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Sample records for background tuberculosis remains

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

    PubMed Central

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

    2008-01-01

    Background In the present pilot study we applied recently published protocols for detecting Mycobacterium tuberculosis in human remains. We screened long bones from an 18th century cemetery and skulls from the anatomical "Weisbach collection" (19th century). In addition, besides the study of abundance of tuberculosis in inmates of the poorhouse itself, we were interested to test whether in this particular instance tuberculosis can be identified from cortical bones, which are rarely affected by tuberculosis, but mostly better preserved than the vertebral bodies or epiphyses. Method The DNA extractions from the bone samples were obtained following established ancient DNA protocols. Subsequently extracts were subjected to a series of PCR amplifications using primer pairs published previously [1,2]. PCR products of the expected size were subsequently sequenced. Results Only primers targeting the repetitive IS6110 insertion sequence yielded PCR products of appropriate size. In one sample only (skull sample WB354 of the "Weisbach collection") sequence analysis revealed an authentic M. tuberculosis sequence that matched to a reference sequence from GenBank. Conclusion With a variety of established PCR approaches we failed to detect M. tuberculosis DNA in historic human femurs from an 18th century cemetery relating to a poor house in Kaiserebersdorf, Austria. Our data may indicate that in this particular case, thoracic or lumbar vertebrae, i.e. bones that are severely affected by the disease, would be more suitable for molecular diagnostics than long bones. However, the unpredictable state of DNA preservation in bones from museum collections does not allow any general recommendation of any type of bone. PMID:18799009

  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. PMID:24343882

  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. PMID:25802030

  5. 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

  6. 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 espaol Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...

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

    PubMed

    Psa, Annamria; Maixner, Frank; Mende, Balzs Gusztv; Khler, Kitti; Oszts, Anett; Sola, Christophe; Dutour, Olivier; Masson, Muriel; Molnr, Erika; Plfi, Gyrgy; Zink, Albert

    2015-06-01

    Alsnyk-Btaszk 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

  8. 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

  9. 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 ...

  10. 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 ...

  11. Hepatic tuberculosis: a rare cause of fluorodeoxyglucose hepatic superscan with background suppression on positron emission tomography

    PubMed Central

    Wong, Simon Sin Man; Yuen, Hok Yuen; Ahuja, Anil T

    2014-01-01

    Fluorodeoxyglucose (FDG) hepatic superscan refers to the diffuse intense uptake of 18F-FDG in the liver on positron emission tomography (PET), with reduced physiological activity in the brain and heart. The common causes include lymphoma and metastasis. In this case report, we describe the imaging features of tuberculosis as a rare cause of FDG hepatic superscan. PET imaging may be the only clue to a diagnosis of hepatic tuberculosis, as other imaging modalities may demonstrate only nonspecific hepatomegaly. It is important to consider this entity in the differential diagnosis of patients presenting with FDG hepatic superscan and proceed with liver biopsy for a definitive diagnosis. PMID:24347039

  12. Primary gastric tuberculosis report of 5 cases

    PubMed Central

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

    2003-01-01

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

  13. Tuberculosis.

    PubMed

    2016-02-24

    Essential facts Tuberculosis (TB) is an infection that mainly affects the lungs, however it can affect any part of the body, including the bones, nervous system and skin. More than 6,500 cases of TB were reported in England in 2014; of those more than 2,500 were in London. Rates in the UK are high compared with those in other western European countries. Many cases of TB can be prevented through public health measures and most people can be cured if treated properly. PMID:26907122

  14. The epidemiological advantage of preferential targeting of tuberculosis control to the poor

    PubMed Central

    Andrews, Jason R.; Basu, Sanjay; Dowdy, David W.; Murray, Megan B.

    2015-01-01

    Tuberculosis remains disproportionately concentrated among the poor, yet known determinants of tuberculosis reactivation may fail to explain observed disparities in disease rates according to wealth. Reviewing data on tuberculosis disparities in India and the wealth distribution of known tuberculosis risk factors, we describe how social mixing patterns could be contributing to tuberculosis disparities. Wealth-assortative mixing, wherein individuals are more likely to contact others from similar socioeconomic backgrounds, amplifies smaller differences in risk of tuberculosis, resulting in large population-level disparities. As disparities and assortativeness increase, tuberculosis becomes more difficult to control, an effect that is obscured by looking at population averages of epidemiological parameters, such as case detection rates. We illustrate how tuberculosis control efforts may benefit from preferential targeting toward the poor. In India, an equivalent-scale intervention could have a substantially greater impact if targeted to those living below the poverty line, compared with a population-wide strategy. In addition to potential efficiencies in targeting higher-risk populations, tuberculosis control efforts would reduce more secondary tuberculosis cases, per primary case diagnosed, if they were preferentially targeted to the poor. We highlight the need to collect programmatic data on tuberculosis disparities and explicitly incorporate equity considerations in tuberculosis control plans. PMID:25859990

  15. Update on Veterinary Tuberculosis Vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  16. Pulmonary tuberculosis

    MedlinePLUS

    Pulmonary tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis) . TB is contagious. This means ... chap 332. Fitzgerald DW, Sterling TR, Haas DW. Mycobacterium tuberculosis. In: Bennett JE, Dolan R, Blaser MJ, ...

  17. [Tuberculosis and HIV infection].

    PubMed

    Rieder, H L

    1994-02-01

    While HIV has changed the tuberculosis situation in an unprecedented way on a global scale, its impact in western Europe on tuberculosis has remained relatively small, largely due to achievements in control over the past decades. To what extent HIV may thwart these achievements in some population segments (e.g. injection drug users) remains to be seen. Nevertheless, irrespective of the extent of the HIV epidemic, basic principles in tuberculosis control must be upheld, now more than ever: tuberculosis must remain part in the differential diagnosis, and once diagnosed, it must be assured that treatment is not only initiated but brought to successful conclusion. From an individual point of view, preventive therapy with isoniazid for dually infected persons is desirable as it effectively reduces the risk of subsequent tuberculosis even in the presence of HIV infection. PMID:8183866

  18. [Primary infection and pulmonary tuberculosis].

    PubMed

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

    2015-01-01

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

  19. Spontaneous pneumothorax: remaining controversies.

    PubMed

    Subotic, D; Van Schil, P

    2011-08-01

    Despite many guidelines issued by national and professional societies, a detailed literature survey between the late 1940s and 2010 clearly demonstrates that several aspects of pneumothorax pathogenesis and treatment still remain controversial. Related to pathogenesis of primary pneumothorax, the current manuscript highlights why further studies are needed to explain 1) mechanism of the oxygenation impairment in presence of a large pneumothorax; 2) oxygenation differences between age and sex-matched patients with a pneumothorax of the same size; and 3) sequence of events in tension pneumothorax. Concerning the overall therapeutic approach, video-assisted technology provides a minimally invasive operative treatment. For this reason methods of recurrence prevention are now shared between interventional pulmonologists and thoracic surgeons. Although a significantly higher recurrence rates was reported in patients with primary spontaneous pneumothorax after simple pleural drainage versus thoracoscopic talc poudrage, (34% and 5% respectively), such a policy is still not widely adopted. Certain concerns that relate to the use of talc in relapse prevention are also discussed, showing that they are mostly dependent on the type of the talc used. Concerning secondary pneumothorax, specificities of different forms related to diagnostics and therapeutic approach are also pointed out. Lung tuberculosis as the underlying cause is particularly addressed, due to the challenge of the timely recognition of specific lesions and prompt initiation of the antituberculous medical treatment . Similarly, lung cancer is mentioned as a possible underlying cause in patients with delayed lung expansion. PMID:21873970

  20. Spinal tuberculosis: A review

    PubMed Central

    Garg, Ravindra Kumar; Somvanshi, Dilip Singh

    2011-01-01

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

  1. Genomic insights into tuberculosis.

    PubMed

    Galagan, James E

    2014-05-01

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

  2. Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment

    PubMed Central

    Cliff, Jacqueline M.; Cho, Jang-Eun; Lee, Ji-Sook; Ronacher, Katharina; King, Elizabeth C.; van Helden, Paul; Walzl, Gerhard; Dockrell, Hazel M.

    2016-01-01

    Background. Currently, there are no tools to accurately predict tuberculosis relapse. This study aimed to determine whether patients who experience tuberculosis relapse have different immune responses to mycobacteria in vitro than patients who remain cured for 2 years. Methods. Patients with an initial episode of pulmonary tuberculosis were recruited in South Africa. Diluted blood, collected at diagnosis and after 2 and 4 weeks of treatment, was cultured with live Mycobacterium tuberculosis for 6 days, and cellular RNA was frozen. Gene expression in samples from 10 patients who subsequently experienced relapse, confirmed by strain genotyping, was compared to that in samples from patients who remained cured, using microarrays. Results. At diagnosis, expression of 668 genes was significantly different in samples from patients who experienced relapse, compared with expression in patients who remained successfully cured; these differences persisted for at least 4 weeks. Gene ontology and biological pathways analyses revealed significant upregulation of genes involved in cytotoxic cell-mediated killing. Results were confirmed by real-time quantitative reverse-transcription polymerase chain reaction analysis in a wider patient cohort. Conclusions. These data show that patients who will subsequently experience relapse exhibit altered immune responses, including excessively robust cytolytic responses to M. tuberculosis in vitro, at the time of diagnosis, compared with patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited in drug development. PMID:26351358

  3. The Detection of Airborne Transmission of Tuberculosis from HIV-Infected Patients, Using an In Vivo Air Sampling Model

    PubMed Central

    Escombe, A. Roderick; Oeser, Clarissa; Gilman, Robert H.; Navincopa, Marcos; Ticona, Eduardo; Martínez, Carlos; Caviedes, Luz; Sheen, Patricia; Gonzalez, Armando; Noakes, Catherine; Moore, David A. J.; Friedland, Jon S.; Evans, Carlton A.

    2010-01-01

    Background Nosocomial transmission of tuberculosis remains an important public health problem. We created an in vivo air sampling model to study airborne transmission of tuberculosis from patients coinfected with human immunodeficiency virus (HIV) and to evaluate environmental control measures. Methods An animal facility was built above a mechanically ventilated HIV-tuberculosis ward in Lima, Peru. A mean of 92 guinea pigs were continuously exposed to all ward exhaust air for 16 months. Animals had tuberculin skin tests performed at monthly intervals, and those with positive reactions were removed for autopsy and culture for tuberculosis. Results Over 505 consecutive days, there were 118 ward admissions by 97 patients with pulmonary tuberculosis, with a median duration of hospitalization of 11 days. All patients were infected with HIV and constituted a heterogeneous group with both new and existing diagnoses of tuberculosis. There was a wide variation in monthly rates of guinea pigs developing positive tuberculin test results (0%–53%). Of 292 animals exposed to ward air, 159 developed positive tuberculin skin test results, of which 129 had laboratory confirmation of tuberculosis. The HIV-positive patients with pulmonary tuberculosis produced a mean of 8.2 infectious quanta per hour, compared with 1.25 for HIV-negative patients with tuberculosis in similar studies from the 1950s. The mean monthly patient infectiousness varied greatly, from production of 0–44 infectious quanta per hour, as did the theoretical risk for a health care worker to acquire tuberculosis by breathing ward air. Conclusions HIV-positive patients with tuberculosis varied greatly in their infectiousness, and some were highly infectious. Use of environmental control strategies for nosocomial tuberculosis is therefore a priority, especially in areas with a high prevalence of both tuberculosis and HIV infection. PMID:17443474

  4. Genomics and the evolution, pathogenesis, and diagnosis of tuberculosis

    PubMed Central

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

    2007-01-01

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

  5. 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

  6. Tuberculosis mortality in Finland

    PubMed Central

    1955-01-01

    The present report, analysing the official statistics on tuberculosis mortality in Finland during the past 75 years, was undertaken to provide a background for studying the course of tuberculosis after the nation-wide BCG vaccination campaign of 1948-49. Tuberculosis mortality in Finland has been high compared with other European countries: before the end of the first World War the death-rate from respiratory tuberculosis fluctuated between 250 and 300 per 100,000; by 1953 it had dropped to 56 for males and 27 for females. Age-specific death-rates for respiratory tuberculosis usually showed peaks for infancy, young adulthood, and old age. For many years the highest mortality-rates for females were in young adulthood, and a high proportion of all deaths from respiratory tuberculosis, in both males and females, was in the age-group 15-40 years. Tuberculosis proportionate mortality was also high in this age-group: 30%-50% for males and 40%-60% for females. In recent years the pattern has changed, the weight in the age distribution of the number of deaths has shifted towards higher ages. The death-rates for non-respiratory tuberculosis, with tuberculous meningitis the most important, are several times higher in infancy than the rates for respiratory tuberculosis. Non-respiratory tuberculosis is of little importance in adults. The cohort curves for respiratory tuberculosis differ in two important ways from the classic curves for Massachusetts. The peaks of the Finnish curves in adult ages shift to lower ages with each succeeding cohort, and the curves often cross each other. Tuberculosis mortality in Finland, as in almost every other country, has decreased very rapidly since the second World War, particularly in the younger age-groups. However, as a similar pattern is found in countries where BCG has not been used, there seems to be little compelling evidence to support a belief that the nation-wide BCG programme caused much, if any, of the recent precipitous drop in mortality-rates. Other factors having a strong influence on tuberculosis mortality have undoubtedly been operating in Finland as almost everywhere. ImagesFIG. 13FIG. 13 (Contd.) PMID:14351976

  7. Tuberculosis (TB)

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    ... 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 ...

  8. Tuberculosis Prevention

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    ... Skip Content Marketing Share this: Main Content Area Tuberculosis (TB) Prevention TB is an airborne disease and ... patients. Many people who are infected with Mycobacterium tuberculosis ( Mtb ) do not get sick or spread the ...

  9. Tuberculosis (TB)

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    ... 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. PMID:25131367

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

    PubMed Central

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

    2006-01-01

    Background Molecular typing of Mycobacterium tuberculosis strains has become a valuable tool in the epidemiology of tuberculosis (TB) by allowing detection of outbreaks, tracking of epidemics, identification of genotypes and transmission events among patients who would have remained undetected by conventional contact investigation. This is the first genetic biodiversity study of M. tuberculosis in Venezuela. Thus, we investigated the genetic patterns of strains isolated in the first survey of anti-tuberculosis drug-resistance realised as part of the Global Project of Anti-tuberculosis Drug Resistance Surveillance (WHO/IUATLD). Results Clinical isolates (670/873) were genotyped by spoligotyping. The results were compared with the international spoligotyping database (SpolDB4). Multidrug resistant (MDR) strains (14/18) were also analysed by IS6110-RFLP assays, and resistance to isoniazid and rifampicin was characterised. Spoligotyping grouped 82% (548/670) of the strains into 59 clusters. Twenty new spoligotypes (SITs) specific to Venezuela were identified. Eight new inter-regional clusters were created. The Beijing genotype was not found. The genetic network shows that the Latin American and Mediterranean family constitutes the backbone of the genetic TB population-structure in Venezuela, responsible of >60% of total TB cases studied. MDR was 0.5% in never treated patients and 13.5% in previously treated patients. Mutations in rpoB gene and katG genes were detected in 64% and 43% of the MDR strains, respectively. Two clusters were found to be identical by the four different analysis methods, presumably representing cases of recent transmission of MDR tuberculosis. Conclusion This study gives a first overview of the M. tuberculosis strains circulating in Venezuela during the first survey of anti-tuberculosis drug-resistance. It may aid in the creation of a national database that will be a valuable support for further studies. PMID:17032442

  13. Antigen smuggling in tuberculosis.

    PubMed

    Hudrisier, Denis; Neyrolles, Olivier

    2014-06-11

    The importance of CD4 T lymphocytes in immunity to M. tuberculosis is well established; however, how dendritic cells activate T cells in vivo remains obscure. In this issue of Cell Host & Microbe, Srivastava and Ernst (2014) report a mechanism of antigen transfer for efficient activation of antimycobacterial T cells. PMID:24922567

  14. Tuberculosis of the pancreas.

    PubMed Central

    Varshney, S.; Johnson, C. D.

    1995-01-01

    Tuberculosis of the pancreas is extremely rare. We report a case which demonstrates the diagnostic confusion which may arise in this condition. A 55-year-old alcoholic caucasian man presented with loss of weight and obstructive jaundice. Ultrasonography, endoscopic retrograde cholangiopancreatography and computed tomography showed a mass lesion in the head of the pancreas, diagnosed as probably malignant. He underwent a Whipple's pancreatoduodencetomy and made a good recovery. Histological examination showed typical features of tuberculosis. In the absence of other foci of active disease chemotherapy was not given. He remains well 12 months after operation. Images Figure 1 Figure 2 PMID:7479475

  15. Health system delay in pulmonary tuberculosis treatment in a country with an intermediate burden of tuberculosis: a cross-sectional study

    PubMed Central

    2013-01-01

    Background Delayed diagnosis and treatment of tuberculosis increase both the severity of the disease and the duration of infectivity. A number of studies have addressed the issue of health system delays in the treatment of tuberculosis, but mostly in countries with a high or low incidence of the disease. Our understanding of delay is quite limited in settings with an intermediate burden of tuberculosis. We explore the duration and factors associated with delays in the Croatian health system which has free health care and a sufficient network of health services providing tuberculosis diagnosis and care. Methods A total of 241 consecutive adults with culture-confirmed pulmonary tuberculosis were interviewed in seven randomly selected Croatian counties and their medical records were evaluated. A health system delay was defined as the number of days from the first consultation with a physician to the initiation of anti-tuberculosis treatment. A long delay was defined as a period exceeding the median delay, while an extreme delay was considered to be above the 75th percentile delay. Results The median health system delay was 15days while the 75th percentile was 42days (the 5th and 95th percentile being 1 and 105days respectively). Almost 30% of tuberculosis patients remained undiagnosed for more than 30days after the initial health care visit. Female patients (p?=?0.005), patients with a negative sputum smear (p?=?0.002) and patients having symptoms other than the usual ones (0.027) were found to be in significant correlation with a long delay. In a multivariate model, a long delay remained associated with the same variables (p?=?0.008, p?=?0.003, and p?=?0.037, respectively). A significant association was demonstrated between both the female gender (p?=?0.042) and a negative sputum smear (p?remained significant in the multivariate analysis. Conclusions Our findings suggest that some groups of tuberculosis patients experienced a health system delay. In such a setting where tuberculosis incidence is decreasing, which leads to a lack of physician experience and expertise, training in tuberculosis is required. Such measure may be useful in reducing the number of missed opportunities for tuberculosis diagnosis. PMID:23517315

  16. An audit of diagnosis and treatment of tuberculosis in Ethiopia

    PubMed Central

    Aragaw, Getahun S.

    2014-01-01

    Abstract Background Despite the existence of national tuberculosis guidelines (NTG) in Ethiopia, the incidence and prevalence of tuberculosis did not decline markedly. Audits could attempt to determine whether or not healthcare professionals actually implemented these guidelines, as non-implementation could contribute to suboptimal tuberculosis treatment outcomes. Aim To evaluate healthcare providers implementation of Ethiopia's NTG during the diagnosis and treatment of tuberculosis in order to enhance tuberculosis treatment outcomes. Methods A descriptive, cross-sectional study design was used. Results Healthcare providers implemented the NTG during tuberculosis diagnosis for female (60.9%; n = 67) and male (56.1%; n = 69) patients. The correct numbers of anti-tuberculosis pills, complying with the NTG recommendations, were prescribed for 91.8% (n = 101) of the women and for 90.2% (n = 111) of the men. However, both over- and under-prescriptions of anti-tuberculosis drugs occurred. There was an over-diagnosis of smear-negative pulmonary tuberculosis. Only 2.6% (n = 2) of the 76 smear-negative pulmonary tuberculosis patients had been diagnosed correctly. Conclusion Implementation of the NTG should be enhanced, especially with regard to the diagnosis of smear-negative pulmonary tuberculosis patients and the correct prescription of anti-tuberculosis drugs. This would help to increase the number of correctly-diagnosed and -treated tuberculosis patients, improve tuberculosis treatment outcomes, decrease the spread of tuberculosis and prevent the development of multi-drug-resistant tuberculosis strains. PMID:26245405

  17. [Epidemiology of tuberculosis].

    PubMed

    2004-01-01

    Tuberculosis mortality and morbidity has decreased in Europe since the XIX century. In the 1950s, this decrease accelerated with the discovery of efficient antimycobacterial drugs. However, tuberculosis is still a current issue. It remains a long neglected public health problem. According to WHO evaluation ten million people are infected every year and more than three million die every year. Tuberculosis is the first cause of mortality in the world due to a single infectious agent. In 2000 (www.eurotb.org), the incidence of tuberculosis strongly varied according to three geographical areas: 13 case for 100,000 inhabitants in Western Europe, 40 cases for 100,000 in Central Europe, and 90 cases for 100,000 in Eastern Europe. Between 1972 and 1988, the number of tuberculosis cases reported in Metropolitan France fell to 71% (31,167 to 9,191 cases). The incidence decreased from 60 cases for 100,000 inhabitants in 1972 to 16 case for 100,000 in 1988, with a regular decrease of the incidence ranging around 7% per year. This evolution decreased to -2.5% per year between 1988 and 1991. PMID:15622975

  18. 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

  19. Tuberculosis (For Parents)

    MedlinePLUS

    ... Allergy Emergency Cerebral Palsy: Caring for Your Child Tuberculosis KidsHealth > For Parents > Tuberculosis Print A A A Text Size What's in ... When to You Call the Doctor en espaol Tuberculosis Tuberculosis (popularly known as "TB") is a disease ...

  20. Genitourinary tuberculosis masquerading as a ureteral calculus

    PubMed Central

    Wong, Nathan; Hoag, Nathan A.; Jones, Edward C.; Rowley, Allen; McLoughlin, Martin G.; Paterson, Ryan F.

    2013-01-01

    The genitourinary tract is a common extrapulmonary site of tuberculosis infection, yet remains a rare clinical entity in North America. We report the case of a 37-year-old man who presented for extracorporeal shock wave lithotripsy for a suspected ureteral stone on imaging. Further workup confirmed a diagnosis of genitourinary tuberculosis. Medical management was undertaken and, ultimately, nephrectomy performed. This case highlights the importance of maintaining a high index of clinical suspicion for genitourinary tuberculosis. PMID:23766841

  1. [Extrapulmonary tuberculosis].

    PubMed

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

    2015-01-01

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

  2. Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources.

    PubMed

    Lawn, Stephen D; Wood, Robin; De Cock, Kevin M; Kranzer, Katharina; Lewis, James J; Churchyard, Gavin J

    2010-07-01

    Antiretroviral therapy and isoniazid preventive therapy (IPT) are both effective interventions to prevent HIV-associated tuberculosis, but work via different mechanisms. We propose that these two interventions might best be used as complementary strategies at different stages of HIV progression. At relatively high CD4-cell counts, IPT reduces tuberculosis risk by 64% (95% CI 39-78%) in patients with positive tuberculin skin tests, and is the key tuberculosis preventive intervention before patients are eligible for antiretroviral therapy. However, at low CD4-cell counts, reliable exclusion of active tuberculosis is difficult, fewer patients are eligible for IPT, and waning immune function might limit the durability of its effect. In such patients, antiretroviral therapy is the primary intervention needed, reducing tuberculosis incidence by 67% (95% CI 61-73%). However, tuberculosis risk during long-term antiretroviral therapy remains several times higher than background, especially in those with poor immune recovery. Patients might therefore derive additional benefit from combined use of IPT and antiretroviral therapy to simultaneously treat mycobacterial infection and restore tuberculosis-specific immune function. For those first presenting with advanced immunodeficiency, we propose that concurrent IPT might best be delayed until completion of the first few months of antiretroviral therapy, when active tuberculosis can be more reliably excluded. Data from randomised controlled trials are needed to underpin further development of public-health policy. PMID:20610331

  3. Elevated ex vivo monocyte chemotactic protein-1 (CCL2) in pulmonary as compared with extra-pulmonary tuberculosis

    PubMed Central

    Hasan, Zahra; Zaidi, Irfan; Jamil, Bushra; Khan, M Aslam; Kanji, Akbar; Hussain, Rabia

    2005-01-01

    Background Tuberculosis causes 3 million deaths annually. The most common site of tuberculosis is pulmonary however; extra-pulmonary forms of the disease also remain prevalent. Restriction of Mycobacterium tuberculosis depends on effective recruitment and subsequent activation of T lymphocytes, mononuclear and polymorphonuclear cells to the site of infection. Tumor necrosis factor (TNF)-? is essential for granuloma formation and is a potent activator of monocyte chemotactic protein (MCP-1, CCL2). CCL2 is essential for recruitment of monocytes and T cells and has been shown to play a role in protection against tuberculosis. Interleukin -8 (CXCL8) is a potent activator of neutrophils. Increased levels of CCL2, CXCL8 and TNF? are reported in tuberculosis but their significance in different forms of tuberculosis is as yet unclear. We have used an ex vivo assay to investigate differences in immune parameters in patients with either pulmonary or extra-pulmonary tuberculosis. Methods Serum levels of CCL2, CXCL8 and TNF? were measured in patients with pulmonary tuberculosis (N = 12), extra-pulmonary tuberculosis (N = 8) and BCG-vaccinated healthy volunteers (N = 12). Whole blood cells were stimulated with non-pathogenic Mycobacterium bovis bacille-Calmette Guerin (BCG) vaccine strain or bacterial lipopolysaccharide (LPS) and cyto/chemokines were monitored in supernatants. Results Circulating serum levels of CXCL8 and TNF? were raised in all tuberculosis patients, while CCL2 levels were not. There was no difference in spontaneous cytokine secretion from whole blood cells between patients and controls. M. bovis BCG-induced ex vivo CCL2 secretion was significantly greater in pulmonary as compared with both extra-pulmonary tuberculosis patients and endemic controls. In response to LPS stimulation, patients with pulmonary tuberculosis showed increased CCL2 and TNF? responses as compared with the extra-pulmonary group. BCG-, and LPS-induced CXCL8 secretion was comparable between patients and controls. Conclusion CCL2 is activated by TNF? and is essential for recruitment of monocytes and T cells to the site of mycobacterial infection. Increased CCL2 activation in pulmonary tuberculosis may result in a stronger cellular response as compared with extra-pulmonary tuberculosis patients, and this may contribute to the localization of infection to the pulmonary site. PMID:16001981

  4. A Case Report of Primary Duodenal Tuberculosis Mimicking a Malignant Tumor

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. [Chest tuberculosis imaging].

    PubMed

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

    2015-01-01

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

  7. Pancreatic tuberculosis.

    PubMed

    Sharma, Vishal; Rana, Surinder S; Kumar, Amit; Bhasin, Deepak K

    2016-02-01

    Pancreatic tuberculosis is very rare, but recently, there has been a spurt in the number of reports on pancreatic involvement by tuberculosis. It closely mimics pancreatic cancer, and before the advent of better imaging modalities it was often detected as a histological surprise in patients resected for a presumed pancreatic malignancy. The usual presentation involves abdominal pain, loss of appetite and weight, jaundice which can be associated with cholestasis, fever and night sweats, palpable abdominal lump, and peripheral lymphadenopathy. Computed tomography (CT) of the abdomen is an important tool for evaluation of patients with pancreatic tuberculosis. This CT imaging yields valuable information about the size and nature of tubercular lesions along with the presence of ascites and lymphadenopathy. However, there are no distinctive features on CT that distinguish it from pancreatic carcinoma. Endoscopic ultrasound provides high resolution images of the pancreatic lesions as well as an opportunity to sample these lesions for cytological confirmation. The presence of granulomas is the most common finding on histological/cytological examination with the presence of acid fast bacilli being observed only in minority of patients. As there are no randomized or comparative studies on treatment of pancreatic tuberculosis it is usually treated like other forms of tuberculosis. Excellent cure rates are reported with standard anti tubercular therapy given for 6-12?months. PMID:26414325

  8. Postmortem identifications of remains.

    PubMed

    Weedn, V W

    1998-03-01

    Forensic pathologists must identify the bodies and remains falling under their purview in the normal course of death investigation and death certification. Accurate identification is critical and can at times be daunting challenge, especially in mass disaster situations. Many methods can be employed from various scientific disciplines and otherwise, resulting in positive or presumptive identification. Then, proper identification must be maintained and supported where challenged. PMID:9523068

  9. 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.

  10. [Tuberculosis treatment].

    PubMed

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

    2015-01-01

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

  11. 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 ...

  12. 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 ...

  13. Tuberculosis (TB): Treatment

    MedlinePLUS

    ... of TB Diagnosing Tuberculosis Treating Tuberculosis Active TB Disease Drug-Resistant Tuberculosis Latent TB Infection TB Preventive Treatment History of TB Lifestyle Management of TB Risk Factors for TB Types ...

  14. Miliary tuberculosis in an Indian lady: Looking beyond miliary tuberculosis

    PubMed Central

    Lakshman, Arjun; Dhir, Varun; Kumar, Narender; Singhal, Manphool

    2015-01-01

    Presence of miliary shadows in chest imaging in the appropriate clinical setting is often taken as a marker of miliary tuberculosis. If sputum is negative for acid -fast bacillus, empirical anti-tubercular therapy is given without securing a histological or microbiological diagnosis. We report a young female with human immunodeficiency virus infection who had miliary infiltrates on chest radiography. She was started on empirical anti-tubercular therapy. But an alternate diagnosis was achieved later with invasive sampling and ATT was stopped. This case illustrates the need for physicians to remain alert to diseases which mimic tuberculosis in presentation. PMID:26628767

  15. Miliary tuberculosis in an Indian lady: Looking beyond miliary tuberculosis.

    PubMed

    Lakshman, Arjun; Dhir, Varun; Kumar, Narender; Singhal, Manphool

    2015-01-01

    Presence of miliary shadows in chest imaging in the appropriate clinical setting is often taken as a marker of miliary tuberculosis. If sputum is negative for acid -fast bacillus, empirical anti-tubercular therapy is given without securing a histological or microbiological diagnosis. We report a young female with human immunodeficiency virus infection who had miliary infiltrates on chest radiography. She was started on empirical anti-tubercular therapy. But an alternate diagnosis was achieved later with invasive sampling and ATT was stopped. This case illustrates the need for physicians to remain alert to diseases which mimic tuberculosis in presentation. PMID:26628767

  16. Mycobacterium tuberculosis DNA Increases Vitamin D Receptor mRNA Expression and the Production of Nitric Oxide and Cathelicidin in Human Monocytes

    PubMed Central

    SISWANTO, Siswanto; ZUHRIYAH, Lilik; HANDONO, Kusworini; FITRI, Loeki Enggar; PRAWIRO, Sumarno Reto

    2015-01-01

    Background: The innate immune response to tuberculosis infection may involve the increased production of nitric oxide and cathelicidin due to the up-regulated expression of the vitamin D receptor (VDR), though this proposed mechanism remains controversial. The aim of this study was to determine how the exposure of human monocytes to Mycobacterium tuberculosis (M. tuberculosis) DNA affects the production of nitric oxide and cathelicidin, as well as the expression of VDR. Methods: This study was performed using monocytes obtained from healthy donors. After 24 h incubation, monocytes were stimulated with M. tuberculosis DNA for 18 h to determine the expression of VDR mRNA and the production of nitric oxide and cathelicidin versus non-stimulated cells (the control group). Results: The expression of VDR mRNA was higher in the monocytes exposed to M. tuberculosis DNA compared to the control group (P = 0.020). Monocytes exposed to M. tuberculosis DNA also showed significantly increased production of nitric oxide and cathelicidin compared to the control group (P = 0.0001; P = 0.028). Conclusion: The stimulation of human monocytes with M. tuberculosis DNA increases the expression of the VDR mRNA and the production of nitric oxide and cathelicidin. PMID:26715892

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

    PubMed Central

    2014-01-01

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

  18. Tuberculosis and HIV at the National Level in Kenya: Results From the Second Kenya AIDS Indicator Survey

    PubMed Central

    Mbithi, Agneta; Gichangi, Anthony; Kim, Andrea A.; Katana, Abraham; Weyenga, Herman; Williamson, John; Robinson, Katherine; Oluoch, Tom; Maina, William K.; Kellogg, Timothy A.; De Cock, Kevin M.

    2016-01-01

    Background Co-morbidity with tuberculosis and HIV is a common cause of mortality in sub-Saharan Africa. In the second Kenya AIDS Indicator Survey, we collected data on knowledge and experience of HIV and tuberculosis, as well as on access to and coverage of relevant treatment services and antiretroviral therapy (ART) in Kenya. Methods A national, population-based household survey was conducted from October 2012 to February 2013. Information was collected through household questionnaires, and blood samples were taken for HIV, CD4 cell counts, and HIV viral load testing at a central laboratory. Results Overall, 13,720 persons aged 15–64 years participated; 96.7% [95% confidence interval (CI): 96.3 to 97.1] had heard of tuberculosis, of whom 2.0% (95% CI: 1.7 to 2.2) reported having prior tuberculosis. Among those with laboratory-confirmed HIV infection, 11.6% (95% CI: 8.9 to 14.3) reported prior tuberculosis. The prevalence of laboratory-confirmed HIV infection in persons reporting prior tuberculosis was 33.2% (95% CI: 26.2 to 40.2) compared to 5.1% (95% CI: 4.5 to 5.8) in persons without prior tuberculosis. Among those in care, coverage of ART for treatment-eligible persons was 100% for those with prior tuberculosis and 88.6% (95% CI: 81.6 to 95.7) for those without. Among all HIV-infected persons, ART coverage among treatment-eligible persons was 86.9% (95% CI: 74.2 to 99.5) for persons with prior tuberculosis and 58.3% (95% CI: 47.6 to 69.0) for those without. Conclusions Morbidity from tuberculosis and HIV remain major health challenges in Kenya. Tuberculosis is an important entry point for HIV diagnosis and treatment. Lack of knowledge of HIV serostatus is an obstacle to access to HIV services and timely ART for prevention of HIV transmission and HIV-associated disease, including tuberculosis. PMID:24732814

  19. Efficacy of moxifloxacin & econazole against multidrug resistant (MDR) Mycobacterium tuberculosis in murine model

    PubMed Central

    Gupta, U.D.; Vemuri, N.; Gupta, P.; Kumar, V.; Tanushree, P.; Khuller, G.K.

