiological significance of the generation of the short cells through unusually deviated asymmetric cell division is discussed.

  19. Some social and forensic aspects of exhumation and reinterment of industrial revolution remains.

    PubMed

    Duff, E J; Johnson, J S

    1974-03-23

    The aetiological aspects of exhumed remains from two burial sites were examined using 1839 and 1879 as years of comparison. We tried to discover whether the sample of recovered remains was representative of those buried. The state of the remains varied according to the type of soil and coffin material in which they were buried. At the earlier date most deaths were caused by infectious lesions rather than degenerative ones and 76% of those who died were below employable age-whereas in 1879 the commonest causes of death were tuberculosis ("phthisis") and bronchitis, and 42% died before they could be employed. The registration of deaths were recorded more accurately at the later date, and it was easier to build up a picture of the age, sex, and occupation of the people who died.

  20. 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…

  1. 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.

  2. Rapid Reagentless Detection of M. tuberculosis H37Ra in Respiratory Effluents

    SciTech Connect

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

    2008-01-29

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

  3. Leveling of Tuberculosis Incidence - United States, 2013-2015.

    PubMed

    Salinas, Jorge L; Mindra, Godwin; Haddad, Maryam B; Pratt, Robert; Price, Sandy F; Langer, Adam J

    2016-03-25

    After 2 decades of progress toward tuberculosis (TB) elimination with annual decreases of ≥0.2 cases per 100,000 persons (1), TB incidence in the United States remained approximately 3.0 cases per 100,000 persons during 2013-2015. Preliminary data reported to the National Tuberculosis Surveillance System indicate that TB incidence among foreign-born persons in the United States (15.1 cases per 100,000) has remained approximately 13 times the incidence among U.S.-born persons (1.2 cases per 100,000). Resuming progress toward TB elimination in the United States will require intensification of efforts both in the United States and globally, including increasing U.S. efforts to detect and treat latent TB infection, strengthening systems to interrupt TB transmission in the United States and globally, accelerating reductions in TB globally, particularly in the countries of origin for most U.S.

  4. Disseminated tuberculosis presenting with finger swelling in a patient with tuberculous osteomyelitis: a case report

    PubMed Central

    Agarwal, Shradha; Caplivski, Daniel; Bottone, Edward J

    2005-01-01

    Background Extrapulmonary manifestations of tuberculosis have become increasingly important in the era of HIV/AIDS. Case presentation We describe a case of tuberculosis (TB) dactylitis in a patient with AIDS who originated from the Ivory Coast. The diagnosis was established by direct visualization of acid-fast bacilli on joint fluid and bone biopsy of the proximal phalanx. Imaging of the chest revealed multiple bilateral nodules. Confirmation of the diagnosis was made by isolation of Mycobacterium tuberculosis from sputum and bone cultures. Conclusion Tuberculosis should be considered in patients with unusual soft tissue or skeletal lesions, especially when an immunosuppressive condition is present. Ziehl-Neelsen staining and culture of tissue obtained via surgical biopsy offer the most direct approach to diagnosis. PMID:16269085

  5. Tuberculosis and the military.

    PubMed

    O'Shea, Matthew K; Wilson, D

    2013-09-01

    Tuberculosis (TB) causes significant morbidity and mortality among the global civilian population. Historically, TB has also been responsible for a considerable burden of disease among military populations during periods of both peace and conflict. TB will continue to be of importance to the military for several reasons. Military units live and work in confined environments, personnel may deploy to areas highly endemic for TB where there is the potential to be exposed to infected local communities, and they undertake physiologically stressful activities during training and operations. These are just a few of the factors that may increase the risk of acquiring, developing and transmitting TB among military personnel. This review examines the military relevance of TB in the modern era within the context of epidemiological, pathological and clinical considerations of this ancient disease.

  6. Native New Zealand plants with inhibitory activity towards Mycobacterium tuberculosis

    PubMed Central

    2010-01-01

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

  7. Molecular Diversity of Mycobacterium tuberculosis Strains in Northwestern Iran

    PubMed Central

    Pourostadi, Mahya; Rashedi, Jalil; Mahdavi Poor, Behroz; Samadi Kafil, Hossein; Shirazi, Samaneh; Asgharzadeh, Mohammad

    2016-01-01

    Background Years after the development of antituberculosis (TB) drugs, many people continue to suffer from this disease. To control the spread of TB, strains of the Mycobacterium tuberculosis complex need to be determined, and sources of infection must be identified. Such steps should help to prevent transmission of the infection. Objectives The aim of this study was to perform molecular genotyping of isolates of the M. tuberculosis complex obtained from patients in northwestern Iran. Methods One hundred ninety-four culture-positive M. tuberculosis isolates obtained from patients in northwestern Iran were analyzed using the mycobacterial interspersed repetitive unit-exact tandem repeats (MIRU-ETR) method. Results The MIRU-ETR method distinguished 162 different patterns in the 194 isolates, comprising 23 clusters and 139 unique patterns. Its discriminatory power according to the Hunter-Gaston discriminatory index (HGDI) was 0.9978. The largest cluster contained six isolates. Conclusions This research indicated that various strains of M. tuberculosis were responsible for TB and that the majority of cases were due to reactivation. PMID:27800145

  8. Seasonality of tuberculosis in delhi, India: a time series analysis.

    PubMed

    Kumar, Varun; Singh, Abhay; Adhikary, Mrinmoy; Daral, Shailaja; Khokhar, Anita; Singh, Saudan

    2014-01-01

    Background. It is highly cost effective to detect a seasonal trend in tuberculosis in order to optimize disease control and intervention. Although seasonal variation of tuberculosis has been reported from different parts of the world, no definite and consistent pattern has been observed. Therefore, the study was designed to find the seasonal variation of tuberculosis in Delhi, India. Methods. Retrospective record based study was undertaken in a Directly Observed Treatment Short course (DOTS) centre located in the south district of Delhi. Six-year data from January 2007 to December 2012 was analyzed. Expert modeler of SPSS ver. 21 software was used to fit the best suitable model for the time series data. Results. Autocorrelation function (ACF) and partial autocorrelation function (PACF) at lag 12 show significant peak suggesting seasonal component of the TB series. Seasonal adjusted factor (SAF) showed peak seasonal variation from March to May. Univariate model by expert modeler in the SPSS showed that Winter's multiplicative model could best predict the time series data with 69.8% variability. The forecast shows declining trend with seasonality. Conclusion. A seasonal pattern and declining trend with variable amplitudes of fluctuation were observed in the incidence of tuberculosis.

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

    PubMed Central

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

    2014-01-01

    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

  10. Multi-drug-resistant tuberculosis in HIV positive patients in Eastern Europe.

    PubMed

    Post, Frank A; Grint, Daniel; Werlinrud, Anne Marie; Panteleev, Alexander; Riekstina, Vieja; Malashenkov, Evgeniy A; Skrahina, Alena; Duiculescu, Dan; Podlekareva, Daria; Karpov, Igor; Bondarenko, Vasiliy; Chentsova, Nelly; Lundgren, Jens; Mocroft, Amanda; Kirk, Ole; Miro, Jose M

    2014-03-01

    Observational data from Eastern Europe on the management and outcome of multi-drug-resistant tuberculosis (MDR TB) in HIV positive populations remain sparse in the English-language literature. We compared clinical characteristics and outcomes of 55 patients who were diagnosed with HIV and MDR TB in Eastern Europe between 2004 and 2006 to 89 patients whose Mycobacterium tuberculosis isolates were susceptible to isoniazid and rifampicin. Patients with HIV and MDR TB were young and predominantly male with high rates of intravenous drug use, imprisonment and hepatitis C co-infection. Eighty-four per cent of patients with MDR TB had no history of previous TB drug exposure suggesting that the majority of MDR TB resulted from transmission of drug-resistant M. tuberculosis. The use of non-standardized tuberculosis treatment was common, and the use of antiretroviral therapy infrequent. Compared to those with susceptible tuberculosis, patients with MDR TB were less likely to achieve cure or complete tuberculosis treatment (21.8% vs. 62.9%, p < 0.0001), and they were more likely to die (65.5% vs. 27.0%, p < 0.0001). Our study documents suboptimal management and poor outcomes in HIV positive patients with MDR TB. Implementation of WHO guidelines, rapid TB diagnostics and TB drug susceptibility testing for all patients remain a priority in this region. PMID:24247067

  11. Towards host-directed therapies for tuberculosis.

    PubMed

    Zumla, Alimuddin; Maeurer, Markus; Chakaya, Jeremiah; Hoelscher, Michael; Ntoumi, Francine; Rustomjee, Roxana; Vilaplana, Cristina; Yeboah-Manu, Dorothy; Rasolof, Voahangy; Munderi, Paula; Singh, Nalini; Aklillu, Eleni; Padayatchi, Nesri; Macete, Eusebio; Kapata, Nathan; Mulenga, Modest; Kibiki, Gibson; Mfinanga, Sayoki; Nyirenda, Thomas; Maboko, Leonard; Garcia-Basteiro, Alberto; Rakotosamimanana, Niaina; Bates, Matthew; Mwaba, Peter; Reither, Klaus; Gagneux, Sebastien; Edwards, Sarah; Mfinanga, Elirehema; Abdulla, Salim; Cardona, Pere-Joan; Russell, James B W; Gant, Vanya; Noursadeghi, Mahdad; Elkington, Paul; Bonnet, Maryline; Menendez, Clara; Dieye, Tandakha N; Diarra, Bassirou; Maiga, Almoustapha; Aseffa, Abraham; Parida, Shreemanta; Wejse, Christian; Petersen, Eskild; Kaleebu, Pontiano; Oliver, Matt; Craig, Gill; Corrah, Tumena; Tientcheu, Leopold; Antonio, Martin; Rao, Martin; McHugh, Timothy D; Sheikh, Aziz; Ippolito, Giuseppe; Ramjee, Gita; Kaufmann, Stefan H E; Churchyard, Gavin; Steyn, Andrie; Grobusch, Martin; Sanne, Ian; Martinson, Neil; Madansein, Rajhmun; Wilkinson, Robert J; Mayosi, Bongani; Schito, Marco; Wallis, Robert S

    2015-08-01

    The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies. PMID:26184493

  12. Treatment outcome of tuberculosis patients at Gondar University Teaching Hospital, Northwest Ethiopia. A five - year retrospective study

    PubMed Central

    Tessema, Belay; Muche, Abebe; Bekele, Assegedech; Reissig, Dieter; Emmrich, Frank; Sack, Ulrich

    2009-01-01

    Background In Gondar University Teaching Hospital standardized tuberculosis prevention and control programme, incorporating Directly Observed Treatment, Short Course (DOTS) started in 2000. According to the proposal of World Health Organization (WHO), treatment outcome is an important indicator of tuberculosis control programs. This study investigated the outcome of tuberculosis treatment at Gondar University Teaching Hospital in Northwest Ethiopia. Methods We analyzed the records of 4000 tuberculosis patients registered at Gondar University Teaching Hospital from September 2003 to May 2008. Treatment outcome and tuberculosis type were categorized according to the national tuberculosis control program guideline. Multivariate analysis using logistic regression model was used to analyse the association between treatment outcome and potential predictor variables. Results From the total of 4000 patients, tuberculosis type was categorized as extrapulmonary in 1133 (28.3%), smear negative pulmonary tuberculosis in 2196 (54.9%) and smear positive pulmonary tuberculosis in 671 (16.8%) cases. Of all patients, treatment outcome was classified as successfully treated in 1181(29.5%), defaulted in 730 (18.3%), died in 403 (10.1%), treatment failed in six (0.2%) and transferred out in 1680 (42.0%) patients. Males had the trend to be more likely to experience death or default than females, and the elderly were more likely to die than younger. The proportion of default rate was increased across the years from 97(9.2%) to 228(42.9%). Being female, age group 15-24 years, smear positive pulmonary tuberculosis and being urban resident were associated with higher treatment success rate. Conclusion The treatment success rate of tuberculosis patients was unsatisfactorily low (29.5%). A high proportion of patients died (10.1%) or defaulted (18.3%), which is a serious public health concern that needs to be addressed urgently. PMID:19799801

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

    PubMed

    Lou, Zhiyong; Zhang, Xiaoxue

    2010-05-01

    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 and death with emergence of multi-drug-resistant and extensively-drug-resistant forms, it is urgent to identify new drugs with novel targets to ensure future therapeutic success. In this regards, the structural genomics of M. tuberculosis provides important information to identify potential targets, perform biochemical assays, determine crystal structures in complex with potential inhibitor(s), reveal the key sites/residues for biological activity, and thus validate drug targets and discover novel drugs. In this review, we will discuss the recent progress on novel targets for structure-based anti-M. tuberculosis drug discovery.

  14. [Etiology of pleural effusion based on material from the Hospital of Lung Diseases and Tuberculosis].

    PubMed

    Kolczyński, A

    2001-01-01

    The aim of this study was to show the influence of the changes in incidence of tuberculosis and lung cancer on the etiology of pleural effusion among the patients of the Hospital of Lung Diseases and Tuberculosis. To this end 349 patients with pleural effusion were separated from the total number of 9786 patients treated in years 1990-1999. The most numerous group--180 patients (51.58%)--consisted of the cases of malignant neoplasms, 109 (31.25%)--tuberculosis and 60 (17.17%)--remaining diseases altogether. At the time, the statistically significant increase of the whole number of patients with pleural effusion as well as the increase of patients with pleural effusion caused by malignant tumors were recorded. It was shown that the increasing incidence of lung cancer in Silesia at that time caused the change of the profile of the Hospital of Lung Diseases and Tuberculosis.

  15. Cat scratch disease and lymph node tuberculosis in a colon patient with cancer.

    PubMed

    Matias, M; Marques, T; Ferreira, M A; Ribeiro, L

    2013-12-12

    A 71-year-old man operated for a sigmoid tumour remained in the surveillance after adjuvant chemotherapy. After 3 years, a left axillary lymph node was visible on CT scan. The biopsy revealed a necrotising and abscessed granulomatous lymphadenitis, suggestive of cat scratch disease. The patient confirmed having been scratched by a cat and the serology for Bartonella henselae was IgM+/IgG-. Direct and culture examinations for tuberculosis were negative. The patient was treated for cat scratch disease. One year later, the CT scan showed increased left axillary lymph nodes and a left pleural effusion. Direct and cultural examinations to exclude tuberculosis were again negative. Interferon-γ release assay testing for tuberculosis was undetermined and then positive. Lymph node and pleural tuberculosis were diagnosed and treated with a good radiological response. This article has provides evidence of the importance of continued search for the right diagnosis and that two diagnoses can happen in the same patient.

  16. Primary oral tuberculosis in a patient with lepromatous leprosy: Diagnostic dilemma.

    PubMed

    Ganesan, Vithiya; Mandal, Jharna

    2016-03-01

    Pulmonary tuberculosis (TB) is the most common form of TB. Primary infection can also affect the pharynx, cervical lymph node, intestine, or oral mucosa. Historically, the observed incidence of concomitant infection with leprosy and TB is high. However, reports of concomitant infection in modern literature remain scarce. Most cases reported in the literature had borderline/lepromatous leprosy and pulmonary tuberculosis. Extrapulmonary tuberculosis is reported in only 3.2% of leprosy cases. To the best of our knowledge, this is the first case report of primary oral tuberculosis of the tongue in a patient with lepromatous leprosy with Type 2 lepra reaction. The patient was referred to Directly Observed Treatment, Short-Course clinic and started on Category I treatment. She received oral prednisolone for lepra reaction, which was subsequently tapered and stopped, however, she continued to receive other antileprotic drugs (thalidomide and clofazimine). The patient's general condition improved and she is on regular follow up. PMID:26927999

  17. Integration of Published Information Into a Resistance-Associated Mutation Database for Mycobacterium tuberculosis

    PubMed Central

    Salamon, Hugh; Yamaguchi, Ken D.; Cirillo, Daniela M.; Miotto, Paolo; Schito, Marco; Posey, James; Starks, Angela M.; Niemann, Stefan; Alland, David; Hanna, Debra; Aviles, Enrique; Perkins, Mark D.; Dolinger, David L.

    2015-01-01

    Tuberculosis remains a major global public health challenge. Although incidence is decreasing, the proportion of drug-resistant cases is increasing. Technical and operational complexities prevent Mycobacterium tuberculosis drug susceptibility phenotyping in the vast majority of new and retreatment cases. The advent of molecular technologies provides an opportunity to obtain results rapidly as compared to phenotypic culture. However, correlations between genetic mutations and resistance to multiple drugs have not been systematically evaluated. Molecular testing of M. tuberculosis sampled from a typical patient continues to provide a partial picture of drug resistance. A database of phenotypic and genotypic testing results, especially where prospectively collected, could document statistically significant associations and may reveal new, predictive molecular patterns. We examine the feasibility of integrating existing molecular and phenotypic drug susceptibility data to identify associations observed across multiple studies and demonstrate potential for well-integrated M. tuberculosis mutation data to reveal actionable findings. PMID:25765106

  18. [Tuberculosis in 2015: From diagnosis to the detection of multiresistant cases].

    PubMed

    Hervé, C; Bergot, E; Veziris, N; Blanc, F-X

    2015-10-01

    Incidence of pulmonary tuberculosis, a contagious infectious disease, decreases in France with 4934 reported cases in 2013. Tuberculosis remains a global health problem as smear is positive in only 50% cases and culture methods require time. In such a context, genotypic diagnostic tools such as Xpert® MTB/RIF gained interest. This rapid and simple-to-use nucleic acid amplification test allows a diagnosis in two hours and prevents further invasive investigations in pulmonary and mediastinal tuberculosis. Because of its low sensitivity, it cannot be used in pleural fluid. Indirect immunologic tests are of no use to diagnose active tuberculosis disease. Another current area of interest is the emergence of resistant tuberculosis. In France, approximately 100 cases of multidrug resistant tuberculosis and a few extensively drug resistant tuberculosis have been reported in 2014. Even though these forms of tuberculosis are imported, it is crucial to identify hazardous situations and to optimize care of these patients. Xpert® MTB/RIF is again of marked interest here as it detects rifampin resistance with a 95% sensitivity and a 98% specificity. Interpretation of genotypic tests such as Genotype® MTBDR or Xpert® MTB/RIF depends on known detected mutations, although they do not always have a clinical or phenotypic expression. In multidrug resistant tuberculosis, the new drug bedaquiline obtained approval for temporarily use in combination with other molecules when there is no other treatment option. Results of bedaquiline are encouraging but adverse events like QT prolongation or the development of new specific drug resistance should convince clinicians to use it with caution.

  19. 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.

  20. [Bacteriological diagnosis of tuberculosis: current hieratic classification of methods].

    PubMed

    Carbonnelle, B; Carpentier, E

    1995-01-01

    To assure the diagnosis of tuberculosis, one needs the observation, the isolation and the identification of the causative agent Mycobacterium tuberculosis. In this approach, the microscopic exam occurs as a fast but neither sensitive or specific test. The isolation on solid media is slow and needs more than three weeks before becoming positive. Nevertheless, it is a sensitive and specific one. The identification of the isolated strain and the study of sensitivity to antibiotic agents require an equal delay. Then, 2 months are necessary to achieve the analysis. The AIDS epidemic with the increase of opportunistic mycobacterial diseases, and the unexpected arrival of resistant Mycobacteria is creating as a difficult therapeutic problem. The cultivation in liquid media with the radiometric method (Bactec) shortens the time of culture by half. The genomic amplification assay has been hopeful because it allowed results in 2 days. However, some technical difficulties happen when the test is conducted and it is less sensitive than the isolation process. The hierarchical classification of the laboratory useful process to establish the diagnosis of tuberculosis disease remains the microscopic observation of the bacilli and their isolation. Today, the use of PCR alone does not assure the diagnosis of tuberculosis, however it may be used as a additional diagnostic test. PMID:7569420

  1. Ipr1 gene mediates innate immunity to tuberculosis

    PubMed Central

    Pan, Hui; Yan, Bo-Shiun; Rojas, Mauricio; Shebzukhov, Yuriy V.; Zhou, Hongwei; Kobzik, Lester; Higgins, Darren; Daly, Mark; Bloom, Barry R.; Kramnik, Igor

    2005-01-01

    An estimated 8 million people are infected each year with the pathogen, Mycobacterium tuberculosis, and over 2 million die annually1. Yet only about 10% of those infected develop tuberculosis. Genetic variation within host populations is known to play a significant role in humans and animals 2,3, but the nature of genetic control of host resistance to tuberculosis remains poorly understood. Previously we mapped a new genetic locus on mouse chromosome 1, designated sst1 (for supersusceptibility to tuberculosis1)4. Here we demonstrate in sst1 congenic mouse strains that this locus mediates innate immunity, and identify a candidate gene, Intracellular Pathogen Resistance 1 (Ipr1), within the sst1 locus. The Ipr1 gene is upregulated in the sst1 resistant macrophages upon activation and infection, but is not expressed in the sst1 susceptible macrophages. Expression of the Ipr1 transgene in the sst1 susceptible macrophages limits multiplication not only of MTB but also Listeria monocytogenes and switches a cell death pathway of the infected macrophages from necrosis to apoptosis. Our data suggest that the Ipr1 gene product may play a novel role in integrating signals generated by intracellular pathogens with mechanisms controlling innate immunity, cell death and pathogenesis. PMID:15815631

  2. [Bacteriological diagnosis of tuberculosis: current hieratic classification of methods].

    PubMed

    Carbonnelle, B; Carpentier, E

    1995-01-01

    To assure the diagnosis of tuberculosis, one needs the observation, the isolation and the identification of the causative agent Mycobacterium tuberculosis. In this approach, the microscopic exam occurs as a fast but neither sensitive or specific test. The isolation on solid media is slow and needs more than three weeks before becoming positive. Nevertheless, it is a sensitive and specific one. The identification of the isolated strain and the study of sensitivity to antibiotic agents require an equal delay. Then, 2 months are necessary to achieve the analysis. The AIDS epidemic with the increase of opportunistic mycobacterial diseases, and the unexpected arrival of resistant Mycobacteria is creating as a difficult therapeutic problem. The cultivation in liquid media with the radiometric method (Bactec) shortens the time of culture by half. The genomic amplification assay has been hopeful because it allowed results in 2 days. However, some technical difficulties happen when the test is conducted and it is less sensitive than the isolation process. The hierarchical classification of the laboratory useful process to establish the diagnosis of tuberculosis disease remains the microscopic observation of the bacilli and their isolation. Today, the use of PCR alone does not assure the diagnosis of tuberculosis, however it may be used as a additional diagnostic test.

  3. 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

  4. 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

  5. Tuberculosis pharmacotherapy: strategies to optimize patient care

    PubMed Central

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

    2009-01-01

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

  6. Will tuberculosis become resistant to all antibiotics?

    PubMed Central

    Dye, C; Espinal, M A

    2001-01-01

    The discovery of high prevalences of antibiotic resistance in some pathogens, in some parts of the world, has provoked fears of a widespread loss of drug efficacy. Here, we use a mathematical model to investigate the evolution of resistance to four major anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and streptomycin) in 47 sites around the world. The model provides a new method of estimating the relative risk of treatment failure for patients carrying drug-resistant strains and the proportion of patients who develop resistance after failing treatment. Using estimates of these two quantities together with other published data, we reconstructed the epidemic spread of isoniazid resistance over the past 50 years. The predicted median prevalence of resistance among new cases today was 7.0% (range 0.9-64.3%), close to the 6.3% (range 0-28.1%) observed. Predicted and observed prevalences of resistance to isoniazid plus rifampicin (multidrug-resistant or MDR-TB) after 30 years of combined drug use were also similar, 0.9% (0.1-5.9%) and 1.0% (range 0-14.1%), respectively. With current data, and under prevailing treatment practices, it appears that MDR-TB will remain a localized problem, rather than becoming a global obstacle to tuberculosis control. To substantiate this result, further measurements are needed of the relative fitness of drug-resistant strains. PMID:12123297

  7. [Culture based diagnostic methods for tuberculosis].

