[Tuberculosis Among Refugees and Asylum Seekers: Tuberculosis Screening on Arrival and Case Management].

PubMed

Priwitzer, Martin

2018-04-01

The statement of the Federal Association of Physicians of Public Health Services provides recommendations concerning tuberculosis screening of refugees and asylum seekers on arrival specific to different groups of persons (adults, children, pregnant women, unaccompanied minors), taking into account the legal background and the current recommendations of the Robert Koch Institute as well as of the German Society for Pediatric Infectiology. In addition, recommendations are given to ensure treatment success in refugees and asylum seekers with tuberculosis, to carry out contact investigations and for preventive treatment of latent tuberculosis infection among refugees and asylum seekers. © Georg Thieme Verlag KG Stuttgart · New York.

Mycobacterium tuberculosis Metabolism

PubMed Central

Warner, Digby F.

2015-01-01

Metabolism underpins the physiology and pathogenesis of Mycobacterium tuberculosis. However, although experimental mycobacteriology has provided key insights into the metabolic pathways that are essential for survival and pathogenesis, determining the metabolic status of bacilli during different stages of infection and in different cellular compartments remains challenging. Recent advances—in particular, the development of systems biology tools such as metabolomics—have enabled key insights into the biochemical state of M. tuberculosis in experimental models of infection. In addition, their use to elucidate mechanisms of action of new and existing antituberculosis drugs is critical for the development of improved interventions to counter tuberculosis. This review provides a broad summary of mycobacterial metabolism, highlighting the adaptation of M. tuberculosis as specialist human pathogen, and discusses recent insights into the strategies used by the host and infecting bacillus to influence the outcomes of the host–pathogen interaction through modulation of metabolic functions. PMID:25502746

Spoligotyping of Mycobacterium tuberculosis isolates from patients with pulmonary tuberculosis in Mumbai, India.

PubMed

Kulkarni, Savita; Sola, Christophe; Filliol, Ingrid; Rastogi, Nalin; Kadival, Gururaj

2005-05-01

Tuberculosis remains a major health problem in India, with 2 million new cases and 421,000 deaths each year. In this paper, we describe the spoligotyping results of 216 Mycobacterium tuberculosis culture isolates from patients with pulmonary tuberculosis in Mumbai, India. As spoligotyping data from India have rarely been described until now, and as there is limited information on the major circulating clades of M. tuberculosis, the data obtained were also compared to an international spoligotype database (SpolDB4) that contained patterns from 22,546 isolates from more than 100 countries. Eighty-four (39%) of the isolates were definitively marked as orphan strains, indicating the paucity of such data from India. The remaining 132 isolates clustered among 59 shared types; among these, 42 shared types were already present in the database, 17 were newly created, and 5 of them were specifically reported from Mumbai. A total of 9 major types in this study clustered 32% of the isolates. At the phylogenetic level, 30% of the isolates belonged to the Central Asian families CAS1 and CAS2, of the major genetic group (MGG) 1, 29% to MGG 2 and 3 families (spacers 33-36 missing) and 17% to the ancestral East African Indian (EAI) family. Finally, nearly 10% of the isolates belonged to the W-Beijing family in a broad sense, also in the MGG 1 group. In conclusion, historic clones of the MGG 1 group of M. tuberculosis are responsible for roughly 60% of all tuberculosis cases in Mumbai. Together with the fact that organisms presumably of European descent (such as the Haarlem family) were only rarely found, our observations suggest that tuberculosis in Mumbai, India is essentially caused by historical clones of tubercle bacilli undergoing active circulation due to uncontrolled demography, high prevalence of the disease, and a paucity of resources.

Multidrug-resistant tuberculosis.

PubMed

Zager, Ellen M; McNerney, Ruth

2008-01-25

With almost 9 million new cases each year, tuberculosis remains one of the most feared diseases on the planet. Led by the STOP-TB Partnership and WHO, recent efforts to combat the disease have made considerable progress in a number of countries. However, the emergence of mutated strains of Mycobacterium tuberculosis that are resistant to the major anti-tuberculosis drugs poses a deadly threat to control efforts. Multidrug-resistant tuberculosis (MDR-TB) has been reported in all regions of the world. More recently, extensively drug resistant-tuberculosis (XDR-TB) that is also resistant to second line drugs has emerged in a number of countries. To ensure that adequate resources are allocated to prevent the emergence and spread of drug resistance it is important to understand the scale of the problem. In this article we propose that current methods of describing the epidemiology of drug resistant tuberculosis are not adequate for this purpose and argue for the inclusion of population based statistics in global surveillance data. Whereas the prevalence of tuberculosis is presented as the proportion of individuals within a defined population having disease, the prevalence of drug resistant tuberculosis is usually presented as the proportion of tuberculosis cases exhibiting resistance to anti-tuberculosis drugs. Global surveillance activities have identified countries in Eastern Europe, the former Soviet Union and regions of China as having a high proportion of MDR-TB cases and international commentary has focused primarily on the urgent need to improve control in these settings. Other regions, such as sub-Saharan Africa have been observed as having a low proportion of drug resistant cases. However, if one considers the incidence of new tuberculosis cases with drug resistant disease in terms of the population then countries of sub-Saharan Africa have amongst the highest rates of transmitted MDR-TB in the world. We propose that inclusion of population based statistics in

[Skin tuberculin test (STT) for screening tuberculosis in contacts of tuberculosis patients].

PubMed

Toure, N O; Dia, Y; Diatta, A; Ndiaye, E H M; Thiam, K; Niang, A; Fall, N; Kane, M; Mbae, F; Cisse, A; Hane, A A

2006-01-01

Many studies have underlined the theorical and practical role of Skin Tuberculin Test (STT) as an important tool for the diagnosis and for the screening of tuberculosis in the population. This prospective study evaluated STT in 51 smear positive tuberculosis patients and 108 contacts tuberculosis patients apparently in a good health condition. Twenty seven patients have disappeared before the end of the study and 7 patients were excluded for non suitable results. So we analysed only 73 cases. The mean age was 34 years, with extreme of 1 and 77 years. There were 33 male and 40 female patients for a sex-ratio of 0,8. BCG vaccination scar was found in 64% of patients. We calculated the Body-Mass-Index and we found a proteinocaloric malnutrition (BMI<18,5) in 30%. The mean diameter of STT induration was 12,3mm with extremes of 7 and 20mm. Considering a STT < 7 mm as negative, 4 patients (5%) had a negative STT and 69 (95%) a positive STT. 13 of these 69 patients had a STT > 15mm. The age group of the 10 to 50 years had more positive STT. Meanwhile, according to the sexe and to the nutritional status, there was no statistical difference. All patients with a negative STT received BCG vaccination after 2 months of follow-up. Those with STT>15mm were examinated and had a chest X-ray the day of their enrolment, at the second month and at the sixth month and we didn't find any evolutive tuberculosis. According to these results, we can conclude that STT is not an important test for the screening of pulmonary tuberculosis in contact patients. Clinical examination, chest X-ray and sputum smear remain very important for the diagnosis. Despite these results, STT remain the only validated technic between the different tuberculin tests. Its interest was twofold: the research of an acquired immunity against tuberculosis after BCG immunisation and it is clinical test for the diagnosis of tuberculosis in children.

A proposed national strategy for tuberculosis vaccine development.

PubMed

Ginsberg, A M

2000-06-01

The global tuberculosis epidemic causes approximately 5% of deaths worldwide. Despite recent concerted and largely successful tuberculosis control efforts, the incidence of tuberculosis in the United States remains 74-fold higher than the stated elimination goal of <1 case per million population by the year 2010. Current bacille Calmette-Guérin vaccines, although efficacious in preventing extrapulmonary tuberculosis in young children, have shown widely variable efficacy in preventing adult pulmonary tuberculosis, confound skin test screening, and are not recommended for use in the United States. The Advisory Council for Elimination of Tuberculosis recently stated that tuberculosis would not be eliminated from the United States without a more effective vaccine. Recent scientific advances have created unprecedented opportunity for tuberculosis vaccine development. Therefore, members of the broad tuberculosis research and control communities have recently created and proposed a national strategy, or blueprint, for tuberculosis vaccine development, which is presented here.

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

PubMed Central

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

2011-01-01

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

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

PubMed Central

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

2011-01-01

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

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

PubMed Central

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

2015-01-01

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

Genotyping and drug resistance patterns of M. tuberculosis strains in Pakistan

PubMed Central

Tanveer, Mahnaz; Hasan, Zahra; Siddiqui, Amna R; Ali, Asho; Kanji, Akbar; Ghebremicheal, Solomon; Hasan, Rumina

2008-01-01

Background The incidence of tuberculosis in Pakistan is 181/100,000 population. However, information about transmission and geographical prevalence of Mycobacterium tuberculosis strains and their evolutionary genetics as well as drug resistance remains limited. Our objective was to determine the clonal composition, evolutionary genetics and drug resistance of M. tuberculosis isolates from different regions of the country. Methods M. tuberculosis strains isolated (2003–2005) from specimens submitted to the laboratory through collection units nationwide were included. Drug susceptibility was performed and strains were spoligotyped. Results Of 926 M. tuberculosis strains studied, 721(78%) were grouped into 59 "shared types", while 205 (22%) were identified as "Orphan" spoligotypes. Amongst the predominant genotypes 61% were Central Asian strains (CAS ; including CAS1, CAS sub-families and Orphan Pak clusters), 4% East African-Indian (EAI), 3% Beijing, 2% poorly defined TB strains (T), 2% Haarlem and LAM (0.2). Also TbD1 analysis (M. tuberculosis specific deletion 1) confirmed that CAS1 was of "modern" origin while EAI isolates belonged to "ancestral" strain types. Prevalence of CAS1 clade was significantly higher in Punjab (P < 0.01, Pearsons Chi-square test) as compared with Sindh, North West Frontier Province and Balochistan provinces. Forty six percent of isolates were sensitive to five first line antibiotics tested, 45% were Rifampicin resistant, 50% isoniazid resistant. MDR was significantly associated with Beijing strains (P = 0.01, Pearsons Chi-square test) and EAI (P = 0.001, Pearsons Chi-square test), but not with CAS family. Conclusion Our results show variation of prevalent M. tuberculosis strain with greater association of CAS1 with the Punjab province. The fact that the prevalent CAS genotype was not associated with drug resistance is encouraging. It further suggests a more effective treatment and control programme should be successful in reducing the

The dynamic of tuberculosis case finding in the era of the public–private mix strategy for tuberculosis control in Central Java, Indonesia

PubMed Central

Reviono, Reviono; Setianingsih, Wahyu; Damayanti, Kusmadewi Eka; Ekasari, Ratna

2017-01-01

ABSTRACT Background: The public–private mix (PPM) strategy has strengthened tuberculosis care and control in many countries. Indonesia, a country with a high tuberculosis burden, has a low tuberculosis case detection rate (CDR), despite PPM implementation in 2003. The PPM in Indonesia involves primary healthcare centers, hospitals, and specialized chest clinics. The long-term impact of the strategy is unknown. Objective: We aimed to explore the case detection achievements of the tuberculosis program since PPM implementation in Central Java in 2003. Methods: This retrospective cohort study covered the period 1 January 2000 to 31 December 2014. The data from tuberculosis patients treated in all health facilities in Central Java implementing directly observed treatment short-course, recorded via a standardized form, were analyzed after being validated by the Office of Health of Central Java Province. We evaluated the CDR, case notification rate, and total number of cases, using linear regression to analyze the temporal trends of those indicators in the phases of PPM implementation. Results: The CDR increased during the initial phase (2000–2005), decreased during the mid-phase (2006–2009), and increased slightly during the late phase (2010–2014), ranging from 13 to 61.72. These trends were observed despite a steady increase in the number of participating healthcare facilities. The regression analysis showed that the CDR of referral institutions contributed the most to the total CDR of Central Java Province. Many of the smear-negative tuberculosis cases recorded at primary healthcare centers may have been smear positive; this probable misclassification could have been partially avoided if more specific and sensitive diagnostic tools were available. Conclusions: The CDR remains below the national target (70%). Early awareness of a negative trend in certain program indicators is important to ensure program sustainability. Careful observation of the indicator

[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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

PubMed Central

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

2007-01-01

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

What We Know About Tuberculosis Transmission: An Overview.

PubMed

Churchyard, Gavin; Kim, Peter; Shah, N Sarita; Rustomjee, Roxana; Gandhi, Neel; Mathema, Barun; Dowdy, David; Kasmar, Anne; Cardenas, Vicky

2017-11-03

Tuberculosis remains a global health problem with an enormous burden of disease, estimated at 10.4 million new cases in 2015. To stop the tuberculosis epidemic, it is critical that we interrupt tuberculosis transmission. Further, the interventions required to interrupt tuberculosis transmission must be targeted to high-risk groups and settings. A simple cascade for tuberculosis transmission has been proposed in which (1) a source case of tuberculosis (2) generates infectious particles (3) that survive in the air and (4) are inhaled by a susceptible individual (5) who may become infected and (6) then has the potential to develop tuberculosis. Interventions that target these events will interrupt tuberculosis transmission and accelerate the decline in tuberculosis incidence and mortality. The purpose of this article is to provide a high-level overview of what is known about tuberculosis transmission, using the tuberculosis transmission cascade as a framework, and to set the scene for the articles in this series, which address specific aspects of tuberculosis transmission. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Delamanid for multidrug-resistant pulmonary tuberculosis.

PubMed

Gler, Maria Tarcela; Skripconoka, Vija; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Park, Seung-Kyu; Shim, Tae Sun; Suh, Gee Young; Danilovits, Manfred; Ogata, Hideo; Kurve, Anu; Chang, Joon; Suzuki, Katsuhiro; Tupasi, Thelma; Koh, Won-Jung; Seaworth, Barbara; Geiter, Lawrence J; Wells, Charles D

2012-06-07

Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. Delamanid was associated with an increase in sputum-culture conversion at 2

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…

Drug resistant Mycobacterium tuberculosis in Mexico.

PubMed

Zazueta-Beltran, Jorge; León-Sicairos, Claudia; Canizalez-Roman, Adrián

2009-04-30

Tuberculosis (TB) remains a serious public health problem, worsened by an increased frequency of multidrug-resistant (MDR) Mycobacterium tuberculosis strains. The World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD) launched the Global Project on Anti-Tuberculosis Drug Resistance Surveillance to measure the prevalence of drug resistance. Data from the global reports on resistance to anti-tuberculosis (anti-TB) drugs have shown that drug resistance still presents worldwide and that MDR-TB is present in almost all the world. Though the Global Project (WHO) has been operating since 1994, very few countries and states have reported new information. Data from repeated surveys employing comparable methodologies over several years are essential to determine with any certainty in which direction the prevalence of drug resistance is moving. Drug-resistant tuberculosis and MDR-TB have been identified in Mexico, even with the existence of a National Tuberculosis Program based on Directly Observed Treatment, Short-course (DOTS). This review discusses available surveillance data on drug susceptibility data for TB in different states of Mexico.

Evaluation of the ICT Tuberculosis test for the routine diagnosis of tuberculosis

PubMed Central

Ongut, Gozde; Ogunc, Dilara; Gunseren, Filiz; Ogus, Candan; Donmez, Levent; Colak, Dilek; Gultekin, Meral

2006-01-01

Background Rapid and accurate diagnosis of tuberculosis (TB) is crucial to facilitate early treatment of infectious cases and thus to reduce its spread. To improve the diagnosis of TB, more rapid diagnostic techniques such as antibody detection methods including enzyme-linked immunosorbent assay (ELISA)-based serological tests and immunochromatographic methods were developed. This study was designed to evaluate the validity of an immunochromatographic assay, ICT Tuberculosis test for the serologic diagnosis of TB in Antalya, Turkey. Methods Sera from 72 patients with active pulmonary (53 smear-positive and 19 smear-negative cases) and eight extrapulmonary (6 smear-positive and 2 smear-negative cases) TB, and 54 controls from different outpatient clinics with similar demographic characteristics as patients were tested by ICT Tuberculosis test. Results The sensitivity, specificity, and negative predictive value of the ICT Tuberculosis test for pulmonary TB were 33.3%, 100%, and 52.9%, respectively. Smear-positive pulmonary TB patients showed a higher positivity rate for antibodies than smear-negative patients, but the difference was not statistically significant. Of the eight patients with extrapulmonary TB, antibody was detected in four patients. Conclusion Our results suggest that ICT Tuberculosis test can be used to aid TB diagnosis in smear-positive patients until the culture results are available. PMID:16504161

A brief history of tuberculosis in the Czech Lands.

PubMed

Vargová, Lenka; Vymazalová, Kateřina; Horáčková, Ladislava

2017-07-01

Tuberculosis currently remains a serious medical problem, therefore increased attention is being paid to this disease. Paleopathological studies focused on the monitoring of morbid changes in skeletal remains of historical populations facilitate a detailed study of the development of this disease. They provide direct evidence of the existence of tuberculosis and its past forms. In addition to literary and iconographic sources, the present study is focused on recording the findings of bone tuberculosis in historical osteological sets from the Czech Lands and is the starting point for their detailed review. Approximately 76 cases of bone tuberculosis from the Czech Lands have been published and more or less reliably documented from 20 archeological sites dated back from the Eneolithic to the modern period. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cough Aerosols of Mycobacterium tuberculosis in the Prediction of Incident Tuberculosis Disease in Household Contacts.

PubMed

Jones-López, Edward C; Acuña-Villaorduña, Carlos; Ssebidandi, Martin; Gaeddert, Mary; Kubiak, Rachel W; Ayakaka, Irene; White, Laura F; Joloba, Moses; Okwera, Alphonse; Fennelly, Kevin P

2016-07-01

Tuberculosis disease develops in only 5%-10% of humans infected with Mycobacterium tuberculosis The mechanisms underlying this variability remain poorly understood. We recently demonstrated that colony-forming units of M. tuberculosis in cough-generated aerosols are a better predictor of infection than the standard sputum acid-fast bacilli smear. We hypothesized that cough aerosol cultures may also predict progression to tuberculosis disease in contacts. We conducted a retrospective cohort study of 85 patients with smear-positive tuberculosis and their 369 household contacts in Kampala, Uganda. Index case patients underwent a standard evaluation, and we cultured M. tuberculosis from cough aerosols. Contacts underwent a standard evaluation at enrollment, and they were later traced to determine their tuberculosis status. During a median follow-up of 3.9 years, 8 (2%) of the contacts developed tuberculosis disease. In unadjusted and adjusted analyses, incident tuberculosis disease in contacts was associated with sputum Mycobacterial Growth Indicator Tube culture (odds ratio, 8.2; 95% confidence interval, 1.1-59.2; P = .04), exposure to a high-aerosol tuberculosis case patient (6.0, 1.4-25.2; P = .01), and marginally, human immunodeficiency virus in the contact (6.11; 0.89-41.7; P = .07). We present data demonstrating that sputum and aerosol specimens measure 2 related but different phenomena. We found an increased risk of tuberculosis progression among contacts of high-aerosol case patients. The hypothesis that a larger infectious inoculum, represented by high aerosol production, determines the risk of disease progression deserves evaluation in future prospective studies. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Surgical aspects of pulmonary tuberculosis: an update.

PubMed

Dewan, Ravindra Kumar; Pezzella, A Thomas

2016-10-01

Tuberculosis remains a major global medical challenge and concern. In the world's population of over 7.4 billion people, 8.6 million are estimated to be infected with Mycobacterium tuberculosis; another 2.2 billion have latent tuberculosis. There is an annual incidence of 16,000 new cases in the USA and 7-8 million new cases worldwide, of which 440,000 are multidrug-resistant or extensively multidrug-resistant, mainly in developing countries or emerging economies. According to the World Health Organization, the incidence of tuberculosis is 133 cases per 100,000 of the population; 3.3% new cases are drug resistant and 20% are already treated cases. Of the drug-resistant cases, 9.7% are extensively drug-resistant. The annual global mortality attributable to tuberculosis is over 1.3 million people. The association with HIV/AIDS in 430,000 people has compounded the global concern and challenge. This review presents the historical indications for surgical treatment of tuberculosis, reviews the current literature and clinical experience, and collates this into increased awareness and contemporary understanding of the indications and need for surgery in primary active tuberculosis, adjuvant surgical therapy for multidrug-resistant tuberculosis, and the complications of chronic tuberculosis sequelae or previous tuberculosis surgery. © The Author(s) 2016.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2008-01-01

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

Mortality in Severe Human Immunodeficiency Virus-Tuberculosis Associates With Innate Immune Activation and Dysfunction of Monocytes

PubMed Central

Janssen, Saskia; Schutz, Charlotte; Ward, Amy; Nemes, Elisa; Wilkinson, Katalin A; Scriven, James; Huson, Mischa A; Aben, Nanne; Maartens, Gary; Burton, Rosie; Wilkinson, Robert J; Grobusch, Martin P; Van der Poll, Tom; Meintjes, Graeme

2017-01-01

Abstract Background Case fatality rates among hospitalized patients diagnosed with human immunodeficiency virus (HIV)-associated tuberculosis remain high, and tuberculosis mycobacteremia is common. Our aim was to define the nature of innate immune responses associated with 12-week mortality in this population. Methods This prospective cohort study was conducted at Khayelitsha Hospital, Cape Town, South Africa. Hospitalized HIV-infected tuberculosis patients with CD4 counts <350 cells/µL were included; tuberculosis blood cultures were performed in all. Ambulatory HIV-infected patients without active tuberculosis were recruited as controls. Whole blood was stimulated with Escherichia coli derived lipopolysaccharide, heat-killed Streptococcus pneumoniae, and Mycobacterium tuberculosis. Biomarkers of inflammation and sepsis, intracellular (flow cytometry) and secreted cytokines (Luminex), were assessed for associations with 12-week mortality using Cox proportional hazard models. Second, we investigated associations of these immune markers with tuberculosis mycobacteremia. Results Sixty patients were included (median CD4 count 53 cells/µL (interquartile range [IQR], 22–132); 16 (27%) died after a median of 12 (IQR, 0–24) days. Thirty-one (52%) grew M. tuberculosis on blood culture. Mortality was associated with higher concentrations of procalcitonin, activation of the innate immune system (% CD16+CD14+ monocytes, interleukin-6, tumour necrosis factor-ɑ and colony-stimulating factor 3), and antiinflammatory markers (increased interleukin-1 receptor antagonist and lower monocyte and neutrophil responses to bacterial stimuli). Tuberculosis mycobacteremia was not associated with mortality, nor with biomarkers of sepsis. Conclusions Twelve-week mortality was associated with greater pro- and antiinflammatory alterations of the innate immune system, similar to those reported in severe bacterial sepsis. PMID:28369200

[Tuberculosis in compromised hosts].

PubMed

2003-11-01

Recent development of tuberculosis in Japan tends to converge on a specific high risk group. The proportion of tuberculosis developing particularly from the compromised hosts in the high risk group is especially high. At this symposium, therefore, we took up diabetes mellitus, gastrectomy, dialysis, AIDS and the elderly for discussion. Many new findings and useful reports for practical medical treatment are submitted; why these compromised hosts are predisposed to tuberculosis, tuberculosis diagnostic and remedial notes of those compromised hosts etc. It is an important question for the future to study how to prevent tuberculosis from these compromised hosts. 1. Tuberculosis in diabetes mellitus: aggravation and its immunological mechanism: Kazuyoshi KAWAKAMI (Department of Internal Medicine, Division of Infectious Diseases, Graduate School and Faculty of Medicine, University of the Ryukyus). It has been well documented that diabetes mellitus (DM) is a major aggravating factor in tuberculosis. The onset of this disease is more frequent in DM patients than in individuals with any underlying diseases. However, the precise mechanism of this finding remains to be fully understood. Earlier studies reported that the migration, phagocytosis and bactericidal activity of neutrophils are all impaired in DM patients, which is related to their reduced host defense to infection with extracellular bacteria, such as S. aureus and E. colli. Host defense to mycobacterial infection is largely mediated by cellular immunity, and Th1-related cytokines, such as IFN-gamma and IL-12, play a central role in this response. It is reported that serum level of these cytokines and their production by peripheral blood mononuclear cells (PBMC) are reduced in tuberculosis patients with DM, and this is supposed to be involved in the high incidence of tuberculosis in DM. Our study observed similar findings and furthermore indicated that IFN-gamma and IL-12 production by BCG-stimulated PBMC was lower

Drug-resistant tuberculosis: time for visionary political leadership.

PubMed

Abubakar, Ibrahim; Zignol, Matteo; Falzon, Dennis; Raviglione, Mario; Ditiu, Lucica; Masham, Susan; Adetifa, Ifedayo; Ford, Nathan; Cox, Helen; Lawn, Stephen D; Marais, Ben J; McHugh, Timothy D; Mwaba, Peter; Bates, Matthew; Lipman, Marc; Zijenah, Lynn; Logan, Simon; McNerney, Ruth; Zumla, Adam; Sarda, Krishna; Nahid, Payam; Hoelscher, Michael; Pletschette, Michel; Memish, Ziad A; Kim, Peter; Hafner, Richard; Cole, Stewart; Migliori, Giovanni Battista; Maeurer, Markus; Schito, Marco; Zumla, Alimuddin

2013-06-01

Two decades ago, WHO declared tuberculosis a global emergency, and invested in the highly cost-effective directly observed treatment short-course programme to control the epidemic. At that time, most strains of Mycobacterium tuberculosis were susceptible to first-line tuberculosis drugs, and drug resistance was not a major issue. However, in 2013, tuberculosis remains a major public health concern worldwide, with prevalence of multidrug-resistant (MDR) tuberculosis rising. WHO estimates roughly 630 000 cases of MDR tuberculosis worldwide, with great variation in the frequency of MDR tuberculosis between countries. In the past 8 years, extensively drug-resistant (XDR) tuberculosis has emerged, and has been reported in 84 countries, heralding the possibility of virtually untreatable tuberculosis. Increased population movement, the continuing HIV pandemic, and the rise in MDR tuberculosis pose formidable challenges to the global control of tuberculosis. We provide an overview of the global burden of drug-resistant disease; discuss the social, health service, management, and control issues that fuel and sustain the epidemic; and suggest specific recommendations for important next steps. Visionary political leadership is needed to curb the rise of MDR and XDR tuberculosis worldwide, through sustained funding and the implementation of global and regional action plans. Copyright © 2013 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd. All rights reserved.

Aggressive Regimens for Multidrug-Resistant Tuberculosis Reduce Recurrence

PubMed Central

Franke, Molly F.; Appleton, Sasha C.; Mitnick, Carole D.; Furin, Jennifer J.; Bayona, Jaime; Chalco, Katiuska; Shin, Sonya; Murray, Megan; Becerra, Mercedes C.

2013-01-01

Background. Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatment-related factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. Methods. We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. Results. Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2–53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17–0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17–50.60]; P = .004). Conclusions. Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease. PMID:23223591

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

PubMed Central

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

2014-01-01

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

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

Skin, ear and testis--unusual sites of tuberculosis.

PubMed

Ene, Cătălina Elena; Toma, Claudia; Belaconi, Ionela; Dumitrache-Rujinski, Stefan; Jipa, Daniela; Tudor, Adrian; Leonte, Diana; Bogdan, Miron Alexandru

2016-01-01

Pulmonary localization is the most common site of tuberculosis (TB)and the most contagious form. Extrapulmonary tuberculosis with the rarest and most unexpected localizations represents a significant proportion of all cases of tuberculosis and remains an important public health problem. We report three unusual TB locations: skin, ear and testis occurred in three immunocompetent patients. In the case of skin and testicular lesions, diagnosis was based on pathological confirmation of granulomas with caseous necrosis. In the third case the diagnosis was made possible by identification of positive Acid-Fast Bacilli smear and positive culture from othic drainage fluid. The outcome at all three patients was good with antituberculous treatment. These unusual localization of tuberculosis also highlight the possibility of extrapulmonary tuberculosis as a differential diagnosis in many common diseases.

Drug development against tuberculosis: Impact of alkaloids.

PubMed

Mishra, Shardendu K; Tripathi, Garima; Kishore, Navneet; Singh, Rakesh K; Singh, Archana; Tiwari, Vinod K

2017-09-08

Despite of the advances made in the treatment and management, tuberculosis (TB) still remains one of main public health problem. The contrary effects of first and second-line anti-tuberculosis drugs have generated extended research interest in natural products in the hope of devising new antitubercular leads. Interestingly, plethoras of natural products have been discovered to exhibit activity towards various resistant strains of M. tuberculosis. Extensive applications of alkaloids in the field of therapeutics is well-established and nowday's researches being pursued to develop new potent drugs from natural sources for tuberculosis. Alkaloids are categorized in quite a few groups according to their structures and isolation from both terrestrial and marine sources. These new drugs might be a watershed in the battle against tuberculosis. This review summarizes alkaloids, which were found active against Mycobacteria since last ten years with special attention on the study of structure-activity relationship (SAR) and mode of action with their impact in drug discovery and development against tuberculosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Expansion of Pathogen-Specific T-Helper 1 and T-Helper 17 Cells in Pulmonary Tuberculosis With Coincident Type 2 Diabetes Mellitus

PubMed Central

Kumar, Nathella Pavan; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Nutman, Thomas B.; Babu, Subash

2013-01-01

Background. Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis, although the immunological mechanisms underlying this interaction remain unexplored. The influence of poorly controlled diabetes on pathogen-specific T-helper 1 (Th1) and T-helper 17 (Th17) responses have not been examined. Methods. To identify the role of Th1 and Th17 cells in tuberculosis with coincident DM, we examined mycobacteria-specific immune responses in the whole blood of individuals who had tuberculosis with DM and compared them to those in individuals who had tuberculosis without DM. Results. Tuberculosis coincident with DM is characterized by elevated frequencies of monofunctional and dual-functional CD4+ Th1 cells following Mycobacterium tuberculosis antigen stimulation and elevated frequencies of Th17 subsets at both baseline and following antigen stimulation. This was associated with increased systemic (plasma) levels of both Th1 and Th17 cytokines and decreased baseline frequencies of natural regulatory T cells but not interleukin 10 or transforming growth factor β. Conclusions. Therefore, our data reveal that tuberculosis in persons with DM is characterized by elevated frequencies of Th1 and Th17 cells, indicating that DM is associated with an alteration in the immune response to tuberculosis, leading to a biased induction of Th1- and Th17-mediated cellular responses and likely contributing to increased immune pathology in M. tuberculosis infection. PMID:23715661

Sputum Microscopy With Fluorescein Diacetate Predicts Tuberculosis Infectiousness

PubMed Central

Datta, Sumona; Sherman, Jonathan M; Tovar, Marco A; Bravard, Marjory A; Valencia, Teresa; Montoya, Rosario; Quino, Willi; D’Arcy, Nikki; Ramos, Eric S; Gilman, Robert H; Evans, Carlton A

2017-01-01

Abstract Background Sputum from patients with tuberculosis contains subpopulations of metabolically active and inactive Mycobacterium tuberculosis with unknown implications for infectiousness. Methods We assessed sputum microscopy with fluorescein diacetate (FDA, evaluating M. tuberculosis metabolic activity) for predicting infectiousness. Mycobacterium tuberculosis was quantified in pretreatment sputum of patients with pulmonary tuberculosis using FDA microscopy, culture, and acid-fast microscopy. These 35 patients’ 209 household contacts were followed with prevalence surveys for tuberculosis disease for 6 years. Results FDA microscopy was positive for a median of 119 (interquartile range [IQR], 47–386) bacteria/µL sputum, which was 5.1% (IQR, 2.4%–11%) the concentration of acid-fast microscopy–positive bacteria (2069 [IQR, 1358–3734] bacteria/μL). Tuberculosis was diagnosed during follow-up in 6.4% (13/209) of contacts. For patients with lower than median concentration of FDA microscopy–positive M. tuberculosis, 10% of their contacts developed tuberculosis. This was significantly more than 2.7% of the contacts of patients with higher than median FDA microscopy results (crude hazard ratio [HR], 3.8; P = .03). This association maintained statistical significance after adjusting for disease severity, chemoprophylaxis, drug resistance, and social determinants (adjusted HR, 3.9; P = .02). Conclusions Mycobacterium tuberculosis that was FDA microscopy negative was paradoxically associated with greater infectiousness. FDA microscopy–negative bacteria in these pretreatment samples may be a nonstaining, slowly metabolizing phenotype better adapted to airborne transmission. PMID:28510693

Multidrug resistant tuberculosis diagnosed by synovial fluid analysis.

PubMed

van Zeller, M; Monteiro, R; Ramalho, J; Almeida, I; Duarte, R

2012-01-01

Tuberculosis remains a major public health problem worldwide. HIV co-infection is contributing to an increased incidence of the disease, particularly that caused by multidrug resistant strains of Mycobacterium tuberculosis (MT). We describe an HIV-infected patient with pleural and lymph node tuberculosis diagnosed by pleural effusion characteristics and biopsy specimens, without MT identification, that further presented with knee-joint involvement. Arthrocentesis allowed MT isolation and drug susceptibility testing, resulting in a diagnosis of multidrug-resistant tuberculosis and an appropriate treatment regimen. MT identification and drug susceptibility tests are very important, especially for HIV co-infected patients. Copyright © 2011 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Type I interferons in tuberculosis: Foe and occasionally friend.

PubMed

Moreira-Teixeira, Lúcia; Mayer-Barber, Katrin; Sher, Alan; O'Garra, Anne

2018-05-07

Tuberculosis remains one of the leading causes of mortality worldwide, and, despite its clinical significance, there are still significant gaps in our understanding of pathogenic and protective mechanisms triggered by Mycobacterium tuberculosis infection. Type I interferons (IFN) regulate a broad family of genes that either stimulate or inhibit immune function, having both host-protective and detrimental effects, and exhibit well-characterized antiviral activity. Transcriptional studies have uncovered a potential deleterious role for type I IFN in active tuberculosis. Since then, additional studies in human tuberculosis and experimental mouse models of M. tuberculosis infection support the concept that type I IFN promotes both bacterial expansion and disease pathogenesis. More recently, studies in a different setting have suggested a putative protective role for type I IFN. In this study, we discuss the mechanistic and contextual factors that determine the detrimental versus beneficial outcomes of type I IFN induction during M. tuberculosis infection, from human disease to experimental mouse models of tuberculosis. © 2018 Moreira-Teixeira et al.

Spatial analysis of pulmonary tuberculosis in Antananarivo Madagascar: tuberculosis-related knowledge, attitude and practice.

PubMed

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

2014-01-01

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. 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. 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. 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.

Tuberculosis

MedlinePlus

... Staying Safe Videos for Educators Search English Español Tuberculosis KidsHealth / For Teens / Tuberculosis What's in this article? TB Basics Signs and ... When to Call the Doctor Print en español Tuberculosis TB Basics Tuberculosis (also known as "TB") is ...

Rapid Diagnosis of Tuberculosis by Real-Time High-Resolution Imaging of Mycobacterium tuberculosis Colonies.

PubMed

Ghodbane, Ramzi; Asmar, Shady; Betzner, Marlena; Linet, Marie; Pierquin, Joseph; Raoult, Didier; Drancourt, Michel

2015-08-01

Culture remains the cornerstone of diagnosis for pulmonary tuberculosis, but the fastidiousness of Mycobacterium tuberculosis may delay culture-based diagnosis for weeks. We evaluated the performance of real-time high-resolution imaging for the rapid detection of M. tuberculosis colonies growing on a solid medium. A total of 50 clinical specimens, including 42 sputum specimens, 4 stool specimens, 2 bronchoalveolar lavage fluid specimens, and 2 bronchial aspirate fluid specimens were prospectively inoculated into (i) a commercially available Middlebrook broth and evaluated for mycobacterial growth indirectly detected by measuring oxygen consumption (standard protocol) and (ii) a home-made solid medium incubated in an incubator featuring real-time high-resolution imaging of colonies (real-time protocol). Isolates were identified by Ziehl-Neelsen staining and matrix-assisted laser desorption ionization-time of flight mass spectrometry. Use of the standard protocol yielded 14/50 (28%) M. tuberculosis isolates, which is not significantly different from the 13/50 (26%) M. tuberculosis isolates found using the real-time protocol (P = 1.00 by Fisher's exact test), and the contamination rate of 1/50 (2%) was not significantly different from the contamination rate of 2/50 (4%) using the real-time protocol (P = 1.00). The real-time imaging protocol showed a 4.4-fold reduction in time to detection, 82 ± 54 h versus 360 ± 142 h (P < 0.05). These preliminary data give the proof of concept that real-time high-resolution imaging of M. tuberculosis colonies is a new technology that shortens the time to growth detection and the laboratory diagnosis of pulmonary tuberculosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

[Clinical analysis of patients with tuberculosis admitted on an emergency cases].

PubMed

Okada, Toru; Shibuya, Yasuhiro; Saito, Hitoshi; Enomoto, Tatsuji; Nakamura, Seiichi

2008-08-01

A retrospective study was made of 75 patients with tuberculosis and tuberculous pleurisy who received medical care in our hospital from 2002 through 2006. Of the 75 patients, 9 were admitted as tertiary emergency cases, and 12 patients were admitted by ambulance as secondary emergency cases. We studied the reason for their emergency medical admission, and the process of diagnosing 21 patients as tuberculosis. In some cases, the reasons for emergency admission were cardiorespiratory arrest, loss of consciousness, and injury resulting from a traffic accident, not common symptoms of tuberculosis such as dyspnea, hemoptysis and bloody sputum. Chest radiographic findings of most patients showed tuberculosis, and other cases were likely to be diagnosed as tuberculosis from their medical history or back-ground such as being homeless, previous tuberculosis, and receiving for therapy of tuberculosis. It was not so difficult to diagnose our cases as tuberculosis, nevertheless we may have an unconscious patient with normal chest radiograph. These data suggest that any patients visiting the emergency room may possibly have tuberculosis even if they are without respiratory symptoms.

Distinct Clinical and Epidemiological Features of Tuberculosis in New York City Caused by the RDRio Mycobacterium tuberculosis Sublineage

PubMed Central

Weisenberg, Scott A.; Gibson, Andrea L.; Huard, Richard C.; Kurepina, Natalia; Bang, Heejung; Lazzarini, Luiz C O.; Chiu, Yalin; Li, Jiehui; Ahuja, Shama; Driscoll, Jeff; Kreiswirth, Barry N.; Ho, John L.

2011-01-01

Background Genetic tracking of Mycobacterium tuberculosis is a cornerstone of tuberculosis (TB) control programs. The RDRio M. tuberculosis sublineage was previously associated with TB in Brazil. We investigated 3847 M. tuberculosis isolates and registry data from New York City (NYC) (2001–2005) to: 1) affirm the position of RDRio strains within the M. tuberculosis phylogenetic structure, 2) determine its prevalence, and 3) define transmission, demographic, and clinical characteristics associated with RDRio TB. Methods Isolates classified as RDRio or non-RDRio M. tuberculosis by multiplex PCR were further classified as clustered (≥2 isolates) or unique based primarily upon IS6110-RFLP patterns and lineage-specific cluster proportions were calculated. The secondary case rate of RDRio was compared with other prevalent M. tuberculosis lineages. Genotype data were merged with the data from the NYC TB Registry to assess demographic and clinical characteristics. Results RDRio strains were found to: 1) be restricted to the Latin American-Mediterranean family, 2) cause approximately 8% of TB cases in NYC, and 3) be associated with heightened transmission as shown by: i) a higher cluster proportion compared to other prevalent lineages, ii) a higher secondary case rate, and iii) cases in children. Furthermore, RDRio strains were significantly associated with US-born Black or Hispanic race, birth in Latin American and Caribbean countries, and isoniazid resistance. Conclusions The RDRio genotype is a single M. tuberculosis strain population that is emerging in NYC. The findings suggest that expanded RDRio case and exposure identification could be of benefit due to its association with heightened transmission. PMID:21835266

Recent tuberculosis advances in Latin America

PubMed Central

Pelly, Tom; Moore, David A.J.; Gilman, Robert; Evans, Carlton

2010-01-01

Purpose of review Tuberculosis kills more people than any other infection. Despite advances in diagnostic methods and greater understanding of the reasons for treatment failure, tuberculosis remains common throughout Latin America. Recent findings The impact of HIV and multidrug resistance on tuberculosis control has been enormous. HIV-positive patients may be at 10 times greater risk of multidrug resistant tuberculosis than HIV- negative patients. Hopefully, improved diagnostic techniques will allow more rapid diagnosis of tuberculosis and new colorimetric systems are being developed that will enable expedited drug-sensitivity testing. However, in alarming reports, only 58% of patients were treated with the recommended treatment regime in a Brazilian study, and dropout from treatment in parts of Bolivia was common. Many failings could be combated by rigorous education of patients and physicians. In an encouraging advance, multidrug resistant tuberculosis was successfully treated in a community-based programme, saving an estimated 90% of the cost of hospital-based treatment. An opportunity to identify treatment failure earlier is demonstrated by the finding that 2 months after the initiation of therapy, positive smears were found in only 3% of those whose treatment was successful, but 74% of those whose treatment failed. Summary The importance of inexpensive and widely available drugs to treat HIV and multidrug resistant tuberculosis in Latin America is clear. The need for rapid, affordable tests for tuberculosis diagnosis, and for easy drug sensitivity testing is also evident. Finally, improving treatment success is achievable even in the resource poor setting. PMID:15353958

Recent advances in our understanding of human host responses to tuberculosis

PubMed Central

Schluger, Neil W

2001-01-01

Tuberculosis remains one of the world's greatest public health challenges: 2 billion persons have latent infection, 8 million people develop active tuberculosis annually, and 2–3 million die. Recently, significant advances in our understanding of the human immune response against tuberculosis have occurred. The present review focuses on recent work in macrophage and T-cell biology that sheds light on the human immune response to tuberculosis. The role of key cytokines such as interferon-γ is discussed, as is the role of CD4+ and CD8+ T cells in immune regulation in tuberculosis, particularly with regard to implications for vaccine development and evaluation. PMID:11686880

The Socioeconomic Factors and the Indigenous Component of Tuberculosis in Amazonas

PubMed Central

2016-01-01

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

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

[Ocular tuberculosis : A case series].

PubMed

Koubaa, M; Smaoui, F; Gargouri, S; Ben Ayed, H; Rekik, K; Abid, I; Maaloul, I; Feki, J; Marrakchi, C; Ben Jemaa, M

2018-05-01

Ocular tuberculosis is a rare form of extra pulmonary tuberculosis. It represents 1-2% of all clinical forms. The aim of this work was to focus on diagnostic and therapeutic characteristics of ocular tuberculosis. We report a case series of 14 patients with ocular tuberculosis seen in an infectious diseases department between 2006 and 2015. The diagnosis was retained on clinical data and a positive tuberculin skin test or interferon-gamma release assay. The patient's mean age was 40.7±9years. The most common clinical presentation was uveitis (11 patients and 16 eyes). An extra ocular involvement was associated in three patients. The mean duration of antitubercular therapy was 10±2.5 months. Corticosteroid therapy was associated in 11 cases. The outcome was favorable in all cases. Two patients had maintained visual sequelae. Ocular tuberculosis is a rare disease but still remains a diagnostic problem. It should be considered in case of any chronic ocular symptoms, especially in endemic countries. Early management can improve the visual prognosis. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Understanding Latent Tuberculosis: A Moving Target

PubMed Central

Lin, Philana Ling; Flynn, JoAnne L.