    2015-01-01

    Background & objectives: Studies have shown the bactericidal potential of econazole and clotrimazole against Mycobacterium tuberculosis under in vitro and ex vivo conditions along with their synergism with conventional antituberculosis drugs. These molecules were also found to be effective against different multidrug resistant (MDR) M. tuberculosis isolates in vitro. Hence the present study was designed to evaluate the in vivo antimycobacterial potential of moxifloxacin and econazole alone and in combination against multidrug resistant tuberculosis (MDR-TB) in a mice model. Methods: Mice were infected with 2.5107 bacilli of MDR strain of M. tuberculosis by aerosol route of infection. After four weeks of infection, chemotherapy was started orally by moxifloxacin 8.0 mg/kg body wt and econazole 3.3 mg/kg alone and in combination, as well as with four first line anti-tuberculosis drugs as a positive control. The animals were sacrificed and the lungs and spleen were excised under aspetic conditions. The tissues were homogenized with sterile normal saline, an aliquot of the homogenate was plated on Middlebrook 7H11 agar supplemented with oleate albumin dextrose catalase (OADC) and incubated at 37C for four weeks. The number of visible and individual colonies were counted. Results: The first line anti-tuberculosis drugs (RIF+INH+EMB+PZA) after eight weeks of therapy had no impact as the bacillary load in lungs and spleens remained unchanged. However, econazole, moxifloxacin alone as well as in combination significantly reduced the bacillary load in lungs as well as in spleens of MDR-TB bacilli infected mice. Interpretation & conclusions: Co-administration of the two drugs (econazole and moxifloxacin) to MDR-TB strain JAL-7782 infected mice exhibited additive effect, the efficacy of the drugs in combination being higher as compared with ECZ or MOX alone. These results were substantiated by histopathological studies. This study suggests the utility of econazole for the treatment of MDR tuberculosis and warrants further work in this direction. PMID:26458349

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

    PubMed Central

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

    2011-01-01

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

  1. Spinal Tuberculosis

    PubMed Central

    Ekinci, Safak; Tatar, Oner; Akpancar, Serkan; Bilgic, Serkan; Ersen, Omer

    2015-01-01

    Spinal tuberculosis (TB) is a significant form of TB, causing spinal deformity and paralysis. Early diagnosis and treatment are crucial for avoiding multivertebral destruction and are critical for improving outcomes in spinal TB. We believe that appropriate treatment method should be implemented at the early stage of this disease and that the Gulhane Askeri T?p Akademisi classification system can be considered a practical guide for spinal TB treatment planning in all countries. PMID:26609247

  2. Secular trends of tuberculosis in western Europe.

    PubMed Central

    Raviglione, M. C.; Sudre, P.; Rieder, H. L.; Spinaci, S.; Kochi, A.

    1993-01-01

    Deaths due to tuberculosis have decreased uniformly in all countries in Western Europe, and most have occurred among those aged > or = 65 years. In recent years, tuberculosis case notifications have continued to decline in Belgium, Finland, France, Germany, and Spain, and have levelled off in Sweden and the United Kingdom; increases have, however, been recorded in Austria, Denmark, Ireland, Italy, Netherlands, Norway, and Switzerland. In Denmark, Netherlands, Norway, Sweden, and Switzerland an increasing number of cases of tuberculosis among foreign-born residents has resulted in a change from the expected downward trend. Human immunodeficiency virus (HIV) infection appears to contribute only marginally to the overall tuberculosis morbidity; however, it appears to be important in Paris and its surrounding areas, and tuberculosis is very common among HIV-infected persons in Italy and Spain. Despite these recent changes in the incidence of tuberculosis, there is currently no evidence of its increased transmission among the youngest age groups of the indigenous populations. Properly designed disease surveillance systems are critical for monitoring the tuberculosis trends so that each country can identify its own high-risk groups and target interventions to prevent, diagnose, and treat the disease. Tuberculosis remains a global disease and because of increasing human migrations, its elimination in Western Europe cannot be envisaged without concomitant improvements in its control in high-incidence, resource-poor countries. PMID:8324847

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

    PubMed Central

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

    2013-01-01

    Background.?Nitric oxide (NO), a key macrophage antimycobacterial mediator that ameliorates immunopathology, is measurable in exhaled breath in individuals with pulmonary tuberculosis. We investigated relationships between fractional exhale NO (FENO) and initial pulmonary tuberculosis severity, change during treatment, and relationship with conversion of sputum culture to negative at 2 months. Methods.?In Papua, we measured FENO in patients with pulmonary tuberculosis at baseline and serially over 6 months and once in healthy controls. Treatment outcomes were conversion of sputum culture results at 2 months and time to conversion of sputum microscopy results. Results.?Among 200 patients with pulmonary tuberculosis and 88 controls, FENO was lower for patients with pulmonary tuberculosis at diagnosis (geometric mean FENO, 12.7 parts per billion [ppb]; 95% confidence interval [CI], 11.613.8) than for controls (geometric mean FENO, 16.6 ppb; 95% CI, 14.219.5; P = .002), fell further after treatment initiation (nadir at 1 week), and then recovered by 6 months (P = .03). Lower FENO was associated with more-severe tuberculosis disease, with FENO directly proportional to weight (P < .001) and forced vital-capacity (P = .001) and inversely proportional to radiological score (P = .03). People whose FENO increased or remained unchanged by 2 months were 2.7-fold more likely to achieve conversion of sputum culture than those whose FENO decreased (odds ratio, 2.72; 95% CI, 1.057.12; P = .04). Conclusions.?Among patients with pulmonary tuberculosis, impaired pulmonary NO bioavailability is associated with more-severe disease and delayed mycobacterial clearance. Measures to increase pulmonary NO warrant investigation as adjunctive tuberculosis treatments. PMID:23737604

  4. Tuberculosis (For Parents)

    MedlinePLUS

    ... Caring for Your Child All About Food Allergies 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 ...

  5. Hysterosalpingographic findings in women with genital tuberculosis

    PubMed Central

    Farrokh, Donya; Layegh, Parvaneh; Afzalaghaee, Monavvar; Mohammadi, Mohaddeseh; Fallah Rastegar, Yalda

    2015-01-01

    Background: Genital tuberculosis (TB) is an important cause of infertility in the developing countries, where hysterosalpingography (HSG) remains an initial diagnostic procedure in the evaluation of tubal and peritoneal factors leading to infertility. Objective: The aim of this study was to determine the HSG findings of genital TB in infertile women. Materials and Methods: We retrospectively reviewed HSG findings in 20 women with genital tuberculosis. HSG was performed in these women as part of infertility work up over 5 years. The other diagnostic procedures used included endometrial curettage and biopsy, histological examination, culture, laparoscopy, hysteroscopy and polymerase chain reaction. Results: The mean age of the participants was 30.5±8 years. All women had clinical history of infertility for at least 4 years. Women presented with pelvic abdominal pain (30-35%) and menstrual disturbances (20-25%). Reviewing 20 cases of female genital TB were encountered various presentations on HSG. Conclusion: HSG is an invaluable procedure in suggesting the diagnosis of genital TB in patients being investigated for infertility. PMID:26221129

  6. Health Care Workers and Tuberculosis

    MedlinePLUS

    MENU Health Care Workers and Tuberculosis How can I protect myself from tuberculosis infection? It's important to know which patients ... know if I have contracted tuberculosis? As a health care worker, you should have a tuberculosis skin test ...

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

    PubMed

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

    2012-05-15

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

  8. [Chest wall tuberculosis: report of 3 cases].

    PubMed

    Zidane, A; Bakzaza, O; Afandi, O; Baiz, Y; Chafik, A

    2015-10-01

    Despite the dramatic decline in the incidence of tuberculosis during the last decades, the disease remains a significant public health problem especially in developing countries. Chest wall tuberculosis is a very rare location. Clinically, it can present as a pyogenic abscess or soft tumor, making diagnosis difficult, particularly in the absence of warning signs. Optimal therapeutic management is controversial. Medical treatment alone in often insufficient and must be associated with a surgical excision or debridement. PMID:25725600

  9. Tuberculosis: Epidemiology and Control

    PubMed Central

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

    2014-01-01

    Tuberculosis (TB) is a major public health concern worldwide: despite a regular, although slow, decline in incidence over the last decade, as many as 8.6 million new cases and 1.3 million deaths were estimated to have occurred in 2012. TB is by all means a poverty-related disease, mainly affecting the most vulnerable populations in the poorest countries. The presence of multidrug-resistant strains of M. tuberculosis in most countries, with somewhere prevalence is high, is among the major challenges for TB control, which may hinder recent achievements especially in some settings. Early TB case detection especially in resource-constrained settings and in marginalized groups remains a challenge, and about 3 million people are estimated to remain undiagnosed or not notified and untreated. The World Health Organization (WHO) has recently launched a new global TB strategy for the post-2015 era aimed at ending the global TB epidemic by 2035. This strategy is based on the three pillars that emphasize patient-centred TB care and prevention, bold policies and supportive systems, and intensified research and innovation. This paper aims to provide an overview of the global TB epidemiology as well as of the main challenges that must be faced to eliminate the disease as a public health problem everywhere. PMID:25408856

  10. Tuberculosis burden in China: a high prevalence of pulmonary tuberculosis in household contacts with and without symptoms

    PubMed Central

    2014-01-01

    Background In the context of decreasing tuberculosis prevalence in China, we examined the effectiveness of screening household contacts of tuberculosis patients. Methods A tuberculosis survey was conducted in 2008. All 3,355 household contacts of notified tuberculosis cases were examined with a questionnaire interview, chest X-ray and three sputum smear tests. The effectiveness was examined by comparing the prevalence of pulmonary tuberculosis in household contacts with or without presenting clinical symptoms against the respective notification rates. Regression models were used to evaluate the factors associated with pulmonary tuberculosis. Results Of the 3,355 household contacts, 92 members (2.7%) had pulmonary tuberculosis, among which 46 cases were asymptomatic. The prevalence of pulmonary tuberculosis and smear positive cases in household contacts without symptoms were 20 and 7 times higher than the notification rates in 2008, while those in household contacts with symptoms were 247 and 108 times higher than notification rates, respectively. The patients detected were mainly Index Cases spouses, sisters/brothers and those who were in contact with female Index Cases. Conclusions The present study provides convincing evidence that household contacts of notified tuberculosis cases are at higher risk of developing tuberculosis. Routine screening for household contacts without any symptoms is recommended for sustained tuberculosis control in China as well as in the world. PMID:24502559

  11. Nosocomial tuberculosis.

    PubMed

    Catanzaro, A

    1982-05-01

    Hospital employees are at risk of contracting tuberculosis from patients. The undiagnosed case with sputum-smear positive for acid-fast bacilli is the usual source case. However, even the smear-negative patient may pose a risk. This was documented by a high rate of skin test conversion in hospital staff exposed to a smear-negative, culture-positive patient in a respiratory intensive care unit. The patient required bronchoscopy, intubation, and assisted ventilation. Of susceptible hospital staff members who were exposed to the index case, 14 of 45 (31%) converted their PPD skin test. Ten of 13 (77%) susceptible hospital staff members present at the time of bronchoscopy converted, compared with 4 of 32 (12.5%) who were not present at bronchoscopy (Fischer's exact test p = 0.0006). Rough calculations suggest that during the bronchoscopy and intubation the index case generated at least 249 infectious units per hour. At the ventilation levels in this area, this resulted in 1 infectious unit of tuberculosis in each 68.9 cubic feet of air. Improved ventilation, high efficiency filters, and ultraviolet irradiation are effective recommended ways to clean the air of infectious particles. PMID:7081816

  12. 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 microscopypositive 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. PMID:25537870

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

    PubMed Central

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

    2013-01-01

    Background Captive elephants infected with tuberculosis are implicated as an occupational source of zoonotic tuberculosis. However, accurate estimates of prevalence and incidence of elephant tuberculosis from well-defined captive populations are lacking in the literature. Studies published in recent years contain a wide range of prevalence estimates calculated from summary data. Incidence estimates of elephant tuberculosis in captive elephants are not available. Objective This study estimated the annual point prevalence, annual incidence, cumulative incidence, and incidence density of tuberculosis in captive elephants within the USA during the past 52 years. Animals and Methods We combined existing elephant census records from captive elephants in the USA with tuberculosis culture results obtained from trunk washes or at necropsy. This data set included 15 years where each elephant was screened annually. Results Between 1960 and 1996, the annual point prevalence of tuberculosis complex mycobacteria for both species was 0. From 1997 through 2011, the median point prevalence within the Asian elephant population was 5.1%, with a range from 0.3% to 6.7%. The incidence density was 9.7 cases/1000 elephant years (95% CI: 7.013.4). In contrast, the annual point prevalence during the same time period within the African elephant population remained 0 and the incidence density was 1.5 cases/1000 elephant years (95% CI: 0.74.0). Conclusions The apparent increase in new cases noted after 1996 resulted from a combination of both index cases and the initiation of mandatory annual tuberculosis complex (MTBC) screening in 1997 for all the elephants. This study found lower annual point prevalence estimates than previously reported in the literature. These discrepancies in prevalence estimates are primarily due to differences in terminology and calculation methods. Using the same intensive testing regime, the incidence of tuberculosis differed significantly between Asian and African elephants. Clinical Importance Accurate and species specific knowledge of prevalence and incidence will inform our efforts to mitigate occupational risks associated with captive elephants in the USA. PMID:23477422

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

    PubMed Central

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

    2015-01-01

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

  15. [Control and prevention of tuberculosis in healthcare facilities].

    PubMed

    Sernia, Sabina; Arcaro, Paola; Ortis, Marina; La Torre, Giuseppe

    2013-01-01

    Tuberculosis remains the leading cause of death by a single infectious agent. Healthcare workers who for professional reasons are exposed to infectious patients and to potentially contaminated materials are at high risk of infection. This article provides a review of existing regulations and summarizes national and international guidelines and operational protocols for tuberculosis surveillance in clinical settings. PMID:24316878

  16. Tuberculosis (TB): Treatment

    MedlinePLUS

    ... 2/13 By Dr. Iseman Michael Iseman, MD Tuberculosis (TB): Treatment Given the many effective medications available ... News View Daily Pollen Count Doctors Who Treat Tuberculosis Charles L. Daley more/less Sign Up for ...

  17. 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

  18. 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

  19. Tuberculosis diagnostics: Challenges and opportunities

    PubMed Central

    Nema, Vijay

    2012-01-01

    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

  20. 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

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

    PubMed

    Brites, Daniela; Gagneux, Sebastien

    2015-03-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-04-01

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

  4. 040. Management of patients with tuberculosis in pulmonary clinic of AUTH from June 2011 to September 2014

    PubMed Central

    Kostanta, Soultana; Manika, Katerina; Papadaki, Eleni; Kipourou, Maria; Lada, Martha; Papaioannou, Maria; Zarogoulidis, Konstantinos; Kioumis, Ioannis

    2015-01-01

    Background Despite the effectiveness of the standard regimen in tuberculosis treatment, in clinical practice modification and extension of the regimen is often required due to mycobacterial resistance and drug side effects. Objective Assessment of outcome and average duration of treatment of patients with tuberculosis in the out-patient clinic for tuberculosis, Pulmonary Clinic, AUTH. Methods A total of 101 patients with tuberculosis who were followed in the out-patient clinic for tuberculosis from June 2011 until September 2014 were included in the study. Treatment regimen, duration and outcome were recorded. Results Data on 70 men and 31 women with mean age SD of 48.919.4 years were analyzed. Regarding outcome, 33 patients were cured (32.7%), 37 (36.5%) are still under treatment, six patients died (three of them due to TB (3.0%) and three due to other reasons (3.0%), nine were transferred out (8.9%), 15 (14.9%) defaulted and one failed treatment (1.0%). Out of the 33 patients with successful treatment, 25 (75.76%) received first-line treatment with average duration 10.75 months and whereas in eight (24.24%) a modification of treatment was needed resulting in treatment duration of 18.37 months. The main reasons for prolongation of treatment beyond nine months were extended disease, bad adherence, resistance to first-line drugs and significant side-effects. Conclusions Based on these data, treatment of tuberculosis is more prolonged and complicated than initially anticipated. The rate of default was high and needs to be addressed in the context of public health services. In addition death from tuberculosis still remains a reality.

  5. Multicentric Spinal Tuberculosis with Sternoclavicular Joint Involvement: A Rare Presentation

    PubMed Central

    Meena, Umesh Kumar; Meena, Ramesh Chand

    2014-01-01

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

  6. 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

  7. Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children: a systematic review and meta-analysis

    PubMed Central

    Detjen, Anne K; DiNardo, Andrew R; Leyden, Jacinta; Steingart, Karen R; Menzies, Dick; Schiller, Ian; Dendukuri, Nandini; Mandalakas, Anna M

    2016-01-01

    Summary Background Microbiological confirmation of childhood tuberculosis is rare because of the difficulty of collection of specimens, low sensitivity of smear microscopy, and poor access to culture. We aimed to establish summary estimates for sensitivity and specificity of of the Xpert MTB/RIF assay compared with microscopy in the diagnosis of pulmonary tuberculosis in children. Methods We searched for studies published up to Jan 6, 2015, that used Xpert in any setting in children with and without HIV infection. We systematically reviewed studies that compared the diagnostic accuracy of Xpert MTB/RIF (Xpert) with microscopy for detection of pulmonary tuberculosis and rifampicin resistance in children younger than 16 years against two reference standardsculture results and culture-negative children who were started on anti-tuberculosis therapy. We did meta-analyses using a bivariate random-effects model. Findings We identified 15 studies including 4768 respiratory specimens in 3640 children investigated for pulmonary tuberculosis. Culture tests were positive for tuberculosis in 12% (420 of 3640) of all children assessed and Xpert was positive in 11% (406 of 3640). Compared with culture, the pooled sensitivities and specificities of Xpert for tuberculosis detection were 62% (95% credible interval 5173) and 98% (9799), respectively, with use of expectorated or induced sputum samples and 66% (5181) and 98% (9699), respectively, with use of samples from gastric lavage. Xpert sensitivity was 3644% higher than was sensitivity for microscopy. Xpert sensitivity in culture-negative children started on antituberculosis therapy was 2% (13) for expectorated or induced sputum. Xperts pooled sensitivity and specificity to detect rifampicin resistance was 86% (95% credible interval 5398) and 98% (94100), respectively. Interpretation Compared with microscopy, Xpert offers better sensitivity for the diagnosis of pulmonary tuberculosis in children and its scale-up will improve access to tuberculosis diagnostics for children. Although Xpert helps to provide rapid confirmation of disease, its sensitivity remains suboptimum compared with culture tests. A negative Xpert result does not rule out tuberculosis. Good clinical acumen is still needed to decide when to start antituberculosis therapy and continued research for better diagnostics is crucial. Funding WHO, Global TB Program of Texas Childrens Hospital. PMID:25812968

  8. 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

  9. 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-?(+)/TNF(+)) and IFN-?(+) 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

  10. 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

  11. 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

  12. [Childhood tuberculosis].

    PubMed

    Hamzaoui, A

    2015-01-01

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

  13. Tuberculosis and nutrition

    PubMed Central

    Gupta, Krishna Bihari; Gupta, Rajesh; Atreja, Atulya; Verma, Manish; Vishvkarma, Suman

    2009-01-01

    Malnutrition and tuberculosis are both problems of considerable magnitude in most of the underdeveloped regions of the world. These two problems tend to interact with each other. Tuberculosis mortality rates in different economic groups in a community tend to vary inversely with their economic levels. Similarly, nutritional status is significantly lower in patients with active tuberculosis compared with healthy controls. Malnutrition can lead to secondary immunodeficiency that increases the host's susceptibility to infection. In patients with tuberculosis, it leads to reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and altered metabolism leading to wasting. Both, protein-energy malnutrition and micronutrients deficiencies increase the risk of tuberculosis. It has been found that malnourished tuberculosis patients have delayed recovery and higher mortality rates than well-nourished patients. Nutritional status of patients improves during tuberculosis chemotherapy. High prevalence of human immunodeficiency (HIV) infection in the underdeveloped countries further aggravates the problem of malnutrition and tuberculosis. Effect of malnutrition on childhood tuberculosis and tuberculin skin test are other important considerations. Nutritional supplementation may represent a novel approach for fast recovery in tuberculosis patients. In addition, raising nutritional status of population may prove to be an effective measure to control tuberculosis in underdeveloped areas of world. PMID:20165588

  14. [Smoking and tuberculosis].

    PubMed

    Underner, Michel; Perriot, Jean

    2012-12-01

    Smoking and tuberculosis represent two major world health issues particularly in developing countries. Tobacco smoke increases risk of Mycobaterium tuberculosis infection by several means: alteration of muco-ciliary clearance, reduced alveolar macrophage activity; immune-depression of pulmonary lymphocytes, reduction of cytotoxic activity of natural killer cells, alteration of the activity of the pulmonary dendritic cells. Both active and passive smoking increases the risk of latent tubercular infection and of pulmonary and extra-pulmonary tuberculosis. Active smoking increases the severity of pulmonary tuberculosis (gravity of radiological lesions). The diagnostic delay and recovery details are more important for smokers. Active smoking increases relapses of both pulmonary and extra-pulmonary tuberculosis after treatment with or without the Directly Observed Treatment Short course (DOTS) with poor observance of treatment. The mortality risk from tuberculosis is heightened among smokers. Smoking cessation represents an essential means of controlling tuberculosis epidemics in developing countries. PMID:22465718

  15. Adjusting to a new home: Mycobacterium tuberculosis gene expression in response to an intracellular lifestyle.

    PubMed

    Stokes, Richard W; Waddell, Simon J

    2009-12-01

    Mycobacterium tuberculosis remains the most significant single species of bacteria causing disease in mankind. The ability of M. tuberculosis to survive and replicate within host macrophages is a pivotal step in its pathogenesis. Understanding the microenvironments that M. tuberculosis encounters within the macrophage and the adaptations that the bacterium undergoes to facilitate its survival will lead to insights into possible therapeutic targets for improved treatment of tuberculosis. This is urgently needed with the emergence of multi- and extensively drug resistant strains of M. tuberculosis. Significant advances have been made in understanding the macrophage response on encountering M. tuberculosis. Complementary information is also accumulating regarding the counter responses of M. tuberculosis during the various stages of its interactions with the host. As such, a picture is emerging delineating the gene expression of intracellular M. tuberculosis at different stages of the interaction with macrophages. PMID:19995191

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

    PubMed Central

    Vollrath, Oliver; Lange, Christoph

    2014-01-01

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

  17. A cross-sectional and follow-up study of leukopenia in tuberculosis patients: prevalence, risk factors and impact of anti-tuberculosis treatment

    PubMed Central

    Lin, Fei-Shen; Wu, Mei-Ying; Tu, Wen-Jun; Pan, Hong-Qiu; Zheng, Jian; Shi, Jun-Wei; Fei, Zhong-Ting; Zhang, Rui-Mei; Yan, Wei-Guo; Shang, Ming-Qun; Zheng, Qiang; Wang, Meng-Jie

    2015-01-01

    Background To investigate the prevalence of and risk factors for leukopenia in tuberculosis patients and the impact of anti-tuberculosis regimens on the occurrence of leukopenia in newly treated tuberculosis patients. Methods A total of 1,904 tuberculosis patients were included in the study. A cross-sectional survey of the prevalence of leukopenia was initially conducted, and then factors influencing leukopenia were identified using Logistic regression analysis. Non-treatment factors influencing peripheral blood leukocyte counts were analyzed using univariate COX proportional hazards models. Covariate analysis was used to assess the independent effect of different anti-tuberculosis regimens on peripheral blood leukocyte counts. Results Being female, advanced age and longer duration of previous anti-tuberculosis treatment (>6 month) were risk factors for leukopenia in tuberculosis patients, while secondary pulmonary tuberculosis, higher body mass index (BMI: 24?27.9 kg/m2), and higher degree of education (senior high school or above) were protective factors. Gender, vegetable consumption, drinking, pulmonary infection, other chronic diseases, and use of antibiotics were significantly associated with the development of leukopenia in patients on anti-tuberculosis treatment. In tuberculosis patients treated with anti-tuberculosis regimens not containing antibiotics, peripheral blood leukocyte levels gradually declined with the prolongation of treatment duration. In tuberculosis patients treated with anti-tuberculosis regimens containing antibiotics, peripheral blood leukocyte levels showed a declining trend. Conclusions Female patients, patients at advanced age and recurrent tuberculosis patients having longer previous anti-tuberculosis treatment are high-risk populations for leukopenia. Attention should be paid to the influence of vegetable consumption and drinking, co-morbidities and use of antibiotics during anti-tuberculosis treatment. PMID:26793345

  18. Tuberculosis: a disease without boundaries.

    PubMed

    Fogel, Nicole

    2015-09-01

    Tuberculosis (TB) is an airborne disease caused by Mycobacterium tuberculosis (MTB) that usually affects the lungs leading to severe coughing, fever, and chest pains. Although current research in the past four years has provided valuable insight into TB transmission, diagnosis, and treatment, much remains to be discovered to effectively decrease the incidence of and eventually eradicate TB. The disease still puts a strain on public health, being only second to HIV/AIDS in causing high mortality rates. This review will highlight the history of TB as well as provide an overview of the current literature on epidemiology, pathogenesis and the immune response, treatment, and control of TB. In this race to combat a disease that knows no boundaries, it is necessary to have a conceptual and clear understanding of TB overall with the hope of providing better treatment through novel and collaborative research and public health efforts. PMID:26198113

  19. [Immune response to Mycobacterium tuberculosis].

    PubMed

    Nowag, A; Hartmann, P

    2016-02-01

    Infections with Mycobacterium tuberculosis (MTB) induce complex immune responses involving an orchestrated interplay of innate and adaptive immune mechanisms. Why the immune system fails to eradicate the pathogen and at best achieves control of infection in the latent stage, still remains an unsolved mystery even more than 100 years after the discovery of MTB by Robert Koch. This article provides an overview of the current state of the art in the constantly evolving field of tuberculosis (TB) immunology. This review focuses on a change of paradigm proposing that in the latent stage MTB is anything but dormant and that latent TB is not merely a state of bacterial stasis but a state of dynamic bacterial and immunological equilibrium. The understanding of these dynamics is crucial for the development of new drugs against MTB as well as vaccines that aim to provide effective protection against the disease. PMID:26838368

  20. 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 (http://ifr48.timone.univ-mrs.fr/MST_MTuberculosis/mst). PMID:18560597

  1. Household Contact Screening Adherence among Tuberculosis Patients in Northern Ethiopia

    PubMed Central

    Gebregergs, Gebremedhin Berhe; Alemu, Wondmu Gebeyehu

    2015-01-01

    Background Household contacts of active tuberculosis cases are at high risk of getting tuberculosis disease. Tuberculosis detection rate among contacts of household members is high. Hence, this study investigated household contact screening adherence and associated factors among tuberculosis patients in Amhara region, Ethiopia. Methods A cross-sectional study was conducted from April 10 - June 30, 2013 in five urban districts of Amhara region, where 418 patients receiving treatment at tuberculosis clinic were interviewed. All patients were interviewed using structured and pre-tested questionnaire. Bringing at least one household contact to TB clinic was regarded as adherent to household contacts screening. Bivariate and multiple logistic regressions were used to investigate association. Results The overall adherence to household contact screening in Amhara region was 33.7%. Adherence was higher among Muslims than Christians. Adherence was high if patient took health education from Health Care Worker [AOR: 3.22, 95% CI: 1.88 to 5.51] and 2.17 times higher if patient had sufficient knowledge on tuberculosis [AOR: 2.17, 95% CI: 1.29 to 3.67] during interview. Relationship with contact was a significant [AOR: 0.4, 95% CI: 0.2 to 0.9] social related factor. Conclusion One third of tuberculosis patients adhered to household contact screening in health facilities during their treatment course. Promoting knowledge of tuberculosis in the community and continuous health education to tuberculosis patients are recommended. PMID:25955517

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

    PubMed Central

    2010-01-01

    Background The global financial crisis threatens global health, particularly exacerbating diseases of inequality, e.g. HIV/AIDS, and diseases of poverty, e.g. tuberculosis. The aim of this paper is to reconsider established practices and policies for HIV and tuberculosis epidemic control, aiming at delivering better results and value for money. This may be achieved by promoting greater integration of HIV and tuberculosis control programme activities within a strengthened health system. Discussion HIV and tuberculosis share many similarities in terms of their disease burden and the recommended stratagems for their control. HIV and tuberculosis programmes implement similar sorts of control activities, e.g. case finding and treatment, which depend for success on generic health system issues, including vital registration, drug procurement and supply, laboratory network, human resources, and financing. However, the current health system approach to HIV and tuberculosis control often involves separate specialised services. Despite some recent progress, collaboration between the programmes remains inadequate, progress in obtaining synergies has been slow, and results remain far below those needed to achieve universal access to key interventions. A fundamental re-think of the current strategic approach involves promoting integrated delivery of HIV and tuberculosis programme activities as part of strengthened general health services: epidemiological surveillance, programme monitoring and evaluation, community awareness of health-seeking behavior, risk behaviour modification, infection control, treatment scale-up (first-line treatment regimens), drug-resistance surveillance, containing and countering drug-resistance (second-line treatment regimens), research and development, global advocacy and global partnership. Health agencies should review policies and progress in HIV and tuberculosis epidemic control, learn mutual lessons for policy development and scaling up interventions, and identify ways of joint planning and joint funding of integrated delivery as part of strengthened health systems. Summary As both a danger and an opportunity, the global financial crisis may entail disaster or recovery for global health sector efforts for HIV and tuberculosis epidemic control. Review of policies and progress in control paves the way for identification of synergies between the two programmes, within strengthened health services. The silver lining in the global economic crisis could be better control of the HIV and tuberculosis epidemics, better overall health system performance and outcomes, and better value for money. PMID:20602774

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

    PubMed Central

    2013-01-01

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

  4. 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, ...

  5. 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

  6. 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

  7. 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

  8. [Management of multidrug-resistant tuberculosis].

    PubMed

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

    2015-01-01

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

  9. [Population structure analysis of Mycobacterium tuberculosis Beijing family in Japan].

    PubMed

    Iwamoto, Tomotada

    2009-12-01

    The Beijing family is a genotypic lineage of M. tuberculosis that reportedly predominates throughout eastern Asia and in parts of Russia yet dispersed worldwide. About 80% of clinical isolates in Japan are belonging to this family. The predominance of a narrow range of genotypes, in this case predominance by Beijing family strains, hypothesized that these strains may have a selective advantage either with virulence or transmissibility that led to clonal expansion. The strains are monophyletic within the M. tuberculosis species and also reveal further sublineages within this family. It is believed that the genetic and evolutionary background of M. tuberculosis strains influence on the propensity to gain drug resistance as well as the pathogen's transmissibility. Thus, understanding the population genetic structure and its dynamics of Beijing family strains will undoubtedly help to unravel the basis for the considerable success and spread of this genotype in Japan. During the past few years, we intensively studied this notorious clade, M. tuberculosis Beijing family, to reconstruct their evolutionary events and phylogeny and to elucidate their epidemiological characteristics at the sublineage levels through the population structure analysis. Here, I summarized the findings of our research in the past few years. Singularity of the genetic diversity of Beijing family strains in Japan. We reconstructed the phylogenetic trees of Beijing family strains by the 15-MIRU-VNTR genotyping method and validated them through profiling of the NTF region, large sequence polymorphisms (LSP), and single-nucleotide polymorphisms (SNPs). Interestingly, we could demonstrate that the ancient Beijing sublineage has remained endemic to Japan, in contrast to the worldwide spread of the modern Beijing sublineage. Moreover, we found that the ancient sublineage strains corresponding to four monophyletic subgroups. The singularity of the genetic diversity of Beijing family strains in Japan, i.e., its high diversity and dominance of the ancient sublineage in contrast to the modern sublineage found worldwide, suggested that they became endemic independently from the evolutionary stream that led to the dominant modern Beijing sublineage in outside Japan. Population structure dynamics of Beijing family strains in Japan. We inferred the population structure dynamics of Beijing family strains during the past decades in Japan by comparing the isolates from elderly TB patients (these strains represent the population structure that existed decades ago) and young TB patients (these strains reflect the population structure of currently prevalent strains). The comparison between the cohorts born in different years suggested that the population structure of the M. tuberculosis Beijing family strains in Japan before World War II--when TB was highly prevalent--was significantly different from that of the currently prevalent strains. The results revealed that the spread of a modern sub-lineage that has high transmissibility is currently increasing, while the spread of an ancient sublineage, STK, has significantly decreased in younger generations. It is interesting to assume that the observed trends in the case of the modern and STK strains may be associated with the Mycobacterium bovis bacillus Calmette-Gurin (BCG) vaccination. Association between sublineages of Beijing family and multidrug resistance. Mycobacterium tuberculosis Beijing family strains are suspected to be an evolving lineage of M. tuberculosis that has acquired the advantage of drug resistance. However, the association between this genotype and drug resistance varies in different countries. This may be due to heterogeneity in the fitness of the sublineages of the Beijing family and different proportions of these sublineages in the local population. To determine whether certain sublineages are associated with multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, the population structure of the Beijing strains based on 10 synonymous single nucleotide polymorphisms (sSNPs) was an

  10. RAPID LATERAL-FLOW FOR BOVINE TUBERCULOSIS

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  11. Endobronchial Tuberculosis Mimicking Asthma

    PubMed Central

    Argun Baris, Serap; Onyilmaz, Tu?ba; Basyigit, Ilknur; Boyaci, Hasim

    2015-01-01

    Endobronchial tuberculosis (EBTB) is defined as tuberculosis infection of the tracheobronchial tree with microbial and histopathological evidence. The clinical symptoms of the diseases are nonspecific. Chronic cough is the major symptom of the disease. The diagnosis is often delayed due to its nonspecific presentation and misdiagnosed as bronchial asthma. This case is presented to recall the notion that the endobronchial tuberculosis can mimic asthma and the importance of bronchoscopic evaluation in a patient with chronic cough and treatment resistant asthma.