    PubMed

    Baylan, Orhan

    2005-01-01

    Culture methods providing isolates for identification and drug susceptibility testing, still represent the gold standard for the definitive diagnosis of tuberculosis, although the delay in obtaining results still remains a problem. Traditional solid media are recommended for use along with liquid media in primary isolation of mycobacteria. At present, a number of elaborate culture systems are available commercially. They range from simple bottles and tubes such as MGIT (BD Diagnostic Systems, USA), Septi-Chek AFB (BD, USA) and MB Redox (Biotest Diagnostics, USA) to semiautomated system (BACTEC 460TB, BD, USA) and fully automated systems (BACTEC 9000 MB [BD, USA], BACTEC MGIT 960 [BD, USA], ESP Culture System II [Trek Diagnostics, USA], MB/BacT ALERT 3D System [BioMérieux, NC], TK Culture System [Salubris Inc, Turkey]). Culture methods available today are sufficient to permit laboratories to develop an algoritm that is optimal for patients and administrative needs. In this review article, the culture systems used for the diagnosis of tuberculosis, their mechanisms, advantages and disadvantages have been discussed under the light of recent literature.

  8. The cell envelope glycoconjugates of Mycobacterium tuberculosis

    PubMed Central

    Angala, Shiva Kumar; Belardinelli, Juan Manuel; Huc-Claustre, Emilie; Wheat, William H.; Jackson, Mary

    2015-01-01

    Tuberculosis (TB) remains the second most common cause of death due to a single infectious agent. The cell envelope of Mycobacterium tuberculosis (Mtb), the causative agent of the disease in humans, is a source of unique glycoconjugates and the most distinctive feature of the biology of this organism. It is the basis of much of Mtb pathogenesis and one of the major causes of its intrinsic resistance to chemotherapeutic agents. At the same time, the unique structures of Mtb cell envelope glycoconjugates, their antigenicity and essentiality for mycobacterial growth provide opportunities for drug, vaccine, diagnostic and biomarker development, as clearly illustrated by recent advances in all of these translational aspects. This review focuses on our current understanding of the structure and biogenesis of Mtb glycoconjugates with particular emphasis on one of most intriguing and least understood aspect of the physiology of mycobacteria: the translocation of these complex macromolecules across the different layers of the cell envelope. It further reviews the rather impressive progress made in the last ten years in the discovery and development of novel inhibitors targeting their biogenesis. PMID:24915502

  9. 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.

  10. 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

  11. 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

  12. Mill and the right to remain uninformed.

    PubMed

    Strasser, M

    1986-08-01

    In a recent article in the Journal of Medicine and Philosophy, David Ost (1984) claims that patients do not have a right to waive their right to information. He argues that patients cannot make informed rational decisions without full information and thus, a right to waive information would involve a right to avoid one's responsibility to act as an autonomous moral agent. In support of his position, Ost cites a passage from Mill. Yet, a correct interpretation of the passage in question would support one's right to remain uninformed in certain situations. If the information would hurt one's chances for survival or hurt one's ability to make calm, rational decisions, then one not only does not have a duty to find out the information, but one's exercising one's right to remain uninformed may be the only rational course of action to take.

  13. Explosives remain preferred methods for platform abandonment

    SciTech Connect

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

    1996-05-06

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

  14. 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

  15. Direct Dating of Hominids Remains In Eurasia

    NASA Astrophysics Data System (ADS)

    Yokoyama, Y.; Falguères, C.

    When archaeological sites are associated with human remains, it is relevant to be able to date those valuable remains for different reasons. The main one is that it avoids the stratigraphical problems which can be due to intrusive burials in the sequence. The other reason consists in the fact that human bones may be encountered out of established stratigraphical context. On the other hand, the majority of dating methods currently used are destructive and can not be applied on these precious samples particularly when they are older than 40,000 years and can not be dated by radiocarbon. Since several years, we have developped a completely non-destructive method which consists in the measurement of human remains using the gamma -ray spectrometry. This technique has been used recently by other laboratories. We present here two important cases for the knowledge of human evolution in Eurasia. The first example is Qafzeh site in Israel where many human skeletons have been unearthed from burials associated with fauna and lithic artefacts. This site has been dated by several independent radiometric methods. So, it was possible to compare our gamma results with the other results yielded by the different methods. The second case concerns the most evolved Homo erectus found in Java, Indonesia, at Ngandong site, close to the Solo river. A recent debate has been focused on the age of these fossils and their direct dating is of outmost importance for the knowledge of settlement of Modern Humans in South-East Asia.

  16. Role of Serine140 in the mode of action of Mycobacterium tuberculosis β-ketoacyl-ACP Reductase (MabA)

    PubMed Central

    2012-01-01

    Background Tuberculosis (TB) still remains one of the most deadly infectious diseases in the world. Mycobacterium tuberculosis β-ketoacyl-ACP Reductase (MabA) is a member of the fatty acid elongation system type II, providing precursors of mycolic acids that are essential to the bacterial cell growth and survival. MabA has been shown to be essential for M. tuberculosis survival and to play a role in intracellular signal transduction of bacilli. Findings Here we describe site-directed mutagenesis, recombinant protein expression and purification, steady-state kinetics, fluorescence spectroscopy, and molecular modeling for S140T and S140A mutant MabA enzymes. No enzyme activity could be detected for S140T and S140A. Although the S140T protein showed impaired NADPH binding, the S140A mutant could bind to NADPH. Computational predictions for NADPH binding affinity to WT, S140T and S140A MabA proteins were consistent with fluorescence spectroscopy data. Conclusions The results suggest that the main role of the S140 side chain of MabA is in catalysis. The S140 side chain appears to also play an indirect role in NADPH binding. Interestingly, NADPH titrations curves shifted from sigmoidal for WT to hyperbolic for S140A, suggesting that the S140 residue may play a role in displacing the pre-existing equilibrium between two forms of MabA in solution. The results here reported provide a better understanding of the mode of action of MabA that should be useful to guide the rational (function-based) design of inhibitors of MabA enzyme activity which, hopefully, could be used as lead compounds with anti-TB action. PMID:23006410

  17. 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

  18. 9 CFR 381.81 - Tuberculosis.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned....

  19. 9 CFR 381.81 - Tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned....

  20. 9 CFR 311.2 - Tuberculosis.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Tuberculosis. 311.2 Section 311.2... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The... pathogenesis of tuberculosis in swine, cattle, sheep, goats, and equines. (a) Carcasses condemned. The...

  1. 9 CFR 311.2 - Tuberculosis.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Tuberculosis. 311.2 Section 311.2... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The... pathogenesis of tuberculosis in swine, cattle, sheep, goats, and equines. (a) Carcasses condemned. The...

  2. 38 CFR 3.959 - Tuberculosis.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Tuberculosis. 3.959..., Compensation, and Dependency and Indemnity Compensation Protection § 3.959 Tuberculosis. Any veteran who, on...) tuberculosis may receive compensation under 38 U.S.C. 1114(q) and 1156 as in effect before August 20,...

  3. 38 CFR 3.959 - Tuberculosis.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Tuberculosis. 3.959..., Compensation, and Dependency and Indemnity Compensation Protection § 3.959 Tuberculosis. Any veteran who, on...) tuberculosis may receive compensation under 38 U.S.C. 1114(q) and 1156 as in effect before August 20,...

  4. 9 CFR 311.2 - Tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Tuberculosis. 311.2 Section 311.2... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The... pathogenesis of tuberculosis in swine, cattle, sheep, goats, and equines. (a) Carcasses condemned. The...

  5. 38 CFR 3.959 - Tuberculosis.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Tuberculosis. 3.959..., Compensation, and Dependency and Indemnity Compensation Protection § 3.959 Tuberculosis. Any veteran who, on...) tuberculosis may receive compensation under 38 U.S.C. 1114(q) and 1156 as in effect before August 20,...

  6. 9 CFR 381.81 - Tuberculosis.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned....

  7. 38 CFR 3.959 - Tuberculosis.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Tuberculosis. 3.959..., Compensation, and Dependency and Indemnity Compensation Protection § 3.959 Tuberculosis. Any veteran who, on...) tuberculosis may receive compensation under 38 U.S.C. 1114(q) and 1156 as in effect before August 20,...

  8. 9 CFR 381.81 - Tuberculosis.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned....

  9. 9 CFR 381.81 - Tuberculosis.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Tuberculosis. 381.81 Section 381.81 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... § 381.81 Tuberculosis. Carcasses of poultry affected with tuberculosis shall be condemned....

  10. 9 CFR 311.2 - Tuberculosis.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Tuberculosis. 311.2 Section 311.2... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.2 Tuberculosis. The... pathogenesis of tuberculosis in swine, cattle, sheep, goats, and equines. (a) Carcasses condemned. The...

  11. 38 CFR 3.959 - Tuberculosis.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Tuberculosis. 3.959..., Compensation, and Dependency and Indemnity Compensation Protection § 3.959 Tuberculosis. Any veteran who, on...) tuberculosis may receive compensation under 38 U.S.C. 1114(q) and 1156 as in effect before August 20,...

  12. Old Testament biblical references to tuberculosis.

    PubMed

    Daniel, V S; Daniel, T M

    1999-12-01

    Two probable references to tuberculosis are found in Old Testament books of the Bible dating to a time when the Israelites lived in Egypt, which is known from archeological evidence to be an area where tuberculosis was then prevalent. Other putative biblical references to tuberculosis are less credible.

  13. Tuberculosis Facts - You Can Prevent TB

    MedlinePlus

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

  14. Tuberculosis Facts - TB Can Be Treated

    MedlinePlus

    Tuberculosis (TB) Facts TB Can Be Treated What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination Page 1 of 2 TB Facts: TB ...

  15. Pulmonary Tuberculosis and Lepromatous Leprosy Coinfection

    PubMed Central

    Sendrasoa, F. A.; Ranaivo, I. M.; Raharolahy, O.; Andrianarison, M.; Ramarozatovo, L. S.; Rapelanoro Rabenja, F.

    2015-01-01

    Simultaneous occurrence of leprosy and pulmonary tuberculosis is reported infrequently in the modern era. We report a case of pulmonary tuberculosis diagnosed in patient being treated with glucocorticoids for complications of leprosy (type II reaction). Physicians should recognize that the leprosy patients treated with glucocorticoid may develop tuberculosis. PMID:26504603

  16. Distribution of albatross remains in the Far East regions during the Holocene, based on zooarchaeological remains.

    PubMed

    Eda, Masaki; Higuchi, Hiroyoshi

    2004-07-01

    Many albatross remains have been found in the Japanese Islands and the surrounding areas, such as Sakhalin and South Korea. These remains are interesting for two reasons: numerous sites from which albatross remains have been found are located in coastal regions of the Far East where no albatrosses have been distributed recently, and there are some sites in which albatross remains represent a large portion of avian remains, although albatrosses are not easily preyed upon by human beings. We collected data on albatross remains from archaeological sites in the Far East regions during the Holocene and arranged the remains geographically, temporally and in terms of quantity. Based on these results, we showed that coastal areas along the Seas of Okhotsk and Japan have rarely been used by albatrosses in Modern times, though formerly there were many albatrosses. We proposed two explanations for the shrinkage of their distributional range: excessive hunting in the breeding areas, and distributional changes of prey for albatrosses. PMID:15277721

  17. Tuberculosis screening in patients with HIV: use of audit and feedback to improve quality of care in Ghana

    PubMed Central

    Bjerrum, Stephanie; Bonsu, Frank; Hanson-Nortey, Nii Nortey; Kenu, Ernest; Johansen, Isik Somuncu; Andersen, Aase Bengaard; Bjerrum, Lars; Jarbøl, Dorte; Munck, Anders

    2016-01-01

    Background Tuberculosis screening of people living with HIV (PLHIV) can contribute to early tuberculosis diagnosis and improved patient outcomes. Evidence-based guidelines for tuberculosis screening are available, but literature assessing their implementation and the quality of clinical practice is scarce. Objectives To assess tuberculosis screening practices and the effectiveness of audit and performance feedback to improve quality of tuberculosis screening at HIV care clinics in Ghana. Design Healthcare providers at 10 large HIV care clinics prospectively registered patient consultations during May and October 2014, before and after a performance feedback intervention in August 2014. The outcomes of interest were overall tuberculosis suspicion rate during consultations and provider adherence to the International Standards for Tuberculosis Care and the World Health Organizations’ guidelines for symptom-based tuberculosis screening among PLHIV. Results Twenty-one healthcare providers registered a total of 2,666 consultations; 1,368 consultations before and 1,298 consultations after the feedback intervention. Tuberculosis suspicion rate during consultation increased from 12.6 to 20.9% after feedback (odds ratio, OR 1.83; 95% confidence interval, CI: 1.09–3.09). Before feedback, sputum smear microscopy was requested for 58.7% of patients with suspected tuberculosis, for 47.2% of patients with cough ≥2 weeks, and for 27.5% of patients with a positive World Health Organization (WHO) symptom screen (any of current cough, fever, weight loss or night sweats). After feedback, patients with a positive WHO symptom screen were more likely to be suspected of tuberculosis (OR 2.21; 95% CI: 1.19–4.09) and referred for microscopy (OR 2.71; 95% CI: 1.25–5.86). Conclusions A simple prospective audit tool identified flaws in clinical practices for tuberculosis screening of PLHIV. There was no systematic identification of people with suspected active tuberculosis. We found

  18. Evidence of presence of Mycobacterium tuberculosis in bovine tissue samples by multiplex PCR: possible relevance to reverse zoonosis.

    PubMed

    Mittal, M; Chakravarti, S; Sharma, V; Sanjeeth, B S; Churamani, C P; Kanwar, N S

    2014-04-01

    Bovine tuberculosis, caused by Mycobacterium bovis, remains one of the most important zoonotic health concerns worldwide. The transmission of Mycobacterium tuberculosis from humans to animals also occurs especially in countries where there is close interaction of humans with the animals. In the present study, thirty bovine lung tissue autopsy samples from an organized dairy farm located in North India were screened for the presence of Mycobacterium tuberculosis complex by smear microscopy, histopathological findings and PCR. Differential diagnosis of M. tuberculosis and M. bovis was made based on the deletion of mce-3 operon in M. bovis. The present study found eight of these samples positive for M. tuberculosis by multiplex PCR. Sequencing was performed on two PCR-positive representative samples and on annotation, and BLAST analysis confirmed the presence of gene fragment specific to Mycobacterium tuberculosis. The presence of M. tuberculosis in all the positive samples raises the possibility of human-to-cattle transmission and possible adaptation of this organism in bovine tissues. This study accentuates the importance of screening and differential diagnosis of Mycobacterium tuberculosis complex in humans and livestock for adopting effective TB control and eradication programmes.

  19. Mycobacterium aurum is Unable to Survive Mycobacterium tuberculosis Latency Associated Stress Conditions: Implications as Non-suitable Model Organism.

    PubMed

    Sood, Shivani; Yadav, Anant; Shrivastava, Rahul

    2016-06-01

    Mycobacterium tuberculosis manages to remain latent in the human body regardless of extensive chemotherapy. Complete eradication of tuberculosis (TB) requires treatment strategies targeted against latent form of infection, in addition to the current regimen of antimycobacterials. Many in vitro and in vivo models have been proposed to imitate latent TB infection, yet none of them is able to completely mimic latent infection state of M. tuberculosis. Highly infectious nature of the pathogen requiring BSL3 facilities and its long generation time further add to complications. M. aurum has been proposed as an important model organism for high throughput screening of drugs and exhibits high genomic similarity with that of M. tuberculosis. Thus, the present study was undertaken to explore if M. aurum could be used as a surrogate organism for studies related to M. tuberculosis latent infection. M. aurum was subjected to in vitro conditions of oxygen depletion, lack of nutrients and acidic stress encountered by latent M. tuberculosis bacteria. CFU count of M. aurum cells along with any change in cell shape and size was recorded at regular intervals during the stress conditions. M. aurum cells were unable to survive for extended periods under all three conditions used in the study. Thus, our studies suggest that M. aurum is not a suitable organism to mimic M. tuberculosis persistent infection under in vitro conditions, and further studies are required on different species for the establishment of a fast growing species as a suitable model for M. tuberculosis persistent infection. PMID:27570312

  20. Outbreak of Tuberculosis in a Colony of Rhesus Monkeys (Macaca mulatta) after Possible Indirect Contact with a Human TB Patient.

    PubMed

    Mätz-Rensing, K; Hartmann, T; Wendel, G M; Frick, J S; Homolka, S; Richter, E; Munk, M H; Kaup, F-J

    2015-01-01

    Simian tuberculosis is one of the most important bacterial diseases of non-human primates. Outbreaks of tuberculosis have been reported in primate colonies almost as long as these animals have been used experimentally or kept in zoological gardens. Significant progress has been made in reducing the incidence of tuberculosis in captive non-human primates, but despite reasonable precautions, outbreaks continue to occur. The most relevant reason is the high incidence of tuberculosis (TB) amongst the human population, in which tuberculosis is regarded as an important re-emerging disease. Furthermore, many non-human primate species originate from countries with a high burden of human TB. Therefore, Mycobacterium tuberculosis remains a significant threat in animals imported from countries with high rates of human infection. We report an outbreak of tuberculosis among a group of rhesus monkeys (Macaca mulatta) living in a closed, long-term colony. The outbreak coincided with reactivation of a TB infection in a co-worker who never had direct access to the animal house or laboratories. Eleven of 26 rhesus monkeys developed classical chronic active tuberculosis with typical caseous granulomata of varying size within different organs. The main organ system involved was the lung, suggesting an aerosol route of infection. Such an outbreak has significant economic consequences due to animal loss, disruption of research and costs related to disease control. Precautionary measures must be improved in order to avoid TB in non-human primate colonies.

  1. Diagnostic Value of T-cell Interferon-γ Release Assays on Synovial Fluid for Articular Tuberculosis: A Pilot Study

    PubMed Central

    Cheng, Xin-He; Bian, Sai-Nan; Zhang, Yue-Qiu; Zhang, Li-Fan; Shi, Xiao-Chun; Yang, Bo; Zhang, Feng-Chun; Liu, Xiao-Qing

    2016-01-01

    Background: Tuberculosis (TB) remains a major global public health challenge. Articular TB is an important form of extrapulmonary tuberculosis, and its diagnosis is difficult because of the low sensitivity of traditional methods. The aim of this study was to analyze the diagnostic value of T-SPOT.TB on synovial fluid for the diagnosis of articular TB. Methods: Patients with suspected articular TB were enrolled consecutively between August 2011 and December 2015. T-SPOT.TB was performed on both synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs). The final diagnosis of articular TB was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on SFMCs and PBMCs were analyzed. Results: Twenty patients with suspected articular TB were enrolled. Six were diagnosed with articular TB, and 14 patients were diagnosed with other diseases. Sensitivity and specificity were 83% and 86% for T-SPOT.TB on SFMCs, and 67% and 69% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on SFMCs were 71% and 92%, respectively. The PPV and NPV were 50% and 82% for T-SPOT.TB on PBMCs. Conclusion: Sensitivity, specificity, and NPV of T-SPOT.TB on SFMCs appeared higher than that on PBMCs, indicating that T-SPOT.TB on SFMCs might be a rapid and accurate diagnostic test for articular TB. PMID:27174325

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

    PubMed

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

    2012-01-01

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

  3. Why Do Some Cores Remain Starless?

    NASA Astrophysics Data System (ADS)

    Anathpindika, S.

    2016-08-01

    Prestellar cores, by definition, are gravitationally bound but starless pockets of dense gas. Physical conditions that could render a core starless (in the local Universe) is the subject of investigation in this work. To this end, we studied the evolution of four starless cores, B68, L694-2, L1517B, L1689, and L1521F, a VeLLO. We demonstrate: (i) cores contracted in quasistatic manner over a timescale on the order of ~ 105 yr. Those that remained starless briefly acquired a centrally concentrated density configuration that mimicked the profile of a unstable BonnorEbert sphere before rebounding, (ii) three cores viz. L694-2, L1689-SMM16, and L1521F remained starless despite becoming thermally super-critical. By contrast, B68 and L1517B remained sub-critical; L1521F collapsed to become a VeLLO only when gas-cooling was enhanced by increasing the size of dust-grains. This result is robust, for other starless cores viz. B68, L694-2, L1517B, and L1689 could also be similarly induced to collapse. The temperature-profile of starless cores and those that collapsed was found to be radically different. While in the former type, only very close to the centre of a core was there any evidence of decline in gas temperature, by contrast, a core of the latter type developed a more uniformly cold interior. Our principle conclusions are: (a) thermal super-criticality of a core is insufficient to ensure it will become protostellar, (b) potential star-forming cores (the VeLLO L1521F here), could be experiencing dust-coagulation that must enhance gasdust coupling and in turn lower gas temperature, thereby assisting collapse. This also suggests, mere gravitational/virial boundedness of a core is insufficient to ensure it will form stars.

  4. So close: remaining challenges to eradicating polio.

    PubMed

    Toole, Michael J

    2016-01-01

    The Global Polio Eradication Initiative, launched in 1988, is close to achieving its goal. In 2015, reported cases of wild poliovirus were limited to just two countries - Afghanistan and Pakistan. Africa has been polio-free for more than 18 months. Remaining barriers to global eradication include insecurity in areas such as Northwest Pakistan and Eastern and Southern Afghanistan, where polio cases continue to be reported. Hostility to vaccination is either based on extreme ideologies, such as in Pakistan, vaccination fatigue by parents whose children have received more than 15 doses, and misunderstandings about the vaccine's safety and effectiveness such as in Ukraine. A further challenge is continued circulation of vaccine-derived poliovirus in populations with low immunity, with 28 cases reported in 2015 in countries as diverse as Madagascar, Ukraine, Laos, and Myanmar. This paper summarizes the current epidemiology of wild and vaccine-derived poliovirus, and describes the remaining challenges to eradication and innovative approaches being taken to overcome them.

  5. Decomposition Technique for Remaining Useful Life Prediction

    NASA Technical Reports Server (NTRS)

    Saha, Bhaskar (Inventor); Goebel, Kai F. (Inventor); Saxena, Abhinav (Inventor); Celaya, Jose R. (Inventor)

    2014-01-01

    The prognostic tool disclosed here decomposes the problem of estimating the remaining useful life (RUL) of a component or sub-system into two separate regression problems: the feature-to-damage mapping and the operational conditions-to-damage-rate mapping. These maps are initially generated in off-line mode. One or more regression algorithms are used to generate each of these maps from measurements (and features derived from these), operational conditions, and ground truth information. This decomposition technique allows for the explicit quantification and management of different sources of uncertainty present in the process. Next, the maps are used in an on-line mode where run-time data (sensor measurements and operational conditions) are used in conjunction with the maps generated in off-line mode to estimate both current damage state as well as future damage accumulation. Remaining life is computed by subtracting the instance when the extrapolated damage reaches the failure threshold from the instance when the prediction is made.