2012-01-01

Tuberculosis (TB) remains a threat to the health of people worldwide. Infection with Mycobacterium tuberculosis can result in active TB or, more commonly, latent infection. Latently infected persons, of which there are estimated to be ~2 billion in the world, represent an enormous reservoir of potential reactivation TB, which can spread to other people. The immunology of TB is complex and multifaceted. Identifying the immune mechanisms that lead to control of initial infection and prevent reactivation of latent infection is crucial to combating this disease. PMID:20562268

Tuberculosis in Far North Queensland, Australia: a retrospective clinical audit.

PubMed

Wilson, Malcolm; Weston, Jana; Mullen, Annette; Knight, Trevor; Simpson, Graham

2018-06-05

Compared with global numbers, Australia has enjoyed relatively good tuberculosis control over the last thirty years with an annual incidence of 5.7 per 100,000 population. 1 Thanks to its unique geography and proximity to high-burden countries, such as Papua New Guinea (PNG), Far North Queensland (FNQ) has previously been shown to have higher rates of tuberculosis compared with both the state and national average. 2,3 AIMS: Document tuberculosis epidemiology in FNQ with comparison to two previous audits of the region. Retrospective clinical audit of all cases of tuberculosis notified to the Cairns Tuberculosis Control Unit between 2006 and 2016. 453 cases were identified, 374 with microbiological/histological confirmation. There were 312 cases of pulmonary tuberculosis; 155 extra-pulmonary; and 21 disseminated. Three-quarters (327/453) were identified in the overseas-born population. Of the remaining 126 cases, 40 were Torres Strait Islander and 19 Aboriginal Australians. Where drug susceptibility was known, two-thirds (247/368) were fully sensitive; 42 mono-resistant; 78 multidrug-resistant; and one extensively drug resistant. Rates of HIV co-infection were less than three percent (10/362). Tuberculosis remains a significant problem in FNQ. Case numbers have increased three-fold since the 1990s. Much of the increase comes from the overseas-born population. Although PNG accounts for the majority, the number of positive notifications amongst those born elsewhere abroad has increased five-fold since 2010. Tuberculosis amongst Aboriginal Australians has decreased following policy changes in response previous audits. Tuberculosis in Torres Strait residents, however, has increased from 12 cases (1993-2002) to 40 (2006-2016). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

Hemostatic Changes Associated With Increased Mortality Rates in Hospitalized Patients With HIV-Associated Tuberculosis: A Prospective Cohort Study

PubMed Central

Schutz, Charlotte; Ward, Amy M.; Huson, Mischa A. M.; Wilkinson, Robert J.; Burton, Rosie; Maartens, Gary; Wilkinson, Katalin A.; Meijers, Joost C. M.; Lutter, René; Grobusch, Martin P.; Meintjes, Graeme; van der Poll, Tom

2017-01-01

Background Mortality rates remain high for human immunodeficiency virus (HIV)–associated tuberculosis, and our knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-tuberculosis were associated with mortality or decreased survival time and the contribution of mycobacteremia to these effects. Methods We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 cell counts <350/µL and microbiologically proved tuberculosis. HIV-infected outpatients without tuberculosis served as controls. Plasma biomarkers reflecting activation of procoagulation and anticoagulation, fibrinolysis, endothelial cell activation, matricellular protein release, and tissue damage were measured at admission. Cox proportional hazard models were used to assess variables associated with 12-week mortality rates. Results Of 59 patients with HIV-tuberculosis, 16 (27%) died after a median of 12 days (interquartile range, 0–24 days); 29 (64%) of the 45 not receiving anticoagulants fulfilled criteria for disseminated intravascular coagulation. Decreased survival time was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release, and tissue damage and with decreased concentrations for markers of anticoagulation. In patients who died, coagulation factors involved in the common pathway were depleted (factor II, V, X), which corresponded to increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality. Conclusions Patients with severe HIV-tuberculosis display a hypercoagulable state and activation of the endothelium, which is associated with mortality. PMID:28363198

Tuberculosis of the head and neck – epidemiological and clinical presentation

PubMed Central

Bruzgielewicz, Antoni; Osuch-Wójcikewicz, Ewa; Niemczyk, Kazimierz; Chmielewski, Rafał

2013-01-01

Introduction The aim of our retrospective study was to review the clinical and epidemiological presentation of head and neck tuberculosis. Material and methods We analyzed the history of 73 patients with head and neck tuberculosis hospitalized in the Department of Otolaryngology, Medical University of Warsaw, between 1983 and 2009. Results We found that 26 (35.6%) patients presented with lymph node tuberculosis, 20 (27.4%) with laryngeal tuberculosis, 10 (13.7%) with oropharyngeal tuberculosis, 9 (12.3%) with salivary gland tuberculosis, 3 (4.1%) with tuberculosis of paranasal sinuses, 3 (4.1%) with aural tuberculosis, and 2 (2.7%) with skin tuberculosis in the head and neck region. Within the group of patients with lymph node tuberculosis in 15 cases there were infected lymph nodes of the 2nd and 3rd cervical region and in 11 infected lymph nodes of the 1st cervical region. In 5 cases of laryngeal tuberculosis there was detected coexistence of cancer. Oropharyngeal tuberculosis in 7 cases was localized in tonsils, where in 1 case coexisting cancer was diagnosed. Chest X-ray was performed in all cases and pulmonary tuberculosis was identified in 26 (35.6%) cases. Conclusions We conclude that tuberculosis still remains a problem and must be taken into consideration in the diagnostic process. The coincidence of tuberculosis and cancer is remarkable in the head and neck region. PMID:25624854

Phenotypic assays for Mycobacterium tuberculosis infection.

PubMed

Song, Ok-Ryul; Deboosere, Nathalie; Delorme, Vincent; Queval, Christophe J; Deloison, Gaspard; Werkmeister, Elisabeth; Lafont, Frank; Baulard, Alain; Iantomasi, Raffaella; Brodin, Priscille

2017-10-01

Tuberculosis (TB) is still a major global threat, killing more than one million persons each year. With the constant increase of Mycobacterium tuberculosis strains resistant to first- and second-line drugs, there is an urgent need for the development of new drugs to control the propagation of TB. Although screenings of small molecules on axenic M. tuberculosis cultures were successful for the identification of novel putative anti-TB drugs, new drugs in the development pipeline remains scarce. Host-directed therapy may represent an alternative for drug development against TB. Indeed, M. tuberculosis has multiple specific interactions within host phagocytes, which may be targeted by small molecules. In order to enable drug discovery strategies against microbes residing within host macrophages, we developed multiple fluorescence-based HT/CS phenotypic assays monitoring the intracellular replication of M. tuberculosis as well as its intracellular trafficking. What we propose here is a population-based, multi-parametric analysis pipeline that can be used to monitor the intracellular fate of M. tuberculosis and the dynamics of cellular events such as phagosomal maturation (acidification and permeabilization), zinc poisoning system or lipid body accumulation. Such analysis allows the quantification of biological events considering the host-pathogen interplay and may thus be derived to other intracellular pathogens. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

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

PubMed Central

2013-01-01

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

Tuberculosis: evidence review for newly arriving immigrants and refugees

PubMed Central

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

2011-01-01

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

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

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

PubMed

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

2016-04-05

Tuberculosis remains a major health threat in much of the world. New vaccines against Mycobacterium tuberculosis are essential for preventing infection, disease, and transmission. However, the host immune responses that need to be induced by an effective vaccine remain unclear. Increasingly, it has become clear that early events in infection are of major importance in the eventual outcome of the infection. Studying such events in humans is challenging, as they occur within the lung and thoracic lymph nodes, and any clinical signs of early infection are relatively nonspecific. Nonetheless, clinical studies and animal models of tuberculosis have provided new insights into the local events that occur in the first few weeks of tuberculosis. Development of an effective vaccine requires a clear understanding of the successful (and detrimental) early host responses against M. tuberculosis, with the goal to improve upon natural immune responses and prevent infection or disease. Copyright © 2016 Cadena et al.

Evaluation of the results of Mycobacterium tuberculosis direct test (MTD) and Mycobacterial culture in urine samples

PubMed Central

Sener, Asli Gamze; Kurultay, Nukhet; Afsar, Ilhan

2008-01-01

Tuberculosis remains a public health problem in Turkey. Rapid detection of Mycobacterium tuberculosis plays a key role in control of infection. In this article, the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) was evaluated for detection of M. tuberculosis in urine samples. The performance of the MTD was very good and appropriate for routine laboratory diagnosis. PMID:24031287

Tuberculosis and infection control.

PubMed

Karim, Kelvin

Against a background of rising tuberculosis (TB) rates, increasing incidence of TB and human immunodeficiency virus (HIV) co-infection, coupled with the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB), the need for effective TB infection control has never been more vital (World Health Organization (WHO), 2009). TB infection control has been defined as 'a combination of measures aimed at minimizing the risk of TB transmission within populations' (WHO, 2009: p.ix). Health professionals are frequently confused about appropriate infection control measures when caring for patients affected by infectious respiratory tuberculosis (Mohandas and Cunniffe, 2009). This article aims to address the key infection control measures required to optimize patient care and reduce the risk of TB transmission within hospital and community settings.

Detection of Drug-Resistant Mycobacterium tuberculosis.

PubMed

Engström, Anna; Juréen, Pontus

2015-01-01

Tuberculosis (TB) remains a global health problem. The increasing prevalence of drug-resistant Mycobacterium tuberculosis, the causative agent of TB, demands new measures to combat the situation. Rapid and accurate diagnosis of the pathogen and its drug susceptibility pattern is essential for timely initiation of optimal treatment, and, ultimately, control of the disease. We have developed a molecular method for detection of first- and second-line drug resistance in M. tuberculosis by Pyrosequencing(®). The method consists of seven Pyrosequencing assays for the detection of mutations in the genes or promoter regions, which are most commonly responsible for resistance to the drugs rifampicin, isoniazid, ethambutol, amikacin, kanamycin, capreomycin, and fluoroquinolones. The method was validated on clinical isolates and it was shown that the sensitivity and specificity of the method were comparable to those of Sanger sequencing. In the protocol in this chapter we describe the steps necessary for setting up and performing Pyrosequencing for M. tuberculosis. The first part of the protocol describes the assay development and the second part of the protocol describes utilization of the method.

Economics of United States tuberculosis airline contact investigation policies: A return on investment analysis

PubMed Central

Coleman, Margaret S.; Marienau, Karen J.; Marano, Nina; Marks, Suzanne M.; Cetron, Martin S.

2017-01-01

Summary Background In 2011, the Centers for Disease Control and Prevention modified its 2008 protocol for flight-related tuberculosis contact investigation initiation. The 2011 Modified protocol was implemented and replaced the 2008 CDC protocol based on comparative epidemiologic and economic analyses; this publication reports the economic analysis results. Methods A return on investment model compared relative changes in tuberculosis disease treatment costs resulting from expenditures on tuberculosis contact investigations and latent tuberculosis infection treatment for the 2008 CDC and Modified protocols. Results At moderate/high rates of latent tuberculosis infection and tuberculosis disease, positive returns on investment indicated each $1.00 spent on tuberculosis contact investigations and latent tuberculosis treatment resulted in more than $1.00 of savings from reduced tuberculosis disease treatment costs. Low rates of latent tuberculosis infection and tuberculosis disease resulted in negative returns on investment, indicating economic losses from tuberculosis disease treatment costs. There were smaller economic losses at low latent tuberculosis infection and tuberculosis disease rates with the Modified protocol in comparison to the 2008 CDC protocol, while both identified comparable numbers of persons at risk for tuberculosis. Conclusion The Modified protocol for conducting flight-related tuberculosis contact investigations represents a better use of resources and protects public health. PMID:24262643

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

[Analysis of misdiagnosis of tuberculosis otitis media and mastoiditis].

PubMed

Li, Zhiyong; Liu, Shixi; Zou, Jian; Huang, Shi

2013-11-01

To investigate the misdiagnosis cause of tuberculosis otitis media and mastoiditis. The clinical data of 9 cases with tubercular otitis media and mastoiditis were analyzed respect. Nine patients, only 1 patient in the preoperative tuberculosis in otitis media and mastoiditis, the remaining eight cases pre-operative misdiagnosed as chronic otitis media the pathologic diagnosis of tuberculous otitis media. The clinical features of tubercular otitis media and mastoiditis was similar easily confused with chronic suppurative otitis media. Clinicians should pay attention to the disease, history of tuberculosis, imaging studies, and pathology, and other special examination to confirm the diagnosis, reduce misdiagnosed.

[Risk management of tuberculosis in medical institutions].

PubMed

Aoki, Masakazu

2006-01-01

As tuberculosis incidence is still high (23.3 per 100,000 in 2004) and infection control measures in hospitals are not so complete that about 8 or more nosocomial group infections are reported annually in these 10 years in Japan. Another reason of rather frequent occurring of group infection is that actual status of tuberculosis infection of medical staff remained unclear for long time because diagnosis of tuberculosis infection is almost impossible due to so wide and so long implementation of BCG vaccination in this country. To improve the present circumstances, the author has discussed on the recent theory and control measures of infection control introducing examples of nosocomial infections and results of studies carried out in many countries in these 10 years.

Comprehensive definition of human immunodominant CD8 antigens in tuberculosis.

PubMed

Lewinsohn, Deborah A; Swarbrick, Gwendolyn M; Park, Byung; Cansler, Meghan E; Null, Megan D; Toren, Katelynne G; Baseke, Joy; Zalwango, Sarah; Mayanja-Kizza, Harriet; Malone, LaShaunda L; Nyendak, Melissa; Wu, Guanming; Guinn, Kristi; McWeeney, Shannon; Mori, Tomi; Chervenak, Keith A; Sherman, David R; Boom, W Henry; Lewinsohn, David M

2017-01-01

Despite widespread use of the Bacillus Calmette-Guerin vaccine, tuberculosis, caused by infection with Mycobacterium tuberculosis , remains a leading cause of morbidity and mortality worldwide. As CD8 + T cells are critical to tuberculosis host defense and a phase 2b vaccine trial of modified vaccinia Ankara expressing Ag85a that failed to demonstrate efficacy, also failed to induce a CD8 + T cell response, an effective tuberculosis vaccine may need to induce CD8 + T cells. However, little is known about CD8, as compared to CD4, antigens in tuberculosis. Herein, we report the results of the first ever HLA allele independent genome-wide CD8 antigen discovery program. Using CD8 + T cells derived from humans with latent tuberculosis infection or tuberculosis and an interferon-γ ELISPOT assay, we screened a synthetic peptide library representing 10% of the Mycobacterium tuberculosis proteome, selected to be enriched for Mycobacterium tuberculosis antigens. We defined a set of immunodominant CD8 antigens including part or all of 74 Mycobacterium tuberculosis proteins, only 16 of which are previously known CD8 antigens. Immunogenicity was associated with the degree of expression of mRNA and protein. Immunodominant antigens were enriched in cell wall proteins with preferential recognition of Esx protein family members, and within proteins comprising the Mycobacterium tuberculosis secretome. A validation study of immunodominant antigens demonstrated that these antigens were strongly recognized in Mycobacterium tuberculosis -infected individuals from a tuberculosis endemic region in Africa. The tuberculosis vaccine field will likely benefit from this greatly increased known repertoire of CD8 immunodominant antigens and definition of properties of Mycobacterium tuberculosis proteins important for CD8 antigenicity.

Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines

PubMed Central

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

2015-01-01

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

Global fund financing of tuberculosis services delivery in prisons.

PubMed

Lee, Donna; Lal, S S; Komatsu, Ryuichi; Zumla, Alimuddin; Atun, Rifat

2012-05-15

Despite concerted efforts to scale up tuberculosis control with large amounts of international financing in the last 2 decades, tuberculosis continues to be a social issue affecting the world's most marginalized and disadvantaged communities. This includes prisoners, estimated at about 10 million globally, for whom tuberculosis is a leading cause of mortality and morbidity. The Global Fund to Fight AIDS, Tuberculosis and Malaria has emerged as the single largest international donor for tuberculosis control, including funding support in delivering tuberculosis treatment for the confined population. The Global Fund grants database, with an aggregate approved investment of $21.7 billion in 150 countries by the end of 2010, was reviewed to identify tuberculosis and human immunodeficiency virus/tuberculosis grants and activities that monitored the delivery of tuberculosis treatment and support activities in penitentiary settings. The distribution and trend of number of countries with tuberculosis prison support was mapped by year, geographic region, tuberculosis or multidrug-resistant tuberculosis burden, and prison population rate. We examined the types of grant recipients managing program delivery, their performance, and the nature and range of services provided. Fifty-three of the 105 countries (50%) with Global Fund-supported tuberculosis programs delivered services within prison settings. Thirty-two percent (73 of 228) of tuberculosis grants, representing $558 million of all disbursements of Global Fund tuberculosis support by the end of 2010, included output indicators related to tuberculosis services delivered in prisons. Nearly two-thirds (64%) of these grants were implemented by governments, with the remaining by civil society and other partners. In terms of services, half (36 of 73) of grants provided diagnosis and treatment and an additional 27% provided screening and monitoring of tuberculosis for prisoners. The range of services tracked was limited in scope

Updates on Knowledge, Attitude and Preventive Practices on Tuberculosis among Healthcare Workers.

PubMed

Wahab, Farhanah Abd; Abdullah, Sarimah; Abdullah, Jafri Malin; Jaafar, Hasnan; Noor, Siti Suraiya Md; Mohammad, Wan Mohd Zahiruddin Wan; Yusoff, Abdul Aziz Mohamed; Tharakan, John; Bhaskar, Shalini; Sangu, Muthuraju; Mahmood, Mohd Shah; Kassim, Fauziah; Rafia, Md Hanip; Haspani, Mohammed Safari Mohammed; Alias, Azmi; Pando, Rogelio Hernández

2016-11-01

Ranking as the most communicable disease killer worldwide, tuberculosis, has accounted with a total of 9.6 million new tuberculosis cases with 1.5 million tuberculosis-related deaths reported globally in 2014. Tuberculosis has remain as an occupational hazard for healthcare workers since 1920s and due to several tuberculosis outbreaks in healthcare settings in the early 1990s, the concern about the transmission to both patients and healthcare workers has been raised. Healthcare workers have two to three folds greater the risk of active tuberculosis than the general population. Several studies on knowledge, attitude and practices on tuberculosis among healthcare workers worldwide have revealed that majority of the participated healthcare workers had good knowledge on tuberculosis. Most of the healthcare workers from South India and South Africa also reported to have positive attitude whereas a study in Thailand reported that most of the healthcare providers have negative attitude towards tuberculosis patients. Nevertheless, majority of the healthcare workers have low level of practice on tuberculosis prevention. An improved communication between healthcare workers and the patients as well as their families is the key to better therapeutic outcomes with good knowledge, attitude and preventive practice towards tuberculosis.

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. Copyright © 2014 Elsevier Inc. All rights reserved.

The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges

PubMed Central

Naidoo, Pren; Theron, Grant; Rangaka, Molebogeng X; Chihota, Violet N; Vaughan, Louise; Brey, Zameer O; Pillay, Yogan

2017-01-01

Abstract Background While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. Methods We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)–coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. Results The overall tuberculosis burden was estimated to be 532005 cases (range, 333760–764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Conclusion Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion. PMID:29117342

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

Molecular & genetic characteristics of Mycobacterium tuberculosis strains circulating in the southern part of West Siberia

PubMed Central

Pasechnik, Oksana; Dymova, Maya Alexandrovna; Stasenko, Vladimir Leonidovich; Blokh, Aleksey Igorevich; Tatarintseva, Marina Petrovna; Kolesnikova, Lyubov Pavlovna; Filipenko, Maksim Leonidovich

2017-01-01

Background & objectives: A complicated epidemiological situation characterized by significantly high tuberculosis (TB) morbidity is observed in West Siberia. This study was aimed to investigate the genetic characteristics of Mycobacterium tuberculosis circulating in the southern part of West Siberia (in the Omsk region). Methods: From March 2013 to January 2015, 100 isolates of M. tuberculosis were obtained from patients with pulmonary TB living in the Omsk region. Drug susceptibility testing was performed on Lowenstein-Jensen medium (absolute concentration method). Genetic typing of isolates was carried out by variable number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) typing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The genetic types and characteristics of cluster strains were determined using 15 MIRU-VNTR loci. Results: Thirty six VNTR types were found. Twenty six (26.0%) isolates had a unique profile, and the remaining 74 were grouped in 10 clusters containing from 2 to 23 isolates. The Beijing genotype was found in 72 isolates, 61 (85.0%) of which were part of five clusters that included two large clusters containing 23 isolates. Other genetic families, such as Latin-American Mediterranean (LAM, 11.0%), S family (2.0%) and Haarlem (4.0%), were also detected. The genetic family of 11 isolates could not be determined. Six different VNTR profiles were found in these non-classified isolates. Only 16 per cent of isolates were sensitive to anti-TB drugs. The katG315 (94.8%) and rpoB531 (92.2%) mutations were identified in 77 multidrug-resistant M. tuberculosis isolates. Interpretation & conclusions: This study showed that the M. tuberculosis population in the Omsk region was heterogeneous. The Beijing genotype predominated and was actively spreading. The findings obtained point to the need for the implementation of more effective preventive measures to stop the spread of drug-resistant M

Towards a 'human-like' model of tuberculosis: intranasal inoculation of LPS induces intragranulomatous lung necrosis in mice infected aerogenically with Mycobacterium tuberculosis.

PubMed

Cardona, P J; Llatjós, R; Gordillo, S; Díaz, J; Viñado, B; Ariza, A; Ausina, V

2001-01-01

It is well known that one of the differences between murine and human tuberculosis is the lack of intragranulomatous necrosis in the former. The aim of this study was to create a feasible and reproducible model of an experimental model of murine tuberculosis in which this necrosis should be present. Considering the Shwartzman reaction as a possible explanation for intragranulomatous necrosis in human tuberculosis, C57Bl/6 mice, infected aerogenically with a virulent strain of Mycobacterium tuberculosis, were intranasally inoculated with lipopolysaccharide (LPS) on day 19 postinfection (p.i.). Twenty-four hours later, neutrophils infiltrated the lung parenchyma in a significant level, and 10 days after necrosis could be detected in the centres of primary granulomas, that showed scanty macrophages and large amounts of collagen on an eosinophilic background. On the other hand, a significant decrease in the concentration of colony forming units (CFU) could be appreciated 24 h after the LPS inoculation. Afterwards, nonbronchogenic spreading of granulomas increased and higher levels of interferon (IFN)-gamma mRNA were detected. These results lend support to the Shwartzman reaction as the origin of the intragranulomatous necrosis in the M. tuberculosis infection, and provides a useful tool to improve experimental murine models in tuberculosis.

Tuberculosis (TB): Treatment

MedlinePlus

... Education & Training Home Conditions Tuberculosis (TB) Tuberculosis: Treatment Tuberculosis: Treatment Make an Appointment Refer a Patient Ask ... or bones is treated longer. NEXT: Preventive Treatment Tuberculosis: Diagnosis Tuberculosis: History Clinical Trials For more than ...

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

Cutaneous Tuberculosis

PubMed Central

Frankel, Amylynne; Penrose, Carolin

2009-01-01

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

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

PubMed Central

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

2014-01-01

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

Why wait? The social determinants underlying tuberculosis diagnostic delay.

PubMed

Bonadonna, Lily Victoria; Saunders, Matthew James; Zegarra, Roberto; Evans, Carlton; Alegria-Flores, Kei; Guio, Heinner

2017-01-01

Early detection and diagnosis of tuberculosis remain major global priorities for tuberculosis control. Few studies have used a qualitative approach to investigate the social determinants contributing to diagnostic delay and none have compared data collected from individual, community, and health-system levels. We aimed to characterize the social determinants that contribute to diagnostic delay among persons diagnosed with tuberculosis living in resource-constrained settings. Data were collected in public health facilities with high tuberculosis incidence in 19 districts of Lima, Peru. Semi-structured interviews with persons diagnosed with tuberculosis (n = 105) and their family members (n = 63) explored health-seeking behaviours, community perceptions of tuberculosis and socio-demographic circumstances. Focus groups (n = 6) were conducted with health personnel (n = 35) working in the National Tuberculosis Program. All interview data were transcribed and analysed using a grounded theory approach. The median delay between symptom onset and the public health facility visit that led to the first positive diagnostic sample was 57 days (interquartile range 28-126). The great majority of persons diagnosed with tuberculosis distrusted the public health system and sought care at public health facilities only after exhausting other options. It was universally agreed that persons diagnosed with tuberculosis faced discrimination by public and health personnel. Self-medication with medicines bought at local pharmacies was reported as the most common initial health-seeking behaviour due to the speed and low-cost of treatment in pharmacies. Most persons diagnosed with tuberculosis initially perceived their illness as a simple virus. Diagnostic delay was common and prolonged. When individuals reached a threshold of symptom severity, they addressed their health with the least time-consuming, most economically feasible, and well-known healthcare option available to them. In high

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

PubMed Central

Pai, Madhukar; Schito, Marco

2015-01-01

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

New drug candidates and therapeutic targets for tuberculosis therapy.

PubMed

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

2006-01-01

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

Procalcitonin as a Diagnostic and Prognostic Factor for Tuberculosis Meningitis

PubMed Central

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

2016-01-01

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

Tuberculosis

USGS Publications Warehouse

Friend, Milton

1999-01-01

Avian tuberculosis is usually caused by the bacterium Mycobacterium avium. At least 20 different types of M. avium have been identified, only three of which are known to cause disease in birds. Other types of Mycobacterium rarely cause tuberculosis in most avian species; however, parrots, macaws, and other large perching birds are susceptible to human and bovine types of tuberculosis bacilli. Avian tuberculosis generally is transmitted by direct contact with infected birds, ingestion of contaminated feed and water, or contact with a contaminated environment. Inhalation of the bacterium can cause respiratory tract infections. Wild bird studies in the Netherlands disclosed tuberculosis-infected puncture-type injuries in birds of prey that fight at the nest site (kestrels) or on the ground (buteo-type buzzards), but tuberculosisinfected injuries were not found in accipiters (falco

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

PubMed Central

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

2012-01-01

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

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.

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. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Various hysterosalpingography findings of female genital tuberculosis: A case series

PubMed Central

Afzali, Nargess; Ahmadi, Firoozeh; Akhbari, Farnaz

2013-01-01

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

Bovine tuberculosis: a retrospective study at Jos abattoir, Plateau State, Nigeria.

PubMed

Okeke, Lilian Akudo; Fawole, Olufunmilayo; Muhammad, Maryam; Okeke, Ikenna Osemeka; Nguku, Patrick; Wasswa, Peter; Dairo, David; Cadmus, Simeon

2016-01-01

Nigeria has the thirteenth highest burden of human tuberculosis. The current increasing incidence of tuberculosis in humans, particularly in immune-compromised persons, has given interest in the zoonotic importance of Mycobacterium bovis in developing countries like Nigeria. This study determined the prevalence of bovine tuberculosis as a background information for effective control measures in Plateau State in cattle population. We reviewed surveillance records on cattle slaughtered and suggestive tuberculosis lesions from cattle slaughtered annually from 2007-2012 in Jos abattoir, Plateau State. Bovine tuberculosis cases at post mortem were based on examination of characteristics TB lesion on organs by Veterinary officers. We performed descriptive analysis using Epi info version 3.5.3 and Microsoft Excel 2007. A total of 52, 262 cattle were slaughtered from 2007-2012, out of which 4, 658 (11.2%) had evidence of tuberculosis lesion at post mortem. The average yearly prevalence was 9.1% but varied from a high of 16.3% in 2007 to a low of 3.1% in 2012. Trend analysis showed that bovine tuberculosis had a seasonal variation and peaked mostly in July and August. The number of suggestive Tb lesion cases was highest in the month of August and lowest in the month of January, 2007-2012. This study shows that bovine tuberculosis is endemic in Plateau State. Trend analysis showed that bovine tuberculosis is seasonal and peaked mostly in July and August. Continuous surveillance through meat inspection is required to prevent zoonotic transmission of bovine tuberculosis.

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

Rapid molecular assays for detection of tuberculosis.

PubMed

Eddabra, Rkia; Ait Benhassou, Hassan

2018-01-01

Tuberculosis (TB) is an infectious disease that remains an important public health problem at the global level. It is one of the main causes of morbidity and mortality, due to the emergence of antibiotic resistant Mycobacterium strains and HIV co-infection. Over the past decade, important progress has been made for better control of the disease. While microscopy and culture continue to be indispensible for laboratory diagnosis of tuberculosis, the range of several molecular diagnostic tests, including the nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have expanded tremendously. They are becoming more accessible not only for detection and identification of Mycobacterium tuberculosis complex in clinical specimens, but now extend to diagnosing multi-drug resistant strains. Molecular diagnostic tests provide timely results useful for high-quality patient care, low contamination risk, and ease of performance and speed. This review focuses on the current diagnostic tests in use, including emerging technologies used for detection of tuberculosis in clinical specimens. The sensitivity and specificity of these tests have also been taken into consideration.

Rapid Detection of Cell-Free Mycobacterium tuberculosis DNA in Tuberculous Pleural Effusion.

PubMed

Che, Nanying; Yang, Xinting; Liu, Zichen; Li, Kun; Chen, Xiaoyou

2017-05-01

Tuberculous pleurisy is one of the most common types of extrapulmonary tuberculosis, but its diagnosis remains difficult. In this study, we report for the first time on the detection of cell-free Mycobacterium tuberculosis DNA in pleural effusion and an evaluation of a newly developed molecular assay for the detection of cell-free Mycobacterium tuberculosis DNA. A total of 78 patients with pleural effusion, 60 patients with tuberculous pleurisy, and 18 patients with alternative diseases were included in this study. Mycobacterial culture, the Xpert MTB/RIF assay, the adenosine deaminase assay, the T-SPOT.TB assay, and the cell-free Mycobacterium tuberculosis DNA assay were performed on all the pleural effusion samples. The cell-free Mycobacterium tuberculosis DNA assay and adenosine deaminase assay showed significantly higher sensitivities of 75.0% and 68.3%, respectively, than mycobacterial culture and the Xpert MTB/RIF assay, which had sensitivities of 26.7% and 20.0%, respectively ( P < 0.01). All four of these tests showed good specificities: 88.9% for the adenosine deaminase assay and 100% for the remaining three assays. The T-SPOT.TB assay with pleural effusion showed the highest sensitivity of 95.0% but the lowest specificity of 38.9%. The cell-free Mycobacterium tuberculosis DNA assay detected as few as 1.25 copies of IS 6110 per ml of pleural effusion and showed good accordance of the results between repeated tests ( r = 0.978, P = 2.84 × 10 -10 ). These data suggest that the cell-free Mycobacterium tuberculosis DNA assay is a rapid and accurate molecular test which provides direct evidence of Mycobacterium tuberculosis etiology. Copyright © 2017 American Society for Microbiology.

Rapid Detection of Cell-Free Mycobacterium tuberculosis DNA in Tuberculous Pleural Effusion

PubMed Central

Yang, Xinting; Liu, Zichen; Li, Kun

2017-01-01

ABSTRACT Tuberculous pleurisy is one of the most common types of extrapulmonary tuberculosis, but its diagnosis remains difficult. In this study, we report for the first time on the detection of cell-free Mycobacterium tuberculosis DNA in pleural effusion and an evaluation of a newly developed molecular assay for the detection of cell-free Mycobacterium tuberculosis DNA. A total of 78 patients with pleural effusion, 60 patients with tuberculous pleurisy, and 18 patients with alternative diseases were included in this study. Mycobacterial culture, the Xpert MTB/RIF assay, the adenosine deaminase assay, the T-SPOT.TB assay, and the cell-free Mycobacterium tuberculosis DNA assay were performed on all the pleural effusion samples. The cell-free Mycobacterium tuberculosis DNA assay and adenosine deaminase assay showed significantly higher sensitivities of 75.0% and 68.3%, respectively, than mycobacterial culture and the Xpert MTB/RIF assay, which had sensitivities of 26.7% and 20.0%, respectively (P < 0.01). All four of these tests showed good specificities: 88.9% for the adenosine deaminase assay and 100% for the remaining three assays. The T-SPOT.TB assay with pleural effusion showed the highest sensitivity of 95.0% but the lowest specificity of 38.9%. The cell-free Mycobacterium tuberculosis DNA assay detected as few as 1.25 copies of IS6110 per ml of pleural effusion and showed good accordance of the results between repeated tests (r = 0.978, P = 2.84 × 10−10). These data suggest that the cell-free Mycobacterium tuberculosis DNA assay is a rapid and accurate molecular test which provides direct evidence of Mycobacterium tuberculosis etiology. PMID:28275073

Tuberculosis Reports - UDOH-EPI

Science.gov Websites

Tuberculosis Tuberculosis Reports Tuberculosis Reports Tuberculosis Utah Reports Tuberculosis in Utah - Five (IBIS-PH) Tuberculosis 2015 Monthy Reports January February March April May June Tuberculosis National Reports National TB Data and Statistics Tuberculosis Global Reports TB Incidence Map by country TB

Pulmonary tuberculosis

MedlinePlus

TB; Tuberculosis - pulmonary; Mycobacterium - pulmonary ... Pulmonary TB is caused by the bacterium Mycobacterium tuberculosis (M tuberculosis) . TB is contagious. This means the bacteria is easily spread from an infected person ...

Biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents.

PubMed

Ma, Junying; Huang, Hongbo; Xie, Yunchang; Liu, Zhiyong; Zhao, Jin; Zhang, Chunyan; Jia, Yanxi; Zhang, Yun; Zhang, Hua; Zhang, Tianyu; Ju, Jianhua

2017-08-30

Tuberculosis remains one of the world's deadliest communicable diseases, novel anti-tuberculosis agents are urgently needed due to severe drug resistance and the co-epidemic of tuberculosis/human immunodeficiency virus. Here, we show the isolation of six anti-mycobacterial ilamycin congeners (1-6) bearing rare L-3-nitro-tyrosine and L-2-amino-4-hexenoic acid structural units from the deep sea-derived Streptomyces atratus SCSIO ZH16. The biosynthesis of the rare L-3-nitrotyrosine and L-2-amino-4-hexenoic acid units as well as three pre-tailoring and two post-tailoring steps are probed in the ilamycin biosynthetic machinery through a series of gene inactivation, precursor chemical complementation, isotope-labeled precursor feeding experiments, as well as structural elucidation of three intermediates (6-8) from the respective mutants. Most impressively, ilamycins E 1 /E 2 , which are produced in high titers by a genetically engineered mutant strain, show very potent anti-tuberculosis activity with an minimum inhibitory concentration value ≈9.8 nM to Mycobacterium tuberculosis H37Rv constituting extremely potent and exciting anti-tuberculosis drug leads.Tuberculosis (TB) remains one of the world's deadliest communicable diseases, novel anti-TB agents are urgently needed due to severe drug resistance and the co-epidemic of TB/HIV. Here, the authors show that anti-mycobacterial ilamycin congeners bearing unusual structural units possess extremely potent anti-tuberculosis activities.

Advances in Mycobacterium tuberculosis therapeutics discovery utlizing structural biology

PubMed Central

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

2013-01-01

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

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

Transmission of Mycobacterium tuberculosis in China: A Population-Based Molecular Epidemiologic Study

PubMed Central

Yang, Chongguang; Shen, Xin; Peng, Ying; Lan, Rushu; Zhao, Yuling; Long, Bo; Luo, Tao; Sun, Guomei; Li, Xia; Qiao, Ke; Gui, Xiaohong; Wu, Jie; Xu, Jiying; Li, Fabin; Li, Dingyue; Liu, Feiying; Shen, Mei; Hong, Jianjun; Mei, Jian; DeRiemer, Kathryn; Gao, Qian

2015-01-01

Background. Understanding the transmission of Mycobacterium tuberculosis is essential for the development of efficient tuberculosis control strategies. China has the second-largest tuberculosis burden in the world. Recent transmission and infection with M. tuberculosis, particularly drug-resistant strains, may account for many new tuberculosis cases. Methods. We performed a population-based molecular epidemiologic study of pulmonary tuberculosis in China during 1 July 2009 to 30 June 2012. We defined clusters as cases with identical variable number tandem repeat genotype patterns and identified the risk factors associated with clustering, by logistic regression. Relative transmission rates were estimated by the sputum smear status and drug susceptibility status of tuberculosis patients. Results. Among 2274 culture-positive tuberculosis patients with genotyped isolates, there were 705 (31.0%) tuberculosis patients in 287 clusters. Multidrug-resistant (MDR) tuberculosis (adjusted odds ratio [aOR], 1.86; 95% confidence interval [CI], 1.25–2.63) and infection with a Beijing family strain (aOR, 1.56; 95% CI, 1.23–2.96) were associated with clustering. Eighty-four of 280 (30.0%) clusters had a putative source case that was sputum smear negative, and 30.6% of their secondary cases were attributed to transmission by sputum smear–negative patients. The relative transmission rate for sputum smear negative compared with sputum smear–positive patients was 0.89 (95% CI, .68–1.10), and was 1.51 (95% CI, 1.00–2.24) for MDR tuberculosis vs drug-susceptible tuberculosis. Conclusions. Recent transmission of M. tuberculosis, including MDR strains, contributes substantially to tuberculosis disease in China. Sputum smear–negative cases were responsible for at least 30% of the secondary cases. Interventions to reduce the transmission of M. tuberculosis should be implemented in China. PMID:25829000

Controlling the Seedbeds of Tuberculosis: Diagnosis and Treatment of Tuberculosis Infection

PubMed Central

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

2015-01-01

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 critical opportunity to interrupt tuberculosis transmission and reduce the global burden of tuberculosis disease. Programs focusing on single strategies rather than comprehensive programs that deliver an integrated arsenal for tuberculosis control may continue to struggle. Tuberculosis preventive therapy is a poorly utilized tool that is essential for controlling the reservoirs of disease that drive the current 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. This paper outlines challenges to implementation of preventive therapy and provides pragmatic suggestions for overcoming them. It further advocates for tuberculosis preventive therapy as the core of a renewed global 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, community engagement, and enhance sustainable large scale implementation of preventive therapy programs. PMID:26515679

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

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.

Transmission of Extensively Drug-Resistant Tuberculosis in South Africa

PubMed Central

Shah, N. Sarita; Auld, Sara C.; Brust, James C.M.; Mathema, Barun; Ismail, Nazir; Moodley, Pravi; Mlisana, Koleka; Allana, Salim; Campbell, Angela; Mthiyane, Thuli; Morris, Natashia; Mpangase, Primrose; van der Meulen, Hermina; Omar, Shaheed V.; Brown, Tyler S.; Narechania, Apurva; Shaskina, Elena; Kapwata, Thandi; Kreiswirth, Barry; Gandhi, Neel R.

2017-01-01

BACKGROUND Drug-resistant tuberculosis threatens recent gains in the treatment of tuberculosis and human immunodeficiency virus (HIV) infection worldwide. A widespread epidemic of extensively drug-resistant (XDR) tuberculosis is occurring in South Africa, where cases have increased substantially since 2002. The factors driving this rapid increase have not been fully elucidated, but such knowledge is needed to guide public health interventions. METHODS We conducted a prospective study involving 404 participants in KwaZulu-Natal Province, South Africa, with a diagnosis of XDR tuberculosis between 2011 and 2014. Interviews and medical-record reviews were used to elicit information on the participants’ history of tuberculosis and HIV infection, hospitalizations, and social networks. Mycobacterium tuberculosis isolates underwent insertion sequence (IS)6110 restriction-fragment– length polymorphism analysis, targeted gene sequencing, and whole-genome sequencing. We used clinical and genotypic case definitions to calculate the proportion of cases of XDR tuberculosis that were due to inadequate treatment of multidrug-resistant (MDR) tuberculosis (i.e., acquired resistance) versus those that were due to transmission (i.e., transmitted resistance). We used social-network analysis to identify community and hospital locations of transmission. RESULTS Of the 404 participants, 311 (77%) had HIV infection; the median CD4+ count was 340 cells per cubic millimeter (interquartile range, 117 to 431). A total of 280 participants (69%) had never received treatment for MDR tuberculosis. Genotypic analysis in 386 participants revealed that 323 (84%) belonged to 1 of 31 clusters. Clusters ranged from 2 to 14 participants, except for 1 large cluster of 212 participants (55%) with a LAM4/KZN strain. Person-to-person or hospital-based epidemiologic links were identified in 123 of 404 participants (30%). CONCLUSIONS The majority of cases of XDR tuberculosis in KwaZulu-Natal, South Africa

Case report : tuberculosis liver abscess in male alcoholism patient

NASA Astrophysics Data System (ADS)

Siahaan, W. P.; Ginting, F.

2018-03-01

A liver abscess often occurs in low-middle income countries such as Indonesia. Two most common liver abscesses are amoebic and pyogenic liver abscess. Data that reported tuberculosis liver abscess (TLA) is extremely rare. A diagnostic criterion for tuberculosis liver abscess is rare and remains unclear. A 52-year-old man developed a TLA which was not associated with any pulmonary or gastrointestinal tract foci of tuberculosis. An ultrasonogram and abdominal scan showed an abscess in the right lobe. We performed paracentesis, and the pus from the lesion was positive tubercular bacilli on acid-fast bacilli staining. The patient was started on systemic antitubercular therapy to which he responded favorably. This report emphasizes the fact that, although a TLA is a very rare entity, it should be included in the differential diagnosis of liver abscess especially in Indonesia where the prevalence of tuberculosis is extremely high.

Tuberculosis and subsequent risk of lung cancer in Xuanwei, China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Engels, E.A.; Shen, M.; Chapman, R.S.

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 subjectsmore » (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.« less

Paleopathology of Human Tuberculosis and the Potential Role of Climate

PubMed Central

Nerlich, Andreas G.; Lösch, Sandra

2009-01-01

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

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

Mycobacterium tuberculosis promotes genomic instability in macrophages

PubMed Central

Castro-Garza, Jorge; Luévano-Martínez, Miriam Lorena; Villarreal-Treviño, Licet; Gosálvez, Jaime; Fernández, José Luis; Dávila-Rodríguez, Martha Imelda; García-Vielma, Catalina; González-Hernández, Silvia; Cortés-Gutiérrez, Elva Irene

2018-01-01

BACKGROUND Mycobacterium tuberculosis is an intracellular pathogen, which may either block cellular defensive mechanisms and survive inside the host cell or induce cell death. Several studies are still exploring the mechanisms involved in these processes. OBJECTIVES To evaluate the genomic instability of M. tuberculosis-infected macrophages and compare it with that of uninfected macrophages. METHODS We analysed the possible variations in the genomic instability of Mycobacterium-infected macrophages using the DNA breakage detection fluorescence in situ hybridisation (DBD-FISH) technique with a whole human genome DNA probe. FINDINGS Quantitative image analyses showed a significant increase in DNA damage in infected macrophages as compared with uninfected cells. DNA breaks were localised in nuclear membrane blebs, as confirmed with DNA fragmentation assay. Furthermore, a significant increase in micronuclei and nuclear abnormalities were observed in infected macrophages versus uninfected cells. MAIN CONCLUSIONS Genomic instability occurs during mycobacterial infection and these data may be seminal for future research on host cell DNA damage in M. tuberculosis infection. PMID:29412354

Mycobacterium tuberculosis effectors interfering host apoptosis signaling.

PubMed

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

2015-07-01

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

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

PubMed

Chyczewska, Elzbieta

2008-01-01

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

Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations

PubMed Central

Choi, Rihwa; Jeong, Byeong-Ho

2017-01-01

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response. PMID:28028995

Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations.