  12. 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 [730], 36 [1965] and 57.5 [3395] 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

  13. Bilateral Parotid Tuberculosis

    PubMed Central

    Thakur, JS; Thakur, A; Mohindroo, NK; Mohindroo, S; Sharma, DR

    2011-01-01

    Tuberculosis of parotid is a rare clinical entity, and cases of bilateral tubercular parotitis are even rarer. We present a case of bilateral primary parotid tuberculosis in a 49-year-old female. The patient received anti-tuberculosis treatment for six months, resulting in complete resolution of the disease. We also review the theories related to the pathogenesis of tubercular parotitis, and propose a novel hypothesis about greater involvement of parotid gland as compared to other salivary glands in primary tuberculosis. PMID:21887065

  14. Vitamin D and tuberculosis.

    PubMed

    Chocano-Bedoya, Patricia; Ronnenberg, Alayne G

    2009-05-01

    Tuberculosis is highly prevalent worldwide, accounting for nearly two million deaths annually. Vitamin D influences the immune response to tuberculosis, and vitamin D deficiency has been associated with increased tuberculosis risk in different populations. Genetic variability may influence host susceptibility to developing active tuberculosis and treatment response. Studies examining the association between genetic polymorphisms, particularly the gene coding for the vitamin D receptor (VDR), and TB susceptibility and treatment response are inconclusive. However, sufficient evidence is available to warrant larger epidemiologic studies that should aim to identify possible interactions between VDR polymorphisms and vitamin D status. PMID:19386033

  15. TUBERCULOSIS COMO ENFERMEDAD OCUPACIONAL

    PubMed Central

    Mendoza-Ticona, Alberto

    2014-01-01

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

  16. Perinatal malaria and tuberculosis co-infection: a case report.

    PubMed

    Thapa, Rajoo; Mallick, Debkrishna; Biswas, Biswajit

    2010-03-01

    India remains endemic for both vivax malaria and tuberculosis. In spite of the high burden of tuberculosis in the country, reports on congenital tuberculosis in the literature are limited. We report herein an unusual instance of co-occurrence of perinatal falciparum malaria and tuberculosis in a 34-day-old female newborn, who presented with symptoms of sepsis. The diagnosis was based on the demonstration of Plasmodium falciparum on peripheral blood smear and tubercle bacilli in gastric aspirate samples. The maternal history for falciparum malaria was positive during her eighth month of pregnancy and the father was an open case of sputum smear-positive pulmonary tuberculosis. She responded dramatically to combined antimalarial and antitubercular chemotherapy. A search for combined etiologies in presumed 'sepsis' in the newborn, guided by history, physical examination, and laboratory investigations, is warranted. PMID:19647462

  17. 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

  18. 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…

  19. Increased Complement C1q Level Marks Active Disease in Human Tuberculosis

    PubMed Central

    Zhang, Mingxia; Liu, Haiying; Zhang, Guoliang; Deng, Qunyi; Huang, Jian; Gao, Zhiliang; Zhou, Boping; Feng, Carl G.; Chen, Xinchun

    2014-01-01

    Background Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. Methods Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. Results C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. Conclusions C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy. PMID:24647646

  20. 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,

  1. 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,…

  2. Drug-resistance pattern of Mycobacterium tuberculosis strains from patients with pulmonary and extrapulmonary tuberculosis during 2006 to 2013 in a Korean tertiary medical center

    PubMed Central

    Lee, Ho Young; Lee, Jin; Lee, Young Seok; Kim, Mi-Yeong; Lee, Hyun-Kyung; Lee, Young-min; Shin, Jeong Hwan

    2015-01-01

    Background/Aims We evaluated the trend in the rates of drug-resistant tuberculosis (TB) over time, as well as the difference in the drug-resistance pattern between pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) at a private referral center in South Korea. Methods All patients with culture-confirmed TB from 2006 to 2013 were included. Results In total, 1,745 patients were included: 1,431 (82.0%) were new cases, and 314 (18.0%) were cases treated previously; 1,610 (92.3%) were diagnosed with PTB, and 135 (7.7%) were diagnosed with EPTB. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB were detected in 5.8% and 2.0% of new cases and in 20.1% and 8.6% of previously treated cases, respectively. The MDR TB rate during the study period decreased remarkably, whereas the MDR and XDR TB rates decreased significantly in previously treated cases. No difference in the drug-resistance rate was detected between PTB and EPTB. Conclusions The TB drug-resistance rate, particularly that of MDR TB, remained high at a private referral hospital, and the drug-resistance rate did not decrease significantly from 2006 to 2013. This finding underscores the need for a national survey regarding the prevalence of drug-resistant TB to obtain the most accurate and current drug-resistance status in South Korea, including the private sector. PMID:25995663

  3. Risk of travel-associated tuberculosis.

    PubMed

    Rieder, H L

    2001-10-15

    Infection with Mycobacterium tuberculosis might be acquired at home or during travel. The risk is determined by exposure frequency to a source case and the duration of the exposure. Thus, whether travel increases the background risk depends on origin, destination, and duration of travel. Infection might be acquired indoors or outdoors, but the overall risk seems small, whatever the setting. Bacille Calmette-Guérin vaccination and preventive therapy have both been discussed as possible preventive interventions, but the disadvantages associated with both approaches appear to outweigh any benefits. Because the risk of acquisition of infection with M. tuberculosis is small, the most rational approach is likely to delay intervention until a traveler presents with clinically active tuberculosis, as is done with any other patient. PMID:11565081

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

    PubMed Central

    2013-01-01

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

  5. Granuloma Correlates of Protection Against Tuberculosis and Mechanisms of Immune Modulation by Mycobacterium tuberculosis

    PubMed Central

    Mehra, Smriti; Alvarez, Xavier; Didier, Peter J.; Doyle, Lara A.; Blanchard, James L.; Lackner, Andrew A.; Kaushal, Deepak

    2013-01-01

    Background.?The BCG vaccine is ineffective against adult tuberculosis. Hence, new antituberculosis vaccines are needed. Correlates of protection against tuberculosis are not known. We studied the effects of BCG vaccination on gene expression in tuberculosis granulomas using macaques. Methods.?Macaques were BCG-vaccinated or sham-vaccinated and then challenged with virulent Mycobacterium tuberculosis. Lung lesions were used for comparative transcriptomics. Results.?Vaccinated macaques were protected with lower bacterial burden and immunopathology. Lesions from BCG-vaccinated nonhuman primates (NHPs) showed a better balance of ?- and ?-chemokine gene expression with higher levels of ?-chemokine expression relative to nonvaccinated animals. Consistent with this, sham-vaccinated macaques recruited fewer macrophages relative to neutrophils in their lungs. The expression of indoleamine 2,3-dioxygenase (IDO), a known immunosuppressor, was significantly higher in both week 5 and 10 lesions from sham-vaccinated, relative to BCG-vaccinated, NHPs. IDO expression was primarily limited to the nonlymphocytic region of the lesions, within the inner ring structure surrounding the central necrosis. Conclusions.?Our study defines lung gene expression correlates of protective response against tuberculosis, relative to disease, which can potentially be employed to assess the efficacy of candidate antituberculosis vaccines. Mycobacterium tuberculosis may modulate protective immune responses using diverse mechanisms, including increased recruitment of inflammatory neutrophils and the concomitant use of IDO to modulate inflammation. PMID:23255564

  6. 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

  7. Complex sputum microbial composition in patients with pulmonary tuberculosis

    PubMed Central

    2012-01-01

    Background An increasing number of studies have implicated the microbiome in certain diseases, especially chronic diseases. In this study, the bacterial communities in the sputum of pulmonary tuberculosis patients were explored. Total DNA was extracted from sputum samples from 31 pulmonary tuberculosis patients and respiratory secretions of 24 healthy participants. The 16S rRNA V3 hyper-variable regions were amplified using bar-coded primers and pyro-sequenced using Roche 454 FLX. Results The results showed that the microbiota in the sputum of pulmonary tuberculosis patients were more diverse than those of healthy participants (p<0.05). The sequences were classified into 24 phyla, all of which were found in pulmonary tuberculosis patients and 17 of which were found in healthy participants. Furthermore, many foreign bacteria, such as Stenotrophomonas, Cupriavidus, Pseudomonas, Thermus, Sphingomonas, Methylobacterium, Diaphorobacter, Comamonas, and Mobilicoccus, were unique to pulmonary tuberculosis patients. Conclusions This study concluded that the microbial composition of the respiratory tract of pulmonary tuberculosis patients is more complicated than that of healthy participants, and many foreign bacteria were found in the sputum of pulmonary tuberculosis patients. The roles of these foreign bacteria in the onset or development of pulmonary tuberculosis shoud be considered by clinicians. PMID:23176186

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

    PubMed Central

    Rieder, H L

    1989-01-01

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

  9. "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

  10. "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…

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

    PubMed Central

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

    2014-01-01

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

  12. Multidrug-resistant tuberculosis: Treatment and outcomes of 93 patients

    PubMed Central

    Brode, Sarah K; Varadi, Robert; McNamee, Jane; Malek, Nina; Stewart, Sharon; Jamieson, Frances B; Avendano, Monica

    2015-01-01

    BACKGROUND: Tuberculosis (TB) remains a leading cause of death worldwide and the emergence of multidrug-resistant TB (MDR TB) poses a threat to its control. There is scanty evidence regarding optimal management of MDR TB. The majority of Canadian cases of MDR TB are diagnosed in Ontario; most are managed by the Tuberculosis Service at West Park Healthcare Centre in Toronto. The authors reviewed 93 cases of MDR TB admitted from January 1, 2000 to December 31, 2011. RESULTS: Eighty-nine patients were foreign born. Fifty-six percent had a previous diagnosis of TB and most (70%) had only pulmonary involvement. Symptoms included productive cough, weight loss, fever and malaise. The average length of inpatient stay was 126 days. All patients had a peripherally inserted central catheter for the intensive treatment phase because medications were given intravenously. Treatment lasted for 24 months after bacteriologic conversion, and included a mean ( SD) of 51 drugs. A successful outcome at the end of treatment was observed in 84% of patients. Bacteriological conversion was achieved in 98% of patients with initial positive sputum cultures; conversion occurred by four months in 91%. CONCLUSIONS: MDR TB can be controlled with the available anti-TB drugs. PMID:25493698

  13. Sustainable tuberculosis drug development.

    PubMed

    Wallis, Robert S

    2013-01-01

    Six new antituberculosis compounds in 4 classes are presently in clinical trials. Although these show substantial promise for drug-resistant (DR) tuberculosis, the presently planned studies of these compounds will not inform their optimal use, as each will be tested singly vs placebo with existing drugs, rather than in new regimens. Each successive regulatory approval will increase the size, cost, and complexity of trials for those that follow, causing delays during which suboptimal use will occur and resistance will emerge. This paper proposes the development of a novel regimen with the potential for use in both drug-sensitive (DS) and DR tuberculosis. Adaptive licensing for DR tuberculosis based on 2-month sputum culture would shorten time to initial approval by several years. A global outcomes registry would confirm safety and effectiveness in both DS and DR tuberculosis, making possible the second transformation of tuberculosis treatment. We should do our utmost to see it succeed. PMID:23042970

  14. 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

  15. New hominin remains from Uzbekistan.

    PubMed

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

    2008-08-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. Authenticated DNA from Ancient Wood Remains

    PubMed Central

    LIEPELT, SASCHA; SPERISEN, CHRISTOPH; DEGUILLOUX, MARIE-FRANCE; PETIT, REMY J.; KISSLING, ROY; SPENCER, MATTHEW; DE BEAULIEU, JACQUES-LOUIS; TABERLET, PIERRE; GIELLY, LUDOVIC; ZIEGENHAGEN, BIRGIT

    2006-01-01

    Background The reconstruction of biological processes and human activities during the last glacial cycle relies mainly on data from biological remains. Highly abundant tissues, such as wood, are candidates for a genetic analysis of past populations. While well-authenticated DNA has now been recovered from various fossil remains, the final proof is still missing for wood, despite some promising studies. Scope The goal of this study was to determine if ancient wood can be analysed routinely in studies of archaeology and palaeogenetics. An experiment was designed which included blind testing, independent replicates, extensive contamination controls and rigorous statistical tests. Ten samples of ancient wood from major European forest tree genera were analysed with plastid DNA markers. Conclusions Authentic DNA was retrieved from wood samples up to 1000 years of age. A new tool for real-time vegetation history and archaeology is ready to use. PMID:16987920

  18. 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

  19. Genetic Variants in MARCO Are Associated with the Susceptibility to Pulmonary Tuberculosis in Chinese Han Population

    PubMed Central

    Ma, Mai-Juan; Wang, Hai-Bing; Li, Hao; Yang, Jun-Hai; Yan, Yan; Xie, Lan-Pin; Qi, Ying-Cheng; Li, Jun-Lian; Chen, Mei-Juan; Liu, Wei; Cao, Wu-Chun

    2011-01-01

    Background Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk. Principal Findings To specifically investigated whether single nucleotide polymorphisms (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control subjects using a hospital based case-control association study. Single-point and haplotype analysis revealed an association in intron and exon region of MARCO gene. One SNP (rs17009726) was associated with susceptibility to pulmonary tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI?=?1.322.05, pcorrected?=?9.27E5) increased risk of pulmonary tuberculosis. Haplotype analysis revealed that haplotype GC containing G allele of 17009726 and haplotype TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also associated with susceptibility to pulmonary tuberculosis (pcorrected?=?0.0001 and 0.029, respectively). Conclusions Our study suggested that genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population, and the findings emphasize the importance of MARCO mediated immune responses in the pathogenesis of tuberculosis. PMID:21886847

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

    PubMed Central

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

    2009-01-01

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

  1. 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

  2. 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.

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

    PubMed Central

    Dabernat, Henri; Thves, Catherine; Bouakaze, Caroline; Nikolaeva, Dariya; Keyser, Christine; Mokrousov, Igor; Graut, Annie; Duchesne, Sylvie; Grard, Patrice; Alexeev, Anatoly N.; Crubzy, 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 16th19th 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

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

    PubMed

    Dabernat, Henri; Thves, Catherine; Bouakaze, Caroline; Nikolaeva, Dariya; Keyser, Christine; Mokrousov, Igor; Graut, Annie; Duchesne, Sylvie; Grard, Patrice; Alexeev, Anatoly N; Crubzy, 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. PMID:24587092

  5. Long-term survival of tuberculosis complex mycobacteria in soil.

    PubMed

    Ghodbane, Ramzi; Mba Medie, Felix; Lepidi, Hubert; Nappez, Claude; Drancourt, Michel

    2014-03-01

    While there is evidence for the persistence of Mycobacterium bovis in soil, there are no reports for the other Mycobacterium tuberculosis complex (MTC) mycobacteria. Here, soil was inoculated with 10(8) c.f.u. g(-1) M. tuberculosis, M. bovis and M. canettii and subcultured monthly for 12 months. The pathogenicity of mycobacterial colonies, identified by using matrix-assisted laser desorption/ionization time of flight mass spectrometry, was assessed in a mouse model. Moreover, mice were fed with food that contained 16.7% M. tuberculosis-contaminated soil. The three tested MTC species survived in soil for 12 months with a final inoculum of 2 10(3) c.f.u. g(-1) for M. tuberculosis, 150 c.f.u. g(-1) for M. bovis and 2 10(4) c.f.u. g(-1) for M. canettii. In an experiment that included negative controls, all (5/5) mice inoculated with such M. tuberculosis and M. canettii developed 0.03-0.3 granulomas mm(-2) in their lungs and spleen and grew mycobacteria; five mice that were inoculated with M. bovis from soil did not develop granulomas but grew mycobacteria. Furthermore, 0.2-0.4 granulomas mm(-2) were observed in the lungs and spleen of 3/5 mice fed with M. tuberculosis-contaminated soil in the presence of two negative control mice. M. tuberculosis grew in the stomach, intestine, spleen and lung in 5/5 challenged mice, whereas the negative controls remained M. tuberculosis-free (P = 0.008, Fisher exact test). This study provides clear evidence that MTC mycobacteria survive in soil, and that M. tuberculosis remains virulent while in the soil, outside its hosts, for extended periods of time. PMID:24425768

  6. Atypical spinal tuberculosis.

    PubMed

    Pande, Ketan C; Babhulkar, Sudhir S

    2002-05-01

    Typical spinal tuberculosis is readily diagnosed and treated. Certain atypical clinical and radiologic presentations of spinal tuberculosis are described. Failure to recognize these presentations may lead to delay in diagnosis and initiation of treatment. In some atypical forms of the disease, this may have disastrous consequences. The current authors present a new classification for atypical spinal tuberculosis and describe the various presentations. The role of advanced imaging studies such as computed tomography scanning and magnetic resonance imaging and imaging-guided aspiration cytology is discussed. PMID:11964633

  7. 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. PMID:26653188

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

    PubMed Central

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

    2009-01-01

    Background Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFN?, TNF? and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity. Methodology We investigated live M. tuberculosis- and M. bovis BCG- induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and healthy endemic controls (ECs, n?=?36). TB patients comprised pulmonary (PTB, n?=?34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n?=?16) or severe disseminated ETB (D-ETB, n?=?16). Secretion of CCL2, IFN?, IL10 and CCL3, and mRNA expression of CCL2, TNF?, CCL3 and CXCL8 were determined. Results M. tuberculosis- and BCG- induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05, p<0.01) as compared with L-ETB patients. CCL2 secretion in response to M. tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups. M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p?=?0.023), while CCL2 was reduced in L-ETB as compared with D-ETB (p?=?0.005) patients. M. tuberculosis induced IFN? was greater in L-ETB than PTB (p?=?0.04), while BCG-induced IFN? was greater in L-ETB as compared with D-ETB patients (p?=?0.036). TNF? mRNA expression was raised in PTB as compared with L-ETB group in response to M. tuberculosis (p?=?0.02) and BCG (p?=?0.03). Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups. Conclusions The increased CCL2 and TNF? in PTB patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease. PMID:20041183

  9. Tuberculosis and Pregnancy

    MedlinePLUS

    ... Specific Populations Foreign-Born High-Risk Settings Homeless International Occupational Groups Travel TB & HIV Testing & Diagnosis Treatment LTBI Updates Vaccines & Immunizations World TB Day DTBE Authored Journal Articles 2014 2013 2012 2011 2010 2009 Tuberculosis ...

  10. 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. PMID:23468104

  11. Global Tuberculosis (TB)

    MedlinePLUS

    ... Lesotho, Mexico, Mozambique, Peru, Philippines, Russia, Rwanda, South Africa, Thailand, and Vietnam. Learn More » Data and Statistics ... Programmatic Support Site Visits Program Consultant Laws and Policies Menu of Suggested Provisions For State Tuberculosis Prevention ...

  12. 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

  13. Tuberculosis in Blacks

    MedlinePLUS

    ... 1533 non-Hispanic blacks in the United States, accounting for 23% of all people reported with TB ... NTIP): Frequently Asked Questions TB Genotyping TB Genotyping Information Management System (TB GIMS) Drug-Resistant TB Multidrug-Resistant Tuberculosis ( ...

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

    PubMed Central

    2014-01-01

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

  15. Tuberculosis diagnostics in 2015: landscape, priorities, needs, and prospects.

    PubMed

    Pai, Madhukar; Schito, Marco

    2015-04-01

    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

  16. The history of tuberculosis.

    PubMed

    Daniel, Thomas M

    2006-11-01

    Tuberculosis has claimed its victims throughout much of known human history. It reached epidemic proportions in Europe and North America during the 18th and 19th centuries, earning the sobriquet, "Captain Among these Men of Death." Then it began to decline. Understanding of the pathogenesis of tuberculosis began with the work of Thophile Laennec at the beginning of the 19th century and was further advanced by the demonstration of the transmissibility of Mycobacterium tuberculosis infection by Jean-Antoine Villemin in 1865 and the identification of the tubercle bacillus as the etiologic agent by Robert Koch in 1882. Clemens von Pirquet developed the tuberculin skin test in 1907 and 3 years later used it to demonstrate latent tuberculous infection in asymptomatic children. In the late 19th and early 20th centuries sanatoria developed for the treatment of patients with tuberculosis. The rest provided there was supplemented with pulmonary collapse procedures designed to rest infected parts of lungs and to close cavities. Public Health measures to combat the spread of tuberculosis emerged following the discovery of its bacterial cause. BCG vaccination was widely employed following World War I. The modern era of tuberculosis treatment and control was heralded by the discovery of streptomycin in 1944 and isoniazid in 1952. PMID:16949809

  17. Computational genomics-proteomics and Phylogeny analysis of twenty one mycobacterial genomes (Tuberculosis & non Tuberculosis strains)

    PubMed Central

    2012-01-01

    Background The genus Mycobacterium comprises different species, among them the most contagious and infectious bacteria. The members of the complex Mycobacterium tuberculosis are the most virulent microorganisms that have killed human and other mammals since millennia. Additionally, with the many different mycobacterial sequences available, there is a crucial need for the visualization and the simplification of their data. In this present study, we aim to highlight a comparative genome, proteome and phylogeny analysis between twenty-one mycobacterial (Tuberculosis and non tuberculosis) strains using a set of computational and bioinformatics tools (Pan and Core genome plotting, BLAST matrix and phylogeny analysis). Results Considerably the result of pan and core genome Plotting demonstrated that less than 1250 Mycobacterium gene families are conserved across all species, and a total set of about 20,000 gene families within the Mycobacterium pan-genome of twenty one mycobacterial genomes. Viewing the BLAST matrix a high similarity was found among the species of the complex Mycobacterium tuberculosis and less conservation is found with other slow growing pathogenic mycobacteria. Phylogeny analysis based on both protein conservation, as well as rRNA clearly resolve known relationships between slow growing mycobacteria. Conclusion Mycobacteria include important pathogenic species for human and animals and the Mycobacterium tuberculosis complex is the most cause of death of the humankind. The comparative genome analysis could provide a new insight for better controlling and preventing these diseases. PMID:22929624

  18. Multi Drug and Other Forms of Drug Resistant Tuberculosis Are Uncommon among Treatment Nave Tuberculosis Patients in Tanzania

    PubMed Central

    Nagu, Tumaini J.; Aboud, Said; Mwiru, Ramadhani; Matee, Mecky; Fawzi, Wafaie; Mugusi, Ferdinand

    2015-01-01

    Background Surveillance and effective management of drug resistance is important to sustaining tuberculosis (TB) control efforts. We aimed to determine resistance rates to first line anti tuberculosis drugs and to describe factors associated with the resistance to any of the first line anti tuberculosis drugs in Dar es Salaam Tanzania. Materials Newly diagnosed, TB patients with neither history of tuberculosis treatment nor isoniazid prophylaxis were included into the study. Sputum specimens were cultured on either mycobacteria growth indicator tube 960 (MGIT 960) or Lowenstein Jenstein (LJ) medium supplemented with either glycerol (GLJ) or pyruvate (PLJ). Drug susceptibility for isoniazid, rifampicin, streptomycin and ethambutol was determined by either LowensteinJensen (LJ) medium or mycobacteria growth indicator tube 960 (MGIT 960). Results A total of 933 newly diagnosed TB patients, were included into the study. Multi drug resistance (MDR) tuberculosis was detected among 2 (0.2%) patients. Resistance to any of the four tested drugs was detected among 54 (5.8%) patients. Mono-resistance to isoniazid, rifampicin, streptomycin and ethambutol were 21(2.3%), 3 (0.3%), 13 (1.4%), 9 (1.0%) respectively. Conclusion Primary resistance to first line anti tuberculosis drugs is still low in this setting. Continued vigilance including periodic national surveillance of anti-tuberculosis resistance is recommended. PMID:25849784

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

    PubMed Central

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

    2012-01-01

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

  20. 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

  1. Relationship Between Blood Concentrations of Hepcidin and Anemia Severity, Mycobacterial Burden, and Mortality Among Patients With HIV-Associated Tuberculosis

    PubMed Central

    Kerkhoff, Andrew D.; Meintjes, Graeme; Burton, Rosie; Vogt, Monica; Wood, Robin; Lawn, Stephen D.

    2016-01-01

    Background Anemia is very common in patients with human immunodeficiency virus (HIV)associated tuberculosis, and hepcidin may be key in mediating this. We explored the relationship between blood hepcidin concentrations and anemia severity, mycobacterial burden and mortality in patients with HIV-associated tuberculosis. Methods Consecutive unselected HIV-infected adults in South Africa were systematically investigated for tuberculosis. Three groups were studied: 116 hospitalized inpatients with HIV infection and tuberculosis (hereafter, hospitalized patients), 58 ambulatory outpatients with HIV infection and newly diagnosed tuberculosis (hereafter, ambulatory patients with tuberculosis), and 58 ambulatory outpatients with HIV infection and without tuberculosis (hereafter, ambulatory patients without tuberculosis). Blood hepcidin concentrations were determined for all patients. Vital status at 3 months was determined, and independent predictors of mortality were identified. Results Median hepcidin concentrations were 38.8 ng/mL among hospitalized patients, 19.1 ng/mL among ambulatory patients with tuberculosis, and 5.9 ng/mL among ambulatory patients without tuberculosis (P < .001). In both groups with HIV-associated tuberculosis, hepcidin concentrations were strongly associated with greater anemia severity. Additionally, strong, graded associations were observed between hepcidin and composite indices of mycobacterial burden and dissemination. Patients dying within 3 months had significantly higher hepcidin concentrations, which independently predicted mortality. Conclusions High hepcidin concentrations were strongly associated with disseminated disease, anemia, and poor prognosis in patients with HIV-associated tuberculosis. Hepcidin may be a mechanistically important mediator underlying the high prevalence of severe anemia in these patients. PMID:26136467

  2. Mycobacterium tuberculosis: Manipulator of Protective Immunity.

    PubMed

    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

  3. 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 ...

  4. Treatment and developmental therapeutics of Mycobacterium tuberculosis infections.

    PubMed

    St Georgiev, V

    1994-08-01

    Tuberculosis still remains a serious health problem in many regions of the world, especially in developing nations. With the spread of AIDS and the increase in the number of immunocompromised patients, the problem of tuberculosis has been greatly exacerbated because of the susceptibility of such patients to mycobacteria. Currently, chemotherapy using multiple drug regimens with isoniazid, rifampin, streptomycin, pyrazinamide, and ethambutol is the recommended treatment for tuberculosis. The presence of drug resistance is still a major concern and new generations of more effective antimycobacterial agents (antibiotics, fluoroquinolone derivatives) are the subject of active investigation. The search for novel strategies to cure tuberculosis led to studies exploring the role of cytokines in host defenses and the application of adoptive immunotherapy. New and improved methodology for in vitro and in vivo screening of antimycobacterial activity has also been reported. PMID:18611607

  5. 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. PMID:26770228

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

    PubMed Central

    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. PMID:26770228

  7. [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

  8. Mycobacterium tuberculosis: Success through dormancy

    PubMed Central

    Gengenbacher, Martin; Kaufmann, Stefan H. E.

    2012-01-01

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

  9. A case report of peritoneal tuberculosis with multiple miliary peritoneal deposits mimicking advanced ovarian carcinoma

    PubMed Central

    Yazdani, Shahla; Sadeghi, Mahmod; Alijanpour, Abolhasan; Naeimi-rad, Mojgan

    2016-01-01

    Background: Peritoneal tuberculosis accounts 1-2% of all forms of tuberculosis. Peritoneal tuberculosis is an important differential diagnosis for ovarian cancer in women with ascites, adnexal mass and elevated cancer antigen 125 (CA125) levels. We report a case of a 32- year -old woman with multiple miliary peritoneal deposits mimicking advanced ovarian carcinoma. Case Presentation: A 32-year-old drug addicted woman presented with menometrorrhagia, fever and shivering, ascites and pelvis mass. Ultrasonography revealed a 53×65 mm cyst in left ovary and ascites. Multiple miliary peritoneal deposits were observed during laparatomy without any mass, histologic examination confirmed tuberculosis of uterus, tubes, omentum, liver and external surfaces of small intestine. Finally, the patient recovered with anti-tuberculosis treatment. Conclusion: These findings highlight considering tuberculosis in the differential diagnosis of any patients with adnexal mass, ascitis and elevated serum CA125 even with negative cytology and bacteriology test results. PMID:26958336

  10. Calvarial tuberculosis with parenchymal involvement.

    PubMed

    Garca-Garca, Concepcin; Ibarra, Valvanera; Azcona-Gutirrez, Jos M; Oteo, Jos A

    2013-01-01

    Tuberculosis is an infectious disease caused by the acid-fast bacilli Mycobacterium tuberculosis that usually affects the lungs although it may affect any organ. Tuberculous osteitis of the cranial bones is an uncommon manifestation of disseminated tuberculosis known as calvarial tuberculosis. Cases with parenchymal involvement are infrequent in the literature. We report a case of a patient with multiple osteolytic cranial lesions and a tuberculoma. PMID:23267716

  11. [The issue of tuberculosis in the elderly in Japan].

    PubMed

    Toyota, Makoto; Sasaki, Yuka

    2010-12-01

    Tuberculosis in the elderly remains a health burden in Japan. Most of the elderly aged more than 70 years in Japan had become infected with Mycobacterium tuberculosis in their youth, and the elderly represent a population at a special high risk for developing tuberculosis owing to comorbidity and age-related immunosuppression. The characteristics of tuberculosis in the elderly are different from young patients. To reduce active tuberculosis in the elderly, treatment of latent tuberculosis infection for compromised host could be strengthened, however its impact might be limited. Elderly tuberculosis patients have not only clinical problems but also socioeconomic problems. Major problems of elderly tuberculosis patients are concurrent diseases, bed ridden states, necessity of nursing care, undernourished, poor adherence, and poor performance status of patients. With this symposium, we focused on the issue of tuberculosis in the elderly in Japan. The speakers were invited from various areas, including tuberculosis surveillance center, public health center and national hospital organization medical center. (1) Current trend of elderly TB: Masako OHMORI (Tuberculosis Surveillance Center, Research Institute of Tuberculosis, JATA) Although the tuberculosis (TB) incidence rate in Japan reached 19.4 per 100,000 in 2008, the rates among the elderly (65 + yrs) were high, e.g., 29.5 of those aged 64-74 years, 64.2 of those aged 75-84 years and 97.3 of those aged 85 years and over. The proportion of those aged 65 years and over increased from 36.8% in 1987 to 56.7% in 2008. Regarding the delay of case detection among elderly TB patients, the patient's delay tended to be shorter but the doctor's delay was longer. Although most TB patients including elderly TB patients were detected upon visiting a medical institution with some symptoms, in the case of elderly TB more patients were detected as outpatients or inpatients for a disease other than TB. Among TB patients aged 65 years and over, 26.4% died within one year. (2) The issues of elderly tuberculosis--An outbreak of pulmonary tuberculosis at nursing home for the elderly: Michiaki OKUMURA (Public Health Division, Public Health and Welfare Bureau, City of Osaka) I experienced a mass outbreak of pulmonary tuberculosis with 8 patients (including the source of infection) and 6 latent tuberculosis infections. Five patients (including the source) of the 8, I underwent restriction fragment length polymorphism (RFLP) analysis of isolated from the sputum. Five patients showed an identical RFLP pattern. These results showed that the infection had arisen from one source. The disease of 4 patients (aged 74-103) seemed to be caused by exogenous reinfections. The elderly tend to have some complications and to be malnutrition. These factors may be risk factors of tuberculosis reinfection for elderly. (3) The community DOTS in the elderly: Yoko HASHIMOTO (Wakayama Prefecture Gobo Health Center) In Wakayama prefecture, we have established a standard assessment list of adherence for tuberculosis patients. To identify predictors of default in the elderly, we investigated assessment lists of tuberculosis patients registered in Gobo Health Center from 2004 to 2007. Factors associated with default were concurrent diseases, side effects, disability and no family support. We have developed a liaison critical pathway for tuberculosis in Gobo Health Center and Tanabe Health Center since 2007. Introducing the path, we could strengthen community medical cooperation and build a network to support adherence. Health center staff should expand the community DOTS in the elderly with establishing an effective community collaboration. (4) The clinical issue of tuberculosis in the elderly: Takeshi KAWASAKI (Department of Respirology, Graduate School of Medicine, Chiba University, Department of Thoracic Disease, National Hospital Organization Chiba-East National Hospital) To identify the clinical issue of TB in the elderly, 139 cases were studied. There were 63 elderly cases in the 139. In the elderly TB patients, there were many cases of death and moving out, so the clinical results were poor. Some cases take much time to move out. It is important to inform doctors and people who care for the elderly that the elderly are under high risk of tuberculosis, to consider treatment for latent tuberculosis infection of high risk groups of tuberculosis, and that experts in tuberculosis, local doctors, health care center and geriatric facilities have close relation. (5) Problems and measures of tuberculosis in elderly group: Masahiro ABE (National Hospital Organization Ehime National Hospital) The percentage of the aged is high among all of tuberculosis patients, especially in the country compared to the city. I reported problems concerning tuberculosis treatment and ward management for elderly patients. During the hospitalization, the management of underlying diseases and new complications besides tuberculosis treatment is critical. Dysphagia features particularly make difficult to take anti-TB drugs and nutritional state worse. The rehabilitation of swallowing functions is effective to improve these conditions. To make discharge support more helpful, the support system, including regional cooperation path is expected to advance more widely and deeply. PMID:21404574

  12. Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages

    PubMed Central

    Manzanillo, Paolo S.; Shiloh, Michael U.; Portnoy, Daniel A.; Cox, Jeffery S.