  6. Linezolid for Infants and Toddlers With Disseminated Tuberculosis: First Steps

    PubMed Central

    Deshpande, Devyani; Srivastava, Shashikant; Pasipanodya, Jotam G.; Bush, Stephen J.; Nuermberger, Eric; Swaminathan, Soumya; Gumbo, Tawanda

    2016-01-01

    Background. Infants and toddlers often present with disseminated and lymph node tuberculosis, in which Mycobacterium tuberculosis (Mtb) is predominantly intracellular. Linezolid, used to treat tuberculosis in adults, has not been formally studied in infants. Infants clear linezolid 5 times faster than adults and achieve lower 0- to 24-hour area under the concentration-time curves (AUC0–24). Methods. To mimic intracellular disease, we infected human-derived THP-1 macrophages with Mtb and inoculated hollow fiber systems. We performed dose-effect and dose-scheduling studies in which we recapitulated the linezolid half-life of 3 hours encountered in infants. Repetitive sampling for linezolid pharmacokinetics, Mtb intracellular burden, viable monocyte count, and RNA sequencing reads were performed up to 28 days. Results. The linezolid extracellular half-life was 2.64 ± 0.38 hours, whereas intracellular half-life was 8.93 ± 1.30 hours (r2 = 0.89). Linezolid efficacy was linked to the AUC0–24 to minimum inhibitory concentration (MIC) ratio (r2 = 0.98). The exposure associated with maximal Mtb kill was an AUC0–24/MIC of 23.37 ± 1.16. We identified a 414-gene transcript on exposure to toxic linezolid doses. The largest number of genes mapped to ribosomal proteins, a signature hitherto not associated with linezolid toxicity. The second-largest number of differentially expressed genes mapped to mitochondrial enzyme inhibition. Linezolid AUC0–24 best explained the mitochondrial gene inhibition, with 50% inhibition at 94 mg × hour/L (highest r2 = 0.98). Conclusions. We identified the linezolid AUC0–24/MIC target for optimal efficacy against pediatric intracellular tuberculosis, and an AUC0–24 threshold associated with mitochondrial inhibition. These constitute a therapeutic window to be targeted for optimal linezolid doses in children with tuberculosis. PMID:27742638

  7. Drug Resistance Mechanisms in Mycobacterium tuberculosis

    PubMed Central

    Palomino, Juan Carlos; Martin, Anandi

    2014-01-01

    Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease. In recent years, even more serious forms of drug resistance have been reported. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular mechanisms involved will improve the available techniques for rapid drug resistance detection and will help to explore new targets for drug activity and development. This review article discusses the mechanisms of action of anti-tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis. PMID:27025748

  8. Drug Resistance Mechanisms in Mycobacterium tuberculosis.

    PubMed

    Palomino, Juan Carlos; Martin, Anandi

    2014-01-01

    Tuberculosis (TB) is a serious public health problem worldwide. Its situation is worsened by the presence of multidrug resistant (MDR) strains of Mycobacterium tuberculosis, the causative agent of the disease. In recent years, even more serious forms of drug resistance have been reported. A better knowledge of the mechanisms of drug resistance of M. tuberculosis and the relevant molecular mechanisms involved will improve the available techniques for rapid drug resistance detection and will help to explore new targets for drug activity and development. This review article discusses the mechanisms of action of anti-tuberculosis drugs and the molecular basis of drug resistance in M. tuberculosis. PMID:27025748

  9. Transcriptional Profiling of Mycobacterium Tuberculosis During Infection: Lessons Learned

    PubMed Central

    Ward, Sarah K.; Abomoelak, Bassam; Marcus, Sarah A.; Talaat, Adel M.

    2010-01-01

    Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis, is considered one of the biggest infectious disease killers worldwide. A significant amount of attention has been directed toward revealing genes involved in the virulence and pathogenesis of this air-born pathogen. With the advances in technologies for transcriptional profiling, several groups, including ours, took advantage of DNA microarrays to identify transcriptional units differentially regulated by M. tuberculosis within a host. The main idea behind this approach is that pathogens tend to regulate their gene expression levels depending on the host microenvironment, and preferentially express those needed for survival. Identifying this class of genes will improve our understanding of pathogenesis. In our case, we identified an in vivo expressed genomic island that was preferentially active in murine lungs during early infection, as well as groups of genes active during chronic tuberculosis. Other studies have identified additional gene groups that are active during macrophage infection and even in human lungs. Despite all of these findings, one of the lingering questions remaining was whether in vivo expressed transcripts are relevant to the virulence, pathogenesis, and persistence of the organism. The work of our group and others addressed this question by examining the contribution of in vivo expressed genes using a strategy based on gene deletions followed by animal infections. Overall, the analysis of most of the in vivo expressed genes supported a role of these genes in M. tuberculosis pathogenesis. Further, these data suggest that in vivo transcriptional profiling is a valid approach to identify genes required for bacterial pathogenesis. PMID:21738523

  10. Diseases masking and delaying the diagnosis of urogenital tuberculosis

    PubMed Central

    Kulchavenya, Ekaterina; Kholtobin, Denis

    2015-01-01

    As urogenital tuberculosis (UGTB) has no specific clinical features, it is often overlooked. To identify some of the reasons for misdiagnosing UGTB we performed a systematic review. We searched in Medline/PubMed papers with keywords ‘urogenital tuberculosis, rare’ and ‘urogenital tuberculosis, unusual’. ‘Urogenital tuberculosis, rare’ presented 230 articles and ‘urogenital tuberculosis, unusual’ presented 81 articles only, a total of 311 papers. A total of 34 papers were duplicated and so were excluded from the review. In addition, we excluded from the analysis 33 papers on epidemiological studies and literature reviews, papers describing non-TB cases and cases of TB another than urogenital organs (48 articles), cases of congenital TB (three articles), UGTB as a case of concomitant disease (16 articles), and UGTB as a complication of BCG-therapy (eight articles). We also excluded 22 articles dedicated to complications of the therapy, which made a total of 164 articles. Among the remaining 147 articles we selected 43 which described really unusual, difficult to diagnose cases. We also included in our review a WHO report from 2014, and one scientific monograph on TB urology. The most frequent reasons for delayed diagnosis were absence typical clinical features of UGTB, and the tendency of UGTB to hide behind the mask of another disease. We can conclude that actually UGTB is not rare disease, but it is often an overlooked disease. The main reasons for delayed diagnosis are vague, atypical clinical features and a low index of suspicion. PMID:26622318

  11. Tuberculosis in wild birds: implications for captive birds

    USGS Publications Warehouse

    Converse, K. A.; Dein, F. J.

    1990-01-01

    The geographic distribution of avian tuberculosis is widespread but the lack of visible epizootics makes assessment of its impact on wild birds difficult. Generally a low prevalence, widely-scattered, individual animal disease, avian tuberculosis is caused by the same agent in wild and domestic birds. Thus there exists the potential for disease transfer between these two groups in situations that result in direct contact such as wild animals newly captured or transferred from rehabilitation centers, and wild and captive animals intermingling in exhibit areas. During the past 7 yr, tuberculosis caused by Mycobacterium avium, was diagnosed in 64 birds submitted to the National Wildlife Health Research Center from 16 states; avian tuberculosis was the primary diagnosis in 52 of the 64 birds, while the remaining 12 isolates were incidental findings. Twenty-eight of these birds were picked up during epizootics caused by other disease agents including avian cholera, botulism type C, and lead, organophosphorus compound, and cyanide poisoning. Twelve birds were found incidental to birds collected during disease monitoring programs and research projects, and 10 birds were collected by hunters or found sick and euthanatized. Tuberculosis lesions occurred (in order of decreasing frequency) in the liver, intestine, spleen, lung, and air sacs. Several unusual morphological presentations were observed in the gizzard, shoulder joint, jugular vein, face, nares and bill, ureter and bone marrow. Infected birds were collected during all 12 mo of the yr from a variety of species in the Anseriformes, Podicipediformes, Gruiformes, and Falconiformes. Nine of the 46 known age birds were immature indicating that lesions can develop during the first year.

  12. The Pregnane X Receptor in Tuberculosis Therapeutics

    PubMed Central

    Shehu, Amina I.; Li, Guangming; Xie, Wen; Ma, Xiaochao

    2016-01-01

    Introduction Among the infectious diseases, tuberculosis (TB) remains the second cause of death after HIV. TB treatment requires the combination of multiple drugs including the rifamycin class. However, rifamycins are activators of human pregnane X receptor (PXR), a transcription factor that regulates drug metabolism, drug resistance, energy metabolism, and immune response. Rifamycin-mediated PXR activation may affect the outcome of TB therapy. Areas covered This review describes the role of PXR in modulating metabolism, efficacy, toxicity, and resistance to anti-TB drugs; as well as polymorphisms of PXR that potentially affect TB susceptibility. Expert opinion The wide range of PXR functions aside mediating drug metabolism and toxicity in TB therapy is underappreciated and thus understudied. Further studies are needed to determine the overall impact of PXR activation on the outcome of TB therapy. PMID:26592418

  13. Some remaining problems in HCDA analysis. [LMFBR

    SciTech Connect

    Chang, Y.W.

    1981-01-01

    The safety assessment and licensing of liquid-metal fast breeder reactors (LMFBRs) requires an analysis on the capability of the reactor primary system to sustain the consequences of a hypothetical core-disruptive accident (HCDA). Although computational methods and computer programs developed for HCDA analyses can predict reasonably well the response of the primary containment system, and follow up the phenomena of HCDA from the start of excursion to the time of dynamic equilibrium in the system, there remain areas in the HCDA analysis that merit further analytical and experimental studies. These are the analysis of fluid impact on reactor cover, three-dimensional analysis, the treatment of the perforated plates, material properties under high strain rates and under high temperatures, the treatment of multifield flows, and the treatment of prestressed concrete reactor vessels. The purpose of this paper is to discuss the structural mechanics of HCDA analysis in these areas where improvements are needed.

  14. Environmental threats to buried archaeological remains.

    PubMed

    Nord, Anders G; Tronner, Kate; Mattsson, Einar; Borg, Gunnar Ch; Ullén, Inga

    2005-05-01

    The last century's environmental pollution has created health problems, acidification of ground and lakes, and serious damage to our cultural heritage. Outdoor monuments suffer from this pollution, but so do buried archaeological remains. However, research on the deterioration of archaeological artifacts underground has so far been limited, and it is important to draw attention to this neglected field. This article presents results obtained at the Swedish National Heritage Board on the degradation of archaeological objects of bronze and iron and of bones from prehistoric graves, materials of which seem to be most affected by pollutants. The investigation methods, which were employed, are described. Other relevant studies are briefly reviewed. It is obvious that the deterioration rate of archaeological artifacts, especially of inorganic materials, has accelerated in recent years, and that this increased deterioration to a large part can be attributed to anthropogenic pollution. Regions that might be endangered are exemplified.

  15. What's new in tuberculosis vaccines?

    PubMed Central

    Ginsberg, Ann M.

    2002-01-01

    Over the past 10 years, tuberculosis (TB) vaccine development has resurged as an active area of investigation. The renewed interest has been stimulated by the recognition that, although BCG is delivered to approximately 90% of all neonates globally through the Expanded Programme on Immunization, Mycobacterium tuberculosis continues to cause over 8 million new cases of TB and over 2 million deaths annually. Over one hundred TB vaccine candidates have been developed, using different approaches to inducing protective immunity. Candidate vaccines are typically screened in small animal models of primary TB disease for their ability to protect against a virulent strain of M. tuberculosis. The most promising are now beginning to enter human safety trials, marking real progress in this field for the first time in 80 years. PMID:12132007

  16. 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

  17. Optimal intervention strategies for tuberculosis

    NASA Astrophysics Data System (ADS)

    Bowong, Samuel; Aziz Alaoui, A. M.

    2013-06-01

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

  18. Burden of tuberculosis in Kampala, Uganda.

    PubMed Central

    Guwatudde, David; Zalwango, Sarah; Kamya, Moses R.; Debanne, Sara M.; Diaz, Mireya I.; Okwera, Alphonse; Mugerwa, Roy D.; King, Charles; Whalen, Christopher C.

    2003-01-01

    OBJECTIVE: To determine the prevalence and incidence of tuberculosis in one of Uganda's poor peri-urban areas. METHODS: Multi-stage sampling was used to select a sample of households whose members were evaluated for presence of signs and/or symptoms of active tuberculosis; history of tuberculosis treatment; and relevant demographic, socioeconomic, and household environment characteristics. Patients with suspected tuberculosis underwent standardized evaluation for active disease. FINDINGS: A sample of 263 households with 1142 individuals was evaluated. Nineteen people were classified as having had tuberculosis during the one-year reference period (May 2001-April 2002): nine (47%) cases already had been diagnosed through the health care system, while 10 cases (53%) were diagnosed through the survey. The prevalences for all forms of tuberculosis and for sputum smear-positive tuberculosis were 14.0 (95% confidence interval (CI) 7.8-20.3) and 4.4 (CI = 0.83-7.89) per thousand, respectively. The incidences for all forms of tuberculosis and for sputum smear-positive tuberculosis were 9.2 (CI = 3.97-14.4) and 3.7 (CI = 0.39-6.95) per thousand per year, respectively. CONCLUSION: The rate of tuberculosis in this peri-urban community was exceptionally high and may be underestimated by current surveillance systems. The need for interventions aimed at reducing tuberculosis transmission in this, and other similar communities with high case rates, is urgent. PMID:14758406

  19. Building Background Knowledge

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  20. Risk Factors for Tuberculosis

    PubMed Central

    Narasimhan, Padmanesan; Wood, James; MacIntyre, Chandini Raina; Mathai, Dilip

    2013-01-01

    The risk of progression from exposure to the tuberculosis bacilli to the development of active disease is a two-stage process governed by both exogenous and endogenous risk factors. Exogenous factors play a key role in accentuating the progression from exposure to infection among which the bacillary load in the sputum and the proximity of an individual to an infectious TB case are key factors. Similarly endogenous factors lead in progression from infection to active TB disease. Along with well-established risk factors (such as human immunodeficiency virus (HIV), malnutrition, and young age), emerging variables such as diabetes, indoor air pollution, alcohol, use of immunosuppressive drugs, and tobacco smoke play a significant role at both the individual and population level. Socioeconomic and behavioral factors are also shown to increase the susceptibility to infection. Specific groups such as health care workers and indigenous population are also at an increased risk of TB infection and disease. This paper summarizes these factors along with health system issues such as the effects of delay in diagnosis of TB in the transmission of the bacilli. PMID:23476764

  1. The path to impact of operational research on tuberculosis control policies and practices in Indonesia

    PubMed Central

    Probandari, Ari; Widjanarko, Bagoes; Mahendradhata, Yodi; Sanjoto, Hary; Cerisha, Ancila; Nungky, Saverina; Riono, Pandu; Simon, Sumanto; Farid, Muhammad Noor; Giriputra, Sardikin; Putra, Artawan Eka; Burhan, Erlina; Wahyuni, Chatarina U.; Mustikawati, Dyah; Widianingrum, Christina; Tiemersma, Edine W.; Alisjahbana, Bachti

    2016-01-01

    Background Operational research is currently one of the pillars of the global strategy to control tuberculosis. Indonesia initiated capacity building for operational research on tuberculosis over the last decade. Although publication of the research in peer-reviewed journals is an important indicator for measuring the success of this endeavor, the influence of operational research on policy and practices is considered even more important. However, little is known about the process by which operational research influences tuberculosis control policy and practices. Objective We aimed to investigate the influence of operational research on tuberculosis control policy and practice in Indonesia between 2004 and 2014. Design Using a qualitative study design, we conducted in-depth interviews of 50 researchers and 30 policy makers/program managers and performed document reviews. Transcripts of these interviews were evaluated while applying content analysis. Results Operational research contributed to tuberculosis control policy and practice improvements, including development of new policies, introduction of new practices, and reinforcement of current program policies and practices. However, most of these developments had limited sustainability. The path from the dissemination of research results and recommendations to policy and practice changes was long and complex. The skills, interests, and political power of researchers and policy makers, as well as health system response, could influence the process. Conclusions Operational research contributed to improving tuberculosis control policy and practices. A systematic approach to improve the sustainability of the impact of operational research should be explored. PMID:26928217

  2. Can Follow-Up Examination of Tuberculosis Patients Be Simplified? A Study in Chhattisgarh, India

    PubMed Central

    Kundu, Debashish; M. V. Kumar, Ajay; Satyanarayana, Srinath; Dewan, Puneet Kumar; Achuthan Nair, Sreenivas; Khaparde, Kshitij; Nayak, Priyakanta; Van den Bergh, Rafael; Manzi, Marcel; Enarson, Donald A.; Deshpande, Madhav Rao; Chandraker, Sachin

    2012-01-01

    Background Each follow-up during the course of tuberculosis treatment currently requires two sputum examinations. However, the incremental yield of the second sputum sample during follow-up of different types of tuberculosis patients has never been determined precisely. Objectives To assess the incremental yield of the second sputum sample in the follow-up of tuberculosis patients under the Revised National Tuberculosis Control Programme (RNTCP) in Chhattisgarh, India. Methodology A record review of tuberculosis (TB) patients registered in 2009 using a structured proforma from two sources, Tuberculosis and Laboratory Register, was undertaken in the six districts of Chhattisgarh, India. Results In smear positive cases, of 10,048 follow-up examinations, 45 (0.5%) were found to be smear positive only on the second sputum when the result of the first sample was negative. In smear negative pulmonary and extra pulmonary TB patients, of 6,206 follow-up smear examinations, 11(0.2%) were found to be smear positive. Conclusions The incremental yield of a second smear examination was very low, indicating that examination of one sputum sample is enough during follow-up among TB patients. There is insufficient yield to support sputum smear microscopy for monitoring smear negative pulmonary TB and extra pulmonary TB patients. These results indicate that the follow-up smear microscopy can be substantially simplified with favourable resource implications. PMID:23227230

  3. A rare case of pulmonary tuberculosis with simultaneous pulmonary and skin sarcoidosis: a case report

    PubMed Central

    2010-01-01

    Background Tuberculosis and sarcoidosis are chronic diseases that rarely occur concomitantly. Sarcoidosis is a multisystem granulomatous disorder characterized pathologically by the presence of non-caseating granulomas in involved tissues. Tuberculosis is infectious disease caused by Mycobacterium tuberculosis characterized by granulomas with caseous necrosis. Case presentation We present a case of 43-year-old female refugee from Kosovo with microbiological confirmation of pulmonary tuberculosis and pulmonary and skin sarcoidosis at the same time. Three weeks after corticosteroid therapy for pulmonary sarcoidosis was introduced, positive finding of mycobacterium culture of bronchial aspirate was observed. Based on these results, corticosteroid therapy was excluded and antituberculous therapy was introduced for six months. In the meantime, new nodes on face and nose appeared and skin sarcoidosis was diagnosed. The patient was given corticosteroids and colchicine according to the skin and pulmonary sarcoidosis therapy recommendation. Conclusion The authors of this study suggest that in cases when there is a dilemma in diagnosis between tuberculosis and sarcoidosis we should advance with corticosteroid therapy until we have microbiological confirmation of mycobacterium culture. This case is remarkable because this is a third described case of sarcoidosis and tuberculosis together (the first reported in Asia, the second in South Africa), and to authors knowledge, this is a first case report in Europe. PMID:20205764

  4. Seasonality and Temporal Variations of Tuberculosis in the North of Iran

    PubMed Central

    Moosazadeh, Mahmood; Bahrampour, Abbas

    2013-01-01

    Background Determining the temporal variations and seasonal pattern of diseases and forecasting their incidence can help in promoting disease control and management programs. This study was performed to determine the seasonal variation of tuberculosis and forecast its incidence until the year 2015 in one of the northern provinces of Iran. Materials and Methods A longitudinal time series study was conducted. The study interval was from March 2001 to March 2011. The sum of daily registered cases in each month created 132 time points. The Box-Jenkins methods were used for determining the model. The best model was selected by analyzing the residuals and calculating the AIC and BIC. Results A total of 3,313 patients were diagnosed and recorded during this time. The highest number of cases was registered in May and the difference in monthly incidence of tuberculosis was significant (P=0.007). The incidence of tuberculosis was higher in spring and summer than winter (P=0.04). According to the best model which was SARIMA (0, 1, 1)(0, 1, 1)12 , the average incidence of tuberculosis in 2015 is estimated to be 12 in 100,000 persons per year. Conclusion The results of this study showed that in the north of Iran the incidence of tuberculosis has a cyclic pattern and the maximum incidence is in spring (May). Also, the trend of tuberculosis incidence is increasing and needs attention. PMID:25191482

  5. Tuberculosis in Healthcare Workers: A Matched Cohort Study in Taiwan

    PubMed Central

    Pan, Sung-Ching; Chen, Yee-Chun; Wang, Jann-Yuan; Sheng, Wang-Huei; Lin, Hsien-Ho; Fang, Chi-Tai; Chang, Shan-Chwen

    2015-01-01

    Background Proportional mortality ratio data indicate that healthcare workers (HCWs) have an elevated tuberculosis (TB) mortality. Whether this is caused by an increased TB incidence, a worse TB treatment outcome, or a combination of effects, remains unclear. To elucidate the hazard components of occupational TB, we assessed TB incidence and TB treatment outcome among HCWs in Taiwan. Methods We compared the incidence of active TB among HCWs at a major medical center in Taiwan with that of Taiwan general population in 2004–2012. We also compared the TB treatment outcome of HCWs with that of age/sex-matched non-HCW patients treated at the same hospital, as well as that of nationally registered TB patients. Results The standardized TB incidence ratio of the HCWs was 1.9 (95% confidence interval [CI]: 1.2–2.9), compared with the general population. HCWs with pulmonary TB (n = 30) were less likely to have underlying diseases, delay in diagnosis, delay in treatment, or side effects of treatment, compared with age/sex-matched non-HCW TB patients (n = 120) (all Ps<0.05). The TB treatment outcome of HCWs was significantly better than that of non-HCW patients (TB-related mortality: 0.0% vs. 5.8%, P = 0.008, Mantel-Haenszel test). The standardized TB-related mortality rate was 1.08% [95% CI: 0.96% - 1.20%] for all of the nationally registered TB patients in Taiwan. Conclusions HCWs are at increased risk of active TB, compared with general population. To mitigate this occupational hazard, more efforts need to be directed towards the prevention of nosocomial TB transmission. Healthy worker effect, more rapid diagnosis, and less delay in treatment contribute to a lower TB-related mortality in HCWs. PMID:26679188

  6. Vitamin D as Adjunctive Host-Directed Therapy in Tuberculosis: A Systematic Review

    PubMed Central

    Wallis, Robert S.; Zumla, Alimuddin

    2016-01-01

    Vitamin D plays an important role in innate defenses against intracellular pathogens. Seasonal vitamin D insufficiency (VDI) due to reduced sun exposure far from the equator increases tuberculosis risk. Eight randomized controlled trials examined vitamin D as adjunctive therapy during tuberculosis treatment. The studies varied substantially regarding patient genetic backgrounds, the extent of baseline VDI, the administered dose, the study endpoints, and the quality of the reported data. One carefully performed study in which moderately large vitamin D doses were given to markedly VDI patients found a benefit sufficient to support shortening treatment from 6 to 4 months, although other similar studies did not. Vitamin D is thought to have anti-inflammatory effects. However, 2 studies reported 3 vitamin D recipients with severe paradoxical inflammatory reactions. Future studies of vitamin D in tuberculosis in patients with specific genetic backgrounds must monitor these events closely to determine their risks and underlying mechanisms. PMID:27800526

  7. AIDS, individual behaviour and the unexplained remaining variation.

    PubMed

    Katz, Alison

    2002-01-01

    From the start of the AIDS pandemic, individual behaviour has been put forward, implicitly or explicitly, as the main explanatory concept for understanding the epidemiology of HIV infection and in particular for the rapid spread and high prevalence in sub-Saharan Africa. This has had enormous implications for the international response to AIDS and has heavily influenced public health policy and strategy and the design of prevention and care interventions at national, community and individual level. It is argued that individual behaviour alone cannot possibly account for the enormous variation in HIV prevalence between population groups, countries and regions and that the unexplained remaining variation has been neglected by the international AIDS community. Biological vulnerability to HIV due to seriously deficient immune systems has been ignored as a determinant of the high levels of infection in certain populations. This is in sharp contrast to well proven public health approaches to other infectious diseases. In particular, it is argued that poor nutrition and co-infection with the myriad of other diseases of poverty including tuberculosis, malaria, leishmaniasis and parasitic infections, have been neglected as root causes of susceptibility, infectiousness and high rates of transmission of HIV at the level of populations. Vulnerability in terms of non-biological factors such as labour migration, prostitution, exchange of sex for survival, population movements due to war and violence, has received some attention but the solutions proposed to these problems are also inappropriately focused on individual behaviour and suffer from the same neglect of economic and political root causes. As the foundation for the international community's response to the AIDS pandemic, explanations of HIV/AIDS epidemiology in terms of individual behaviour are not only grossly inadequate, they are highly stigmatising and may in some cases, be racist. They have diverted attention from

  8. 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

  9. Ancient mycobacterial lipids: Key reference biomarkers in charting the evolution of tuberculosis.

    PubMed

    Minnikin, David E; Lee, Oona Y-C; Wu, Houdini H T; Besra, Gurdyal S; Bhatt, Apoorva; Nataraj, Vijayashankar; Rothschild, Bruce M; Spigelman, Mark; Donoghue, Helen D

    2015-06-01

    Mycobacterium tuberculosis has a cell envelope incorporating a peptidoglycan-linked arabinogalactan esterified by long-chain mycolic acids. A range of "free" lipids are associated with the "bound" mycolic acids, producing an effective envelope outer membrane. The distribution of these lipids is discontinuous among mycobacteria and such lipids have proven potential for biomarker use in tracing the evolution of tuberculosis. A plausible evolutionary scenario involves progression from an environmental organism, such as Mycobacterium kansasii, through intermediate "smooth" tubercle bacilli, labelled "Mycobacterium canettii"; cell envelope lipid composition possibly correlates with such a progression. M. kansasii and "M. canettii" have characteristic lipooligosaccharides, associated with motility and biofilms, and glycosyl phenolphthiocerol dimycocerosates ("phenolic glycolipids"). Both these lipid classes are absent in modern M. tuberculosis sensu stricto, though simplified phenolic glycolipids remain in certain current biotypes. Dimycocerosates of the phthiocerol family are restricted to smaller phthiodiolone diesters in M. kansasii. Diacyl and pentaacyl trehaloses are present in "M. canettii" and M. tuberculosis, accompanied in the latter by related sulfated acyl trehaloses. In comparison with environmental mycobacteria, subtle modifications in mycolic acid structures in "M. canettii" and M. tuberculosis are notable. The probability of essential tuberculosis evolution taking place in Pleistocene megafauna, rather than Homo sapiens, is reemphasised.