PubMed

Choi, Rihwa; Jeong, Byeong Ho; Koh, Won Jung; Lee, Soo Youn

2017-03-01

Although tuberculosis is largely a curable disease, it remains a major cause of morbidity and mortality worldwide. Although the standard 6-month treatment regimen is highly effective for drug-susceptible tuberculosis, the use of multiple drugs over long periods of time can cause frequent adverse drug reactions. In addition, some patients with drug-susceptible tuberculosis do not respond adequately to treatment and develop treatment failure and drug resistance. Response to tuberculosis treatment could be affected by multiple factors associated with the host-pathogen interaction including genetic factors and the nutritional status of the host. These factors should be considered for effective tuberculosis control. Therefore, therapeutic drug monitoring (TDM), which is individualized drug dosing guided by serum drug concentrations during treatment, and pharmacogenetics-based personalized dosing guidelines of anti-tuberculosis drugs could reduce the incidence of adverse drug reactions and increase the likelihood of successful treatment outcomes. Moreover, assessment and management of comorbid conditions including nutritional status could improve anti-tuberculosis treatment response.

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

PubMed Central

2011-01-01

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

Inflammation responses in patients with pulmonary tuberculosis in an intensive care unit

PubMed Central

Liu, Qiu-Yue; Han, Fen; Pan, Li-Ping; Jia, Hong-Yan; Li, Qi; Zhang, Zong-De

2018-01-01

Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global problem. Inflammatory responses are the primary characteristics of patients with pulmonary tuberculosis in intensive care units (ICU). The aim of the present study was to investigate the clinical importance of inflammatory cells and factors for patients with pulmonary tuberculosis in ICU. A total of 124 patients with pulmonary tuberculosis in ICU were recruited for the present study. The inflammatory responses in patients with pulmonary tuberculosis in ICU were examined by changes in inflammatory cells and factors in the serum. The results indicated that serum levels of lymphocytes, plasma cells, granulocytes and monocytes were increased in patients with pulmonary tuberculosis in ICU compared with healthy controls. The serum levels of inflammatory factors interleukin (IL)-1, IL-6, IL-10, IL-12, and IL-4 were upregulated in patients with pulmonary tuberculosis in ICU. Lower plasma concentrations of IL-2, IL-15 and interferon-γ were detected in patients with pulmonary tuberculosis compared with healthy controls. It was demonstrated that high mobility group box-1 protein expression levels were higher in the serum of patients with pulmonary tuberculosis compared with healthy controls. Notably, an imbalance of T-helper cell (Th)1/Th2 cytokines was observed in patients with pulmonary tuberculosis. Pulmonary tuberculosis caused by M. tuberculosis also upregulated expression of matrix metalloproteinase (MMP)-1 and MMP-9 in hPMCs. In conclusion, these outcomes demonstrated that inflammatory responses and inflammatory factors are associated with the progression of pulmonary tuberculosis, suggesting that inhibition of inflammatory responses and inflammatory factors may be beneficial for the treatment of patients with pulmonary tuberculosis in ICU. PMID:29456674

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. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A 10-year experience of tuberculosis in solid-organ transplant recipients.

PubMed

Ulubay, Gaye; Kupeli, Elif; Duvenci Birben, Ozlem; Seyfettin, Emine Pinar; Dogrul, Mustafa Ilgaz; Ozsancak Ugurlu, Aylin; Oner Eyuboglu, Fusun; Haberal, Mehmet

2015-04-01

Tuberculosis remains an important problem in solid-organ transplant patients due to their immunocompromised state. The objective of the present study was to report the incidence, demographic characteristics, and various presentations of tuberculosis in solid-organ transplant recipients. We evaluated a total of 999 patients (male/female = 665/334, 661 renal and 338 liver transplants) who underwent solid-organ transplant between 2003 and 2013. The medical records of all patients were retrospectively reviewed. Patients' demographics, transplant type, primary site of tuberculosis specimen culture and pathology results, chest radiograph, and thoracic computed tomography findings, total blood count and chemistry were all recorded. Among the 999 subjects, 19 patients (1.9%) (male/female: 15/4, mean ± SD age, 42 ± 18.5 y) were diagnosed with tuberculosis. The majority of patients (85%) were diagnosed with tuberculosis within 6 months after transplant, and 15% were diagnosed within 3 months. Most diagnoses of tuberculosis were based on histopathologic examination of biopsy material. Of these patients, 9 were diagnosed with pulmonary tuberculosis, 8 had extrapulmonary tuberculosis, and 2 had both. Nontuberculosis mycobacteria infections were detected in 3 patients. Even with a negative exposure history, tuberculosis can manifest as different clinic presentations in solid-organ transplant patients on immunosuppressive drugs, particularly in the first 6 months after transplant. Therefore, clinicians should always consider tuberculosis as the potential cause of an infectious disease with unknown cause to successfully diagnose and manage solid-organ transplant recipients.

Proteome Analysis of the Plasma Membrane of Mycobacterium Tuberculosis

PubMed Central

Arora, Shalini; Kosalai, K.; Namane, Abdelkader; Pym, Alex S.; Cole, Stewart T.

2002-01-01

The plasma membrane of Mycobacterium tuberculosis is likely to contain proteins that could serve as novel drug targets, diagnostic probes or even components of a vaccine against tuberculosis. With this in mind, we have undertaken proteome analysis of the membrane of M. tuberculosis H37Rv. Isolated membrane vesicles were extracted with either a detergent (Triton X114) or an alkaline buffer (carbonate) following two of the protocols recommended for membrane protein enrichment. Proteins were resolved by 2D-GE using immobilized pH gradient (IPG) strips, and identified by peptide mass mapping utilizing the M. tuberculosis genome database. The two extraction procedures yielded patterns with minimal overlap. Only two proteins, both HSPs, showed a common presence. MALDI–MS analysis of 61 spots led to the identification of 32 proteins, 17 of which were new to the M. tuberculosis proteome database. We classified 19 of the identified proteins as ‘membrane-associated’; 14 of these were further classified as ‘membrane-bound’, three of which were lipoproteins. The remaining proteins included four heat-shock proteins and several enzymes involved in energy or lipid metabolism. Extraction with Triton X114 was found to be more effective than carbonate for detecting ‘putative’ M. tuberculosis membrane proteins. The protocol was also found to be suitable for comparing BCG and M. tuberculosis membranes, identifying ESAT-6 as being expressed selectively in M. tuberculosis. While this study demonstrates for the first time some of the membrane proteins of M. tuberculosis, it also underscores the problems associated with proteomic analysis of a complex membrane such as that of a mycobacterium. PMID:18629250

Identifying Hotspots of Multidrug-Resistant Tuberculosis Transmission Using Spatial and Molecular Genetic Data

PubMed Central

Zelner, Jonathan L.; Murray, Megan B.; Becerra, Mercedes C.; Galea, Jerome; Lecca, Leonid; Calderon, Roger; Yataco, Rosa; Contreras, Carmen; Zhang, Zibiao; Manjourides, Justin; Grenfell, Bryan T.; Cohen, Ted

2016-01-01

Background. We aimed to identify and determine the etiology of “hotspots” of concentrated multidrug-resistant tuberculosis (MDR-tuberculosis) risk in Lima, Peru. Methods. From 2009 to 2012, we conducted a prospective cohort study among households of tuberculosis cases from 106 health center (HC) areas in Lima, Peru. All notified tuberculosis cases and their household contacts were followed for 1 year. Symptomatic individuals were screened by microscopy and culture; positive cultures were tested for drug susceptibility (DST) and genotyped by 24-loci mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR). Results. 3286 individuals with culture-confirmed disease, DST, and 24-loci MIRU-VNTR were included in our analysis. Our analysis reveals: (1) heterogeneity in annual per-capita incidence of tuberculosis and MDR-tuberculosis by HC, with a rate of MDR-tuberculosis 89 times greater (95% confidence interval [CI], 54,185) in the most-affected versus the least-affected HC; (2) high risk for MDR-tuberculosis in a region spanning several HCs (odds ratio = 3.19, 95% CI, 2.33, 4.36); and (3) spatial aggregation of MDR-tuberculosis genotypes, suggesting localized transmission. Conclusions. These findings reveal that localized transmission is an important driver of the epidemic of MDR-tuberculosis in Lima. Efforts to interrupt transmission may be most effective if targeted to this area of the city. PMID:26175455

Factors determining ethnic differences in the incidence of bacteriologically confirmed genitourinary tuberculosis in south east England.

PubMed

Grange, J M; Yates, M D; Ormerod, L P

1995-01-01

In South East England, genitourinary (GU) tuberculosis is a much less common manifestation of non-respiratory tuberculosis in patients of Indian subcontinent (ISC) ethnic origin than in those of European ethnic origin. When considered in relation to all bacteriologically confirmed cases of tuberculosis, both respiratory and non-respiratory, the ethnic difference in the occurrence of GU tuberculosis is much less evident, while there is a highly significant excess of other forms of non-respiratory tuberculosis among the ethnic ISC patients. Unlike other forms of non-respiratory tuberculosis, GU disease tends to occur in an older age range in the ethnic ISC population and, when stratified for age, the ethnic difference in the occurrence of this form of tuberculosis is not significant while that of lymph node tuberculosis remains significantly high. Thus, after elimination of the confounding factor of age, the occurrence of GU tuberculosis is very similar in the two ethnic groups while other forms of non-respiratory tuberculosis differ considerably.

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

PubMed Central

2011-01-01

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

Bovine Tuberculosis

USDA-ARS?s Scientific Manuscript database

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...

Bovine tuberculosis

USDA-ARS?s Scientific Manuscript database

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 cat...

[Endobronchial tuberculosis].

PubMed

Manal, E; Nahid, Z; Hanane, B; Najiba, Y

2017-04-01

The endobronchial tuberculosis (EBTB) is an uncommon type of tuberculosis. The respiratory symptoms in EBTB are usually nonspecific and misleading. The aim of the study is to determine the clinical features and diagnostic aspects of EBTB. Twenty-eight cases of endobronchial tuberculosis collected from January 2009 to October 2015. EBTB was found in 16 females and 12 males. The mean age was 48 years. The history of tuberculosis and tuberculosis contagion were not found in any case. The respiratory symptoms were dominated by cough and dyspnea. Hemoptysis was found in 7 cases. The chest X-ray showed associated pulmonary lesions in 26 cases. Bronchoscopy finded an endobronchial granular lesion in 15 cases, a tumorous pattern in 7 cases; a thickening spurs in 4 cases and ganglio-bronchial fistula in two cases. Bronchial biopsies had found a caseo-follicular tuberculosis in 27 cases. Pleural biopsy confirmed associated pleural tuberculosis in one case. The research of Koch bacillus in the sputum was positive in 13 cases and culture in 6 cases. The antituberculosis treatment was started in all patients and an oral corticosteroids treatment was associated in 5 cases. The evolution was good in 26 cases. This study showed clinical, radiological and endoscopic bronchial tuberculosis polymorphism making its diagnosis difficult and the importance of a bacteriological and/or histological confirmation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings

PubMed Central

Luetkemeyer, Anne F.; Firnhaber, Cynthia; Kendall, Michelle A.; Wu, Xingye; Mazurek, Gerald H.; Benator, Debra A.; Arduino, Roberto; Fernandez, Michel; Guy, Elizabeth; Johnson, Pamela; Metchock, Beverly; Sattler, Fred; Telzak, Edward; Wang, Yun F.; Weiner, Marc; Swindells, Susan; Sanne, Ian M.; Havlir, Diane V.; Grinsztejn, Beatriz; Alland, David

2016-01-01

Background. The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well as rpoB mutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. Methods. Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. Results. Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB+] sputum, 59.3% with AFB smear-negative [AFB–] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB+, 71.4% if AFB–), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB+/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin-resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. Conclusions. In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation

Transmission of Mycobacterium tuberculosis between farmers and cattle in central Ethiopia.

PubMed

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

2013-01-01

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

Direct comparison of the diagnostic yield of ultrasound-assisted Abrams and Tru-Cut needle biopsies for pleural tuberculosis.

PubMed

Koegelenberg, Coenraad Frederik N; Bolliger, Christoph Thomas; Theron, Johan; Walzl, Gerhard; Wright, Colleen Anne; Louw, Mercia; Diacon, Andreas Henri

2010-10-01

Tuberculous pleuritis remains the commonest cause of exudative effusions in areas with a high prevalence of tuberculosis and histological and/or microbiological confirmation on pleural tissue is the gold standard for its diagnosis. Uncertainty remains regarding the choice of closed pleural biopsy needles. This prospective study compared ultrasound-assisted Abrams and Tru-Cut needle biopsies with regard to their diagnostic yield for pleural tuberculosis. 89 patients (54 men) of mean ± SD age 38.7 ± 16.7 years with pleural effusions and a clinical suspicion of tuberculosis were enrolled in the study. Transthoracic ultrasound was performed on all patients, who were then randomly assigned to undergo ≥ 4 Abrams needle biopsies followed by ≥ 4 Tru-Cut needle biopsies or vice versa. Medical thoracoscopy was performed on cases with non-diagnostic closed biopsies. Histological and/or microbiological proof of tuberculosis on any pleural specimen was considered the gold standard for pleural tuberculosis. Pleural tuberculosis was diagnosed in 66 patients, alternative diagnoses were established in 20 patients and 3 remained undiagnosed. Pleural biopsy specimens obtained with Abrams needles contained pleural tissue in 81 patients (91.0%) and were diagnostic for tuberculosis in 54 patients (sensitivity 81.8%), whereas Tru-Cut needle biopsy specimens only contained pleural tissue in 70 patients (78.7%, p=0.015) and were diagnostic in 43 patients (sensitivity 65.2%, p=0.022). Ultrasound-assisted pleural biopsies performed with an Abrams needle are more likely to contain pleura and have a significantly higher diagnostic sensitivity for pleural tuberculosis.

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

PubMed

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

2014-02-01

Tuberculosis is known to have afflicted humans throughout history and re-emerged towards the end of the 20th century, to an extent that it was declared a global emergency in 1993. The aim of this study was to apply a rigorous analytical regime to the detection of Mycobacterium tuberculosis complex (MTBC) DNA in 77 bone and tooth samples from 70 individuals from Britain and continental Europe, spanning the 1st-19th centuries AD. We performed the work in dedicated ancient DNA facilities designed to prevent all types of modern contamination, we checked the authenticity of all products obtained by the polymerase chain reaction, and we based our conclusions on up to four replicate experiments for each sample, some carried out in an independent laboratory. We identified 12 samples that, according to our strict criteria, gave definite evidence for the presence of MTBC DNA, and another 22 that we classified as "probable" or "possible." None of the definite samples came from vertebrae displaying lesions associated with TB. Instead, eight were from ribs displaying visceral new bone formation, one was a tooth from a skeleton with rib lesions, one was taken from a skeleton with endocranial lesions, one from an individual with lesions to the sacrum and sacroiliac joint and the last was from an individual with no lesions indicative of TB or possible TB. Our results add to information on the past temporal and geographical distribution of TB and affirm the suitability of ribs for studying ancient TB. Copyright © 2013 Wiley Periodicals, Inc.

Testing the influenza–tuberculosis selective mortality hypothesis with Union Army data⋆

PubMed Central

Noymer, Andrew

2009-01-01

Using Cox regression, this paper shows a weak association between having tuberculosis and dying from influenza among Union Army veterans in late nineteenth-century America. It has been suggested elsewhere [Noymer, A. and M. Garenne (2000). The 1918 influenza epidemic’s effects on sex differentials in mortality in the United States. Population and Development Review 26(3), 565–581.] that the 1918 influenza pandemic accelerated the decline of tuberculosis, by killing many people with tuberculosis. The question remains whether individuals with tuberculosis were at greater risk of influenza death, or if the 1918/post-1918 phenomenon arose from the sheer number of deaths in the influenza pandemic. The present findings, from microdata, cautiously point toward an explanation of Noymer and Garenne’s selection effect in terms of age-overlap of the 1918 pandemic mortality and tuberculosis morbidity, a phenomenon I term “passive selection”. Another way to think of this is selection at the cohort, as opposed to individual, level. PMID:19304361

Performance of a Highly Sensitive Mycobacterium tuberculosis Complex Real-Time PCR Assay for Diagnosis of Pulmonary Tuberculosis in a Low-Prevalence Setting: a Prospective Intervention Study.

PubMed

Vinuesa, Víctor; Borrás, Rafael; Briones, María Luisa; Clari, María Ángeles; Cresencio, Vicenta; Giménez, Estela; Muñoz, Carmen; Oltra, Rosa; Servera, Emilio; Scheelje, Talia; Tornero, Carlos; Navarro, David

2018-05-01

The potential impact of routine real-time PCR testing of respiratory specimens from patients with presumptive tuberculosis in terms of diagnostic accuracy and time to tuberculosis treatment inception in low-prevalence settings remains largely unexplored. We conducted a prospective intervention cohort study. Respiratory specimens from 1,020 patients were examined by acid-fast bacillus smear microscopy, tested by a real-time Mycobacterium tuberculosis complex PCR assay (Abbott RealTi me MTB PCR), and cultured in mycobacterial media. Seventeen patients tested positive by PCR (5 were acid-fast bacillus smear positive and 12 acid-fast bacillus smear negative), and Mycobacterium tuberculosis was recovered from cultures for 12 of them. Patients testing positive by PCR and negative by culture ( n = 5) were treated and deemed to have responded to antituberculosis therapy. There were no PCR-negative/culture-positive cases, and none of the patients testing positive for nontuberculous mycobacteria ( n = 20) yielded a positive PCR result. The data indicated that routine testing of respiratory specimens from patients with presumptive tuberculosis by the RealTi me MTB PCR assay improves the tuberculosis diagnostic yield and may reduce the time to antituberculosis treatment initiation. On the basis of our data, we propose a novel mycobacterial laboratory algorithm for tuberculosis diagnosis. Copyright © 2018 American Society for Microbiology.

Drug resistant Skeletal Tuberculosis in a tertiary care centre in South India.

PubMed

Arockiaraj, J; Balaji, G S; Cherian, V M; T S, Jepegnanam; Thomas, B P; Michael, Joy S; Poonnoose, P M

2018-03-01

Drug resistant tuberculosis is alarmingly on the rise especially in developing countries. Skeletal tuberculosis accounts up to 10% of all extra pulmonary tuberculosis. World Health Organisation (WHO) has not formulated guidelines for the management of Multi-drug resistant skeletal tuberculosis. A retrospective analysis of patients treated for musculoskeletal tuberculosis was done, to study drug resistance patterns. The outcome was assessed both clinically and radiologically.898 patients were treated for skeletal tuberculosis during the period of 2006-2013 (96 months). 478 (53.2%) patients were treated for tubercular spondylitis and 420 (46.8%) for extra-spinal skeletal tuberculosis. Ninety two patients (10.2%) had documented resistance to the anti-tubercular drugs. There were 42 mono resistant tuberculosis cases (4.7%), 13 poly resistant cases (1.4%), 33 multi-drug resistant cases (MDR TB) (3.7%) and 4 (0.4%) extremely drug resistant tuberculosis cases (XDR). All the patients were treated medically as per drug susceptibility patterns and protocols. Surgery was performed when indicated in 59 (66%) cases. 85% completed their course of treatment and were successfully healed as per pre-set clinical, biochemical and radiological criteria. The remaining were lost to follow up. One patient died as a result of post op respiratory infection. The prevalence of Multi-drug resistant tuberculosis patients in our centre was 3.7% and that of Extremely drug resistant tuberculosis cases was 0.4%. A Multi-disciplinary approach with drug susceptibility tests, sensitive drugs, and surgery if required is essential. Health education is essential to improve awareness among health care professionals about the danger of drug resistance in tuberculosis.

Immunogenic Properties of Lactobacillus plantarum Producing Surface-Displayed Mycobacterium tuberculosis Antigens

PubMed Central

Kleiveland, Charlotte R.; Minic, Rajna; Moen, Lars F.; Øverland, Lise; Tjåland, Rannei; Carlsen, Harald; Lea, Tor; Eijsink, Vincent G. H.

2016-01-01

ABSTRACT Tuberculosis (TB) remains among the most deadly diseases in the world. The only available vaccine against tuberculosis is the bacille Calmette-Guérin (BCG) vaccine, which does not ensure full protection in adults. There is a global urgency for the development of an effective vaccine for preventing disease transmission, and it requires novel approaches. We are exploring the use of lactic acid bacteria (LAB) as a vector for antigen delivery to mucosal sites. Here, we demonstrate the successful expression and surface display of a Mycobacterium tuberculosis fusion antigen (comprising Ag85B and ESAT-6, referred to as AgE6) on Lactobacillus plantarum. The AgE6 fusion antigen was targeted to the bacterial surface using two different anchors, a lipoprotein anchor directing the protein to the cell membrane and a covalent cell wall anchor. AgE6-producing L. plantarum strains using each of the two anchors induced antigen-specific proliferative responses in lymphocytes purified from TB-positive donors. Similarly, both strains induced immune responses in mice after nasal or oral immunization. The impact of the anchoring strategies was reflected in dissimilarities in the immune responses generated by the two L. plantarum strains in vivo. The present study comprises an initial step toward the development of L. plantarum as a vector for M. tuberculosis antigen delivery. IMPORTANCE This work presents the development of Lactobacillus plantarum as a candidate mucosal vaccine against tuberculosis. Tuberculosis remains one of the top infectious diseases worldwide, and the only available vaccine, bacille Calmette-Guérin (BCG), fails to protect adults and adolescents. Direct antigen delivery to mucosal sites is a promising strategy in tuberculosis vaccine development, and lactic acid bacteria potentially provide easy, safe, and low-cost delivery vehicles for mucosal immunization. We have engineered L. plantarum strains to produce a Mycobacterium tuberculosis fusion antigen and

Immunogenic Properties of Lactobacillus plantarum Producing Surface-Displayed Mycobacterium tuberculosis Antigens.

PubMed

Kuczkowska, Katarzyna; Kleiveland, Charlotte R; Minic, Rajna; Moen, Lars F; Øverland, Lise; Tjåland, Rannei; Carlsen, Harald; Lea, Tor; Mathiesen, Geir; Eijsink, Vincent G H

2017-01-15

Tuberculosis (TB) remains among the most deadly diseases in the world. The only available vaccine against tuberculosis is the bacille Calmette-Guérin (BCG) vaccine, which does not ensure full protection in adults. There is a global urgency for the development of an effective vaccine for preventing disease transmission, and it requires novel approaches. We are exploring the use of lactic acid bacteria (LAB) as a vector for antigen delivery to mucosal sites. Here, we demonstrate the successful expression and surface display of a Mycobacterium tuberculosis fusion antigen (comprising Ag85B and ESAT-6, referred to as AgE6) on Lactobacillus plantarum The AgE6 fusion antigen was targeted to the bacterial surface using two different anchors, a lipoprotein anchor directing the protein to the cell membrane and a covalent cell wall anchor. AgE6-producing L. plantarum strains using each of the two anchors induced antigen-specific proliferative responses in lymphocytes purified from TB-positive donors. Similarly, both strains induced immune responses in mice after nasal or oral immunization. The impact of the anchoring strategies was reflected in dissimilarities in the immune responses generated by the two L. plantarum strains in vivo The present study comprises an initial step toward the development of L. plantarum as a vector for M. tuberculosis antigen delivery. This work presents the development of Lactobacillus plantarum as a candidate mucosal vaccine against tuberculosis. Tuberculosis remains one of the top infectious diseases worldwide, and the only available vaccine, bacille Calmette-Guérin (BCG), fails to protect adults and adolescents. Direct antigen delivery to mucosal sites is a promising strategy in tuberculosis vaccine development, and lactic acid bacteria potentially provide easy, safe, and low-cost delivery vehicles for mucosal immunization. We have engineered L. plantarum strains to produce a Mycobacterium tuberculosis fusion antigen and to anchor this

Impact of previous ART and of ART initiation on outcome of HIV-associated tuberculosis.

PubMed

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

2012-01-01

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

Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test

PubMed Central

Lawn, Stephen D; Mwaba, Peter; Bates, Matthew; Piatek, Amy; Alexander, Heather; Marais, Ben J; Cuevas, Luis E; McHugh, Timothy D; Zijenah, Lynn; Kapata, Nathan; Abubakar, Ibrahim; McNerney, Ruth; Hoelscher, Michael; Memish, Ziad A; Migliori, Giovanni Battista; Kim, Peter; Maeurer, Markus; Schito, Marco; Zumla, Alimuddin

2015-01-01

Rapid progress has been made in the development of new diagnostic assays for tuberculosis in recent years. New technologies have been developed and assessed, and are now being implemented. The Xpert MTB/RIF assay, which enables simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance, was endorsed by WHO in December, 2010. This assay was specifically recommended for use as the initial diagnostic test for suspected drug-resistant or HIV-associated pulmonary tuberculosis. By June, 2012, two-thirds of countries with a high tuberculosis burden and half of countries with a high multidrug-resistant tuberculosis burden had incorporated the assay into their national tuberculosis programme guidelines. Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event, clinical and programmatic effects and cost-effectiveness remain to be defined. We review the rapidly growing body of scientific literature and discuss the advantages and challenges of using the Xpert MTB/RIF assay in areas where tuberculosis is endemic. We also review other prospects within the developmental pipeline. A rapid, accurate point-of-care diagnostic test that is affordable and can be readily implemented is urgently needed. Investment in the tuberculosis diagnostics pipeline should remain a major priority for funders and researchers. PMID:23531388

The tuberculosis hospital in Hohenkrug, Stettin. Department of Genitourinary Tuberculosis.

PubMed

Zajaczkowski, Tadeusz

2012-01-01

Towards the end of the 19th century, Europe turned particular attention to the problem of tuberculosis, at that time the most serious social disease. In the majority of cases, pulmonary tuberculosis had a fatal outcome owing to the lack of effective drugs and methods of treatment. Due to poor sanitary conditions, particularly as regards dwellings, pulmonary tuberculosis was able to spread rapidly. Hospital departments were reluctant to admit patients suffering from tuberculosis. It was only after the discoveries of Robert Koch (bacillus tubercle in 1882) that the cause of the disease became understood and methods of treatment began to be developed. A modern sanatorium and hospital with 270 beds was erected in Hohenkrug (today Szczecin-Zdunowo) between 1915 and 1930. Patients could now be treated with modern methods, surgically in most cases. After the Second World War, pulmonary tuberculosis was still an enormous epidemiologic problem. In 1949, the Polish authorities opened a 400-bed sanatoriumin Zdunowo. The methods of treatment were not much different from pre-war practice and it was only the routine introduction of antituberculotic drugs during the fifties of the past century that brought about a radical change in the fight against tuberculosis. The growing numbers of patients with tuberculosis of the genitourinary system led to the opening in 1958 of a 40-bed specialist ward at the Tuberculosis Sanatorium in Zdunowo. It should be emphasized that the Department of Genitourinary Tuberculosis in Szczecin-Zdunowo was a historical necessity and a salvation for thousands of patients from Northern Poland. The Department totally fulfilled its social duties thanks to the commitment of many outstanding persons dedicated to helping the patients. This unit was finally closed in 1987 because the demand for surgical treatment of tuberculosis was declining concurrently with the advent of new and potent antituberculotics and falling number of new cases of genitourinary

The Association between Mycobacterium Tuberculosis Genotype and Drug Resistance in Peru

PubMed Central

Grandjean, Louis; Iwamoto, Tomotada; Lithgow, Anna; Gilman, Robert H; Arikawa, Kentaro; Nakanishi, Noriko; Martin, Laura; Castillo, Edith; Alarcon, Valentina; Coronel, Jorge; Solano, Walter; Aminian, Minoo; Guezala, Claudia; Rastogi, Nalin; Couvin, David; Sheen, Patricia; Zimic, Mirko; Moore, David AJ

2015-01-01

Background The comparison of Mycobacterium tuberculosis bacterial genotypes with phenotypic, demographic, geospatial and clinical data improves our understanding of how strain lineage influences the development of drug-resistance and the spread of tuberculosis. Methods To investigate the association of Mycobacterium tuberculosis bacterial genotype with drug-resistance. Drug susceptibility testing together with genotyping using both 15-loci MIRU-typing and spoligotyping, was performed on 2,139 culture positive isolates, each from a different patient in Lima, Peru. Demographic, geospatial and socio-economic data were collected using questionnaires, global positioning equipment and the latest national census. Results The Latin American Mediterranean (LAM) clade (OR 2.4, p<0.001) was significantly associated with drug-resistance and alone accounted for more than half of all drug resistance in the region. Previously treated patients, prisoners and genetically clustered cases were also significantly associated with drug-resistance (OR's 2.5, 2.4 and 1.8, p<0.001, p<0.05, p<0.001 respectively). Conclusions Tuberculosis disease caused by the LAM clade was more likely to be drug resistant independent of important clinical, genetic and socio-economic confounding factors. Explanations for this include; the preferential co-evolution of LAM strains in a Latin American population, a LAM strain bacterial genetic background that favors drug-resistance or the "founder effect" from pre-existing LAM strains disproportionately exposed to drugs. PMID:25984723

Characterisation of methionine adenosyltransferase from Mycobacterium smegmatis and M. tuberculosis

PubMed Central

Berger, Bradley J; Knodel, Marvin H

2003-01-01

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

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

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

PubMed Central

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

2015-01-01

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

[Amendment of tuberculosis prevention law and prospect of tuberculosis control program].

PubMed

Ushio, Mitsuhiro

2005-07-01

Tuberculosis Control Law, which provides a legal basis for national tuberculosis control, was amended in 2004 and entered into force on April 1, 2005. As it is more than half a century since its initial enactment, the law has been drastically amended based on some of the relatively new important ideas such as up-to-date scientific evidence, recent epidemiological conditions of tuberculosis, decentralization and respect for human rights. Japan has once seen a time when considerable part of producing population were affected with tuberculosis which caused severe infliction on the whole Japanese society including economical damage. With progress in medical technology such as development of chemotherapy and improvement of sanitary conditions, there was a major decline in incidence rate and death rate during the 1960s and 1970s. However, the decrease in TB incidence began to stagnate in the 1980s, partly explained by aging of the overall society and worsening of the urban tuberculosis conditions. Since then, there has been a discussion on review of national tuberculosis control program, and the increase in the number of tuberculosis patients in 1997, which happened for the first time in 38 years, precipitated the process. In 1999, 'Tuberculosis Emergency Declaration' was announced by the Minister of Health, which led to emergency national tuberculosis survey in 2000, and based on the result came forward the Recommendation on Comprehensive Review of National Tuberculosis Plan. Main ideas and spirits of the Recommendation were taken full account of during the process of the amendment of the law and were mostly reflected on the final outcome. Five key elements include; Establishment of National Tuberculosis Fundamental Guideline and Prefectural Tuberculosis Prevention Plan, Review on TB screening, Review on BCG vaccination policy, Promotion of a Japanese version of DOTS, Review on Tuberculosis Advisory Committee 1. Establishment of National Tuberculosis Fundamental

Tuberculosis

MedlinePlus

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

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

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-term Protection From Isoniazid Preventive Therapy for Tuberculosis in HIV-Infected Patients in a Medium-Burden Tuberculosis Setting: The TB/HIV in Rio (THRio) Study

PubMed Central

Golub, Jonathan E.; Cohn, Silvia; Saraceni, Valeria; Cavalcante, Solange C.; Pacheco, Antonio G.; Moulton, Lawrence H.; Durovni, Betina; Chaisson, Richard E.

2015-01-01

Background. The duration of protection against tuberculosis provided by isoniazid preventive therapy is not known for human immunodeficiency virus (HIV)-infected individuals living in settings of medium tuberculosis incidence. Methods. We conducted an individual-level analysis of participants in a cluster-randomized, phased-implementation trial of isoniazid preventive therapy. HIV-infected patients who had positive tuberculin skin tests (TSTs) were followed until tuberculosis diagnosis, death, or administrative censoring. Nelson–Aalen cumulative hazard plots were generated and hazards were compared using the log-rank test. Cox proportional hazards models were fitted to investigate factors associated with tuberculosis diagnosis. Results. Between 2003 and 2009, 1954 patients with a positive TST were studied. Among these, 1601 (82%) initiated isoniazid. Overall tuberculosis incidence was 1.39 per 100 person-years (PY); 0.53 per 100 PY in those who initiated isoniazid and 6.52 per 100 PY for those who did not (adjusted hazard ratio [aHR], 0.17; 95% confidence interval [CI], .11–.25). Receiving antiretroviral therapy at time of a positive TST was associated with a reduced risk of tuberculosis (aHR, 0.69; 95% CI, .48–1.00). Nelson–Aalen plots of tuberculosis incidence showed a constant risk, with no acceleration in 7 years of follow-up for those initiating isoniazid preventive therapy. Conclusions. Isoniazid preventive therapy significantly reduced tuberculosis risk among HIV-infected patients with a positive TST. In a medium-prevalence setting, 6 months of isoniazid in HIV-infected patients with positive TST reduces tuberculosis risk over 7 years of follow-up, in contrast to results of studies in higher-burden settings in Africa. PMID:25365974

PknB remains an essential and a conserved target for drug development in susceptible and MDR strains of M. Tuberculosis.

PubMed

Gupta, Anamika; Pal, Sudhir K; Pandey, Divya; Fakir, Najneen A; Rathod, Sunita; Sinha, Dhiraj; SivaKumar, S; Sinha, Pallavi; Periera, Mycal; Balgam, Shilpa; Sekar, Gomathi; UmaDevi, K R; Anupurba, Shampa; Nema, Vijay

2017-08-18

The Mycobacterium tuberculosis (M.tb) protein kinase B (PknB) which is now proved to be essential for the growth and survival of M.tb, is a transmembrane protein with a potential to be a good drug target. However it is not known if this target remains conserved in otherwise resistant isolates from clinical origin. The present study describes the conservation analysis of sequences covering the inhibitor binding domain of PknB to assess if it remains conserved in susceptible and resistant clinical strains of mycobacteria picked from three different geographical areas of India. A total of 116 isolates from North, South and West India were used in the study with a variable profile of their susceptibilities towards streptomycin, isoniazid, rifampicin, ethambutol and ofloxacin. Isolates were also spoligotyped in order to find if the conservation pattern of pknB gene remain consistent or differ with different spoligotypes. The impact of variation as found in the study was analyzed using Molecular dynamics simulations. The sequencing results with 115/116 isolates revealed the conserved nature of pknB sequences irrespective of their susceptibility status and spoligotypes. The only variation found was in one strains wherein pnkB sequence had G to A mutation at 664 position translating into a change of amino acid, Valine to Isoleucine. After analyzing the impact of this sequence variation using Molecular dynamics simulations, it was observed that the variation is causing no significant change in protein structure or the inhibitor binding. Hence, the study endorses that PknB is an ideal target for drug development and there is no pre-existing or induced resistance with respect to the sequences involved in inhibitor binding. Also if the mutation that we are reporting for the first time is found again in subsequent work, it should be checked with phenotypic profile before drawing the conclusion that it would affect the activity in any way. Bioinformatics analysis in our study

Women and tuberculosis.

PubMed

Connolly, M; Nunn, P

1996-01-01

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

Regulatory RNA in Mycobacterium tuberculosis, back to basics.

PubMed

Schwenk, Stefan; Arnvig, Kristine B

2018-06-01

Since the turn of the millenium, RNA-based control of gene expression has added an extra dimension to the central dogma of molecular biology. Still, the roles of Mycobacterium tuberculosis regulatory RNAs and the proteins that facilitate their functions remain elusive, although there can be no doubt that RNA biology plays a central role in the baterium's adaptation to its many host environments. In this review, we have presented examples from model organisms and from M. tuberculosis to showcase the abundance and versatility of regulatory RNA, in order to emphasise the importance of these 'fine-tuners' of gene expression.

Population aging and migrant workers: bottlenecks in tuberculosis control in rural China.

PubMed

Bele, Sumedh; Jiang, Wei; Lu, Hui; You, Hua; Fan, Hong; Huang, Lifang; Wang, Qungang; Shen, Hongbing; Wang, Jianming

2014-01-01

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

Developing a customised approach for strengthening tuberculosis laboratory quality management systems toward accreditation

PubMed Central

Trollip, Andre; Erni, Donatelle; Kao, Kekeletso

2017-01-01

Background Quality-assured tuberculosis laboratory services are critical to achieve global and national goals for tuberculosis prevention and care. Implementation of a quality management system (QMS) in laboratories leads to improved quality of diagnostic tests and better patient care. The Strengthening Laboratory Management Toward Accreditation (SLMTA) programme has led to measurable improvements in the QMS of clinical laboratories. However, progress in tuberculosis laboratories has been slower, which may be attributed to the need for a structured tuberculosis-specific approach to implementing QMS. We describe the development and early implementation of the Strengthening Tuberculosis Laboratory Management Toward Accreditation (TB SLMTA) programme. Development The TB SLMTA curriculum was developed by customizing the SLMTA curriculum to include specific tools, job aids and supplementary materials specific to the tuberculosis laboratory. The TB SLMTA Harmonized Checklist was developed from the World Health Organisation Regional Office for Africa Stepwise Laboratory Quality Improvement Process Towards Accreditation checklist, and incorporated tuberculosis-specific requirements from the Global Laboratory Initiative Stepwise Process Towards Tuberculosis Laboratory Accreditation online tool. Implementation Four regional training-of-trainers workshops have been conducted since 2013. The TB SLMTA programme has been rolled out in 37 tuberculosis laboratories in 10 countries using the Workshop approach in 32 laboratories in five countries and the Facility-based approach in five tuberculosis laboratories in five countries. Conclusion Lessons learnt from early implementation of TB SLMTA suggest that a structured training and mentoring programme can build a foundation towards further quality improvement in tuberculosis laboratories. Structured mentoring, and institutionalisation of QMS into country programmes, is needed to support tuberculosis laboratories to achieve

Novel Mycobacterium tuberculosis complex pathogen, M. mungi.

PubMed

Alexander, Kathleen A; Laver, Pete N; Michel, Anita L; Williams, Mark; van Helden, Paul D; Warren, Robin M; Gey van Pittius, Nicolaas C

2010-08-01

Seven outbreaks involving increasing numbers of banded mongoose troops and high death rates have been documented. We identified a Mycobacterium tuberculosis complex pathogen, M. mungi sp. nov., as the causative agent among banded mongooses that live near humans in Chobe District, Botswana. Host spectrum and transmission dynamics remain unknown.

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

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

PubMed Central

Chang, C. L.; Lee, E. Y.; Son, H. C.; Park, S. K.

2000-01-01

Background—Early diagnosis of tuberculosis is crucial, especially in Korea, where tuberculosis is endemic. Aims—To evaluate the validity of the ICT tuberculosis test (ICT) in early diagnosis of tuberculosis. Methods—Sixty eight patients with tuberculosis were tested; 37 had no history of previous tuberculosis (patient group 1), and 31 had reactivated tuberculosis (patient group 2). The control groups comprised 77 subjects: 25 healthy adults, 35 hospital workers, and 17 inpatients with non-tuberculous respiratory diseases. Results—The diagnostic sensitivities of ICT were 73% in patient group 1 and 87.1% in patient group 2. In two patients with extrapulmonary tuberculosis, both tested positive using ICT. The specificities of ICT were 88%, 94%, and 94% in healthy adults, hospital workers, and non-tuberculous patients, respectively. Conclusions—ICT is a useful tool for the diagnosis of tuberculosis. Key Words: serological diagnosis of tuberculosis • ICT tuberculosis test PMID:11041064

Molecular Diagnosis of Tuberculosis.

PubMed

Nurwidya, Fariz; Handayani, Diah; Burhan, Erlina; Yunus, Faisal

2018-01-01

Tuberculosis (TB) is one of the leading causes of adult death in the Asia-Pacific Region, including Indonesia. As an infectious disease caused by Mycobacterium tuberculosis (MTB), TB remains a major public health issue especially in developing nations due to the lack of adequate diagnostic testing facilities. Diagnosis of TB has entered an era of molecular detection that provides faster and more cost-effective methods to diagnose and confirm drug resistance in TB cases, meanwhile, diagnosis by conventional culture systems requires several weeks. New advances in the molecular detection of TB, including the faster and simpler nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have resulted in a shorter time for diagnosis and, therefore, faster TB treatments. In this review, we explored the current findings on molecular diagnosis of TB and drug-resistant TB to see how this advancement could be integrated into public health systems in order to control TB.

Ethical aspects of directly observed treatment for tuberculosis: a cross-cultural comparison

PubMed Central

2013-01-01

Background Tuberculosis is a major global public health challenge, and a majority of countries have adopted a version of the global strategy to fight Tuberculosis, Directly Observed Treatment, Short Course (DOTS). Drawing on results from research in Ethiopia and Norway, the aim of this paper is to highlight and discuss ethical aspects of the practice of Directly Observed Treatment (DOT) in a cross-cultural perspective. Discussion Research from Ethiopia and Norway demonstrates that the rigid enforcement of directly observed treatment conflicts with patient autonomy, dignity and integrity. The treatment practices, especially when imposed in its strictest forms, expose those who have Tuberculosis to extra burdens and costs. Socially disadvantaged groups, such as the homeless, those employed as day labourers and those lacking rights as employees, face the highest burdens. Summary From an ethical standpoint, we argue that a rigid practice of directly observed treatment is difficult to justify, and that responsiveness to social determinants of Tuberculosis should become an integral part of the management of Tuberculosis. PMID:23819555

Global control of tuberculosis: from extensively drug-resistant to untreatable tuberculosis

PubMed Central

Dheda, Keertan; Gumbo, Tawanda; Gandhi, Neel R; Murray, Megan; Theron, Grant; Udwadia, Zarir; Migliori, G B; Warren, Robin

2017-01-01

Extensively drug-resistant tuberculosis is a burgeoning global health crisis mainly affecting economically active young adults, and has high mortality irrespective of HIV status. In some countries such as South Africa, drug-resistant tuberculosis represents less than 3% of all cases but consumes more than a third of the total national budget for tuberculosis, which is unsustainable and threatens to destabilise national tuberculosis programmes. However, concern about drug-resistant tuberculosis has been eclipsed by that of totally and extremely drug-resistant tuberculosis—ie, resistance to all or nearly all conventional first-line and second-line antituberculosis drugs. In this Review, we discuss the epidemiology, pathogenesis, diagnosis, management, implications for health-care workers, and ethical and medicolegal aspects of extensively drug-resistant tuberculosis and other resistant strains. Finally, we discuss the emerging problem of functionally untreatable tuberculosis, and the issues and challenges that it poses to public health and clinical practice. The emergence and growth of highly resistant strains of tuberculosis make the development of new drugs and rapid diagnostics for tuberculosis—and increased funding to strengthen global control efforts, research, and advocacy—even more pressing. PMID:24717628

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

CD8+ T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

PubMed Central

Nyendak, Melissa; Kiguli, Sarah; Zalwango, Sarah; Mori, Tomi; Mayanja-Kizza, Harriet; Balyejusa, Stephen; Null, Megan; Baseke, Joy; Mulindwa, Deo; Byrd, Laura; Swarbrick, Gwendolyn; Scott, Christine; Johnson, Denise F.; Malone, LaShaunda; Mudido-Musoke, Philipa; Boom, W. Henry; Lewinsohn, David M.; Lewinsohn, Deborah A.