    2013-01-01

    Summary Cytosolic bacterial pathogens activate the cytosolic surveillance pathway (CSP) and induce innate immune responses, but how the host detects vacuolar pathogens like Mycobacterium tuberculosis is poorly understood. We show that M. tuberculosis also initiates the CSP upon macrophage infection via limited perforation of the phagosome membrane mediated by the ESX-1 secretion system. Although the bacterium remains within the phagosome, this permeabilization results in phagosomal and cytoplasmic mixing and allows extracellular mycobacterial DNA to access host cytosolic receptors, thus blurring the distinction between vacuolar and cytosolic pathogens. Activation of cytosolic receptors induces signaling through the STING/TBK1/IRF3 axis, resulting in IFN-? production. Surprisingly, IRF3?/? mice, which cannot respond to cytosolic DNA, are resistant to long-term M. tuberculosis infection, suggesting that the CSP promotes M. tuberculosis infection. Thus, cytosolic sensing of mycobacterial DNA plays a key role in M. tuberculosis pathogenesis and likely contributes to the high type I IFN signature in tuberculosis. PMID:22607800

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

    PubMed Central

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

    2014-01-01

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

  14. Human immunodeficiency virus and tuberculosis co-infection in Saudi Arabia.

    PubMed

    Alrajhi, A A; Nematallah, A; Abdulwahab, S; Bukhary, Z

    2002-11-01

    Our study determined the rate of screening tuberculosis patients for HIV co-infection and the HIV seroprevalence among them. We retrospectively reviewed medical charts of 437 patients diagnosed with tuberculosis from 1995-2000 in Riyadh, Saudi Arabia. Screening was done for 178 (41%) patients: 2 (1.1%) of these were found to be HIV positive. Prior to screening, 4 patients were already known to be HIV positive. Males were screened more often than females (45% and 36% respectively). All HIV positive patients were males. Screening was not affected by origin of the patient, history of prior tuberculosis or treatment, type of tuberculosis involvement or resistance to first line anti-tuberculosis agents. In Saudi Arabia, screening for HIV in tuberculosis patients remains underutilized. Among screened patients, seropositivity was low. PMID:15568451

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

    PubMed Central

    Connell, Tom G.; Zar, Heather J.

    2011-01-01

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

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

    PubMed Central

    Lyashchenko, Konstantin P.; Greenwald, Rena; Esfandiari, Javan; Lecu, Alexis; Waters, W. Ray; Posthaus, Horst; Bodmer, Thomas; Janssens, Jean-Paul; Aloisio, Fabio; Graubner, Claudia; Grosclaude, Elonore; 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

  17. 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

  18. 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

  19. 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

  20. 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…

  1. 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…

  2. 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…

  3. 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. ...

  4. Factors associated with default from treatment among tuberculosis patients in nairobi province, Kenya: A case control study

    PubMed Central

    2011-01-01

    Background Successful treatment of tuberculosis (TB) involves taking anti-tuberculosis drugs for at least six months. Poor adherence to treatment means patients remain infectious for longer, are more likely to relapse or succumb to tuberculosis and could result in treatment failure as well as foster emergence of drug resistant tuberculosis. Kenya is among countries with high tuberculosis burden globally. The purpose of this study was to determine the duration tuberculosis patients stay in treatment before defaulting and factors associated with default in Nairobi. Methods A Case-Control study; Cases were those who defaulted from treatment and Controls those who completed treatment course between January 2006 and March 2008. All (945) defaulters and 1033 randomly selected controls from among 5659 patients who completed treatment course in 30 high volume sites were enrolled. Secondary data was collected using a facility questionnaire. From among the enrolled, 120 cases and 154 controls were randomly selected and interviewed to obtain primary data not routinely collected. Data was analyzed using SPSS and Epi Info statistical software. Univariate and multivariate logistic regression analysis to determine association and Kaplan-Meier method to determine probability of staying in treatment over time were applied. Results Of 945 defaulters, 22.7% (215) and 20.4% (193) abandoned treatment within first and second months (intensive phase) of treatment respectively. Among 120 defaulters interviewed, 16.7% (20) attributed their default to ignorance, 12.5% (15) to traveling away from treatment site, 11.7% (14) to feeling better and 10.8% (13) to side-effects. On multivariate analysis, inadequate knowledge on tuberculosis (OR 8.67; 95% CI 1.47-51.3), herbal medication use (OR 5.7; 95% CI 1.37-23.7), low income (OR 5.57, CI 1.07-30.0), alcohol abuse (OR 4.97; 95% CI 1.56-15.9), previous default (OR 2.33; 95% CI 1.16-4.68), co-infection with Human immune-deficient Virus (HIV) (OR 1.56; 95% CI 1.25-1.94) and male gender (OR 1.43; 95% CI 1.15-1.78) were independently associated with default. Conclusion The rate of defaulting was highest during initial two months, the intensive phase of treatment. Multiple factors were attributed by defaulting patients as cause for abandoning treatment whereas several were independently associated with default. Enhanced patient pre-treatment counseling and education about TB is recommended. PMID:21906291

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

    PubMed Central

    Merchant, Suleman; Bharati, Alpa; Merchant, Neesha

    2013-01-01

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

  6. Decline in Tuberculosis among Mexico-Born Persons in the United States, 20002010

    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 StatesMexico 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 nonrecently 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-bornspecific 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 nonrecently arrived Mexico-born persons. The extent of the decline was dampened by an unchanged tuberculosis case rate among newly arrived persons from Mexico and a large increase in the nonrecently arrived Mexico-born population. If current trends continue, tuberculosis morbidity among Mexico-born persons will be increasingly driven by those who have been living in the United States for more than 5 years. PMID:24708206

  7. New approaches in the diagnosis and treatment of latent tuberculosis infection

    PubMed Central

    2010-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  9. 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 important to consider in TB surveillance programs to prevent the spread of MDR-TB isolates in the population. PMID:26396714

  10. Tuberculosis and HIV Coinfection.

    PubMed

    Bruchfeld, Judith; Correia-Neves, Margarida; Källenius, Gunilla

    2015-07-01

    Tuberculosis (TB) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) constitute the main burden of infectious disease in resource-limited countries. In the individual host, the two pathogens, Mycobacterium tuberculosis and HIV, potentiate one another, accelerating the deterioration of immunological functions. In high-burden settings, HIV coinfection is the most important risk factor for developing active TB, which increases the susceptibility to primary infection or reinfection and also the risk of TB reactivation for patients with latent TB. M. tuberculosis infection also has a negative impact on the immune response to HIV, accelerating the progression from HIV infection to AIDS. The clinical management of HIV-associated TB includes the integration of effective anti-TB treatment, use of concurrent antiretroviral therapy (ART), prevention of HIV-related comorbidities, management of drug cytotoxicity, and prevention/treatment of immune reconstitution inflammatory syndrome (IRIS). PMID:25722472

  11. CT of abdominal tuberculosis

    SciTech Connect

    Epstein, B.M.; Mann, J.H.

    1982-11-01

    Intraabdominal tuberculosis (TB) presents with a wide variety of clinical and radiologic features. Besides the reported computed tomographic (CT) finding of high-density ascites in tuberculous peritonitis, this report describes additional CT features highly suggestive of abdominal tuberculosis in eight cases: (1) irregular soft-tissue densities in the omental area; (2) low-density masses surrounded by thick solid rims; (3) a disorganized appearance of soft-tissue densities, fluid, and bowel loops forming a poorly defined mass; (4) low-density lymph nodes with a multilocular appearance after intravenous contrast administration; and (5) possibly high-density ascites. The differential diagnosis of these features include lymphoma, various forms of peritonitis, peritoneal carcinomatosis, and peritoneal mesothelioma. It is important that the CT features of intraabdominal tuberculosis be recognized in order that laparotomy be avoided and less invasive procedures (e.g., laparoscopy, biopsy, or a trial of antituberculous therapy) be instituted.

  12. 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. PMID:26409271

  13. The global emergency of tuberculosis: what is the cause?

    PubMed

    Grange, J M; Zumla, A

    2002-06-01

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

  14. 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

  15. Ruxolitinib Associated Tuberculosis Presenting as a Neck Lump

    PubMed Central

    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

  16. Immunodiagnosis of tuberculosis: new questions, new tools conference 2008

    PubMed Central

    2010-01-01

    Human infection with Mycobacterium tuberculosis exists as a spectrum of conditions ranging from asymptomatic infection to active disease. Novel, accurate tuberculosis immunodiagnostics have been introduced over the last decade, but it remains challenging to timely diagnose active disease and to accurately distinguish asymptomatic M. tuberculosis infection from immune memory resulting from a prior infection eradicated by the host response. The conference titled Immunodiagnosis of Tuberculosis: New Questions, New Tools, which was held on September 21-23, 2008 in Virginia Beach, Virginia, United States, brought together basic scientists and clinical experts to discuss recent progress in tuberculosis research and diagnosis. Global analyses of M. tuberculosis biology and the host immune response, with emphasis on systems approaches to the study of host-pathogen interactions, were presented. Moreover, conference participants discussed new tests in the pipeline and reviewed new technologies leading to novel assay formats. The discussion included technologies ranging from simple, inexpensive point-of-care tests to automated molecular platforms for detection of multiple infections based on the “lab on a chip” concept. It was also recognized that the utility of any new diagnostic relies on laboratory capacity, accessibility, costs, and test deployment. The conference included lessons from the field. For example, the application of existing technologies to neglected areas, such as diagnosis in children and HIV+ populations, was discussed. PMID:21172041

  17. Pulmonary tuberculosis among people living with HIV/AIDS attending care and treatment in rural northern Tanzania

    PubMed Central

    Ngowi, Bernard J; Mfinanga, Sayoki G; Bruun, Johan N; Morkve, Odd

    2008-01-01

    Background Tuberculosis is the commonest opportunistic infection and the number one cause of death in HIV/AIDS patients in developing countries. To address the extent of the tuberculosis HIV coinfection in rural Tanzania we conducted a cross sectional study including HIV/AIDS patients attending care and treatment clinic from September 2006 to March 2007. Methods Sputum samples were collected for microscopy, culture and drug susceptibility testing. Chest X-ray was done for those patients who consented. Blood samples were collected for CD4+ T cells count. Results The prevalence of tuberculosis was 20/233 (8.5%). Twenty (8.5%) sputum samples were culture positive. Eight of the culture positive samples (40%) were smear positive. Fifteen (75%) of these patients neither had clinical symptoms nor chest X-ray findings suggestive of tuberculosis. Nineteen isolates (95%) were susceptible to rifampicin, isoniazid, streptomycin and ethambutol (the first line tuberculosis drugs). One isolate (5%) from HIV/tuberculosis coinfected patients was resistant to isoniazid. No cases of multi- drug resistant tuberculosis were identified. Conclusion We found high prevalence of tuberculosis disease in this setting. Chest radiograph suggestive of tuberculosis and clinical symptoms of fever and cough were uncommon findings in HIV/tuberculosis coinfected patients. Tuberculosis can occur at any stage of CD4+T cells depletion. PMID:18826574

  18. 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

  19. 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

  20. Hypercalcaemia: atypical presentation of miliary tuberculosis

    PubMed Central

    So, Edison; Bolger, Dennis Thomas

    2014-01-01

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

  1. Tuberculosis Incidence in HIV/AIDS Patients in Israel, 19832010

    PubMed Central

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

    2013-01-01

    Objectives People living with HIV/AIDS (PLWHA) who develop tuberculosis disease are at greater mortality-risk. This study aimed to assess tuberculosis disease incidence among all PLWHA in Israel and identify populations at high-risk for developing tuberculosis. Design and Methods Retrospective cohort-study based on the National HIV and Tuberculosis Registries, which were cross-matched and followed for the last 28-years. PLWHA who developed tuberculosis were compared to those who did not by the Cox-proportional analysis to generate hazard-ratios, and survival-analysis was performed by Log-Rank test. Results Of all the 6579 PLWHA reported between 1983 and 2010, corresponding to 55737 person-years, 384 (5.8%) developed tuberculosis. Of those, 14 were Israeli-born and 370 were non-Israeli born. The overall tuberculosis incidence-density was 6.9 cases/1000 person-years (95% CI 1.812.0). The cumulative tuberculosis-incidence among PLWHA in 2010 was 586 times higher than in HIV-negative individuals (3400 and 5.8 cases per 100000 population, respectively). Higher hazard-ratios to developing tuberculosis were found in migrant citizens PLWHA who were males, non-Israeli born, those who were diagnosed with HIV/AIDS after 1997, those who originated in high-tuberculosis prevalence country and those who acquired HIV by heterosexual or drug-injection transmission. PLWHA who developed tuberculosis had higher odds of dying than other PLWHA (36.5% and 16.6%, respectively, p<0.001, odds ratio?=?2.8, 95% confidence-interval 2.33.6). In survival-analysis, time to develop tuberculosis was shorter among males than females, in PLWHA who were reported with HIV after 1997, in heterosexual who originated in high-tuberculosis countries, followed by injecting drug-users, heterosexual from low-tuberculosis burden countries and men who have sex with men. Conclusion Tuberculosis-incidence is higher among non-Israeli born PLWHA, with decreasing trends from 1991. Despite the moderate TB-rate disease among PLWHA, it remains an important cause for severe morbidity and mortality. Tuberculosis in PLWHA reflects mainly the tuberculosis-burden in the originating country and possibly also the mode of HIV-transmission. PMID:24278157

  2. Socioeconomic Factors Associated with Knowledge on Tuberculosis among Adults in Ethiopia

    PubMed Central

    Gelaw, Sifrash Meseret

    2016-01-01

    Background. Ethiopia is among highly tuberculosis affected countries. This might be related to low level of awareness on the disease in the population. The objective of the study was to determine the level of tuberculosis knowledge and socioeconomic factors associated with it. Methods. The 2011 Ethiopia health and demographic survey data were used. Overall tuberculosis knowledge score was computed to evaluate the outcome variable. Multivariable logistic regression was employed to identify independent socioeconomic factors associated with low tuberculosis knowledge. Results. The overall tuberculosis knowledge was low, 44.05% (95% CI: 42.05–46.24%) among women and 32.3% (95% CI: 30.34–34.32%) among men. Rural women (AOR = 1.22) and youth, no formal education (women: AOR = 3.28, men: AOR = 7.42), attending only primary education (women: AOR = 1.95, men: AOR = 3.49), lowest wealth quintiles (women: AOR = 1.4, Men: AOR = 1.28), unskilled female manual workers (AOR = 4.15), female agricultural employee (AOR = 2.28), and lack of access to media (women: AOR = 1.52, men: AOR = 1.71) are significantly associated with low tuberculosis knowledge. Conclusion. The level of tuberculosis knowledge among adults in Ethiopia is low and varied by socioeconomic groups. Tuberculosis control programs should consider appropriate strategies for tuberculosis education, promotion, communication, and social mobilization to address the rural women, youths, the poor, less educated people, and unskilled workers. PMID:26949546

  3. Socioeconomic Factors Associated with Knowledge on Tuberculosis among Adults in Ethiopia.

    PubMed

    Gelaw, Sifrash Meseret

    2016-01-01

    Background. Ethiopia is among highly tuberculosis affected countries. This might be related to low level of awareness on the disease in the population. The objective of the study was to determine the level of tuberculosis knowledge and socioeconomic factors associated with it. Methods. The 2011 Ethiopia health and demographic survey data were used. Overall tuberculosis knowledge score was computed to evaluate the outcome variable. Multivariable logistic regression was employed to identify independent socioeconomic factors associated with low tuberculosis knowledge. Results. The overall tuberculosis knowledge was low, 44.05% (95% CI: 42.05-46.24%) among women and 32.3% (95% CI: 30.34-34.32%) among men. Rural women (AOR = 1.22) and youth, no formal education (women: AOR = 3.28, men: AOR = 7.42), attending only primary education (women: AOR = 1.95, men: AOR = 3.49), lowest wealth quintiles (women: AOR = 1.4, Men: AOR = 1.28), unskilled female manual workers (AOR = 4.15), female agricultural employee (AOR = 2.28), and lack of access to media (women: AOR = 1.52, men: AOR = 1.71) are significantly associated with low tuberculosis knowledge. Conclusion. The level of tuberculosis knowledge among adults in Ethiopia is low and varied by socioeconomic groups. Tuberculosis control programs should consider appropriate strategies for tuberculosis education, promotion, communication, and social mobilization to address the rural women, youths, the poor, less educated people, and unskilled workers. PMID:26949546

  4. 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 140TB 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

  5. Hysterosalpingographic appearances of female genital tract tuberculosis: part I. Fallopian tube.

    PubMed

    Ahmadi, Firoozeh; Zafarani, Fatemeh; Shahrzad, Gholam

    2014-01-01

    Female genital tuberculosis (TB) remains as a major cause of tubal obstruction leading to infertility, especially in developing countries. The global prevalence of genital tuberculosis has increased during the past two decades due to increasing acquired immunodeficiency syndrome (AIDS). Genital TB is commonly asymptomatic, and it is diagnosed during infertility investigations. Despite of recent advances in imaging tools, such as computerized tomography (CT) scan, magnetic resonance imaging (MRI) and ultrasongraphy, hysterosalpingography is still the standard screening test for evaluation of tubal infertility and a valuable tool for diagnosis of female genital tuberculosis. Tuberculosis gives rise to various appearances on hysterosalpingography (HSG) from non-specific changes to specific findings. The present pictorial review illustrates and describes specific and non-specific radiographic features of female genital tuberculosis in two parts. Part I presents specific findings of tuberculosis related to tubes such as "beaded tube", "golf club tube", "pipestem tube", "cobble stone tube" and "leopard skin tube". Part II describes adverse effects of tuberculosis on structure of endometrium and radiological specific findings such as "dwarfed" uterus with lymphatic intravasation and occluded tubes, "T-shaped" tuberculosis uterus, "pseudounicornuate" uterus and "Collar-stud abscess", which have not been encountered in the majority of non-tuberculosis cases. PMID:24520493

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

    PubMed Central

    Joint, T

    2000-01-01

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

  7. The Effect of HIV-Related Immunosuppression on the Risk of Tuberculosis Transmission to Household Contacts

    PubMed Central

    Huang, Chuan-Chin; Tchetgen, Eric Tchetgen; Becerra, Mercedes C.; Cohen, Ted; Hughes, Katherine C.; Zhang, Zibiao; Calderon, Roger; Yataco, Rosa; Contreras, Carmen; Galea, Jerome; Lecca, Leonid; Murray, Megan

    2014-01-01

    Background. Coinfection with human immunodeficiency virus (HIV) may modify the risk of transmitting tuberculosis. Some previous investigations suggest that patients coinfected with HIV and tuberculosis are less likely to transmit infection, whereas others do not support this conclusion. Here, we estimated the relative risk of tuberculosis transmission from coinfected patients compared to HIV-negative patients with tuberculosis. Methods. Between September 2009 and August 2012, we identified and enrolled 4841 household contacts of 1608 patients with drug-sensitive tuberculosis in Lima, Peru. We assessed the HIV status and CD4 counts of index patients, as well as other risk factors for infection specific to the index patient, the household, and the exposed individuals. Contacts underwent tuberculin skin testing to determine tuberculosis infection status. Results. After adjusting for covariates, we found that household contacts of HIV-infected tuberculosis patients with a CD4 count ≤250 cells/µL were less likely to be infected with tuberculosis (risk ratio = 0.49 [95% confidence interval, .24–.96]) than the contacts of HIV-negative tuberculosis patients. No children younger than 15 years who were exposed to HIV-positive patients with a CD4 count ≤250 cells/µL were infected with tuberculosis, compared to 22% of those exposed to non-HIV-infected patients. There was no significant difference in the risk of infection between contacts of HIV-infected index patients with CD4 counts >250 cells/µL and contacts of index patients who were not HIV-infected. Conclusions. We found a reduced risk of tuberculosis infection among the household contacts of patients with active tuberculosis who had advanced HIV-related immunosuppression, suggesting reduced transmission from these index patients. PMID:24368620

  8. 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

  9. [Surgery for thoracic tuberculosis].

    PubMed

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

    2015-01-01

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

  10. Comparative proteomic analysis of sequential isolates of Mycobacterium tuberculosis from a patient with pulmonary tuberculosis turning from drug sensitive to multidrug resistant

    PubMed Central

    Singh, Amit; Gopinath, Krishnamoorthy; Sharma, Prashant; Bisht, Deepa; Sharma, Pawan; Singh, Niti; Singh, Sarman

    2015-01-01

    Background & objectives: Tuberculosis is a major health problem in India, and the emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis (Mtb) has further complicated the situation. Though several studies characterizing drug sensitive and drug resistant strains are available in literature, almost all studies are done on unrelated strains. Therefore, the objective of this study was to compare the proteomic data of four sequential isolates of Mtb from a single patient who developed MDR-TB during the course of anti-tuberculosis therapy (ATT). Methods: In this study, using two-dimensional (2D) gel electrophoresis and MALDI-TOF mass spectrometry, we compared and analyzed the cell lysate proteins of Mtb sequential clinical isolates from a patient undergoing anti-TB treatment. The mRNA expression levels of selected identified proteins were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The genotypes of all four isolates remained homologous, indicating no re-infection. The initial isolate (before treatment) was sensitive to all first-line drugs, but the consecutive isolates were found to be resistant to isoniazid (INH) and rifampicin (RIF) and developed mutations in the katG, inhA and rpoB. The intensities of 27 protein spots were found to be consistently overexpressed in INH and RIF resistant isolates. The most prominent and overexpressed proteins found during the development of drug resistance were GarA (Rv1827), wag31 (Rv2145c), Rv1437 and Rv2970c. Interpretation & conclusions: This preliminary proteomic study provides an insight about the proteins that are upregulated during drug resistance development. These upregulated proteins, identified here, could prove useful as immunodiagnostic and possibly drug resistant markers in future. However, more studies are required to confirm these findings. PMID:25857493

  11. A Mycobacterial Perspective on Tuberculosis in West Africa: Significant Geographical Variation of M. africanum and Other M. tuberculosis Complex Lineages

    PubMed Central

    Gehre, Florian; Kumar, Samrat; Kendall, Lindsay; Ejo, Mebrat; Secka, Oumie; Ofori-Anyinam, Boatema; Abatih, Emmanuel; Antonio, Martin; Berkvens, Dirk; de Jong, Bouke C.

    2016-01-01

    Background Phylogenetically distinct Mycobacterium tuberculosis lineages differ in their phenotypes and pathogenicity. Consequently, understanding mycobacterial population structures phylogeographically is essential for design, interpretation and generalizability of clinical trials. Comprehensive efforts are lacking to date to establish the West African mycobacterial population structure on a sub-continental scale, which has diagnostic implications and can inform the design of clinical TB trials. Methodology/Principal Findings We collated novel and published genotyping (spoligotyping) data and classified spoligotypes into mycobacterial lineages/families using TBLineage and Spotclust, followed by phylogeographic analyses using statistics (logistic regression) and lineage axis plot analysis in GenGIS, in which a phylogenetic tree constructed in MIRU-VNTRplus was analysed. Combining spoligotyping data from 16 previously published studies with novel data from The Gambia, we obtained a total of 3580 isolates from 12 countries and identified 6 lineages comprising 32 families. By using stringent analytical tools we demonstrate for the first time a significant phylogeographic separation between western and eastern West Africa not only of the two M. africanum (West Africa 1 and 2) but also of several major M. tuberculosis sensu stricto families, such as LAM10 and Haarlem 3. Moreover, in a longitudinal logistic regression analysis for grouped data we showed that M. africanum West Africa 2 remains a persistent health concern. Conclusions/Significance Because of the geographical divide of the mycobacterial populations in West Africa, individual research findings from one country cannot be generalized across the whole region. The unequal geographical family distribution should be considered in placement and design of future clinical trials in West Africa. PMID:26964059

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

    PubMed Central

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

    2015-01-01

    Background Monitoring tuberculosis (TB) treatment response remains challenging due to lack of reliable laboratory markers. In recent years, increased efforts have been exerted toward development of new biomarkers reflecting treatment response appropriately. While performance of interferon-gamma release assays (IGRAs) to monitor anti-TB treatment has been extensively evaluated, there is no data about post-treatment changes in Mycobacterium tuberculosis (MTB) antigen-stimulated tumor necrosis factor-alpha (TNF-α) release in active TB patients. Herein, we explored whether the MTB antigen-stimulated TNF-α release would be useful for monitoring responses to anti-TB treatment. Methods We compared unstimulated (TNF-αNil), MTB antigen-stimulated (TNF-αAg), and MTB antigen-stimulated minus unstimulated TNF-α levels (TNF-αAg-Nil) in supernatants from QuantiFERON-TB Gold In-Tube tests before and after treatment in 16 active TB patients, 25 latent TB infection (LTBI) subjects, and 10 healthy controls (HC). Results TNF-αAg and TNF-αAg-Nil levels decreased significantly after treatment in patients with active TB. In addition, TNF-αNil, TNF-αAg, and TNF-αAg-Nil levels were significantly higher in untreated active TB patients compared to LTBI subjects and HC. Conclusions This finding cautiously suggests that MTB Ag-stimulated TNF-α response may be a potential adjunctive marker for monitoring treatment response in active TB patients. PMID:26101647

  13. Oral tuberculosis involving maxillary gingiva

    PubMed Central

    Jaiswal, Rohit; Singh, Anil; Badni, Manjunath; Singh, Priyanka

    2011-01-01

    Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis, which is transmitted by aerosolized saliva droplets among individuals in close contact with expelled sputum of a diseased patient. However, TB lesions of the oral cavity are often overlooked in the differential diagnosis. We report here a case of tuberculosis of oral cavity affecting the gingiva of a 24-year-old male. PMID:22639508

  14. [Treatment of tuberculosis : Current standards].

    PubMed

    Schaberg, T

    2015-12-01

    The treatment of drug-sensitive tuberculosis consists of 2months of isoniazid, rifampin, pyrazinamide and ethambutol, followed by 4months of isoniazid and rifampin. These drugs are well tolerated and cure rate are above 95?%. In contrast the treatment of drug-resistent tuberculosis is difficult, mostly due to side effects of the drugs used under these circumstances. Therefore, any treatment of drug-resistant tuberculosis has to be done by experts. PMID:26631087

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2006-01-01

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

  17. Does Non-Central Nervous System Tuberculosis Increase the Risk of Ischemic Stroke? A Population-Based Propensity Score-Matched Follow-Up Study

    PubMed Central

    Wu, Chueh-Hung; Chen, Li-Sheng; Yen, Ming-Fang; Chiu, Yueh-Hsia; Fann, Ching-Yuan; Chen, Hsiu-Hsi; Pan, Shin-Liang

    2014-01-01

    Background Previous studies on the association between tuberculosis and the risk of developing ischemic stroke have generated inconsistent results. We therefore performed a population-based, propensity score-matched longitudinal follow-up study to investigate whether contracting non-central nervous system (CNS) tuberculosis leads to an increased risk of ischemic stroke. Methods We used a logistic regression model that includes age, sex, pre-existing comorbidities and socioeconomic status as covariates to compute the propensity score. A total of 5804 persons with at least three ambulatory visits in 2001 with the principal diagnosis of non-CNS tuberculosis were enrolled in the tuberculosis group. The non-tuberculosis group consisted of 5804, propensity score-matched subjects without tuberculosis. The three-year ischemic stroke-free survival rates for these 2 groups were estimated using the Kaplan-Meier method. The stratified Cox proportional hazards regression was used to estimate the effect of tuberculosis on the occurrence of ischemic stroke. Results During three-year follow-up, 176 subjects in the tuberculosis group (3.0%) and 207 in the non-tuberculosis group (3.6%) had ischemic stroke. The hazard ratio for developing ischemic stroke in the tuberculosis group was 0.92 compared to the non-tuberculosis group (95% confidence interval: 0.73–1.14, P = 0.4299). Conclusions Non-CNS tuberculosis does not increase the risk of subsequent ischemic stroke. PMID:25048551

  18. Mycobacterium tuberculosis and Mycobacterium africanum in Stools from Children in an Immunization Clinic in Ibadan, Nigeria

    PubMed Central

    CADMUS, SIB; JENKINS, AO; GODFROID, J; OSINUSI, K; ADEWOLE, IF; MURPHY, RL; TAIWO, BO

    2010-01-01

    Background Tuberculosis is a major cause of childhood morbidity and mortality in Nigeria. Diagnosis of childhood tuberculosis is a global challenge making early treatment a mirage. We investigated the stool of children for the presence of mycobacteria Methods Stool samples from children aged 3 days to 3 years who presented for postnatal immunization at a large university-based clinic in Nigeria were subjected to Ziehl-Neelsen staining. Samples with acid-fast bacilli were further processed using mycobacterial culture, spoligotyping and deletion typing. Results 192 stool samples from different children were collected and processed. Thirty (15.6%) had acid-fast bacilli. Of these, 8/30 had Mycobacterium tuberculosis and 1/30 had M. africanum. Conclusions About 5 percent (9/192) of apparently well children had evidence of potentially serious tuberculosis infection. The usefulness of stool specimens for diagnosing pediatric tuberculosis warrants further investigation. PMID:19188084

  19. 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

  20. 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; Knig, Claudia; Ammerman, Nicole C; Barrio, Mara Beln; Borchers, Kai; Bordon-Pallier, Florence; Brnstrup, 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; Mller, Rolf

    2015-06-01

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

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

    PubMed Central

    2010-01-01

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

  2. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis.