  10. Dual-Reporter Mycobacteriophages (Φ2DRMs) Reveal Preexisting Mycobacterium tuberculosis Persistent Cells in Human Sputum

    PubMed Central

    Jain, Paras; Weinrick, Brian C.; Kalivoda, Eric J.; Yang, Hui; Munsamy, Vanisha; Vilcheze, Catherine; Weisbrod, Torin R.; Larsen, Michelle H.; O’Donnell, Max R.; Pym, Alexander

    2016-01-01

    ABSTRACT Persisters are the minor subpopulation of bacterial cells that lack alleles conferring resistance to a specific bactericidal antibiotic but can survive otherwise lethal concentrations of that antibiotic. In infections with Mycobacterium tuberculosis, such persisters underlie the need for long-term antibiotic therapy and contribute to treatment failure in tuberculosis cases. Here, we demonstrate the value of dual-reporter mycobacteriophages (Φ2DRMs) for characterizing M. tuberculosis persisters. The addition of isoniazid (INH) to exponentially growing M. tuberculosis cells consistently resulted in a 2- to 3-log decrease in CFU within 4 days, and the remaining ≤1% of cells, which survived despite being INH sensitive, were INH-tolerant persisters with a distinct transcriptional profile. We fused the promoters of several genes upregulated in persisters to the red fluorescent protein tdTomato gene in Φ2GFP10, a mycobacteriophage constitutively expressing green fluorescent protein (GFP), thus generating Φ2DRMs. A population enriched in INH persisters exhibited strong red fluorescence, by microscopy and flow cytometry, using a Φ2DRM with tdTomato controlled from the dnaK promoter. Interestingly, we demonstrated that, prior to INH exposure, a population primed for persistence existed in M. tuberculosis cells from both cultures and human sputa and that this population was highly enriched following INH exposure. We conclude that Φ2DRMs provide a new tool to identify and quantitate M. tuberculosis persister cells. PMID:27795387

  11. Tuberculosis cross-species transmission in Tanzania: towards a One-Health concept.

    PubMed

    Mbugi, Erasto V; Katale, Bugwesa Z; Kendall, Sharon; Good, Liam; Kibiki, Gibson S; Keyyu, Julius D; Godfrey-Faussett, Peter; Van Helden, Paul; Matee, Mecky I

    2012-07-20

    For centuries, tuberculosis, which is a chronic infection caused by the bacillus Mycobacterium tuberculosis has remained a global health problem. The global burden of tuberculosis has increased, particularly in the Southern African region, mainly due to HIV, and inadequate health systems which has in turn given rise to emergent drug resistant tuberculosis (TB) strains. Bovine tuberculosis (BTB) has also emerged as a significant disease with the tendency for inter-species spread. The extent of interspecies BTB transmission both in urban and rural communities has not been adequately assessed. The phenomenon is of particular importance in rural communities where people share habitats with livestock and wildlife (particularly in areas near national parks and game reserves). Aerosol and oral intake are the major routes of transmission from diseased to healthy individuals, with health care workers often contracting infection nosocomially. Although TB control has increasingly been achieved in high-income countries, the disease, like other poverty-related infections, has continued to be a disaster in countries with low income economies. Transmission of infections occurs not only amongst humans but also between animals and humans (and occasionally vice versa) necessitating assessment of the extent of transmission at their interface. This review explores tuberculosis as a disease of humans which can cross-transmit between humans, livestock and wildlife. The review also addresses issues underlying the use of molecular biology, genetic sequencing and bioinformatics as t tools to understand the extent of inter-species cross-transmission of TB in a 'One Health' context.

  12. Phosphoproteomics analysis of a clinical Mycobacterium tuberculosis Beijing isolate: expanding the mycobacterial phosphoproteome catalog

    PubMed Central

    Fortuin, Suereta; Tomazella, Gisele G.; Nagaraj, Nagarjuna; Sampson, Samantha L.; Gey van Pittius, Nicolaas C.; Soares, Nelson C.; Wiker, Harald G.; de Souza, Gustavo A.; Warren, Robin M.

    2015-01-01

    Reversible protein phosphorylation, regulated by protein kinases and phosphatases, mediates a switch between protein activity and cellular pathways that contribute to a large number of cellular processes. The Mycobacterium tuberculosis genome encodes 11 Serine/Threonine kinases (STPKs) which show close homology to eukaryotic kinases. This study aimed to elucidate the phosphoproteomic landscape of a clinical isolate of M. tuberculosis. We performed a high throughput mass spectrometric analysis of proteins extracted from an early-logarithmic phase culture. Whole cell lysate proteins were processed using the filter-aided sample preparation method, followed by phosphopeptide enrichment of tryptic peptides by strong cation exchange (SCX) and Titanium dioxide (TiO2) chromatography. The MaxQuant quantitative proteomics software package was used for protein identification. Our analysis identified 414 serine/threonine/tyrosine phosphorylated sites, with a distribution of S/T/Y sites; 38% on serine, 59% on threonine and 3% on tyrosine; present on 303 unique peptides mapping to 214 M. tuberculosis proteins. Only 45 of the S/T/Y phosphorylated proteins identified in our study had been previously described in the laboratory strain H37Rv, confirming previous reports. The remaining 169 phosphorylated proteins were newly identified in this clinical M. tuberculosis Beijing strain. We identified 5 novel tyrosine phosphorylated proteins. These findings not only expand upon our current understanding of the protein phosphorylation network in clinical M. tuberculosis but the data set also further extends and complements previous knowledge regarding phosphorylated peptides and phosphorylation sites in M. tuberculosis. PMID:25713560

  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. The role of Xpert MTB/RIF in diagnosing pulmonary tuberculosis in post-mortem tissues

    PubMed Central

    García-Basteiro, Alberto L.; Ismail, Mamudo R.; Carrilho, Carla; Ussene, Esperança; Castillo, Paola; Chitsungo, Dércio; Rodríguez, Cristina; Lovane, Lucília; Vergara, Andrea; López-Varela, Elisa; Mandomando, Inacio; Lorenzoni, Cesaltina; Ordi, Jaume; Menéndez, Clara; Bassat, Quique; Martínez, Miguel J.

    2016-01-01

    The extent to which the Xpert MTB/RIF (Gene Xpert) contributes to tuberculosis (TB) diagnosis in samples other than sputum and cerebrospinal fluid remains uncertain. We aimed to assess the role of Xpert MTB/RIF for detecting M. tuberculosis in post-mortem tissues. We conducted a study among 30 complete diagnostic autopsies (CDA) performed at the Maputo Central Hospital (Mozambique). Lung tissues were screened for TB in all cases. In addition other tissues were tested when compatible lesions were identified in the histological exam. We used in-house real time PCR and LAMP assays to confirm the presence of M. tuberculosis DNA. The diagnosis of tuberculosis at death was established based on microbiological and histopathological results. Eight out of 30 cases (26.7%) were diagnosed of tuberculosis. Xpert had a sensitivity to detect TB in lung tissue of 87.5% (95% CI 47.3–99.7) and a specificity of 95.7% (95% CI: 78.1–99.9). In-house DNA amplification methods and Xpert showed 93.6% concordance for lung tissue and 100% concordance for brain and liver tissues. The final cause of death was attributable to tuberculosis in four cases. Xpert MTB/RIF may represent a valuable, easy-to perform technique for post-mortem TB diagnosis. PMID:26860394

  15. Tuberculosis cross-species transmission in Tanzania: towards a One-Health concept.

    PubMed

    Mbugi, Erasto V; Katale, Bugwesa Z; Kendall, Sharon; Good, Liam; Kibiki, Gibson S; Keyyu, Julius D; Godfrey-Faussett, Peter; Van Helden, Paul; Matee, Mecky I

    2012-01-01

    For centuries, tuberculosis, which is a chronic infection caused by the bacillus Mycobacterium tuberculosis has remained a global health problem. The global burden of tuberculosis has increased, particularly in the Southern African region, mainly due to HIV, and inadequate health systems which has in turn given rise to emergent drug resistant tuberculosis (TB) strains. Bovine tuberculosis (BTB) has also emerged as a significant disease with the tendency for inter-species spread. The extent of interspecies BTB transmission both in urban and rural communities has not been adequately assessed. The phenomenon is of particular importance in rural communities where people share habitats with livestock and wildlife (particularly in areas near national parks and game reserves). Aerosol and oral intake are the major routes of transmission from diseased to healthy individuals, with health care workers often contracting infection nosocomially. Although TB control has increasingly been achieved in high-income countries, the disease, like other poverty-related infections, has continued to be a disaster in countries with low income economies. Transmission of infections occurs not only amongst humans but also between animals and humans (and occasionally vice versa) necessitating assessment of the extent of transmission at their interface. This review explores tuberculosis as a disease of humans which can cross-transmit between humans, livestock and wildlife. The review also addresses issues underlying the use of molecular biology, genetic sequencing and bioinformatics as t tools to understand the extent of inter-species cross-transmission of TB in a 'One Health' context. PMID:23327386

  16. The endothelin system has a significant role in the pathogenesis and progression of Mycobacterium tuberculosis infection.

    PubMed

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

    2014-12-01

    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.

  17. Phosphoproteomics analysis of a clinical Mycobacterium tuberculosis Beijing isolate: expanding the mycobacterial phosphoproteome catalog.

    PubMed

    Fortuin, Suereta; Tomazella, Gisele G; Nagaraj, Nagarjuna; Sampson, Samantha L; Gey van Pittius, Nicolaas C; Soares, Nelson C; Wiker, Harald G; de Souza, Gustavo A; Warren, Robin M

    2015-01-01

    Reversible protein phosphorylation, regulated by protein kinases and phosphatases, mediates a switch between protein activity and cellular pathways that contribute to a large number of cellular processes. The Mycobacterium tuberculosis genome encodes 11 Serine/Threonine kinases (STPKs) which show close homology to eukaryotic kinases. This study aimed to elucidate the phosphoproteomic landscape of a clinical isolate of M. tuberculosis. We performed a high throughput mass spectrometric analysis of proteins extracted from an early-logarithmic phase culture. Whole cell lysate proteins were processed using the filter-aided sample preparation method, followed by phosphopeptide enrichment of tryptic peptides by strong cation exchange (SCX) and Titanium dioxide (TiO2) chromatography. The MaxQuant quantitative proteomics software package was used for protein identification. Our analysis identified 414 serine/threonine/tyrosine phosphorylated sites, with a distribution of S/T/Y sites; 38% on serine, 59% on threonine and 3% on tyrosine; present on 303 unique peptides mapping to 214 M. tuberculosis proteins. Only 45 of the S/T/Y phosphorylated proteins identified in our study had been previously described in the laboratory strain H37Rv, confirming previous reports. The remaining 169 phosphorylated proteins were newly identified in this clinical M. tuberculosis Beijing strain. We identified 5 novel tyrosine phosphorylated proteins. These findings not only expand upon our current understanding of the protein phosphorylation network in clinical M. tuberculosis but the data set also further extends and complements previous knowledge regarding phosphorylated peptides and phosphorylation sites in M. tuberculosis.

  18. First-Line Anti-Tubercular Drug Resistance of Mycobacterium tuberculosis in IRAN: A Systematic Review

    PubMed Central

    Pourakbari, Babak; Mamishi, Setareh; Mohammadzadeh, Mona; Mahmoudi, Shima

    2016-01-01

    Background: The spread of drug-resistant tuberculosis (TB) is one of the major public health problems through the world. Surveillance of anti-TB drug resistance is essential for monitoring of TB control strategies. The occurrence of drug resistance, particularly multi-drug resistance Mycobacterium tuberculosis (MDR), defined as resistance to at least rifampicin (RIF) and isoniazid (INH), has become a significant public health dilemma. The status of drug-resistance TB in Iran, one of the eastern Mediterranean countries locating between Azerbaijan and Armenia and high-TB burden countries (such as Afghanistan and Pakistan) has been reported inconsistently. Therefore, the aim of this study was to summarize reports of first-line anti-tubercular drug resistance in M. tuberculosis in Iran. Material and Methods: We systematically reviewed published studies on drug-resistant M. tuberculosis in Iran. The search terms were “Mycobacterium tuberculosis susceptibility” or “Mycobacterium tuberculosis resistant” and Iran. Results: Fifty-two eligible articles, published during 1998–2014, were included in this review. Most of the studies were conducted in Tehran. The most common used laboratory method for detecting M. tuberculosis drug resistant was Agar proportion. The highest resistance to first-line drugs was seen in Tehran, the capital city of Iran. The average prevalence of isoniazid (INH), rifampin (RIF), streptomycin (SM), and ethambotol (EMB) resistance via Agar proportion method in Tehran was 26, 23, 22.5, and 16%, respectively. In general, resistance to INH was more common than RIF, SM, and EMB in Tehran Conclusions: In conclusion, this systematic review summarized the prevalence and distribution of first-line anti-tubercular drug resistance of M. tuberculosis in Iran. Our results suggested that effective strategies to minimize the acquired drug resistance, to control the transmission of resistance and improve the diagnosis measures for TB control in Iran. PMID

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed Central

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

    1999-01-01

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

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

    PubMed Central

    2013-01-01

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

  2. Transmitted Extended-Spectrum Extensively Drug-Resistant Tuberculosis in Beijing, China, with Discordant Whole-Genome Sequencing Analysis Results

    PubMed Central

    Li, Hao; Kayani, Masood ur Rehman; Gu, Yunting; Wang, Xiaobo; Zhu, Ting; Duan, Hongfei; Ma, Yifeng

    2015-01-01

    Drug resistance to tuberculosis remains a major public health threat. Here, we report two cases of extended-spectrum extensively drug-resistant (XXDR) tuberculosis showing resistance to most first- and second-line agents. The results of a correlation of whole-genome sequencing (WGS) and phenotypic testing were discordant, suggesting that overreliance on WGS may miss clinically relevant resistance in extensively drug-resistant disease. PMID:26063862

  3. Spatial patterning of vulture scavenged human remains.

    PubMed

    Spradley, M Katherine; Hamilton, Michelle D; Giordano, Alberto

    2012-06-10

    This article presents the results of a pilot study on the effects of vulture modification to human remains. A donated body from the Willed Body Donation Program was placed at the Forensic Anthropology Research Facility (FARF), an outdoor human decomposition laboratory located at Texas State University-San Marcos. The effects of vulture scavenging on the timing and sequence, and the rate of skeletonization, disarticulation, and dispersal were observed via a motion sensing camera and direct observation. Using GIS (Geographic Information Systems) and GPS (Global Positioning System) technologies and spatial analytical methods, the transport of skeletal elements was mapped in order to analyze dispersal and terrain-influenced patterns of active vulture scavenging. Results showed that the initial scavenging took place 37 days after placement at FARF. This delay in scavenging differs from previous research. After the initial appearance of the vultures, the body was reduced from a fully-fleshed individual to a skeleton within only 5h. This underscores the potential for errors in postmortem interval estimations made at vulture scavenged scenes. Additionally, spatial analysis showed that skeletal elements were dispersed by vultures to lower elevations, and that the disarticulation and dispersal of the skeletal elements occurs early in the scavenging sequence.

  4. Smart Point Cloud: Definition and Remaining Challenges

    NASA Astrophysics Data System (ADS)

    Poux, F.; Hallot, P.; Neuville, R.; Billen, R.

    2016-10-01

    Dealing with coloured point cloud acquired from terrestrial laser scanner, this paper identifies remaining challenges for a new data structure: the smart point cloud. This concept arises with the statement that massive and discretized spatial information from active remote sensing technology is often underused due to data mining limitations. The generalisation of point cloud data associated with the heterogeneity and temporality of such datasets is the main issue regarding structure, segmentation, classification, and interaction for an immediate understanding. We propose to use both point cloud properties and human knowledge through machine learning to rapidly extract pertinent information, using user-centered information (smart data) rather than raw data. A review of feature detection, machine learning frameworks and database systems indexed both for mining queries and data visualisation is studied. Based on existing approaches, we propose a new 3-block flexible framework around device expertise, analytic expertise and domain base reflexion. This contribution serves as the first step for the realisation of a comprehensive smart point cloud data structure.

  5. Inhaler devices: what remains to be done?

    PubMed

    Smith, Ian J; Bell, John; Bowman, Nic; Everard, Mark; Stein, Stephen; Weers, Jeffry G

    2010-12-01

    The 1000 Years of Pharmaceutical Aerosols Conference convened posing the question; "what remains to be done?" When applying this question to the topic of inhaler devices, two hugely different perspectives could be taken. On the one hand, it could be argued that because there is an array of delivery systems available and the industry, prescribing physicians and patients alike have considerable choice, why would we believe it necessary to do anything further? On the other hand, as an industry, we are constantly reminded by our "customers" that the inhaler devices available are less than adequate, and in some cases woefully inadequate, that they are not "patient" friendly, not intuitive to use and importantly do nothing to encourage the patient to take the medication as intended and as prescribed. So, taking the second point of view as more reflective of reality--the Voice of the Customer--our starting point must be that there is still much to do in the field of inhaler devices. The purpose of this article is to outline some key basic requirements for inhaler design and perhaps to question some of the entrenched thinking that has pervaded inhaler product design for too many years.

  6. ‘Complex’ but coping: experience of symptoms of tuberculosis and health care seeking behaviours - a qualitative interview study of urban risk groups, London, UK

    PubMed Central

    2014-01-01

    Background Tuberculosis awareness, grounded in social cognition models of health care seeking behaviour, relies on the ability of individuals to recognise symptoms, assess their risk and access health care (passive case finding). There is scant published research into the health actions of ‘hard-to-reach’ groups with tuberculosis, who represent approximately 17% of the London TB caseload. This study aimed to analyse patients’ knowledge of tuberculosis, their experiences of symptoms and their health care seeking behaviours. Methods Qualitative interviews were conducted with 17 participants, predominantly homeless and attending a major tuberculosis centre in London, UK. Most had complex medical and social needs including drug and alcohol use or immigration problems affecting entitlement to social welfare. Analytical frameworks aimed to reflect the role of broader social structures in shaping individual health actions. Results Although participants demonstrated some knowledge of tuberculosis their awareness of personal risk was low. Symptoms commonly associated with tuberculosis were either not recognised or were attributed to other causes for which participants would not ordinarily seek health care. Many accessed health care by chance and, for some, for health concerns other than tuberculosis. Conclusions Health education, based on increasing awareness of symptoms, may play a limited role in tuberculosis care for populations with complex health and social needs. The findings support the intensification of outreach initiatives to identify groups at risk of tuberculosis and the development of structured care pathways which support people into prompt diagnosis and treatment. PMID:24943308

  7. P2X7 and NRAMP1/SLC11 A1 gene polymorphisms in Mexican mestizo patients with pulmonary tuberculosis

    PubMed Central

    Niño-Moreno, P; Portales-Pérez, D; Hernández-Castro, B; Portales-Cervantes, L; Flores-Meraz, V; Baranda, L; Gómez-Gómez, A; Acuña-Alonzo, V; Granados, J; González-Amaro, R

    2007-01-01

    Tuberculosis remains one of the most important infectious diseases worldwide. Several studies have suggested that genetic factors may affect susceptibility to tuberculosis, but the specific genes involved have not yet been fully characterized. NRAMP1/SLC11 A1 and P2X7 genes have been linked to increased risk for tuberculosis in some African and Asiatic populations. To explore the potential role of these genes in the susceptibility to pulmonary tuberculosis in a Mexican mestizo population, we evaluated the association of D543N and 3′-UTR polymorphisms in NRAMP1/SLC11 A1 and − 762 and A1513C polymorphisms in P2X7 genes with the risk for tuberculosis. Polymerase chain reaction (PCR) amplification of genomic DNA followed by restriction fragment length polymorphism analysis, and allelic-specific PCR was employed. We found no significant differences in allelic frequency in NRAMP1/SLC11 A1 gene polymorphisms in 94 patients with tuberculosis compared to 100 healthy contacts. Similarly, no significant association of the P2X7−762 gene polymorphism with tuberculosis was detected. In contrast, the P2X7 A1513C polymorphism was associated significantly with tuberculosis (P= 0·02, odds ratio = 5·28, 95% CI, 0·99–37·69), an association that had not been reported previously. However, when the function of P2X7 was assessed by an l-selectin loss assay, we did not find significant differences in patients compared to healthy contacts or between PPD+ and PPD– control individuals. This study further supports the complex role of P2X7 gene in host regulation of Mycobacterium tuberculosis infection, and demonstrates that different associations of gene polymorphisms and tuberculosis are found in distinct racial populations. PMID:17493019

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

    PubMed Central

    2011-01-01

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

  9. Risk factors associated with kanamycin-resistant tuberculosis in a Beijing tuberculosis referral hospital.

    PubMed

    Yu, Hao Tian; Wang, Qi; Yang, Nan; Li, Hong Min; Liang, Jian Qin; Liu, Cui Hua

    2012-07-01

    The rapidly increasing number of multidrug-resistant tuberculosis (MDR-TB) cases worldwide underlines the necessity for the rational use of key second-line drugs such as kanamycin. In this study, we determined the prevalence of, and risk factors associated with, kanamycin-resistant tuberculosis (TB) in 309 Hospital, Beijing, China, with the aim of providing information for better case management in order to minimize further development of extensively drug-resistant TB (XDR-TB). Drug susceptibility testing results and clinical data were retrospectively analysed for hospitalized TB patients for whom such data were available in 309 Hospital for the period 1997-2009. Univariate and multivariate analyses were used to determine the risk factors associated with kanamycin-resistant TB. During 1997-2009, 553 (14.4 %) of 3843 tested Mycobacterium tuberculosis isolates from hospitalized TB patients were kanamycin-resistant. The increasing trend of resistance to kanamycin was reversed since 2000. The independent risk factors associated with kanamycin-resistant TB included living in urban areas [adjusted odds ratio (OR) = 1.89], being retreated for repeat cases (adjusted OR = 1.60), being smear-positive for acid-fast bacilli at admission to the hospital (adjusted OR = 1.39), having ofloxacin-resistant (adjusted OR = 1.61) or para-aminosalicylic acid-resistant TB (adjusted OR = 1.47), having MDR-TB (adjusted OR = 5.10), having MDR-TB plus ofloxacin resistance (adjusted OR = 4.27) and having poly-resistant TB (adjusted OR = 3.94). The remaining rate of kanamycin resistance is still high despite the reversal of the increasing trend during the past decade. Surveillance of kanamycin resistance, especially among high-risk populations, should be continued to closely monitor trends so that appropriate action can be taken.