2012-01-01

Rationale: The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis–specific CD8+ T cells are generated in response to high bacillary loads occurring during tuberculosis. Objectives: To determine if M. tuberculosis–specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis. Methods: Enzyme-linked immunosorbent spot assays were used to measure IFN-γ production in response to M. tuberculosis–specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8+ T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62). Measurements and Main Results: The proportion of positive CD8+ T-cell assays and magnitude of CD8+ T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis–specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups. Conclusions: Among young children, M. tuberculosis–specific CD8+ T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-γ–producing M. tuberculosis–specific CD8+ T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease. PMID:22071329

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 ...

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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Allopatric tuberculosis host–pathogen 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 host–pathogen 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 host–pathogen 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 host–pathogen 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 host–pathogen relationship and heavy cigarette consumption, but not phylogenetic lineage alone. Patients who had disease resulting from allopatric�

Characteristics of childhood tuberculosis patients registered under RNTCP in Varanasi, Uttar Pradesh.

PubMed

Thakur, Harshad P

2013-01-01

Childhood tuberculosis (TB) reflects on-going transmission. Data on childhood TB from TB registers under Revised National Tuberculosis Control Program of 2008 and 2009 in Varanasi district was analyzed. Proportion of childhood TB was 8.3% of total registered cases 12,242. It was lower than estimated 10-20% in endemic areas. In rural Tuberculosis Units childhood case detection was poor. Case detection in ≤5 years was very less. The childhood cases were detected mainly in adolescent age group. Thus, childhood TB is remaining a under diagnosed/under reported disease in India. It needs attention to increase the detection of childhood TB cases to control TB in general population.

Tuberculosis--triumph and tragedy.

PubMed

Singh, M M

2003-03-01

Tuberculosis has been making havoc worldwide with an 11.9 million cases to be involved by the year 2005. In India, about 2 million cases are infected every year. Regarding triumphs and tragedies in the control of tuberculosis some points as follows are discussed. (1) Tuberculosis Control Programmes from National Tuberculosis Programme (NTP) to Revised National Tuberculosis Control Programme (RNTCP) and Directly Observed Treatment, Short course (DOTS). (2) Problem of multidrug resistance (MDR) tuberculosis and (3) HIV and tuberculosis. DOTS being largely based on Indian research. It is now being applied worldwide. MDR is strictly a man made problem. Poor prescriptions, poor case management, lack of coordinated education and haphazard treatment research result in drug resistance. Treatment of MDR is difficult. The drug acceptability, tolerance and toxicity have to be considered. HIV and tuberculosis form a deadly duo. They mean more cases, more costs and more national losses.

Descriptive review of tuberculosis surveillance systems across the circumpolar regions

PubMed Central

Bourgeois, Annie-Claude; Zulz, Tammy; Soborg, Bolette; Koch, Anders

2016-01-01

Background Tuberculosis is highly prevalent in many Arctic areas. Members of the International Circumpolar Surveillance Tuberculosis (ICS-TB) Working Group collaborate to increase knowledge about tuberculosis in Arctic regions. Objective To establish baseline knowledge of tuberculosis surveillance systems used by ICS-TB member jurisdictions. Design Three questionnaires were developed to reflect the different surveillance levels (local, regional and national); all 3 were forwarded to the official representative of each of the 15 ICS-TB member jurisdictions in 2013. Respondents self-identified the level of surveillance conducted in their region and completed the applicable questionnaire. Information collected included surveillance system objectives, case definitions, data collection methodology, storage and dissemination. Results Thirteen ICS-TB jurisdictions [Canada (Labrador, Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Sweden, Russian Federation (Arkhangelsk, Khanty-Mansiysk Autonomous Okrug, Yakutia (Sakha Republic), United States (Alaska)] voluntarily completed the survey – representing 2 local, 7 regional and 4 national levels. Tuberculosis reporting is mandatory in all jurisdictions, and case definitions are comparable across regions. The common objectives across systems are to detect outbreaks, and inform the evaluation/planning of public health programmes and policies. All jurisdictions collect data on confirmed active tuberculosis cases and treatment outcomes; 11 collect contact tracing results. Faxing of standardized case reporting forms is the most common reporting method. Similar core data elements are collected; 8 regions report genotyping results. Data are stored using customized programmes (n=7) and commercial software (n=6). Nine jurisdictions provide monthly, bi-annual or annual reports to principally government and/or scientific/medical audiences. Conclusion This review successfully establishes baseline knowledge

Descriptive review of tuberculosis surveillance systems across the circumpolar regions.

PubMed

Bourgeois, Annie-Claude; Zulz, Tammy; Soborg, Bolette; Koch, Anders; On Behalf Of The International Circumpolar Surveillance-Tuberculosis Working Group

2016-01-01

Background Tuberculosis is highly prevalent in many Arctic areas. Members of the International Circumpolar Surveillance Tuberculosis (ICS-TB) Working Group collaborate to increase knowledge about tuberculosis in Arctic regions. Objective To establish baseline knowledge of tuberculosis surveillance systems used by ICS-TB member jurisdictions. Design Three questionnaires were developed to reflect the different surveillance levels (local, regional and national); all 3 were forwarded to the official representative of each of the 15 ICS-TB member jurisdictions in 2013. Respondents self-identified the level of surveillance conducted in their region and completed the applicable questionnaire. Information collected included surveillance system objectives, case definitions, data collection methodology, storage and dissemination. Results Thirteen ICS-TB jurisdictions [Canada (Labrador, Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Sweden, Russian Federation (Arkhangelsk, Khanty-Mansiysk Autonomous Okrug, Yakutia (Sakha Republic), United States (Alaska)] voluntarily completed the survey - representing 2 local, 7 regional and 4 national levels. Tuberculosis reporting is mandatory in all jurisdictions, and case definitions are comparable across regions. The common objectives across systems are to detect outbreaks, and inform the evaluation/planning of public health programmes and policies. All jurisdictions collect data on confirmed active tuberculosis cases and treatment outcomes; 11 collect contact tracing results. Faxing of standardized case reporting forms is the most common reporting method. Similar core data elements are collected; 8 regions report genotyping results. Data are stored using customized programmes (n=7) and commercial software (n=6). Nine jurisdictions provide monthly, bi-annual or annual reports to principally government and/or scientific/medical audiences. Conclusion This review successfully establishes baseline knowledge on

Molecular Strain Typing of Mycobacterium tuberculosis: a Review of Frequently Used Methods

PubMed Central

2016-01-01

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, remains one of the most serious global health problems. Molecular typing of M. tuberculosis has been used for various epidemiologic purposes as well as for clinical management. Currently, many techniques are available to type M. tuberculosis. Choosing the most appropriate technique in accordance with the existing laboratory conditions and the specific features of the geographic region is important. Insertion sequence IS6110-based restriction fragment length polymorphism (RFLP) analysis is considered the gold standard for the molecular epidemiologic investigations of tuberculosis. However, other polymerase chain reaction-based methods such as spacer oligonucleotide typing (spoligotyping), which detects 43 spacer sequence-interspersing direct repeats (DRs) in the genomic DR region; mycobacterial interspersed repetitive units–variable number tandem repeats, (MIRU-VNTR), which determines the number and size of tandem repetitive DNA sequences; repetitive-sequence-based PCR (rep-PCR), which provides high-throughput genotypic fingerprinting of multiple Mycobacterium species; and the recently developed genome-based whole genome sequencing methods demonstrate similar discriminatory power and greater convenience. This review focuses on techniques frequently used for the molecular typing of M. tuberculosis and discusses their general aspects and applications. PMID:27709842

Molecular Strain Typing of Mycobacterium tuberculosis: a Review of Frequently Used Methods.

PubMed

Ei, Phyu Win; Aung, Wah Wah; Lee, Jong Seok; Choi, Go Eun; Chang, Chulhun L

2016-11-01

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, remains one of the most serious global health problems. Molecular typing of M. tuberculosis has been used for various epidemiologic purposes as well as for clinical management. Currently, many techniques are available to type M. tuberculosis. Choosing the most appropriate technique in accordance with the existing laboratory conditions and the specific features of the geographic region is important. Insertion sequence IS6110-based restriction fragment length polymorphism (RFLP) analysis is considered the gold standard for the molecular epidemiologic investigations of tuberculosis. However, other polymerase chain reaction-based methods such as spacer oligonucleotide typing (spoligotyping), which detects 43 spacer sequence-interspersing direct repeats (DRs) in the genomic DR region; mycobacterial interspersed repetitive units-variable number tandem repeats, (MIRU-VNTR), which determines the number and size of tandem repetitive DNA sequences; repetitive-sequence-based PCR (rep-PCR), which provides high-throughput genotypic fingerprinting of multiple Mycobacterium species; and the recently developed genome-based whole genome sequencing methods demonstrate similar discriminatory power and greater convenience. This review focuses on techniques frequently used for the molecular typing of M. tuberculosis and discusses their general aspects and applications.

A spatial analysis of social and economic determinants of tuberculosis in Brazil.

PubMed

Harling, Guy; Castro, Marcia C

2014-01-01

We investigated the spatial distribution, and social and economic correlates, of tuberculosis in Brazil between 2002 and 2009 using municipality-level age/sex-standardized tuberculosis notification data. Rates were very strongly spatially autocorrelated, being notably high in urban areas on the eastern seaboard and in the west of the country. Non-spatial ecological regression analyses found higher rates associated with urbanicity, population density, poor economic conditions, household crowding, non-white population and worse health and healthcare indicators. These associations remained in spatial conditional autoregressive models, although the effect of poverty appeared partially confounded by urbanicity, race and spatial autocorrelation, and partially mediated by household crowding. Our analysis highlights both the multiple relationships between socioeconomic factors and tuberculosis in Brazil, and the importance of accounting for spatial factors in analysing socioeconomic determinants of tuberculosis. © 2013 Published by Elsevier Ltd.

Host-pathogen redox dynamics modulate Mycobacterium tuberculosis pathogenesis.

PubMed

Pacl, Hayden T; Reddy, Vineel P; Saini, Vikram; Chinta, Krishna C; Steyn, Adrie J C

2018-07-01

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, encounters variable and hostile environments within the host. A major component of these hostile conditions is reductive and oxidative stresses induced by factors modified by the host immune response, such as oxygen tension, NO or CO gases, reactive oxygen and nitrogen intermediates, the availability of different carbon sources and changes in pH. It is therefore essential for Mtb to continuously monitor and appropriately respond to the microenvironment. To this end, Mtb has developed various redox-sensitive systems capable of monitoring its intracellular redox environment and coordinating a response essential for virulence. Various aspects of Mtb physiology are regulated by these systems, including drug susceptibility, secretion systems, energy metabolism and dormancy. While great progress has been made in understanding the mechanisms and pathways that govern the response of Mtb to the host's redox environment, many questions in this area remain unanswered. The answers to these questions are promising avenues for addressing the tuberculosis crisis.

Four-gene Pan-African Blood Signature Predicts Progression to Tuberculosis.

PubMed

Suliman, Sara; Thompson, Ethan; Sutherland, Jayne; Weiner Rd, January; Ota, Martin O C; Shankar, Smitha; Penn-Nicholson, Adam; Thiel, Bonnie; Erasmus, Mzwandile; Maertzdorf, Jeroen; Duffy, Fergal J; Hill, Philip C; Hughes, E Jane; Stanley, Kim; Downing, Katrina; Fisher, Michelle L; Valvo, Joe; Parida, Shreemanta K; van der Spuy, Gian; Tromp, Gerard; Adetifa, Ifedayo M O; Donkor, Simon; Howe, Rawleigh; Mayanja-Kizza, Harriet; Boom, W Henry; Dockrell, Hazel; Ottenhoff, Tom H M; Hatherill, Mark; Aderem, Alan; Hanekom, Willem A; Scriba, Thomas J; Kaufmann, Stefan He; Zak, Daniel E; Walzl, Gerhard

2018-04-06

Contacts of tuberculosis (TB) patients constitute an important target population for preventative measures as they are at high risk of infection with Mycobacterium tuberculosis and progression to disease. We investigated biosignatures with predictive ability for incident tuberculosis. In a case-control study nested within the Grand Challenges 6-74 longitudinal HIV-negative African cohort of exposed household contacts, we employed RNA sequencing, polymerase chain reaction (PCR) and the Pair Ratio algorithm in a training/test set approach. Overall, 79 progressors, who developed tuberculosis between 3 and 24 months following exposure, and 328 matched non-progressors, who remained healthy during 24 months of follow-up, were investigated. A four-transcript signature (RISK4), derived from samples in a South African and Gambian training set, predicted progression up to two years before onset of disease in blinded test set samples from South Africa, The Gambia and Ethiopia with little population-associated variability and also validated on an external cohort of South African adolescents with latent Mycobacterium tuberculosis infection. By contrast, published diagnostic or prognostic tuberculosis signatures predicted on samples from some but not all 3 countries, indicating site-specific variability. Post-hoc meta-analysis identified a single gene pair, C1QC/TRAV27, that would consistently predict TB progression in household contacts from multiple African sites but not in infected adolescents without known recent exposure events. Collectively, we developed a simple whole blood-based PCR test to predict tuberculosis in household contacts from diverse African populations, with potential for implementation in national TB contact investigation programs.

Inhibiting Mycobacterium tuberculosis within and without.

PubMed

Cole, Stewart T

2016-11-05

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

Tuberculosis Fluoroscopy

Cancer.gov

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

[Perinatal tuberculosis].

PubMed

Sáenz-Gómez, Jessica; Karam Bechara, José; Jamaica Balderas, Lourdes

Perinatal tuberculosis is acquired during birth or during the early neonatal period. Although its incidence is unknown, a search was conducted in Medline and 28 cases were found of perinatal tuberculosis reported from 1983 to 2011. Diagnosis of this disease is important due to having nonspecific symptoms that are mistaken for other infectious diseases. The disease has a high mortality rate (60%); therefore, it requires prompt diagnostic suspicion by the medical staff to prevent a fatal outcome. We describe the case of a 3-month-old male whose 29-year-old mother died of septic shock at 15 days of delivery. The infant's condition began within 30 days of age with cough and difficulty breathing with a diagnosis of multiple foci pneumonia. The infant presented respiratory impairment, meriting change of antibiotics twice, without improvement. The autopsy report of the mother revealed peritoneal tuberculosis. PCR was carried out using tracheal aspirate and pleural fluid of the patient, which were positive for Mycobacterium tuberculosis. Perinatal diagnosis of tuberculosis was established. No hepatic granuloma was found. Perinatal infection should be suspected in children with sepsis and/or pneumonia unresponsive to antibiotics. In this care, the history of tuberculosis in the mother should have oriented the diagnosis. Copyright © 2014 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Temporal analysis of reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012.

PubMed

Gaspar, Renato Simões; Nunes, Natália; Nunes, Marina; Rodrigues, Vandilson Pinheiro

2016-01-01

To investigate the reported cases of tuberculosis and of tuberculosis-HIV co-infection in Brazil between 2002 and 2012. This was an observational study based on secondary time series data collected from the Brazilian Case Registry Database for the 2002-2012 period. The incidence of tuberculosis was stratified by gender, age group, geographical region, and outcome, as was that of tuberculosis-HIV co-infection. Nationally, the incidence of tuberculosis declined by 18%, whereas that of tuberculosis-HIV co-infection increased by 3.8%. There was an overall decrease in the incidence of tuberculosis, despite a significant increase in that of tuberculosis-HIV co-infection in women. The incidence of tuberculosis decreased only in the 0- to 9-year age bracket, remaining stable or increasing in the other age groups. The incidence of tuberculosis-HIV co-infection increased by 209% in the ≥ 60-year age bracket. The incidence of tuberculosis decreased in all geographical regions except the south, whereas that of tuberculosis-HIV co-infection increased by over 150% in the north and northeast. Regarding the outcomes, patients with tuberculosis-HIV co-infection, in comparison with patients infected with tuberculosis only, had a 48% lower chance of cure, a 50% greater risk of treatment nonadherence, and a 94% greater risk of death from tuberculosis. Our study shows that tuberculosis continues to be a relevant public health issue in Brazil, because the goals for the control and cure of the disease have yet to be achieved. In addition, the sharp increase in the incidence of tuberculosis-HIV co-infection in women, in the elderly, and in the northern/northeastern region reveals that the population of HIV-infected individuals is rapidly becoming more female, older, and more impoverished. Investigar os casos notificados de tuberculose e de sua coinfecção com o HIV na população brasileira no período entre 2002 e 2012. Realizou-se um estudo observacional de série temporal, no qual

[Tuberculosis in ancient Egypt].

PubMed

Ziskind, B; Halioua, B

2007-12-01

Did Tuberculosis plague Ancient Egypt five millennia ago? Some medical papyri appear to evoke tuberculosis. Egyptian physicians did not individualize it, but they seem to have noticed some of its clinical expressions, such as cough, cervical adenitis, and cold abscesses. In Egyptian iconography, some cases of hump-backs were probably due to Pott's disease of the spine Descriptive paleopathology, born with the 20th century, has identified pulmonary and especially spinal lesions compatible with tuberculosis. Progress of molecular biology has made a decisive contribution with the diagnosis of tuberculosis on ancient samples. Tuberculosis has been identified using PCR in nearly a third of the Egyptian mummies recently examined. Spoligotyping has made it possible to re-evaluate the phylogenic tree of the Mycobacterium tuberculosis complex in Ancient Egypt. Tuberculosis certainly plagued the Nile Valley and appears to have been an important cause of mortality in Ancient Egypt.

Drivers of Tuberculosis Transmission.

PubMed

Mathema, Barun; Andrews, Jason R; Cohen, Ted; Borgdorff, Martien W; Behr, Marcel; Glynn, Judith R; Rustomjee, Roxana; Silk, Benjamin J; Wood, Robin

2017-11-03

Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon γ-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Spatial pattern and temporal trend of mortality due to tuberculosis 10

PubMed Central

de Queiroz, Ana Angélica Rêgo; Berra, Thaís Zamboni; Garcia, Maria Concebida da Cunha; Popolin, Marcela Paschoal; Belchior, Aylana de Souza; Yamamura, Mellina; dos Santos, Danielle Talita; Arroyo, Luiz Henrique; Arcêncio, Ricardo Alexandre

2018-01-01

ABSTRACT Objectives: To describe the epidemiological profile of mortality due to tuberculosis (TB), to analyze the spatial pattern of these deaths and to investigate the temporal trend in mortality due to tuberculosis in Northeast Brazil. Methods: An ecological study based on secondary mortality data. Deaths due to TB were included in the study. Descriptive statistics were calculated and gross mortality rates were estimated and smoothed by the Local Empirical Bayesian Method. Prais-Winsten’s regression was used to analyze the temporal trend in the TB mortality coefficients. The Kernel density technique was used to analyze the spatial distribution of TB mortality. Results: Tuberculosis was implicated in 236 deaths. The burden of tuberculosis deaths was higher amongst males, single people and people of mixed ethnicity, and the mean age at death was 51 years. TB deaths were clustered in the East, West and North health districts, and the tuberculosis mortality coefficient remained stable throughout the study period. Conclusions: Analyses of the spatial pattern and temporal trend in mortality revealed that certain areas have higher TB mortality rates, and should therefore be prioritized in public health interventions targeting the disease. PMID:29742272

Rifampin vs. rifapentine: what is the preferred rifamycin for tuberculosis?

PubMed

Alfarisi, Omamah; Alghamdi, Wael A; Al-Shaer, Mohammad H; Dooley, Kelly E; Peloquin, Charles A

2017-10-01

One-third of the world's population is infected with Mycobacterium tuberculosis (M.tb.). Latent tuberculosis infection (LTBI) can progress to tuberculosis disease, the leading cause of death by infection. Rifamycin antibiotics, like rifampin and rifapentine, have unique sterilizing activity against M.tb. What are the advantages of each for LTBI or tuberculosis treatment? Areas covered: We review studies assessing the pharmacokinetics (PK), pharmacodynamics (PD), drug interaction risk, safety, and efficacy of rifampin and rifapentine and provide basis for comparing them. Expert commentary: Rifampin has shorter half-life, higher MIC against M.tb, lower protein binding, and better distribution into cavitary contents than rifapentine. Drug interactions for the two drugs maybe similar in magnitude. For LTBI, rifapentine is effective as convenient, once-weekly, 12-week course of treatment. Rifampin is also effective for LTBI, but must be given daily for four months, therefore, drug interactions are more problematic. For drug-sensitive tuberculosis disease, rifampin remains the standard of care. Safety profile of rifampin is better-described; adverse events differ somewhat for the two drugs. The registered once-weekly rifapentine regimen is inadequate, but higher doses of either drugs may shorten the treatment duration required for effective management of TB. Results of clinical trials evaluating high-dose rifamycin regimens are eagerly awaited.

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

PubMed

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

2001-08-01

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

Diabetes Mellitus and Latent Tuberculosis Infection: A Systemic Review and Metaanalysis

PubMed Central

Lee, Meng-Rui; Huang, Ya-Ping; Kuo, Yu-Ting; Luo, Chen-Hao; Shih, Yun-Ju; Shu, Chin-Chung; Wang, Jann-Yuan; Ko, Jen-Chung; Yu, Chong-Jen

2017-01-01

Abstract Background. Despite the well-documented association between diabetes and active tuberculosis, evidence of the association between diabetes and latent tuberculosis infection (LTBI) remains limited and inconsistent. Methods. We included observational studies that applied either the tuberculin skin test or the interferon gamma release assay for diagnosis of LTBI and that provided adjusted effect estimate for the association between diabetes and LTBI. We searched PubMed and EMBASE through 31 January 2016. The risk of bias of included studies was assessed using a quality assessment tool modified from the Newcastle-Ottawa scale. Results. Thirteen studies (1 cohort study and 12 cross-sectional studies) were included, involving 38263 participants. The cohort study revealed an increased but nonsignificant risk of LTBI among diabetics (risk ratio, 4.40; 95% confidence interval [CI], 0.50–38.55). For the cross-sectional studies, the pooled odds ratio from the random-effects model was 1.18 (95% CI, 1.06–1.30), with a small statistical heterogeneity across studies (I2, 3.5%). The risk of bias assessment revealed several methodological issues, but the overall direction of biases would reduce the positive causal association between diabetes and LTBI. Conclusions. Diabetes was associated with a small but statistically significant risk for LTBI. Findings from this review could be used to inform future cost-effectiveness analysis on the impact of LTBI screening programs among diabetics. PMID:27986673

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

PubMed Central

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

2016-01-01

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

Addison's Disease Caused by Tuberculosis with Atypical Hyperpigmentation and Active Pulmonary Tuberculosis

PubMed Central

Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi

2017-01-01

We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity. PMID:28717080

Addison's Disease Caused by Tuberculosis with Atypical Hyperpigmentation and Active Pulmonary Tuberculosis.

PubMed

Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi

2017-01-01

We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity.

Childhood tuberculosis and malnutrition.

PubMed

Jaganath, Devan; Mupere, Ezekiel

2012-12-15

Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on the mechanisms that underlie this relationship. From available research, it appears that malnutrition is a predictor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines of evidence, including the role of vitamin D receptor genotypes, malnutrition's effects on immune development, respiratory infections among malnourished children, and limited work specifically on pediatric tuberculosis and malnutrition. Nutritional supplementation has yet to suggest significant benefits on the course of tuberculosis in children. There is a critical need for research on childhood tuberculosis, specifically on how nutritional status affects the risk and progression of tuberculosis and whether nutritional supplementation improves clinical outcomes or prevents disease.

Childhood Tuberculosis and Malnutrition

PubMed Central

Jaganath, Devan; Mupere, Ezekiel

2012-01-01

Despite the burden of both malnutrition and tuberculosis in children worldwide, there are few studies on the mechanisms that underlie this relationship. From available research, it appears that malnutrition is a predictor of tuberculosis disease and is associated with worse outcomes. This is supported through several lines of evidence, including the role of vitamin D receptor genotypes, malnutrition's effects on immune development, respiratory infections among malnourished children, and limited work specifically on pediatric tuberculosis and malnutrition. Nutritional supplementation has yet to suggest significant benefits on the course of tuberculosis in children. There is a critical need for research on childhood tuberculosis, specifically on how nutritional status affects the risk and progression of tuberculosis and whether nutritional supplementation improves clinical outcomes or prevents disease. PMID:23033147

Induced sputum and bronchoscopy in the diagnosis of pulmonary tuberculosis

PubMed Central

McWilliams, T; Wells, A; Harrison, A; Lindstrom, S; Cameron, R; Foskin, E

2002-01-01

Background: Previous studies suggest that bronchoscopy and a single induced sputum sample are equally effective for diagnosing pulmonary tuberculosis. Methods: In a prospective study of subjects with possibly active pulmonary tuberculosis, the diagnostic yield of three induced sputum tests was compared with that of bronchoscopy. Subjects either produced no sputum or (acid fast) smear negative sputum. Bronchoscopy was only performed if at least two induced sputum samples were smear negative. Results: Of 129 subjects who completed all tests, 27 (21%) had smear negative and culture positive specimens, 14 (52%) on bronchoscopy and 26 (96%) on induced sputum (p<0.005). One patient was culture positive on bronchoscopy alone compared with 13 on induced sputum alone; 13 were culture positive on both tests. Induced sputum positivity was strikingly more prevalent when chest radiographic appearances showed any features of active tuberculosis (20/63, 32%) than when appearances suggested inactivity (1/44, 2%; p<0.005). Induced sputum costs were about one third those of bronchoscopy, and the ratio of costs of the two tests per case of tuberculosis diagnosed could be as much as 1:6. Conclusions: In subjects investigated for possibly active or inactive tuberculosis who produce no sputum or have smear negative sputum, the most cost effective strategy is to perform three induced sputum tests without bronchoscopy. Induced sputum testing carries a high risk of nosocomial tuberculosis unless performed in respiratory isolation conditions. The cost benefits shown could be lost if risk management measures are not observed. PMID:12454293

Global Tuberculosis Report 2016

MedlinePlus

... Alt+0 Navigation Alt+1 Content Alt+2 Tuberculosis (TB) Menu Tuberculosis Data and statistics Regional Framework Resources Meetings and events Global tuberculosis report 2017 WHO has published a global TB ...

Development of Low-Cost Inverted Microscope to Detect Early Growth of Mycobacterium tuberculosis in MODS Culture

PubMed Central

Zimic, Mirko; Velazco, Abner; Comina, Germán; Coronel, Jorge; Fuentes, Patricia; Luna, Carmen G.; Sheen, Patricia; Gilman, Robert H.; Moore, David A. J.

2010-01-01

Background The microscopic observation drug susceptibility (MODS) assay for rapid, low-cost detection of tuberculosis and multidrug resistant tuberculosis depends upon visualization of the characteristic cording colonies of Mycobacterium tuberculosis in liquid media. This has conventionally required an inverted light microscope in order to inspect the MODS culture plates from below. Few tuberculosis laboratories have this item and the capital cost of $5,000 for a high-end microscope could be a significant obstacle to MODS roll-out. Methodology We hypothesized that the precise definition provided by costly high-specification inverted light microscopes might not be necessary for pattern recognition. Significance In this work we describe the development of a low-cost artesenal inverted microscope that can operate in both a standard or digital mode to effectively replace the expensive commercial inverted light microscope, and an integrated system that could permit a local and remote diagnosis of tuberculosis. PMID:20351778

Influence of HTLV-1 on the clinical, microbiologic and immunologic presentation of tuberculosis

PubMed Central

2012-01-01

Background HTLV-1 is associated with increased susceptibility to Mycobacterium tuberculosis infection and severity of tuberculosis. Although previous studies have shown that HTLV-1 infected individuals have a low frequency of positive tuberculin skin test (TST) and decreasing in lymphoproliferative responses compared to HTLV-1 uninfected persons, these studies were not performed in individuals with history of tuberculosis or evidence of M. tuberculosis infection. Therefore the reasons why HTLV-1 infection increases susceptibility to infection and severity of tuberculosis are not understood.The aim of this study was to evaluate how HTLV-1 may influence the clinical, bacteriologic and immunologic presentation of tuberculosis. Methods The study prospectively enrolled and followed 13 new cases of tuberculosis associated with HTLV-1 (cases) and 25 patients with tuberculosis without HTLV-1 infection (controls). Clinical findings, bacterial load in the sputum, x-rays, immunological response and death were compared in the two groups. Results There were no differences in the demographic, clinical and TST response between the two study groups. IFN-γ and TNF-α production was higher in unstimulated cultures of mononuclear cells of case than in control patients (p < 0.01). While there was no difference in IFN-γ production in PPD stimulated cultures, TNF-α levels were lower in cases than in controls (p = 0.01). There was no difference in the bacterial load among the groups but sputum smear microscopy results became negative faster in cases than in controls. Death only occurred in two co-infected patients. Conclusion While the increased susceptibility for tuberculosis infection in HTLV-1 infected subjects may be related to impairment in TNF-α production, the severity of tuberculosis in co-infected patients may be due to the enhancement of the Th1 inflammatory response, rather than in their decreased ability to control bacterial growth. PMID:22925731

Determinants of tuberculosis transmission and treatment abandonment in Fortaleza, Brazil.

PubMed

Harling, Guy; Lima Neto, Antonio S; Sousa, Geziel S; Machado, Marcia M T; Castro, Marcia C

2017-05-25

Tuberculosis (TB) remains a public health problem, despite recent achievements in reducing incidence and mortality rates. In Brazil, these achievements were above the worldwide average, but marked by large regional heterogeneities. In Fortaleza (5th largest city in Brazil), the tuberculosis cure rate has been declining and treatment abandonment has been increasing in the past decade, despite a reduction in incidence and an increase in directly observed therapy (DOT). These trends put efforts to eliminate tuberculosis at risk. We therefore sought to determine social and programmatic determinants of tuberculosis incidence and treatment abandonment in Fortaleza. We analyzed sociodemographic and clinical data for all new tuberculosis cases notified in the Notifiable Diseases Information System (SINAN) from Fortaleza between 2007 and 2014. We calculated incidence rates for 117 neighborhoods in Fortaleza, assessed their spatial clustering, and used spatial regression models to quantify associations between neighborhood-level covariates and incidence rates. We used hierarchical logistic regression models to evaluate how individual- and neighborhood-level covariates predicted tuberculosis treatment abandonment. There were 12,338 new cases reported during the study period. Case rates across neighborhoods were significantly positively clustered in two low-income areas close to the city center. In an adjusted model, tuberculosis rates were significantly higher in neighborhoods with lower literacy, higher sewerage access and homicide rates, and a greater proportion of self-reported black residents. Treatment was abandoned in 1901 cases (15.4%), a rate that rose by 71% between 2007 and 2014. Abandonment was significantly associated with many individual sociodemographic and clinical factors. Notably, being recommended for DOT was protective for those who completed DOT, but associated with abandonment for those who did not. Low socioeconomic status areas have higher tuberculosis

Drug therapy in spinal tuberculosis.

PubMed

Rajasekaran, S; Khandelwal, Gaurav

2013-06-01

Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.

Effect of diabetes on tuberculosis control in 13 countries with high tuberculosis: a modelling study.

PubMed

Pan, Sung-Ching; Ku, Chu-Chang; Kao, Diana; Ezzati, Majid; Fang, Chi-Tai; Lin, Hsien-Ho

2015-05-01

Diabetes increases the risk of tuberculosis incidence and the risk of adverse treatment outcomes in patients with tuberculosis. Because prevalence of diabetes is increasing in low-income and middle-income countries where the burden of tuberculosis is high, prevention of diabetes carries the potential to improve tuberculosis control worldwide. We used dynamic tuberculosis transmission models to analyse the potential effect of diabetes on tuberculosis epidemiology in 13 countries with high tuberculosis burden. We used data for previous diabetes prevalence in each country and constructed scenarios to represent the potential ranges of future diabetes prevalence. The country-specific model was calibrated to the estimated trend of tuberculosis incidence. We estimated the tuberculosis burden that can be reduced by alternative scenarios of diabetes prevention. If the prevalence of diabetes continues to rise as it has been in the past decade in the 13 countries (base case scenario), by 2035, the cumulative reduction in tuberculosis incidence would be 8·8% (95% credible interval [CrI] 4·0-15·8) and mortality would be 34·0% (30·3-39·6). Lowering the prevalence of diabetes by an absolute level of 6·6-13·8% could accelerate the decline of tuberculosis incidence by an absolute level of 11·5-25·2% and tuberculosis mortality by 8·7-19·4%. Compared with the base case scenario, stopping the rise of diabetes would avoid 6·0 million (95% CrI 5·1-6·9) incident cases and 1·1 million (1·0-1·3) tuberculosis deaths in 13 countries during 20 years. If interventions reduce diabetes incidence by 35% by 2025, 7·8 million (6·7-9·0) tuberculosis cases and 1·5 million (1·3-1·7) tuberculosis deaths could be averted by 2035. The diabetes epidemic could substantially affect tuberculosis epidemiology in high burden countries. The communicable disease and non-communicable disease sectors need to move beyond conventional boundaries and link with each other to form a joint

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

Implementation of HIV and Tuberculosis Diagnostics: The Importance of Context

PubMed Central

Dominique, Joyelle K.; Ortiz-Osorno, Alberto A.; Fitzgibbon, Joseph; Gnanashanmugam, Devasena; Gilpin, Christopher; Tucker, Timothy; Peel, Sheila; Peter, Trevor; Kim, Peter; Smith, Steven

2015-01-01

Background. Novel diagnostics have been widely applied across human immunodeficiency virus (HIV) and tuberculosis prevention and treatment programs. To achieve the greatest impact, HIV and tuberculosis diagnostic programs must carefully plan and implement within the context of a specific healthcare system and the laboratory capacity. Methods. A workshop was convened in Cape Town in September 2014. Participants included experts from laboratory and clinical practices, officials from ministries of health, and representatives from industry. Results. The article summarizes best practices, challenges, and lessons learned from implementation experiences across sub-Saharan Africa for (1) building laboratory programs within the context of a healthcare system; (2) utilizing experience of clinicians and healthcare partners in planning and implementing the right diagnostic; and (3) evaluating the effects of new diagnostics on the healthcare system and on patient health outcomes. Conclusions. The successful implementation of HIV and tuberculosis diagnostics in resource-limited settings relies on careful consideration of each specific context. PMID:26409272

Chewing the fat: lipid metabolism and homeostasis during M. tuberculosis infection.

PubMed

Lovewell, Rustin R; Sassetti, Christopher M; VanderVen, Brian C

2016-02-01

The interplay between Mycobacterium tuberculosis lipid metabolism, the immune response and lipid homeostasis in the host creates a complex and dynamic pathogen-host interaction. Advances in imaging and metabolic analysis techniques indicate that M. tuberculosis preferentially associates with foamy cells and employs multiple physiological systems to utilize exogenously derived fatty-acids and cholesterol. Moreover, novel insights into specific host pathways that control lipid accumulation during infection, such as the PPARγ and LXR transcriptional regulators, have begun to reveal mechanisms by which host immunity alters the bacterial micro-environment. As bacterial lipid metabolism and host lipid regulatory pathways are both important, yet inherently complex, components of active tuberculosis, delineating the heterogeneity in lipid trafficking within disease states remains a major challenge for therapeutic design. Copyright © 2015. Published by Elsevier Ltd.

Occupational Risk Factors for Tuberculosis Among Healthcare Workers in KwaZulu-Natal, South Africa

PubMed Central

Tudor, Carrie; Van der Walt, Martie L.; Margot, Bruce; Dorman, Susan E.; Pan, William K.; Yenokyan, Gayane; Farley, Jason E.

2016-01-01

Background. Tuberculosis is a known occupational hazard for healthcare workers (HCWs), especially in countries with a high burden of tuberculosis. It is estimated that HCWs have a 2- to 3-fold increased risk of developing tuberculosis compared with the general population. The objective of this study was to identify occupational risk factors for tuberculosis among HCWs in 3 district hospitals with specialized multidrug-resistant tuberculosis wards in KwaZulu-Natal, South Africa. Methods. We conducted a case-control study of HCWs diagnosed with tuberculosis between January 2006 and December 2010. Cases and controls were asked to complete a self-administered questionnaire regarding potential risk factors for tuberculosis. Results. Of 307 subjects selected, 145 (47%) HCWs responded to the questionnaire; 54 (37%) tuberculosis cases and 91 (63%) controls. Cases occurred more frequently among clinical staff 46% (n = 25) and support staff 35% (n = 19). Thirty-two (26% [32/125]) HCWs were known to be infected with human immunodeficiency virus (HIV), including 45% (21/54) of cases. HCWs living with HIV (odds ratio [OR], 6.35; 95% confidence interval [CI], 3.54–11.37) and those who spent time working in areas with patients (OR, 2.24; 95% CI, 1.40–3.59) had significantly greater odds of developing tuberculosis, controlling for occupation, number of wards worked in, and household crowding. Conclusions. HIV was the major independent risk factor for tuberculosis among HCWs in this sample. These findings support the need for HCWs to know their HIV status, and for HIV-infected HCWs to be offered antiretroviral therapy and isoniazid preventive therapy. Infection prevention and control should also be improved to prevent transmission of tuberculosis in healthcare settings to protect both HCWs and patients. PMID:27118855

Origin, Spread and Demography of the Mycobacterium tuberculosis Complex

PubMed Central

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

2008-01-01

The evolutionary timing and spread of the Mycobacterium tuberculosis complex (MTBC), one of the most successful groups of bacterial pathogens, remains largely unknown. Here, using mycobacterial tandem repeat sequences as genetic markers, we show that the MTBC consists of two independent clades, one composed exclusively of M. tuberculosis lineages from humans and the other composed of both animal and human isolates. The latter also likely derived from a human pathogenic lineage, supporting the hypothesis of an original human host. Using Bayesian statistics and experimental data on the variability of the mycobacterial markers in infected patients, we estimated the age of the MTBC at 40,000 years, coinciding with the expansion of “modern” human populations out of Africa. Furthermore, coalescence analysis revealed a strong and recent demographic expansion in almost all M. tuberculosis lineages, which coincides with the human population explosion over the last two centuries. These findings thus unveil the dynamic dimension of the association between human host and pathogen populations. PMID:18802459

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

PubMed

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

2012-05-19

Tuberculosis is still one of the most important causes of death worldwide. The 2010 Lancet tuberculosis series provided a comprehensive overview of global control efforts and challenges. In this update we review recent progress. With improved control efforts, the world and most regions are on track to achieve the Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception is Africa. Despite these advances, full scale-up of tuberculosis and HIV collaborative activities remains challenging and emerging drug-resistant tuberculosis is a major threat. Recognition of the effect that non-communicable diseases--such as smoking-related lung disease, diet-related diabetes mellitus, and alcohol and drug misuse--have on individual vulnerability, as well as the contribution of poor living conditions to community vulnerability, shows the need for multidisciplinary approaches. Several new diagnostic tests are being introduced in endemic countries and for the first time in 40 years a coordinated portfolio of promising new tuberculosis drugs exists. However, none of these advances offer easy solutions. Achievement of international tuberculosis control targets and maintenance of these gains needs optimum national health policies and services, with ongoing investment into new approaches and strategies. Despite growing funding in recent years, a serious shortfall persists. International and national financial uncertainty places gains at serious risk. Perseverance and renewed commitment are needed to achieve global control of tuberculosis, and ultimately, its elimination. Copyright © 2012 Elsevier Ltd. All rights reserved.

Laboratory Diagnosis and Susceptibility Testing for Mycobacterium tuberculosis.

PubMed

Procop, Gary W

2016-12-01

The laboratory, which utilizes some of the most sophisticated and rapidly changing technologies, plays a critical role in the diagnosis of tuberculosis. Some of these tools are being employed in resource-challenged countries for the rapid detection and characterization of Mycobacterium tuberculosis. Foremost, the laboratory defines appropriate specimen criteria for optimal test performance. The direct detection of mycobacteria in the clinical specimen, predominantly done by acid-fast staining, may eventually be replaced by rapid-cycle PCR. The widespread use of the Xpert MTB/RIF (Cepheid) assay, which detects both M. tuberculosis and key genetic determinants of rifampin resistance, is important for the early detection of multidrug-resistant strains. Culture, using both broth and solid media, remains the standard for establishing the laboratory-based diagnosis of tuberculosis. Cultured isolates are identified far less commonly by traditional biochemical profiling and more commonly by molecular methods, such as DNA probes and broad-range PCR with DNA sequencing. Non-nucleic acid-based methods of identification, such as high-performance liquid chromatography and, more recently, matrix-assisted laser desorption/ionization-time of flight mass spectrometry, may also be used for identification. Cultured isolates of M. tuberculosis should be submitted for susceptibility testing according to standard guidelines. The use of broth-based susceptibility testing is recommended to significantly decrease the time to result. Cultured isolates may also be submitted for strain typing for epidemiologic purposes. The use of massive parallel sequencing, also known as next-generation sequencing, promises to continue to this molecular revolution in mycobacteriology, as whole-genome sequencing provides identification, susceptibility, and typing information simultaneously.

Invasive Pulmonary Aspergillosis-mimicking Tuberculosis.

PubMed

Kim, Sung-Han; Kim, Mi Young; Hong, Sun In; Jung, Jiwon; Lee, Hyun Joo; Yun, Sung-Cheol; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee

2015-07-01

Pulmonary tuberculosis is occasionally confused with invasive pulmonary aspergillosis (IPA) in transplant recipients, since clinical suspicion and early diagnosis of pulmonary tuberculosis and IPA rely heavily on imaging modes such as computed tomography (CT). We therefore investigated IPA-mimicking tuberculosis in transplant recipients. All adult transplant recipients who developed tuberculosis or IPA at a tertiary hospital in an intermediate tuberculosis-burden country during a 6-year period were enrolled. First, we tested whether experienced radiologists could differentiate pulmonary tuberculosis from IPA. Second, we determined which radiologic findings could help us differentiate them. During the study period, 28 transplant recipients developed pulmonary tuberculosis after transplantation, and 80 patients developed IPA after transplantation. Two experienced radiologists scored blindly 28 tuberculosis and 50 randomly selected IPA cases. The sensitivities of radiologists A and B for IPA were 78% and 68%, respectively (poor agreement, kappa value = 0.25). The sensitivities of radiologists A and B for tuberculosis were 64% and 61%, respectively (excellent agreement, kappa value = 0.77). We then compared the CT findings of the 28 patients with tuberculosis and 80 patients with IPA. Infarct-shaped consolidations and smooth bronchial wall thickening were more frequent in IPA, and mass-shaped consolidations and centrilobular nodules (<10 mm, clustered) were more frequent in tuberculosis. Certain CT findings appear to be helpful in differentiating between IPA and tuberculosis. Nevertheless, the CT findings of about one-third of pulmonary tuberculosis cases in transplant recipients are very close to those of IPA. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

PubMed Central

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

2013-01-01

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

Integrating knowledge of Mycobacterium tuberculosis pathogenesis for the design of better vaccines.

PubMed

Mascart, Françoise; Locht, Camille

2015-01-01

Today, tuberculosis (TB) still remains one of the main global causes of mortality and morbidity, and an effective vaccine against both TB disease and Mycobacterium tuberculosis infection is essential to reach the updated post-2015 Millennium development goal of eradicating TB by 2050. During the last two decades much knowledge has accumulated on the pathogenesis of TB and the immune responses to infection by M. tuberculosis. Furthermore, many vaccine candidates are under development, and close to 20 of them have entered clinical assessment at various levels. Nevertheless, the M. tuberculosis-host interaction is very complex, and the full complexity of this interaction is still not sufficiently well understood to develop novel, rationally designed vaccines. However, some of the recent knowledge is now integrated into the design of various types of vaccine candidates to be used either as pre-exposure, as post-exposure or as therapeutic vaccines, as will be discussed in this paper.