    PubMed

    Gagneux, Sebastien; Long, Clara Davis; Small, Peter M; Van, Tran; Schoolnik, Gary K; Bohannan, Brendan J M

    2006-06-30

    Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates. PMID:16809538

  3. 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

  4. 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

  5. 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

  6. Endotracheal tuberculosis with obstruction.

    PubMed

    Uar, Yildiz; Szener, Zeynep Celebi; Karnak, Demet

    2010-05-01

    Endotracheal involvement of tuberculosis (TB), a type of endobronchial TB, is defined as granulomatous infection of the tracheobronchial tree. We present the case of a 33 year-old female agriculture engineer with endotracheal tuberculosis (ETTB). It was treated successfully with prompt long-course antituberculous medication without complications or need for endotracheal intervention. This unusual case of ETTB, diagnosed promptly by fiberoptic bronchoscopy, and microbiological studies, is presented to emphasize the importance of macroscopic recognition to start anti-TB therapy in cases with significant airway obstruction. This case is important for countries where the various presentations of TB are encountered as well as in countries where TB is not endemic. PMID:20578548

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

    PubMed Central

    2013-01-01

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

  8. Diagnostic Utility of QuantiFERON-TB Gold (QFT-G) in Active Pulmonary Tuberculosis

    PubMed Central

    Anwar, Ahmed; Hamdan, AL-Jahdali; Salim, Baharoon; Yosra, Ali; Hani, Mohamed; Abdullah, AL-Harbi

    2015-01-01

    Background: The utility of QuantiFERON-TB Gold In-Tube (QFT-G) test in the diagnosis of tuberculosis disease has been validated in high and low tuberculosis-prevalent (TB) countries. Aim: The aim of this study is to assess the performance of the QFT-G test in the diagnosis of tuberculosis disease among tuberculosis patients in an intermediate prevalent country. Setting and Design: A retrospective study at the King Abdulaziz Medical City-Riyadh (KAMC-R) Materials and Methods: We retrospectively reviewed all the patients with a diagnosis of pneumonia, including tuberculosis, admitted to KAMC-R between 1 January 2009 and 31 December 2013. We included only patients with an available result of the QFT-G test. A total of 142 tuberculosis cases and 226 pneumonia cases were studied, to assess the utility of the QFT-G test in diagnosing tuberculosis cases. Results: Among the tuberculosis (n = 142) cases, the QFT-G tested positive in 68.3%, negative in 23.2%, and indeterminate in 12 cases (8.5%). Of the 226 pneumonia cases, the QFT-G tested positive in only 20.4%, while a majority of 66.4% tested negative, with 30 cases (13.3%) being indeterminate. When we excluded 42 patients with indeterminate results, the QFT-G test achieved a sensitivity of 74.6% [95% CI: 66.09 to 81.65%] and specificity of 76.53 % [95% CI: 69.85 to 82.15%] in the diagnosis of tuberculosis cases. Conclusions: This study concludes that the QFT-G test is a useful tool for detecting tuberculosis disease when used as an adjunct tool for the diagnosis of active TB cases. It certainly cannot be used solely and indiscriminately, separate from other clinical and radiological information, in the diagnosis of active tuberculosis cases. PMID:26392718

  9. Epidemiological basis of tuberculosis eradication in an advanced country

    PubMed Central

    Groth-Petersen, E.; Knudsen, Jrgen; 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

  10. Genetic polymorphisms in TNF genes and tuberculosis in North Indians

    PubMed Central

    2010-01-01

    Background Pulmonary tuberculosis, the most common clinical form of mycobacterial diseases, is a granulomatous disease of the lungs caused by Mycobaterium tuberculosis. A number of genes have been identified in studies of diverse origins to be important in tuberculosis. Of these, both tumor necrosis factor ? (TNF-?) and lymphotoxin ? (LT-?) play important immunoregulatory roles. Methods To investigate the association of TNF polymorphisms with tuberculosis in the Asian Indians, we genotyped five potentially functional promoter polymorphisms in the TNFA gene and a LTA_NcoI polymorphism (+252 position) of the LTA gene in a clinically well-defined cohort of North-Indian patients with tuberculosis (N = 185) and their regional controls (N = 155). Serum TNF-? (sTNF-?) levels were measured and correlated with genotypes and haplotypes. Results The comparison of the allele frequencies for the various loci investigated revealed no significant differences between the tuberculosis patients and controls. Also, when the patients were sub-grouped into minimal, moderately advanced and far advanced disease on the basis of chest radiographs, TST and the presence/absence of cavitary lesions, none of the polymorphisms showed a significant association with any of the patient sub-groups. Although a significant difference was observed in the serum TNF-? levels in the patients and the controls, none of the investigated polymorphisms were found to affect the sTNF-? levels. Interestingly, it was observed that patients with minimal severity were associated with lower log sTNF-? levels when compared to the patients with moderately advanced and far advanced severity. However, none of these differences were found to be statistically significant. Furthermore, when haplotypes were analyzed, no significant difference was observed. Conclusions Thus, our findings exclude the TNF genes as major risk factor for tuberculosis in the North Indians. PMID:20537163

  11. Selection of Nucleic Acid Aptamers Specific for Mycobacterium tuberculosis.

    PubMed

    Mozioglu, Erkan; Gokmen, Ozgur; Tamerler, Candan; Kocagoz, Zuhtu Tanil; Akgoz, Muslum

    2016-02-01

    Tuberculosis (TB) remains to be a major global health problem, with about 9 million new cases and 1.4 million deaths in 2011. For the control of tuberculosis as well as other infectious diseases, WHO recommended "ASSURED" (Affordable, Sensitive, Specific, User-friendly, Rapid and robust, Equipment-free, and Deliverable to the end user) diagnostic tools that can easily be maintained and used in developing countries. Aptamers are promising tools for developing point-of-care diagnostic assays for TB. In this study, ssDNA aptamers that recognize Mycobacterium tuberculosis H37Ra were selected by systematic evolution of ligands by exponential enrichment (SELEX). For this purpose, two different selection protocols, ultrafiltration and centrifugation, were applied. A total of 21 TB specific aptamers were selected. These aptamers exhibited "G-rich" regions on the 3' terminus of the aptamers, including a motif of "TGGGG," "GTGG," or "CTGG." Binding capability of selected aptamers were investigated by quantitative PCR and Mtb36 DNA aptamer was found the most specific aptamer to M. tuberculosis H37Ra. The dissociation constant (K d) of Mtb36 aptamer was calculated as 5.09 ± 1.43 nM in 95 % confidence interval. Relative binding ratio of Mtb36 aptamer to M. tuberculosis H37Ra over Mycobacterium bovis and Escherichia coli was also determined about 4 times and 70 times more, respectively. Mtb36 aptamer is highly selective for M. tuberculosis, and it can be used in an aptamer-based biosensor for the detection of M. tuberculosis. PMID:26541162

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

    PubMed Central

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

    2005-01-01

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

  13. CT of abdominal tuberculosis.

    PubMed

    Epstein, B M; Mann, J H

    1982-11-01

    Intraabdominal tuberculosis (TB) presents with a wide variety of clinical and radiologic features. Besides the reported computed tomographic (CT) finding of high-density ascites in tuberculous peritonitis, this report describes additional CT features highly suggestive of abdominal tuberculosis in eight cases: (1)irregular soft-tissue densities in the omental area; (2) low-density masses surrounded by thick solid rims; (3) a disorganized appearance of soft-tissue densities, fluid, and bowel loops forming a disorganized appearance of soft-tissue densities, fluid, and bowel loops forming a poorly defined mass; (4) low-density lymph nodes with a multilocular appearance after intravenous contrast administration; and (5) possibly high-density ascites. The differential diagnosis of these features include lymphoma, various forms of peritonitis, peritoneal carcinomatosis, and peritoneal mesothelioma. It is important that the CT features of intraabdominal tuberculosis be recognized in order that laparotomy be avoided and less invasive procedures (e.g., laparoscopy, biopsy, or a trail of antituberculous therapy) be instituted. PMID:6981966

  14. Safety and effectiveness of HAART in tuberculosis-HIV co-infected patients in Brazil

    PubMed Central

    dos Santos, A. P. G.; Pacheco, A. G.; Staviack, A.; Golub, J. E.; Chaisson, R. E.; Rolla, V. C.; Kritski, A. L.; Passos, S. R. L.; de Queiroz Mello, F. C.

    2013-01-01

    SUMMARY BACKGROUND Antiretroviral therapy (ART) significantly reduces tuberculosis (TB) incidence among persons with human immunodeficiency virus (HIV), but the safety and effectiveness of concomitant treatment for both diseases remain unclear. OBJECTIVE To evaluate the impact of ART and anti-tuberculosis treatment on survival and risk of adverse events (AE) among co-infected individuals. METHODS In a retrospective cohort study, clinical data were collected from 618 TB-HIV patients treated with rifampin, isoniazid and pyrazinamide ethambutol between 1 January 1995 and 31 December 2003. Patients were categorized into two groups: highly active ART (HAART) or no ART. Different HAART regimens were evaluated. Bivariate analysis, multivariate logistic regression and survival analysis using Cox proportional hazards regression were used. RESULTS One-year mortality was lower for patients receiving HAART (adjusted hazard ratio [aHR] 0.17, 95%CI 0.090.31) compared to no ART. HAART increased the risk of AE (aHR 2.08, 95%CI 1.293.36). The odds of AE when receiving a ritonavir + saquinavir HAART regimen was eight-fold higher compared to no ART (OR 8.31, 95%CI 3.0422.69), while efavirenz-based HAART was not associated with a significantly increased risk of AE (OR 1.42, 95%CI 0.762.65). CONCLUSION HIV patients with TB have significantly better survival if they receive HAART during anti-tuberculosis treatment. Efavirenz-based HAART is associated with fewer AEs than protease inhibitor-based HAART. PMID:23317954

  15. 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

  16. 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

  17. Mycobacterium tuberculosis infection in a HIV-positive patient

    PubMed Central

    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

  18. Ghost Remains After Black Hole Eruption

    NASA Astrophysics Data System (ADS)

    2009-05-01

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

  19. Vitamin D and solar ultraviolet radiation in the risk and treatment of tuberculosis.

    PubMed

    Ralph, Anna P; Ralph, Anna R; Lucas, Robyn M; Norval, Mary

    2013-01-01

    Improved understanding of the association between tuberculosis and vitamin D is needed to inform clinical practice. Vitamin D has both immunostimulatory and immunosuppressive effects relevant to human antimycobacterial responses. Ultraviolet radiation, the main source of vitamin D, also induces immunomodulation and could affect the relation between vitamin D and tuberculosis. Clinical trials of vitamin D supplementation in patients with tuberculosis have produced largely negative results, prompting the review of dosing regimens-an explanation for low 25-hydroxyvitamin D status in patients with active tuberculosis is also needed. The reporting of vitamin D deficiency needs to address assay inaccuracies, rising thresholds to define sufficiency, and scarce knowledge of the concentrations needed for optimum immune responses. Future research to measure the effect of the inflammatory setting on serum concentrations of 25-hydroxyvitamin D, at tuberculosis diagnosis and during recovery, could help to account for 25-hydroxyvitamin D changes in these concentrations in patients with tuberculosis. Studies into the role of vitamin D supplementation in latent tuberculosis justify clinical trials in this population, but pose methodological challenges. Vitamin D trials in patients with active tuberculosis should be done in well selected populations using adequate vitamin D doses, although such doses remain undefined. PMID:23257233

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

    PubMed

    Raviglione, Mario; Marais, Ben; Floyd, Katherine; Lnnroth, 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

  1. The Assessment of Viability of M. Tuberculosis after Exposure to CPC Using Different Methods

    PubMed Central

    Sekar, Gomathi; Lakshmi, R.; Selvakumar, N.

    2014-01-01

    Settings. National Institute for Research in Tuberculosis, Chennai. Objective. To assess the proportion of metabolically active cells of Mycobacterium tuberculosis after exposed to CPC using FDA-EB vital staining and viable counts on LJ medium. Mycolic acid content in M. tuberculosis after exposure to CPC was estimated using HPLC. Methods. Clinical isolates of M. tuberculosis and standard reference strain M. tuberculosis H37Rv were used for FDA-EB, viable count, and HPLC. Results. FDA/EB consistently stained 7090% of log phase cells as green and the remaining cells as red-orange. After CPC treatment, 6570% of the cells stained red-orange. The viability counts were comparable to 0-day controls. Synthesis of mycolic acids in mycobacteria was reduced when exposed to CPC using HPLC due to the decreased metabolic activity of the organisms. Conclusion. The cells are metabolically inactive during storage with CPC but these cells grew well on LJ medium after removal of CPC. The viability of M. tuberculosis was maintained in CPC with minimal reduction. Mycolic acid content was reduced if the cells of M. tuberculosis were treated with CPC for 7 days. All the above findings provide yet another evidence for the damage of cell wall of M. tuberculosis. PMID:26904736

  2. 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. This study explores the potential of mHealth to support DOTS strategy. It will gather new evidence on the effectiveness of mHealth-based interventions and SMS reminders in the improvement of treatment adherence and the cure rate of tuberculosis patients, especially in a low-resource country such as Cameroon. Trial registration The trial is registered on the Pan-African Clinical Trials Registry (http://www.pactr.org) under unique identification number: PACTR201307000583416. PMID:24460827

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

    PubMed Central

    Sanjuan-Jimenez, Rocio; Morata, Pilar; Bermdez, Pilar; Bravo, M. Jos; Colmenero, Juan D.

    2013-01-01

    Background Both brucellosis and tuberculosis are chronic-debilitating systemic granulomatous diseases with a high incidence in many countries in Africa, Central and South America, the Middle East and the Indian subcontinent. Certain focal complications of brucellosis and extrapulmonary tuberculosis are very difficult to differentiate clinically, biologically and radiologically. As the conventional microbiological methods for the diagnosis of the two diseases have many limitations, as well as being time-consuming, multiplex real time PCR (M RT-PCR) could be a promising and practical approach to hasten the differential diagnosis and improve prognosis. Methodology/Principal Findings We designed a SYBR Green single-tube multiplex real-time PCR protocol targeting bcsp31 and the IS711 sequence detecting all pathogenic species and biovars of Brucella genus, the IS6110 sequence detecting Mycobacterium genus, and the intergenic region senX3-regX3 specifically detecting Mycobacterium tuberculosis complex. The diagnostic yield of the M RT-PCR with the three pairs of resultant amplicons was then analyzed in 91 clinical samples corresponding to 30 patients with focal complications of brucellosis, 24 patients with extrapulmonary tuberculosis, and 36 patients (Control Group) with different infectious, autoimmune or neoplastic diseases. Thirty-five patients had vertebral osteomyelitis, 21 subacute or chronic meningitis or meningoencephalitis, 13 liver or splenic abscess, eight orchiepididymitis, seven subacute or chronic arthritis, and the remaining seven samples were from different locations. Of the three pairs of amplicons (senX3-regX3+ bcsp3, senX3-regX3+ IS711 and IS6110+ IS711) only senX3-regX3+ IS711 was 100% specific for both the Brucella genus and M. tuberculosis complex. For all the clinical samples studied, the overall sensitivity, specificity, and positive and negative predictive values of the M RT-PCR assay were 89.1%, 100%, 85.7% and 100%, respectively, with an accuracy of 93.4%, (95% CI, 88.396.5%). Conclusions/Significance In this study, a M RT-PCR strategy with species-specific primers based on senX3-regX3+IS711 sequences proved to be a sensitive and specific test, useful for the highly efficient detection of M. tuberculosis and Brucella spp in very different clinical samples. It thus represents an advance in the differential diagnosis between some forms of extrapulmonary tuberculosis and focal complications of brucellosis. PMID:24349599

  4. Noninvasive Test for Tuberculosis Detection among Primates

    PubMed Central

    Mugisha, Lawrence; Shoyama, Fernanda Miyagaki; OMalley, 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

  5. Diseases masking and delaying the diagnosis of urogenital tuberculosis.

    PubMed

    Kulchavenya, Ekaterina; Kholtobin, Denis

    2015-12-01

    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

  6. Recombinant reporter assay using transcriptional machinery of Mycobacterium tuberculosis.

    PubMed

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

    2015-02-01

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

  7. 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

  8. Tuberculosis of the pubic symphysis

    PubMed Central

    Gothwal, Sudarshan; Varshney, Peeyush; Mathur, Shivank; Songra, Bhupen

    2014-01-01

    Tuberculosis is one of India’s public health problems. It involves various systems of the body, including the skeletal system. Osteoarticular tuberculosis is the second most common form of extrapulmonary tuberculosis next to lymph nodes and constitutes about 13% of all extrapulmonary cases. It is generally accepted that osteoarticular tuberculosis is the result of a haematogenous or lymphatic spread from a reactivated latent focus, usually pulmonary; however, previous infection is not always encountered, and in only 40–50% of the cases, it is possible to demonstrate another active infection site. The commonest site for skeletal tuberculosis is the spine followed by the hip, knee and ankle joints. Tuberculosis can involve literally any bone or joint. Pubic symphysis is an uncommon site for tuberculosis in the case of the skeletal system. We present a rare case of pubic symphysis tuberculosis in a 25-year-old woman presented to the general surgical department with a swelling in the right thigh region. PMID:24515233

  9. 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. PMID:26890215

  10. Where do those remains come from?

    PubMed

    Nociarov, Dominika; Adserias, M Jose; Malgosa, Assumpci; Galts, Ignasi

    2014-10-14

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

  11. Integrated surveillance of pulmonary tuberculosis and paragonimiasis in Zamboanga del Norte, the Philippines

    PubMed Central

    Belizario, Vicente; Totanes, Francis Isidore; Asuncion, Camille Ann; Leon, Winifreda De; Jorge, Manuel; Ang, Concepcion; Naig, June Rose

    2014-01-01

    Background Pulmonary tuberculosis (PTB) and paragonimiasis remain as health problems in certain areas in the Philippines. Both share similar clinical manifestations, which include chronic productive cough, hemoptysis, dyspnea, fever, weight loss, and night sweats. This study aimed to determine the prevalence of PTB, paragonimiasis, and co-infections in Zamboanga del Norte, Philippines. Methods This study was conducted in selected villages in two municipalities in Zamboanga del Norte. Patients with chronic cough were interviewed, examined, and requested to submit two sputum samples which were processed using ZiehlNeelsen method to detect acid-fast bacilli (AFB), and NaOH concentration technique for the detection of Paragonimus ova. Results A total of 836 patients submitted sputum samples for examination. Prevalence was 6.7% (2.512.7%) for paragonimiasis and 1.9% (0.96.3%) for PTB. Co-infection rate was 0.3%, with two identified cases. Positivity rates for males and females were 9.6 and 5.8% for paragonimiasis and 3.4 and 1.2% for PTB. Conclusion Pulmonary tuberculosis and paragonimiasis are co-endemic in Zamboanga del Norte, suggesting the need to integrate surveillance and control efforts. Strengthening local health systems through collaboration between different sectors is recommended for effective disease control. Development of more sensitive diagnostic tests is important for more accurate disease surveillance. PMID:24601907

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

    PubMed Central

    Qadeer, Ejaz; Mrkve, Odd

    2013-01-01

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

  13. Tuberculosis on the flight deck.

    PubMed

    Parmet, A J

    1999-08-01

    Tuberculosis in commercial aircraft has been a concern since a 1995 incident of possible transmission from an active case of tuberculosis to passengers in the cabin of a 747. Subsequently, commercial air carriers have been vigilant in cooperating with public health authorities in tracking all known exposures to tuberculosis. In 1998, a pilot of a commercial airliner was diagnosed with active tuberculosis. Company records demonstrated that in the previous 6 mo, the pilot had flown with 48 other pilots. Every exposed pilot was contacted and evaluated by skin testing (IPPD) or chest x-ray if previously positive. There were no skin test conversions and no changes on x-rays. This study demonstrates that transmission of tuberculosis in the aircraft cabin environment, even under close and continuous exposure to an active case, is a rare event. PMID:10447057

  14. 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. PMID:26458772

  15. 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. PMID:26409279

  16. 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

  17. Paraspinal tuberculosis mimicking malignancy.

    PubMed

    Alherabi, Ameen Z; Marglani, Osama A; Gazzaz, Malak J; Abbas, Mohammed M

    2013-12-01

    Tuberculosis (TB) of the paraspinal muscles is a rare clinical entity. We present a case of an 18-year-old, Saudi male patient presenting with the clinical picture of a paraspinal mass that turned out to be paraspinal TB. It originated from the paraspinal tissues and muscles, and invaded the C6 and C7 vertebrae. Initially, it was highly suspicious for malignancy. A biopsy confirmed the diagnosis of TB, and the patient was treated successfully with anti-TB therapy. It is important to be aware that paraspinal TB can mimic malignancy. PMID:24343472

  18. 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.

  19. Tuberculosis mimicking lung cancer

    PubMed Central

    Hammen, I.

    2015-01-01

    Tuberculosis (TB) is well known as a diagnostic chameleon and can resemble malignancy. In thorax TB can be manifested as pulmonary infiltrates and/or mediastinal lymphadenopathy. In low incident countries with high incidence of lung cancer and varying clinical presentations, TB often gets misdiagnosed with the result of delayed treatment start and unnecessary diagnostic procedures. Our case report presents two patients, who were referred to the Thorax diagnostic centre at the Department of Respiratory Medicine, Odense University Hospital, with presumptive diagnosis of neoplasm and had proved lung TB with no evidence of malignancy instead. In the first case diagnosis was confirmed after thoracotomy, in the second case after bronchoscopy. PMID:26744652

  20. Tuberculosis mimicking lung cancer.

    PubMed

    Hammen, I

    2015-01-01

    Tuberculosis (TB) is well known as a diagnostic chameleon and can resemble malignancy. In thorax TB can be manifested as pulmonary infiltrates and/or mediastinal lymphadenopathy. In low incident countries with high incidence of lung cancer and varying clinical presentations, TB often gets misdiagnosed with the result of delayed treatment start and unnecessary diagnostic procedures. Our case report presents two patients, who were referred to the Thorax diagnostic centre at the Department of Respiratory Medicine, Odense University Hospital, with presumptive diagnosis of neoplasm and had proved lung TB with no evidence of malignancy instead. In the first case diagnosis was confirmed after thoracotomy, in the second case after bronchoscopy. PMID:26744652

  1. Ability of PCR assay to identify Mycobacterium tuberculosis in BACTEC 12B vials.

    PubMed

    Forbes, B A; Hicks, K E

    1994-07-01

    Introduction of PCR to directly detect Mycobacterium tuberculosis in clinical specimens has shown promise; however, interfering substances in clinical material have contributed to lowered assay sensitivities. We evaluated the ability of a PCR assay to detect M. tuberculosis in BACTEC 12B broth cultures. Clinical specimens were processed and inoculated into BACTEC 12B vials. Evaluation was approached in two phases, starting with an initial evaluation in which an aliquot of 12B broth was removed when the growth index (GI) was > or = 10 and stored at 4 degrees C until assayed by PCR. Of the 290 specimens initially assayed, 129 were culture negative for mycobacteria as well as PCR negative for M. tuberculosis. Except for one, cultures (n = 102) which grew mycobacteria other than M. tuberculosis were all PCR negative. The remaining 59 broths were all culture and PCR positive for M. tuberculosis; 39% (n = 23) of these cultures when assayed by PCR had GIs of < or = 50. Following initial evaluation, 200 12B BACTEC vials with GIs of > or = 10 were assayed in a similar manner except that specimens were amplified twice weekly to determine PCR's impact on the length of time to identification of M. tuberculosis as compared with standard laboratory practices. Utilization of PCR resulted in a mean time to detection of M. tuberculosis of 14 days, compared with 29 days by using commercially available nucleic acid probes to identify M. tuberculosis complex from growth of BACTEC 12B subcultures on solid media. In light of an overall sensitivity and specificity of 100 and 99.7%, respectively, coupled with the ability to identify M. tuberculosis days or weeks before other methods can be applied, we conclude that PCR might prove to be a rapid alternative for identification of M. tuberculosis in culture and allow for earlier setup of susceptibility testing. PMID:7929765

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

    PubMed

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

    2014-01-01

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

  3. Phagosomal Rupture by Mycobacterium tuberculosis Results in Toxicity and Host Cell Death

    PubMed Central

    Lippmann, Juliane; Bitter, Wilbert; Majlessi, Laleh; Brosch, Roland; Enninga, Jost

    2012-01-01

    Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting cells are still under debate. To get novel insights into this matter, we used a single-cell fluorescence resonance energy transfer (FRET)-based method to investigate the potential cytosolic access of M. tuberculosis and the resulting cellular consequences in an unbiased, quantitative way. Analysis of thousands of THP-1 macrophages infected with selected wild-type or mutant strains of the M. tuberculosis complex unambiguously showed that M. tuberculosis induced a change in the FRET signal after 3 to 4 days of infection, indicating phagolysosomal rupture and cytosolic access. These effects were not seen for the strains M. tuberculosisΔRD1 or BCG, both lacking the ESX-1 secreted protein ESAT-6, which reportedly shows membrane-lysing properties. Complementation of these strains with the ESX-1 secretion system of M. tuberculosis restored the ability to cause phagolysosomal rupture. In addition, control experiments with the fish pathogen Mycobacterium marinum showed phagolysosomal translocation only for ESX-1 intact strains, further validating our experimental approach. Most importantly, for M. tuberculosis as well as for M. marinum we observed that phagolysosomal rupture was followed by necrotic cell death of the infected macrophages, whereas ESX-1 deletion- or truncation-mutants that remained enclosed within phagolysosomal compartments did not induce such cytotoxicity. Hence, we provide a novel mechanism how ESX-1 competent, virulent M. tuberculosis and M. marinum strains induce host cell death and thereby escape innate host defenses and favor their spread to new cells. In this respect, our results also open new research directions in relation with the extracellular localization of M. tuberculosis inside necrotic lesions that can now be tackled from a completely new perspective. PMID:22319448

  4. 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

  5. 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

  6. Phage lysin to control the overgrowth of normal flora in processed sputum samples for the rapid and sensitive detection of Mycobacterium tuberculosis by luciferase reporter phage assay

    PubMed Central

    2013-01-01

    Background Phage lysin, extracted from three bacteriophages was used in place of antibiotics to control the overgrowth of normal flora in processed sputum samples leading to the sensitive detection of Mycobacterium tuberculosis using diagnostic luciferase reporter phage assay (DLRPA). Methods A total of 129 sputum samples were processed by modified Petroff’s method. Two Lowenstein Jensen slopes were inoculated from the processed sputum deposit thus obtained. The remaining deposits were transferred to 7 ml of Middlebrook 7H9 complete medium supplemented with phage lysin and incubated at 37°C. DLRPA was done using phAE129 at days 7, 9, 14 and 21. At the end of day 21, the samples were centrifuged and the pellets were inoculated on to 2 more LJ slopes to validate DLRPA results. Results The sensitivity and specificity of DLRPA in detecting M. tuberculosis from sputum specimens was 90% and 81% respectively compared to conventional LJ culture. The agreement between the methods was 87%. The rate of contamination for DLRPA using phage lysin was 9.3%. Conclusion Phage lysin can be used to decontaminate sputum samples for the detection of M. tuberculosis by DLRPA directly from processed sputum specimens. PMID:23356428

  7. The tuberculosis vaccine candidate Bacillus Calmette-Gurin ?ureC::hly coexpressing human interleukin-7 or -18 enhances antigen-specific T cell responses in mice.

    PubMed

    Rao, Martin; Vogelzang, Alexis; Kaiser, Peggy; Schuerer, Stefanie; Kaufmann, Stefan H E; Gengenbacher, Martin

    2013-01-01

    Bacillus Calmette-Gurin (BCG), the only approved tuberculosis vaccine, provides only limited protection. Previously, we generated a recombinant derivative (BCG ?ureC::hly), which secretes the pore-forming toxin listeriolysin O (LLO) of Listeria monocytogenes. This vaccine shows superior protection against tuberculosis in preclinical models and is safe in humans. Here we describe two new vaccine strains which express human interleukin-7 (hIL)-7 or hIL-18 in the genetic background of BCG ?ureC::hly to modulate specific T cell immunity. Both strains exhibited an uncompromised in vitro growth pattern, while inducing a proinflammatory cytokine profile in human dendritic cells (DCs). Human DCs harbouring either strain efficiently promoted secretion of IL-2 by autologous T cells in a coculture system, suggesting superior immunogenicity. BALB/c mice vaccinated with BCG ?ureC::hly, BCG ?ureC::hly_hIL7 or BCG ?ureC::hly_hIL18 developed a more robust Th1 response than after vaccination with parental BCG. Both strains provided significantly better protection than BCG in a murine Mycobacterium tuberculosis challenge model but efficacy remained comparable to that afforded by BCG ?ureC::hly. We conclude that expression of hIL-7 or hIL-18 enhanced specific T cell responses but failed to improve protection over BCG ?ureC::hly in mice. PMID:24236077

  8. Pulmonary tuberculosis in diabetes mellitus.

    PubMed

    Doost, J Y; Vessal, K

    1975-12-01

    In 217 patients with diabetes mellitus, 32 (14.7%) had also pleuropulmonary tuberculosis confirmed by bacteriologic or histologic means. Either unilateral or bilateral lower lobe involvement was seen in 20 patients (62.5%). Of these, 75% were febrile, the response to antituberculous drugs was slower than in patients with apical lesions. Confirmation of tuberculosis was also more difficult in patients with lower lobe disease. The prevalence of tuberculosis in diabetic patients must be considered and the disease should be especially suspected in diabetic patients with lower lobe lesions. PMID:1216313

  9. Whole genome sequencing of Mycobacterium tuberculosis reveals slow growth and low mutation rates during latent infections in humans.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

    Very little is known about the growth and mutation rates of Mycobacterium tuberculosis during latent infection in humans. However, studies in rhesus macaques have suggested that latent infections have mutation rates that are higher than that observed during active tuberculosis disease. Elevated mutation rates are presumed risk factors for the development of drug resistance. Therefore, the investigation of mutation rates during human latency is of high importance. We performed whole genome mutation analysis of M. tuberculosis isolates from a multi-decade tuberculosis outbreak of the New Zealand Rangipo strain. We used epidemiological and phylogenetic analysis to identify four cases of tuberculosis acquired from the same index case. Two of the tuberculosis cases occurred within two years of exposure and were classified as recently transmitted tuberculosis. Two other cases occurred more than 20 years after exposure and were classified as reactivation of latent M. tuberculosis infections. Mutation rates were compared between the two recently transmitted pairs versus the two latent pairs. Mean mutation rates assuming 20 hour generation times were 5.5X10?10 mutations/bp/generation for recently transmitted tuberculosis and 7.3X10?11 mutations/bp/generation for latent tuberculosis. Generation time versus mutation rate curves were also significantly higher for recently transmitted tuberculosis across all replication rates (p?=?0.006). Assuming identical replication and mutation rates among all isolates in the final two years before disease reactivation, the u20hr mutation rate attributable to the remaining latent period was 1.610?11 mutations/bp/generation, or approximately 30 fold less than that calculated during the two years immediately before disease. Mutations attributable to oxidative stress as might be caused by bacterial exposure to the host immune system were not increased in latent infections. In conclusion, we did not find any evidence to suggest elevated mutation rates during tuberculosis latency in humans, unlike the situation in rhesus macaques. PMID:24618815

  11. Clinical peculiarities of tuberculosis

    PubMed Central

    2014-01-01

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

  12. [Tuberculosis and traveling].

    PubMed

    2004-01-01

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

  13. Prevalence of tuberculosis in Faridabad district, Haryana State, India

    PubMed Central

    Sharma, S.K.; Goel, Ashish; Gupta, S.K.; Mohan, Krishna; Sreenivas, V.; Rai, S.K.; Singh, U.B.; Chauhan, L.S.

    2015-01-01

    Background & objectives: Epidemiological information on tuberculosis (TB) has always been vital for planning control strategies. It has now gained further importance for monitoring the impact of interventions to control the disease. The present study was done to estimate the prevalence of bacillary tuberculosis in the district of Faridabad in Haryana State of India among persons aged older than 15 years. Methods: In this cross-sectional study, residents of Faridabad district were assessed for the prevalence of tuberculosis. Twelve rural and 24 urban clusters with estimated populations of 41,106 and 64,827 individuals were selected for the study. Two sputum samples were collected from individuals found eligible for inclusion. The samples were also cultured by modified Petroff's method and were examined for growth of Mycobacterium tuberculosis once a week for eight weeks. A person found positive by smear and/or culture was identified as sputum-positive pulmonary TB positive. Results: A total of 105,202 subjects were enumerated in various clusters of the Faridabad district. There were 50,057 (47.58%) females and 55,145 (52.42%) males. Of these 98,599 (93.7%) were examined by the study group (47,976 females; 50,623 males). The overall prevalence of sputum smear or culture positive pulmonary tuberculosis in our study was found to be 101.4 per 100,000 population. Interpretation & conclusions: The present results showed that the prevalence of sputum positive pulmonary tuberculosis was higher in Faridabad district than the notification rates recorded by the World Health Organization for the contemporary period, a disparity that could be explained by a difference in case detection strategy employed for the study. PMID:25900959

  14. Allopatric tuberculosis hostpathogen relationships are associated with greater pulmonary impairment

    PubMed Central

    Pasipanodya, Jotam G.; Moonan, Patrick K.; Vecino, Edgar; Miller, Thaddeus L.; Fernandez, Michel; Slocum, Philip; Drewyer, Gerry; Weis, Stephen E.