  10. Achievements in and Challenges of Tuberculosis Control in South Korea.

    PubMed

    Kim, Ji Han; Yim, Jae-Joon

    2015-11-01

    After the Korean War (1950-1953), nearly 6.5% of South Korea's population had active tuberculosis (TB). In response, South Korea implemented the National Tuberculosis Program in 1962. From 1965 to 1995, the prevalence of bacteriologically confirmed pulmonary TB in South Korea decreased from 940 to 219 cases per 100,000 population. Astounding economic growth might have contributed to this result; however, TB incidence in South Korea remains the highest among high-income countries. The rate of decrease in TB incidence seems to have slowed over the past 15 years. A demographic shift toward an older population, many of whom have latent TB and various concurrent conditions, is challenging TB control efforts in South Korea. The increasing number of immigrants also plays a part in the prolonged battle against TB. A historical review of TB in South Korea provides an opportunity to understand national TB control efforts that are applicable to other parts of the world.

  11. 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

  12. Implementing a Large-Scale Systematic Tuberculosis Screening Program in Correctional Facilities in South Africa

    PubMed Central

    Zishiri, Vincent; Charalambous, Salome; Shah, Maunank R.; Chihota, Violet; Page-Shipp, Liesl; Churchyard, Gavin J.; Hoffmann, Christopher J.

    2015-01-01

    Background. Tuberculosis (TB) prevalence is high in correctional facilities in southern Africa. With support from local South African nongovernmental organizations, the South African Department of Correctional Services initiated a program of systematically screening newly admitted and current inmates for symptoms followed by GeneXpert Mycobacterium tuberculosis (MTB)/rifampicin (Rif) for microbiologic testing of symptomatic inmates. Methods. We conducted a program evaluation during a 5-month window describing program reach, effectiveness, adoption within the facilities, cost, and opportunities for sustainability. This evaluation included 4 facilities (2 large and 2 smaller) with a total daily census of 20 700 inmates. Results. During the 5-month evaluation window from May to September 2013, 7426 inmates were screened at the 4 facilities. This represents screening 87% of all new admits (the remaining new admits were screened by correctional staff only and are not included in these statistics) and 23% of the daily inmate census, reaching 55% of the overall screening target as calculated per annum. The reach ranged from 57% screened during these 5 months at one of the smaller facilities to 13% at the largest facility. Two hundred one cases of pulmonary TB were diagnosed, representing 2.1% of the screened population; 93% had documented initiation of TB treatment. The cost per TB case identified was $1513, excluding treatment costs (with treatment costs it was $1880). Conclusions. We reached a large number of inmates with high-volume screening and effectively used GeneXpert MTB/Rif to diagnose pulmonary TB and rapidly initiate treatment. The cost was comparable to other screening programs. PMID:25884008

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

    PubMed Central

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

    2006-01-01

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

  14. CUTANEOUS TUBERCULOSIS: A 26-YEAR RETROSPECTIVE STUDY IN AN ENDEMIC AREA OF TUBERCULOSIS, VITÓRIA, ESPÍRITO SANTO, BRAZIL

    PubMed Central

    SPELTA, Karla; DINIZ, Lucia M.

    2016-01-01

    SUMMARY Background: Tuberculosis is a serious health problem in Brazil so that the knowledge on the aspects of cutaneous tuberculosis is medically important. Objective: To assess the characteristics of patients with cutaneous tuberculosis treated at the Cassiano Antonio Moraes University Hospital, located in the city of Vitória, State of Espírito Santo, Brazil. Methods: This is a retrospective, descriptive, observational and cross-sectional study using the medical records of 29 patients with cutaneous tuberculosis treated at the Dermatology and Pulmonology services of the hospital from 1986 to 2011. The inclusion criterion was the confirmation of cutaneous tuberculosis taking into account clinical, epidemiological, immunological, and bacteriological findings, as well as the response to specific treatment. Results: Of the 29 studied patients; 18 (62%) were women with average age of 37 years; the predominant clinical condition was erythema induratum of Bazin in 12 (41.4%) cases; and the cutaneous lesions were in the lower limbs in 19 (65.8%) patients. Extra-cutaneous involvement occurred in eight (27.6%) cases. The tuberculin tests were positive in 15 (79%) individuals and the assessment of the infectious agent was negative in most of the investigated cases. Conclusion: The study found a low frequency (0.44%) of cutaneous tuberculosis in an endemic area of tuberculosis. There was a predominance of infection in women aged thirty to forty years. Erythema induratum was the most common clinical condition, affecting mainly the lower limbs, in contrast to other Brazilian studies that found scrofuloderma as the most common manifestation, predominating in the cervical region of male children and adolescents. PMID:27410909

  15. Genetic polymorphisms of IL-17A, IL-17F, TLR4 and miR-146a in association with the risk of pulmonary tuberculosis.

    PubMed

    Wang, Min; Xu, Guisheng; Lü, Lingshuang; Xu, Kun; Chen, Yongzhong; Pan, Hongqiu; Burstrom, Bo; Burstrom, Kristina; Wang, Jianming

    2016-01-01

    Genetic factors affect host susceptibility to pathogens. In this population-based case control study, we explored the genetic polymorphisms of IL-17, TLR4 and miR-146a in association with pulmonary tuberculosis in a Chinese Han population. We recruited 1601 pulmonary tuberculosis patients matched with 1526 healthy controls and genotyped twelve functional single nucleotide polymorphisms (SNPs). After the correction for multiple comparisons, two SNPs (rs10759932 and rs2737190) in the TLR4 gene remained significant. Individuals carrying the rs2737190-AG genotype (vs. AA) had a significantly increased risk of either clinical tuberculosis (OR: 1.31, 95% CI: 1.11-1.53) or sputum smear-positive tuberculosis (OR: 1.35, 95% CI: 1.13-1.61). Stratification analysis revealed that the effects of genetic variations on tuberculosis were more evident among non-smokers. People with haplotype TLR4 rs10983755G-rs10759932C had a significantly increased risk of tuberculosis (OR: 3.43, 95% CI: 2.34-5.05). Moreover, we found that SNPs of rs3819024 in IL-17A and rs763780 in IL-17F were weakly related to a prognosis of tuberculosis. Our results suggest that genetic polymorphisms of IL-17 and TLR4 may play a role in host susceptibility to tuberculosis in the Chinese Han population. More work is necessary to identify specific causative variants of tuberculosis underlying the observed associations. PMID:27339100

  16. Genetic polymorphisms of IL-17A, IL-17F, TLR4 and miR-146a in association with the risk of pulmonary tuberculosis

    PubMed Central

    Wang, Min; Xu, Guisheng; Lü, Lingshuang; Xu, Kun; Chen, Yongzhong; Pan, Hongqiu; Burstrom, Bo; Burstrom, Kristina; Wang, Jianming

    2016-01-01

    Genetic factors affect host susceptibility to pathogens. In this population-based case control study, we explored the genetic polymorphisms of IL-17, TLR4 and miR-146a in association with pulmonary tuberculosis in a Chinese Han population. We recruited 1601 pulmonary tuberculosis patients matched with 1526 healthy controls and genotyped twelve functional single nucleotide polymorphisms (SNPs). After the correction for multiple comparisons, two SNPs (rs10759932 and rs2737190) in the TLR4 gene remained significant. Individuals carrying the rs2737190-AG genotype (vs. AA) had a significantly increased risk of either clinical tuberculosis (OR: 1.31, 95% CI: 1.11–1.53) or sputum smear-positive tuberculosis (OR: 1.35, 95% CI: 1.13–1.61). Stratification analysis revealed that the effects of genetic variations on tuberculosis were more evident among non-smokers. People with haplotype TLR4 rs10983755G–rs10759932C had a significantly increased risk of tuberculosis (OR: 3.43, 95% CI: 2.34–5.05). Moreover, we found that SNPs of rs3819024 in IL-17A and rs763780 in IL-17F were weakly related to a prognosis of tuberculosis. Our results suggest that genetic polymorphisms of IL-17 and TLR4 may play a role in host susceptibility to tuberculosis in the Chinese Han population. More work is necessary to identify specific causative variants of tuberculosis underlying the observed associations. PMID:27339100

  17. [Zoonotic tuberculosis in Argentina].

    PubMed

    Kantor, Isabel N de; Torres, Pedro M; Morcillo, Nora; Imaz, María S; Sequeira, María D

    2012-01-01

    There are significant achievements in the control of animal tuberculosis (tB) in Argentina. the percentage of bovines with apparent tB lesions at the slaughterhouse inspection decreased from 6.7% to 0.6% between 1969 and 2011. on the other hand, the mean percentage of human tB cases due to M. bovis among all those bacteriologically confirmed, was in Santa Fe, an agro-industrial province, 2.3% in the period 1977-2001. It fell to 1.6% by 2011. In the Cetrángolo Hospital (Buenos Aires), it was 0.34% in the period 2001-2005, and 0.36% in 2006-2011. At the Muñiz Hospital, these percentages decreased from 1.75% in 1971 to 0.22% in 2006. Frequency of HIV infection among M. bovis cases varied from 5.9% in santa Fe to 11.1% and 20.5% respectively, in Cetrángolo and Muñiz Hospitals (a reference institution for aids) in Buenos Aires. According to these data M. bovis infection predominates in agro-industrial/ rural areas, showing a slow decrease there as well as in Buenos Aires. Co-infection with HIV is more frequent among patients with M. bovis that in all cases of tB. The situation of M. bovis in Argentina is here compared with that in USA and in several European and Latin American countries. Trends followed by tB in cattle, in humans, and the percentages of M. bovis among them, are not always closely related to move towards the common goal of eradicating tB; the employment of appropriate strategies and the strengthening of control measures are critical in both programs.

  18. Schistosome Soluble Egg Antigen Decreases Mycobacterium tuberculosis-Specific CD4+ T-Cell Effector Function With Concomitant Arrest of Macrophage Phago-Lysosome Maturation.

    PubMed

    DiNardo, Andrew R; Mace, Emily M; Lesteberg, Kelsey; Cirillo, Jeffrey D; Mandalakas, Anna M; Graviss, Edward A; Orange, Jordan S; Makedonas, George

    2016-08-01

    Helminth-infected individuals possess a higher risk of developing tuberculosis, but the precise immunologic mechanism of Mycobacterium tuberculosis control remains unclear. We hypothesized that a perturbation of the M. tuberculosis-specific CD4(+) T-cell response weakens the ability of macrophages to contain M. tuberculosis We exposed peripheral blood mononuclear cells from M. tuberculosis-infected humans to schistosome soluble egg antigen (SEA) and then profiled M. tuberculosis-specific CD4(+) T cells via multiparametric flow cytometry. SEA decreased the frequency of cells producing interferon γ (6.79% vs 3.20%; P = .017) and tumor necrosis factor α (6.98% vs 2.96%; P = .012), with a concomitant increase in the median fluorescence intensity of interleukin 4 (IL-4; P < .05) and interleukin 10 (IL-10; 1440 vs 1273; P < .05). Macrophages polarized with SEA-exposed, autologous CD4(+) T-cell supernatant had a 2.19-fold decreased colocalization of lysosomes and M. tuberculosis (P < .05). When polarized with IL-4 or IL-10, macrophages had increased expression of CD206 (P < .0001), 1.5-fold and 1.9 fold increased intracellular numbers of M. tuberculosis per macrophage (P < .0005), and 1.4-fold and 1.7-fold decreased colocalization between M. tuberculosis and lysosomes (P < .001). This clarifies a relationship in which helminth-induced CD4(+) T cells disrupt M. tuberculosis control by macrophages, thereby providing a mechanism for the observation that helminth infection advances the progression of tuberculosis among patients with M. tuberculosis infection. PMID:27389351

  19. Latent Tuberculosis in Pregnancy: A Systematic Review

    PubMed Central

    Malhamé, Isabelle; Cormier, Maxime; Sugarman, Jordan; Schwartzman, Kevin

    2016-01-01

    Background In countries with low tuberculosis (TB) incidence, immigrants from higher incidence countries represent the major pool of individuals with latent TB infection (LTBI). The antenatal period represents an opportunity for immigrant women to access the medical system, and hence for potential screening and treatment of LTBI. However, such screening and treatment during pregnancy remains controversial. Objectives In order to further understand the prevalence, natural history, screening and management of LTBI in pregnancy, we conducted a systematic literature review addressing the screening and treatment of LTBI, in pregnant women without known HIV infection. Methods A systematic review of 4 databases (Embase, Embase Classic, Medline, Cochrane Library) covering articles published from January 1st 1980 to April 30th 2014. Articles in English, French or Spanish with relevant information on prevalence, natural history, screening tools, screening strategies and treatment of LTBI during pregnancy were eligible for inclusion. Articles were excluded if (1) Full text was not available (2) they were case series or case studies (3) they focused exclusively on prevalence, diagnosis and treatment of active TB (4) the study population was exclusively HIV-infected. Results Of 4,193 titles initially identified, 208 abstracts were eligible for review. Of these, 30 articles qualified for full text review and 22 were retained: 3 cohort studies, 2 case-control studies, and 17 cross-sectional studies. In the USA, the estimated prevalence of LTBI ranged from 14 to 48% in women tested, and tuberculin skin test (TST) positivity was associated with ethnicity. One study suggested that incidence of active TB was significantly increased during the 180 days postpartum (Incidence rate ratio, 1.95 (95% CI 1.24–3.07). There was a high level of adherence with both skin testing (between 90–100%) and chest radiography (93–100%.). In three studies from low incidence settings, concordance

  20. Tuberculosis in otorhinolaryngology: clinical presentation and diagnostic challenges.

    PubMed

    Michael, Rajiv C; Michael, Joy S

    2011-01-01

    Tuberculosis affects all tissues of the body, although some more commonly than the others. Pulmonary tuberculosis is the most common type of tuberculosis accounting for approximately 80% of the tuberculosis cases. Tuberculosis of the otorhinolaryngeal region is one of the rarer forms of extrapulmonary tuberculosis but still poses a significant clinical and diagnostic challenge. Over three years, only five out of 121 patients suspected to have tuberculosis of the otorhinolaryngeal region (cervical adenitis excluded) had Mycobacterium tuberculosis culture-proven disease. Additional 7 had histology-proven tuberculosis. Only one patient had concomitant sputum-positive pulmonary tuberculosis. We look at the various clinical and laboratory aspects of tuberculosis of the otorhinolaryngeal region that would help to diagnose this uncommon but important form of extrapulmonary tuberculosis.

  1. Effects of Fluroquinolones in Newly Diagnosed, Sputum-Positive Tuberculosis Therapy: A Systematic Review and Network Meta-Analysis

    PubMed Central

    Li, Dandan; Wang, Tiansheng; Shen, Su; Cheng, Sheng; Yu, Junxian; Zhang, Yang; Zhang, Chao; Tang, Huilin

    2015-01-01

    Background Tuberculosis is a major public health problem especially in developing countries, the comparative efficacy and safety of fluroquinolones (FQs) for adult patients with newly diagnosed, sputum-positive tuberculosis remains controversial. We aimed to investigate the benefits and risks of FQs-containing (addition/substitution) regimens in this population. Methods A network meta-analysis was performed to compare FQs (C: ciprofloxacin; O: ofloxacin; Lo: levofloxacin; M: moxifloxacin; G: gatifloxacin) addition/substitution regimen with standard HRZE regimen (ie isoniazid, rifampicin, pyrazinamide and ethambutol) in newly diagnosed, sputum-positive tuberculosis. Medline, Embase and Cochrane Central Register of Controlled Trials were systematically searched, randomized trials with duration longer than 8 weeks were included. The primary outcome was week-8 sputum negativity, and secondary outcomes included treatment failure, serious adverse events and death from all cause. Results Twelve studies comprising 6465 participants were included in the network meta-analysis. Löwenstein-Jensen culture method showed that HRZEM (OR 4.96, 95% CI 2.83–8.67), MRZE (OR 1.48, 95% CI 1.19–1.84) and HRZM (OR 1.32, 95% CI 1.08–1.62) had more sputum conversion than HRZE by the eighth week, whereas HRC (OR 0.39, 95% CI 0.19–0.77) and HRZO (OR 0.47, 95% CI 0.24–0.92) were worse than HRZE. Moxifloxacin-containing regimens showed more conversion than HRZE by liquid method at the end of two months. But by the end of treatment, FQs-containing regimens didn’t show superiority than HRZE on treatment failure. There were no significant differences between any regimens on other outcomes like serious adverse events and all-cause death. Conclusion This comprehensive network meta-analysis showed that compared with HRZE, moxifloxacin-containing regimens could significantly increase sputum conversion by the eighth week for patients with newly diagnosed pulmonary tuberculosis while HRC

  2. Development of new vaccines for tuberculosis. Recommendations of the Advisory Council for the Elimination of Tuberculosis (ACET).

    PubMed

    1998-08-21

    Tuberculosis (TB) remains a major, global public health problem, particularly in low-income countries. Better application of current diagnostic, treatment, and prevention strategies could lead to gradual decreases in the disease, but eliminating TB completely in the United States and internationally will require new tools. The greatest impact could come from a new vaccine, and recent technological advances have provided the basis for new vaccine development. However, sustained support is required to move the research from the laboratory to field trials of vaccines and to implement new vaccine programs. Recognizing the importance of TB vaccines, the Advisory Council for the Elimination of Tuberculosis (ACET) recommends that public agencies and vaccine manufacturers develop a comprehensive, consensual strategy to achieve these goals. This report outlines the elements that should be considered in devising a strategic plan for vaccine development.

  3. Tuberculosis and Cardiovascular Disease: Linking the Epidemics

    PubMed Central

    Huaman, Moises A.; Henson, David; Ticona, Eduardo; Sterling, Timothy R.; Garvy, Beth A.

    2016-01-01

    The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, subsets of mycobacteria actively replicate during latent tuberculosis infection (LTBI), and recent studies suggest that LTBI is associated with persistent chronic inflammation that may lead to CVD. Recent epidemiologic work has shown that the risk of CVD in persons who develop tuberculosis is higher than in persons without a history of tuberculosis, even several years after recovery from tuberculosis. Together, these data suggest that tuberculosis may play a role in the pathogenesis of CVD. Further research to investigate a potential link between tuberculosis and CVD is warranted. PMID:26835156

  4. [AIDS and tuberculosis in central Tunisia].

    PubMed

    Jemni, L; Bahri, S; Saadi, M; Letaif, A; Dhidah, M; Lahdhiri, H; Bouchoucha, S

    1991-05-01

    7 men and 2 women seropositive for HIV were carefully screened for tuberculosis in the internal medicine service of a hospital in Sousse, central Tunisia, and all tuberculosis patients aged 20-50 years registered at the tuberculosis treatment center in Sousse between May 1987-December 1988 were screened for HIV infections using the ELISA test. The HIV seropositive patients ranged in age from 21-42 years and averaged 28 at the time of diagnosis. Marriage to an HIV-positive man was the only risk factor for the 2 seropositive women. 1 of the men had hemophilia and the rest had travelled abroad and used drugs or had homosexual or heterosexual relations while outside Tunisia. 4 of the 9 HIV positive patients were diagnoses with tuberculosis, 2 with isolated pulmonary tuberculosis, 1 with pulmonary and hepatoslenic tuberculosis, and 1 with a cervical ganglionary tuberculosis. 3 of the 4 with tuberculosis had apparently normal thoracic X-rays. The 4 were treated with the normal course of antitubercular drugs for a year or more. Screening for HIV in the 104 tuberculosis patients aged 20-50 years revealed no cases of HIV infection. Tuberculosis appears to be 1 of the most frequent opportunistic infections among patients seropositive for HIV, but it is not an indicator or predictor of HIV infection in central Tunisia as it reportedly is in some African countries.

  5. Ciguatera: recent advances but the risk remains.

    PubMed

    Lehane, L; Lewis, R J

    2000-11-01

    Ciguatera is an important form of human poisoning caused by the consumption of seafood. The disease is characterised by gastrointestinal, neurological and cardiovascular disturbances. In cases of severe toxicity, paralysis, coma and death may occur. There is no immunity, and the toxins are cumulative. Symptoms may persist for months or years, or recur periodically. The epidemiology of ciguatera is complex and of central importance to the management and future use of marine resources. Ciguatera is an important medical entity in tropical and subtropical Pacific and Indian Ocean regions, and in the tropical Caribbean. As reef fish are increasingly exported to other areas, it has become a world health problem. The disease is under-reported and often misdiagnosed. Lipid-soluble, polyether toxins known as ciguatoxins accumulated in the muscles of certain subtropical and tropical marine finfish cause ciguatera. Ciguatoxins arise from biotransformation in the fish of less polar ciguatoxins (gambiertoxins) produced by Gambierdiscus toxicus, a marine dinoflagellate that lives on macroalgae, usually attached to dead coral. The toxins and their metabolites are concentrated in the food chain when carnivorous fish prey on smaller herbivorous fish. Humans are exposed at the end of the food chain. More than 400 species of fish can be vectors of ciguatoxins, but generally only a relatively small number of species are regularly incriminated in ciguatera. Ciguateric fish look, taste and smell normal, and detection of toxins in fish remains a problem. More than 20 precursor gambiertoxins and ciguatoxins have been identified in G. toxicus and in herbivorous and carnivorous fish. The toxins become more polar as they undergo oxidative metabolism and pass up the food chain. The main Pacific ciguatoxin (P-CTX-1) causes ciguatera at levels=0.1 microg/kg in the flesh of carnivorous fish. The main Caribbean ciguatoxin (C-CTX-1) is less polar and 10-fold less toxic than P-CTX-1. Ciguatoxins

  6. Tuberculosis Prevention in College Students

    ERIC Educational Resources Information Center

    Lerman, Stephen J.; Bernardo, John; Daly, Jennifer S.; Husson, Robert

    2004-01-01

    To help college health services in all parts of the country improve their approach to latent tuberculosis, two Listservs were provided for them to post their questions on dealing with TB infection. In this article, the authors present some of the questions posted in the Listservs and their corresponding answers. In their answers, the authors have…

  7. Tuberculosis and HIV infection worldwide.

    PubMed

    Murray, J F

    1995-12-01

    The incidence of HIV-associated tuberculosis is increasing worldwide and will continue to increase during the foreseeable future, especially in developing countries. HIV infection appears to increase the opportunity for M. tuberculosis to succeed in causing infection after inhalation into the lungs. Moreover, there is persuasive evidence that in the presence of HIV infection, new-onset tuberculous infection will progress rapidly to clinically significant disease and the likelihood that latent tuberculous infection will reactivate is enormously increased. The accelerating and amplifying influence of HIV infection is contributing to the increasing incidence of disease caused by multidrug-resistant strains of M. tuberculosis. Neither clinical or radiographic features reliably distinguish the majority of patients with HIV-associated tuberculosis from those who are non-HIV-infected. The remainder, however, may have atypical manifestations and be difficult to diagnose. Six months of chemotherapy with conventional antituberculosis drugs cures most patients, but many die during or after treatment of other AIDS-related complications.

  8. Pilonidal sinus disease and tuberculosis.

    PubMed

    Gupta, P J

    2012-01-01

    Pilonidal disease is a disease of young people, usually men, which can result in an abscess, draining sinus tracts, and moderate debility for some. It probably results from hair penetration beneath the skin, for reasons that are not totally clear. A pilonidal sinus in the sacrococcygeal region is associated with recurrent infection, abscess formation, cellulitis, and fistulae. The infection is usually chronic and non-specific. However, few reports of granulomatous infection like tuberculosis and actinomycosis in pilonidal sinus have been observed. The presentation of tuberculosis in these sinuses may have wide forms, with atypical and uncharacteristic clinical picture, making it difficult to make a diagnosis preoperatively. This paper discusses about pilonidal sinus disease and tubercular infiltration in these sinuses. The diagnosis of tuberculosis in pilonidal sinus disease is elusive, necessitating a high index of suspicion. The literature on the tubercular affliction of pilonidal sinus is scant. Novel diagnostic modalities such as adenosine deaminase levels and polymerase chain reaction (PCR) can be useful in doubtful situations. Physicians should obtain a thorough history focusing on risk behaviors for human immunodeficiency virus infection (HIV) and tuberculosis. Treatment comprises of standard regimen of antitubercular medication and a modest surgical approach towards the sinuses. PMID:22338544

  9. The Cosmic Background Explorer.

    ERIC Educational Resources Information Center

    Gulkis, Samuel; And Others

    1990-01-01

    Outlines the Cosmic Background Explorer (COBE) mission to measure celestial radiation. Describes the instruments used and experiments involving differential microwave radiometers, and a far infrared absolute spectrophotometer. (YP)

  10. Epidemiology and clinical management of tuberculosis in children in Canada.

    PubMed

    Morris, Shaun K; Demers, Anne-Marie; Lam, Ray; Pell, Lisa G; Giroux, Ryan Jp; Kitai, Ian

    2015-03-01

    Although often regarded as a foreign disease, latent tuberculosis or tuberculosis disease will be encountered in many clinical situations by the Canadian child health practitioner. There are key differences between tuberculosis in children and adults. In the present article, the changing epidemiology of tuberculosis in children in Canada and around the world, the pathogenesis of infection, diagnostic tests, and clinical management of childhood latent tuberculosis and tuberculosis disease are reviewed.