A cannonball through the chest: disseminated tuberculosis, threatening the aortic arch.

PubMed

Feldman, Henry J; Somai, Melek; Dweck, Ezra

2014-01-01

In 2012 the World Health Organization reported 8.7 million new cases of Tuberculosis worldwide, causing 1.4 million deaths (1). Despite modern drug therapy, this disease continues to present in novel ways and mimic other diseases causing misdiagnosis. We report this case to educate on the reason to suspect atypical Tuberculosis presentation, even if a common disease is diagnosed, when Tuberculosis remains in the differential. We also demonstrate that with globalization and patient moving between countries, that these presentations can occur in locations, where such atypical manifestations are very uncommon. We report on a 48 year old man with one month of malaise, fever, productive cough, night sweats, chills, pleuritic chest pain, weight loss and progressive non-painful swelling on his thorax. Initial diagnoses of interstitial pneumonia and a thoracic subcutaneous abscess were made. Needle drainage was attempted, with thick purulent material returned. When the sternum was not struck with the needle, a thoracic computed tomography scan was performed. A milliary pattern was noted in the lungs, with a large abscess present anteriorly, completely obliterating the manubrium, approaching the aorta with distant lesions. Subsequent analysis showed the material to be pan-sensitive M. Tuberculosis. The issue that this case raises is that when tuberculosi is in the differential, even common diseases may in fact be atypical manifestations of tuberculosis. In addition, when a shallow surgical procedure is going to be performed on the thoracic soft tissues, particularly when tuberculosis is suspected, imaging of the thorax should be obtained.

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

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

PubMed

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

2005-01-01

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

Vulnerability of Homeless People in Tehran, Iran, to HIV, Tuberculosis and Viral Hepatitis

PubMed Central

Bagheri Amiri, Fahimeh; Gouya, Mohammad Mehdi; Saifi, Mahnaz; Rohani, Mehdi; Tabarsi, Payam; Sedaghat, Abbas; Fahimfar, Noushin; Memarnejadian, Arash; Aghasadeghi, Mohammad Reza; Haghdoost, Ali Akbar; Jahanbakhsh, Fatemeh; Nasehi, Mahshid; Mostafavi, Ehsan

2014-01-01

Background Homeless people are at risk of contracting communicable infectious diseases, as they indulge in risky behaviours and lifestyle. This study was conducted to determine the prevalence of the aforementioned infections and related risk behaviours among homeless people in Tehran. Methods In this study a convenience sample of 593 homeless individuals was studied. The ELISA method was used for the detection of HIV, HCV and HBV. Clinical symptoms, sputum cultures, acid fast bacilli smears, and chest X-rays were used to identify active pulmonary tuberculosis, and the Interferon Gamma Release Assay (IGRA) test was used to identify latent tuberculosis. Results The prevalence of HIV, HBV, HCV and latent tuberculosis was 3.4%, 2.6%, 23.3% and 46.7%, respectively. Active pulmonary tuberculosis was found in 7 persons (1.2%). Injection drug use was an independent risk factor for HIV, HCV and HBV infections. Older people had a higher proportion of Mycobacterium tuberculosis infection (OR: 2.6, 95%CI: 1.9, 3.7) and HCV positivity (OR: 1.7, 95% CI: 1.1, 2.5). Conclusion Our findings highlighted that much more attention needs to be paid to the health of homeless people. PMID:24896247

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

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

PubMed Central

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

2016-01-01

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

A rare complication of pulmonary tuberculosis: a case report.

PubMed

Kumarihamy, Kulatunga Wijekoon Mudiyanselage Pramitha Prabhashini; Ralapanawa, Dissanayake Mudiyanselage Priyantha Udaya Kumara; Jayalath, Widana Arachchilage Thilak Ananda

2015-02-10

Pulmonary tuberculosis remains an important public health problem globally and one of the most prevalent infectious diseases in Sri Lanka. It can cause a wide variety of complications but hematological manifestations are rare. According to our literature survey, this is the first reported case of the disease associated with deep vein thrombosis in Sri Lanka. A 37 year old Sri Lankan Sinhalese female presented with fever of one month's duration with productive cough and two weeks painless left lower limb swelling. Chest X-ray showed bilateral inflammatory shadows with a cavitatory lesion on the right apical region. A computed tomographic pulmonary angiography scan excluded pulmonary embolism. She had rising mycoplasma antibody titre (four fold). Acute deep vein thrombosis of the left lower limb was confirmed by venous duplex. Pulmonary tuberculosis was confirmed with positive culture for Mycobacterium tuberculosis. She was treated with clarythromycin, enoxaparin, warfarin and anti tuberculus drugs. It was difficult to maintain her International Normalizing Ratio in the therapeutic range due to drug interactions and poor compliance. At five months of presentation she died of massive pulmonary embolism. Our case emphasizes that patients with severe pulmonary tuberculosis are at risk of developing thromboembolism and superadded infections. It should be noted that even though starting anti tuberculosis drugs improved haemostatic disturbances, achieving the target International Normalizing Ratio was difficult due to drug interactions. Therefore these patients should be closely followed up to prevent complications and death from pulmonary embolism.

Genetics of human susceptibility to active and latent tuberculosis: present knowledge and future perspectives.

PubMed

Abel, Laurent; Fellay, Jacques; Haas, David W; Schurr, Erwin; Srikrishna, Geetha; Urbanowski, Michael; Chaturvedi, Nimisha; Srinivasan, Sudha; Johnson, Daniel H; Bishai, William R

2018-03-01

Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable diseases with 10 million incident cases and 1·8 million deaths in 2015 alone based on the annual WHO report, due to inadequate health service resources in less-developed regions of the world, and exacerbated by the HIV/AIDS pandemic and emergence of multidrug-resistant strains of Mycobacterium tuberculosis. Recent findings from studies of tuberculosis infection and of patients with Mendelian predisposition to severe tuberculosis have started to reveal human loci influencing tuberculosis outcomes. In this Review, we assess the current understanding of the contribution of host genetics to disease susceptibility and to drug treatment. Despite remarkable progress in technology, only a few associated genetic variants have so far been identified, strongly indicating the need for larger global studies that investigate both common and under-represented rare variants to develop new approaches to combat the disease. Pharmacogenomic discoveries are also likely to lead to more efficient drug design and development, and ultimately safer and more effective therapies for tuberculosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2015-01-01

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

Gastrointestinal tuberculosis.

PubMed

Galloway, D J; Scott, R N

1986-10-01

In the developed countries gastrointestinal tuberculosis is no longer common in clinical practice. In this setting the importance of the condition lies in the vagaries of its presentation and the fact that it is eminently treatable, usually by a combination of chemotherapy and surgery. The clinical features and complications of gastrointestinal tuberculosis are highlighted by the seven cases which we report. Diagnosis and treatment of this condition is discussed and attention is drawn to the importance of case notification. Clinicians should bear in mind the diagnosis of gastrointestinal tuberculosis when dealing with any patient with non-specific abdominal symptoms.

Social and cultural factors in the successful control of tuberculosis.

PubMed Central

Rubel, A J; Garro, L C

1992-01-01

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

International standards for tuberculosis care.

PubMed

Hopewell, Philip C; Pai, Madhukar; Maher, Dermot; Uplekar, Mukund; Raviglione, Mario C

2006-11-01

Part of the reason for failing to bring about a more rapid reduction in tuberculosis incidence worldwide is the lack of effective involvement of all practitioners-public and private-in the provision of high quality tuberculosis care. While health-care providers who are part of national tuberculosis programmes have been trained and are expected to have adopted proper diagnosis, treatment, and public-health practices, the same is not likely to be true for non-programme providers. Studies of the performance of the private sector conducted in several different parts of the world suggest that poor quality care is common. The basic principles of care for people with, or suspected of having, tuberculosis are the same worldwide: a diagnosis should be established promptly; standardised treatment regimens should be used with appropriate treatment support and supervision; response to treatment should be monitored; and essential public-health responsibilities must be carried out. Prompt and accurate diagnosis, and effective treatment are essential for good patient care and tuberculosis control. All providers who undertake evaluation and treatment of patients with tuberculosis must recognise that not only are they delivering care to an individual, but they are also assuming an important public-health function. The International Standards for Tuberculosis Care (ISTC) describe a widely endorsed level of care that all practitioners should seek to achieve in managing individuals who have, or are suspected of having, tuberculosis. The document is intended to engage all care providers in delivering high quality care for patients of all ages, including those with smear-positive, smear-negative, and extra-pulmonary tuberculosis, tuberculosis caused by drug-resistant Mycobacterium tuberculosis complex, and tuberculosis combined with HIV infection.

Genotyping and drug resistance patterns of M. tuberculosis strains in Pakistan.

PubMed

Tanveer, Mahnaz; Hasan, Zahra; Siddiqui, Amna R; Ali, Asho; Kanji, Akbar; Ghebremicheal, Solomon; Hasan, Rumina

2008-12-24

The incidence of tuberculosis in Pakistan is 181/100,000 population. However, information about transmission and geographical prevalence of Mycobacterium tuberculosis strains and their evolutionary genetics as well as drug resistance remains limited. Our objective was to determine the clonal composition, evolutionary genetics and drug resistance of M. tuberculosis isolates from different regions of the country. M. tuberculosis strains isolated (2003-2005) from specimens submitted to the laboratory through collection units nationwide were included. Drug susceptibility was performed and strains were spoligotyped. Of 926 M. tuberculosis strains studied, 721(78%) were grouped into 59 "shared types", while 205 (22%) were identified as "Orphan" spoligotypes. Amongst the predominant genotypes 61% were Central Asian strains (CAS ; including CAS1, CAS sub-families and Orphan Pak clusters), 4% East African-Indian (EAI), 3% Beijing, 2% poorly defined TB strains (T), 2% Haarlem and LAM (0.2). Also TbD1 analysis (M. tuberculosis specific deletion 1) confirmed that CAS1 was of "modern" origin while EAI isolates belonged to "ancestral" strain types.Prevalence of CAS1 clade was significantly higher in Punjab (P < 0.01, Pearsons Chi-square test) as compared with Sindh, North West Frontier Province and Balochistan provinces. Forty six percent of isolates were sensitive to five first line antibiotics tested, 45% were Rifampicin resistant, 50% isoniazid resistant. MDR was significantly associated with Beijing strains (P = 0.01, Pearsons Chi-square test) and EAI (P = 0.001, Pearsons Chi-square test), but not with CAS family. Our results show variation of prevalent M. tuberculosis strain with greater association of CAS1 with the Punjab province. The fact that the prevalent CAS genotype was not associated with drug resistance is encouraging. It further suggests a more effective treatment and control programme should be successful in reducing the tuberculosis burden in Pakistan.

Incident Mycobacterium tuberculosis infection in household contacts of infectious tuberculosis patients in Brazil.

PubMed

Jones-López, Edward C; Acuña-Villaorduña, Carlos; Fregona, Geisa; Marques-Rodrigues, Patricia; White, Laura F; Hadad, David Jamil; Dutra-Molina, Lucilia Pereira; Vinhas, Solange; McIntosh, Avery I; Gaeddert, Mary; Ribeiro-Rodrigues, Rodrigo; Salgame, Padmini; Palaci, Moises; Alland, David; Ellner, Jerrold J; Dietze, Reynaldo

2017-08-18

In household contact investigations of tuberculosis (TB), a second tuberculin skin test (TST) obtained several weeks after a first negative result consistently identifies individuals that undergo TST conversion. It remains unclear whether this delay in M. tuberculosis infection is related to differences in the infectious exposure, TST boosting, partial host resistance, or some other factor. We conducted a household contact study Vitória, Brazil. Between 2008 and 2013, we identified culture-positive pulmonary TB patients and evaluated their household contacts with both a TST and interferon gamma release assay (IGRA), and identified TST converters at 8-12 weeks post study enrollment. Contacts were classified as TST-positive (≥10 mm) at baseline, TST converters, or persistently TST-negative. We compared TST converters to TST-positive and to TST-negative contacts separately, using generalized estimating equations. We enrolled 160 index patients and 838 contacts; 523 (62.4%) were TST+, 62 (7.4%) TST converters, and 253 (30.2%) TST-. TST converters were frequently IGRA- at 8-12 weeks. In adjusted analyses, characteristics distinguishing TST converters from TST+ contacts (no contact with another TB patient and residence ownership) were different than those differentiating them from TST- contacts (stronger cough in index patient and contact BCG scar). The individual risk and timing of M. tuberculosis infection within households is variable and dependent on index patient, contact and environmental factors within the household, and the surrounding community. Our findings suggest a threshold effect in the risk of infection in humans.

The dynamic of tuberculosis case finding in the era of the public-private mix strategy for tuberculosis control in Central Java, Indonesia.

PubMed

Reviono, Reviono; Setianingsih, Wahyu; Damayanti, Kusmadewi Eka; Ekasari, Ratna

2017-01-01

The public-private mix (PPM) strategy has strengthened tuberculosis care and control in many countries. Indonesia, a country with a high tuberculosis burden, has a low tuberculosis case detection rate (CDR), despite PPM implementation in 2003. The PPM in Indonesia involves primary healthcare centers, hospitals, and specialized chest clinics. The long-term impact of the strategy is unknown.  We aimed to explore the case detection achievements of the tuberculosis program since PPM implementation in Central Java in 2003. This retrospective cohort study covered the period 1 January 2000 to 31 December 2014. The data from tuberculosis patients treated in all health facilities in Central Java implementing directly observed treatment short-course, recorded via a standardized form, were analyzed after being validated by the Office of Health of Central Java Province. We evaluated the CDR, case notification rate, and total number of cases, using linear regression to analyze the temporal trends of those indicators in the phases of PPM implementation. The CDR increased during the initial phase (2000-2005), decreased during the mid-phase (2006-2009), and increased slightly during the late phase (2010-2014), ranging from 13 to 61.72. These trends were observed despite a steady increase in the number of participating healthcare facilities. The regression analysis showed that the CDR of referral institutions contributed the most to the total CDR of Central Java Province. Many of the smear-negative tuberculosis cases recorded at primary healthcare centers may have been smear positive; this probable misclassification could have been partially avoided if more specific and sensitive diagnostic tools were available. The CDR remains below the national target (70%). Early awareness of a negative trend in certain program indicators is important to ensure program sustainability. Careful observation of the indicator pattern will secure the long-term success of the program.

[Tuberculosis as occupational disease].

PubMed

Mendoza-Ticona, Alberto

2012-06-01

There is enough evidence to declare tuberculosis as an occupational disease among healthcare workers. In Peru, there are regulations granting employment rights regarding tuberculosis as an occupational disease, such as healthcare coverage for temporary or permanent disability. However, these rights have not been sufficiently socialized. This study presents information on the risk of acquiring tuberculosis in the workplace, and a review of the evidence to declare tuberculosis as an occupational disease among health care workers, presenting the current Peruvian law related.

Interventions to increase tuberculosis case detection at primary healthcare or community-level services

PubMed Central

Mhimbira, Francis A; Cuevas, Luis E.; Dacombe, Russell; Mkopi, Abdallah; Sinclair, David

2017-01-01

Background Pulmonary tuberculosis is usually diagnosed when symptomatic individuals seek care at healthcare facilities, and healthcare workers have a minimal role in promoting the health-seeking behaviour. However, some policy specialists believe the healthcare system could be more active in tuberculosis diagnosis to increase tuberculosis case detection. Objectives To evaluate the effectiveness of different strategies to increase tuberculosis case detection through improving access (geographical, financial, educational) to tuberculosis diagnosis at primary healthcare or community-level services. Search methods We searched the following databases for relevant studies up to 19 December 2016: the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library, Issue 12, 2016; MEDLINE; Embase; Science Citation Index Expanded, Social Sciences Citation Index; BIOSIS Previews; and Scopus. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the metaRegister of Controlled Trials (mRCT) for ongoing trials. Selection criteria Randomized and non-randomized controlled studies comparing any intervention that aims to improve access to a tuberculosis diagnosis, with no intervention or an alternative intervention. Data collection and analysis Two review authors independently assessed trials for eligibility and risk of bias, and extracted data. We compared interventions using risk ratios (RR) and 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach. Main results We included nine cluster-randomized trials, one individual randomized trial, and seven non-randomized controlled studies. Nine studies were conducted in sub-Saharan Africa (Ethiopia, Nigeria, South Africa, Zambia, and Zimbabwe), six in Asia (Bangladesh, Cambodia, India, Nepal, and Pakistan), and two in South America

Association of Body Mass Index with Timing of Death during Tuberculosis Treatment

PubMed Central

Lai, Yun-Ju; Yen, Yung-Feng

2017-01-01

Background The association between body mass index and mortality in patients with tuberculosis has not been extensively studied, and the existing evidence is inconsistent. This study aimed to investigate the impact of body mass index on timing of death in patients with tuberculosis. Methods All Taiwanese adults with tuberculosis in Taipei, Taiwan, were included in a retrospective cohort study in 2011–2012. Multinomial logistic regression was used to evaluate the association between body mass index and timing of death in patients with tuberculosis. Results Among 1557 eligible patients, 84.1% (1310), 8.2% (128), and 7.6% (119) underwent successful treatment, early death, and late death, respectively. The mean age of the patients with tuberculosis was 64.2 years old, and 67.7% were male. After controlling for potential confounding variables, underweight with body mass index less than 18.5 kg/ m2 was significantly associated with elevated risk of all-cause mortality [Adjusted odds ratio (AOR), 1.64; 95% confidence interval (CI), 1.17–2.30]. Considering timing of death, underweight with body mass index less than 18.5 was significantly associated only with elevated risk of early mortality within the first 8 weeks of treatment onset (AOR, 2.22; 95% CI, 1.45–3.40) Conclusions For patients with tuberculosis infection, underweight with body mass index less than 18.5 kg/ m2 is an independent predictor for early mortality within the first 8 weeks of treatment. PMID:28085951

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

PubMed Central

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

2011-01-01

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

Tuberculosis-resistant transgenic cattle

USDA-ARS?s Scientific Manuscript database

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. ...

[Research and control of relapse tuberculosis cases].

PubMed

Yamagishi, Fumio; Toyota, Makoto

2009-12-01

were recognized more significantly in male cases aged 70's. In the cases that deviated from the standard treatment and that became impossible to use rifampicin, it should be careful to emergence of isoniazid resistance. 3. The current status of the recurrence tuberculosis cases in Tokyo: Michiko NAGAMINE (Specific Disease Control Section, Tokyo Metropolitan Government Bureau of Social Welfare and Public Health). As for the background of the patient whose disease has relapsed, unstable elements are observed. After any symptom, more patients are diagnosed as a relapse case rather than finding by a medical check up. And more than half are related to homeless or life without fixed address. Their status of insurance is the livelihood protection, no insurance or the national health insurance. By RFLP analysis in Shinjuku city, some clusters have recurrent cases, one of clusters has both a relapse and exogenous reinfection. This is able to elucidate an infectious state. Like this, the analysis of each cluster can help effective countermeasures. 4. Recurrence of tuberculosis in the City of Yokohama between 2004 and 2008: Michihiko YOSHIDA (Shinagawa Public Health Center), Takahiro TOYOZAWA (Yokohama Public Health Center). To identify the TB recurrence rate, we studied a cohort of 40 cases (treatment completion 36 cases, interruption 4 cases) of whom had a previous history of TB treatment including isoniazid and rifampicin. The time for relapse was 7.9 +/- 8.6 years and the overall relapse rate was 0.6% (0.47-0.7%). Our study suggested the relapse was almost equal to the low incident countries but the long-term follow-up and surveillance data should be carefully evaluated. 5. Comparison of the retreatment cases of pulmonary tuberculosis: Yuka SASAKI (National Hospital Organization Chiba-East National Hospital). To investigate the factors of the retreatment of pulmonary tuberculosis, 134 retreatment cases were studied. The factors leading to retreatment were cavitary and large

Finding the Missing Patients With Tuberculosis: Lessons Learned From Patient-Pathway Analyses in 5 Countries

PubMed Central

Hanson, Christy; Osberg, Mike; Brown, Jessie; Durham, George; Chin, Daniel P

2017-01-01

Abstract Background Despite significant progress in diagnosis and treatment of tuberculosis over the past 2 decades, millions of patients with tuberculosis go unreported every year. The patient-pathway analysis (PPA) is designed to assess the alignment between tuberculosis care-seeking patterns and the availability of tuberculosis services. The PPA can help programs understand where they might find the missing patients with tuberculosis. Methods This analysis aggregates and compares the PPAs from case studies in Kenya, Ethiopia, Indonesia, the Philippines, and Pakistan. Results Across the 5 countries, 24% of patients with tuberculosis initiated care seeking in a facility with tuberculosis diagnostic capacity. Forty-two percent of patients sought care at level 0 facilities, where there was generally no tuberculosis diagnostic capacity; another 42% of patients sought care at level 1 facilities, of which 39% had diagnostic capacity. Sixty-six percent of patients initially sought care in private facilities, which had considerably less tuberculosis diagnostic capacity than public facilities; only 7% of notified cases were from the private sector. The GeneXpert system was available in 14%–41% of level 2 facilities in the 3 countries for which there were data. Tuberculosis treatment capacity tracked closely with the availability of diagnostic capacity. There were substantial subnational differences in care-seeking patterns and service availability. Discussion The PPA can be a valuable planning and programming tool to ensure that diagnostic and treatment services are available to patients where they seek care. Patient-centered care will require closing the diagnostic gap and engaging the private sector. Extensive subnational differences in patient pathways to care call for differentiated approaches to patient-centered care. PMID:29117351

Nonlinear pattern of pulmonary tuberculosis among migrants at entry in Kuwait: 1997–2006

PubMed Central

Akhtar, Saeed; Mohammad, Hameed GHH

2008-01-01

Background There is a paucity of published data on the pattern of pulmonary tuberculosis among migrant workers entering Middle Eastern countries particularly Kuwait. The objectives of this study were to use routine health surveillance data i) to estimate the prevalence of pulmonary tuberculosis among migrant workers at entry in Kuwait and ii) to determine the occurrence of any time trends in the proportions of pulmonary tuberculosis positive workers over the study period. Methods The monthly aggregates of daily number of migrants tested and the number of pulmonary tuberculosis cases detected during routine health examinations of migrant workers from tuberculosis high-prevalence countries were used to generate the monthly series of proportions (per 100,000) of pulmonary tuberculosis cases over 120 months between January 1, 1997 and December 31, 2006 and analysed using time series methods. Results The overall prevalence (per 100,000) of documented pulmonary tuberculosis cases among screened migrants was 198 (4608/2328582). Year-specific prevalence (per 100,000) of tuberculosis cases consistently declined from 456 (95% CI: 424 – 490) in 1997 to 124 (95% CI: 110 – 140) in 2002 before showing a steady increase up to 183 (95% CI: 169–197) in 2006. The second-order polynomial regression model revealed significant (P < 0.001) initial decline, followed by a significant (P < 0.001) increasing trend thereafter in monthly proportions of tuberculosis cases among migrant workers. Conclusion The proportions of documented tuberculosis cases among migrant workers showed a significant nonlinear pattern, with an initial decline followed by a significant increasing trend towards the end of the study period. These findings underscore the need to maintain the current policy of migrants' screening for tuberculosis at entry. The public health authorities in Kuwait and perhaps other countries in the region may consider complementing the current screening protocol with interferon

Genetic diversity of drug and multidrug-resistant Mycobacterium tuberculosis circulating in Veracruz, Mexico

PubMed Central

Munro-Rojas, Daniela; Fernandez-Morales, Esdras; Zarrabal-Meza, José; Martínez-Cazares, Ma. Teresa; Parissi-Crivelli, Aurora; Fuentes-Domínguez, Javier; Séraphin, Marie Nancy; Lauzardo, Michael; González-y-Merchand, Jorge Alberto; Rivera-Gutierrez, Sandra

2018-01-01

Background Mexico is one of the most important contributors of drug and multidrug-resistant tuberculosis in Latin America; however, knowledge of the genetic diversity of drug-resistant tuberculosis isolates is limited. Methods In this study, the genetic structure of 112 Mycobacterium tuberculosis strains from the southeastern Mexico was determined by spoligotyping and 24-loci MIRU-VNTRs. Findings The results show eight major lineages, the most of which was T1 (24%), followed by LAM (16%) and H (15%). A total of 29 (25%) isolates were identified as orphan. The most abundant SITs were SIT53/T1 and SIT42/LAM9 with 10 isolates each and SIT50/H3 with eight isolates. Fifty-two spoligotype patterns, twenty-seven clusters and ten clonal complexes were observed, demonstrating an important genetic diversity of drug and multidrug-resistant tuberculosis isolates in circulation and transmission level of these aggravated forms of tuberculosis. Being defined as orphan or as part of an orphan cluster, was a risk factor for multidrug resistant-tuberculosis (OR 2.5, IC 1.05–5.86 and OR 3.3, IC 1–11.03, respectively). Multiple correspondence analyses showed association of some clusters and SITs with specific geographical locations. Conclusions Our study provides one of the most detailed description of the genetic structure of drug and multidrug-resistant tuberculosis strains in southeast Mexico, establishing for the first time a baseline of the genotypes observed in resistant isolates circulating, however further studies are required to better elucidate the genetic structure of tuberculosis in region and the factors that could be participating in their dispersion. PMID:29543819

High frequencies of circulating IFN-gamma-secreting CD8 cytotoxic T cells specific for a novel MHC class I-restricted Mycobacterium tuberculosis epitope in M. tuberculosis-infected subjects without disease.

PubMed

Pathan, A A; Wilkinson, K A; Wilkinson, R J; Latif, M; McShane, H; Pasvol, G; Hill, A V; Lalvani, A

2000-09-01

MHC class I-restricted CD8 cytotoxic T lymphocytes (CTL) are essential for protective immunity to Mycobacterium tuberculosis in animal models but their role in humans remains unclear. We therefore studied subjects who had successfully contained M. tuberculosis infection in vivo, i.e. exposed healthy household contacts and individuals with inactive self-healed pulmonary tuberculosis. Using the ELISPOT assay for IFN-gamma, we screened peptides from ESAT-6, a secreted antigen that is highly specific for M. tuberculosis. We identified a novel nonamer epitope: unstimulated peripheral blood-derived CD8 T cells displayed peptide-specific IFN-gamma release ex vivo while CD8 T cell lines and clones exhibited HLA-A68.02-restricted cytolytic activity and recognized endogenously processed antigen. The frequency of CD8 CTL specific for this single M. tuberculosis epitope, 1/2500 peripheral blood lymphocytes, was equivalent to the combined frequency of all IFN-gamma-secreting purified protein derivative-reactive T cells ex vivo. This highly focused CTL response was maintained in an asymptomatic contact over 2 years and is the most potent antigen-specific antimycobacterial CD8 CTL response hitherto described. Thus, human M. tuberculosis-specific CD8 CTL are not necessarily associated with active disease per se. Rather, our results are consistent with a protective role for these ESAT-6-specific CD8 T cells in the long-term control of M. tuberculosis in vivo in humans.

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.

The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection

PubMed Central

Lin, Philana Ling; Dietrich, Jes; Tan, Esterlina; Abalos, Rodolfo M.; Burgos, Jasmin; Bigbee, Carolyn; Bigbee, Matthew; Milk, Leslie; Gideon, Hannah P.; Rodgers, Mark; Cochran, Catherine; Guinn, Kristi M.; Sherman, David R.; Klein, Edwin; Janssen, Christopher; Flynn, JoAnne L.; Andersen, Peter

2011-01-01

It is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis. Infection typically remains latent, but it can reactivate to cause clinical disease. The only vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is largely ineffective, and ways to enhance its efficacy are being developed. Of note, the candidate booster vaccines currently under clinical development have been designed to improve BCG efficacy but not prevent reactivation of latent infection. Here, we demonstrate that administering a multistage vaccine that we term H56 in the adjuvant IC31 as a boost to vaccination with BCG delays and reduces clinical disease in cynomolgus macaques challenged with M. tuberculosis and prevents reactivation of latent infection. H56 contains Ag85B and ESAT-6, which are two of the M. tuberculosis antigens secreted in the acute phase of infection, and the nutrient stress–induced antigen Rv2660c. Boosting with H56/IC31 resulted in efficient containment of M. tuberculosis infection and reduced rates of clinical disease, as measured by clinical parameters, inflammatory markers, and improved survival of the animals compared with BCG alone. Boosted animals showed reduced pulmonary pathology and extrapulmonary dissemination, and protection correlated with a strong recall response against ESAT-6 and Rv2660c. Importantly, BCG/H56-vaccinated monkeys did not reactivate latent infection after treatment with anti-TNF antibody. Our results indicate that H56/IC31 boosting is able to control late-stage infection with M. tuberculosis and contain latent tuberculosis, providing a rationale for the clinical development of H56. PMID:22133873

Changes in healthcare workers' knowledge about tuberculosis following a tuberculosis training programme.

PubMed

Naidoo, S; Taylor, M; Esterhuizen, T M; Nordstrom, D L; Mohamed, O; Knight, S E; Jinabhai, C C

2011-08-01

In resource-limited countries, health policy makers and practitioners need to know whether healthcare workers have sufficient knowledge of tuberculosis and its management. We conducted a study to: (1) measure knowledge changes among healthcare workers who participated in a tuberculosis training programme; and (2) make recommendations about future tuberculosis training for healthcare workers in the KwaZulu-Natal Department of Health. A cross-sectional study conducted in 2007 measured changes in tuberculosis knowledge of doctors, nurses and other healthcare workers after a training programme based on World Health Organization tuberculosis training modules. Data were collected before and after training using a self-administered, 98-item questionnaire covering eight components. A total of 267 healthcare workers, mean age 40.7 years, answered both pre- and post-training questionnaires. Mean total knowledge scores were low despite significant changes (p<0.001) from a pre-training score of 59.5% to a post-training score of 66.5%. Nurses showed significant improvements in mean total knowledge scores (p<0.001) but had the lowest mean total knowledge score post-training, 63.2%. Doctors had significantly better pre-training (p<0.001) and post-training (p<0.001) mean total knowledge scores compared to nurses. Improvement in healthcare workers' overall knowledge of tuberculosis during a training programme was not clinically significant. Periodic field training and supervision should be considered to ensure tuberculosis knowledge improvements.

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

PubMed Central

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

2016-01-01

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

Cost-effectiveness study of the microbiological diagnosis of tuberculosis using geneXpert MTB/RIF®.

PubMed

Herráez, Óscar; Asencio-Egea, María Ángeles; Huertas-Vaquero, María; Carranza-González, Rafael; Castellanos-Monedero, Jesús; Franco-Huerta, María; Barberá-Farré, José Ramón; Tenías-Burillo, José María

To perform a cost-effectiveness analysis of a molecular biology technique for the diagnosis of tuberculosis compared to the classical diagnostic alternative. A cost-effectiveness analysis was performed to evaluate the theoretical implementation of a molecular biology method including two alternative techniques for early detection of Mycobacterium tuberculosis Complex, and resistance to rifampicin (alternative1: one determination in selected patients; alternative2: two determinations in all the patients). Both alternatives were compared with the usual procedure for microbiological diagnosis of tuberculosis (staining and microbiological culture), and was accomplished on 1,972 patients in the period in 2008-2012. The effectiveness was measured in QALYs, and the uncertainty was assessed by univariate, multivariate and probabilistic analysis of sensitivity. A value of €8,588/QALYs was obtained by the usual method. Total expenditure with the alternative1 was €8,487/QALYs, whereas with alternative2, the cost-effectiveness ratio amounted to €2,960/QALYs. Greater diagnostic efficiency was observed by applying the alternative2, reaching a 75% reduction in the number of days that a patient with tuberculosis remains without an adequate treatment, and a 70% reduction in the number of days that a patient without tuberculosis remains in hospital. The implementation of a molecular microbiological technique in the diagnosis of tuberculosis is extremely cost-effective compared to the usual method. Its introduction into the routine diagnostic procedure could lead to an improvement in quality care for patients, given that it would avoid both unnecessary hospitalisations and treatments, and reflected in economic savings to the hospital. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

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

PubMed

Arega, Sintayehu Mulugeta; Conraths, Franz Josef; Ameni, Gobena

2013-05-06

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

Tuberculosis associated chronic obstructive pulmonary disease.

PubMed

Sarkar, Malay; Srinivasa; Madabhavi, Irappa; Kumar, Kushal

2017-05-01

Reviewed the epidemiology, clinical characteristics, mechanisms, and treatment of tuberculosis associated chronic obstructive pulmonary disease. We searched PubMed, EMBASE, and the CINAHL from inception to June 2016. We used the following search terms: Tuberculosis, COPD, Tuberculosis associated COPD, and so forth. All types of study were chosen. Chronic obstructive pulmonary disease (COPD) and tuberculosis are significant public health problems, particularly in developing countries. Although, smoking is the conventional risk factor for COPD, nonsmoking related risk factors such as biomass fuel exposure, childhood lower-respiratory tract infections, chronic asthma, outdoor air pollution, and prior history of pulmonary tuberculosis have become important risk factors of COPD, particularly in developing countries. Past history of tuberculosis as a risk factor of chronic airflow obstruction has been reported in several studies. It may develop during the course of tuberculosis or after completion of tuberculosis treatment. Developing countries with large burden of tuberculosis can contribute significantly to the burden of chronic airflow obstruction. Prompt diagnosis and treatment of tuberculosis should be emphasized to lessen the future burden of chronic airflow obstruction. © 2017 John Wiley & Sons Ltd.

Prediction of host - pathogen protein interactions between Mycobacterium tuberculosis and Homo sapiens using sequence motifs.

PubMed

Huo, Tong; Liu, Wei; Guo, Yu; Yang, Cheng; Lin, Jianping; Rao, Zihe

2015-03-26

Emergence of multiple drug resistant strains of M. tuberculosis (MDR-TB) threatens to derail global efforts aimed at reigning in the pathogen. Co-infections of M. tuberculosis with HIV are difficult to treat. To counter these new challenges, it is essential to study the interactions between M. tuberculosis and the host to learn how these bacteria cause disease. We report a systematic flow to predict the host pathogen interactions (HPIs) between M. tuberculosis and Homo sapiens based on sequence motifs. First, protein sequences were used as initial input for identifying the HPIs by 'interolog' method. HPIs were further filtered by prediction of domain-domain interactions (DDIs). Functional annotations of protein and publicly available experimental results were applied to filter the remaining HPIs. Using such a strategy, 118 pairs of HPIs were identified, which involve 43 proteins from M. tuberculosis and 48 proteins from Homo sapiens. A biological interaction network between M. tuberculosis and Homo sapiens was then constructed using the predicted inter- and intra-species interactions based on the 118 pairs of HPIs. Finally, a web accessible database named PATH (Protein interactions of M. tuberculosis and Human) was constructed to store these predicted interactions and proteins. This interaction network will facilitate the research on host-pathogen protein-protein interactions, and may throw light on how M. tuberculosis interacts with its host.

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

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

PubMed Central

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

2011-01-01

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

Risk factors for pulmonary tuberculosis in Croatia: a matched case–control study

PubMed Central

2013-01-01

Background Mycobacterium tuberculosis is a necessary, but not sufficient, cause of tuberculosis. A number of studies have addressed the issue of risk factors for tuberculosis development. Croatia is a European country with an incidence rate of 14/100 000 which is slowly decreasing. The aim of this study is to evaluate the potential demographic, socioeconomic, behavioural and biological risk factors for tuberculosis in Croatia in comparison to other high-income, low-incidence European countries. Methods A total of 300 tuberculosis patients were matched for age, sex and county of residence to 300 controls randomly selected from general practitioners’ registers. They were interviewed and their medical records were evaluated for variables broadly described as potential risk factors. Results In multiple logistic regression, the following factors were significant: parents born in a particular neighbouring county (Bosnia and Herzegovina) (OR = 3.90, 95% CI 2.01-7.58), the lowest level of education (OR = 3.44, 95% CI 1.39-8.50), poor household equipment (OR = 4.72, 95% CI 1.51-14.76), unemployment (OR = 2.69, 95% CI 1.18-6.16), contact with tuberculosis (OR = 2.19, 95% CI 1.27-3.77), former (OR = 2.27, 95% CI 1.19-4.33) and current smoking habits (OR = 2.35, 95% CI 1.27-4.36), diabetes (OR = 2.38, 95% CI 1.05-5.38), a malignant disease (OR = 5.79, 95% CI 1.49-22.42), being underweight in the previous year (OR = 13.57, 95% CI 1.21-152.38). Conclusion In our study, the identified risk groups for tuberculosis reflect a complex interaction between socioeconomic conditions, lifestyle and non-communicable diseases. Interventions focused on poverty will undoubtedly be useful, but not sufficient. Tuberculosis control would benefit from a combination of broad public health activities aimed at the prevention and control of risky lifestyles and non-communicable diseases, interventions outside the health sector, and efforts to constantly

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

PubMed

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

2013-12-12

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

T7 Phage Display Library a Promising Strategy to Detect Tuberculosis Specific Biomarkers.

PubMed

Talwar, Harvinder; Talreja, Jaya; Samavati, Lobelia

2016-06-01

One-third of the world's population is infected with tuberculosis, only 10% will develop active disease and the remaining 90% is considered to have latent TB (LTB). While active TB is contagious and can be lethal, the LTB can evolve to active TB. The diagnosis of TB can be challenging, especially in the early stages, due to the variability in presentation and nonspecific signs and symptoms. Currently, we have limited tools available to diagnose active TB, predict treatment efficacy and cure of active tuberculosis, the reactivation of latent tuberculosis infection, and the induction of protective immune responses through vaccination. Therefore, the identification of robust and accurate tuberculosis-specific biomarkers is crucial for the successful eradication of TB. In this commentary, we summarized the available methods for diagnosis and differentiation of active TB from LTB and their limitations. Additionally, we present a novel peptide microarray platform as promising strategy to identify TB biomarkers.

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, ...

First Insights into the Phylogenetic Diversity of Mycobacterium tuberculosis in Nepal

PubMed Central

Malla, Bijaya; Stucki, David; Borrell, Sonia; Feldmann, Julia; Maharjan, Bhagwan; Shrestha, Bhawana

2012-01-01

Background Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. Methods and Findings We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42–4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43–5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. Conclusions We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian

Using Patient-Pathway Analysis to Inform a Differentiated Program Response to Tuberculosis: The Case of Kenya

PubMed Central

Masini, Enos; Hanson, Christy; Ogoro, Jeremiah; Brown, Jessie; Ngari, Faith; Mingkwan, Pia; Makayova, Julia; Osberg, Mike

2017-01-01

Abstract Background A recent tuberculosis prevalence survey in Kenya found that the country is home to nearly twice as many patients with tuberculosis as previously estimated. Kenya has prioritized identifying and treating the unnotified or missing cases of tuberculosis. This requires a better understanding of patient care seeking and system weaknesses. Methods A patient-pathway analysis (PPA) was completed to assess the alignment between patient care seeking and the availability of tuberculosis diagnostic and treatment services at the national level and for all 47 counties at the subnational level in Kenya. Results It was estimated that more than half of patients initiate care in the public sector. Nationally, just under half of patients encountered tuberculosis diagnostic and treatment capacity where they initiated care. Overall, there was distinct variation in diagnostic and treatment availability across counties and facility levels. Discussion The PPA results emphasized the need for a differentiated approach to tuberculosis care, by county, and the distinct need for better referral systems. The majority of Kenyans actively sought care; improving diagnostic and treatment capacity in the formal and informal private sector, as well as in the public sector, could help identify the majority of missing cases. PMID:29117349

First case of sexual transmitted asymptomatic female genital tuberculosis from spousal epididymal tuberculosis diagnosed by active screening.

PubMed

Kimura, Muneyoshi; Araoka, Hideki; Baba, Hiromi; Okada, Chikako; Murase, Yoshiro; Takaki, Akiko; Mitarai, Satoshi; Yoneyama, Akiko

2018-06-04

Tuberculosis screening was performed for a healthy asymptomatic woman to determine whether she had been infected with active genital tuberculosis via sexual intercourse with her husband who had epididymal tuberculosis. Vaginal swab culture yielded Mycobacterium tuberculosis. Furthermore, whole genome sequencing revealed that the two causative isolates were genetically identical. To the best of our knowledge, this is the first report on sexual transmission of genital tuberculosis from a man to an asymptomatic woman detected by active screening for genital tuberculosis and molecular analysis, including whole-genome-sequencing. Active screening for genital tuberculosis in the female partner should be considered soon after diagnosis of male genital tuberculosis even when the female partner is asymptomatic. Copyright © 2018. Published by Elsevier Ltd.

Genotyping of ancient Mycobacterium tuberculosis strains reveals historic genetic diversity.

PubMed

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

2014-04-22

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

Using Patient Pathway Analysis to Design Patient-centered Referral Networks for Diagnosis and Treatment of Tuberculosis: The Case of the Philippines

PubMed Central

Garfin, Celine; Mantala, Mariquita; Yadav, Rajendra; Hanson, Christy L; Osberg, Mike; Hymoff, Aaron; Makayova, Julia

2017-01-01

Abstract Background Tuberculosis (TB) is the 8th leading cause of death in the Philippines. A recent prevalence survey found that there were nearly 70% more cases of tuberculosis than previously estimated. Given these new data, the National TB Program (NTP), operating through a decentralized health system, identified about 58% of the estimated new drug-sensitive (DS) TB patients in 2016. However, the NTP only identified and commenced treatment for around 17% of estimated new drug-resistant patients. In order to reach the remaining 42% of drug-sensitive patients and 83% of drug-resistant patients, it is necessary to develop a better understanding of where patients seek care. Methods National and regional patient pathway analyses (PPAs) were undertaken using existing national survey and NTP data. The PPA assessed the alignment between patient care seeking and the availability of TB diagnostic and treatment services. Results Systemic referral networks from the community-level Barangay Health Stations (BHSs) to diagnostic facilities have enabled more efficient detection of drug-sensitive tuberculosis in the public sector. Approximately 36% of patients initiated care in the private sector, where there is limited coverage of appropriate diagnostic technologies. Important differences in the alignment between care seeking patterns and diagnostic and treatment availability were found between regions. Conclusions The PPA identified opportunities for strengthening access to care for all forms of tuberculosis and for accelerating the time to diagnosis by aligning services to where patients initiate care. Geographic variations in care seeking may guide prioritization of some regions for intensified engagement with the private sector. PMID:29117352

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

USDA-ARS?s Scientific Manuscript database

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...

Potential market for novel tuberculosis diagnostics: worth the investment?