    2015-01-01

    Background Host pathogen relationships can be classified as allopatric, when the pathogens originated from separate, non-overlapping geographic areas from the host; or sympatric, when host and pathogen shared a common ancestral geographic location. It remains unclear if hostpathogen relationships, as defined by phylogenetic lineage, influence clinical outcome. We sought to examine the association between allopatric and sympatric phylogenetic Mycobacterium tuberculosis lineages and pulmonary impairment after tuberculosis (PIAT). Methods Pulmonary function tests were performed on patients 16 years of age and older who had received ?20 weeks of treatment for culture-confirmed M. tuberculosis complex. Forced Expiratory Volume in 1 min (FEV1) ?80%, Forced Vital Capacity (FVC) ?80% and FEV1/FVC >70% of predicted were considered normal. Other results defined pulmonary impairment. Spoligotype and 12-locus mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) were used to assign phylogenetic lineage. PIAT severity was compared between hostpathogen relationships which were defined by geography and ethnic population. We used multivariate logistic regression modeling to calculate adjusted odds ratios (aOR) between phylogenetic lineage and PIAT. Results Self-reported continental ancestry was correlated with Mycobacterium. tuberculosis lineage (p < 0.001). In multivariate analyses adjusting for phylogenetic lineage, age and smoking, the overall aOR for subjects with allopatric hostpathogen relationships and PIAT was 1.8 (95% confidence interval [CI]: 1.1, 2.9) compared to sympatric relationships. Smoking >30 pack-years was also associated with PIAT (aOR: 3.2; 95% CI: 1.5, 7.2) relative to smoking <1 pack-years. Conclusions PIAT frequency and severity varies by hostpathogen relationship and heavy cigarette consumption, but not phylogenetic lineage alone. Patients who had disease resulting from allopatrichostpathogen relationship were more likely to have PIAT than patients with disease from sympatrichostpathogen relationship infection. Further study of this association may identify ways that treatment and preventive efforts can be tailored to specific lineages and racial/ethnic populations. PMID:23501297

  15. 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 T1T4) 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, 2734%). There were no individual-level risk factors for clustering, apart from borderline evidence for being nonSouth 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

  16. 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

  17. Association between HIV/AIDS and Multi-Drug Resistance Tuberculosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Mesfin, Yonatan Moges; Hailemariam, Damen; Biadglign, Sibhatu; Kibret, Kelemu Tilahun

    2014-01-01

    Background Human immunodeficiency virus (HIV), multi-drug resistant tuberculosis (MDR) is emerging as major challenge facing tuberculosis control programs worldwide particularly in Asia and Africa. Findings from different studies on associations of HIV co-infection and drug resistance among patients with TB have been contradictory (discordant). Some institution based studies found strongly increased risks for multi-drug resistant TB (MDR TB) among patients co-infected with TB and HIV, whereas other studies found no increased risk (it remains less clear in community based studies. The aim was to conduct a systematic review and meta-analysis of the association between multi-drug resistant tuberculosis and HIV infection. Methods and findings Systematic review of the published literature of observational studies was conducted. Original studies were identified using databases of Medline/Pubmed, Google Scholar and HINARI. The descriptions of original studies were made using frequency and forest plot. Publication bias was assessed using Funnel plot graphically and Egger weighted and Begg rank regression tests statistically. Heterogeneity across studies was checked using Cochrane Q test statistic and I2. Pool risk estimates of MDR-TB and sub-grouping analysis were computed to analyze associations with HIV. Random effects of the meta-analysis of all 24 observational studies showed that HIV is associated with a marginal increased risk of multi-drug resistant tuberculosis (estimated Pooled OR 1.24; 95%, 1.04–1.43). Subgroup analyses showed that effect estimates were higher (Pooled OR 2.28; 95%, 1.52–3.04) for primary multi-drug resistance tuberculosis and moderate association between HIV/AIDS and MDR-TB among population based studies and no significant association in institution settings. Conclusions This study demonstrated that there is association between MDR-TB and HIV. Capacity for diagnosis of MDR-TB and initiating and scale up of antiretroviral treatment, and collaborations between HIV and TB control programs need to be considered and strengthened. PMID:24416139

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

    PubMed Central

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

    2012-01-01

    Background Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circulating Mycobacterium tuberculosis genotypic lineages, important to understand the dynamic of the disease, was hereby addressed for the first time at a national level. Methodology/Principal Findings Spoligotyping was performed on a panel of 592 M. tuberculosis complex strains covering a 2-year period (20042006). It identified 129 patterns: 105 (n?=?568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1 ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2 modern/TbD1?/PGG1 group (Beijing, CAS), group 3 evolutionary recent/TbD1?/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n?=?5, CAS n?=?1), and 3 strains (BOV_1 n?=?2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n?=?114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%. Conclusion The M. tuberculosis population structure in Morocco is highly homogeneous, and is characterized by the predominance of the Euro-American lineages, namely LAM, Haarlem, and T, which belong to the evolutionary recent TbD1?/PGG2/3 phylogenetic group. The combination of spoligotyping and MIRUs decreased the clustering rate significantly, and should now be systematically applied in larger studies. The methods used in this study appear well suited to monitor the M. tuberculosis population structure for an enhanced TB management program in Morocco. PMID:23077552

  19. Constitutive expression of SMAR1 confers susceptibility to Mycobacterium tuberculosis infection in a transgenic mouse model

    PubMed Central

    Yadav, Bhawna; Malonia, Sunil K.; Majumdar, Subeer S.; Gupta, Pushpa; Wadhwa, Neerja; Badhwar, Archana; Gupta, Umesh D.; Katoch, Vishwa M.; Chattopadhyay, Samit

    2015-01-01

    Background & objectives: Studies involving animal models of experimental tuberculosis have elucidated the predominant role of cytokines secreted by T cells and macrophages to be an essential component of the immune response against Mycobacterium tuberculosis infection. The immune activities of CD4+ T cells are mediated in part by Th1 cytokine interferon gamma (IFN-γ) which is produced primarily by T cells and natural killer (NK) cells and critical for initiating the immune response against intracellular pathogen such as M. tuberculosis. Nuclear matrix protein SMAR1 plays an important role in V(D)J recombination, T helper cell differentiation and inflammatory diseases. In this study a transgenic mouse model was used to study the role of SMAR1 in M. tuberculosis infection. Methods: Wild type BALB/c, C57BL/6, BALB/c-EGFP-SMAR1 and C57BL/6-SMAR1 transgenic mice were infected with M. tuberculosis (H37Rv). A dose of 100 bacilli was used for infection via respiratory route. Bacterial load in lung and spleen of infected mice was determined at 2, 4, 6 and 8 wk post-infection. Gene expression analysis for Th1 cytokines and inducible nitric oxide synthase (iNOS) was performed in infected lung tissues by quantitative reverse transcription (RT)-PCR. Results: SMAR1 transgenic mice from both BALB/c and C57BL/6 genetic background displayed higher bacillary load and susceptibility to M. tuberculosis infection compared to wild type mice. This susceptibility was attributed due to compromised of Th1 response exhibited by transgenic mice. Interpretation & conclusions: SMAR1 transgenic mice exhibited susceptibility to M. tuberculosis infection in vivo irrespective of genetic background. This susceptibility was attributed to downregulation of Th1 response and its hallmark cytokine IFN-γ. Hence, SMAR1 plays an important role in modulating host immune response after M. tuberculosis infection. PMID:26831422

  20. Biological functions of Mycobacterium tuberculosis-specific CD4+T cells were impaired by tuberculosis pleural fluid.

    PubMed

    Li, Qin; Li, Li; Liu, Yun; Fu, Xiaoying; Wang, Hui; Lao, Suihua; Yang, Binyan; Wu, Changyou

    2011-08-30

    The local milieu at the site of Mycobacterium tuberculosis infection that modulates T-cell functions is the main battleground for the host to build counter-M. tuberculosis immune responses. CD4+T cells are enriched predominantly in tuberculosis pleurisy and their roles are of considerable importance, but their nature and functional profiles linked with local condition remain elusive. Here we evaluated the functions of M. tuberculosis-specific CD4+T cells from the major three profiles: cytokines production, cell activation and division. Results showed that pleural fluid (PF) from tuberculosis patients in a dose dependent manner inhibited the production of IFN-γ, IL-2 and TNF-α by M. tuberculosis-specific peptides or BCG activated CD4+T cells from pleural fluid mononuclear cells (PFMCs). Surface staining for activation molecules indicated that PF could also blunt cell activation process. CFSE labeling showed that antigen-specific CD4+T cell division ceased following co-incubation with PF. Pre- or post-treatment with PF could disturb subsequent cell activities. The strong inhibitory effect mediated by PF on CD4+T cells was functional predominance. Moreover, application of inhibitors of IDO, adenosine, neutralizing Abs to IL-10 and TGF-β could partially reverse IFN-γ production. Our current research provided novel information that the functions of antigen-specific CD4+T cells coincubated with PF were apparently impaired, which were distinct from cells that cultured in fresh culture medium. We concluded that CD4+T cell mediated antigen-specific cellular immune response that occurred locally might be impaired by PF. PMID:21549757

  1. Tuberculosis care: an evaluability study

    PubMed Central

    Coelho, Ardigleusa Alves; Martiniano, Cludia Santos; Brito, Ewerton Willian Gomes; Negro, Oswaldo Gomes Corra; Arcncio, Ricardo Alexandre; Ucha, Severina Alice da Costa

    2014-01-01

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

  2. Tuberculosis treatment and drug regimens.

    PubMed

    Sotgiu, Giovanni; Centis, Rosella; D'ambrosio, Lia; Migliori, Giovanni Battista

    2015-05-01

    Tuberculosis is an airborne infectious disease treated with combination therapeutic regimens. Adherence to long-term antituberculosis therapy is crucial for maintaining adequate blood drug level. The emergence and spread of drug-resistant Mycobacterium tuberculosis strains are mainly favored by the inadequate medical management of the patients. The therapeutic approach for drug-resistant tuberculosis is cumbersome, because of the poor, expensive, less-effective, and toxic alternatives to the first-line drugs. New antituberculosis drugs (bedaquiline and delamanid) have been recently approved by the health authorities, but they cannot represent the definitive solution to the clinical management of drug-resistant tuberculosis forms, particularly in intermediate economy settings where the prevalence of drug resistance is high (China, India, and former Soviet Union countries). New research and development activities are urgently needed. Public health policies are required to preserve the new and old therapeutic options. PMID:25573773

  3. Tuberculosis in Hispanics/Latinos

    MedlinePLUS

    ... 3,008 Hispanics/Latinos in the United States, accounting for 29% of all people reported with TB ... NTIP): Frequently Asked Questions TB Genotyping TB Genotyping Information Management System (TB GIMS) Drug-Resistant TB Multidrug-Resistant Tuberculosis ( ...

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Cheng, Yong; Schorey, Jeffery S.

    2014-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  8. Characterization of Mycobacterium tuberculosis complex isolated from iranian and afghani patients by spoligotyping method

    PubMed Central

    Ramazanzadeh, Rashid; Farnia, Parisa; Amirmozafari, Nour

    2009-01-01

    Designing newer drugs, vaccines, and diagnostic techniques is dependent on better understanding of M. tuberculosis virulence mechanism. In this study the prevalence of pcaA gene was determined in M. tuberculosis strains typed by spoligotyping. The associated risk factors among patients with different nationalities residing in Iran were also determined. The isolated M. tuberculosis strains have been characterized by performing susceptibility tests against four first-line antituberculosis drugs and were then subjected to spoligotyping characterization. PCR was used for detection of pcaA gene and its nucleotide sequence was also determined. Spoligotyping of M. tuberculosis strains resulted in 140 different patterns. One hundred twenty two (87.1%) of these spoligotype isolates were unique and reported for the first time. The remaining18 (12.8%) spoligotype patterns were previously reported from other geographical regions of the world. Haarlem family was most prevalent than other genotype. Antibiotic resistances were higher in those isolated from the Iranian patients. The pcaA gene was detected in M. tuberculosis clinical isolates but not in saprophyte strains such as M. kansasi. The results showed that, spread of M. tuberculosis strains belonging to the Beijing family among Iranian patients has to be considered seriously. This study confirmed the widespread existence of pcaA gene in almost all the clinical isolates. It is also important to undertake studies to identify which factors are the most significant to consider in tuberculosis control program. PMID:24031364

  9. Mediastinal Lymphadenopathy: Melioidosis Mimicking Tuberculosis.

    PubMed

    Chan, Hiang Ping; Yip, Hwee Seng

    2015-06-01

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

  10. Tuberculosis of the foot: An osteolytic variety

    PubMed Central

    Dhillon, Mandeep S; Aggarwal, Sameer; Prabhakar, Sharad; Bachhal, Vikas

    2012-01-01

    Background: Foot involvement in osteoarticular tuberculosis is uncommon and isolated bony involvement of foot bones with an osteolytic defect is even more rare; diagnostic and therapeutic delays can occur, worsening the prognosis. We present a retrospective series of osteolytic variety of foot tuberculosis. Materials and Methods: We present 24 osteolytic variety of foot tuberculosis (Eleven calcaneus, four cuboid, two cunieforms, one talus, three metatarsals, three phalanges) out of 92 foot TB cases collected over last 20 years. There were 16 adults and eight children. Tissue diagnosis was established in 23 of 24 cases based on PCR AFB staining, culture, and histopathology. Surgical intervention was reserved for patients with either a juxtaarticular focus threatening to involve a joint or an impending collapse of a midfoot bone with cystic destruction. Results: Fifteen cases had an osteolytic lesion on the radiographs resembling a space-occupying lesion, five had patchy osteolysis, while four showed coke like sequestra; one patient had a lesion in two bones. Antitubercular chemotherapy after biopsy was sufficient to heal the lesion in 19 cases, while in five cases surgical debridement needed to be done. The lesions healed eventually. At an average followup of 8.3 years, (range 2-15 years) there were no recurrences and all patients were free from pain, with no restriction of movements. Six patients complained of occasional pain during walking on uneven ground. Conclusion: When tuberculous pathology is limited to the bone, the prognosis is better than in articular disease, as there is less deformity, and hence, less residual pain and disability. PMID:22448060

  11. 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

  12. The case for fencing remains intact.

    PubMed

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

    2013-11-01

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

  13. Odor analysis of decomposing buried human remains

    SciTech Connect

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

    2008-01-01

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

  14. Juveniles' Motivations for Remaining in Prostitution

    ERIC Educational Resources Information Center

    Hwang, Shu-Ling; Bedford, Olwen

    2004-01-01

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

  15. Coal remains a hot commodity for Australia

    SciTech Connect

    Bram, L.

    2006-02-15

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

  16. Remaining issues for hazardous waste incineration

    SciTech Connect

    Dempsey, C.R.

    1993-10-01

    While thermal destruction represents the most effective and widely applicable control technology available today for the disposal or organic hazardous waste, a number of issues remain concerning its use in the long term. These include: Destruction effectiveness on untested/unique wastes; Control of metal emissions; Emissions of combustion byproducts; Detection of process failure; Real-time performance assurance; and Role of innovative technology.

  17. 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.

  18. [Gastrointestinal tuberculosis--case report].

    PubMed

    Kos?ak, Darko; Lovri?, Josip; Koprek, Damir; Kos?ak, Kristina

    2007-09-01

    Isolated tuberculosis of gastrointestinal tract is a very rare disease most commonly localized in the ileo-cecal region (over 85% of the cases). The main object of surgical therapy is intraperitoneal tuberculosis (IP-TB), which leads to complications such as bowel obstruction, perforation, fistulation and bleeding. Since gastrointestinal tuberculosis can mimic symptoms found in Crohns' disease and ileocecal cancer, definitive diagnosis can only be obtained by the finding of Mycobacterium tuberculosis in tissue and stool sample as well as by positive microbacterial cultivation. A 35 year old female patient was admitted to surgical ward with clinical and radiological signs of ileus. From personal medical history as well as previous medical documentation we learned that the patient had been treated in 1995 for lung and larynx tuberculosis at Jordanovac Hospital in Zagreb. After preoperative preparation, the patient underwent surgery during which we found numerous stenoses in the region of terminal ileum and cecum. Due to the patient's general condition, surgical treatment was performed in two acts. In the first we established an L-L ileotransverse anastomosis, and in the second we made the resection. The diagnosis was confirmed by histological findings of Mycobaterium tuberculosis in stool and tissue samples as well as in resection material during operation. The early postoperative period proceeded free from complications and after surgical treatment the patient was referred to the Klenovnik Special Hospital for Pulmonary Diseases. On follow up 18 months after the surgery, there were no signs of gastrointestinal involvement. PMID:18044483

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

    PubMed Central

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

    2014-01-01

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

  20. 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. PMID:24481536

  1. Mycobacterium tuberculosis Complex Mycobacteria as Amoeba-Resistant Organisms

    PubMed Central

    Mba Medie, Felix; Ben Salah, Iskandar; Henrissat, Bernard; Raoult, Didier; Drancourt, Michel

    2011-01-01

    Background Most environmental non-tuberculous mycobacteria have been demonstrated to invade amoebal trophozoites and cysts, but such relationships are largely unknown for members of the Mycobacterium tuberculosis complex. An environmental source has been proposed for the animal Mycobacterium bovis and the human Mycobacterium canettii. Methodology/Principal Findings Using optic and electron microscopy and co-culture methods, we observed that 890.6% of M. canettii, 12.40.3% of M. tuberculosis, 11.72% of M. bovis and 11.20.5% of Mycobacterium avium control organisms were phagocytized by Acanthamoeba polyphaga, a ratio significantly higher for M. canettii (P?=?0.03), correlating with the significantly larger size of M. canetti organisms (P?=?0.035). The percentage of intraamoebal mycobacteria surviving into cytoplasmic vacuoles was 322% for M. canettii, 261% for M. tuberculosis, 282% for M. bovis and 362% for M. avium (P?=?0.57). M. tuberculosis, M. bovis and M. avium mycobacteria were further entrapped within the double wall of <1% amoebal cysts, but no M. canettii organisms were observed in amoebal cysts. The number of intracystic mycobacteria was significantly (P?=?10?6) higher for M. avium than for the M. tuberculosis complex, and sub-culturing intracystic mycobacteria yielded significantly more (P?=?0.02) M. avium organisms (34104 CFU/mL) than M. tuberculosis (42101 CFU/mL) and M. bovis (35101 CFU/mL) in the presence of a washing fluid free of mycobacteria. Mycobacteria survived in the cysts for up to 18 days and cysts protected M. tuberculosis organisms against mycobactericidal 5 mg/mL streptomycin and 2.5% glutaraldehyde. Conclusions/Significance These data indicate that M. tuberculosis complex organisms are amoeba-resistant organisms, as previously demonstrated for non-tuberculous, environmental mycobacteria. Intercystic survival of tuberculous mycobacteria, except for M. canettii, protect them against biocides and could play a role in their life cycle. PMID:21673985

  2. Extrapulmonary tuberculosis by nationality, The Netherlands, 1993-2001.

    PubMed

    te Beek, Lowieke A M; van der Werf, Marieke J; Richter, Clemens; Borgdorff, Martien W

    2006-09-01

    This study describes the epidemiology of extrapulmonary tuberculosis (TB) in the Netherlands from 1993 through 2001. We assessed whether the increasing numbers of inhabitants with a non-Western ethnic background had an effect on the number of extrapulmonary patients. We used data from the Netherlands Tuberculosis Register and included all cases of TB diagnosed in the Netherlands between January 1, 1993, and December 31, 2001. Information on age, sex, nationality, year of diagnosis, culture result, anatomic location of the site of disease, and HIV status was retrieved from the register. Of 13,258 patients with TB, 8216 (62%) had pulmonary TB, and 5042 (38%) had extrapulmonary TB. Non-Dutch nationals were more likely to have most types of extrapulmonary TB. The growth of the number of inhabitants with a non-Western ethnic background in the Netherlands explains the proportional growth of extrapulmonary TB. Physicians need to be aware of the changing clinical picture of TB. PMID:17073086

  3. Typical and unusual cases of female genital tuberculosis

    PubMed Central

    Kulchavenya, E.; Dubrovina, S.

    2014-01-01

    Tuberculosis is a disease with myriad presentations and manifestations; it can affect any organ or tissue, excluding only hair and nails. Doctors who are not familiar with extrapulmonary tuberculosis often overlook this disease. Urogenital tuberculosis (UGTB) is the second most common form of TB in countries with severe epidemic situation and the third most common form in regions with low incidence of TB. The term Urogenital tuberculosis includes kidney tuberculosis; male and female tuberculosis and urinary tract tuberculosis as complication of kidney tuberculosis. We describe rarest case of tuberculosis of a placenta in young woman, suffered from genital tuberculosis, which was overlooked before delivery, as well as typical tubo-ovarian tuberculomas.

  4. 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. PMID:24109141

  5. [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 populations. These factors pose particular problems for implementing DOTS in various ways. Socio-cultural and environmental factors are particularly important in Nepal, and several measures have been developed to overcome these difficulties. One is active community participation through the DOTS committee. The committee consists of a group of motivated people, including social workers, political leaders, health services providers, journalists, teachers, students, representatives of local organizations, medical schools and colleges, industries, private practitioners, and TB patients. One DOTS committee is formed in every treatment center. A key role of the DOTS committee is to identify local problems and their solutions. It increases public awareness about TB and DOTS; supports people with TB in the community by providing treatment observers and tracing late patients; and encourages cooperation among health institutions, health workers, NGOs, and political leaders. The case finding rate is now 69%, and nearly 95% of diagnosed TB cases are being treated under DOTS. The treatment success rate of new smear-positive cases is nearly 90%. Thus, DOTS increases the case finding and treatment success. 3. Cambodia: HIV/TB and the health sector reform: Tan Eang Mao (National Center for Tuberculosis and Leprosy Control, Cambodia) Cambodia is one of the 23 high burden countries of tuberculosis in the world. Moreover, HIV/AIDS has been spreading rapidly since 1990s, which is worsening the tuberculosis epidemics. To cope with the burden, Cambodia has started implementation of DOTS in 1994 and has expanded it to most of public hospitals across the country by 1998. NTP of Cambodia is now enjoying high cure rate of more than 90%. However, due to the constraints such as weak infrastructure and the poverty, it is proved that many of TB sufferers do not have access to the TB services, resulting in still low case detection rate. It is for this reason that the NTP has decided to expand DOTS to health center and community level based on the new health system. Its pilot program that has been

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

    PubMed Central

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

    2014-01-01

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

  7. 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

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

    PubMed

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

    2013-01-01

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

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

    PubMed

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

    2014-12-01

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

  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. 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.

  12. Remaining coverage in associative desorption process

    NASA Astrophysics Data System (ADS)

    Furlong, O.; Manzi, S.; Costanza, G.; Pereyra, V. D.

    2004-08-01

    In this paper the kinetic of dissociative adsorption of dimers followed by associative desorption is analyzed. The coupled differential equations which describe the kinetics of the process were obtained by applying the so-called local evolution rules. Particular interest presents the irreversible desorption process. In fact, given that desorption proceeds from the reacting nearest-neighbor monomers, a remaining coverage results from those isolated particles when the mobility is neglected, therefore, the resulting configuration can be considered as a jamming state of the system. The exact solution for the remaining coverage is obtained in one-dimensional chain, where the effect of the lateral interactions are also included. The two-dimensional case is analyzed by using Monte Carlo simulation. The equilibrium solutions and the thermal desorption spectra are also studied.

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

    PubMed

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

    2011-01-01

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

  14. 13C-Flux Spectral Analysis of Host-Pathogen Metabolism Reveals a Mixed Diet for Intracellular Mycobacterium tuberculosis

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

    Background: Rapid differentiation of the Mycobacterium tuberculosis complex (MTBC) and mycobacteria other than tuberculosis (MOTT) is crucial to facilitate early and effective treatment of the patients. Clinical presentation of MTBC and MOTT is not always very clear and routine conventional methods are time consuming. Materials and Methods: In the present study, the MPT64 protein detection-based immunochomatographic test (SD Bioline Kit, Standard Diagnostics, Inc., Korea) was compared with the conventional biochemical method. Results: The sensitivity, specificity, positive predictive, and negative predictive values of the SD AgMPT64 kit were found to be 100, 96.4, 98.72, and 100%, respectively. Conclusions: Our results have demonstrated that the SD bioline kit is a rapid, reliable method and it can be used in the Revised National Tuberculosis Control Program (RNTCP) of India, for the appropriate management of tuberculosis. PMID:26069425

  16. A case of isolated splenic tuberculosis

    PubMed Central

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

    2014-01-01

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

  17. Tuberculosis, advanced - chest x-rays (image)

    MedlinePLUS

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

  18. Global Alliance for Tuberculosis Drug Development

    MedlinePLUS

    ... and development of better, faster-acting, and affordable tuberculosis drugs that are available to those who need ... to act. The TB Facts 1.5 Million Tuberculosis (TB) is a global pandemic, killing someone approximately ...

  19. 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

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

    PubMed

    Tang, XieMei; Deng, Wanyan; Xie, Jianping

    2012-01-01

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

  1. 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

  2. Direct Dating of Hominids Remains In Eurasia

    NASA Astrophysics Data System (ADS)

    Yokoyama, Y.; Falgures, 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.

  3. 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.

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

    PubMed Central

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

    2013-01-01

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

  5. Failure to detect tuberculosis in Black lechwe antelopes (Kobus leche smithemani) in Zambia

    PubMed Central

    2011-01-01

    Background Two types of lechwe antelopes exclusively exist in their natural ecosystems in Zambia; the Black lechwe (Kobus leche smithemani) and the Kafue lechwe (Kobus leche kafuensis). Despite inhabiting similar ecosystems, tuberculosis has been reported in Kafue lechwe without its documentation in Black lechwe antelopes. However, the past few decades have seen a drastic decline in both lechwe populations. Whereas studies have postulated that infectious diseases such as tuberculosis are having a negative impact on the Kafue lechwe population, no information is available on Black lechwe antelopes. Thus this study was conducted to investigate tuberculosis in Black lechwe antelopes of the Bangweulu swamps in comparison with the Kafue lechwe antelopes of Lochinvar. Findings A total of 44 lechwe antelopes (Black (n = 30): Kafue (n = 14) were sampled from Bangweulu and Lochinvar respectively. A positive case was defined with findings of gross lesions with Ziehl Nielsen and culture confirmation. Out of the 14 animals examined in Lochinvar, 21.4% [95% CI: 15.4, 44.4%] had necropsy lesions consistent with tuberculosis. The corresponding samples from 30 Black lechwe of Bangweulu yielded negative results on all the three tests. Conclusions Current findings from this study intimate the possible absence of tuberculosis in Black lechwe antelopes whilst confirming the presence of tuberculosis in Kafue lechwe of the Kafue basin. The absence of tuberculosis in the Black lechwe suggests that the observed population decline may not be caused by tuberculosis. However, without detailed molecular epidemiological studies it is not possible to determine the association of M. bovis infection in sympatric animal populations. The possible role of transmission of tuberculosis between wildlife and cattle is discussed herein. Findings PMID:21729320

  6. A Molecular Biological and Biochemical Investigation on Mycobacterium tuberculosis MutT Protein

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  8. Biochemical and physiological characterization of the GTP-binding protein Obg of Mycobacterium tuberculosis

    PubMed Central

    2011-01-01

    Background Obg is a highly conserved GTP-binding protein that has homologues in bacteria, archaea and eukaryotes. In bacteria, Obg proteins are essential for growth, and they participate in spore formation, stress adaptation, ribosome assembly and chromosomal partitioning. This study was undertaken to investigate the biochemical and physiological characteristics of Obg in Mycobacterium tuberculosis, which causes tuberculosis in humans. Results We overexpressed M. tuberculosis Obg in Escherichia coli and then purified the protein. This protein binds to, hydrolyzes and is phosphorylated with GTP. An anti-Obg antiserum, raised against the purified Obg, detects a 55 kDa protein in immunoblots of M. tuberculosis extracts. Immunoblotting also discloses that cultured M. tuberculosis cells contain increased amounts of Obg in the late log phase and in the stationary phase. Obg is also associated with ribosomes in M. tuberculosis, and it is distributed to all three ribosomal fractions (30 S, 50 S and 70 S). Finally, yeast two-hybrid analysis reveals that Obg interacts with the stress protein UsfX, indicating that M. tuberculosis Obg, like other bacterial Obgs, is a stress related protein. Conclusions Although its GTP-hydrolyzing and phosphorylating activities resemble those of other bacterial Obg homologues, M. tuberculosis Obg differs from them in these respects: (a) preferential association with the bacterial membrane; (b) association with all three ribosomal subunits, and (c) binding to the stress protein UsfX, rather than to RelA. Generation of mutant alleles of Obg of M. tuberculosis, and their characterization in vivo, may provide additional insights regarding its role in this important human pathogen. PMID:21352546

  9. Triple valve endocarditis by mycobacterium tuberculosis. A case report

    PubMed Central

    2012-01-01

    Background Granulomas caused by Mycobacterium Tuberculosis have been observed at autopsy in the heart, pre-dominantly in the myocardium and endocardium, but rarely involving the coronary vessels and valvular structures. Mycobacterium tuberculosis valvular endocarditis is extremely rare, with most reports coming from autopsy series. Case presentation We report the case of a 17 year old immunocompetent girl who presented with history of fever, malaise, foot gangrene and a left sided hemiparesis. On investigation she was found to have infective endocarditis involving the aortic, mitral and tricuspid valves. She had developed a right middle cerebral artery stroke. She underwent dual valve replacement and tricuspid repair. The vegetations showed granulomatous inflammation but blood cultures and other biological specimen cultures were negative for any organisms. She was started on antituberculous treatment and anticoagulation. Conclusion This is the first reported case of triple valve endocarditis by Mycobacterium Tuberculosis in an immunocompetent host. Especially important is the fact that the right heart is involved which has been historically described in the setting of intravenous drug abuse. This implies that Tuberculosis should be considered in cases of culture negative endocarditis in endemic areas like Pakistan even in immunocompetent hosts. PMID:23013220

  10. 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

  11. Forecasting Tuberculosis Incidence in Iran Using Box-Jenkins Models

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    Herv, 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. PMID:26169235

  13. Immunotherapy of tuberculosis with Mycobacterium vaccae NCTC 11659.

    PubMed

    Stanford, J L; Stanford, C A

    1994-10-01

    The history of immunotherapy for tuberculosis is briefly reviewed, and the early appreciation of the importance of secreted antigens, common mycobacterial antigens and stress proteins is noted. The methods by which Mycobacterium vaccae strain NCTC 11659 was selected for special attention, and results of some of the pilot studies of its use as an immunotherapeutic for tuberculosis are reviewed. The results suggested that immunotherapy with M. vaccae may be an important step forward in the treatment and eventual control of tuberculosis. Used in combination with modern short course chemotherapy, treatment failures and deaths during treatment can be significantly reduced. Preliminary data suggests that shortened courses of chemotherapy may be possible when combined with immunotherapy, and such treatment may also be effective in patients co-infected with HIV. Studies at several centers show that M. vaccae may have an important part to play in the treatment of multi-drug resistant tuberculosis, especially when resistance is of the primary type. The mechanism by which M. vaccae achieves these results may be through adrenal endocrine influences on immunity, but remains speculative. PMID:7713570

  14. Molecular genetics of drug resistance in Mycobacterium tuberculosis.

    PubMed

    Zhang, Y; Young, D

    1994-09-01

    Tuberculosis (TB) is the single largest killer among infectious diseases. The recent resurgence of TB together with outbreaks of multidrug resistant tuberculosis has focused attention on understanding the mechanisms of such drug resistance. Because of the relative neglect of TB research in the past and late arrival of mycobacterial genetic tools, the molecular mechanisms of drug resistance in TB remained largely unknown until very recently. In this paper we review recent progress on the mechanisms of resistance to three major anti-TB drugs; isoniazid, rifampicin and streptomycin. While the resistance mechanisms for rifampicin and streptomycin are similar to those found in other bacteria, isoniazid susceptibility and resistance is unique to Mycobacterium tuberculosis. So far, mutations in two chromosomal loci, katG and inhA have been found to be involved in isoniazid resistance in TB. Identification and characterization of mutations responsible for resistance opens up new possibilities for rapid detection of drug resistant strains. Molecular understanding of drug resistance and drug action in M. tuberculosis may eventually lead to rational design of new anti-TB drugs. PMID:7829406

  15. Understanding Rifampicin Resistance in Tuberculosis through a Computational Approach.

    PubMed

    Kumar, Satish; Jena, Lingaraja

    2014-12-01

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

  16. 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

  17. Bovine tuberculosis in Canadian wildlife: An updated history

    PubMed Central

    Wobeser, Gary

    2009-01-01

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

  18. Enhanced Specialized Transduction Using Recombineering in Mycobacterium tuberculosis

    PubMed Central

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

    2014-01-01

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

  19. Identification of Mycobacterium tuberculosis Antigens of High Serodiagnostic Value?

    PubMed Central

    Ireton, Gregory C.; Greenwald, Rena; Liang, Hong; Esfandiari, Javan; Lyashchenko, Konstantin P.; Reed, Steven G.

    2010-01-01

    Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis, with several million new cases detected each year. Current methods of diagnosis are time-consuming and/or expensive or have a low level of accuracy. Therefore, new diagnostics are urgently needed to address the global tuberculosis burden and to improve control programs. Serological assays remain attractive for use in resource-limited settings because they are simple, rapid, and inexpensive and offer the possibility of detecting cases often missed by routine sputum smear microscopy. The aim of this study was to identify M. tuberculosis seroreactive antigens from a panel of 103 recombinant proteins selected as diagnostic candidates. Initial library screening by protein array analysis and enzyme-linked immunosorbent assay (ELISA) identified 42 antigens with serodiagnostic potential. Among these, 25 were novel proteins. The reactive antigens demonstrated various individual sensitivities, ranging from 12% to 78% (specificities, 76 to 100%). When the antigens were analyzed in combinations, up to 93% of antibody responders could be identified among the TB patients. Selected seroreactive proteins were used to design 3 new polyepitope fusion proteins. Characterization of these antigens by multiantigen print immunoassay (MAPIA) revealed that the vast majority of the TB patients (90%) produced antibody responses. The results confirmed that due to the remarkable variation in immune recognition patterns, an optimal multiantigen cocktail should be designed to cover the heterogeneity of antibody responses and thus achieve the highest possible test sensitivity. PMID:20719988

  20. 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

  1. 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, Brnice; Khawam, Rima; Coqueugniot, Eric; Helmer, Daniel; Le Mort, Franoise; Perrin, Pascale; Gourichon, Lionel; Dutailly, Bruno; Plfi, Gyrgy; Coqueugniot, Hlne; 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

  2. The cell envelope glycoconjugates of Mycobacterium tuberculosis.

    PubMed

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

    2014-01-01

    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 the 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 10 years in the discovery and development of novel inhibitors targeting their biogenesis. PMID:24915502

  3. Will tuberculosis become resistant to all antibiotics?

    PubMed

    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

  4. Macrophages in tuberculosis: friend or foe.

    PubMed

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

    2013-09-01

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

  5. Macrophages in Tuberculosis: Friend or Foe

    PubMed Central

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

    2013-01-01

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

  6. 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

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

    PubMed Central

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

    2013-01-01

    Background The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. Methods HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. Results Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 1447). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 716) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 923). Two patients died due to CNS TB-IRIS. Lower CD4+ T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. Conclusion Paradoxical TBIRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions. PMID:23691062

  8. Rapid diagnosis of pulmonary tuberculosis

    PubMed Central

    Sarmiento, Jos Mauricio Hernndez; Restrepo, Natalia Builes; Meja, 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

  9. A Country-Wide Study of Spoligotype and Drug Resistance Characteristics of Mycobacterium tuberculosis Isolates from Children in China

    PubMed Central

    Zhao, Xiuqin; Dong, Fang; Dong, Haiyan; Huang, Hairong; Tian, Jianling; Li, Qinjing; Lian, Lulu; Yin, Qingqin; Song, Wenqi; Wan, Kanglin; Shen, A-dong

    2013-01-01

    Background Tuberculosis (TB) is still a big threat to human health, especially in children. However, an isolation of Mycobacterium tuberculosis culture from pediatric cases remains a challenge. In order to provide some scientific basis for children TB control, we investigated the genotyping and drug resistance characteristics of M. tuberculosis isolates from pediatric cases in China. Methodology/Principal Findings In this study, a total of 440 strains including 90 from children (<15 years), 159 from adolescents (1518 years) and 191 from adults (>18 years) isolated in 25 provinces across China were subjected to spoligotyping and drug susceptibility testing. As a result, Beijing family strains were shown to remain predominant in China (85.6%, 81.1% and 75.4% in three above groups, respectively), especially among new children cases (91.0% vs. 69.6% in previously treated cases, P?=?0.03). The prevalence of the Beijing genotype isolates was higher in northern and central China in the total collection (85.1% in northern and 83.9% in central vs. 61.6% in southern China, P<0.001) and a similar trend was seen in all three age groups (P?=?0.708, <0.001 and 0.025, respectively). In adolescents, the frequencies of isoniazid (INH)-resistant and ethambutol (EMB)-resistant isolates were significantly higher among Beijing strains compared to non-Beijing genotype strains (P?=?0.028 for INH and P?=?0.027 for EMB). Furthermore, strong association was observed between resistance to rifampicine (RIF), streptomycin (STR) and multidrug resistance (MDR) among Beijing compared to non-Beijing strains in previously treated cases of children (P?=?0.01, 0.01 and 0.025, respectively). Conclusion/Significance Beijing family was more prevalent in northern and central China compared to southern China and these strains were predominant in all age groups. The genetic diversity of M. tuberculosis isolates from children was similar to that found in adolescents and adults. Beijing genotype was associated with RIF, STR and MDR resistance in previously treated children. PMID:24386365

  10. Gene Regulatory Networks Activated during Chronic Tuberculosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic tuberculosis represents a burden for most of worlds population. Several genes were found to be up-regulated at the late stage of chronic tuberculosis when DNA microarray protocol was used to analyze murine tuberculosis. Rv0348 is a potential transcriptional regulator that is highly expresse...