  11. Epidemiology and clinical management of tuberculosis in children in Canada

    PubMed Central

    Morris, Shaun K; Demers, Anne-Marie; Lam, Ray; Pell, Lisa G; Giroux, Ryan JP; Kitai, Ian

    2015-01-01

    Although often regarded as a foreign disease, latent tuberculosis or tuberculosis disease will be encountered in many clinical situations by the Canadian child health practitioner. There are key differences between tuberculosis in children and adults. In the present article, the changing epidemiology of tuberculosis in children in Canada and around the world, the pathogenesis of infection, diagnostic tests, and clinical management of childhood latent tuberculosis and tuberculosis disease are reviewed. PMID:25838781

  12. Impact of HIV Status on Treatment Outcome of Tuberculosis Patients Registered at Arsi Negele Health Center, Southern Ethiopia: A Six Year Retrospective Study

    PubMed Central

    Gebremariam, Gebreslassie; Asmamaw, Getachew; Hussen, Muktar; Hailemariam, Mengistu Z.; Asegu, Demissie; Astatkie, Ayalew; Amsalu, Anteneh G.

    2016-01-01

    Background Despite implementation of different strategies, the burden and mortality of human immunodeficiency virus (HIV)-associated tuberculosis (TB) remains a challenge in Ethiopia. The aim of this study was to assess the impact of HIV status on treatment outcome of tuberculosis patients registered at Arsi Negele Health Center, Southern Ethiopia. Methods A six-year retrospective data (from September 2008 to August 2014) of tuberculosis patients (n = 1649) registered at the directly observed therapy short-course (DOTS) clinic of Arsi Negele Health Center was reviewed. Treatment outcome and tuberculosis type were categorized according to the national tuberculosis control program guideline. Data were entered and analyzed using SPSS version 20. Multinomial logistic regression analysis was used to examine the effect of HIV status separately on default/failure and death in relation to those who were successfully treated. Odds ratios with 95% confidence intervals were used to check the presence and strength of association between TB treatment outcome and HIV status and other independent variables. Results Out of the 1649 TB patients, 94.7% (1562) have been tested for HIV of whom 156(10%) were HIV co-infected. The mean (standard deviation) age of the patients was 28.5(15.5) years. The majority were new TB cases (96.7%), male (53.7%), urban (54.7%), and had smear negative pulmonary TB (44.1%). Overall, the treatment success rate of TB patients with or without HIV was 87.3%. Using cure/completion as reference, patients without known HIV status had significantly higher odds of default /failure [aOR, 4.26; 95%CI, 1.684–10.775] and transfer-out [aOR, 2.92; 95%CI, 1.545–5.521] whereas those who tested positive for HIV had a significantly higher odds of death [aOR, 6.72; 95%CI, 3.704–12.202] and transfer-out [aOR, 2.02; 95%CI, 1.111–3.680]. Conclusion Overall, treatment outcome and HIV testing coverage for TB patients is promising to reach the WHO target in the study

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

    PubMed Central

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

    2014-01-01

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

  14. Implementation of latent tuberculosis screening in HIV care centres: evaluation in a low tuberculosis incidence setting.

    PubMed

    Wyndham-Thomas, C; Schepers, K; Dirix, V; Mascart, F; Van Vooren, J-P; Goffard, J-C

    2016-03-01

    The screening and treatment of latent tuberculosis infection (LTBI) to prevent active tuberculosis (TB) is recommended by the WHO in all HIV-infected patients. The aim of this study was to evaluate its implementation within Belgium's HIV care. A multiple-choice questionnaire was sent to 55 physicians working in the country's AIDS reference centres. Response rate reached 62%. Only 20% screened all their HIV-infected patients for LTBI. Screening methods used and their interpretation vary from one physician to another. The main barriers to the implementation of LTBI screening and treatment, as perceived by the participants, are lack of sensitivity of screening tools, risks associated with polypharmacy and toxicity of treatment. The poor coverage of LTBI screening reported here and the inconsistency in methods used raises concern. However, this was not unexpected as, in low-TB incidence countries, who, when and how to screen for LTBI remains unclear and published guidelines show important disparities. Recently, a targeted approach in which only HIV-infected patients at highest risk of TB are screened has been suggested. Such a strategy would limit unnecessary exposure to LTBI treatment. This methodology was approved by 80% of the participants and could therefore achieve greater coverage. Its clinical validation is still pending.

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

    PubMed Central

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

    2011-01-01

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

  16. 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

  17. 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...

  18. Correlators in nontrivial backgrounds

    SciTech Connect

    Mello Koch, Robert de; Ives, Norman; Stephanou, Michael

    2009-01-15

    Operators in N=4 super Yang-Mills theory with an R-charge of O(N{sup 2}) are dual to backgrounds which are asymtotically AdS{sub 5}xS{sup 5}. In this article we develop efficient techniques that allow the computation of correlation functions in these backgrounds. We find that (i) contractions between fields in the string words and fields in the operator creating the background are the field theory accounting of the new geometry, (ii) correlation functions of probes in these backgrounds are given by the free field theory contractions but with rescaled propagators and (iii) in these backgrounds there are no open string excitations with their special end point interactions; we have only closed string excitations.

  19. Activation of JAK2/STAT1-alpha-dependent signaling events during Mycobacterium tuberculosis-induced macrophage apoptosis.

    PubMed

    Rojas, Mauricio; Olivier, Martin; García, Luis F

    2002-01-01

    Induction of apoptosis by Mycobacterium tuberculosis in murine macrophage involves TNF-alpha and nitric oxide (NO) production and caspase cascade activation; however, the intracellular signaling pathways implicated remain to be established. Our results indicate that infection of the B10R murine macrophage line with M. tuberculosis induces apoptosis independent of mycobacterial phagocytosis and that M. tuberculosis induces protein tyrosine kinase (PTK) activity, JAK2/STAT1-alpha phosphorylation, and STAT1-alpha nuclear translocation. Inhibitors of PTK (AG-126), or JAK2 (AG-490) inhibited TNF-alpha and NO production, caspase 1 activation and apoptosis, suggesting that M. tuberculosis-induction of these events depends on JAK2/STAT1-alpha activation. In addition, we have obtained evidence that ManLAM capacity to inhibit M. tuberculosis-induced apoptosis involves the activation of the PTP SHP-1. The finding that M. tuberculosis infection activate JAK2/STAT1-alpha pathway suggests that M. tuberculosis might mimic macrophage-activating stimuli.

  20. 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 IFNγ 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

  1. Efficacy of the Revised National Tuberculosis Programme.

    PubMed

    Jhunjhunwala, B

    1995-01-01

    In India, the standard regimen (SR) for treating tuberculosis consisted of a 2-month intensive treatment by 2-3 inexpensive drugs followed by a 10-month course using 2 drugs. In the 1980s, this course was shortened to 6 months owing to the powerful drugs rifampicin and pyrazinamide. Thiacetazone was also replaced by the more expensive but less toxic ethambutol. The result was a short-course chemotherapy (SCC) employing 4 drugs for 2 months, followed by 2-3 drugs for 4 months of follow-up. The SCC is being pilot-tested as the Revised National Tuberculosis Program (RNTP); this RNTP strategy is being implemented in Delhi, Bombay, and Mehsana with the assistance of the Swedish international agency. The World Bank also endorsed RNTP, as SCC regimens under it were cost-effective. The SR and SCC regimens were also compared for Malawi, Mozambique, and Tanzania, and relatively minor differences were found in lives saved for expenditures. The claim that the rates of default under SR and SCC remain unchanged over time and the cure rates of the regimens must be challenged. The estimated cure rates of 60% for SR and 85% for SCC do not correspond to the reality in India, where 41% of patients completed treatment under SR versus 47% under SCC. The cost of treatment under SR does not have to be a 5-drug regimen; re-treatment can be a 3-drug regimen, whereby the cost would be lower than assumed. The Ministry of Health and Family Welfare (MHF) was probing 253 district SCCs even in 1992-93 and accepted SCC because the World Health Organization recommended a vastly improved administration for implementation and there was a felt need from patients for speedy cure. If the SCC is administered properly, it may increase the cure rate, even if cost-ineffective; if poorly managed, increased drug resistance of TB bacteria could result, which may be the present situation.

  2. [A clinical observation on urogenital tuberculosis].

    PubMed

    Noguchi, S; Shuin, T; Kitajima, N; Ishizuka, E

    1986-05-01

    A clinical observation was made on 30 cases of urogenital tuberculosis diagnosed and treated at the urological department of our Hospital between January, 1976 and December, 1984. Furthermore, 20 of them were examined for drug resistance and investigated for this tendency. They accounted for 0.23% of the outpatients. Male to female ratio was 2 to 1, but on urological tuberculosis this ratio was even. The average age was 43.7 and 50% of the patients who had a history of tuberculosis. Mycobacterium tuberculosis could be detected in 24 of the 30 cases (80%) and 18 of the 21 cases (85.4%) of urological tuberculosis. Drug resistance was examined in 20 patients. The resistant ratio of M. tuberculosis against primary drugs such as SM, PAS, INAH was low and a high resistant ratio was observed on secondary drugs such as EB, RFP, TH. These clinical observations are reported and herein discussed.

  3. Atypical presentation of oral tuberculosis ulcer.

    PubMed

    Mahajan, Sumita; Srikant, Natarajan; George, Thomas

    2007-11-01

    Tuberculosis is a chronic infectious disease that can affect any part of the body, including the mouth. An upsurge in the number of tuberculosis cases, with a strong association with HIV infection, has been noted. We present a case of tuberculosis that clinically resembles a malignant chronic ulcer in the retromolar trigone-an uncommon site of occurrence. Histologically, the case demonstrated an atypical epitheloid granuloma with reduced lymphocyte count. The diagnosis of tuberculosis was confirmed following sputum culture of M tuberculosis. Antitubercular therapy improved the patient's condition. Although rare, tuberculosis must be considered as a differential diagnosis in chronic ulcers in the oral region; and its association with HIV must not be overlooked.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  5. Mycobacterium tuberculosis infection in women with unexplained infertility

    PubMed Central

    Eftekhar, Maryam; Pourmasumi, Soheila; Sabeti, Parvin; Aflatoonian, Abbas; Sheikhha, Mohammad Hasan

    2015-01-01

    Background: Genital tuberculosis (GTB) is an important cause of female infertility, especially in developing countries. The positive results of polymerase chain reaction (PCR) in endometrial GTB in the absence of tubal damage raise the possibility of the detection of sub-clinical or latent disease, with doubtful benefits of treatment. Objective: To evaluate the mycobacterium tuberculosis infection in endometrial biopsy samples collected from unexplained infertile women attending Yazd Research and Clinical Center for Infertility by using PCR techniques. Materials and Methods: In this cross sectional study, 144 infertile women with unexplained infertility aged 20-35 years old and normal Histro-saplango graphy findings were enrolled. Endometrial biopsy samples from each participant were tested for mycobacterium tuberculosis detecting by PCR. In 93 patients, peritoneal fluid was also taken for culture and PCR. Results: The PCR results of endometrial specimens were negative in all cases, demonstrating that there was no GTB infection among our patients. Conclusion: Our results showed that GTB could not be considered as a major problem in women with unexplained infertility. Although, studies have indicated that PCR is a useful method in diagnosing early GTB disease in infertile women with no demonstrable evidence of tubal or endometrial involvement. PMID:27141534

  6. 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

  7. Dormancy models for Mycobacterium tuberculosis: A minireview

    PubMed Central

    Alnimr, Amani M.

    2015-01-01

    Dormancy models for Mycobacterium tuberculosis play important roles in understanding various aspects of tuberculosis pathogenesis and in the testing of novel therapeutic regimens. By simulating the latent tuberculosis infection, in which the bacteria exist in a non-replicative state, the models demonstrate reduced susceptibility to antimycobacterial agents. This minireview outlines the models available for simulating latent tuberculosis both in vitro and in several animal species. Additionally, this minireview discusses the advantages and disadvantages of these models for investigating the bacterial subpopulations and susceptibilities to sterilization by various antituberculosis drugs. PMID:26413043

  8. [Oral blastomycosis, laryngeal papillomatosis and esophageal tuberculosis].

    PubMed

    Montoya, Manuel; Chumbiraico, Robert; Ricalde, Melvin; Cazorla, Ernesto; Hernández-Córdova, Gustavo

    2012-06-01

    Esophageal involvement is an extremely rare complication of tuberculosis even in countries with high prevalence of infection. We report the case of a 57 year-old hiv-seronegative patient with simultaneous diagnoses of oral blastomycosis and laryngeal papillomatosis. Both were confirmed by anatomopathological analysis. The esophageal biopsy revealed granulomatous esophagitis with necrosis and ziehl-neelsen stain showed acid-fast alcohol resistant bacilli suggestive of tuberculosis. The patient's history included pulmonary tuberculosis twice and previous abandonment of therapy. Thus, it was necessary to use oral itraconazole combined with second-line anti-tuberculosis drugs administered through a gastrostomy tube. The clinical development was favorable. PMID:22858774

  9. Cutaneous tuberculosis and squamous-cell carcinoma.

    PubMed

    Ljubenovic, Milanka S; Ljubenovic, Dragisa B; Binic, Ivana I; Jankovic, Aleksandar S; Jancic, Snezana A

    2011-01-01

    The incidence of all forms of cutaneous tuberculosis, including lupus vulgaris (the most common form) decreased progressively in developed countries during the twentieth century, this change being attributed to improved living standards and specific therapy. Despite the decrease in cutaneous tuberculosis, some cases are still found and correct diagnosis and management are fundamental, both for the patients and for public health. Long lasting, misdiagnosed or untreated cutaneous tuberculosis may lead to different forms of cancer. This case report involves a 74-year old male farmer with lupus vulgaris on his face. During anti-tuberculosis treatment he developed a tumor on his forehead, which was histologically confirmed as a squamous cell carcinoma.

  10. A historical case of disseminated chronic tuberculosis.

    PubMed

    Nores, J M; Yakovleff, Y

    1995-01-01

    A British author has put forward a new explanation for Joan of Arc's behaviour. This author suggests that the voices Joan of Arc heard were due to the presence of a temporal lobe tuberculoma in the context of widespread chronic tuberculosis (exposure to bovine tuberculosis, amenorrhoea, heart and intestines incombustible). We consider that some elements are incompatible with widespread tuberculosis. It is difficult to draw final conclusions, but it would seem unlikely that widespread tuberculosis, a serious disease, was present in this 'patient' whose life-style and activities would surely have been impossible had such a serious disease been present. PMID:7477805

  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. [THE ORGANIZATION OF MEDICAL CARE OF PATIENTS WITH SEVERE AND CHRONIC FORMS OF TUBERCULOSIS].

    PubMed

    Pianzova, T V; Kopilova, I F

    2015-01-01

    The demand in palliative care was analyzed using sampling of 43 patients with severe and chronic forms of tuberculosis. The study applied hospital Anxiety and Depression Scale (HADS), Charlson scale and visual analogue pain scale. The patients had both various physical symptoms and psychological and social problems. It is demonstrated that patients with severe forms of tuberculosis in 50% of cases had high level of comorbidity at the expense of severe concomitant and background diseases requiring simultaneous therapy and dynamic monitoring by physicians of various specialties, including participation of psychologist and psychotherapist.

  13. A novel tuberculosis antigen identified from human tuberculosis granulomas.

    PubMed

    Yu, Yang; Jin, Dongdong; Hu, Shizong; Zhang, Yan; Zheng, Xiaojing; Zheng, Jianhua; Liao, Mingfeng; Chen, Xinchun; Graner, Michael; Liu, Haiying; Jin, Qi

    2015-04-01

    Tuberculosis is a global infectious disease caused by Mycobacterium tuberculosis (Mtb). Although novel Mtb biomarkers from both the pathogen and host have been studied, more breakthroughs are still needed to meet different clinic requirements. In an effort to identify Mtb antigens, chaperone-peptide complexes were purified from TB infected lungs using free-solution isoelectric focusing combined with high resolution LTQ Orbitrap Velos mass spectrometry. Antigen specific cellular immune responses in vitro were then examined. Those efforts led to the identification of six Mtb peptides only identified in Tuberculosis lung samples and that were not found in the control samples. Additionally, antigen-specific IFN-γ secretion, T-cell proliferation, cytokine expression, and a cytotoxic assay were also evaluated. Among the peptides isolated, we identified a 34 amino acid peptide named PKAp belonging to a serine/threonine-protein kinase, as being able to generate Mtb-specific cellular immune responses as noted by elevated antigen-specific cytokine secretion levels, increased CD8(+) T-cell proliferation and a strong cytotoxic lymphocyte (CTL) response. Moreover, the immune stimulating abilities of PKAp were further validated in vivo, with target peptide immunized mice showing an increased cellular IFN-γ in both the lungs and spleen without causing immunopathogenesis. In conclusion, we identified novel functional Mtb antigens directly from the granulomatous lesions of Tuberculosis patients, inducing not only significant antigen-specific IFN-γ secretion but also a marked cytotoxic lymphocyte functional response. These findings indicated that PKAp has potential as a novel antigen biomarker for vaccine development. PMID:25605460

  14. Mycobacterium tuberculosis: ecology and evolution of a human bacterium.

    PubMed

    Bañuls, Anne-Laure; Sanou, Adama; Anh, Nguyen Thi Van; Godreuil, Sylvain

    2015-11-01

    Some species of the Mycobacterium tuberculosis complex (MTBC), particularly Mycobacterium tuberculosis, which causes human tuberculosis (TB), are the first cause of death linked to a single pathogen worldwide. In the last decades, evolutionary studies have much improved our knowledge on MTBC history and have highlighted its long co-evolution with humans. Its ability to remain latent in humans, the extraordinary proportion of asymptomatic carriers (one-third of the entire human population), the deadly epidemics and the observed increasing level of resistance to antibiotics are proof of its evolutionary success. Many MTBC molecular signatures show not only that these bacteria are a model of adaptation to humans but also that they have influenced human evolution. Owing to the unbalance between the number of asymptomatic carriers and the number of patients with active TB, some authors suggest that infection by MTBC could have a protective role against active TB disease and also against other pathologies. However, it would be inappropriate to consider these infectious pathogens as commensals or symbionts, given the level of morbidity and mortality caused by TB.

  15. Microchip-based ultrafast serodiagnostic assay for tuberculosis

    PubMed Central

    Mani, Vigneshwaran; Paleja, Bhairav; Larbi, Karima; Kumar, Pavanish; Tay, Jo Ann; Siew, Jie Yee; Inci, Fatih; Wang, ShuQi; Chee, Cynthia; Wang, Yee Tang; Demirci, Utkan; De Libero, Gennaro; Singhal, Amit

    2016-01-01

    Access to point-of-care (POC), rapid, inexpensive, sensitive, and instrument-free tests for the diagnosis of tuberculosis (TB) remains a major challenge. Here, we report a simple and low-cost microchip-based TB ELISA (MTBE) platform for the detection of anti-mycobacterial IgG in plasma samples in less than 15 minutes. The MTBE employs a flow-less, magnet-actuated, bead-based ELISA for simultaneous detection of IgG responses against multiple mycobacterial antigens. Anti-trehalose 6,6′-dimycolate (TDM) IgG responses were the strongest predictor for differentiating active tuberculosis (ATB) from healthy controls (HC) and latent tuberculosis infections (LTBI). The TDM-based MTBE demonstrated superior sensitivity compared to sputum microscopy (72% vs. 56%) with 80% and 63% positivity among smear-positive and smear-negative confirmed ATB samples, respectively. Receiver operating characteristic analysis indicated good accuracy for differentiating ATB from HC (AUC = 0.77). Thus, TDM-based MTBE can be potentially used as a screening device for rapid diagnosis of active TB at the POC. PMID:27775039

  16. 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

  17. Expressions of Antimicrobial Peptides LL-37, Human Beta Defensin-2 and -3 in the Lesions of Cutaneous Tuberculosis and Tuberculids

    PubMed Central

    Zhao, Zheng; Mu, Zhang-Lei; Liu, Xi-Wan; Liu, Xiao-Jing; Jia, Jun; Cai, Lin; Zhang, Jian-Zhong

    2016-01-01

    Background: Antimicrobial peptides, including cathelicidin LL-37, human beta defensin (HBD)-2, and HBD-3, are important elements of the innate immune response and involved in modulation of the adaptive immunity, and they also play an important role in cutaneous defense against Mycobacterium tuberculosis. Methods: The fresh skin tissues and paraffin-embedded biopsy samples from three cutaneous tuberculosis, two tuberculids, and ten healthy individuals were collected. The expressions of LL-37, HBD-2, and HBD-3 mRNA in the lesions of three cutaneous tuberculosis and two tuberculids were detected by quantitative real-time polymerase chain reaction; the protein expressions were detected by immunohistochemistry and Western blotting methods. Results: The expressions of LL-37 mRNA and protein in the lesions of cutaneous tuberculosis and tuberculids were similar to that of normal skin. The expression of HBD-2 mRNA had an increasing trend in the lesions of cutaneous tuberculosis and tuberculids compared with that of normal skin; however, the expression of HBD-2 protein in the lesions of cutaneous tuberculosis had a decreasing trend compared with that of normal skin, and the expression of HBD-2 protein in the lesions of tuberculids was similar to that of normal skin. The expressions of HBD-3 mRNA and protein in lesions of cutaneous tuberculosis and tuberculids were similar to that of normal skin. Conclusions: Our study indicated that the expression of HBD-2 and HBD-3 mRNA and protein in lesions of cutaneous tuberculosis may be not consistent with that of tuberculids. However, an inherent limitation of the present study was that the sample size was small, and the roles and regulation mechanisms of LL-37, HBD-2, and HBD-3 in cutaneous tuberculosis and tuberculids need to be further investigated. PMID:26960373

  18. Detection of Tuberculosis Infection Hotspots Using Activity Spaces Based Spatial Approach in an Urban Tokyo, from 2003 to 2011

    PubMed Central

    Izumi, Kiyohiko; Ohkado, Akihiro; Uchimura, Kazuhiro; Murase, Yoshiro; Tatsumi, Yuriko; Kayebeta, Aya; Watanabe, Yu; Ishikawa, Nobukatsu

    2015-01-01

    Background Identifying ongoing tuberculosis infection sites is crucial for breaking chains of transmission in tuberculosis-prevalent urban areas. Previous studies have pointed out that detection of local accumulation of tuberculosis patients based on their residential addresses may be limited by a lack of matching between residences and tuberculosis infection sites. This study aimed to identify possible tuberculosis hotspots using TB genotype clustering statuses and a concept of “activity space”, a place where patients spend most of their waking hours. We further compared the spatial distribution by different residential statuses and describe urban environmental features of the detected hotspots. Methods Culture-positive tuberculosis patients notified to Shinjuku city from 2003 to 2011 were enrolled in this case-based cross-sectional study, and their demographic and clinical information, TB genotype clustering statuses, and activity space were collected. Spatial statistics (Global Moran’s I and Getis-Ord Gi* statistics) identified significant hotspots in 152 census tracts, and urban environmental features and tuberculosis patients’ characteristics in these hotspots were assessed. Results Of the enrolled 643 culture-positive tuberculosis patients, 416 (64.2%) were general inhabitants, 42 (6.5%) were foreign-born people, and 184 were homeless people (28.6%). The percentage of overall genotype clustering was 43.7%. Genotype-clustered general inhabitants and homeless people formed significant hotspots around a major railway station, whereas the non-clustered general inhabitants formed no hotspots. This suggested the detected hotspots of activity spaces may reflect ongoing tuberculosis transmission sites and were characterized by smaller residential floor size and a higher proportion of non-working households. Conclusions Activity space-based spatial analysis suggested possible TB transmission sites around the major railway station and it can assist in further

  19. The GLAST Background Model

    SciTech Connect

    Ormes, J.F.; Atwood, W.; Burnett, T.; Grove, E.; Longo, F.; McEnery, J.; Mizuno, T.; Ritz, S.; /NASA, Goddard

    2007-10-17

    In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

  20. Tuberculosis and nature's pharmacy of putative anti-tuberculosis agents.

    PubMed

    Chinsembu, Kazhila C

    2016-01-01

    Due to the growing problem of drug resistant Mycobacterium tuberculosis strains, coupled with the twinning of tuberculosis (TB) to human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), the burden of TB is now difficult to manage. Therefore, new antimycobacterial agents are being sought from natural sources. This review focuses on natural antimycobacterial agents from endophytes and medicinal plants of Africa, Europe, Asia, South America and Canada. In the countries mentioned in this review, numerous plant species display putative anti-TB activity. Several antimycobacterial chemical compounds have also been isolated, including: ellagitannin punicalagin, allicin, anthraquinone glycosides, iridoids, phenylpropanoids, beta-sitosterol, galanthimine, crinine, friedelin, gallic acid, ellagic acids, anthocyanidin, taraxerol, termilignan B, arjunic acid, glucopyranosides, 1-epicatechol, leucopelargonidol, hydroxybenzoic acids, benzophenanthridine alkaloids, neolignans, and decarine. These compounds may provide leads to novel and more efficacious drugs to lessen the global burden of TB and drug-resistant M. tuberculosis strains. If there is a long-term remedy for TB, it must lie in nature's pharmacy of putative antimycobacterial agents.