PubMed

Kik, Sandra V; Denkinger, Claudia M; Jefferson, Carole; Ginnard, Janet; Pai, Madhukar

2015-04-01

The potential available market (PAM) for new diagnostics for tuberculosis that meet the specifications of the high-priority target product profiles (TPPs) is currently unknown. We estimated the PAM in 2020 in 4 high-burden countries (South Africa, Brazil, China, and India) for tests that meet the specifications outlined in the TPPs. The yearly PAM was estimated for the most likely application of each TPP. In 2020 the PAM for all 4 countries together was estimated to be (1) 12M tests/year with a value of 48M-71M USD for a sputum smear-replacement test; (2) 16M tests/year with a value of 65M-97M USD for a biomarker test; (3) 18M tests/year with a value of 18M-35M USD for a triage test; (4) 12M tests/year with a value of 59M-2238M USD for a tuberculosis detection plus drug susceptibility test (DST) all-in-one or 1.5M tests/year for a DST that follows a positive tuberculosis detection test with a corresponding value of 75M-121M for both tuberculosis detection and DST. Although there is a considerable potential market for novel tuberculosis diagnostics that fit the specification of the TPPs in the 4 high-burden countries, the actual market for an individual product remains uncertain. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Extensive Drug Resistance Acquired During Treatment of Multidrug-Resistant Tuberculosis

PubMed Central

Cegielski, J. Peter; Dalton, Tracy; Yagui, Martin; Wattanaamornkiet, Wanpen; Volchenkov, Grigory V.; Via, Laura E.; Van Der Walt, Martie; Tupasi, Thelma; Smith, Sarah E.; Odendaal, Ronel; Leimane, Vaira; Kvasnovsky, Charlotte; Kuznetsova, Tatiana; Kurbatova, Ekaterina; Kummik, Tiina; Kuksa, Liga; Kliiman, Kai; Kiryanova, Elena V.; Kim, HeeJin; Kim, Chang-ki; Kazennyy, Boris Y.; Jou, Ruwen; Huang, Wei-Lun; Ershova, Julia; Erokhin, Vladislav V.; Diem, Lois; Contreras, Carmen; Cho, Sang Nae; Chernousova, Larisa N.; Chen, Michael P.; Caoili, Janice Campos; Bayona, Jaime; Akksilp, Somsak; Calahuanca, Gloria Yale; Wolfgang, Melanie; Viiklepp, Piret; Vasilieva, Irina A.; Taylor, Allison; Tan, Kathrine; Suarez, Carmen; Sture, Ingrida; Somova, Tatiana; Smirnova, Tatyana G.; Sigman, Erika; Skenders, Girts; Sitti, Wanlaya; Shamputa, Isdore C.; Riekstina, Vija; Pua, Kristine Rose; Therese, M.; Perez, C.; Park, Seungkyu; Norvaisha, Inga; Nemtsova, Evgenia S.; Min, Seonyeong; Metchock, Beverly; Levina, Klavdia; Lei, Yung-Chao; Lee, Jongseok; Larionova, Elena E.; Lancaster, Joey; Jeon, Doosoo; Jave, Oswaldo; Khorosheva, Tatiana; Hwang, Soo Hee; Huang, Angela Song-En; Gler, M. Tarcela; Dravniece, Gunta; Eum, Seokyong; Demikhova, Olga V.; Degtyareva, Irina; Danilovits, Manfred; Cirula, Anda; Cho, Eunjin; Cai, Ying; Brand, Jeanette; Bonilla, Cesar; Barry, Clifton E.; Asencios, Luis; Andreevskaya, Sofia N.; Akksilp, Rattanawadee

2014-01-01

Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16–.47) for XDR tuberculosis, 0.28 (.17–.45) for FQ, and 0.15 (.06–.39) to 0.60 (.34–1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07–.62) for acquired XDR tuberculosis and 0.23 (.09–.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards. PMID:25057101

Time of default in tuberculosis patients on directly observed treatment.

PubMed

Pardeshi, Geeta S

2010-09-01

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

Mycobacterium tuberculosis: ecology and evolution of a human bacterium.

PubMed

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

2015-11-01

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

The Mycobacterium tuberculosis Complex has a Pathway for the Biosynthesis of 4-Formamido-4,6-Dideoxy-d-Glucose.

PubMed

Brown, Haley A; Vinogradov, Evgeny; Gilbert, Michel; Holden, Hazel M

2018-05-15

Recent studies have demonstrated that the O-antigens of some pathogenic bacteria such as Brucella abortus, Francisella tularensis, and Campylobacter jejuni contain quite unusual N-formylated sugars (3-formamido-3,6-dideoxy-d-glucose or 4-formamido-4,6-dideoxy-d-glucose). Typically, four enzymes are required for the formation of such sugars: a thymidylyltransferase, a 4,6-dehydratase, a pyridoxal 5'-phosphate or PLP-dependent aminotransferase, and an N-formyltransferase. To date, there have been no published reports of N-formylated sugars associated with Mycobacterium tuberculosis. A recent investigation from our laboratories, however, has demonstrated that one gene product from M. tuberculosis, Rv3404c, functions as a sugar N-formyltransferase. Given that M. tuberculosis produces l-rhamnose, both a thymidylyltransferase (Rv0334) and a 4,6-dehydratase (Rv3464) required for its formation have been identified. Thus, there is one remaining enzyme needed for the production of an N-formylated sugar in M. tuberculosis, namely a PLP-dependent aminotransferase. Here we demonstrate that the M. tuberculosis rv3402c gene encodes such an enzyme. Our data prove that M. tuberculosis contains all of the enzymatic activities required for the formation of dTDP-4-formamido-4,6-dideoxy-d-glucose. Indeed, the rv3402c gene product likely contributes to virulence or persistence during infection, though its temporal expression and location remain to be determined. This article is protected by copyright. All rights reserved. © 2018 The Protein Society.

[Tuberculosis and HIV infection: experience of the national tuberculosis prevention program in Djibouti: 1990-1996].

PubMed

Renoux, E; Matan, A Barreh; Sevre, J P; Mohamed Ali, I; Chami, D; Vincent, V

2002-01-01

Based on analysis of data collected from the national tuberculosis prevention program in Djibouti between 1990 and 1996, the authors analyzed the relationship between HIV infection and tuberculosis. The study cohort comprised a total of 22,000 patients including 14,000 with documented HIV infection. Although HIV infection probably worsened the situation, it was neither the only nor the main factor involved in the resurgence of tuberculosis. Demographic growth, higher population density, and increasing poverty as well as the quality of the national tuberculosis prevention program must be taken into account. The incidence of smear-negative tuberculosis was not significantly higher in HIV-infected patients (incidence of smear positive cases, > 92%). Extrapulmonary tuberculosis especially of pleural involvement was more common (15% versus 9.4%). Treatment was effective in HIV-infected patients. If directly observed (DOT) therapy was used, there was no risk of emergence of multidrug-resistant tuberculosis strains. Drug side-effects associated with the protocols used in Djibouti were not greater in HIV-infected patients. Most additional mortality observed in HIV-infected tuberculosis patients (10.5% versus 2%) was due to progression of HIV infection.

Intensive short course chemotherapy for treatment of Greek children with tuberculosis.

PubMed

Tsakalidis, D; Pratsidou, P; Hitoglou-Makedou, A; Tzouvelekis, G; Sofroniadis, I

1992-12-01

This prospective study with an 18-month posttreatment follow-up evaluated the efficacy of intensive short course chemotherapy in Greek children with pulmonary or extrapulmonary tuberculosis. Between November, 1988, and March 1991 a 2-month regimen of rifampin, 10 to 12 mg/kg/day, isoniazid, 10 to 12 mg/kg/day, and pyrazinamide, 30 to 35 mg/kg/day, followed by rifampin and isoniazid for the remaining 4 months, was administered orally to 36 children with tuberculosis. Twenty-three boys and 13 girls ages 8 months to 12 years (mean, 5 1/2 years) were enrolled in the study. The diagnostic criteria for establishing tuberculosis were tuberculin skin test reactivity, radiographic findings compatible with tuberculosis, epidemiological data and clinical and laboratory findings. Four children had extrapulmonary and 32 had pulmonary tuberculosis; 9 of the latter were asymptomatic. Among the pulmonary cases there were 2 children with pleural effusion. Clinical response to therapy was apparent within 7 to 14 days; the pleural effusions resolved in 2 to 6 weeks and the pulmonary infiltrates cleared in 2 to 6 months. Hilar adenopathy regressed within 18 months or longer. No serious problems with drug tolerance or toxicity were noted during the treatment period. Temporary hyperuricemia and transient elevation in serum transaminases were observed in 11 patients but no drug modification was required. There were no posttreatment relapses. These findings suggest that intensive short course chemotherapy for the treatment of Greek children with pulmonary or extrapulmonary tuberculosis appears to be effective, safe, of good patient compliance and comparable to the longer treatment regimens.

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

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

Tuberculosis and Diabetes

MedlinePlus

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

[Tuberculosis and drug-resistance tuberculosis in prisoners. Colombia, 2010-2012].

PubMed

Gómez, Ingrid T; Llerena, Claudia R; Zabaleta, Angie P

2015-01-01

To characterize tuberculosis drug-resistance using anti-tuberculosis drug-sensitivity tests in Colombian prisoners. Descriptive-retrospective analyses were performed on cases of tuberculosis in prisoners. Samples were evaluated by the National Reference Laboratory. Conditions like gender, TB/VIH co-infection and drug-resistance were evaluated. Anti-tuberculosis drug-sensitivity tests were carried out on 72 prisoners. Results showed a distribution of 90.7 % of cases in males and 9.3 % of cases in females. 12 % of cases were TB/VIH co-infections, 94 % of the cases had not received any anti-tuberculosis treatment before, six isolates were drug-resistant corresponding to 8.8 % of total cases, and two cases were multi drug-resistant representing 1.3 % of the cases. Of the drug-resistant cases, 83.3 % were TB/VIH co-infected. Previously treated cases corresponded to 5.6 % of the total cases analyzed. One case with TB/VIH co-infection and rifampicin resistance was observed, representing 1.3 % of the total cases. The government must create a clear policy for prisoners in Colombia, because a high rate of disease in prisoners was observed. In addition, the results showed an association between drug-resistance and TB/VIH co-infection. Overcrowding and low quality of life in penitentiaries could become an important public health problem.

Epidemiologic Consequences of Microvariation in Mycobacterium tuberculosis

PubMed Central

Mathema, Barun; Kurepina, Natalia; Yang, Guibin; Shashkina, Elena; Manca, Claudia; Mehaffy, Carolina; Bielefeldt-Ohmann, Helle; Ahuja, Shama; Fallows, Dorothy A.; Izzo, Angelo; Bifani, Pablo; Dobos, Karen; Kaplan, Gilla

2012-01-01

Background. Evidence from genotype-phenotype studies suggests that genetic diversity in pathogens have clinically relevant manifestations that can impact outcome of infection and epidemiologic success. We studied 5 closely related Mycobacterium tuberculosis strains that collectively caused extensive disease (n = 862), particularly among US-born tuberculosis patients. Methods. Representative isolates were selected using population-based genotyping data from New York City and New Jersey. Growth and cytokine/chemokine response were measured in infected human monocytes. Survival was determined in aerosol-infected guinea pigs. Results. Multiple genotyping methods and phylogenetically informative synonymous single nucleotide polymorphisms showed that all strains were related by descent. In axenic culture, all strains grew similarly. However, infection of monocytes revealed 2 growth phenotypes, slower (doubling ∼55 hours) and faster (∼25 hours). The faster growing strains elicited more tumor necrosis factor α and interleukin 1β than the slower growing strains, even after heat killing, and caused accelerated death of infected guinea pigs (∼9 weeks vs 24 weeks) associated with increased lung inflammation/pathology. Epidemiologically, the faster growing strains were associated with human immunodeficiency virus and more limited in spread, possibly related to their inherent ability to induce a strong protective innate immune response in immune competent hosts. Conclusions. Natural variation, with detectable phenotypic changes, among closely related clinical isolates of M. tuberculosis may alter epidemiologic patterns in human populations. PMID:22315279

[Pneumonectomy for tuberculosis destroyed lung: A series of 26 operated cases].

PubMed

Issoufou, I; Sani, R; Belliraj, L; Ammor, F Z; Moussa Ounteini, A; Ghalimi, J; Lakranbi, M; Ouadnouni, Y; Smahi, M

2016-10-01

Pneumonectomy keeps a greatest place in the treatment of tuberculosis lung destroyed despite high morbidity and mortality. The aim of our study was to analyze the results of pneumonectomy in the treatment of tuberculosis lung destroyed in our institution. A retrospective study over a period of 5 years (2009 to 2014) was realized. Are involved in the study all patients admitted to the thoracic surgery department of CHU Hassan II with tuberculosis lung destroyed and operated during the study period. This is a series of 26 patients, including 17 men and 9 women treated and cured for pulmonary tuberculosis of which 2 for multiresistant tuberculosis. The average age was 38.8 years. Hemoptysis (77 %) and recurrent respiratory infections (65.4 %) were the major clinical signs. Aspergilloma have been reported on cavitary lesion in 23 % of cases and in 11.5 % pyothorax was associated. Extra-pericardial pneumonectomy was performed in 65.4 %, intra-pericardial pneumonectomy in 19.3 % and pleural-pneumonectomy in 15.3 %. The outcome was favorable in 23 patients. We noted a pyothorax on pneumonectomy cavity in 3 patients. Postoperative mortality was 7.7 %. The regularly clinical and radiological control of all patients is satisfactory with a mean of 41 months. Pneumonectomy for tuberculosis lung destroyed remains effective in young patients with an acceptable complication rate. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mycobacterium tuberculosis Hip1 Dampens Macrophage Proinflammatory Responses by Limiting Toll-Like Receptor 2 Activation▿

PubMed Central

Madan-Lala, Ranjna; Peixoto, Katia Vitorello; Re, Fabio; Rengarajan, Jyothi

2011-01-01

Mycobacterium tuberculosis is a highly successful human pathogen that evades host innate immunity by interfering with macrophage functions. In addition to avoiding macrophage microbicidal activities, M. tuberculosis triggers secretion of proinflammatory cytokines and chemokines in macrophages. The levels of proinflammatory cytokines induced by clinical M. tuberculosis isolates are thought to play an important role in determining tuberculosis disease progression and severity, but the mechanisms by which M. tuberculosis modulates the magnitude of inflammatory responses remain unclear. Here we show that M. tuberculosis restricts robust macrophage activation and dampens proinflammatory responses through the cell envelope-associated serine hydrolase Hip1 (hydrolase important for pathogenesis 1). By transcriptionally profiling macrophages infected with either wild-type or hip1 mutant bacteria, we found that the hip1 mutant induced earlier and significantly higher levels of several proinflammatory cytokines and chemokines. We show that increased activation of Toll-like receptor 2 (TLR2)- and MyD88-dependent signaling pathways mediates the enhanced cytokine secretion induced by the hip1 mutant. Thus, Hip1 restricts the onset and magnitude of proinflammatory cytokines by limiting TLR2-dependent activation. We also show that Hip1 dampens TLR2-independent activation of the inflammasome and limits secretion of interleukin-18 (IL-18). Dampening of TLR2 signaling does not require viable M. tuberculosis or phagocytosis but does require Hip1 catalytic activity. We propose that M. tuberculosis restricts proinflammatory responses by masking cell surface interactions between TLR2 agonists on M. tuberculosis and TLR2 on macrophages. This strategy may allow M. tuberculosis to evade early detection by host immunity, delay the onset of adaptive immune responses, and accelerate disease progression. PMID:21947769

Mycobacterium tuberculosis Hip1 dampens macrophage proinflammatory responses by limiting toll-like receptor 2 activation.

PubMed

Madan-Lala, Ranjna; Peixoto, Katia Vitorello; Re, Fabio; Rengarajan, Jyothi

2011-12-01

Mycobacterium tuberculosis is a highly successful human pathogen that evades host innate immunity by interfering with macrophage functions. In addition to avoiding macrophage microbicidal activities, M. tuberculosis triggers secretion of proinflammatory cytokines and chemokines in macrophages. The levels of proinflammatory cytokines induced by clinical M. tuberculosis isolates are thought to play an important role in determining tuberculosis disease progression and severity, but the mechanisms by which M. tuberculosis modulates the magnitude of inflammatory responses remain unclear. Here we show that M. tuberculosis restricts robust macrophage activation and dampens proinflammatory responses through the cell envelope-associated serine hydrolase Hip1 (hydrolase important for pathogenesis 1). By transcriptionally profiling macrophages infected with either wild-type or hip1 mutant bacteria, we found that the hip1 mutant induced earlier and significantly higher levels of several proinflammatory cytokines and chemokines. We show that increased activation of Toll-like receptor 2 (TLR2)- and MyD88-dependent signaling pathways mediates the enhanced cytokine secretion induced by the hip1 mutant. Thus, Hip1 restricts the onset and magnitude of proinflammatory cytokines by limiting TLR2-dependent activation. We also show that Hip1 dampens TLR2-independent activation of the inflammasome and limits secretion of interleukin-18 (IL-18). Dampening of TLR2 signaling does not require viable M. tuberculosis or phagocytosis but does require Hip1 catalytic activity. We propose that M. tuberculosis restricts proinflammatory responses by masking cell surface interactions between TLR2 agonists on M. tuberculosis and TLR2 on macrophages. This strategy may allow M. tuberculosis to evade early detection by host immunity, delay the onset of adaptive immune responses, and accelerate disease progression.

Anti-tubercular therapy for intraocular tuberculosis: A systematic review and meta-analysis

PubMed Central

Kee, Ae Ra; Gonzalez-Lopez, Julio J.; Al-Hity, Aws; Gupta, Bhaskar; Lee, Cecilia S.; Gunasekeran, Dinesh Visva; Jayabalan, Nirmal; Grant, Robert; Kon, Onn Min; Gupta, Vishali; Westcott, Mark; Pavesio, Carlos; Agrawal, Rupesh

2016-01-01

Intraocular tuberculosis remains a diagnostic and management conundrum for both ophthalmologists and pulmonologists. We analyze the efficacy and safety of anti-tubercular therapy (ATT) in patients with intraocular tuberculosis and factors associated with favorable outcome. Twenty-eight studies are included in this review, with a total of 1,917 patients. Nonrecurrence of inflammation was observed in pooled estimate of 84% of ATT-treated patients (95% CI 79–89). There was minimal difference in the outcome between patients treated with ATT alone (85% successful outcome; 95% CI 25–100) and those with concomitant systemic corticosteroid (82%; 95% CI 73–90). The use of ATT may be of benefit to patients with suspected intraocular tuberculosis; however, this conclusion is limited by the lack of control group analysis and standardized recruitment and treatment protocols. PMID:26970263

Multiple cytokine responses in discriminating between active tuberculosis and latent tuberculosis infection.

PubMed

Wu, Jing; Wang, Sen; Lu, Chanyi; Shao, Lingyun; Gao, Yan; Zhou, Zumo; Huang, Heqing; Zhang, Ying; Zhang, Wenhong

2017-01-01

Cytokines play an important role in cell-mediated immune responses against Mycobacterium tuberculosis (Mtb) infection. Cytokine profile specifically associated with active tuberculosis (ATB) patients, subjects with latent tuberculosis infection (LTBI) and non-infected individuals remains to be determined. We enrolled a total of 92 subjects including patients with ATB (n = 25), LTBI (n = 36) and healthy controls (HC, n = 31) to investigate the cytokine production by peripheral blood mononuclear cells after Mtb purified protein derivative (PPD) stimulation which was evaluated by a beads-based multiplex assay system. The production of IL-1β, IL-2, IL-6, IL-10, IL-17, G-CSF, IFN-γ, IP-10, MIP-1α and TNF-α was abundantly induced by PPD in all three groups. The levels of IL-2, IL-10, IFN-γ, IP-10 and TNF-α were significantly higher in LTBI group than in ATB group. The combination of PPD-stimulated IL-2 and IL-10 accurately identified 84.0% of ATB and 88.9% of LTBI. We validated the use of PPD-stimulated IL-2 and IL-10 test combined with T-SPOT.TB test in a cohort of 44 subjects with TB suspicion. The sensitivity and specificity of the combined test were 83.3% and 92.3%, respectively. The PPD-stimulated IL-2/IFN-γ ratio (p < 0.001) in LTBI subjects was significantly higher than in active TB patients. Our study identified cytokine patterns characteristic of ATB and LTBI. Cytokines such as IL-2 and IL-10 may serve as biomarkers for distinguishing ATB from LTBI and healthy control and may contribute to intervention and improvement in TB diagnosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Associations between national tuberculosis program budgets and tuberculosis outcomes: an ecological study.

PubMed

Chapple, Will; Katz, Alan Roy; Li, Dongmei

2012-01-01

The objective of this study is to explore the associations between national tuberculosis program (NTP) budget allocation and tuberculosis related outcomes in the World Health Organization's 22 high burden countries from 2007-2009. This ecological study used mixed effects and generalized estimating equation models to identify independent associations between NTP budget allocations and various tuberculosis related outcomes. Models were adjusted for a number of independent variables previously noted to be associated with tuberculosis incidence. Increasing the percent of the NTP budget for advocacy, communication and social mobilization was associated with an increase in the case detection rate. Increasing TB-HIV funding was associated with an increase in HIV testing among TB patients. Increasing the percent of the population covered by the Directly Observed Therapy (DOT) program was associated with an increase in drug susceptibility testing. Laboratory funding was positively associated with tuberculosis notification. Increasing the budgets for first line drugs, management and multi-drug resistant tuberculosis (MDR-TB) was associated with a decrease in smear positive deaths. Effective TB control is a complex and multifaceted challenge. This study revealed a number of budget allocation related factors associated with improved TB outcome parameters. If confirmed with future longitudinal studies, these findings could help guide NTP managers with allocation decisions.

Associations between national tuberculosis program budgets and tuberculosis outcomes: an ecological study

PubMed Central

Chapple, Will; Katz, Alan Roy; Li, Dongmei

2012-01-01

Introduction The objective of this study is to explore the associations between national tuberculosis program (NTP) budget allocation and tuberculosis related outcomes in the World Health Organization's 22 high burden countries from 2007–2009. Methods This ecological study used mixed effects and generalized estimating equation models to identify independent associations between NTP budget allocations and various tuberculosis related outcomes. Models were adjusted for a number of independent variables previously noted to be associated with tuberculosis incidence. Results Increasing the percent of the NTP budget for advocacy, communication and social mobilization was associated with an increase in the case detection rate. Increasing TB-HIV funding was associated with an increase in HIV testing among TB patients. Increasing the percent of the population covered by the Directly Observed Therapy (DOT) program was associated with an increase in drug susceptibility testing. Laboratory funding was positively associated with tuberculosis notification. Increasing the budgets for first line drugs, management and multi-drug resistant tuberculosis (MDR-TB) was associated with a decrease in smear positive deaths. Conclusion Effective TB control is a complex and multifaceted challenge. This study revealed a number of budget allocation related factors associated with improved TB outcome parameters. If confirmed with future longitudinal studies, these findings could help guide NTP managers with allocation decisions. PMID:23024825

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

Prevalence of Mycobacterium tuberculosis strain genotypes in Taiwan reveals a close link to ethnic and population migration.

PubMed

Dou, Horng-Yunn; Chen, Yih-Yuan; Kou, Shu-Chen; Su, Ih-Jen

2015-06-01

Taiwan is a relatively isolated island, serving as a mixing vessel for colonization by different waves of ethnic and migratory groups over the past 4 centuries. The potential transmission pattern of Mycobacterium tuberculosis in different ethnic and migratory populations remains to be elucidated. By using mycobacterial tandem repeat sequences as genetic markers, the prevalence of M. tuberculosis strains in Taiwan revealed a close link to the historical migration. Interestingly, the M. tuberculosis strain in the aborigines of Eastern and Central Taiwan had a dominance of the Haarlem (Dutch) strain while those in Southern Taiwan had a dominance of the East-African Indian (EAI) strain. The prevalence of different M. tuberculosis strains in specific ethnic populations suggests that M. tuberculosis transmission is limited and restricted to close contact. The prevalence of the Beijing modern strain in the young population causes a concern for M. tuberculosis control, because of high virulence and drug resistance. Furthermore, our data using molecular genotyping should provide valuable information on the historical study of the origin and migration of aborigines in Taiwan. Copyright © 2014. Published by Elsevier B.V.

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

Identification of risk factors for extrapulmonary tuberculosis.

PubMed

Yang, Zhenhua; Kong, Ying; Wilson, Frank; Foxman, Betsy; Fowler, Annadell H; Marrs, Carl F; Cave, M Donald; Bates, Joseph H

2004-01-15

The proportion of extrapulmonary tuberculosis cases in the United States has increased from 16% of tuberculosis cases, in 1991, to 20%, in 2001. To determine associations between the demographic, clinical, and life style characteristics of patients with tuberculosis and the occurrence of extrapulmonary tuberculosis, a retrospective case-control study was conducted. This study included 705 patients with tuberculosis, representing 98% of the culture-proven cases of tuberculosis in Arkansas from 1 January 1996 through 31 December 2000. A comparison between 85 patients with extrapulmonary tuberculosis (case patients) and 620 patients with pulmonary tuberculosis (control patients) showed women (OR, 1.98; 95% CI, 1.25-3.13), non-Hispanic blacks (OR, 2.38; 95% CI, 1.42-3.97), and HIV-positive persons (OR, 4.93; 95% CI, 1.95-12.46) to have a significantly higher risk for extrapulmonary tuberculosis than men, non-Hispanic whites, and HIV-negative persons. This study expands the knowledge base regarding the epidemiology of extrapulmonary tuberculosis and enhances our understanding of the relative contribution of host-related factors to the pathogenesis of tuberculosis.

Broad-range PCR coupled with mass-spectrometry for the detection of Mycobacterium tuberculosis drug resistance

PubMed Central

Florea, Dragoş; Oţelea, Dan; Olaru, Ioana D.; Hristea, Adriana

2016-01-01

Background The need to limit the spread of drug-resistant Mycobacterium tuberculosis requires rapid detection of resistant strains. The present study aimed to evaluate a commercial assay using broad-range PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) for the rapid detection of isoniazid (INH) and rifampin (RIF) resistance in M. tuberculosis strains isolated from Romanian patients with pulmonary tuberculosis. Methods PCR/ESI-MS was used to detect genotypic resistance to RIF and INH in a panel of 63 M. tuberculosis isolates phenotypically characterized using the absolute concentration method on Löwenstein-Jensen medium. Results Thirty-eight (60%) strains were susceptible to both drugs, 22 (35%) were RIF and INH resistant, one was INH mono-resistant and two were RIF mono-resistant. The sensitivity for INH and RIF resistance mutations detection were 100% and 92% respectively, with a specificity of more than 95% for each drug. Conclusion PCR/ESI-MS is a good method for the detection of RIF and INH resistance and might represent an alternative to other rapid diagnostic tests for the detection of genetic markers of resistance in M. tuberculosis isolates. PMID:27019827

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

PubMed Central

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

2015-01-01

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

Targeting phenotypically tolerant Mycobacterium tuberculosis

PubMed Central

Gold, Ben; Nathan, Carl

2016-01-01

While the immune system is credited with averting tuberculosis in billions of individuals exposed to Mycobacterium tuberculosis, the immune system is also culpable for tempering the ability of antibiotics to deliver swift and durable cure of disease. In individuals afflicted with tuberculosis, host immunity produces diverse microenvironmental niches that support suboptimal growth, or complete growth arrest, of M. tuberculosis. The physiological state of nonreplication in bacteria is associated with phenotypic drug tolerance. Many of these host microenvironments, when modeled in vitro by carbon starvation, complete nutrient starvation, stationary phase, acidic pH, reactive nitrogen intermediates, hypoxia, biofilms, and withholding streptomycin from the streptomycin-addicted strain SS18b, render M. tuberculosis profoundly tolerant to many of the antibiotics that are given to tuberculosis patients in a clinical setting. Targeting nonreplicating persisters is anticipated to reduce the duration of antibiotic treatment and rate of post-treatment relapse. Some promising drugs to treat tuberculosis, such as rifampicin and bedaquiline, only kill nonreplicating M. tuberculosis in vitro at concentrations far greater than their minimal inhibitory concentrations against replicating bacilli. There is an urgent demand to identify which of the currently used antibiotics, and which of the molecules in academic and corporate screening collections, have potent bactericidal action on nonreplicating M. tuberculosis. With this goal, we review methods of high throughput screening to target nonreplicating M. tuberculosis and methods to progress candidate molecules. A classification based on structures and putative targets of molecules that have been reported to kill nonreplicating M. tuberculosis revealed a rich diversity in pharmacophores. However, few of these compounds were tested under conditions that would exclude the impact of adsorbed compound acting during the recovery phase of

Progress on the biomarkers for tuberculosis diagnosis.

PubMed

Fu, Tiwei; Xie, Jianping

2011-01-01

Tuberculosis (TB) remains a major threat to global health. Biomarkers derived from pathogen-host interaction can facilitate the monitoring of active TB. The recent progress regarding such biomarkers is summarized, including those can be used from serum, sputum, urine, or breath monitoring. A wide range of potential biomarkers such as protein antigens, cell-free nucleic acids, and lipoarabinomannose were compiled. The possible use of biomarkers for infection identification and monitoring drug efficacy are also presented.

Increasing Access to Tuberculosis Services in Ethiopia: Findings From a Patient-Pathway Analysis.

PubMed

Fekadu, Lelisa; Hanson, Christy; Osberg, Mike; Makayova, Julia; Mingkwan, Pia; Chin, Daniel

2017-11-06

In Ethiopia, extensive scale-up of the availability of health extension workers (HEWs) at the community level has been credited with increased identification and referral of patients with presumptive tuberculosis, which has contributed to increased tuberculosis case notification and better treatment outcomes. However, nearly 30% of Ethiopia's estimated 191000 patients with tuberculosis remained unnotified in 2015. A better understanding of patient care-seeking practices may inform future government action to reach all patients with tuberculosis. A patient-pathway analysis was completed to assess the alignment between patient care initiation and the availability of diagnostic and treatment services at the national level. More than one third of patients initiated care with HEWs, who refer patients to health centers for diagnosis. An additional one third of patients initiated care at health centers. Of those health centers, >80% had microscopy services, but few had access to Xpert. Despite an extensive microscopy and radiography network at middle levels of the health system, a quarter of all notified patients with tuberculosis had no bacteriological confirmation of disease. While 30% of patients reported receiving some form of care from the private sector, private-sector facilities, especially pharmacies, were not widely accessed for tuberculosis diagnosis. The availability of HEWs can increase access to tuberculosis diagnostic and treatment support services, particularly for rural populations. Continued strengthening of referral systems from HEWs and health posts are needed to enable consistent and timely access to Xpert as an initial diagnostic test and to drug resistance screening. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Tuberculosis (For Parents)

MedlinePlus

... is a disease caused by the bacteria Mycobacterium tuberculosis . It mainly infects the lungs, although it also can affect other organs. When ... it can progress and spread all over the lungs (called progressive tuberculosis) or to other organs. This causes signs and ...

Nutritional supplements for people being treated for active tuberculosis

PubMed Central

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

2016-01-01

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

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

PubMed

Duff, E J; Johnson, J S

1974-03-23

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

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. ...

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. ...

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. ...

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. ...

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. ...

Common Polymorphisms in the PKP3-SIGIRR-TMEM16J Gene Region Are Associated With Susceptibility to Tuberculosis

PubMed Central

Randhawa, April K.; Chau, Tran T. H.; Bang, Nguyen D.; Yen, Nguyen T. B.; Farrar, Jeremy J.; Dunstan, Sarah J.; Hawn, Thomas R.

2012-01-01

(See the editorial commentary by Wilkinson, on pages 525–7.) Background. Tuberculosis has been associated with genetic variation in host immunity. We hypothesized that single-nucleotide polymorphisms (SNPs) in SIGIRR, a negative regulator of Toll-like receptor/IL-1R signaling, are associated with susceptibility to tuberculosis. Methods. We used a case-population study design in Vietnam with cases that had either tuberculous meningitis or pulmonary tuberculosis. We genotyped 6 SNPs in the SIGIRR gene region (including the adjacent genes PKP3 and TMEM16J) in a discovery cohort of 352 patients with tuberculosis and 382 controls. Significant associations were genotyped in a validation cohort (339 patients with tuberculosis, 376 controls). Results. Three SNPs (rs10902158, rs7105848, rs7111432) were associated with tuberculosis in discovery and validation cohorts. The polymorphisms were associated with both tuberculous meningitis and pulmonary tuberculosis and were strongest with a recessive genetic model (odds ratios, 1.5–1.6; P = .0006–.001). Coinheritance of these polymorphisms with previously identified risk alleles in Toll-like receptor 2 and TIRAP was associated with an additive risk of tuberculosis susceptibility. Conclusions. These results demonstrate a strong association of SNPs in the PKP3-SIGIRR-TMEM16J gene region and tuberculosis in discovery and validation cohorts. To our knowledge, these are the first associations of polymorphisms in this region with any disease. PMID:22223854

Pictorial essay: Orbital tuberculosis

PubMed Central

Narula, Mahender K; Chaudhary, Vikas; Baruah, Dhiraj; Kathuria, Manoj; Anand, Rama

2010-01-01

Tuberculosis of the orbit is rare, even in places where tuberculosis is endemic. The disease may involve soft tissue, the lacrimal gland, or the periosteum or bones of the orbital wall. Intracranial extension, in the form of extradural abscess, and infratemporal fossa extension has been described. This pictorial essay illustrates the imaging findings of nine histopathologically confirmed cases of orbital tuberculosis. All these patients responded to antituberculous treatment. PMID:20351984

Tuberculosis in Auckland autopsies, revisited.

PubMed

Lum, Dennis; Koelmeyer, Timothy

2005-03-11

To review the cases of tuberculosis found at autopsy in the Auckland Coronial Autopsy Service in the previous 10 years, and compare the results with that of a similar study for the period 1975 to 1992. Cases which were not diagnosed prior to autopsy are scrutinised as to why the diagnosis may have been missed. A computerised search of the Forensic Pathology Department database at Auckland Hospital for cases of tuberculosis or atypical mycobacterial infection found at autopsy was done. Basic demographic data, past medical history, and police reports were analysed. The cases were placed into five groups for analysis. A total of 30 cases of tuberculosis (including 3 cases of atypical mycobacterial infection) were found. A large proportion (70%) was undiagnosed before death, and each case was potentially infective. Two cases had respiratory symptoms suggestive of tuberculosis, and a further 5 cases had generalised symptoms which were unexplained yet tuberculosis was not considered. In those cases that were missed, the autopsy played a vital role by identifying the previously undiagnosed cases of tuberculosis and ensuring contact screening. Awareness of tuberculosis and its increasing prevalence in New Zealand is essential for minimising missed diagnoses.

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

PubMed Central

Devrim, İlker; Aktürk, Hüseyin; Bayram, Nuri; Apa, Hurşit; Tulumoğlu, Şener; Devrim, Fatma; Erdem, Tülin; Gulfidan, Gamze; Ayhan, Yüce; Tamsel, İpek; Can, Demet; Alper, Hüdaver

2014-01-01

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

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

PubMed Central

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

2016-01-01

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

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

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…

[Immigrants treated for tuberculosis in Mazovian Center for Treatment of Lung Diseases and Tuberculosis in Otwock].

PubMed

Jagodziński, Jacek; Zielonka, Tadeusz M

2010-01-01

Migration of population contributes to the transmission of tuberculosis (TB), particularly multidrug-resistant tuberculosis. In the countries of Western Europe, the immigrants' inflow contributes to the deterioration of the epidemiological situation. Majority of newly detected TB cases in some countries were affirmed among immigrant and foreign born population. In Poland, this problem has not been investigated up to 2005. The aim of the study was the assessment of the occurrence of tuberculosis in foreigners treated in the Mazovian Centre for Treatment of Lung Diseases and Tuberculosis in Otwock. This work had a retrospective character. The number of cases of tuberculosis in foreigners admitted between 2002 and 2007 was calculated from the data base of the Mazovian Centre for Treatment of Lung Diseases and Tuberculosis; 125 patients, whose basic demographic data, bacteriological status and the radiological changes suggested TB, were included in the study. The foreigners made up to 0.5-1.7% all tuberculosis cases treated in Mazovian Centre for Treatment of Lung Diseases and Tuberculosis. Among confirmed cases, twenty four nationalities were seen. Nationals of the Russian Federation (coming from the Republic of Chechnya) formed the biggest group (24%), followed by the Vietnamese (21%) and the Ukrainians (12%). Most of all cases were young men (77%; average age - 34 years). Children made up to 12% of all cases. Tuberculosis of lungs was predominating, and there were culture confirmed extrapulmonary locations in 13.6% of cases. Bacteriological confirmation was achieved in 53% of cases, but up to 22.7% cases were resistant to one of the antituberculosis medicines and 13.6% was multidrug-resistant. Despite the fact, that foreigners made up a small proportion among all the patient treated for tuberculosis in Mazovia, their number systematically increases. High proportion of multidrug-resistant tuberculosis reported in foreign-born cases is a concern.

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

PubMed

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

2014-04-01

Bovine tuberculosis, caused by Mycobacterium bovis, remains one of the most important zoonotic health concerns worldwide. The transmission of Mycobacterium tuberculosis from humans to animals also occurs especially in countries where there is close interaction of humans with the animals. In the present study, thirty bovine lung tissue autopsy samples from an organized dairy farm located in North India were screened for the presence of Mycobacterium tuberculosis complex by smear microscopy, histopathological findings and PCR. Differential diagnosis of M. tuberculosis and M. bovis was made based on the deletion of mce-3 operon in M. bovis. The present study found eight of these samples positive for M. tuberculosis by multiplex PCR. Sequencing was performed on two PCR-positive representative samples and on annotation, and BLAST analysis confirmed the presence of gene fragment specific to Mycobacterium tuberculosis. The presence of M. tuberculosis in all the positive samples raises the possibility of human-to-cattle transmission and possible adaptation of this organism in bovine tissues. This study accentuates the importance of screening and differential diagnosis of Mycobacterium tuberculosis complex in humans and livestock for adopting effective TB control and eradication programmes. © 2014 Blackwell Verlag GmbH.

Implementation of a national anti-tuberculosis drug resistance survey in Tanzania

PubMed Central

Chonde, Timothy M; Doulla, Basra; van Leth, Frank; Mfinanga, Sayoki GM; Range, Nyagosya; Lwilla, Fred; Mfaume, Saidi M; van Deun, Armand; Zignol, Matteo; Cobelens, Frank G; Egwaga, Saidi M

2008-01-01

Background A drug resistance survey is an essential public health management tool for evaluating and improving the performance of National Tuberculosis control programmes. The current manuscript describes the implementation of the first national drug resistance survey in Tanzania. Methods Description of the implementation process of a national anti-tuberculosis drug resistance survey in Tanzania, in relation to the study protocol and Standard Operating Procedures. Results Factors contributing positively to the implementation of the survey were a continuous commitment of the key stakeholders, the existence of a well organized National Tuberculosis Programme, and a detailed design of cluster-specific arrangements for rapid sputum transportation. Factors contributing negatively to the implementation were a long delay between training and actual survey activities, limited monitoring of activities, and an unclear design of the data capture forms leading to difficulties in form-filling. Conclusion Careful preparation of the survey, timing of planned activities, a strong emphasis on data capture tools and data management, and timely supervision are essential for a proper implementation of a national drug resistance survey. PMID:19116022

[Submitting to disease, controlling disease, industrialization and medical technology: the case of tuberculosis].

PubMed

Thebaud, A; Lert, F

1985-01-01

This article presents an overview of the research work undertaken in France and Algeria on tuberculosis and the application of tuberculosis treatments. Tuberculosis is one of the best medical pointers to social inequality. The disease is seen here as typical of the links between industrialization and health, with regard to the evolution of the epidemiological model and the influence of innovational+ treatments, based on chemotherapy, on the organization of care for tubercular patients, together with the socio-economic and cultural changes that have affected both French and Algerian society during the twentieth century. The first part of the article shows how the epidemiology of tuberculosis tends to vary in accordance with the dynamic evolution of social relationships as industrialization occurs in each country, and how world-wide epidemiological trends are one of the best medical pointers to the North-South divide. The second part of the article is given over to a study of the way in which the application of tuberculosis treatments in both France and Algeria is a function of the organization of the health system in each country, of the status and power of the medical profession within society, and of the impact of technical innovations on the changing forms of care for tubercular patients in both countries. In France, it can be seen that the structure of the system set up to combat tuberculosis in the inter-war years has tended to remain unchanged, despite the opportunities for re-organization of tuberculosis treatment and for making therapy less onerous which have arisen as the incidence of the disease has dropped and antibiotics have been introduced. This resistance to change seems due primarily to the difficulty of achieving redeployment of medical staff, and the inertia caused by the rigid structure of tuberculosis care within the French socio-medical system.(ABSTRACT TRUNCATED AT 250 WORDS)

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 entire...

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 entire...

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 entire...

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 entire...

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 entire...

Critical role of toll-like receptor 9 in morphine and Mycobacterium tuberculosis-Induced apoptosis in mice.

PubMed

Chen, Lin; Shi, Wanliang; Li, Hui; Sun, Xiuli; Fan, Xionglin; Lesage, Gene; Li, Hui; Li, Yi; Zhang, Yi; Zhang, Xiumei; Zhang, Ying; Yin, Deling

2010-02-19

Although it is established that opioid and Mycobacterium tuberculosis are both public health problems, the mechanisms by which they affect lung functions remain elusive. We report here that mice subjected to chronic morphine administration and M. tuberculosis infection exhibited significant apoptosis in the lung in wild type mice as demonstrated by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. Morphine and M. tuberculosis significantly induced the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, deficiency in TLR9 significantly inhibited the morphine and M. tuberculosis induced apoptosis in the lung. In addition, chronic morphine treatment and M. tuberculosis infection enhanced the levels of cytokines (TNF-alpha, IL-1beta, and IL-6) in wild type mice, but not in TLR9 knockout (KO) mice. The bacterial load was much lower in TLR9 KO mice compared with that in wild type mice following morphine and M. tuberculosis treatment. Morphine alone did not alter the bacterial load in either wild type or TLR9 KO mice. Moreover, administration of morphine and M. tuberculosis decreased the levels of phosphorylation of Akt and GSK3beta in the wild type mice, but not in TLR9 KO mice, suggesting an involvement of Akt/GSK3beta in morphine and M. tuberculosis-mediated TLR9 signaling. Furthermore, administration of morphine and M. tuberculosis caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type mice, but not in TLR9 KO mice, indicating a role of Bcl-2 family in TLR9-mediated apoptosis in the lung following morphine and M. tuberculosis administration. These data reveal a role for TLR9 in the immune response to opioids during M. tuberculosis infection.

Antibodies and tuberculosis: finally coming of age?

PubMed

Li, Hao; Javid, Babak

2018-06-05

Are antibodies important for protection against tuberculosis? The jury has been out for more than 100 years. B cell depletion in experimental Mycobacterium tuberculosis infection failed to identify a major role for these cells in immunity to tuberculosis. However, recent identification of naturally occurring antibodies in humans that are protective during M. tuberculosis infection has reignited the debate. Here, we discuss the evidence for a protective role for antibodies in tuberculosis and consider the feasibility of designing novel tuberculosis vaccines targeting humoral immunity.

[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.

The Role of B Cells and Humoral Immunity in Mycobacterium tuberculosis Infection

PubMed Central

Kozakiewicz, Lee; Phuah, Jiayao; Flynn, JoAnne

2014-01-01

Tuberculosis (TB) remains a serious threat to public health, causing 2 million deaths annually world-wide. The control of TB has been hindered by the requirement of long duration of treatment involving multiple chemotherapeutic agents, the increased susceptibility to Mycobacterium tuberculosis infection in the HIV-infected population, and the development of multi-drug resistant and extensively resistant strains of tubercle bacilli. An efficacious and cost-efficient way to control TB is the development of effective anti-TB vaccines. This measure requires thorough understanding of the immune response to M. tuberculosis. While the role of cell-mediated immunity in the development of protective immune response to the tubercle bacillus has been well established, the role of B cells in this process is not clearly understood. Emerging evidence suggests that B cells and humoral immunity can modulate the immune response to various intracellular pathogens, including M. tuberculosis. These lymphocytes form conspicuous aggregates in the lungs of tuberculous humans, non-human primates, and mice, which display features of germinal center B cells. In murine TB, it has been shown that B cells can regulate the level of granulomatous reaction, cytokine production, and the T cell response. This chapter discusses the potential mechanisms by which specific functions of B cells and humoral immunity can shape the immune response to intracellular pathogens in general, and to M. tuberculosis in particular. Knowledge of the B cell-mediated immune response to M. tuberculosis may lead to the design of novel strategies, including the development of effective vaccines, to better control TB. PMID:23468112

Mycobacterium tuberculosis and non-tuberculous mycobacteria isolates from HIV-infected patients in Guangxi, China.