  11. 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

  12. 9 CFR 311.2 - Tuberculosis.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 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...

  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. 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....

  15. 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,...

  16. 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...

  17. 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,...

  18. 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....

  19. 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,...

  20. 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...

  1. 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,...

  2. 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....

  3. 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...

  4. 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....

  5. 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...

  6. 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 ...

  7. 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....

  8. 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,...

  9. [Genetic background of preeclampsia].

    PubMed

    Seremak-Mrozikiewicz, Agnieszka; Drews, Krzysztof

    2007-10-01

    Population studies have been suggesting genetic predisposition to the appearance of preeclampsia (PE) for a considerable period of time now. In familial occurrence of the disease higher frequency of preeclampsia has been observed in mothers, daughters and sisters of women burned of this poor medical history and higher risk to severe PE development. Although a single gene may contribute to the development of the patomechanizm of PE, most authors focus on the analysis of the common influence of candidate genes which are involved in a series of pathophysiological processes of PE. Thus, PE is often believed to be the final phenotype (increase of blood pressure and multiorgan complications development), being the result of intermediate phenotypes acting at the same time and being modulated by environmental factors. PE belongs to the complex human disease. The results of the findings connected with the contribution of maternal, paternal and fetal genotypes in PE development remain unclear, though a stronger influence of maternal genes, with a weaker influence of those transferred from the father, may be observed. Despite the existing divergences (the findings on the genetic background of PE are in conflict, no doubt due to the population differences and small number of investigated groups), the results obtained so far stress the necessity to discover the genetic risk factors as it may do both: facilitate the identification of groups of women predisposed to preeclampsia and allow for an early prophylactic administration. PMID:18200973

  10. 51-L Challenger Crew Remains Transferred

    NASA Technical Reports Server (NTRS)

    1988-01-01

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

  11. A Broad Set of Different Llama Antibodies Specific for a 16 kDa Heat Shock Protein of Mycobacterium tuberculosis

    PubMed Central

    Trilling, Anke K.; de Ronde, Hans; Noteboom, Linda; van Houwelingen, Adèle; Roelse, Margriet; Srivastava, Saurabh K.; Haasnoot, Willem; Jongsma, Maarten A.; Kolk, Arend; Zuilhof, Han; Beekwilder, Jules

    2011-01-01

    Background Recombinant antibodies are powerful tools in engineering of novel diagnostics. Due to the small size and stable nature of llama antibody domains selected antibodies can serve as a detection reagent in multiplexed and sensitive assays for M. tuberculosis. Methodology/Principal Findings Antibodies for Mycobacterium tuberculosis (M. tb) recognition were raised in Alpaca, and, by phage display, recombinant variable domains of heavy-chain antibodies (VHH) binding to M. tuberculosis antigens were isolated. Two phage display selection strategies were followed: one direct selection using semi-purified protein antigen, and a depletion strategy with lysates, aiming to avoid cross-reaction to other mycobacteria. Both panning methods selected a set of binders with widely differing complementarity determining regions. Selected recombinant VHHs were produced in E. coli and shown to bind immobilized lysate in direct Enzymelinked Immunosorbent Assay (ELISA) tests and soluble antigen by surface plasmon resonance (SPR) analysis. All tested VHHs were specific for tuberculosis-causing mycobacteria (M. tuberculosis, M. bovis) and exclusively recognized an immunodominant 16 kDa heat shock protein (hsp). The highest affinity VHH had a dissociation constant (KD) of 4×10−10 M. Conclusions/Significance A broad set of different llama antibodies specific for 16 kDa heat shock protein of M. tuberculosis is available. This protein is highly stable and abundant in M. tuberculosis. The VHH that detect this protein are applied in a robust SPR sensor for identification of tuberculosis-causing mycobacteria. PMID:22046343

  12. 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. PMID:26971523

  13. 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.

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

    PubMed Central

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

    2012-01-01

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

  15. [Tuberculosis control in Eastern Europe].

    PubMed

    van Olmen, J; Veen, J

    2002-02-01

    The annual incidence of tuberculosis in Eastern Europe has increased from an average of 40 per 100,000 in 1990 to 60 per 100,000 in 1998. In particular, the increase in multi-drug resistant tuberculosis, which is difficult to treat, is a great cause for concern due to increasing migration. The breakdown in the healthcare infrastructure, which has jeopardised medicine supplies, is largely to blame for this increased incidence. Eastern Europe has a long standing tuberculosis control system which is characterised by extensive and specialised knowledge about the disease, but also by a lack of knowledge concerning its control. A great deal of attention is paid to the number of medical procedures carried out, but the results are ignored. For a few years now, Western aid organisations have been involved in tuberculosis control in Eastern Europe and have introduced the WHO DOTS strategy ('directly observed treatment, short-course'), with emphasis on case detection by sputum smear microscopy, directly observed uninterrupted treatment with short-course intensive chemotherapy and evaluation of treatment outcome. The Netherlands play a prominent role in these activities. The DOTS strategy is only slowly becoming accepted in Eastern Europe, particularly in Russia. It is in Western Europe's interest to help Eastern Europe rebuild their tuberculosis control system. Education and training are important elements to prepare doctors for their new role, in which public health should be given greater emphasis. PMID:11851086

  16. How to optimize tuberculosis case finding: explorations for Indonesia with a health system model

    PubMed Central

    2009-01-01

    Background A mathematical model was designed to explore the impact of three strategies for better tuberculosis case finding. Strategies included: (1) reducing the number of tuberculosis patients who do not seek care; (2) reducing diagnostic delay; and (3) engaging non-DOTS providers in the referral of tuberculosis suspects to DOTS services in the Indonesian health system context. The impact of these strategies on tuberculosis mortality and treatment outcome was estimated using a mathematical model of the Indonesian health system. Methods The model consists of multiple compartments representing logical movement of a respiratory symptomatic (tuberculosis suspect) through the health system, including patient- and health system delays. Main outputs of the model are tuberculosis death rate and treatment outcome (i.e. full or partial cure). We quantified the model parameters for the Jogjakarta province context, using a two round Delphi survey with five Indonesian tuberculosis experts. Results The model validation shows that four critical model outputs (average duration of symptom onset to treatment, detection rate, cure rate, and death rate) were reasonably close to existing available data, erring towards more optimistic outcomes than are actually reported. The model predicted that an intervention to reduce the proportion of tuberculosis patients who never seek care would have the biggest impact on tuberculosis death prevention, while an intervention resulting in more referrals of tuberculosis suspects to DOTS facilities would yield higher cure rates. This finding is similar for situations where the alternative sector is a more important health resource, such as in most other parts of Indonesia. Conclusion We used mathematical modeling to explore the impact of Indonesian health system interventions on tuberculosis treatment outcome and deaths. Because detailed data were not available regarding the current Indonesian population, we relied on expert opinion to quantify the parameters. The fact that the model output showed similar results to epidemiological data suggests that the experts had an accurate understanding of this subject, thereby reassuring the quality of our predictions. The model highlighted the potential effectiveness of active case finding of tuberculosis patients with limited access to DOTS facilities in the developing country setting. PMID:19505296

  17. International Monetary Fund Programs and Tuberculosis Outcomes in Post-Communist Countries

    PubMed Central

    Stuckler, David; King, Lawrence P; Basu, Sanjay

    2008-01-01

    Background Previous studies have indicated that International Monetary Fund (IMF) economic programs have influenced health-care infrastructure in recipient countries. The post-communist Eastern European and former Soviet Union countries experienced relatively similar political and economic changes over the past two decades, and participated in IMF programs of varying size and duration. We empirically examine how IMF programs related to changes in tuberculosis incidence, prevalence, and mortality rates among these countries. Methods and Findings We performed multivariate regression of two decades of tuberculosis incidence, prevalence, and mortality data against variables potentially influencing tuberculosis program outcomes in 21 post-communist countries for which comparative data are available. After correcting for confounding variables, as well as potential detection, selection, and ecological biases, we observed that participating in an IMF program was associated with increased tuberculosis incidence, prevalence, and mortality rates by 13.9%, 13.2%, and 16.6%, respectively. Each additional year of participation in an IMF program was associated with increased tuberculosis mortality rates by 4.1%, and each 1% increase in IMF lending was associated with increased tuberculosis mortality rates by 0.9%. On the other hand, we estimated a decrease in tuberculosis mortality rates of 30.7% (95% confidence interval, 18.3% to 49.5%) associated with exiting the IMF programs. IMF lending did not appear to be a response to worsened health outcomes; rather, it appeared to be a precipitant of such outcomes (Granger- and Sims-causality tests), even after controlling for potential political, socioeconomic, demographic, and health-related confounders. In contrast, non-IMF lending programs were connected with decreased tuberculosis mortality rates (−7.6%, 95% confidence interval, −1.0% to −14.1%). The associations observed between tuberculosis mortality and IMF programs were similar to those observed when evaluating the impact of IMF programs on tuberculosis incidence and prevalence. While IMF programs were connected with large reductions in generalized government expenditures, tuberculosis program coverage, and the number of physicians per capita, non-IMF lending programs were not significantly associated with these variables. Conclusions IMF economic reform programs are associated with significantly worsened tuberculosis incidence, prevalence, and mortality rates in post-communist Eastern European and former Soviet countries, independent of other political, socioeconomic, demographic, and health changes in these countries. Future research should attempt to examine how IMF programs may have related to other non-tuberculosis–related health outcomes. PMID:18651786

  18. Drilling remains brisk off northern Europe

    SciTech Connect

    Not Available

    1991-09-02

    This paper reports on drilling activity which remains high off Northern Europe, drawing in newly built rigs and units from other parts of the world. Midway through the region's peak summer drilling season there were 138 rigs available in northern Europe - eight more than at the same time last year. Of these, 13 were idle (seven semis, five jack ups, and a drillship). Ninety-four of the rigs were drilling, six more than last year. The rest were being used as accommodation or production units or were undergoing conversion or maintenance. Britain continues to dominate the drilling activity. Sixty of the 94 drilling units were in U.K. waters, five more than in summer 1990. Norway accounted for 15 active rigs, compared with 11 at the same time last year.

  19. 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.

  20. Space Weathering of Asteroids: Issues Remain

    NASA Astrophysics Data System (ADS)

    Chapman, C. R.

    2003-05-01

    After decades of debate, consensus now exists that asteroid reflectance spectra are affected by space weathering. Based on a recent consensus [1] about the physical processes that space weather the Moon, we can realistically hypothesize about the causes of asteroidal space weathering and about how the processes might be manifested on different types of asteroids. But issues and questions remain. While vapor deposition on grains dominates lunar space weathering, for asteroids the relative vapor production by solar wind sputtering versus micrometeorite impact (or even other processes masked on the Moon) remains uncertain. Particularly troublesome are the different styles of space weathering on Ida and Eros; these otherwise similarly sized SIV asteroids differ mainly in being either in the belt or in near-Earth space, but how does that affect space weathering so dramatically? A vital issue is the timescale for space weathering to be manifested, or to mature, under various conditions (e.g. in or out of the belt, for different taxonomic types, or for different sizes). An extraordinary discovery may finally help provide an answer. Nesvorny et al. [2,3] have discovered how to date the creation of specific asteroids (i.e. in a catastrophic collisional break-up) with a robust precision of several percent, competitive with meteoritic age-dating techniques except that we know which specific asteroids the dates pertain to. The Karin cluster, within the S-type Koronis family, formed 5.8 +/-0.2 Myr ago. This age is of the order of estimates of space-weathering/regolith-evolution timescales. Spectral studies of Karin cluster members, and members of other dated families, may determine the absolute rates of space weathering processes. That in turn can elucidate the physical processes and permit better extrapolation to other asteroids. References: [1] B. Hapke (2001) J. Geophys. Res. 106, 10039-10073; [2] D. Nesvorny et al. (2002) Nature 417, 720-722; [3] D. Nesvorny et al. (2003) Astrophys. J. 591, 486-497.

  1. 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

  2. The Past and Future of Tuberculosis Research

    PubMed Central

    Comas, Iñaki; Gagneux, Sebastien

    2009-01-01

    Renewed efforts in tuberculosis (TB) research have led to important new insights into the biology and epidemiology of this devastating disease. Yet, in the face of the modern epidemics of HIV/AIDS, diabetes, and multidrug resistance—all of which contribute to susceptibility to TB—global control of the disease will remain a formidable challenge for years to come. New high-throughput genomics technologies are already contributing to studies of TB's epidemiology, comparative genomics, evolution, and host–pathogen interaction. We argue here, however, that new multidisciplinary approaches—especially the integration of epidemiology with systems biology in what we call “systems epidemiology”—will be required to eliminate TB. PMID:19855821

  3. Counting children with tuberculosis: why numbers matter.

    PubMed

    Seddon, J A; Jenkins, H E; Liu, L; Cohen, T; Black, R E; Vos, T; Becerra, M C; Graham, S M; Sismanidis, C; Dodd, P J

    2015-12-01

    In the last 5 years, childhood tuberculosis (TB) has received increasing attention from international organisations, national TB 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 why 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, and 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 the childhood TB burden, it remains substantially incomplete. PMID:26564535

  4. Protein tyrosine phosphorylation in Mycobacterium tuberculosis.

    PubMed

    Chow, K; Ng, D; Stokes, R; Johnson, P

    1994-12-01

    Crude cell extracts from three strains of Mycobacterium tuberculosis were analyzed for the presence of proteins possessing phosphorylated tyrosine residues. A protein migrating at approximately 55 kDa was detected using an antiphosphotyrosine monoclonal antibody. In addition, less predominant bands were observed between 50 kDa and 60 kDa. That M. tuberculosis contains specific tyrosine phosphorylated proteins implies that M. tuberculosis has tyrosine kinase activity. Examination of other, non-pathogenic mycobacterium species yielded no major antiphosphotyrosine reactive proteins. This suggests that the antiphosphotyrosine reactive protein is specific to M. tuberculosis strains. These results provide evidence that M. tuberculosis contains an antiphosphotyrosine reactive protein. PMID:7529204

  5. Crescentic Glomerulonephritis Associated with Pulmonary Tuberculosis

    PubMed Central

    Vanikar, A.V.; Patel, R.D.; Suthar, K. S.; Trivedi, H. L.

    2016-01-01

    Tuberculosis of kidney and urinary tract is caused by members of the Mycobacterium tuberculosis complex. Kidney is usually infected by haematogenous spread of bacilli from focus of infection in the lungs. Glomerular involvement in tuberculosis presenting as a rapidly progressive glomerulonephritis is a rare entity. We report a rare case of crescentic glomerulonephritis associated with pulmonary tuberculosis in a 26-year-old man. Patient was treated with corticosteroids, haemodialysis, intravenous immunoglobulin and four cycles of plasmapheresis. He did not respond to 4-drug anti-tuberculosis treatment for renal pathology and was switched over to maintenance haemodialysis. However, he responded to pulmonary TB. PMID:26894074

  6. Crescentic Glomerulonephritis Associated with Pulmonary Tuberculosis.

    PubMed

    Kanodia, K V; Vanikar, A V; Patel, R D; Suthar, K S; Trivedi, H L

    2016-01-01

    Tuberculosis of kidney and urinary tract is caused by members of the Mycobacterium tuberculosis complex. Kidney is usually infected by haematogenous spread of bacilli from focus of infection in the lungs. Glomerular involvement in tuberculosis presenting as a rapidly progressive glomerulonephritis is a rare entity. We report a rare case of crescentic glomerulonephritis associated with pulmonary tuberculosis in a 26-year-old man. Patient was treated with corticosteroids, haemodialysis, intravenous immunoglobulin and four cycles of plasmapheresis. He did not respond to 4-drug anti-tuberculosis treatment for renal pathology and was switched over to maintenance haemodialysis. However, he responded to pulmonary TB. PMID:26894074

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

    PubMed

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

    2009-01-01

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

  8. 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.

  9. Significance of nutrition in pulmonary tuberculosis.

    PubMed

    Kant, Surya; Gupta, Harshita; Ahluwalia, Savita

    2015-01-01

    Malnutrition and tuberculosis are both problems mostly of the developing countries. Tuberculosis can lead to malnutrition and malnutrition may predispose to tuberculosis. Poor nutrition leads to protein-energy malnutrition and micronutrients deficiencies which lead to immunodeficiency. This secondary immunodeficiency increases the host's susceptibility to infection and hence increase the risk for developing tuberculosis. Tuberculosis itself leads to reduction in appetite, nutrient malabsorption, micronutrient malabsorption, and altered metabolism leading to wasting and poor nutritional status. Nutritional status and dietary intake and hence nutritional status of patients get improved during antituberculosis treatment. PMID:24915351

  10. 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.

  11. 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

  12. 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.

  13. Tracheobronchial Tuberculosis Without Lung Involvement

    PubMed Central

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

    2015-01-01

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

  14. 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

  15. [Job's syndrome and miliary tuberculosis].

    PubMed

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

    2014-01-01

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

  16. The spectrum of human tuberculosis.

    PubMed Central

    Lenzini, L; Rottoli, P; Rottoli, L

    1977-01-01

    Clinical, morphological and immunological studies of human tuberculosis have enabled the spectrum of the disease to be determined. We have investigated the cell-mediated immune responses by means of skin tests and leucocyte migration inhibition to PPD, and the humoral immune responses by means of immunodiffusion and haemagglutination tests. Patients with tuberculosis can be classified into two polar groups--reactive (RR) and unreactive (UU), the former showing good cell-mediated immunity and little or no antibody formation and the latter poor cellular responses and exuberant antibody production. The intermediate forms show characteristics of the neighbouring polar groups. The existence of a spectrum of immune response in tuberculosis, which has long been suspected, is now demonstrated. PMID:849655

  17. 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

  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. 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 poverty and powerlessness as root causes of vulnerability to infection and as such they are a waste of scarce resources. A return to a basic needs approach to all the diseases of poverty is nothing more than proven public health wisdom and experience. A sustainable and meaningful response to AIDS is simultaneously a sustainable and meaningful response to all the diseases of poverty. The obstacles to the adoption of this approach are economic and political and must be confronted at the level of international financial institutions, the globalisation of neoliberal economic systems, the growing power imbalances between and within nations and the undermining of democracy and national sovereignty. An alternative strategy for AIDS and the other diseases of poverty would build on macroeconomic reforms for a fair, rational and sustainable international economic order so that democratically elected governments may meet their people's basic needs, including health, without external interference. PMID:25871816

  20. 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.

  1. Turbidite plays` immaturity means big potential remains

    SciTech Connect

    Pettingill, H.S.

    1998-10-05

    The international exploration and production industry is increasingly focusing on deepwater plays. Turbidites are not the only reservoir type that occurs in deepwater frontiers, but they are the primary reservoir type of those plays. A worldwide data base assembled from published information on 925 fields and discoveries with deepwater clastic reservoirs (turbidites sensu lato) has been employed to investigate the large-scale exploration and production trends. Coverage of the Former Soviet Union, China, and the Indian subcontinent has been minor, but with the large data base of fields and discoveries from the rest of the world, the broad conclusions should remain valid. This article describes the global turbidite play in terms of: (1) basins of the world where turbidite fields have been discovered; (2) the five largest basins in terms of total discovered resources; and (3) a summary of trap type, which is a critical geological factor in turbidite fields. The second article will summarize a population of the world`s 43 largest turbidite fields and discoveries.

  2. Oral cobalamin remains medicine's best kept secret.

    PubMed

    Graham, Ian D; Jette, Nathalie; Tetroe, Jacqueline; Robinson, Nicole; Milne, Sarah; Mitchell, Susan L

    2007-01-01

    A cross-sectional survey was conducted in order to describe the use of oral cobalamin among geriatricians, hematologists, and general practitioners, and to explore factors related to its use. The study population consisted of all geriatricians (n = 138) and hematologists (n = 317) listed in the Canadian Medical Directory plus a random sample of 307 general practitioners. The overall response rate was 40%. Intramuscular and oral cobalamin was prescribed by 76 and 32% of the respondents, respectively. Twenty seven percent reported using both oral and intramuscular cobalamin and 6% reported using only oral cobalamin. Only 25% of respondents indicated they were aware of a RCT demonstrating the efficacy of oral cobalamin prior to reading a synopsis of the study in the survey. After multivariate adjustment, only the belief that oral cobalamin was effective and certainty about who carried oral preparations remained independently associated with oral cobalamin use. Oral cobalamin has been shown to be an efficacious, cost efficient and safe method of treating cobalamin deficiency. Nonetheless, it is not used by the majority of physicians treating this condition. Strategies to promote the use of oral cobalamin should be directed at educating physicians of its efficacy and providing them with prescribing information on where it can be purchased. PMID:16672168

  3. Population remains top priority for China.

    PubMed

    Li, H

    1998-04-01

    China, whose population was 430 million in 1840, is facing a population total of 1.3 billion in 2000. Population increased rapidly in the country during the 1950s, but early efforts at population control were abandoned from the start of the Cultural Revolution in 1966 until the 1970s. Today, the importance of family planning (FP) is recognized throughout Chinese society. With 20 million newborns adding 13 million people to the population each year, controlling the population increase will remain a top priority of China's population policy. Other priorities include 1) increasing the quality of life of the population by improving health, promoting literacy, and developing human resources; 2) facing the impact of population aging; 3) struggling to overcome the poverty experienced by 50 million people; and 4) dealing with the imbalanced sex ratio of newborns. China has been attempting to institute strategies to implement the Program of Action adopted by the 1994 International Conference on Population and Development and is attempting to adopt an integrated approach to population programs that combines FP with development measures and the delivery of multiple services to enhance reproductive health. Since 1984, China has worked with Japan's JOICFP on an Integrated Project that offers FP, maternal and child health services, and parasite control. PMID:12348548

  4. Cranial remains of an Eocene tarsier

    PubMed Central

    Rossie, James B.; Ni, Xijun; Beard, K. Christopher

    2006-01-01

    The phylogenetic position of tarsiers relative to anthropoids and Paleogene omomyids remains a subject of lively debate that lies at the center of research into anthropoid origins. Omomyids have long been regarded as the nearest relatives of tarsiers, but a sister group relationship between anthropoids and tarsiers has also been proposed. These conflicting phylogenetic reconstructions rely heavily on comparisons of cranial anatomy, but until now, the fossil record of tarsiers has been limited to a single jaw and several isolated teeth. In this article, we describe cranial material of a fossil tarsiid from the middle-Eocene Shanghuang fissure-fillings in southern Jiangsu Province, China. This facial fragment, which is allocated to Tarsius eocaenus, is virtually identical to the corresponding anatomy in living tarsiers and differs substantially from that of early anthropoids such as Bahinia, Phenacopithecus, and Parapithecus. This new specimen indicates that tarsiers already possessed greatly enlarged orbits and a haplorhine oronasal configuration by the time they are first documented in the fossil record during the middle Eocene. PMID:16537385

  5. 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. PMID:22204892

  6. 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 20042012. 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]: 1.22.9), 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

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

    PubMed Central

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

    2009-01-01

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

  8. 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

  9. 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

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

    PubMed Central

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

    2014-01-01

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

  11. 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. PMID:25736170

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2014-09-01

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

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

    PubMed

    Garca-Basteiro, Alberto L; Ismail, Mamudo R; Carrilho, Carla; Ussene, Esperana; Castillo, Paola; Chitsungo, Drcio; Rodrguez, Cristina; Lovane, Luclia; Vergara, Andrea; Lpez-Varela, Elisa; Mandomando, Inacio; Lorenzoni, Cesaltina; Ordi, Jaume; Menndez, Clara; Bassat, Quique; Martnez, 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. Development of a novel anti ESAT-6 monoclonal antibody for screening of Mycobacterium tuberculosis

    PubMed Central

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

    2014-01-01

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

  16. 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

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

    PubMed Central

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

    2015-01-01

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

  18. 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

  19. 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

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

    PubMed Central

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

    2012-01-01

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

  1. Analysis of undiagnosed tuberculosis-related deaths identified at post-mortem among HIV-infected patients in Russia: a descriptive study

    PubMed Central

    2011-01-01

    Background Tuberculosis remains a serious public health threat and economic burden in Russia with escalating rates of drug resistance against a background of growing HIV-epidemic. Samara Oblast is one of the regions of the Russian Federation where more than 1% of the population is affected by the HIV-epidemic; almost half of the cases are concentrated in the largely-industrial city of Togliatti with a population of 800 000. Methods We conducted a retrospective analysis of errors leading to death of HIV-positive patients in general health care hospitals in Togliatti, Russia, in 2008. All (n = 29) cases when tuberculosis was established at autopsy as a cause of death were included. Results Median length of hospital stay was 20 days; in 11 cases the death occurred within the first 24 hours of admission. All cases were known to be HIV-positive prior to admission, however HAART was not initiated for any case, and no relevant tests to assess severity of immunosupression were performed despite their availability. No appropriate diagnostic algorithms were applied to confirm tuberculosis. Major gaps were identified in the work of hospital and consulting physicians including insufficient records keeping. In almost all patients earlier regular HIV-relevant tests were not performed due to poor compliance of patients, many of whom abused alcohol and drugs. Conclusions We conclude that introduction of prompt and accurate diagnostics tests, adequate treatment protocols and intensive training of physicians in management of AIDS and TB is vital. This should include reviewing standards of care for HIV-positive individuals with accompanying social problems. PMID:22008481

  2. Rapid DNA detection of Mycobacterium tuberculosis-towards single cell sensitivity in point-of-care diagnosis

    PubMed Central

    Ng, Benjamin Y.C.; Wee, Eugene J.H.; West, Nicholas P.; Trau, Matt

    2015-01-01

    Although there have been many recent advances in Tuberculosis (TB) detection technologies, there still remains a major need to develop simpler point-of-care techniques. In an effort towards such a diagnostic test for resource-poor settings, we have designed a bioassay based on detecting amplified DNA via bridging flocculation. The assay is cheap, with a sensitivity approaching a single cell of Mycobacterium tuberculosis and the potential for translation into broader applications.

  3. 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

  4. Acute Monoarthritis of the Wrist Joint: Tuberculosis or Not?

    PubMed

    Desikan, Prabha; Verma, Rahul; Tiwari, Karuna; Panwalkar, Nikita

    2016-03-01

    Background?Extrapulmonary tuberculosis (EPTB) is known to have many and varied presentations. However, isolated involvement of bone with tubercular infection is uncommon. The clinical features of such infections are known to mimic chronic pyogenic osteomyelitis, Brodie abscess, or tumors, but not acute monoarthritis. Case Description?We describe here an unusual case of tuberculous osteomyelitis that mimicked features of acute monoarthritis of the wrist joint. Literature Review?Extraspinal tuberculous osteomyelitis is rare and comprises only about 2 to 3% of all cases of osteoarticular tuberculosis, with the hip and knee joints being the most commonly involved. An extensive literature review did not show any published report of tuberculous osteomyelitis presenting as acute monoarthritis of the wrist joint. Clinical Relevance?This case underlines the importance of making EPTB an important differential diagnosis even in cases with clinical features that are completely inconsistent with tubercular infections. PMID:26855841

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

    PubMed Central

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

    2013-01-01

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

  6. Cell substrates: lessons learned and challenges remaining.

    PubMed

    Petricciani, J C

    1999-01-01

    The history of cell substrates for the manufacture of biological products is directly related to a series of technical advances and challenges to the status quo, some of which were accepted quickly while others took more than a decade to resolve. The development of cell culture techniques in the 1950s opened the door to the manufacture of a wide range of biological products. The first major challenge occurred in the late 1960s when human diploid cells (HDCs) were developed and proposed as an alternative to primary cell cultures for the production of live viral vaccines such as polio, which up to that point had been produced in primary cells of various species. In the 1970s, attention was focussed on the use of continuous cell lines (CCLs) for the production of non-replicating biological products such as interferon (IFN). The next significant technical advance and challenge was the development of recombinant DNA and monoclonal antibody technologies in the 1980s, both of which required the use of CCLs. Although most of the issues relating to CCLs in the manufacture of biological products have been resolved, issues related to their use as substrates for live viral vaccines remain to be fully addressed. Those experiences in the past teach us clearly that a system in which regulatory authorities, industry, and the general biomedical community cooperate in finding solutions to problems and in reaching consensus on issues raised by technical advances is ultimately in everyone's best interest. The World Health Organization has played a major role in that regard, and it should continue to provide leadership in this area. PMID:10616176

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

    PubMed Central

    Hollo, V.; Huitric, E.; Kdmn, 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

  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: 24.032.6) in first-, 10.2 (95%CI: 6.116.6) in second generation migrants, and 4.6 (95%CI: 3.75.6) 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. Multiple, large granulomas in a patient with extensive intestinal tuberculosis

    PubMed Central

    Massalis, Ioannis; Lampropoulos, Christos; Efthymiou, Giorgos; Papadima, Efi

    2012-01-01

    A 42-year-old patient presented with low-grade fever, pain of the right iliac fossa, constipation and tendency to vomit. Clinical examination revealed abdominal wall rigidity and rebound tenderness of the right iliac fossa. The patient was operated immediately because of an acute abdomen and the probable diagnosis of ruptured appendicitis. In laparotomy, terminal ileum, ileocaecal valve and the entire ascending colon, up to the right colic flexure, were occupied and distorted by multiple, large masses. In addition, many enlarged lymph nodes were scattered in the mesentery and the mesocolon. A right hemicolectomy was performed. Pathological examination of biopsy specimens revealed findings compatible with tuberculosis. The patient was started on empirical anti-tuberculosis treatment with a four-drug regimen. He was discharged 10 days later with marked improvement. Six months after surgery, the patient remains in very good condition without any symptoms. PMID:23234821

  10. Disseminated tuberculosis following liver transplant presenting with an axillary abscess

    PubMed Central

    Ladds, Emma

    2014-01-01

    Four years after an orthoptic liver transplant for hepatocellular carcinoma secondary to alcoholic liver disease, the patient presented in a crescendo manner with skin infections and finally a septic right arm wound. The abscess was drained and cultures grew Mycobacterium tuberculosis. The patient reported a previous episode of pneumonia and subsequent hospitalisations for recurrent chest infections, and following further investigation, he was diagnosed with disseminated tuberculosis. The infection responded to triple therapy, but primary closure of the arm wound was unsuccessful and it was treated conservatively with negative pressure wound therapy. The patient remains an inpatient 3?months after his presentation, responding well to therapy and anticipating imminent discharge. The patient's case serves as a reminder that infections are common in solid organ transplant recipients and clinicians should be aware of unusual or recurrent presentations in these patients, to allow for early diagnosis and timely management. PMID:24510698

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

    PubMed Central

    Jindal, Neerja; Bansal, Renu; Arora, Shilpa

    2015-01-01

    Background and Objective Tuberculosis (TB) is one of the commonest opportunistic infection and the leading cause of death in HIV patients in developing countries. HIV infection is a well recognised risk factor for both activation of initial infection and reactivation of latent infection. This study was done to find out the co-prevalence and the trend of HIV infection among tuberculosis patients and to determine the prevalence of MDR Tuberculosis in HIV positive patients using Xpert MTB/RIF assay (Cepheid, Sunnyvale, CA, United States). Materials and Methods The sputum samples are received from five districts of Punjab. Sputum samples of the patients with symptoms suggestive of pulmonary tuberculosis including both new cases and on treatment are received from the various district and civil hospitals of five districts. Sputum specimen was processed for TB detection by Cartridge Based Nucleic Acid Amplification testing (CB-NAAT) using Xpert MTB/RiF assay technology. Results The study period is from October 2013 to September 2014. A total of 907 patients with symptoms suggestive of pulmonary tuberculosis including both new cases and on treatment. Out of these patients 733 were reported MTB detected. Out of these 907 patients 29 were reported HIV positive and out of 733 patients 19(2.5%) were reported positive for (HIV +TUBERCULOSIS). Of these 19 cases 16(84.21%) cases were sensitive to rifampicin (RIF) and 3(15.78%) cases were showing resistance to rifampicin (RIF) Drug. Conclusion Co-existence of HIV and tuberculosis is high and there is high Prevalence of MDR tuberculosis in HIV patients. PMID:26155475

  12. Extrapulmonary tuberculosis, human immunodeficiency virus, and foreign birth in North Carolina, 1993 – 2006

    PubMed Central

    Kipp, Aaron M; Stout, Jason E; Hamilton, Carol Dukes; Van Rie, Annelies

    2008-01-01

    Background The proportion of extrapulmonary tuberculosis (EPTB) reported in the United States has been gradually increasing. HIV infection and foreign birth are increasingly associated with tuberculosis and understanding their effect on the clinical presentation of tuberculosis is important. Methods Case-control study of 6,124 persons with tuberculosis reported to the North Carolina Division of Public health from January 1, 1993 to December 31, 2006. Multivariate logistic regression was used to obtain adjusted odds ratios measuring the associations of foreign birth region and US born race/ethnicity, by HIV status, with EPTB. Results Among all patients with tuberculosis, 1,366 (22.3%) had EPTB, 563 (9.2%) were HIV co-infected, and 1,299 (21.2%) were foreign born. Among HIV negative patients, EPTB was associated with being foreign born (adjusted ORs 1.36 to 5.09, depending on region of birth) and with being US born, Black/African American (OR 1.84; 95% CI 1.42, 2.39). Among HIV infected patients, EPTB was associated with being US born, Black/African American (OR 2.60; 95% CI 1.83, 3.71) and with foreign birth in the Americas (OR 5.12; 95% CI 2.84, 9.23). Conclusion Foreign born tuberculosis cases were more likely to have EPTB than US born tuberculosis cases, even in the absence of HIV infection. Increasing proportions of foreign born and HIV-attributable tuberculosis cases in the United States will likely result in a sustained burden of EPTB. Further research is needed to explore why the occurrence and type of EPTB differs by region of birth and whether host genetic and/or bacterial variation can explain these differences in EPTB. PMID:18394166