  1. Tuberculosis and nature's pharmacy of putative anti-tuberculosis agents.

    PubMed

    Chinsembu, Kazhila C

    2016-01-01

    Due to the growing problem of drug resistant Mycobacterium tuberculosis strains, coupled with the twinning of tuberculosis (TB) to human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), the burden of TB is now difficult to manage. Therefore, new antimycobacterial agents are being sought from natural sources. This review focuses on natural antimycobacterial agents from endophytes and medicinal plants of Africa, Europe, Asia, South America and Canada. In the countries mentioned in this review, numerous plant species display putative anti-TB activity. Several antimycobacterial chemical compounds have also been isolated, including: ellagitannin punicalagin, allicin, anthraquinone glycosides, iridoids, phenylpropanoids, beta-sitosterol, galanthimine, crinine, friedelin, gallic acid, ellagic acids, anthocyanidin, taraxerol, termilignan B, arjunic acid, glucopyranosides, 1-epicatechol, leucopelargonidol, hydroxybenzoic acids, benzophenanthridine alkaloids, neolignans, and decarine. These compounds may provide leads to novel and more efficacious drugs to lessen the global burden of TB and drug-resistant M. tuberculosis strains. If there is a long-term remedy for TB, it must lie in nature's pharmacy of putative antimycobacterial agents. PMID:26464047

  2. Indoor solid fuel use and tuberculosis in China: a matched case-control study

    PubMed Central

    2011-01-01

    Background China ranks second among the 22 high burden countries for tuberculosis. A modeling exercise showed that reduction of indoor air pollution could help advance tuberculosis control in China. However, the association between indoor air pollution and tuberculosis is not yet well established. A case control study was conducted in Anhui, China to investigate whether use of solid fuel is associated with tuberculosis. Methods Cases were new sputum smear positive tuberculosis patients. Two controls were selected from the neighborhood of each case matched by age and sex using a pre-determined procedure. A questionnaire containing demographic information, smoking habits and use of solid fuel for cooking or heating was used for interview. Solid fuel (coal and biomass) included coal/lignite, charcoal, wood, straw/shrubs/grass, animal dung, and agricultural crop residue. A household that used solid fuel either for cooking and (/or) heating was classified as exposure to combustion of solid fuel (indoor air pollution). Odds ratios and their corresponding 95% confidence limits for categorical variables were determined by Mantel-Haenszel estimate and multivariate conditional logistic regression. Results There were 202 new smear positive tuberculosis cases and 404 neighborhood controls enrolled in this study. The proportion of participants who used solid fuels for cooking was high (73.8% among cases and 72.5% among controls). The majority reported using a griddle stove (85.2% among cases and 86.7% among controls), had smoke removed by a hood or chimney (92.0% among cases and 92.8% among controls), and cooked in a separate room (24.8% among cases and 28.0% among controls) or a separate building (67.8% among cases and 67.6% among controls). Neither using solid fuel for cooking (odds ratio (OR) 1.08, 95% CI 0.62-1.87) nor using solid fuel for heating (OR 1.04, 95% CI 0.54-2.02) was significantly associated with tuberculosis. Determinants significantly associated with

  3. Activity of 5-chloro-pyrazinamide in mice infected with Mycobacterium tuberculosis or Mycobacterium bovis

    PubMed Central

    Ahmad, Zahoor; Tyagi, Sandeep; Minkowski, Austin; Almeida, Deepak; Nuermberger, Eric L.; Peck, Kaitlin M.; Welch, John T.; Baughn, Anthony D.; Jacobs, Williams R.; Grosset, Jacques H.

    2012-01-01

    Background & objectives: Pyrazinamide is an essential component of first line anti-tuberculosis regimen as well as most of the second line regimens. This drug has a unique sterilizing activity against Mycobacterium tuberculosis. Its unique role in tuberculosis treatment has lead to the search and development of its structural analogues. One such analogue is 5-chloro-pyrazinamide (5-Cl-PZA) that has been tested under in vitro conditions against M. tuberculosis. The present study was designed with an aim to assess the activity of 5-Cl-PZA, alone and in combination with first-line drugs, against murine tuberculosis. Methods: The minimum inhibitory concentration (MIC) of 5-Cl-PZA in Middlebrook 7H9 broth (neutral pH) and the inhibitory titre of serum from mice that received a 300 mg/kg oral dose of 5-Cl-PZA 30 min before cardiac puncture were determined. To test the tolerability of orally administered 5-Cl-PZA, uninfected mice received doses up to 300 mg/kg for 2 wk. Four weeks after low-dose aerosol infection either with M. tuberculosis or M. bovis, mice were treated 5 days/wk with 5-Cl-PZA, at doses ranging from 37.5 to 150 mg/kg, either alone or in combination with isoniazid and rifampicin. Antimicrobial activity was assessed by colony-forming unit counts in lungs after 4 and 8 wk of treatment. Results: The MIC of 5-Cl-PZA against M. tuberculosis was between 12.5 and 25 μg/ml and the serum inhibitory titre was 1:4. Under the same experimental conditions, the MIC of pyrazinamide was >100 μg/ml and mouse serum had no inhibitory activity after a 300 mg/kg dose; 5-Cl-PZA was well tolerated in uninfected and infected mice up to 300 and 150 mg/kg, respectively. While PZA alone and in combination exhibited its usual antimicrobial activity in mice infected with M. tuberculosis and no activity in mice infected with M. bovis, 5-Cl-PZA exhibited antimicrobial activity neither in mice infected with M. tuberculosis nor in mice infected with M. bovis. Interpretation

  4. 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

  5. Tuberculosis notifications in Australia, 2012 and 2013.

    PubMed

    Toms, Cindy; Stapledon, Richard; Waring, Justin; Douglas, Paul

    2015-06-30

    The National Notifiable Diseases Surveillance System received 1,317 tuberculosis (TB) notifications in 2012 and 1,263 notifications in 2013. This represents a rate of 5.8 per 100,000 population in 2012 and 5.5 per 100,000 population in 2013 and a reversal of the upward trend in TB incidence reported since 2007. In 2012 and 2013, Australia's overseas-born population continued to represent the majority of TB notifications with an incidence rate of 19.5 per 100,000 and 18.4 per 100,000 respectively. The incidence of TB in the Australian-born Indigenous population has fluctuated over the last decade; however, it remained reasonably steady in 2012 and 2013 with an incidence rate of 4.5 per 100,000 and 4.6 per 100,000 respectively. The incidence of TB in the Australian-born non-Indigenous population has continued to remain low at 0.7 per 100,000 in 2012 and 0.8 per 100,000 in 2013. Australia continued to record only a small number of multi-drug resistant TB cases nationally (2012: n=20; 2013: n=22) of which nearly all were identified in the overseas-born population. This report demonstrates excellent and sustained control of TB in Australia and reflects Australia's commitment to reducing the global burden of TB.

  6. Eighteenth-century genomes show that mixed infections were common at time of peak tuberculosis in Europe

    PubMed Central

    Kay, Gemma L.; Sergeant, Martin J.; Zhou, Zhemin; Chan, Jacqueline Z.-M.; Millard, Andrew; Quick, Joshua; Szikossy, Ildikó; Pap, Ildikó; Spigelman, Mark; Loman, Nicholas J.; Achtman, Mark; Donoghue, Helen D.; Pallen, Mark J.

    2015-01-01

    Tuberculosis (TB) was once a major killer in Europe, but it is unclear how the strains and patterns of infection at ‘peak TB' relate to what we see today. Here we describe 14 genome sequences of M. tuberculosis, representing 12 distinct genotypes, obtained from human remains from eighteenth-century Hungary using metagenomics. All our historic genotypes belong to M. tuberculosis Lineage 4. Bayesian phylogenetic dating, based on samples with well-documented dates, places the most recent common ancestor of this lineage in the late Roman period. We find that most bodies yielded more than one M. tuberculosis genotype and we document an intimate epidemiological link between infections in two long-dead individuals. Our results suggest that metagenomic approaches usefully inform detection and characterization of historical and contemporary infections. PMID:25848958

  7. Unexpected abundance of coenzyme F(420)-dependent enzymes in Mycobacterium tuberculosis and other actinobacteria.

    PubMed

    Selengut, Jeremy D; Haft, Daniel H

    2010-11-01

    Regimens targeting Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), require long courses of treatment and a combination of three or more drugs. An increase in drug-resistant strains of M. tuberculosis demonstrates the need for additional TB-specific drugs. A notable feature of M. tuberculosis is coenzyme F(420), which is distributed sporadically and sparsely among prokaryotes. This distribution allows for comparative genomics-based investigations. Phylogenetic profiling (comparison of differential gene content) based on F(420) biosynthesis nominated many actinobacterial proteins as candidate F(420)-dependent enzymes. Three such families dominated the results: the luciferase-like monooxygenase (LLM), pyridoxamine 5'-phosphate oxidase (PPOX), and deazaflavin-dependent nitroreductase (DDN) families. The DDN family was determined to be limited to F(420)-producing species. The LLM and PPOX families were observed in F(420)-producing species as well as species lacking F(420) but were particularly numerous in many actinobacterial species, including M. tuberculosis. Partitioning the LLM and PPOX families based on an organism's ability to make F(420) allowed the application of the SIMBAL (sites inferred by metabolic background assertion labeling) profiling method to identify F(420)-correlated subsequences. These regions were found to correspond to flavonoid cofactor binding sites. Significantly, these results showed that M. tuberculosis carries at least 28 separate F(420)-dependent enzymes, most of unknown function, and a paucity of flavin mononucleotide (FMN)-dependent proteins in these families. While prevalent in mycobacteria, markers of F(420) biosynthesis appeared to be absent from the normal human gut flora. These findings suggest that M. tuberculosis relies heavily on coenzyme F(420) for its redox reactions. This dependence and the cofactor's rarity may make F(420)-related proteins promising drug targets.

  8. Serodiagnosis of Tuberculosis in Asian Elephants (Elephas maximus) in Southern India: A Latent Class Analysis

    PubMed Central

    Dendukuri, Nandini; Cheeran, Jacob Varghese; Sukumar, Raman

    2012-01-01

    Background Mycobacterium tuberculosis, a causative agent of chronic tuberculosis disease, is widespread among some animal species too. There is paucity of information on the distribution, prevalence and true disease status of tuberculosis in Asian elephants (Elephas maximus). The aim of this study was to estimate the sensitivity and specificity of serological tests to diagnose M. tuberculosis infection in captive elephants in southern India while simultaneously estimating sero-prevalence. Methodology/Principal Findings Health assessment of 600 elephants was carried out and their sera screened with a commercially available rapid serum test. Trunk wash culture of select rapid serum test positive animals yielded no animal positive for M. tuberculosis isolation. Under Indian field conditions where the true disease status is unknown, we used a latent class model to estimate the diagnostic characteristics of an existing (rapid serum test) and new (four in-house ELISA) tests. One hundred and seventy nine sera were randomly selected for screening in the five tests. Diagnostic sensitivities of the four ELISAs were 91.3–97.6% (95% Credible Interval (CI): 74.8–99.9) and diagnostic specificity were 89.6–98.5% (95% CI: 79.4–99.9) based on the model we assumed. We estimate that 53.6% (95% CI: 44.6–62.8) of the samples tested were free from infection with M. tuberculosis and 15.9% (97.5% CI: 9.8 - to 24.0) tested positive on all five tests. Conclusions/Significance Our results provide evidence for high prevalence of asymptomatic M. tuberculosis infection in Asian elephants in a captive Indian setting. Further validation of these tests would be important in formulating area-specific effective surveillance and control measures. PMID:23166708

  9. Unexpected Abundance of Coenzyme F420-Dependent Enzymes in Mycobacterium tuberculosis and Other Actinobacteria▿ †

    PubMed Central

    Selengut, Jeremy D.; Haft, Daniel H.

    2010-01-01

    Regimens targeting Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), require long courses of treatment and a combination of three or more drugs. An increase in drug-resistant strains of M. tuberculosis demonstrates the need for additional TB-specific drugs. A notable feature of M. tuberculosis is coenzyme F420, which is distributed sporadically and sparsely among prokaryotes. This distribution allows for comparative genomics-based investigations. Phylogenetic profiling (comparison of differential gene content) based on F420 biosynthesis nominated many actinobacterial proteins as candidate F420-dependent enzymes. Three such families dominated the results: the luciferase-like monooxygenase (LLM), pyridoxamine 5′-phosphate oxidase (PPOX), and deazaflavin-dependent nitroreductase (DDN) families. The DDN family was determined to be limited to F420-producing species. The LLM and PPOX families were observed in F420-producing species as well as species lacking F420 but were particularly numerous in many actinobacterial species, including M. tuberculosis. Partitioning the LLM and PPOX families based on an organism's ability to make F420 allowed the application of the SIMBAL (sites inferred by metabolic background assertion labeling) profiling method to identify F420-correlated subsequences. These regions were found to correspond to flavonoid cofactor binding sites. Significantly, these results showed that M. tuberculosis carries at least 28 separate F420-dependent enzymes, most of unknown function, and a paucity of flavin mononucleotide (FMN)-dependent proteins in these families. While prevalent in mycobacteria, markers of F420 biosynthesis appeared to be absent from the normal human gut flora. These findings suggest that M. tuberculosis relies heavily on coenzyme F420 for its redox reactions. This dependence and the cofactor's rarity may make F420-related proteins promising drug targets. PMID:20675471

  10. 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

  11. Diabetes mellitus: an important risk factor for reactivation of tuberculosis

    PubMed Central

    Rivera, Carmen; Mangual, Michelle; Martinez, José; Rivera, Kelvin; Fernandez, Ricardo

    2016-01-01

    Summary Diabetes mellitus was identified as a risk factor for developing tuberculosis (TB) infection, and relapse after therapy. The risk of acquiring TB is described as comparable to that of HIV population. The fact that diabetics are 3× times more prone to develop pulmonary TB than nondiabetics cannot be overlooked. With DM recognized as global epidemic, and TB affecting one-third of the world population, physicians must remain vigilant. We present a 45-year-old woman born in Dominican Republic (DR), with 10-year history of T2DM treated with metformin, arrived to our Urgency Room complaining of dry cough for the past 3months. Interview unveiled unintentional 15lbs weight loss, night sweats, occasional unquantified fever, and general malaise but denied bloody sputum. She traveled to DR 2years before, with no known ill exposure. Physical examination showed a thin body habitus, otherwise well appearing woman with stable vital signs, presenting solely right middle lung field ronchi. LDH, ESR, hsCRP and Hg A1C were elevated. Imaging revealed a right middle lobe cavitation. Sputum for AFB disclosed active pulmonary TB. Our case portrays that the consideration of TB as differential diagnosis in diabetics should be exercised with the same strength, as it is undertaken during the evaluation of HIV patients with lung cavitation. Inability to recognize TB will endanger the patient, hospital dwellers and staff, and perpetuate this global public health menace. Learning points Diabetes mellitus should be considered an important risk factor for the reactivation of pulmonary tuberculosis. High clinical suspicious should be taken into consideration as radiological findings for pulmonary tuberculosis in patients with diabetes mellitus may be atypical, involving middle and lower lobes. Inability to recognize pulmonary tuberculosis will endanger the patient, hospital dwellers and staff, and perpetuate this global public health menace. PMID:27482384

  12. [Delays in diagnosing and treating tuberculosis in Croatia].

    PubMed

    Jurčev-Savičević, Anamarija; Popović-Grle, Sanja; Mulić, Rosanda; Smoljanović, Mladen; Miše, Kornelija

    2012-09-01

    The aim of this study was to determine factors causing delay in tuberculosis diagnosis and treatment in Croatia. It included 240 adults with pulmonary tuberculosis, who were interviewed for demographics, socioeconomic, lifestyle, and personal health data. Total delay was defined as a number of days from the onset of symptoms to the initiation of therapy. The median and the 75th percentile of the total delay were 68 and 120 days, respectively: 16.7 % of the patients initiated treatment within the first month, 23.8 % within the second month, 23.3 % within the third month, 12.9 % within the fourth month, and 23.3 % more than four months after the symptoms appeared. Long delay (exceeding median delay) was strongly associated with drug abuse (p=0.021). Extreme delay (75th percentile of delay) was significantly associated with the lowest level of education (p=0.021), below minimal income (p=0.039), minimal to average income (p=0.020), current smoking (p=0.050), and co-morbidity (p=0.048). In the multivariate model, long delay remained associated with drug abuse, while extreme delay was associated with the lowest level of education (p=0.033) and current (p=0.017) and ex-smoking (p=0.045).In a setting with decreasing TB incidence, the reported delay can be reduced by increasing health education, not only about tuberculosis per se, but about health in general and attitudes towards prevention and early care. It is also important to increase tuberculosis knowledge among healthcare workers as well as their diagnostic skills.

  13. 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.

  14. Ambient aerosols remain highly acidic despite dramatic sulfate reductions

    NASA Astrophysics Data System (ADS)

    Nenes, Athanasios; Weber, Rodney; Guo, Hongyu; Russell, Armistead

    2016-04-01

    The pH of fine particles has many vital environmental impacts. By affecting aerosol concentrations, chemical composition and toxicity, particle pH is linked to regional air quality and climate, and adverse effects on human health. Sulfate is often the main acid component that drives pH of fine particles (i.e., PM2.5) and is neutralized to varying degrees by gas phase ammonia. Sulfate levels have decreased by approximately 70% over the Southeastern United States in the last fifteen years, but measured ammonia levels have been fairly steady implying the aerosol may becoming more neutral. Using a chemically comprehensive data set, combined with a thermodynamic analysis, we show that PM2.5 in the Southeastern U.S. is highly acidic (pH between 0 and 2), and that pH has remained relatively unchanged throughout the past decade and a half of decreasing sulfate. Even with further sulfate reductions, pH buffering by gas-particle partitioning of ammonia is expected to continue until sulfate drops to near background levels, indicating that fine particle pH will remain near current levels into the future. These results are non-intuitive and reshape expectations of how sulfur emission reductions impact air quality in the Southeastern U.S. and possibly other regions across the globe.

  15. Tuberculosis 2004: Challenges and Opportunities

    PubMed Central

    Glassroth, Jeffrey

    2005-01-01

    Tuberculosis (TB) continues as a major public health challenge worldwide. HIV-TB coinfection is especially concerning as it accelerates progression of infection to active disease and amplifies spread of TB including drug resistant disease. Application of molecular biology and insights from classic microbiology to TB control have resulted in important innovations in diagnosis and treatment. Radiometric assay and, particularly, PCR, with nucleic acid probing, have reduced the time to diagnosis. Moreover, the sensitivity of these techniques is potentially log orders of magnitude more sensitive. Molecular techniques can be adapted to drug susceptibility testing. The differential activity and post-antibiotic effect of various drugs against TB have led to highly effective briefer regimens and to directly observed therapy. Insights into basic host defense against TB and description of the M. tuberculosis genome have created optimism for developing new treatments and effective vaccines in the years to come. PMID:16555622

  16. Tuberculosis and migration: a review.

    PubMed

    Kronfol, N M; Mansour, Z

    2013-08-01

    In the past decade, the number of new cases of tuberculosis worldwide has barely declined and national tuberculosis control and elimination programmes in many high-income countries worldwide are increasingly challenged to address the problem of disease in foreign-born residents and migrant workers. Routine immigration medical screening, either before or after arrival in the recipient country, is designed to avoid the admission of migrants who pose a public health threat. Screening measures, however, have changed with time largely based on respect for individuals' rights. This paper reviews the measures that are being used by countries to screen immigrants and improve their health well-being, and presents cases studies from two Eastern Mediterranean Region countries.

  17. 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

  18. Detection of IgG1 antibodies against Mycobacterium tuberculosis DosR and Rpf antigens in tuberculosis patients before and after chemotherapy.

    PubMed

    Mattos, Ana Márcia Menezes; Chaves, Alexandre Silva; Franken, Kees L M C; Figueiredo, Bárbara Bruna Muniz; Ferreira, Ana Paula; Ottenhoff, Tom H M; Teixeira, Henrique Couto

    2016-01-01

    Diagnosis of tuberculosis (TB) remains challenging. Serum IgG1 antibodies against Mycobacterium tuberculosis active growth phase antigens (ESAT-6/CFP-10, Rv0717 and Rv3353), DosR regulon-encoded proteins (Rv1733, Rv1737, Rv2628 and Rv2029), and resuscitation-promoting factors (Rv0867 and Rv2389) were evaluated in TB patients using ELISA. Active TB patients showed elevated levels of IgG1 antibodies against ESAT-6/CFP-10, Rv0717, Rv3353, Rv1733, Rv2628, Rv2029 and Rv0867 in comparison to healthy controls (p < 0.001). These levels remained high after the initiation of treatment, while responses to Rv0717 and Rv1733 peaked early during treatment. IgG1 responses to ESAT-6/CFP-10, Rv3353, Rv2628, Rv2029 and Rv0867 declined to control levels after the completion of 6 months chemotherapy. ROC analysis confirmed the good diagnostic performance of Rv0717, Rv1733, Rv3353, Rv2628, Rv2029 and Rv0867antigens. These data suggest that detecting IgG1 antibodies against M. tuberculosis antigens, including DosR and Rpf proteins, may represent an additional tool in the diagnosis of tuberculosis.