PubMed

Lan, R; Yang, C; Lan, L; Ou, J; Qiao, K; Liu, F; Gao, Q

2011-12-01

Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV) infected persons. The prevalence of infection with Mycobacterium tuberculosis and non-tuberculous mycobacteria (NTM) in HIV-infected patients in China is unknown. To estimate the prevalence of M. tuberculosis and NTM in HIV-infected patients in Guangxi Province, determine their drug resistance profiles, and evaluate the genotype patterns of M. tuberculosis strains. Samples were collected from two HIV designated hospitals in Guangxi Province between 2005 and 2008. HIV-infected patients who were culture-positive for mycobacteria were included. Drug susceptibility testing was performed for mycobacterial isolates. NTM species was identified by sequencing, and M. tuberculosis isolates were genotyped using the variable number of tandem repeats method. M. tuberculosis and NTM were identified in respectively 117 (53%) and 102 (47%) HIV-infected patients. Drug resistance was found in 27% and multi-drug-resistant TB (MDR-TB) in 11% of the patients with TB. Previous treatment for TB was significantly associated with MDR-TB. Twenty (17%) TB patients belonged to eight VNTR-defined clusters. The high frequency of NTM among HIV-infected patients raises concerns about accurate species identification before the determination of appropriate treatment. The potential for TB transmission exists among HIV-infected patients. Intensified screening and effective treatment of TB-HIV co-infected patients is urgently needed.

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.

Conventional and molecular epidemiology of Tuberculosis in Manitoba

PubMed Central

Blackwood, Kym S; Al-Azem, Assaad; Elliott, Lawrence J; Hershfield, Earl S; Kabani, Amin M

2003-01-01

Background To describe the demographic and geographic distribution of tuberculosis (TB) in Manitoba, thus determining risk factors associated with clustering and higher incidence rates in distinct subpopulations. Methods Data from the Manitoba TB Registry was compiled to generate a database on 855 patients with tuberculosis and their contacts from 1992–1999. Recovered isolates of M. tuberculosis were typed by IS6110 restriction fragment length polymorphisms. Bivariate and multivariate logistic regression models were used to identify risk factors involved in clustering. Results A trend to clustering was observed among the Canadian-born treaty Aboriginal subgroup in contrast to the foreign-born. The dominant type, designated fingerprint type 1, accounts for 25.8% of total cases and 75.3% of treaty Aboriginal cases. Among type 1 patients residing in urban areas, 98.9% lived in Winnipeg. In rural areas, 92.8% lived on Aboriginal reserves. Statistical models revealed that significant risk factors for acquiring clustered tuberculosis are gender, age, ethnic origin and residence. Those at increased risk are: males (p < 0.05); those under age 65 (p < 0.01 for each age subgroup); treaty Aboriginals (p < 0.001), and those living on reserve land (p < 0.001). Conclusion Molecular typing of isolates in conjunction with contact tracing data supports the notion of the largest ongoing transmission of a single strain of TB within the treaty-status population of Canada recorded to date. This data demonstrates the necessity of continued surveillance of countries with low prevalence of the disease in order to determine and target high-risk populations for concentrated prevention and control measures. PMID:12917019

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. Copyright © 2015 The Authors.

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…

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…

Mycobacterium tuberculosis genome-wide screen exposes multiple CD8+ T cell epitopes

PubMed Central

Hammond, A S; Klein, M R; Corrah, T; Fox, A; Jaye, A; McAdam, K P; Brookes, R H

2005-01-01

Mounting evidence suggests human leucocyte antigen (HLA) class I-restricted CD8+ T cells play a role in protective immunity against tuberculosis yet relatively few epitopes specific for the causative organism, Mycobacterium tuberculosis, are reported. Here a total genome-wide screen of M. tuberculosis was used to identify putative HLA-B*3501 T cell epitopes. Of 479 predicted epitopes, 13 with the highest score were synthesized and used to restimulate lymphocytes from naturally exposed HLA-B*3501 healthy individuals in cultured and ex vivo enzyme-linked immunospot (ELISPOT) assays for interferon (IFN)-γ. All 13 peptides elicited a response that varied considerably between individuals. For three peptides CD8+ T cell lines were expanded and four of the 13 were recognized permissively through the HLA-B7 supertype family. Although further testing is required we show the genome-wide screen to be feasible for the identification of unknown mycobacterial antigens involved in immunity against natural infection. While the mechanisms of protective immunity against M. tuberculosis infection remain unclear, conventional class I-restricted CD8+ T cell responses appear to be widespread throughout the genome. PMID:15762882

Urogenital tuberculosis: definition and classification.

PubMed

Kulchavenya, Ekaterina

2014-10-01

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

Tuberculosis and HIV at the national level in Kenya: results from the Second Kenya AIDS Indicator Survey.

PubMed

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

2014-05-01

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. 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. 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. 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.

Extrapulmonary involvement in pediatric tuberculosis.

PubMed

Kritsaneepaiboon, Supika; Andres, Mariaem M; Tatco, Vincent R; Lim, Cielo Consuelo Q; Concepcion, Nathan David P

2017-09-01

Tuberculosis in childhood is clinically challenging, but it is a preventable and treatable disease. Risk factors depend on age and immunity status. The most common form of pediatric tuberculosis is pulmonary disease, which comprises more than half of the cases. Other forms make up the extrapulmonary tuberculosis that involves infection of the lymph nodes, central nervous system, gastrointestinal system, hepatobiliary tree, and renal and musculoskeletal systems. Knowledge of the imaging characteristics of pediatric tuberculosis provides clues to diagnosis. This article aims to review the imaging characteristics of common sites for extrapulmonary tuberculous involvement in children.

Tackling tuberculosis: Insights from an international TB Summit in London

PubMed Central

Maitra, Arundhati; Danquah, Cynthia A; Scotti, Francesca; Howard, Tracey K; Kamil, Tengku K; Bhakta, Sanjib

2015-01-01

Tuberculosis (TB) poses a grave predicament to the world as it is not merely a scientific challenge but a socio-economic burden as well. A prime cause of mortality in human due to an infectious disease; the malady and its cause, Mycobacterium tuberculosis have remained an enigma with many questions that remain unanswered. The ability of the pathogen to survive and switch between varied physiological states necessitates a protracted therapeutic regimen that exerts an excessive strain on low-resource countries. To complicate things further, there has been a significant rise of antimicrobial resistance. Existing control measures, including treatment regimens have remained fairly uniform globally for at least half a century and require reinvention. Overcoming the societal and scientific challenges requires an increase in dialog to identify key regions that need attention and effective partners with whom successful collaborations can be fostered. In this report, we explore the discussions held at the International TB Summit 2015 hosted by EuroSciCon, which served as an excellent platform for researchers to share their recent findings. Ground-breaking results require outreach to affect policy design, governance and control of the disease. Hence, we feel it is important that meetings such as these reach a wider, global audience. PMID:26151309

Nutritional supplements for people being treated for active tuberculosis.

PubMed

Sinclair, David; Abba, Katharine; Grobler, Liesl; Sudarsanam, Thambu D

2011-11-09

benefit on treatment completion, and clearance of the bacteria from the sputum, but these findings have not been confirmed in larger trials elsewhere (VERY LOW quality evidence).The provision of free food or high-energy nutritional products probably does produce a modest increase in weight gain during treatment for active tuberculosis (MODERATE quality evidence). Two small studies provide some evidence that physical function and quality of life may also be improved but the trials were too small to have much confidence in the result (LOW quality evidence). These effects were not seen in the one trial which included only human immunodeficiency virus (HIV)-positive patients.Micronutrient supplementation Five trials assessed multi-micronutrient supplementation in doses up to ten times the dietary reference intake, and 12 trials assessed single or dual micronutrient supplementation.There is insufficient evidence to judge whether multi-micronutrients have a beneficial effect on mortality in HIV- negative patients with tuberculosis (VERY LOW quality evidence), but the available studies show that multi-micronutrients probably have little or no effect on mortality in HIV-positive patients with tuberculosis (MODERATE quality evidence). No studies have assessed the effects of multi-micronutrients on cure, or treatment completion.Multi-micronutrient supplements may have little or no effect on the proportion of tuberculosis patients remaining sputum positive during the first eight weeks (LOW quality evidence), and probably have no effect on weight gain during treatment (MODERATE quality evidence). No studies have assessed quality of life.Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation. In contrast, plasma levels of zinc, vitamin D and E, and selenium may be improved by supplementation during the early stages of tuberculosis treatment, but a consistent benefit on tuberculosis treatment outcomes or nutritional

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, 1968...

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, 1968...

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, 1968...

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, 1968...

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, 1968...

Highly Sensitive Detection of Isoniazid Heteroresistance in Mycobacterium tuberculosis by DeepMelt Assay.

PubMed

Liang, Bin; Tan, Yaoju; Li, Zi; Tian, Xueshan; Du, Chen; Li, Hui; Li, Guoli; Yao, Xiangyang; Wang, Zhongan; Xu, Ye; Li, Qingge

2018-02-01

Detection of heteroresistance of Mycobacterium tuberculosis remains challenging using current genotypic drug susceptibility testing methods. Here, we described a melting curve analysis-based approach, termed DeepMelt, that can detect less-abundant mutants through selective clamping of the wild type in mixed populations. The singleplex DeepMelt assay detected 0.01% katG S315T in 10 5 M. tuberculosis genomes/μl. The multiplex DeepMelt TB/INH detected 1% of mutant species in the four loci associated with isoniazid resistance in 10 4 M. tuberculosis genomes/μl. The DeepMelt TB/INH assay was tested on a panel of DNA extracted from 602 precharacterized clinical isolates. Using the 1% proportion method as the gold standard, the sensitivity was found to be increased from 93.6% (176/188, 95% confidence interval [CI] = 89.2 to 96.3%) to 95.7% (180/188, 95% CI = 91.8 to 97.8%) compared to the MeltPro TB/INH assay. Further evaluation of 109 smear-positive sputum specimens increased the sensitivity from 83.3% (20/24, 95% CI = 64.2 to 93.3%) to 91.7% (22/24, 95% CI = 74.2 to 97.7%). In both cases, the specificity remained nearly unchanged. All heteroresistant samples newly identified by the DeepMelt TB/INH assay were confirmed by DNA sequencing and even partially by digital PCR. The DeepMelt assay may fill the gap between current genotypic and phenotypic drug susceptibility testing for detecting drug-resistant tuberculosis patients. Copyright © 2018 American Society for Microbiology.

Networks and tuberculosis: an undetected community outbreak involving public places.

PubMed

Klovdahl, A S; Graviss, E A; Yaganehdoost, A; Ross, M W; Wanger, A; Adams, G J; Musser, J M

2001-03-01

After decades of decline in developed countries, there was a resurgence of tuberculosis in the mid-1980s accompanied by increased recognition that this infectious disease has long remained a major public health problem at the global level. New methods from molecular biology, in particular DNA 'fingerprinting' (of Mycobacterium tuberculosis), made it clear that current transmission and recent infection (in contrast to reactivation of earlier, latent infection) were much more significant than previously believed. Studies of tuberculosis outbreaks using these new tools pointed to complex networks through which infection was spreading and highlighted the need for new approaches to outbreak investigation and disease control. In the study reported here a new approach--combining methods from molecular biology, epidemiology and network analysis--was used to examine an outbreak of tuberculosis in Houston, Texas. Initial investigation using conventional strategies revealed few contacts among 37 patients with identical (six-band) DNA (IS6110-based) fingerprints but subsequent research uncovered over 40 places (including many gay bars) to which patients in this outbreak could be linked. Network methods were used to reconstruct an outbreak network and to quantify the relative importance (here, 'betweenness' centrality) of different actors (persons and places) playing a role in the outbreak. The multidisciplinary work provides the basis for a new approach to outbreak investigation and disease control.

Tolerability and Healthcare Utilization in Maintenance Hemodialysis Patients Undergoing Treatment for Tuberculosis-Related Conditions

PubMed Central

Hamadah, Abdurrahman M.; Beaulieu, Lynn M.; Wilson, John W.; Aksamit, Timothy R.; Gregoire, James R.; Williams, Amy W.; Dillon, John J.; Albright, Robert C.; Onuigbo, Macaulay; Iyer, Venkateshwaran K.; Hickson, LaTonya J.

2016-01-01

Background The incidence of tuberculosis in end-stage renal disease is significantly higher than the general population. Among those with kidney dysfunction, anti-tuberculosis treatment is associated with increased side effects, but the effect on healthcare utilization is unknown. Methods/Aim To assess patient-reported symptoms, adverse effects and describe changes in healthcare utilization patterns during treatment for tuberculosis, we conducted a case series (n=12) of patients receiving maintenance hemodialysis from Mayo Clinic Dialysis Services and concurrent drug therapy for tuberculosis from January 2002 through May 2014. Healthcare utilization (hospitalizations and emergency department visits independent of hospital admission) was compared before and during treatment. Results Patients were treated for latent (n=7) or active (n=5) tuberculosis. The majority of patients with latent disease were treated with isoniazid (n=5, 71%), while active-disease patients received a 4-drug regimen. Adverse effects were reported in 83% of patients. Compared to measurements prior to drug initiation, serum albumin and dialysis weights were similar at 3 months. Commonly reported anti-tuberculosis drug toxicities were described. More than half (58%) of patients were hospitalized at least once. No emergency department or hospital admissions occurred in the period prior to drug therapy, but healthcare utilization increased during treatment in the latent disease group (hospitalization rate per person-month: pre, 0 vs. post, 1). Conclusions Among hemodialysis patients, anti-tuberculosis therapy is associated with frequent patient-reported symptoms and increased healthcare utilization. Patients receiving treatment for latent disease may have the greatest increase in healthcare use. Careful monitoring and early complication detection may help optimize medication adherence and minimize hospitalizations. PMID:26859893

Overt diabetes mellitus among newly diagnosed Ugandan tuberculosis patients: a cross sectional study.

PubMed

Kibirige, Davis; Ssekitoleko, Richard; Mutebi, Edrisa; Worodria, William

2013-03-05

There is a documented increase of diabetes mellitus in Sub Saharan Africa, a region where tuberculosis is highly endemic. Currently, diabetes mellitus is one of the recognised risk factors of tuberculosis. No study has reported the magnitude of diabetes mellitus among tuberculosis patients in Uganda, one of the countries with a high burden of tuberculosis. This was a cross-sectional study conducted among 260 consenting adult patients with a confirmed diagnosis of tuberculosis admitted on the pulmonology wards of Mulago national referral and teaching hospital in Kampala, Uganda to determine the prevalence of diabetes mellitus and associated clinical factors. Laboratory findings as well as the socio-demographic and clinical data collected using a validated questionnaire was obtained. Point of care random blood sugar (RBS) testing was performed on all the patients prior to initiation of anti tuberculosis treatment. Diabetes mellitus was diagnosed if the RBS level was ≥ 200mg/dl in the presence of the classical symptoms of diabetes mellitus. The prevalence of diabetes mellitus among the admitted patients with tuberculosis was 8.5%. Only 5 (1.9%) patients with TB had a known diagnosis of diabetes mellitus at enrolment. Majority of the study participants with TB-DM co-infection had type 2 diabetes mellitus (n=20, 90.9%).At bivariate analysis, raised mean ALT concentrations of ≥80 U/L were associated with DM (OR-6.1, 95% CI 1.4-26.36, p=0.032) and paradoxically, HIV co-infection was protective of DM (OR-0.32, 95% CI 0.13-0.79, P=0.016). The relationship between DM and HIV as well as that with ALT remained statistically significant at multivariate analysis (HIV: OR- 0.17 95%CI 0.06-0.51, p=0.002 and ALT: OR-11.42 95%CI 2.15-60.59, p=0.004). This study demonstrates that diabetes mellitus is common among hospitalized tuberculosis patients in Uganda. The significant clinical predictors associated with diabetes mellitus among tuberculosis patients were HIV co-infection and

Localized hepatic tuberculosis presenting as severe hypercalcemia.

PubMed

Arrais Morais, Matheus; Cardoso Teixeira, Lorena Lane; de Sousa Brandão Torres, Dennyse; da Rocha Klautau Neto, Prócion Barreto; Machado Kahwage, Amanda

2018-04-01

Hypercalcemia might present itself in association with granulomatous diseases such as tuberculosis. We report a rare case of a 62-year-old man with hypercalcemia due to hepatic tuberculosis. The diagnosis was based on laparoscopic and a histopathological examination. After treatment with anti-tuberculosis medication, the patient's serum calcium levels were within normal limits. Tuberculosis needs to be excluded as a diagnosis in any febrile patient with hypercalcemia, especially in countries where tuberculosis is endemic. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

2011-01-01

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

Initial experience with GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.

PubMed

Patil, Naveen; Saba, Hamida; Marco, Asween; Samant, Rohan; Mukasa, Leonard

2014-01-01

Mycobacterium tuberculosis remains one of the most significant causes of death from an infectious agent. Rapid and accurate diagnosis of pulmonary and extra-pulmonary tuberculosis (TB) is still a great challenge. The GeneXpert MTB/RIF assay is a novel integrated diagnostic system for the diagnosis of tuberculosis and rapid detection of Rifampin (RIF) resistance in clinical specimens. In 2012, the Arkansas Tuberculosis Control Program introduced GeneXpert MTB/RIF assay to replace the labour-intensive Mycobacterium Tuberculosis Direct (MTD) assay. To rapidly diagnose TB within two hours and to simultaneously detect RIF resistance. Describe the procedure used to introduce GeneXpert MTB/RIF assay in the Arkansas Tuberculosis Control Program.Characterise the current gap in rapid M. tuberculosis diagnosis in Arkansas.Assess factors that predict acid fast bacilli (AFB) smearnegative but culture-positive cases in Arkansas.Illustrate, with two case reports, the role of GeneXpert MTB/RIF assay in reduction of time to confirmation of M. tuberculosis diagnosis in the first year of implementation. Between June 2012 and June 2013, all AFB sputum smearpositive cases and any others, on request by the physician, had GeneXpert MTB/RIF assay performed as well as traditional M. tuberculosis culture and susceptibilities using Mycobacteria Growth Indicator Tube (MGIT) 960 and Löwenstein-Jensen (LJ) slants. Surveillance data for January 2009-June 2013 was analysed to characterise sputum smear-negative but culture-positive cases. Seventy-one TB cases were reported from June 2012- June 2013. GeneXpert MTB/RIF assay identified all culture-positive cases as well as three cases that were negative on culture. Also, this rapid assay identified all six smear-negative but M. tuberculosis culture-positive cases; two of these cases are described as case reports. GeneXpert MTB/RIF assay has made rapid TB diagnosis possible, with tremendous potential in determining isolation of TB suspects on one

Unique Regulation of the DosR Regulon in the Beijing Lineage of Mycobacterium tuberculosis.

PubMed

Domenech, Pilar; Zou, Jason; Averback, Alexandra; Syed, Nishath; Curtis, Daniele; Donato, Samuel; Reed, Michael B

2017-01-15

The DosR regulon, a set of 48 genes normally expressed in Mycobacterium tuberculosis under conditions that inhibit aerobic respiration, is controlled via the DosR-DosS/DosT two-component system. While the regulon requires induction in most M. tuberculosis isolates, for members of the Beijing lineage, its expression is uncoupled from the need for signaling. In our attempts to understand the mechanistic basis for this uncoupling in the Beijing background, we previously reported the identification of two synonymous single-nucleotide polymorphisms (SNPs) within the adjacent Rv3134c gene. In the present study, we have interrogated the impact of these SNPs on dosR expression in wild-type strains, as well as a range of dosR-dosS-dosT mutants, for both Beijing and non-Beijing M. tuberculosis backgrounds. In this manner, we have unequivocally determined that the C601T dosR promoter SNP is the sole requirement for the dramatic shift in the pattern of DosR regulon expression seen in this globally important lineage. Interestingly, we also show that DosT is completely nonfunctional within these strains. Thus, a complex series of evolutionary steps has led to the present-day Beijing DosR phenotype that, in turn, potentially confers a fitness advantage in the face of some form of host-associated selective pressure. Mycobacterium tuberculosis strains of the Beijing lineage have been described as being of enhanced virulence compared to other lineages, and in certain regions, they are associated with the dramatic spread of multidrug-resistant tuberculosis (TB). In terms of trying to understand the functional basis for these broad epidemiological phenomena, it is interesting that, in contrast to the other major lineages, the Beijing strains all constitutively overexpress members of the DosR regulon. Here, we identify the mutational events that led to the evolution of this unique phenotype. In addition, our work highlights the fact that important phenotypic differences exist between

Tuberculosis in Poland in 2012.

PubMed

Korzeniewska-Koseła, Maria

2014-01-01

To evaluate the main features of TB epidemiology in 2012 in Poland and to compare with the corresponding EU data. Analysis of case- based clinical and demographic data on TB patients from Central TB Register, of data submitted by laboratories on anti-TB drug susceptibility testing results in cases notified in 2012, data from National Institute of Public Health - National Institute of Hygiene on cases of tuberculosis as AIDS-defining disease, from Central Statistical Office on deaths from tuberculosis based on death certificates, data from ECDC report "Tuberculosis Surveillance in Europe, 2014 (situation in 2012). 7 542 TB cases were reported in Poland in 2012. The incidence rate was 19.6 cases per 100 000, with large variability between voivodships from 10.6 to 30.2. The mean annual decrease of TB incidence in 2008-2012 was 2.4%. 6 665 cases had no history of previous treatment; 17.3 per 100 000. The number of all notified pulmonary tuberculosis cases was 7 018; 18.2 per 100 000. The proportion of extrapulmonary tuberculosis among all registered cases was 6.9% (524 cases). In 2012, 36 patients had fibrous-cavernous pulmonary tuberculosis (0.5% of all cases of pulmonary tuberculosis). TB was diagnosed in 95 children (1.3% of all cases, incidence 1.6). The incidence of tuberculosis increased progressively with age to 34.8 among patients 65 years old and older. The mean age of new TB cases was 53.1 years. The incidence among men (27.4) was more than two times higher than among women (12.2). The incidence rate in rural population was lower than in urban; 20.2 vs. 18.6. Bacteriologically confirmed pulmonary cases (4870) constituted 69,4% of all pulmonary TB cases. The number of smear positive pulmonary TB cases was 2 778 (39.6% of all pulmonary cases). In 2012 in the all group of TB patients in Poland there were 276 (3.7%) of homeless and 1 905 (25.3%) of unemployed. There were 48 foreigners registered among all cases of tuberculosis in Poland (0.6%) and 243 cases

Domestic returns from investment in the control of tuberculosis in other countries.

PubMed

Schwartzman, Kevin; Oxlade, Olivia; Barr, R Graham; Grimard, Franque; Acosta, Ivelisse; Baez, Jeannette; Ferreira, Elizabeth; Melgen, Ricardo Elías; Morose, Willy; Salgado, Arturo Cruz; Jacquet, Vary; Maloney, Susan; Laserson, Kayla; Mendez, Ariel Pablos; Menzies, Dick

2005-09-08

We hypothesized that investments to improve the control of tuberculosis in selected high-incidence countries would prove to be cost saving for the United States by reducing the incidence of the disease among migrants. Using decision analysis, we estimated tuberculosis-related morbidity, mortality, and costs among legal immigrants and refugees, undocumented migrants, and temporary visitors from Mexico after their entry into the United States. We assessed the current strategy of radiographic screening of legal immigrants plus current tuberculosis-control programs alone and with the addition of either U.S.-funded expansion of the strategy of directly observed treatment, short course (DOTS), in Mexico or tuberculin skin testing to screen legal immigrants from Mexico. We also examined tuberculosis-related outcomes among migrants from Haiti and the Dominican Republic using the same three strategies. As compared with the current strategy, expanding the DOTS program in Mexico at a cost to the United States of 34.9 million dollars would result in 2591 fewer cases of tuberculosis in the United States, with 349 fewer deaths from the disease and net discounted savings of 108 million dollars over a 20-year period. Adding tuberculin skin testing to radiographic screening of legal immigrants from Mexico would result in 401 fewer cases of tuberculosis in the United States but would cost an additional 329 million dollars. Expansion of the DOTS program would remain cost saving even if the initial investment were doubled, if the United States paid for all antituberculosis drugs in Mexico, or if the decline in the incidence of tuberculosis in Mexico was less than projected. A 9.4 million dollars investment to expand the DOTS program in Haiti and the Dominican Republic would result in net U.S. savings of 20 million dollars over a 20-year period. U.S.-funded efforts to expand the DOTS program in Mexico, Haiti, and the Dominican Republic could reduce tuberculosis-related morbidity and

Delivering Patient-Centered Care in a Fragile State: Using Patient-Pathway Analysis to Understand Tuberculosis-Related Care Seeking in Pakistan

PubMed Central

Fatima, Razia; Haq, Mahboob Ul; Yaqoob, Aashifa; Mahmood, Nasir; Ahmad, Khawaja Laeeq; Osberg, Mike; Makayova, Julia; Hymoff, Aaron; Hanson, Christy

2017-01-01

Abstract Background Pakistan has the sixth largest population in the world and boasts the fifth greatest burden of tuberculosis. The Government of Pakistan has set the ambitious goal of zero deaths due to tuberculosis and universal access to tuberculosis care by 2020. Successfully reaching these goals is dependent on the country’s capacity to diagnose and successfully treat an estimated 200000 unnotified or missing patients with tuberculosis. Methods A patient-pathway analysis (PPA) was conducted at the national level, as well as for each of the 4 provinces, to assess the alignment between patient care seeking and the availability of tuberculosis diagnostic and treatment services. Results Almost 90% of patients initiated care in the private sector, which accounts for only 15% of facilities with the capacity for tuberculosis diagnosis and treatment. Across the country, nearly 50% of tuberculosis microscopy laboratories were located in public-sector–basic health units and regional health centers. However, very few patients initiated care in these facilities. Overall, tuberculosis case detection was high given the low likelihood of patients reaching facilities with the capacity for tuberculosis service delivery during their first visit. Discussion Improving the engagement of the informal sector and lower-level clinicians will improve the efficiency and timeliness of tuberculosis diagnosis for patients in Pakistan. Concurrently, the apparent strength of the referral networks connecting community-level workers and private clinicians to the public sector for tuberculosis diagnosis and treatment suggests that strengthening the capacity of the public sector could be valuable. PMID:29117348

[Multidrug-resistant tuberculosis (MDR-TB) in a black African carceral area: Experience of Mali].

PubMed

Toloba, Y; Ouattara, K; Soumaré, D; Kanouté, T; Berthé, G; Baya, B; Konaté, B; Keita, M; Diarra, B; Cissé, A; Camara, F S; Diallo, S

2018-02-01

Prison constitutes a risk factor for the emergence of multi-drug resistance of tuberculosis (MDR-TB). The aim of this work was to study MDR-TB in a black African carceral center. Prospective study from January to December 2016 at the central house of arrest for men, Bamako. The study population was composed of tuberculous detainee. The suspicion of MDR-TB was done in any tuberculosis case remained positive in the second month of first-line treatment or in contact with an MDR-TB case. Among 1622 detainee, 21 cases of pulmonary tuberculosis were notified (1.29%), with an annual incidence of 13 cases/1000 detainee, they were 16 cases of SP-PTB (microscopy smear positive tuberculosis) and five cases of microscopy smear negative tuberculosis. The mean age was 28±7 years, extremes of 18 and 46 years. A negative association was found between the notion of smoking and occupation in the occurrence of tuberculosis (OR=0.036, [95% CI: 0.03-0.04], P=0.03. Among the 21 tuberculosis cases notified, one confirmed case of MDR-TB was detected (4.7%). In the first semester of 2016 cohort, we notified a cure rate of 87.5% (7/8 SP-PTB cases), and the confirmed MDR-TB case on treatment (21-month regimen), evolution enameled of pulmonary and hearing sequelae at seven months treatment. It was the first case of MDR-TB detected in a prison in Mali. Late diagnosis, evolution is enameled of sequelae and side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Some Social and Forensic Aspects of Exhumation and Reinterment of Industrial Revolution Remains

PubMed Central

Duff, E. J.; Johnson, J. S.

1974-01-01

The aetiological aspects of exhumed remains from two burial sites were examined using 1839 and 1879 as years of comparison. We tried to discover whether the sample of recovered remains was representative of those buried. The state of the remains varied according to the type of soil and coffin material in which they were buried. At the earlier date most deaths were caused by infectious lesions rather than degenerative ones and 76% of those who died were below employable age—whereas in 1879 the commonest causes of death were tuberculosis (“phthisis”) and bronchitis, and 42% died before they could be employed. The registration of deaths were recorded more accurately at the later date, and it was easier to build up a picture of the age, sex, and occupation of the people who died. ImagesFIG. 1FIG. 2 PMID:4593709

[Treatment of tuberculosis in patients with comorbidities].

PubMed

Abe, Masahiro; Fujita, Akira

2013-12-01

Early detection and appropriate treatment are the keys to tuberculosis control. In particular, providing appropriate treatment for tuberculosis in patients with HIV infection, rheumatoid arthritis (RA), chronic hepatic disease, or renal failure necessitating hemodialysis, and taking appropriate measures against adverse reactions to antituberculosis drugs are issues of critical importance. This mini-symposium, four experts explained the current status of "treatment of tuberculosis in patients with comorbidities" and proposed measures to address these problems. Dr. Aoki talked about "HIV infection complicated by tuberculosis." To the next, Dr. Yoshinaga gave a talk on "treatment of tuberculosis in RA patients receiving biological agents. Further, Dr. Sasaki lectured on "tuberculosis in patients with hepatic disease/impairment". Lastly, Dr. Takamori gave a lecture on "tuberculosis in patients with renal disease and those on hemodialysis. Tuberculosis patients often have some underlying diseases, and adverse reactions caused by antituberculosis drugs, such as hepatic and renal impairments, are matters of concern. I believe that this mini-symposium has provided useful information for physicians engaged in tuberculosis treatment and for many other healthcare professionals as well.

The effect of tuberculosis and tuberculosis contact tracing on school function: an exploratory focus group study.

PubMed

Upshur, R E; Deadman, L; Howorth, P; Shortt, L

1999-01-01

Selected schools in East York, an ethnically diverse municipality of 110,000 people within Toronto. To explore school staff's attitudes and beliefs about the nature of tuberculosis and its possible effect on the function and culture of schools. Four focus groups of 6-8 school staff, lasting from 1 to 1.5 hours, were held in the spring of 1997 at four different schools deemed to be at high risk for tuberculosis contact tracing. The study identified the following dominant themes: fear of tuberculosis and its impact on school, lack of knowledge and the need for education concerning tuberculosis, and issues in multiculturalism. Tuberculosis was perceived by staff of East York schools to be a source of fear. Lack of accurate and reliable information concerning tuberculosis contributes to this situation. Staff identified age-specific and culturally relevant, educational initiatives as means to reduce this fear.

Vegetarian diet as a risk factor for tuberculosis in immigrant south London Asians.

PubMed Central

Strachan, D. P.; Powell, K. J.; Thaker, A.; Millard, F. J.; Maxwell, J. D.

1995-01-01

BACKGROUND--In a previous retrospective study of tuberculosis in south London among Asian immigrants from the Indian subcontinent Hindu Asians were found to have a significantly increased risk for tuberculosis compared with Muslims. This finding has been further investigated by examining the role of socioeconomic and lifestyle variables, including diet, as risk factors for tuberculosis in Asian immigrants from the Indian subcontinent resident in south London. METHODS--Using a case-control study technique Asian immigrants from the Indian subcontinent diagnosed with tuberculosis during the past 10 years and two Asian control groups (community and outpatient clinic controls) from the Indian subcontinent were investigated. Cases and community controls were approached by letter. A structured questionnaire concerning a range of demographic, migration, socioeconomic, dietary, and health topics was administered by a single trained interviewer to subjects (56 cases and 100 controls) who agreed to participate. RESULTS--The results confirmed earlier findings that Hindu Asians had an increased risk of tuberculosis compared with Muslims. However, further analysis revealed that religion had no independent influence after adjustment for vegetarianism (common among Hindu Asians). Unadjusted odds ratios for tuberculosis among vegetarians were 2.7 (95% CI 1.1 to 6.4) using community controls, and 4.3 (95% CI 1.8 to 10.4) using clinic controls. There was a trend of increasing risk of tuberculosis with decreasing frequency of meat or fish consumption. Lactovegetarians had an 8.5 fold risk (95% CI 1.6 to 45.4) compared with daily meat/fish eaters. Adjustment for a range of other socioeconomic, migration, and lifestyle variables made little difference to the relative risks derived using either community or clinic controls. CONCLUSIONS--These results indicate that a vegetarian diet is an independent risk factor for tuberculosis in immigrant Asians. The mechanism is unexplained. However

Childhood tuberculosis: progress requires an advocacy strategy now

PubMed Central

Sandgren, Andreas; Cuevas, Luis E.; Dara, Masoud; Gie, Robert P.; Grzemska, Malgorzata; Hawkridge, Anthony; Hesseling, Anneke C.; Kampmann, Beate; Lienhardt, Christian; Manissero, Davide; Wingfield, Claire; Graham, Stephen M.

2012-01-01

Childhood tuberculosis (TB) is a preventable and curable infectious disease that remains overlooked by public health authorities, health policy makers and TB control programmes. Childhood TB contributes significantly to the burden of disease and represents the failure to control transmission in the community. Furthermore, the pool of infected children constitutes a reservoir of infection for the future burden of TB. It is time to prioritise childhood TB, advocate for addressing the challenges and grasp the opportunities in its prevention and control. Herein, we propose a scientifically informed advocacy agenda developed at the International Childhood TB meeting held in Stockholm, Sweden, from March 17 to 18, 2011, which calls for a renewed effort to improve the situation for children affected by Mycobacterium tuberculosis exposure, infection or disease. The challenges and needs in childhood TB are universal and apply to all settings and must be addressed more effectively by all stakeholders. PMID:22337859

Tuberculosis Data and Statistics

MedlinePlus

... TB programs can use to design and prioritize effective public health interventions. Tuberculosis — United States, 2017 (Provisional Data) Take on Tuberculosis Infographic and Social Media Graphics Customizable Take on TB Infographic with Instructions ...

Tuberculosis Treatment and Pregnancy

MedlinePlus

... Search Form Controls Cancel Submit Search The CDC Tuberculosis (TB) Note: Javascript is disabled or is not ... message, please visit this page: About CDC.gov . Tuberculosis Basic TB Facts How TB Spreads Latent TB ...

Impact of DOTS compared with DOTS-plus on multidrug resistant tuberculosis and tuberculosis deaths: decision analysis.

PubMed

Sterling, Timothy R; Lehmann, Harold P; Frieden, Thomas R

2003-03-15

This study sought to determine the impact of the World Health Organization's directly observed treatment strategy (DOTS) compared with that of DOTS-plus on tuberculosis deaths, mainly in the developing world. Decision analysis with Monte Carlo simulation of a Markov decision tree. People with smear positive pulmonary tuberculosis. Analyses modelled different levels of programme effectiveness of DOTS and DOTS-plus, and high (10%) and intermediate (3%) proportions of primary multidrug resistant tuberculosis, while accounting for exogenous reinfection. The cumulative number of tuberculosis deaths per 100 000 population over 10 years. The model predicted that under DOTS, 276 people would die from tuberculosis (24 multidrug resistant and 252 not multidrug resistant) over 10 years under optimal implementation in an area with 3% primary multidrug resistant tuberculosis. Optimal implementation of DOTS-plus would result in four (1.5%) fewer deaths. If implementation of DOTS-plus were to result in a decrease of just 5% in the effectiveness of DOTS, 16% more people would die with tuberculosis than under DOTS alone. In an area with 10% primary multidrug resistant tuberculosis, 10% fewer deaths would occur under optimal DOTS-plus than under optimal DOTS, but 16% more deaths would occur if implementation of DOTS-plus were to result in a 5% decrease in the effectiveness of DOTS CONCLUSIONS: Under optimal implementation, fewer tuberculosis deaths would occur under DOTS-plus than under DOTS. If, however, implementation of DOTS-plus were associated with even minimal decreases in the effectiveness of treatment, substantially more patients would die than under DOTS.

Tuberculosis among physicians in training.

PubMed

Rao, K G; Aggarwal, A N; Behera, D

2004-11-01

A total of 478 resident doctors working at our hospital were interviewed regarding development of tuberculosis after joining the hospital. Nine residents had developed tuberculosis, yielding an overall risk of 11.2 cases per 1000 person-years of exposure. Another 231 resident doctors newly admitted to the residency programme over a 1-year period were prospectively followed up over the next year. Four residents in this group developed tuberculosis within 1 year of joining the hospital, yielding an overall incidence of 17.3/1000. Physicians in training have a high risk of developing active tuberculosis after nosocomial transmission.

Microarray analysis of Mycobacterium tuberculosis-infected monocytes reveals IL26 as a new candidate gene for tuberculosis susceptibility.

PubMed

Guerra-Laso, José M; Raposo-García, Sara; García-García, Silvia; Diez-Tascón, Cristina; Rivero-Lezcano, Octavio M

2015-02-01

Differences in the activity of monocytes/macrophages, important target cells of Mycobacterium tuberculosis, might influence tuberculosis progression. With the purpose of identifying candidate genes for tuberculosis susceptibility we infected monocytes from both healthy elderly individuals (a tuberculosis susceptibility group) and elderly tuberculosis patients with M. tuberculosis, and performed a microarray experiment. We detected 78 differentially expressed transcripts and confirmed these results by quantitative PCR of selected genes. We found that monocytes from tuberculosis patients showed similar expression patterns for these genes, regardless of whether they were obtained from younger or older patients. Only one of the detected genes corresponded to a cytokine: IL26, a member of the interleukin-10 (IL-10) cytokine family which we found to be down-regulated in infected monocytes from tuberculosis patients. Non-infected monocytes secreted IL-26 constitutively but they reacted strongly to M. tuberculosis infection by decreasing IL-26 production. Furthermore, IL-26 serum concentrations appeared to be lower in the tuberculosis patients. When whole blood was infected, IL-26 inhibited the observed pathogen-killing capability. Although lymphocytes expressed IL26R, the receptor mRNA was not detected in either monocytes or neutrophils, suggesting that the inhibition of anti-mycobacterial activity may be mediated by lymphocytes. Additionally, IL-2 concentrations in infected blood were lower in the presence of IL-26. The negative influence of IL-26 on the anti-mycobacterial activity and its constitutive presence in both serum and monocyte supernatants prompt us to propose IL26 as a candidate gene for tuberculosis susceptibility. © 2014 John Wiley & Sons Ltd.

Tag Array gene chip rapid diagnosis anti-tuberculosis drug resistance in pulmonary tuberculosis -a feasibility study.

PubMed

Wu, Wenjie; Cheng, Peng; Lyu, Jingtong; Zhang, Zehua; Xu, Jianzhong

2018-05-01

We developed a Tag Array chip for detecting first- and second-line anti tuberculosis drug resistance in pulmonary tuberculosis and compared the analytical performance of the gene chip to that of phenotypic drug susceptibility testing (DST). From November 2011 to April 2016.234 consecutive culture-confirmed, clinically and imaging diagnosed patients with pulmonary tuberculosis from Southwest Hospital, Chongqing were enrolled into the study. Specimens collected during sputum or bronchoalveolar lavage fluid from the pulmonary tuberculosis patients were subjected to M. tuberculosis species identification and drug-resistance detection by the Tag Array gene chip, and evaluate the sensitivity and specificity of chip. A total of 186 patients was diagnosed drug-resistant tuberculosis. The detection of rifampicin (RFP), isoniazid (INH), fluoroquinolones (FQS), streptomycin (SM) resistance genes was highly sensitive and specific: however, for detection of amikacin (AMK), capreomycin (CPM), Kanamycin (KM), specificity was higher, but sensitivity was lower. Sensitivity for the detection of a mutation in the eis promoter region could be improved. The detection sensitivity of the EMB resistance gene was low, therefore it is easy to miss a diagnosis of EMB drug resistance, but its specificity was high. Tag Array chip can achieve rapid, accurate and high-throughput detection of tuberculosis resistance in pulmonary tuberculosis, which has important clinical significance and feasibility. Copyright © 2018. Published by Elsevier Ltd.

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

Evaluation of profile and functionality of memory T cells in pulmonary tuberculosis.

PubMed

Tonaco, Marcela M; Moreira, Jôsimar D; Nunes, Fernanda F C; Loures, Cristina M G; Souza, Larissa R; Martins, Janaina M; Silva, Henrique R; Porto, Arthur Henrique R; Toledo, Vicente Paulo C P; Miranda, Silvana S; Guimarães, Tânia Mara P D

2017-12-01

The cells T CD4+ T and CD8+ can be subdivided into phenotypes naïve, T of central memory, T of effector memory and effector, according to the expression of surface molecules CD45RO and CD27. The T lymphocytes are cells of long life with capacity of rapid expansion and function, after a new antigenic exposure. In tuberculosis, it was found that specific memory T cells are present, however, gaps remain about the role of such cells in the disease immunology. In this study, the phenotypic profile was analyzed and characterized the functionality of CD4+ T lymphocytes and CD8+ T cells of memory and effector, in response to specific stimuli in vitro, in patients with active pulmonary TB, compared to individuals with latent infection with Mycobacterium tuberculosis the ones treated with pulmonary TB. It was observed that the group of patients with active pulmonary tuberculosis was the one which presented the highest proportion of cells T CD4+ of central memory IFN-ɣ+ e TNF-α+, suggesting that in TB, these T of central memory cells would have a profile of protective response, being an important target of study for the development of more effective vaccines; this group also developed lower proportion of CD8+ T effector lymphocytes than the others, a probable cause of specific and less effective response against the bacillus in these individuals; the ones treated for pulmonary tuberculosis were those who developed higher proportion of T CD4+ of memory central IL-17+ cells, indicating that the stimulation of long duration, with high antigenic load, followed by elimination of the pathogen, contribute to more significant generation of such cells; individuals with latent infection by M. tuberculosis and treated for pulmonary tuberculosis, showed greater response of CD8+ T effector lymphocytes IFN-ɣ+ than the controls, suggesting that these cells, as well as CD4+ T lymphocytes, have crucial role of protection against M. tuberculosis. These findings have contributed to a better

Anti-tubercular therapy for intraocular tuberculosis: A systematic review and meta-analysis.

PubMed

Kee, Ae Ra; Gonzalez-Lopez, Julio J; Al-Hity, Aws; Gupta, Bhaskar; Lee, Cecilia S; Gunasekeran, Dinesh Visva; Jayabalan, Nirmal; Grant, Robert; Kon, Onn Min; Gupta, Vishali; Westcott, Mark; Pavesio, Carlos; Agrawal, Rupesh

2016-01-01

Intraocular tuberculosis remains a diagnostic and management conundrum for both ophthalmologists and pulmonologists. We analyze the efficacy and safety of anti-tubercular therapy (ATT) in patients with intraocular tuberculosis and factors associated with favorable outcome. Twenty-eight studies are included in this review, with a total of 1,917 patients. Nonrecurrence of inflammation was observed in pooled estimate of 84% of ATT-treated patients (95% CI 79-89). There was minimal difference in the outcome between patients treated with ATT alone (85% successful outcome; 95% CI 25-100) and those with concomitant systemic corticosteroid (82%; 95% CI 73-90). The use of ATT may be of benefit to patients with suspected intraocular tuberculosis; however, this conclusion is limited by the lack of control group analysis and standardized recruitment and treatment protocols. We propose further prospective studies to better establish the efficacy of ATT and ascertain the factors associated with favorable treatment outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

[Miliary tuberculosis].