  13. 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 products safety, efficacy and quality. Good practices for storage, transport, distribution and quality control procedures must follow. In contrast to other high-burden countries, Brazil produces tuberculosis drugs through a strong network of public sector drug manufacturers regulated by a World Health Organization-certified national sanitary authority. The installed capacity for production surpasses the 71,000 needed treatments in the country. However, in order to be prepared to act as a global supplier, important bottlenecks are to be overcome. This article presents an in-depth analysis of the current status of production of tuberculosis drugs in Brazil and the bottlenecks and opportunities for the country to sustain national demand and play a role as a potential global supplier. Raw material and drug production, quality control, international certification and pre-qualification, political commitment and regulatory aspects are discussed, as well recommendations for tackling these bottlenecks. This discussion becomes more important as new drugs and regimens to treat tuberculosis are expected in a close future. Summary International manufacturers of raw material for tuberculosis treatment should undergo certification and pre-qualify their active pharmaceutical ingredients as a first step to ensure quality of tuberculosis drugs. At the country level, Brazilian public manufacturers should apply for international certification and tuberculosis drugs should be pre-qualified by international organisms. Finally, only with political commitment and large-scale production will Brazilian public sector manufacturers be able to partially supply the global market. PMID:23537151

  14. Controlling the seedbeds of tuberculosis: diagnosis and treatment of tuberculosis infection.

    PubMed

    Rangaka, Molebogeng X; Cavalcante, Solange C; Marais, Ben J; Thim, Sok; Martinson, Neil A; Swaminathan, Soumya; Chaisson, Richard E

    2015-12-01

    The billions of people with latent tuberculosis infection serve as the seedbeds for future cases of active tuberculosis. Virtually all episodes of tuberculosis disease are preceded by a period of asymptomatic Mycobacterium tuberculosis infection; therefore, identifying infected individuals most likely to progress to disease and treating such subclinical infections to prevent future disease provides a crucial opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programmes focusing on single strategies rather than comprehensive programmes that deliver an integrated arsenal for tuberculosis control might continue to struggle. Tuberculosis preventive therapy is a poorly used method that is essential for controlling the reservoirs of disease that drive the epidemic. Comprehensive control strategies that combine preventive therapy for the most high-risk populations and communities with improved case-finding and treatment, control of transmission, and health systems strengthening could ultimately lead to worldwide tuberculosis elimination. In this Series paper we outline challenges to implementation of preventive therapy and provide pragmatic suggestions for overcoming them. We further advocate for tuberculosis preventive therapy as the core of a renewed worldwide focus to implement a comprehensive epidemic control strategy that would reduce new tuberculosis cases to elimination targets. This strategy would be underpinned by accelerated research to further understand the biology of subclinical tuberculosis infections, develop novel diagnostics and drug regimens specifically for subclinical tuberculosis infection, strengthen health systems and community engagement, and enhance sustainable large scale implementation of preventive therapy programmes. PMID:26515679

  15. ‘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

  16. Biomarkers on patient T cells diagnose active tuberculosis and monitor treatment response

    PubMed Central

    Adekambi, Toidi; Ibegbu, Chris C.; Cagle, Stephanie; Kalokhe, Ameeta S.; Wang, Yun F.; Hu, Yijuan; Day, Cheryl L.; Ray, Susan M.; Rengarajan, Jyothi

    2015-01-01

    BACKGROUND. The identification and treatment of individuals with tuberculosis (TB) is a global public health priority. Accurate diagnosis of pulmonary active TB (ATB) disease remains challenging and relies on extensive medical evaluation and detection of Mycobacterium tuberculosis (Mtb) in the patient’s sputum. Further, the response to treatment is monitored by sputum culture conversion, which takes several weeks for results. Here, we sought to identify blood-based host biomarkers associated with ATB and hypothesized that immune activation markers on Mtb-specific CD4+ T cells would be associated with Mtb load in vivo and could thus provide a gauge of Mtb infection. METHODS. Using polychromatic flow cytometry, we evaluated the expression of immune activation markers on Mtb-specific CD4+ T cells from individuals with asymptomatic latent Mtb infection (LTBI) and ATB as well as from ATB patients undergoing anti-TB treatment. RESULTS. Frequencies of Mtb-specific IFN-γ+CD4+ T cells that expressed immune activation markers CD38 and HLA-DR as well as intracellular proliferation marker Ki-67 were substantially higher in subjects with ATB compared with those with LTBI. These markers accurately classified ATB and LTBI status, with cutoff values of 18%, 60%, and 5% for CD38+IFN-γ+, HLA-DR+IFN-γ+, and Ki-67+IFN-γ+, respectively, with 100% specificity and greater than 96% sensitivity. These markers also distinguished individuals with untreated ATB from those who had successfully completed anti-TB treatment and correlated with decreasing mycobacterial loads during treatment. CONCLUSION. We have identified host blood-based biomarkers on Mtb-specific CD4+ T cells that discriminate between ATB and LTBI and provide a set of tools for monitoring treatment response and cure. TRIAL REGISTRATION. Registration is not required for observational studies. FUNDING. This study was funded by Emory University, the NIH, and the Yerkes National Primate Center. PMID:25822019

  17. 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

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

    PubMed Central

    2012-01-01

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

  19. 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

  20. 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 activate sodium ion (Na ) channels, causing cell membrane excitability and instability. Worldwide coral bleaching is now well documented, and there is a strong association between global warming and the bleaching and death of coral. This, together with natural environmental factors such as earthquakes and hurricanes, and man-made factors such as tourism, dock construction, sewage and eutrophication, may create more favourable environments for G. toxicus. While low levels of G. toxicus are found throughout tropical and subtropical waters, the presence of bloom numbers is unpredictable and patchy. Only certain genetic strains produce ciguatoxins, and environmental triggers for increasing toxin production are unknown. PMID:11078162

  1. [Pathogenetic therapy in pulmonary tuberculosis].

    PubMed

    Starostenko, E V

    1989-01-01

    Clinico-biochemical comparisons with an account of the peculiar characteristics of the tuberculosis process showed that it was advisable to use antioxidants as antifibrotic pathogenetic agents. The most pronounced effect was observed when combinations of two antioxidants or one antioxidant with lidase were applied. PMID:2748555

  2. 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

  3. 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…

  4. HIV and tuberculosis in India.

    PubMed

    Swaminathan, Soumya; Nagendran, G

    2008-11-01

    The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as the leading cause of death. Further,there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. The diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography,which has problems of specificity. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resourc-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping drug toxicities,risk of immune reconstitution inflammatory syndrome (IRIS) and challenges related to adherence. From a programmatic point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control programs, in India. PMID:19208978

  5. Epidemiological basis of tuberculosis eradication

    PubMed Central

    Horwitz, Ole; Payne, Penelope G.; Wilbek, Erik

    1966-01-01

    As knowledge of the epidemiology of tuberculosis in Greenland has increased, it has become evident that the majority of cases develop long after the primary infection and that it would therefore be valuable from the public health point of view if the disease rate among naturally infected persons could be reduced. To examine the possibility of achieving this, a double-blind drug trial with isoniazid and a placebo was conducted among some 70% of the adult population of western Greenland. The results show that throughout the six years of the study the incidence of tuberculosis was lower in the group treated with isoniazid and that this reduction occurred whether the initial X-rays pictures were normal or showed suspicious or healed lesions. It is concluded that chemoprophylaxis programmes should probably be administered only to selected groups of the population. The delimitation of such groups is discussed on the basis of their tuberculosis risk and of the expected yield in terms of reduction in tuberculosis prevalence. PMID:5335457

  6. Unusual manifestations of osteoarticular tuberculosis.

    PubMed

    Babhulkar, Sudhir S; Pande, Sonali K

    2002-05-01

    Unusual manifestations of osteoarticular tuberculosis, especially tubercular osteomyelitis, are described. Diagnostic problems may arise and lead to delay in treatment if these conditions are not considered in the differential diagnosis. The importance of bacteriologic and histopathologic confirmation of the disease is stressed. PMID:11964639

  7. 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

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

    PubMed Central

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

    2010-01-01

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

  9. 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 and HRZO regimens were inferior. But all the FQs-containing regimens did not show superiority in other outcomes (such as treatment failure, serious adverse events and all-cause death). Thus, HRZE is still an effective regimen for this population. Although moxifloxacin-containing regimens have deomonstrated their potential, FQs-containing regimens should be used with great caution to avoid widespread FQs-resistance worldwide. PMID:26669635

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

    PubMed Central

    Raman, Karthik; Yeturu, Kalidas; Chandra, Nagasuma

    2008-01-01

    Background Tuberculosis still remains one of the largest killer infectious diseases, warranting the identification of newer targets and drugs. Identification and validation of appropriate targets for designing drugs are critical steps in drug discovery, which are at present major bottle-necks. A majority of drugs in current clinical use for many diseases have been designed without the knowledge of the targets, perhaps because standard methodologies to identify such targets in a high-throughput fashion do not really exist. With different kinds of 'omics' data that are now available, computational approaches can be powerful means of obtaining short-lists of possible targets for further experimental validation. Results We report a comprehensive in silico target identification pipeline, targetTB, for Mycobacterium tuberculosis. The pipeline incorporates a network analysis of the protein-protein interactome, a flux balance analysis of the reactome, experimentally derived phenotype essentiality data, sequence analyses and a structural assessment of targetability, using novel algorithms recently developed by us. Using flux balance analysis and network analysis, proteins critical for survival of M. tuberculosis are first identified, followed by comparative genomics with the host, finally incorporating a novel structural analysis of the binding sites to assess the feasibility of a protein as a target. Further analyses include correlation with expression data and non-similarity to gut flora proteins as well as 'anti-targets' in the host, leading to the identification of 451 high-confidence targets. Through phylogenetic profiling against 228 pathogen genomes, shortlisted targets have been further explored to identify broad-spectrum antibiotic targets, while also identifying those specific to tuberculosis. Targets that address mycobacterial persistence and drug resistance mechanisms are also analysed. Conclusion The pipeline developed provides rational schema for drug target identification that are likely to have high rates of success, which is expected to save enormous amounts of money, resources and time in the drug discovery process. A thorough comparison with previously suggested targets in the literature demonstrates the usefulness of the integrated approach used in our study, highlighting the importance of systems-level analyses in particular. The method has the potential to be used as a general strategy for target identification and validation and hence significantly impact most drug discovery programmes. PMID:19099550

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

    PubMed Central

    2010-01-01

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

  13. 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)

  14. Tuberculosis Incidence in Prisons: A Systematic Review

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2014-01-01

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

  16. 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. PMID:26211466

  17. 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 influence the cytokine response profile among those with LTBI. Prior BCG exposure may reduce Th1 cytokine responses in LTBI. PMID:25372043

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

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

    2015-01-01

    Introduction. Tuberculosis is still one of the most important health problems in developing countries and increasing drug resistance is the main concern for its treatment. This study was designed to characterize the drug resistant Mycobacterium tuberculosis isolated from patients suffering from pulmonary tuberculosis in northeast of Iran. Method. In this cross-sectional study during 2012-2013, drug susceptibility testing was performed on Mycobacterium tuberculosis isolated in northeast of Iran using proportional method. Epidemiological data concerning these strains were also analyzed. Results. Among 125 studied isolates, 25 mycobacteria (20%) were diagnosed as nontuberculosis mycobacteria. Among the remaining 100 Mycobacterium tuberculosis isolates, the resistance rates were 7%, 7%, 3%, and 9% against isoniazid, rifampin, ethambutol, and streptomycin, respectively. Four isolates were resistant against both isoniazid and rifampin (MDR tuberculosis). The highest resistance rate was observed among 1545-year-old patients. The MDR tuberculosis was much more prevalent among those who had previous history of treatment. Conclusion. Considering these findings, DOTS strategy should be emphasized and promptly used in order to prevent further resistance. Regarding the high rate of nontuberculosis mycobacteria, it is recommended that confirmatory tests were performed before any therapeutic decision. PMID:26064950

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

    PubMed

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

    2005-01-01

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

  1. Evidence of probable tuberculosis in Lithuanian mummies.

    PubMed

    Piombino-Mascali, D; Jankauskas, R; Tamoi?nas, A; Valan?ius, R; Gill-Frerking, H; Spigelman, M; Panzer, S

    2015-10-01

    Tuberculosis has affected Europe for millennia and continues to be a burden upon modern society. It is estimated that one-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of this condition. Despite the introduction of control strategies, the disease continues to be one of the most common causes of death globally. Within the framework of the Lithuanian Mummy Project, seven spontaneously mummified human bodies from a church crypt in Vilnius, dating from the 18th and 19th century, were CT-scanned to assess the presence of tuberculosis or other lung diseases. We encountered pulmonary lesions suggestive of cases of pulmonary tuberculosis. In addition, one case might have been affected by extra-pulmonary tuberculosis. This report replicates the image findings from previous studies on ancient mummies that provided evidence of tuberculosis in soft tissues, thus helping reconstruct the history of this disease over time. PMID:26048368

  2. 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...

  3. Evaluation of ethanol vortex ELISA for detection of bovine tuberculosis in cattle and deer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background The use of serological assays for diagnosis of bovine tuberculosis (TB) has been intensively studied and use of specific antigens have aided in improving the diagnostic accuracy of the assays. In the present study, we report an in-house enzyme linked immunosorbent assay (ELISA), developed...

  4. 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.

  5. The Athena Background

    NASA Astrophysics Data System (ADS)

    Piro, Luigi; Lotti, Simone; Macculi, Claudio; Molendi, Silvano; Eraerds, Tanja; Laurent, Philippe

    2015-09-01

    Estimating, reducing and controlling the residual particle background is fundamental for achieving the objectives of several science topics of Athena, in particular those connected with background dominated observations of faint and/or diffuse sources. This requires assessing the particle environment in L2, propagating the various particle components throughout the mirror, spacecraft, and instruments via proper modelling and simulations of various physical processes, implementing design and h/w measures at instrument and mission level to reduce the un-rejected background and identifying proper calibration methods to control the background variations. Likewise, an adequate knowledge of the XRB, made of components that may vary spatially or temporally, is required as well. Here we will review the present status of the background knowledge, and summarize the activities on-going within Athena at various levels.

  6. 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 ...

  7. Abdominal Tuberculosis: Observations in Three Cases

    PubMed Central

    Smith, Robert J.

    1978-01-01

    Although pulmonary tuberculosis has decreased, extra pulmonary tuberculosis has shown a relative increase in frequency during the past decade. This paper discusses three cases of extrapulmonary tuberculosis which presented with abdominal signs. The patients were completely evaluated and surgery was done, followed by antituberculosis therapy with survival and rehabilitation of all three patients. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:702550

  8. Monkey Models of Tuberculosis: Lessons Learned

    PubMed Central

    Peña, Juliet C.

    2014-01-01

    The use of animal models has been invaluable for studying the pathogenesis of Mycobacterium tuberculosis infection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research. PMID:25547788

  9. 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

  10. Monkey models of tuberculosis: lessons learned.

    PubMed

    Pea, Juliet C; Ho, Wen-Zhe

    2015-03-01

    The use of animal models has been invaluable for studying the pathogenesis of Mycobacterium tuberculosis infection, as well as for testing the efficacy of vaccines and drug regimens for tuberculosis. Among the applied animal models, nonhuman primates, particularly macaques, share the greatest anatomical and physiological similarities with humans. As such, macaque models have been used for investigating tuberculosis pathogenesis and preclinical testing of drugs and vaccines. This review focuses on published major studies which illustrate how the rhesus and cynomolgus macaques have enriched and may continue to advance the field of global tuberculosis research. PMID:25547788

  11. Isolated hepatosplenic tuberculosis: a rare presentation.

    PubMed

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

    2015-01-01

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

  12. 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

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

    PubMed Central

    2014-01-01

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

  14. DR*W201/P65 Tetramer Visualization of Epitope-Specific CD4 T-Cell during M. tuberculosis Infection and Its Resting Memory Pool after BCG Vaccination

    PubMed Central

    Wei, Huiyong; Wang, Richard; Yuan, Zhuqing; Chen, Crystal Y.; Huang, Dan; Halliday, Lisa; Zhong, Weihua; Zeng, Gucheng; Shen, Yun; Shen, Ling; Wang, Yunqi; Chen, Zheng W.

    2009-01-01

    Background In vivo kinetics and frequencies of epitope-specific CD4 T cells in lymphoid compartments during M. tuberculosis infection and their resting memory pool after BCG vaccination remain unknown. Methodology/Findings Macaque DR*W201 tetramer loaded with Ag85B peptide 65 was developed to directly measure epitope-specific CD4 T cells in blood and tissues form macaques after M. tuberculosis infection or BCG vaccination via direct staining and tetramer-enriched approach. The tetramer-based enrichment approach showed that P65 epitope-specific CD4 T cells emerged at mean frequencies of ∼500 and ∼4500 per 107 PBL at days 28 and 42, respectively, and at day 63 increased further to ∼22,000/107 PBL after M. tuberculosis infection. Direct tetramer staining showed that the tetramer-bound P65-specific T cells constituted about 0.2–0.3% of CD4 T cells in PBL, lymph nodes, spleens, and lungs at day 63 post-infection. 10-fold expansion of these tetramer-bound epitope-specific CD4 T cells was seen after the P65 peptide stimulation of PBL and tissue lymphocytes. The tetramer-based enrichment approach detected BCG-elicited resting memory P65-specific CD4 T cells at a mean frequency of 2,700 per 107 PBL. Significance Our work represents the first elucidation of in vivo kinetics and frequencies for tetramer-bound epitope-specific CD4 T cells in the blood, lymphoid tissues and lungs over times after M. tuberculosis infection, and BCG immunization. PMID:19730727

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

    PubMed Central

    Mller, 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 secondnineteenth 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 eighteenthnineteenth 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

  16. Childhood tuberculosis (Part-I). Epidemiology, pathogenesis, clinical profile.

    PubMed

    Mubarik, M; Nabi, B; Ladakhi, G M; Sethi, A S

    2000-01-01

    This paper focuses on the pathogenesis and clinical profile of tuberculosis (TB), a bacterial infection caused by Mycobacterium tuberculosis characterized by granuloma formation in infected tissues and by cell-mediated hypersensitivity. TB remains a major cause of morbidity and mortality worldwide and is the most common cause of death from a single infectious disease, particularly in children. Nearly 40 million children are likely to be exposed to the risk of TB and nearly 3-4 million children below age 5 years are estimated to be infected and may progress to disease. TB accounts for 10-15% of all pediatric deaths in a number of Indian hospitals. Factors such as low socioeconomic status, infections, drugs such as steroids, and age predisposes a person to TB. Childhood TB is classified as follows: 1) asymptomatic mantoux positive, 2) symptomatic mantoux positive, 3) primary pulmonary complex, 4) progressive pulmonary disease, 5) disseminated TB, 6) cervical and abdominal TB, 7) tubercular meningitis, 8) progressive bacillus Calmette-Guerin (BCG) disease, and 9) congenital tuberculosis. Among the various symptom complexes of childhood TB are failure to gain weight or weight loss, sudden onset of fever with erythema nodosum and phlyctenular conjunctivitis, failure to gain weight with respiratory wheezing. The direct and indirect impact of HIV infection on the development of TB in children is also discussed. PMID:12295956

  17. Current tuberculosis diagnostic tools & role of urease breath test.

    PubMed

    Maiga, Mamoudou; Abaza, Ahmed; Bishai, William R

    2012-05-01

    Tuberculosis (TB) remains a significant public health issue worldwide especially in developing countries, where the disease is endemic, and effective TB diagnostic as well as treatment-monitoring tools are serious barriers to defeating the disease. Detection of pathogen-specific metabolic pathways offers a potential alternative to current methods, which focus on bacterial growth, bacterial nucleic acid amplification, or detection of host immune response to the pathogen. Metabolic pathway detection may provide rapid and effective new tools for TB that can improve TB diagnostics for children and HIV infected patients. Metabolic breath tests are attractive because these are safe, and provide an opportunity for rapid point of care diagnostics and tool for drug efficacy evaluation during clinical trials. Our group has developed a rabbit urease breath test model to evaluate the sensitivity and the specificity of urease based detection of Mycobacterium tuberculosis. TB infected rabbits were given stable isotopically labelled urea as the substrate. The urea tracer was metabolized to 13 C-CO 2 and detected in exhaled breaths using portable infrared spectrometers. The signal correlated with bacterial load both for primary diagnostics and treatment monitoring. Clinical trials are currently ongoing to evaluate the value of the test in clinical management settings. Urea breath testing may provide a useful diagnostic and biomarker assay for tuberculosis and treatment response. PMID:22771606

  18. Adaptive background model

    NASA Astrophysics Data System (ADS)

    Lu, Xiaochun; Xiao, Yijun; Chai, Zhi; Wang, Bangping

    2007-11-01

    An adaptive background model aiming at outdoor vehicle detection is presented in this paper. This model is an improved model of PICA (pixel intensity classification algorithm), it classifies pixels into K-distributions by color similarity, and then a hypothesis that the background pixel color appears in image sequence with a high frequency is used to evaluate all the distributions to determine which presents the current background color. As experiments show, the model presented in this paper is a robust, adaptive and flexible model, which can deal with situations like camera motions, lighting changes and so on.

  19. The cosmic neutrino background

    NASA Technical Reports Server (NTRS)

    Dar, Arnon

    1991-01-01

    The cosmic neutrino background is expected to consist of relic neutrinos from the big bang, of neutrinos produced during nuclear burning in stars, of neutrinos released by gravitational stellar collapse, and of neutrinos produced by cosmic ray interactions with matter and radiation in the interstellar and intergalactic medium. Formation of baryonic dark matter in the early universe, matter-antimatter annihilation in a baryonic symmetric universe, and dark matter annihilation could have also contributed significantly to the cosmic neutrino background. The purpose of this paper is to review the properties of these cosmic neutrino backgrounds, the indirect evidence for their existence, and the prospects for their detection.

  20. Background Underground at WIPP

    NASA Astrophysics Data System (ADS)

    Esch, Ernst-Ingo; Hime, A.; Bowles, T. J.

    2001-04-01

    Recent interest to establish a dedicated underground laboratory in the United States prompted an experimental program at to quantify the enviromental backgrounds underground at the Waste Isolation Pilot Plant (WIPP) in Carlsbad, New Mexico. An outline of this program is provided along with recent experimental data on the cosmic ray muon flux at the 650 meter level of WIPP. The implications of the cosmic ray muon and fast neutron background at WIPP will be discussed in the context of new generation, low background experiments envisioned in the future.

  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. Navicular tuberculosis: A rare localization of bone tuberculosis

    PubMed Central

    Lemnouer, Abdelhay; Frikh, Mohammed; Belfquih, Bouchra; Jaafar, Abdelwahab; Bouya, Ayoub; Jidal, Mohamed; Boussouga, Mustapha; Elouennass, Mostafa

    2015-01-01

    Tuberculosis (TB) is a global public health problem endemic to Morocco. While extrapulmonary TB uncommonly presents in osteoarticular anatomic locations, tarsal or metatarsal osteitis can occur when TB presents in the tarsal bones. Clinical symptoms are often insidious causing a delay in diagnosis that may lead to bone destruction. While diagnosis can be guided by X-ray imaging, bacteriologic and histologic examination of the tissue allows for pathogen isolation, identification of the bacillus and strain sensitivity to antibacillary treatment. We report a rare case of navicular osteitis associated with tarso-metatarsal arthritis caused by tuberculosis in a 68-year-old man. This case illustrates an exceptional location of osteoarticular TB and support diagnostic difficulties encountered: (i) imaging is not specific; (ii) lesions are paucibacillary which reduces conventional microbiological methods sensitivity and (iii) the peripheral location of the Koch bacillus within the lesion dictates surgical biopsy than percutaneous puncture. We recommend testing for tuberculosis in any case of chronic osteolysis and/or arthritis of the foot, especially in TB endemic countries. PMID:26793464

  3. The role of moxifloxacin in tuberculosis therapy.

    PubMed

    Gillespie, Stephen H

    2016-03-01

    Tuberculosis (TB) remains a global threat with more than 9 million new infections. Treatment remains difficult and there has been no change in the duration of the standard regimen since the early 1980s. Moreover, many patients are unable to tolerate this treatment and discontinue therapy, increasing the risk of resistance. There is a growing tide of multidrug resistance and few effective antibiotics to tackle the problem. Since the turn of the millennium there has been a surge in interest in developing new therapies for TB and a number of new drugs have been developed. In this review the repurposing of moxifloxacin, an 8-methoxy-fluoroquinolone, for TB treatment is discussed. The evidence that underpins the development of this agent is reviewed. The results of the recently completed phase III trials are summarised and the reasons for the unexpected outcome are explored. Finally, the design of new trials that incorporate moxifloxacin, and that address both susceptible disease and multidrug resistance, is described. PMID:26929417

  4. 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

  5. Amplification of DNA of Mycobacterium tuberculosis from peripheral blood of patients with pulmonary tuberculosis.

    PubMed

    Schluger, N W; Condos, R; Lewis, S; Rom, W N

    1994-07-23

    Sputum examination for rapid diagnosis of pulmonary tuberculosis is not always satisfactory. We examined peripheral blood with the polymerase chain reaction (PCR). Blood samples were collected from 8 consecutive patients with suspected pulmonary tuberculosis and from 18 healthy controls, half of whom were tuberculin skin-test positive. All 8 patients had evidence of circulating Mycobacterium tuberculosis DNA in the lymphocyte fraction of peripheral blood, and positive sputum cultures indicating active pulmonary tuberculosis. None of the healthy controls had positive PCR results. This PCR technique may prove useful for the rapid diagnosis of tuberculosis. PMID:7913158

  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. 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.

  8. The GLAST Background Model

    SciTech Connect

    Ormes, J. F.; Atwood, W.; Burnett, T.; Grove, E.; Longo, F.; McEnery, J.; Ritz, S.; Mizuno, T.

    2007-07-12

    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.

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

    PubMed Central

    2010-01-01

    Background To date, the function of many hypothetical membrane proteins of Mycobacterium tuberculosis is still unknown and their involvement in pathogen-host interactions has not been yet clearly defined. In this study, the biological activity of peptides derived from the hypothetical membrane protein Rv0679c of M. tuberculosis and their involvement in pathogen-host interactions was assessed. Transcription of the Rv0679c gene was studied in 26 Mycobacterium spp. Strains. Antibodies raised against putative B-cell epitopes of Rv0679c were used in Western blot and immunoelectron microscopy assays. Synthetic peptides spanning the entire length of the protein were tested for their ability to bind to A549 and U937 cells. High-activity binding peptides (HABPs) identified in Rv0679c were tested for their ability to inhibit mycobacterial invasion into cells. Results The gene encoding Rv0679c was detected in all strains of the M. tuberculosis complex (MTC), but was only transcribed in M. tuberculosis H37Rv, M. tuberculosis H37Ra and M. africanum. Anti-Rv0679c antibodies specifically recognized the protein in M. tuberculosis H37Rv sonicate and showed its localization on mycobacterial surface. Four HABPs inhibited invasion of M. tuberculosis to target cells by up to 75%. Conclusions The results indicate that Rv0679c HABPs and in particular HABP 30979 could be playing an important role during M. tuberculosis invasion of host cells, and therefore could be interesting research targets for studies aimed at developing strategies to control tuberculosis. PMID:20388213

  10. 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 Morans 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 comprehension of TB transmission dynamics in an urban setting in Japan. PMID:26382251

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

    PubMed Central

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

    2013-01-01

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

  12. 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.

  13. [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. PMID:23152388

  14. The impact of diabetes on tuberculosis treatment outcomes: A systematic review

    PubMed Central

    2011-01-01

    Background Multiple studies of tuberculosis treatment have indicated that patients with diabetes mellitus may experience poor outcomes. We performed a systematic review and meta-analysis to quantitatively summarize evidence for the impact of diabetes on tuberculosis outcomes. Methods We searched PubMed, EMBASE and the World Health Organization Regional Indexes from 1 January 1980 to 31 December 2010 and references of relevant articles for reports of observational studies that included people with diabetes treated for tuberculosis. We reviewed the full text of 742 papers and included 33 studies of which 9 reported culture conversion at two to three months, 12 reported the combined outcome of failure and death, 23 reported death, 4 reported death adjusted for age and other potential confounding factors, 5 reported relapse, and 4 reported drug resistant recurrent tuberculosis. Results Diabetes is associated with an increased risk of failure and death during tuberculosis treatment. Patients with diabetes have a risk ratio (RR) for the combined outcome of failure and death of 1.69 (95% CI, 1.36 to 2.12). The RR of death during tuberculosis treatment among the 23 unadjusted studies is 1.89 (95% CI, 1.52 to 2.36), and this increased to an effect estimate of 4.95 (95% CI, 2.69 to 9.10) among the 4 studies that adjusted for age and other potential confounding factors. Diabetes is also associated with an increased risk of relapse (RR, 3.89; 95% CI, 2.43 to 6.23). We did not find evidence for an increased risk of tuberculosis recurrence with drug resistant strains among people with diabetes. The studies assessing sputum culture conversion after two to three months of tuberculosis therapy were heterogeneous with relative risks that ranged from 0.79 to 3.25. Conclusions Diabetes increases the risk of failure and death combined, death, and relapse among patients with tuberculosis. This study highlights a need for increased attention to treatment of tuberculosis in people with diabetes, which may include testing for suspected diabetes, improved glucose control, and increased clinical and therapeutic monitoring. PMID:21722362

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

    PubMed Central

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

    2007-01-01

    Background The global tuberculosis epidemic results in nearly 2 million deaths and 9 million new cases of the disease a year. The vast majority of tuberculosis patients live in developing countries, where the diagnosis of tuberculosis relies on the identification of acid-fast bacilli on unprocessed sputum smears using conventional light microscopy. Microscopy has high specificity in tuberculosis-endemic countries, but modest sensitivity which varies among laboratories (range 20% to 80%). Moreover, the sensitivity is poor for paucibacillary disease (e.g., pediatric and HIV-associated tuberculosis). Thus, the development of rapid and accurate new diagnostic tools is imperative. Immune-based tests are potentially suitable for use in low-income countries as some test formats can be performed at the point of care without laboratory equipment. Currently, dozens of distinct commercial antibody detection tests are sold in developing countries. The question is do they work? Methods and Findings We conducted a systematic review to assess the accuracy of commercial antibody detection tests for the diagnosis of pulmonary tuberculosis. Studies from all countries using culture and/or microscopy smear for confirmation of pulmonary tuberculosis were eligible. Studies with fewer than 50 participants (25 patients and 25 control participants) were excluded. In a comprehensive search, we identified 68 studies. The results demonstrate that (1) overall, commercial tests vary widely in performance; (2) sensitivity is higher in smear-positive than smear-negative samples; (3) in studies of smear-positive patients, Anda-TB IgG by enzyme-linked immunosorbent assay shows limited sensitivity (range 63% to 85%) and inconsistent specificity (range 73% to 100%); (4) specificity is higher in healthy volunteers than in patients in whom tuberculosis disease is initially suspected and subsequently ruled out; and (5) there are insufficient data to determine the accuracy of most commercial tests in smear microscopynegative patients, as well as their performance in children or persons with HIV infection. Conclusions None of the commercial tests evaluated perform well enough to replace sputum smear microscopy. Thus, these tests have little or no role in the diagnosis of pulmonary tuberculosis. Lack of methodological rigor in these studies was identified as a concern. It will be important to review the basic science literature evaluating serological tests for the diagnosis of pulmonary tuberculosis to determine whether useful antigens have been described but their potential has not been fully exploited. Activities leading to the discovery of new antigens with immunodiagnostic potential need to be intensified. PMID:17564490

  16. 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 (20102013) 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 0.340.90, p = 0.017). The inference of transmission in this study was limited by the lack of genotyping data for household contacts. Capturing incident disease only among household contacts may also limit the extrapolation of these findings to the community setting. Conclusions The low relative fitness of MDRTB estimated by this study improves the chances of controlling drug-resistant tuberculosis. However, fitter multidrug-resistant strains that emerge over time may make this increasingly difficult. PMID:26103620

  17. 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 tuberculosis were household tuberculosis contact (adjusted OR, 27.23, 95% CI 8.19-90.58) and ever smoking tobacco (adjusted OR 1.64, 96% CI 1.01-2.66). Conclusion In a population where the majority had proper ventilation in cooking places, the association between use of solid fuel for cooking or for heating and tuberculosis was not statistically significant. PMID:21702987

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

    PubMed Central

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

    2001-01-01

    Mycobacterium tuberculosis is a facultative intracellular pathogen that has evolved the ability to survive and multiply within human macrophages. It is not clear how M. tuberculosis avoids the destructive action of macrophages, but this ability is fundamental in the pathogenicity of tuberculosis. A gene previously identified in M. tuberculosis, designated eis, was found to enhance intracellular survival of Mycobacterium smegmatis in the human macrophage-like cell line U-937 (J. Wei et al., J. Bacte