  19. Novel approaches in diagnosing tuberculosis

    NASA Astrophysics Data System (ADS)

    Kolk, Arend H. J.; Dang, Ngoc A.; Kuijper, Sjoukje; Gibson, Tim; Anthony, Richard; Claassens, Mareli M.; Kaal, Erwin; Janssen, Hans-Gerd

    2011-06-01

    The WHO declared tuberculosis (TB) a global emergency. An estimated 8-9 million new cases occur each year with 2-3 million deaths. Currently, TB is diagnosed mostly by chest-X ray and staining of the mycobacteria in sputum with a detection limit of 1x104 bacteria /ml. There is an urgent need for better diagnostic tools for TB especially for developing countries. We have validated the electronic nose from TD Technology for the detection of Mycobacterium tuberculosis by headspace analysis of 284 sputum samples from TB patients. We used linear discriminant function analysis resulting in a sensitivity of 75% a specificity of 67% and an accuracy of 69%. Further research is still required to improve the results by choosing more selective sensors and sampling techniques. We used a fast gas chromatography- mass spectrometry method (GC-MS). The automated procedure is based on the injection of sputum samples which are methylated inside the GC injector using thermally assisted hydrolysis and methylation (THM-GC-MS). Hexacosanoic acid in combination with tuberculostearic acid was found to be specific for the presence of M. tuberculosis. The detection limit was similar to microscopy. We found no false positives, all microscopy and culture positive samples were also found positive with the THM-GC-MS method. The detection of ribosomal RNA from the infecting organism offers great potential since rRNA molecules outnumber chromosomal DNA by a factor 1000. It thus may possible to detect the organism without amplification of the nucleic acids (NA). We used a capture and a tagged detector probe for the direct detection of M. tuberculosis in sputum. So far the detection limit is 1x106 bacteria / ml. Currently we are testing a Lab-On-A-Chip Interferometer detection system.

  20. Is micropapular sarcoidosis tuberculosis?1

    PubMed Central

    Ridgway, Hilary A; Ryan, Terence J

    1981-01-01

    Three cases of micropapular sarcoidosis are reported. Two of the cases have a history of tuberculosis and all three cases have atypical patterns of Kveim and Mantoux reactivity. The similarities between this form of sarcoidosis and lichen scrofulosorum or lichenoid tuberculid are observed and the evidence is presented for a tuberculoid aetiology in certain forms of sarcoidosis. ImagesFigure 1.Figure 2.Figure 3.Figure 4. PMID:7205849

  1. Osteoarticular tuberculosis dactylitis: Four cases.

    PubMed

    Sbai, Mohamed Ali; Benzarti, Sofien; Sahli, Hana; Sbei, Feten; Maalla, Riadh

    2015-09-01

    Tuberculosis dactylitis is exceptional. We report 4 cases of osteoarticular tuberculous dactylitis in 3 women and 1 man. The diagnosis was suspected on chronic and insidious clinical presentation, and confirmed by histology. Patients were treated by anti-tubercular drugs with good functional and radiological outcome in all cases. Clinical and therapeutic issues are discussed by the authors in the context of an endemic country. PMID:27649874

  2. A Comparative Study of Induced Sputum and Bronchial Washings in Diagnosing Sputum Smear Negative Pulmonary Tuberculosis

    PubMed Central

    Mandava, Venu; Namballa, Usha Rani; Makala, Sravani

    2016-01-01

    Introduction Tuberculosis is one of the most important public health problem worldwide. Detecting patients with active pulmonary Koch’s disease is an important component of tuberculosis control programs. However, at times in patients even with a compatible clinical picture, sputum smears do not reveal acid-fast bacilli and smear-negative pulmonary tuberculosis remains a common problem. Aim The present study is aimed to compare the results of induced sputum and bronchial washings smear in patients suspected to have sputum smear negative pulmonary tuberculosis. Materials and Methods A prospective study conducted from August 2014 to July 2015, comprising 120 patients fulfilling study criteria. Patients with respiratory symptoms and chest roentgenogram suspicious of pulmonary tuberculosis with no previous history of anti-tuberculosis treatment and two spontaneous sputum smear samples negative for acid fast bacilli were included. Patients with active haemoptysis and sputum positive were excluded from the study. Sputum induction was done by using 5-10 ml of 3% hypertonic saline through ultrasonic nebulizer taking safety precautions. All the patient underwent fibreoptic bronchoscopy after six hours fasting on the same day. About 20 ml of normal saline instilled into the suspected pathology area and washings were taken with gentle suction. The sample processing and fluorescent staining for acid fast bacilli was done in a designated microscopy lab. Results Out of 120 sputum smear negative pulmonary tuberculosis patients, induced sputum smear examination detected acid fast bacilli in 76 patients (63.3%) and acid fast bacilli detected from bronchial washings in 94 patients (78.3%). Smear positivity was higher in cavitary and infiltrative lesions as compared to consolidation and infrahilar pattern disease. Conclusion Even though both induced sputum and bronchial washings procedures were valuable for the diagnosis of sputum smear negative, sputum induction with hypertonic

  3. 78 FR 690 - Guidelines for the Control of Tuberculosis in Elephants

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-04

    ... Tuberculosis in Elephants'' developed by The National Tuberculosis Working Group for Zoo and Wildlife Species... National Tuberculosis Working Group for Zoo and Wildlife Species, approved revisions to the...

  4. Phylogenetic assignment of Mycobacterium tuberculosis Beijing clinical isolates in Japan by maximum a posteriori estimation.

    PubMed

    Seto, Junji; Wada, Takayuki; Iwamoto, Tomotada; Tamaru, Aki; Maeda, Shinji; Yamamoto, Kaori; Hase, Atsushi; Murakami, Koichi; Maeda, Eriko; Oishi, Akira; Migita, Yuji; Yamamoto, Taro; Ahiko, Tadayuki

    2015-10-01

    Intra-species phylogeny of Mycobacterium tuberculosis has been regarded as a clue to estimate its potential risk to develop drug-resistance and various epidemiological tendencies. Genotypic characterization of variable number of tandem repeats (VNTR), a standard tool to ascertain transmission routes, has been improving as a public health effort, but determining phylogenetic information from those efforts alone is difficult. We present a platform based on maximum a posteriori (MAP) estimation to estimate phylogenetic information for M. tuberculosis clinical isolates from individual profiles of VNTR types. This study used 1245 M. tuberculosis clinical isolates obtained throughout Japan for construction of an MAP estimation formula. Two MAP estimation formulae, classification of Beijing family and other lineages, and classification of five Beijing sublineages (ST11/26, STK, ST3, and ST25/19 belonging to the ancient Beijing subfamily and modern Beijing subfamily), were created based on 24 loci VNTR (24Beijing-VNTR) profiles and phylogenetic information of the isolates. Recursive estimation based on the formulae showed high concordance with their authentic phylogeny by multi-locus sequence typing (MLST) of the isolates. The formulae might further support phylogenetic estimation of the Beijing lineage M. tuberculosis from the VNTR genotype with various geographic backgrounds. These results suggest that MAP estimation can function as a reliable probabilistic process to append phylogenetic information to VNTR genotypes of M. tuberculosis independently, which might improve the usage of genotyping data for control, understanding, prevention, and treatment of TB.

  5. Ethical aspects of directly observed treatment for tuberculosis: a cross-cultural comparison

    PubMed Central

    2013-01-01

    Background Tuberculosis is a major global public health challenge, and a majority of countries have adopted a version of the global strategy to fight Tuberculosis, Directly Observed Treatment, Short Course (DOTS). Drawing on results from research in Ethiopia and Norway, the aim of this paper is to highlight and discuss ethical aspects of the practice of Directly Observed Treatment (DOT) in a cross-cultural perspective. Discussion Research from Ethiopia and Norway demonstrates that the rigid enforcement of directly observed treatment conflicts with patient autonomy, dignity and integrity. The treatment practices, especially when imposed in its strictest forms, expose those who have Tuberculosis to extra burdens and costs. Socially disadvantaged groups, such as the homeless, those employed as day labourers and those lacking rights as employees, face the highest burdens. Summary From an ethical standpoint, we argue that a rigid practice of directly observed treatment is difficult to justify, and that responsiveness to social determinants of Tuberculosis should become an integral part of the management of Tuberculosis. PMID:23819555

  6. Assessment of potential causes of falsely positive Mycobacterium tuberculosis breath test.

    PubMed

    Scott-Thomas, Amy; Syhre, Mona; Epton, Michael; Murdoch, David R; Chambers, Stephen T

    2013-05-01

    A suite of volatiles have previously been identified as specific markers of Mycobacterium tuberculosis metabolism in vitro. These markers - methyl phenylacetate, methyl p-anisate, methyl nicotinate, o-phenylanisole with the addition of methyl salicylate, may also be derived from other sources and confound development of a breath test for tuberculosis. To identify potential sources of these potential biomarkers food products, cosmetics, TB medication, environmental air and cigarette smoke were analysed for these markers using solid phase microextraction coupled with Gas Chromatography/Mass Spectrometry. Breath from healthy subjects, including smokers was also tested. Methyl salicylate was commonly detected, making this unsuitable as a specific marker for M. tuberculosis. Methyl nicotinate was detected repeatedly in cigarettes. Methyl phenylacetate was detected in 1.7% of healthy subjects and o-phenylanisole in just 1% of healthy breath indicating these may be more suitable for inclusion in the tuberculosis breath test due to their low "background" level. These results justify further clinical studies to further explore these markers as specific indicators of M. tuberculosis infection.

  7. Tuberculosis and pulmonary candidiasis co-infection present in a previously healthy patient

    PubMed Central

    Jiménez Borré, Gustavo; Gómez Camargo, Doris; Chalavé Jiménez, Neylor; Bellido Rodríguez, Javier; Cuadrado Cano, Bernarda; Navarro Gómez, Shirley

    2016-01-01

    Background: The coexistance among fungal pathogens and tuberculosis pulmonary is a clinical condition that generally occurs in immunosuppressive patients, however, immunocompetent patients may have this condition less frequently. Objective: We report the case of an immunocompetent patient diagnosed with coinfection Mycobacterium tuberculosis and Candida albicans. Case Description: A female patient, who is a 22-years old, with fever and a new onset of hemoptysis. Clinical findings and diagnosis: Diminished vesicular breath sounds in the apical region and basal crackling rales in the left lung base were found in the physical examination. Microbiological tests include: chest radiography and CAT scan pictograms in high resolution, Ziehl-Neelsen stain, growth medium for fungus and mycobacteria through Sabouraudís agar method with D-glucose. Medical examinations showed Candida albicans fungus and Mycobacterium tuberculosis present in the patient. Treatment and Outcome: Patient was treated with anti-tuberculosis and anti-fungal medications, which produced good responses. Clinical relevance: Pulmonary tuberculosis and fungal co-infection are not common in immunocompetent patients. However, we can suspect that there is a presence of these diseases by detecting new onset of hemoptysis in patients. PMID:27546933

  8. Leveraging Advances in Tuberculosis Diagnosis and Treatment to Address Nontuberculous Mycobacterial Disease.

    PubMed

    Raju, Ravikiran M; Raju, Sagar M; Zhao, Yanlin; Rubin, Eric J

    2016-03-01

    The nontuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium tuberculosis or Mycobacterium leprae, are a diverse group of pathogens that collectively cause a substantive but often unappreciated worldwide burden of illness. Although NTMs may cause illness similar to M. tuberculosis, these pathogens generally do not respond to classic tuberculosis (TB) drug regimens, resulting in misdiagnosis and poor treatment, particularly in resource-poor settings. Although a few high-quality epidemiologic surveys have been made on the topic, existing evidence suggests that NTM-associated disease is much more common than previously thought: more common than TB in the industrialized world and likely increasing in prevalence globally. Despite this evidence, these organisms remain markedly understudied, and few international grants support basic science and clinical research. Here we suggest that the considerable efforts in developing new treatments and diagnostics for TB can be harnessed in the fight against NTM-associated illnesses.

  9. Transgenic Carrot Expressing Fusion Protein Comprising M. tuberculosis Antigens Induces Immune Response in Mice

    PubMed Central

    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 γ-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

  10. Tuberculosis in an Indochinese refugee camp: epidemiology, management and therapeutic results.

    PubMed

    Rieder, H L

    1985-09-01

    In a 3-year period tuberculosis was diagnosed in 629 patients in Thailand's largest camp for Kampuchean refugees: 62% had pulmonary disease and 38% extrapulmonary forms. Tuberculosis of lymph nodes was the most important extrapulmonary manifestation (50%). The mean annual notification rates were 0.5% and 0.24% for all forms and smear-positive pulmonary tuberculosis respectively. There was a steep rise in the annual notification rate with increasing age. A 6-month course of fully supervised chemotherapy efficiently counteracted defaulting, early absconding and initial drug resistance. Seventy-three per cent of all patients remained on chemotherapy for the planned period; only 2% of the smear-positive patients failed bacteriologically on chemotherapy. Of the patients with the most common forms of extrapulmonary disease, 90% showed a favourable response to chemotherapy.

  11. The risk of tuberculosis transmission to free-ranging great apes.

    PubMed

    Wolf, Tiffany M; Sreevatsan, Srinand; Travis, Dominic; Mugisha, Lawrence; Singer, Randall S

    2014-01-01

    Pathogen exchange between humans and primates has been facilitated by anthropogenic disturbances, such as changing land use patterns, habitat destruction, and poaching, which decrease population sizes and increase levels of primate-human interaction. As a result, human and domestic animal diseases have become a recognized threat to endangered primate populations. Tuberculosis is a major global human and animal health concern, especially in equatorial Africa where many of the remaining free-living great ape populations exist in proximity with exposed and/or infected human populations and their domestic animals. Increased anthropogenic pressure creates an opportunity for the anthropozoonotic spread of this disease. This review examines current evidence of the risk of tuberculosis transmission to great apes, the benefits and limitations of current detection methods, the impact of current great ape conservation and management strategies on this risk, and the need for an ecosystem health-based approach to mitigating the risks of tuberculosis transmission to great apes.

  12. Anti-tubercular therapy for intraocular tuberculosis: A systematic review and meta-analysis.

    PubMed

    Kee, Ae Ra; Gonzalez-Lopez, Julio J; Al-Hity, Aws; Gupta, Bhaskar; Lee, Cecilia S; Gunasekeran, Dinesh Visva; Jayabalan, Nirmal; Grant, Robert; Kon, Onn Min; Gupta, Vishali; Westcott, Mark; Pavesio, Carlos; Agrawal, Rupesh

    2016-01-01

    Intraocular tuberculosis remains a diagnostic and management conundrum for both ophthalmologists and pulmonologists. We analyze the efficacy and safety of anti-tubercular therapy (ATT) in patients with intraocular tuberculosis and factors associated with favorable outcome. Twenty-eight studies are included in this review, with a total of 1,917 patients. Nonrecurrence of inflammation was observed in pooled estimate of 84% of ATT-treated patients (95% CI 79-89). There was minimal difference in the outcome between patients treated with ATT alone (85% successful outcome; 95% CI 25-100) and those with concomitant systemic corticosteroid (82%; 95% CI 73-90). The use of ATT may be of benefit to patients with suspected intraocular tuberculosis; however, this conclusion is limited by the lack of control group analysis and standardized recruitment and treatment protocols. We propose further prospective studies to better establish the efficacy of ATT and ascertain the factors associated with favorable treatment outcomes. PMID:26970263

  13. 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

  14. Advanced development of the digital tuberculosis tester for MDR-TB screening

    NASA Astrophysics Data System (ADS)

    Smith, Jason E.; Simkulet, Michelle D.; Gutin, Alexander; Gutin, Alexy; Bardarov, Savco; Jacobs, William R., Jr.; Castracane, James; Tang, Oliver; Riska, Paul

    2001-05-01

    Tuberculosis (TB) remains the leading cause of death in the world from a single infectious disease, and the threat is becoming more critical with the spread of multi-drug resistant Tuberculosis (MDR-TB). TB detection, and susceptibility testing for drug resistant strain identification, is advancing with the development of Luciferase Reporter Mycobacteriophages (LRM). LRM will emit visible light at very low intensity when in the presence of live mycobacteria cells such as Tuberculosis strains. InterScience, Inc., together with its collaboration, is developing a highly sensitive, real-time digital detection system for the analysis of luminescent assays. Recent advances in system sensitivity, design, and implementation, as well as preliminary results of the development of individual test cartridges, will be presented. The ultimate goal of this work is to provide a versatile luminescence detection tool for widespread research and clinical applications.

  15. Zoonotic tuberculosis due to Mycobacterium bovis in developing countries.

    PubMed Central

    Cosivi, O.; Grange, J. M.; Daborn, C. J.; Raviglione, M. C.; Fujikura, T.; Cousins, D.; Robinson, R. A.; Huchzermeyer, H. F.; de Kantor, I.; Meslin, F. X.

    1998-01-01

    The World Health Organization (WHO) estimates that human tuberculosis (TB) incidence and deaths for 1990 to 1999 will be 88 million and 30 million, respectively, with most cases in developing countries. Zoonotic TB (caused by Mycobacterium bovis) is present in animals in most developing countries where surveillance and control activities are often inadequate or unavailable; therefore, many epidemiologic and public health aspects of infection remain largely unknown. We review available information on zoonotic TB in developing countries, analyze risk factors that may play a role in the disease, review recent WHO activities, and recommend actions to assess the magnitude of the problem and control the disease in humans and animals. PMID:9452399

  16. Family history of immigration from a tuberculosis endemic country and low family income are associated with a higher BCG vaccination coverage in Ile-de-France region, France.

    PubMed

    Guthmann, Jean-Paul; Chauvin, Pierre; Le Strat, Yann; Soler, Marion; Fonteneau, Laure; Lévy-Bruhl, Daniel

    2013-11-19

    After withdrawal of multipuncture BCG device from the French market in January 2006, vaccination coverage (VC) with the intradermal device has dropped and since remained sub-optimal in Ile-de-France, the only region of mainland France where BCG is recommended to all children. We conducted a cross-sectional study to identify socio-economic factors associated with BCG VC in children of Paris metropolitan area born after January 2006. Two-stage random sampling was used to include 425 children up to 5 years old from Paris and its suburbs. Information was collected through face-to-face interviews and vaccination status confirmed by a vaccination document. Poisson regression analyzed the association between VC and potential determinants. VC of children from families with the lowest incomes (first quartile of family income/consumption unit (CU) (<883 €) was close to 100% regardless of family origin. In families with higher incomes (≥ 883 €/CU), VC was significantly higher among children born to families from a tuberculosis highly endemic country (98.2%) compared with other children (76.2%) (p=0.004). Children of low socio-economic background as well as those with a family history of immigration, regardless of family income, are correctly identified as being at high risk of tuberculosis and properly vaccinated with BCG in this area.

  17. Genotypic Detection of rpoB and katG Gene Mutations Associated with Rifampicin and Isoniazid Resistance in Mycobacterium Tuberculosis Isolates: A Local Scenario (Kelantan)

    PubMed Central

    Ismail, Nurul-Ain; Ismail, Mohd Fazli; Noor, Siti Suraiya MD; Camalxaman, Siti Nazrina

    2016-01-01

    Background Drug resistant tuberculosis (DR-TB) remains a public health issue that is of major concern on a global scale. The characterisation of clinical isolates may provide key information regarding the underlying mechanisms of drug resistance, and helps to augment therapeutic options. This study aims to evaluate the frequency of gene mutations associated with Rifampicin (RIF) and Isoniazid (INH) resistance among nine clinical isolates. Methods A total of nine drug resistant Mycobacterium tuberculosis clinical isolates were screened for genetic mutations in rpoB and katusing polymerase chain reaction (PCR) amplification and DNA sequencing. Genotypic analysis was performed to detect the mutations in the sequence of the target genes. Results Our findings reveal that 80% of the isolates possess mutations at codon 119 (His119Tyr) and 135 (Arg135Trp and Ser135Leu) within the rpoB gene; and 70% possess mutations in the katG gene at codon 238 with amino acid change (Leu238Arg). Conclusion Findings from this study provide an overview of the current situation of RIF and INH resistance in a hospital Universiti Sains Malaysia (HUSM) located in Kelantan, Malaysia, which could facilitate molecular-based detection methods of drug-resistant strains. Further information regarding the molecular mechanisms involved in resistance in RR-/MDR-TB should be addressed in the near future. PMID:27540322

  18. The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection

    PubMed Central

    Lin, Philana Ling; Dietrich, Jes; Tan, Esterlina; Abalos, Rodolfo M.; Burgos, Jasmin; Bigbee, Carolyn; Bigbee, Matthew; Milk, Leslie; Gideon, Hannah P.; Rodgers, Mark; Cochran, Catherine; Guinn, Kristi M.; Sherman, David R.; Klein, Edwin; Janssen, Christopher; Flynn, JoAnne L.; Andersen, Peter

    2011-01-01

    It is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis. Infection typically remains latent, but it can reactivate to cause clinical disease. The only vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is largely ineffective, and ways to enhance its efficacy are being developed. Of note, the candidate booster vaccines currently under clinical development have been designed to improve BCG efficacy but not prevent reactivation of latent infection. Here, we demonstrate that administering a multistage vaccine that we term H56 in the adjuvant IC31 as a boost to vaccination with BCG delays and reduces clinical disease in cynomolgus macaques challenged with M. tuberculosis and prevents reactivation of latent infection. H56 contains Ag85B and ESAT-6, which are two of the M. tuberculosis antigens secreted in the acute phase of infection, and the nutrient stress–induced antigen Rv2660c. Boosting with H56/IC31 resulted in efficient containment of M. tuberculosis infection and reduced rates of clinical disease, as measured by clinical parameters, inflammatory markers, and improved survival of the animals compared with BCG alone. Boosted animals showed reduced pulmonary pathology and extrapulmonary dissemination, and protection correlated with a strong recall response against ESAT-6 and Rv2660c. Importantly, BCG/H56-vaccinated monkeys did not reactivate latent infection after treatment with anti-TNF antibody. Our results indicate that H56/IC31 boosting is able to control late-stage infection with M. tuberculosis and contain latent tuberculosis, providing a rationale for the clinical development of H56. PMID:22133873

  19. Tackling tuberculosis: Insights from an international TB Summit in London

    PubMed Central

    Maitra, Arundhati; Danquah, Cynthia A; Scotti, Francesca; Howard, Tracey K; Kamil, Tengku K; Bhakta, Sanjib

    2015-01-01

    Tuberculosis (TB) poses a grave predicament to the world as it is not merely a scientific challenge but a socio-economic burden as well. A prime cause of mortality in human due to an infectious disease; the malady and its cause, Mycobacterium tuberculosis have remained an enigma with many questions that remain unanswered. The ability of the pathogen to survive and switch between varied physiological states necessitates a protracted therapeutic regimen that exerts an excessive strain on low-resource countries. To complicate things further, there has been a significant rise of antimicrobial resistance. Existing control measures, including treatment regimens have remained fairly uniform globally for at least half a century and require reinvention. Overcoming the societal and scientific challenges requires an increase in dialog to identify key regions that need attention and effective partners with whom successful collaborations can be fostered. In this report, we explore the discussions held at the International TB Summit 2015 hosted by EuroSciCon, which served as an excellent platform for researchers to share their recent findings. Ground-breaking results require outreach to affect policy design, governance and control of the disease. Hence, we feel it is important that meetings such as these reach a wider, global audience. PMID:26151309

  20. High mortality in tuberculosis patients despite HIV interventions in Swaziland

    PubMed Central

    van Griensven, J.; Hinderaker, S. G.; Kizito, W.; Sikhondze, W.; Manzi, M.; Dlamini, T.; Harries, A. D.

    2016-01-01

    Setting: All health facilities providing tuberculosis (TB) care in Swaziland. Objective: To describe the impact of human immunodeficiency virus (HIV) interventions on the trend of TB treatment outcomes during 2010–2013 in Swaziland; and to describe the evolution in TB case notification, the uptake of HIV testing, antiretroviral therapy (ART) and cotrimoxazole preventive therapy (CPT), and the proportion of TB-HIV co-infected patients with adverse treatment outcomes, including mortality, loss to follow-up and treatment failure. Design: A retrospective descriptive study using aggregated national TB programme data. Results: Between 2010 and 2013, TB case notifications in Swaziland decreased by 40%, HIV testing increased from 86% to 96%, CPT uptake increased from 93% to 99% and ART uptake among TB patients increased from 35% to 75%. The TB-HIV co-infection rate remained around 70% and the proportion of TB-HIV cases with adverse outcomes decreased from 36% to 30%. Mortality remained high, at 14–16%, over the study period, and anti-tuberculosis treatment failure rates were stable over time (<5%). Conclusion: Despite high CPT and ART uptake in TB-HIV patients, mortality remained high. Further studies are required to better define high-risk patient groups, understand the reasons for death and design appropriate interventions. PMID:27358803