PubMed

Zaghba, N; El Hachimi, K; Benjelloun, H; Yassine, N

2018-02-01

Tuberculosis miliary is a severe and rare form of tuberculosis. It is often due to a haematogenous spread of the bacillus of Koch and represents less than 2 % of tuberculosis. We conducted a retrospective study of 81 cases of tuberculous miliary collected at the Department of respiratory diseases of the Ibn Rochd university hospital in Casablanca between September 2003 and November 2016. A female predominance was noted with 58 % of the cases. The average age was 36 years. The history of tuberculosis was found in eight cases and tuberculous tuberculosis in eleven cases, postpartum in five cases, diabetes in three cases and trisomy 21 in one case. The clinical picture was dominated by altered general status in all cases, and fever in 69 cases (86 %). Chest x-ray showed a miliary aspect in all cases, cardiomegaly in two cases, pyopneumothorax in three cases, and opacities excavated in five other cases. The intradermal tuberculin reaction, performed in all cases, was positive in 26 cases, and sputum oscillations were positive in 21 cases. The dissemination report found cerebromeningeal involvement in nine cases, with cerebral tuberculomas in five cases, pericarditis in four cases, mediastinal and peripheral adenopathies in nine cases each. Bouchut tubercles were found in nine cases. Antibacillary therapy was started as a matter of urgency, according to the national TB control program with the old regimen (2SHRZ/7RH) and the new regimen (2RHZEb/7RH) in all cases. The outcome was good in 55 cases (68.9 %), 17 patients were lost to follow-up, and 11 deaths were reported. We insist on this work on the severity of the tuberculous miliary and the need for early and urgent therapeutic management. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The effects of poverty and ageing on the increase in tuberculosis.

PubMed

Davies, P D

1999-04-01

Among the causes of the current increase in tuberculosis worldwide are poverty and ageing. It has been widely accepted that tuberculosis and poverty have been closely linked since the scientific study of the disease began. The decline of tuberculosis in developed countries before the arrival of specific chemotherapy was largely attributed to improvement in social conditions. With the rapidly increasing world population and the wider disparity of income, more and more people are falling into poverty, whichever way it is defined. Studies in the developed world show that the close association between tuberculosis and poverty remains. Some workers in the field even suggest that tuberculosis cannot be controlled until the issue of global poverty has been addressed. This may be too pessimistic. It may be possible to define accurately which aspects of poverty are most closely associated with tuberculosis and to deal with those specifically. Within developed countries longevity is increasing. The population now in their seventies, or older, even in developed countries, will have been alive when the disease was highly prevalent in the communities in which they lived. The majority will, therefore, have acquired infection, and in a substantial minority of these infection may reactivate to cause disease as the ageing process weakens host immunity. In the indigenous Caucasian population of Western Europe, rates of disease are highest in elderly males. Previous research showed that beyond the age of forty, the incidence of disease declined with increasing age. The higher rates in the elderly were a result of the residue of higher rates from birth cohorts born earlier. Data presented in this article suggest that this pattern may be altering such that the incidence of disease actually increases after a certain age is reached. This could have important repercussions for disease incidence in the emerging economies of the Pacific Rim, where longevity is increasing most rapidly.

[Tuberculosis among Trio-Indians in Surinam].

PubMed

van Crevel, R; van Doorninck, D J; van Ams, J E; Fat, H Tjon; Vreden, S G; van der Meer, J M

2004-02-28

Evaluation of the extent and possible causes of the increased incidence of tuberculosis among Amazonian Indians in Surinam. Descriptive. In two cross-sectional surveys in 1998 and 2000, the inhabitants of Kwamalasamutu, a village of Trio-Indians in Surinam, were examined for the presence of active and latent tuberculosis. Previous cases from the period 1995-2000 were evaluated retrospectively by consulting individual physicians and the archives of the 'Medische Zending' (Medical Mission), the 'Diakonessenhuis' hospital, the clinic for pulmonary diseases, and the Central Laboratory. Family ties and other factors that might be associated with tuberculosis were examined. Spoligotyping was done on all patient isolates. Between 1995 and 2000, active tuberculosis was diagnosed in 25 Indians from Kwamalasamutu, equal to 4.2 cases/1000 person-years (95% CI: 2.7-6.1). Tuberculin skin tests were positive in 105/733 Indians (14.3%). Cases of tuberculosis were found predominantly within certain families, who were genetically related. Spoligotyping of 5 Mycobacterium tuberculosis isolates from Trio-Indians showed unique patterns, which were also found in 34 isolates from elsewhere in Surinam. Tuberculosis was relatively common among Trio-Indians, clustering in certain families. This isolated tribe may have a genetic predisposition for tuberculosis, but their lifestyle and limited access to health care certainly play a role as well.

Mortality in Severe Human Immunodeficiency Virus-Tuberculosis Associates With Innate Immune Activation and Dysfunction of Monocytes.

PubMed

Janssen, Saskia; Schutz, Charlotte; Ward, Amy; Nemes, Elisa; Wilkinson, Katalin A; Scriven, James; Huson, Mischa A; Aben, Nanne; Maartens, Gary; Burton, Rosie; Wilkinson, Robert J; Grobusch, Martin P; Van der Poll, Tom; Meintjes, Graeme

2017-07-01

Case fatality rates among hospitalized patients diagnosed with human immunodeficiency virus (HIV)-associated tuberculosis remain high, and tuberculosis mycobacteremia is common. Our aim was to define the nature of innate immune responses associated with 12-week mortality in this population. This prospective cohort study was conducted at Khayelitsha Hospital, Cape Town, South Africa. Hospitalized HIV-infected tuberculosis patients with CD4 counts <350 cells/µL were included; tuberculosis blood cultures were performed in all. Ambulatory HIV-infected patients without active tuberculosis were recruited as controls. Whole blood was stimulated with Escherichia coli derived lipopolysaccharide, heat-killed Streptococcus pneumoniae, and Mycobacterium tuberculosis. Biomarkers of inflammation and sepsis, intracellular (flow cytometry) and secreted cytokines (Luminex), were assessed for associations with 12-week mortality using Cox proportional hazard models. Second, we investigated associations of these immune markers with tuberculosis mycobacteremia. Sixty patients were included (median CD4 count 53 cells/µL (interquartile range [IQR], 22-132); 16 (27%) died after a median of 12 (IQR, 0-24) days. Thirty-one (52%) grew M. tuberculosis on blood culture. Mortality was associated with higher concentrations of procalcitonin, activation of the innate immune system (% CD16+CD14+ monocytes, interleukin-6, tumour necrosis factor-ɑ and colony-stimulating factor 3), and antiinflammatory markers (increased interleukin-1 receptor antagonist and lower monocyte and neutrophil responses to bacterial stimuli). Tuberculosis mycobacteremia was not associated with mortality, nor with biomarkers of sepsis. Twelve-week mortality was associated with greater pro- and antiinflammatory alterations of the innate immune system, similar to those reported in severe bacterial sepsis. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

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

IFNγ Response to Mycobacterium tuberculosis, Risk of Infection and Disease in Household Contacts of Tuberculosis Patients in Colombia

PubMed Central

Marín, Nancy D.; Marín, Diana M.; López, Lucelly; Henao, Hanna M.; Martínez, Teresita; Villa, Liliana; Barrera, Luis F.; Ortiz, Blanca L.; Ramírez, María E.; Montes, Carlos J.; Oquendo, María C.; Arango, Lisandra M.; Riaño, Felipe; Aguirre, Carlos; Bustamante, Alberto; Belisle, John T.; Dobos, Karen; Mejía, Gloria I.; Giraldo, Margarita R.; Brennan, Patrick J.; Robledo, Jaime; Arbeláez, María P.; Rojas, Carlos A.; García, Luis F.

2009-01-01

Objectives Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNγ produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNγ levels in HHCs correlate with tuberculosis development. Methods A cohort of 2060 HHCs was followed for 2–3 years after exposure to a tuberculosis case. Besides TST, IFNγ responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. Results Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNγ response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNγ responders to CFP-10 (HR 1.82 95% CI 0.79–4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNγ producers was observed (trend Log rank p = 0.007). Discussion CFP-10-induced IFNγ production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high

Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice.

PubMed

Reece, Stephen T; Vogelzang, Alexis; Tornack, Julia; Bauer, Wolfgang; Zedler, Ulrike; Schommer-Leitner, Sandra; Stingl, Georg; Melchers, Fritz; Kaufmann, Stefan H E

2018-04-23

Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M. tuberculosis propagate hallmarks of disease if nitric oxide-mediated killing of bacteria is defective.

Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice

PubMed Central

Reece, Stephen T; Vogelzang, Alexis; Tornack, Julia; Bauer, Wolfgang; Zedler, Ulrike; Schommer-Leitner, Sandra; Stingl, Georg; Melchers, Fritz; Kaufmann, Stefan H E

2018-01-01

Abstract Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M. tuberculosis propagate hallmarks of disease if nitric oxide-mediated killing of bacteria is defective. PMID:29471332

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.

Expression of fibroblast specific protein-1 in pleural tuberculosis and its clinical biological significance

PubMed Central

2014-01-01

Background Fibroblast specific protein-1 (S100A4) is related with many fibrotic diseases, but its role in the pathogenesis of pleural fibrosis has not been fully elucidated. Then we aim to investigate the expression and effect of fibroblast specific protein-1 (S100A4) in pleural tuberculosis and, subsequently, pleural fibrosis. Methods The expression of S100A4 in pleura was examined in 30 patients with pleural tuberculosis and 5 control (disease-free) patients by immunohistochemistry using the streptavidin-peroxidase (S-P) conjugated method. Results The expression of S100A4 in pleura was mainly distributed in the nucleus and cytoplasm of fibroblasts and vascular endothelial cells, and the positive rate was 90.0% (27 out of 30 patients with pleural tuberculosis). There were no expressions of S100A4 in the control group. In the pleura of all 30 patients with pleural tuberculosis, S100A4 had a higher expression in the two- to eight-week duration of the disease. Conclusions S100A4 plays an important role in the phenotypic transformation of pleural mesothelial cells and the development of pleural fibrosis. PMID:24885536

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

PubMed Central

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

2012-01-01

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

Association of tuberculosis with multimorbidity and social networks

PubMed Central

Valenzuela-Jiménez, Hiram; Manrique-Hernández, Edgar Fabian; Idrovo, Alvaro Javier

2017-01-01

ABSTRACT The combination of tuberculosis with other diseases can affect tuberculosis treatment within populations. In the present study, social network analysis of data retrieved from the Mexican National Epidemiological Surveillance System was used in order to explore associations between the number of contacts and multimorbidity. The node degree was calculated for each individual with tuberculosis and included information from 242 contacts without tuberculosis. Multimorbidity was identified in 49.89% of individuals. The node degrees were highest for individuals with tuberculosis + HIV infection (p < 0.04) and lowest for those with tuberculosis + pulmonary edema (p < 0.07). Social network analysis should be used as a standard method for monitoring tuberculosis and tuberculosis-related syndemics. PMID:28125153

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

USDA-ARS?s Scientific Manuscript database

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...

Polymorphisms in the prostaglandin receptor EP2 gene confers susceptibility to tuberculosis.

PubMed

Liang, Li; Zhang, Qing; Luo, Liu-Lin; Yue, Jun; Zhao, Yan-Lin; Han, Min; Liu, Li-Rong; Xiao, He-Ping

2016-12-01

Prostaglandin E2 (PGE2) is an important lipid mediator of the inflammatory immune response during acute and chronic infections. PGE2 modulates a variety of immune functions via four receptors (EP1-EP4), which mediate distinct PGE2 effects. Mice lacking EP2 are more susceptible to infection by Mycobacterium tuberculosis (M.tb), have a higher bacterial load, and increase size and number of granulomatous lesions. Our aim was to assess whether single nucleotide polymorphisms (SNPs) in EP2 increase the risk of tuberculosis. DNA re-sequencing revealed five common EP2 variants in the Chinese Han population. We sequenced the EP2 gene from 600 patients and 572 healthy controls to measure SNP frequencies in association with tuberculosis infections (TB) within the population. The rs937337 polymorphism is associated with increased risk to tuberculosis (p=0.0044, odds ratio [OR], 1.67; 95% confidential interval,1.22-2.27). The rs937337 AA genotype and the rs1042618 CC genotype were significantly associated with TB. An estimation of the frequencies of haplotypes revealed a single protective haplotype GACGC for tuberculosis (p=0.00096, odds ratio [OR], 0.56; 95% confidential interval, 0.41-0.77). Furthermore, we determined that the remaining SNPs of EP2 were nominally associated with clinical patterns of disease. We identified genetic polymorphisms in EP2 associated with susceptibility to tuberculosis within a Chinese population. Our data support that EP2 SNPs are genetic predispositions of increased susceptibility to TB and to different clinical patterns of disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Diagnostic Performance of Tuberculosis-Specific IgG Antibody Profiles in Patients with Presumptive Tuberculosis from Two Continents.

PubMed

Broger, Tobias; Basu Roy, Robindra; Filomena, Angela; Greef, Charles H; Rimmele, Stefanie; Havumaki, Joshua; Danks, David; Schneiderhan-Marra, Nicole; Gray, Christen M; Singh, Mahavir; Rosenkrands, Ida; Andersen, Peter; Husar, Gregory M; Joos, Thomas O; Gennaro, Maria L; Lochhead, Michael J; Denkinger, Claudia M; Perkins, Mark D

2017-04-01

Development of rapid diagnostic tests for tuberculosis is a global priority. A whole proteome screen identified Mycobacterium tuberculosis antigens associated with serological responses in tuberculosis patients. We used World Health Organization (WHO) target product profile (TPP) criteria for a detection test and triage test to evaluate these antigens. Consecutive patients presenting to microscopy centers and district hospitals in Peru and to outpatient clinics at a tuberculosis reference center in Vietnam were recruited. We tested blood samples from 755 HIV-uninfected adults with presumptive pulmonary tuberculosis to measure IgG antibody responses to 57 M. tuberculosis antigens using a field-based multiplexed serological assay and a 132-antigen bead-based reference assay. We evaluated single antigen performance and models of all possible 3-antigen combinations and multiantigen combinations. Three-antigen and multiantigen models performed similarly and were superior to single antigens. With specificity set at 90% for a detection test, the best sensitivity of a 3-antigen model was 35% (95% confidence interval [CI], 31-40). With sensitivity set at 85% for a triage test, the specificity of the best 3-antigen model was 34% (95% CI, 29-40). The reference assay also did not meet study targets. Antigen performance differed significantly between the study sites for 7/22 of the best-performing antigens. Although M. tuberculosis antigens were recognized by the IgG response during tuberculosis, no single antigen or multiantigen set performance approached WHO TPP criteria for clinical utility among HIV-uninfected adults with presumed tuberculosis in high-volume, urban settings in tuberculosis-endemic countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Drug Penetration Gradients Associated with Acquired Drug Resistance in Tuberculosis Patients.

PubMed

Dheda, Keertan; Lenders, Laura; Magombedze, Gesham; Srivastava, Shashikant; Raj, Prithvi; Arning, Erland; Ashcraft, Paula; Bottiglieri, Teodoro; Wainwright, Helen; Pennel, Timothy; Linegar, Anthony; Moodley, Loven; Pooran, Anil; Pasipanodya, Jotam G; Sirgel, Frederick A; van Helden, Paul D; Wakeland, Edward; Warren, Robin M; Gumbo, Tawanda

2018-06-07

Acquired resistance is an important driver of multidrug-resistant tuberculosis, even with good treatment adherence. However, exactly what initiates the resistance, and how it arises remains poorly understood. To identify the relationship between drug concentrations and drug susceptibility readouts (MICs) in the tuberculosis cavity. We recruited patients with medically incurable tuberculosis who were undergoing therapeutic lung resection whilst on treatment with the cocktail of second line anti-tuberculosis drugs. On the day of surgery antibiotic concentrations were measured in the blood and at seven pre-specified biopsy sites within each cavity. Mycobacterium tuberculosis was grown from each biopsy site, MICs of each drug identified, and whole genome sequencing performed. Spearman correlation coefficients between drug concentration and MIC were calculated. Fourteen patients treated for a median of 13 (range: 5-31) months were recruited. MICs and drug resistance-associated single nucleotide variants differed between the different geospatial locations within each cavity, and with pretreatment and serial sputum isolates, consistent with ongoing acquisition of resistance. However, pre-treatment sputum MIC had an accuracy of only 49.48% in predicting cavitary MICs. There were large concentration-distance gradients for each antibiotic. The location-specific concentrations inversely correlated with MICs (p<0.05), and therefore acquired resistance. Moreover, pharmacokinetic/pharmacodynamic exposures known to amplify drug-resistant subpopulations were encountered in all positions. These data inform interventional strategies relevant to drug delivery, dosing, and diagnostics to prevent the development of acquired resistance. The role of high intracavitary penetration as a biomarker of antibiotic efficacy, when assessing new regimens, requires clarification.

Mycobacterium tuberculosis Transcriptome Profiling in Mice with Genetically Different Susceptibility to Tuberculosis.

PubMed

Skvortsov, T A; Ignatov, D V; Majorov, K B; Apt, A S; Azhikina, T L

2013-04-01

Whole transcriptome profiling is now almost routinely used in various fields of biology, including microbiology. In vivo transcriptome studies usually provide relevant information about the biological processes in the organism and thus are indispensable for the formulation of hypotheses, testing, and correcting. In this study, we describe the results of genome-wide transcriptional profiling of the major human bacterial pathogen M. tuberculosis during its persistence in lungs. Two mouse strains differing in their susceptibility to tuberculosis were used for experimental infection with M. tuberculosis. Mycobacterial transcriptomes obtained from the infected tissues of the mice at two different time points were analyzed by deep sequencing and compared. It was hypothesized that the changes in the M. tuberculosis transcriptome may attest to the activation of the metabolism of lipids and amino acids, transition to anaerobic respiration, and increased expression of the factors modulating the immune response. A total of 209 genes were determined whose expression increased with disease progression in both host strains (commonly upregulated genes, CUG). Among them, the genes related to the functional categories of lipid metabolism, cell wall, and cell processes are of great interest. It was assumed that the products of these genes are involved in M. tuberculosis adaptation to the host immune system defense, thus being potential targets for drug development.

[Risk groups for tuberculosis in Chile].

PubMed

Herrera, Tania

2015-02-01

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

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. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Tuberculosis in Hispanics/Latinos

MedlinePlus

... Compartir ( PDF – 672k) Spanish Tuberculosis in Hispanics/Latinos Tuberculosis (TB) is a disease that is spread from person to person through the air. TB bacteria usually attack the lungs, but it can attack any part of the ...

Simplified Automated Image Analysis for Detection and Phenotyping of Mycobacterium tuberculosis on Porous Supports by Monitoring Growing Microcolonies

PubMed Central

den Hertog, Alice L.; Visser, Dennis W.; Ingham, Colin J.; Fey, Frank H. A. G.; Klatser, Paul R.; Anthony, Richard M.

2010-01-01

Background Even with the advent of nucleic acid (NA) amplification technologies the culture of mycobacteria for diagnostic and other applications remains of critical importance. Notably microscopic observed drug susceptibility testing (MODS), as opposed to traditional culture on solid media or automated liquid culture, has shown potential to both speed up and increase the provision of mycobacterial culture in high burden settings. Methods Here we explore the growth of Mycobacterial tuberculosis microcolonies, imaged by automated digital microscopy, cultured on a porous aluminium oxide (PAO) supports. Repeated imaging during colony growth greatly simplifies “computer vision” and presumptive identification of microcolonies was achieved here using existing publically available algorithms. Our system thus allows the growth of individual microcolonies to be monitored and critically, also to change the media during the growth phase without disrupting the microcolonies. Transfer of identified microcolonies onto selective media allowed us, within 1-2 bacterial generations, to rapidly detect the drug susceptibility of individual microcolonies, eliminating the need for time consuming subculturing or the inoculation of multiple parallel cultures. Significance Monitoring the phenotype of individual microcolonies as they grow has immense potential for research, screening, and ultimately M. tuberculosis diagnostic applications. The method described is particularly appealing with respect to speed and automation. PMID:20544033

Tuberculosis and liver disease: management issues.

PubMed

Sonika, Ujjwal; Kar, Premashis

2012-01-01

Tuberculosis is one of the most common diseases in India and has attained epidemic proportions. Tuberculosis and liver are related in many ways. Liver disease can occur due to hepatic tuberculosis or the treatment with various anti-tubercular drugs may precipitate hepatic injury or patients with chronic liver disease may develop tuberculosis and pose special management problems. Tuberculosis per se can affect liver in three forms. The most common form is the diffuse hepatic involvement, seen along with pulmonary or miliary tuberculosis. The second is granulomatous hepatitis and the third, much rarer form presents as focal/local tuberculoma or abscess. Tubercular disease of liver occurring along with pulmonary involvement as in disseminated tuberculosis is treated with standard regimen for pulmonary tuberculosis. Granulomatous hepatitis and tubercular liver abscess are treated like any other extra-pulmonary tubercular lesions without any extra risk of hepatotoxicity by anti-tubercular drugs. Treatment of tuberculosis in patients who already have a chronic liver disease poses various clinical challenges. There is an increased risk of drug induced hepatitis in these patients and its implications are potentially more serious in these patients as their hepatic reserve is already depleted. However, hepatotoxic anti-tubercular drugs can be safely used in these patients if the number of drugs used is adjusted appropriately. Thus, the main principle is to closely monitor the patient for signs of worsening liver disease and to reduce the number of hepatotoxic drugs in the anti-tubercular regimen according to the severity of underlying liver disease.

Molecular identification of Mycobacterium tuberculosis in cattle.

PubMed

Sweetline Anne, N; Ronald, B S M; Kumar, T M A Senthil; Kannan, P; Thangavelu, A

2017-01-01

Bovine tuberculosis continued to be a re-emerging problem in some countries especially in endemic areas due to the fact that human and animal health surveillance system is not adopted to diagnose the infection. This crisis can be attributed due to sharing of the same habitat especially in rural areas. In the present study, a total of 148 samples were collected from cattle for isolation over a period of 3 years from cattle with and without lesions, of which 67 isolates were obtained by culture. Fifty one isolates were identified as Mycobacterium tuberculosis complex (MTBC) by IS6110 PCR of which 43 (84.3%) were identified as M. tuberculosis and 08 (15.6%) were identified as M. bovis by using 12.7kb fragment multiplex PCR. Among this, 31 isolates which were positive for IS6110 PCR were subjected to spoligotyping and revealed 28 isolates belonging to MANU1 strain of M. tuberculosis. This study clearly indicates that high prevalence of M. tuberculosis than M. bovis in bovine was identified by means of culture and by molecular methods M. tuberculosis can affect cattle producing lesion in contradiction to the earlier thoughts. This study speculates that M. tuberculosis MANU1 strain infection in cattle could be due to spill over from human or other non specific hosts in tuberculosis endemic areas. Though bovine tuberculosis due to M. tuberculosis in cattle is not considered a serious threat worldwide, in countries where human TB is endemic, M. tuberculosis infection of cattle needs to be considered. Copyright © 2016 Elsevier B.V. All rights reserved.

bioA mutant of Mycobacterium tuberculosis shows severe growth defect and imparts protection against tuberculosis in guinea pigs

PubMed Central

Kar, Ritika; Nangpal, Prachi; Mathur, Shubhita; Singh, Swati

2017-01-01

Owing to the devastation caused by tuberculosis along with the unsatisfactory performance of the Bacillus Calmette–Guérin (BCG) vaccine, a more efficient vaccine than BCG is required for the global control of tuberculosis. A number of studies have demonstrated an essential role of biotin biosynthesis in the growth and survival of several microorganisms, including mycobacteria, through deletion of the genes involved in de novo biotin biosynthesis. In this study, we demonstrate that a bioA mutant of Mycobacterium tuberculosis (MtbΔbioA) is highly attenuated in the guinea pig model of tuberculosis when administered aerogenically as well as intradermally. Immunization with MtbΔbioA conferred significant protection in guinea pigs against an aerosol challenge with virulent M. tuberculosis, when compared with the unvaccinated animals. Booster immunization with MtbΔbioA offered no advantage over a single immunization. These experiments demonstrate the vaccinogenic potential of the attenuated M. tuberculosis bioA mutant against tuberculosis. PMID:28658275

"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…

Dietary Cholesterol Increases the Risk whereas PUFAs Reduce the Risk of Active Tuberculosis in Singapore Chinese12

PubMed Central

Soh, Avril Z; Chee, Cynthia BE; Wang, Yee-Tang; Yuan, Jian-Min; Koh, Woon-Puay

2016-01-01

Background: Experimental studies suggest that cholesterol enhances the intracellular survival of Mycobacterium tuberculosis, whereas marine ω-3 (n–3) and ω-6 (n–6) fatty acids (FAs) may modulate responses to M. tuberculosis in macrophage and animal models. However, there are no epidemiologic data from prospective studies of the relation between dietary cholesterol and FAs and the risk of developing active tuberculosis. Objective: We aimed to investigate the relation between dietary intake of cholesterol and FAs and the risk of active tuberculosis in a prospective cohort in Singapore. Methods: We analyzed data from the Singapore Chinese Health Study, a cohort of 63,257 Chinese men and women aged 45–74 y recruited between 1993 and 1998. Dietary intake of cholesterol and FAs was determined with the use of a validated food-frequency questionnaire. Incident cases of active tuberculosis were identified via linkage with the nationwide tuberculosis registry. Analysis was performed with the use of Cox proportional hazards models. Results: As of 31 December 2013, 1136 incident cases of active tuberculosis were identified. Dietary cholesterol was positively associated with an increased risk of active tuberculosis in a dose-dependent manner. Compared with the lowest intake quartile, the HR was 1.22 (95% CI: 1.00, 1.47) for the highest quartile (P-trend = 0.04). Conversely, dietary marine n–3 and n–6 FAs were associated with a reduced risk of active tuberculosis in a dose-dependent manner. Compared with the lowest quartile, the HR for the highest intake quartile was 0.77 (95% CI: 0.62, 0.95) for marine n–3 FAs (P-trend = 0.01) and 0.82 (95% CI: 0.68, 0.98) for n–6 FAs (P-trend = 0.03). There was no association with saturated, monounsaturated, or plant-based n–3 FA intake. Conclusion: Dietary intake of cholesterol may increase the risk of active tuberculosis, whereas marine n–3 and n–6 FAs may reduce the risk of active tuberculosis in the Chinese population

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

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 ...

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 ...

[Cutaneous tuberculosis in Bamako, Mali].

PubMed

Dicko, Adama; Faye, Ousmane; Fofana, Youssouf; Soumoutera, Moussa; Berthé, Siritio; Touré, Saidou; Traoré, Bekaye; Guindo, Binta; Tall, Koureissi; Keita, Alimata; Kéita, Lassine; Coulibaly, Karim; Keita, Somita

2017-01-01

Tuberculosis is the most common mycobacteriosis in sub-Saharan Africa. Cutaneous tuberculosis is rare and underdiagnosed due to its clinical polymorphism and to the smallness of technical equipment. This study aims to describe the epidemiological, clinical, histopathological aspects of cutaneous tuberculosis in Bamako (Mali). We conducted a cross-sectional descriptive study from January 1991 to December 2008. The study was performed in the Department of Dermatology at the National Center for Disease Control and in the Department of Pneumophtisiology at the Hospital of Point G. The patients with tuberculosis confirmed by histological and/or biological examination were included in the study. Out of 4269 patients? medical records, 61 cases of cutaneous tuberculosis were identified (1.43%). Men accounted for 59% of the cases (36 patients) and women 41% (25 cases); sex-ratio was 1.44. The age of the patients ranged from 3 months to 61 years, with an average age of 27.56 ± 36 years. The average length of follow-up was 10.9 ± 10 months. The identified clinical forms were scrofuloderma (41 cases), ulcerative form (13 cases), verrucous form (4 cases), and tuberculous Lupus (3 cases). Tuberculosis was associated with HIV in 7 cases, with leprosy in 3 cases. Cutaneous tuberculosis is underdiagnosed in Mali. Efforts are needed to improve the accessibility and the technical equipment available in the Departments, in order to conduct an extensive interdisciplinary study on this pathology.

[Risk factors for developing tuberculosis].

PubMed

Skodrić-Trifunović, Vesna

2004-01-01

Application of modern achievements in the field of medicine such as organ transplantation, long-term immunosuppressive therapy in treatment of numerous diseases, dialysis, successful treatment of malignant diseases prolonged duration of life and consequential continuation of long-term immunodeficiency. HIV infection currently represents a major risk factor for reactivation of tuberculosis with its associated relative risk being 30-170 times higher in comparison to the control group, in regard to the number of CD4 T-lymphocytes. Malignant diseases (hematological, lung and breast carcinomas) are important immunocompromising conditions affecting reactivation of tuberculosis, whereas the relative risk is 16. Development of tuberculosis among diabetics is considerably more frequent in comparison to general population (relative risk 2-4). Prominent glycoregulation disorders point to greater liability to development of tuberculosis. Alcoholism is characterized by general reduction of resistance, resulting from alcohol intoxication, malnutrition, irregular life style, etc. In malabsorption, immunosuppression is induced by deficiency of nutritive components and thus, relative risk for reactivation of tuberculosis is 5-12 in gastrectomy and 27-63 in jejunoileal bypass. In patients with chronic renal failur the relative risk ranges from 10 (nephropathies) to 37 (transplantation). Numerous patients use long-term immunosuppressive therapy that contributes to increased risk for developing tuberculosis (relative risk 12) as early as one month after application of a dose above 15 mg/day. There are numerous of risk factors that have frequently combined effects responsible for immunologic imbalance and development of tuberculosis.

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 (2004–2006). It identified 129 patterns: 105 (n = 568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1– ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2– modern/TbD1−/PGG1 group (Beijing, CAS), group 3– evolutionary recent/TbD1−/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n = 5, CAS n = 1), and 3 strains (BOV_1 n = 2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n = 114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%. Conclusion The M. tuberculosis population structure in Morocco is highly homogeneous, and is characterized by the predominance of the Euro-American lineages, namely LAM, Haarlem, and T, which belong to the “evolutionary recent” TbD1−/PGG2/3 phylogenetic group. The combination of spoligotyping and MIRUs decreased the clustering rate significantly, and should now be systematically applied in larger studies. The methods used in this study appear well suited to monitor the M. tuberculosis population

Prevalence of Pulmonary tuberculosis and immunological profile of HIV co-infected patients in Northwest Ethiopia

PubMed Central

2012-01-01

Background In sub-Saharan Africa, as high as 2/3 of tuberculosis patients are HIV/AIDS co-infected and tuberculosis is the most common cause of death among HIV/AIDS patients worldwide. Tuberculosis and HIV co-infections are associated with special diagnostic and therapeutic challenges and constitute an immense burden on healthcare systems of heavily infected countries like Ethiopia. The aim of the study was to determine the prevalence of pulmonary tuberculosis and their immunologic profiles among HIV positive patients. Methods A cross sectional study was conducted among adult HIV-positive patients attending HIV/AIDS clinic of Gondar University Hospital. Clinical and laboratory investigations including chest x-ray and acid fast staining were used to identify tuberculosis cases. Blood samples were collected to determine CD4+ lymphocyte count. A structured questionnaire was used to collect socio-demographic characteristics of study subjects. The data was entered and analyzed using SPSS version 16 software. Results A total of 400 HIV positive study participants were enrolled. Thirty (7.5%, 95%CI: 5.2-10.6%) of the study participants were found to have pulmonary tuberculosis. In multivariate analysis, only CD4+ lymphocyte count (AOR = 2.9; 95% CI: 1.002-8.368) was found to be independently associated with tuberculosis-HIV co-infection. Individuals who had advanced WHO clinical stage were also statistically significant for co-infection. The mean CD4+ lymphocyte count of HIV mono-infected participants were 296 ± 192 Cells/mm3 and tuberculosis-HIV co-infected patients had mean CD4+ lymphocyte count of 199 ± 149 Cells/mm3 with p value of 0.007. Conclusions We found high prevalence of tuberculosis-HIV co-infection. Lower CD4+ lymphocyte count was found to be the only predicting factor for co-infection. Early detection of co-infection is very necessary to prolong their ART initiation time and by then strengthening their immune status. PMID:22738361

The growing impact of HIV infection on the epidemiology of tuberculosis in England and Wales: 1999–2003

PubMed Central

Ahmed, Aliko B; Abubakar, Ibrahim; Delpech, Valerie; Lipman, Marc; Boccia, Delia; Forde, Josh; Antoine, Delphine; Watson, John M

2007-01-01

Background Previous studies have estimated the prevalence of tuberculosis and HIV infection in population subgroups in the UK. This study was undertaken to describe recent trends in the proportion of individuals with HIV infection among reported cases of tuberculosis in England and Wales, and to review the implications for clinical and public health care. Methods A population‐based matching study using national surveillance databases was used to investigate all persons aged 15 years and over reported with a diagnosis of tuberculosis to the Health Protection Agency in England and Wales in 1999–2003. Record linkage was used to match the national tuberculosis and HIV/AIDS surveillance databases to identify all cases of tuberculosis and determine the proportion of patients with tuberculosis co‐infected with HIV. The distribution and characteristics of the cases were determined and the trend examined by year. Results Of 30 670 cases of tuberculosis reported in England and Wales between 1999 and 2003, an estimated 1743 (5.7%) were co‐infected with HIV. There was a year on year increase in the proportion from 3.1% (169/5388) in 1999 to 8.3% (548/6584) in 2003 (p for trend <0.0001). Co‐infected patients contributed to almost a third of the increase in the number of cases of tuberculosis during the 5 year period. Patients co‐infected with HIV were predominantly those born abroad. 18.5% (n = 323) of co‐infected patients had not been reported as active cases of tuberculosis on the national tuberculosis database. Conclusion The proportion of patients with tuberculosis co‐infected with HIV in England and Wales is increasing, with the greatest impact on those born abroad regardless of their ethnic origin. With HIV infection contributing substantially to the increase in the number of cases of tuberculosis, close cooperation in the clinical management and accurate notification of patients is vital if appropriate care and public health action is to be

[Treatment of tuberculosis].

PubMed

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

2015-01-01

The aim of this article is to give practicing physicians a practical approach to the treatment of latent and active tuberculosis. Most patients follow TB standard treatment recommended by WHO that depend on category of patient. It is a combination of four essential tuberculosis drugs of the first group: isoniazid, rifampicin, pyrazinamid and ethambutol; in some cases streptomycin can replace ethambutol. This initial phase of intensive treatment is followed by a consolidation phase. Drugs should be administered in the morning on an empty stomach one hour before meals. Treatment of latent tuberculosis (TB) infection is an important component of TB control programs. Preventive treatment can reduce the risk of developing active TB. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Guidelines for the prevention and control of tuberculosis in health care workers].

PubMed

Casas, Irma; Dominguez, Jose; Rodríguez, Soledad; Matllo, Joan; Altet, Neus

2015-12-21

Tuberculosis remains one of the communicable diseases that cause increased morbidity and mortality worldwide. With an incidence rate of 13,04 per 100,000 population, Spain ranks third among the most affected European countries. These data show a tendency to decrease meaning that it may go unnoticed with the potential to miss the appropriate preventive measures in a suspected case. In centers where patients are treated with tuberculosis, health care worker presents risk of transmission. This risk is higher in some areas or work units. The Occupational health physicians' services, which monitorize the health of health care workers, use different strategies in order to prevent and detect tuberculosis infection. The national guidelines include the tuberculin skin test as a screening test for tuberculosis infection with mention of new diagnostic tests based on the in vitro detection of gamma interferon (IGRA) for certain cases. The purpose of this guide is to establish common criteria for IGRA tests, as a supplementary aid to the tuberculin skin test in health care workers, from the evidence available today. Recommendations for its use have been adapted to the different situations faced by the professionals involved in monitoring the health of health workers. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Pulmonary immune responses to Mycobacterium tuberculosis in exposed individuals

PubMed Central

Ernst, Martin; Lange, Christoph; Stenger, Steffen; Kaufmann, Stefan H. E.; Reiling, Norbert; Schaberg, Tom; van der Merwe, Lize; Maertzdorf, Jeroen

2017-01-01

Background Blood based Interferon-(IFN)-γ release assays (IGRAs) have a poor predictive value for the development of tuberculosis. This study aimed to investigate the correlation between IGRAs and pulmonary immune responses in tuberculosis contacts in Germany. Methods IGRAs were performed on bronchoalveolar lavage (BAL) cells and peripheral blood from close healthy contacts of patients with culturally confirmed tuberculosis. Cellular BAL composition was determined by flow cytometry. BAL cells were co-cultured with three strains of Mycobacterium tuberculosis (Mtb) and Mtb derived antigens including Purified Protein Derivative (PPD), 6 kD Early Secretory Antigenic Target (ESAT-6) and 10 kD Culture Filtrate Protein (CFP-10). Levels of 29 cytokines and chemokines were analyzed in the supernatants by multiplex assay. Associations and effects were examined using linear mixed-effects models. Results There were wide variations of inter-individual cytokine levels in BAL cell culture supernatants. Mycobacterial infection and stimulation with PPD showed a clear induction of several macrophage and lymphocyte associated cytokines, reflecting activation of these cell types. No robust correlation between cytokine patterns and blood IGRA status of the donor was observed, except for slightly higher Interleukin-2 (IL-2) responses in BAL cells from IGRA-positive donors upon mycobacterial infection compared to cells from IGRA-negative donors. Stronger correlations were observed when cytokine patterns were stratified according to BAL IGRA status. BAL cells from donors with BAL IGRA-positive responses produced significantly more IFN-γ and IL-2 upon PPD stimulation and mycobacterial infection than cells from BAL IGRA-negative individuals. Correlations between BAL composition and basal cytokine release from unstimulated cells were suggestive of pre-activated lymphocytes but impaired macrophage activity in BAL IGRA-positive donors, in contrast to BAL IGRA-negative donors. Conclusions In

Tuberculosis control in the era of the HIV epidemic: risk of tuberculosis infection in Tanzania, 1983-1998.

PubMed

2001-02-01

In Tanzania, a national tuberculosis programme (NTP) was established in 1979 based on the principles currently known as the World Health Organization DOTS strategy. From the period 1983-1987 to 1994-1998, notification rates of smear-positive tuberculosis increased from 32 to 69 per 100,000 population, mainly due to the human immunodeficiency virus (HIV) epidemic. To estimate the trend in the annual risk of tuberculosis infection and to establish to what extent the opposing forces of improved tuberculosis control and HIV have had an impact on tuberculosis transmission. Three national surveys were conducted in Tanzania among primary school children at 5-year intervals. The annual risk of tuberculosis infection and its trend were determined by tuberculin skin testing. The annual risk of infection in children without BCG scar using the criterion '17 mm + 2 x 18 mm' or more was estimated at 1.1% in 1983-1987, 1.0 in 1988-1992, and 0.9% in 1993-1998. There appears to have been little change in the annual risk of infection over the study period, either when using other criteria to define infection or in children with a BCG scar. The estimated number of infections per notified case decreased over time from 36 to 19. Despite strongly increased tuberculosis notification rates in adults, associated with the HIV epidemic, the risk of tuberculosis infection in children appears to have been stable over the past 15 years in Tanzania. This remarkable achievement is probably due to the impact of the NTP on tuberculosis transmission.

Adaptive trials for tuberculosis: early reflections on theory and practice.

PubMed

Montgomery, C M

2016-08-01

Adaptive designs (ADs) have been proposed for anti-tuberculosis treatment trials. This call for innovation occurs against the backdrop of fundamental changes in the acceptable evidence base in anti-tuberculosis treatment. To contextualise ADs for tuberculosis (TB) and explore early responses from those working in the field. In this qualitative study investigating processes of theoretical and practical change in randomised controlled trials, 24 interviews were conducted with professionals involved in AD trials, half of whom worked in the TB field. Clinical trialists working on AD trials in TB are positive about the efficiency these designs offer, but remain cautious about their suitability. In addition to technical concerns, informants discussed the challenges of implementing AD in developing countries, including limited regulatory capacity to evaluate proposals, investments needed in infrastructure and site capacity, and challenges regarding informed consent. Respondents identified funding, interdisciplinary communication and regulatory and policy responses as additional concerns potentially affecting the success of AD for TB. Empirical research is needed into patient experiences of AD, including informed consent. Further consideration of the contexts of innovation in trial design is needed. These are fundamental to the successful translation of theory into practice.

International Standards for Tuberculosis Care: revisiting the cornerstones of tuberculosis care and control.

PubMed

Fair, Elizabeth; Hopewell, Philip C; Pai, Madhukar

2007-02-01

Tuberculosis (TB) remains an enormous global health problem. There are 8-9 million new cases and 2 million deaths from TB annually. Despite the overwhelming burden of disease, the basic principles of care for persons with, or suspected of having, TB are the same worldwide: a diagnosis should be established promptly and accurately, standardized treatment regimens of proven efficacy should be used together with appropriate treatment support and supervision, the response to treatment should be monitored, and the essential public health responsibilities must be carried out. As an approach to improving the care of patients with TB, an evidence-based document, the International Standards for Tuberculosis Care (ISTC) was developed and has been endorsed by more than 30 international and national agencies. This special report introduces the ISTC and discusses the fact that accurate diagnosis and effective treatment are not only essential for good patient care, they are the key elements in the public health response to TB and are the cornerstone of TB control. With the recent emergence of extensively drug-resistant TB, there is an urgent need to ensure globally that standards of TB care are based on rigorous scientific findings, are clear and well understood, and are accessible to and applied by all types of healthcare providers in all corners of the world.

Aspartate decarboxylase (PanD) as a new target of pyrazinamide in Mycobacterium tuberculosis.

PubMed

Shi, Wanliang; Chen, Jiazhen; Feng, Jie; Cui, Peng; Zhang, Shuo; Weng, Xinhua; Zhang, Wenhong; Zhang, Ying

2014-08-01

Pyrazinamide (PZA) is a frontline anti-tuberculosis drug that plays a crucial role in the treatment of both drug-susceptible and multidrug-resistant tuberculosis (MDR-TB). PZA is a prodrug that is converted to its active form, pyrazinoic acid (POA), by a nicotinamidase/pyrazinamidase encoded by the pncA gene, the mutation of which is the major cause of PZA resistance. Although RpsA (ribosomal protein S1, involved in trans-translation) has recently been shown to be a target of POA/PZA, whole-genome sequencing has identified mutations in the panD gene encoding aspartate decarboxylase in PZA-resistant strains lacking pncA and rpsA mutations. To gain more insight into a possible new target of PZA, we isolated 30 POA-resistant mutants lacking mutations in pncA and rpsA from M. tuberculosis in vitro, and whole-genome sequencing of 3 mutants identified various mutations in the panD gene. Additionally, sequencing analysis revealed that the remaining 27 POA-resistant mutants all harbored panD mutations affecting the C-terminus of the PanD protein, with PanD M117I being the most frequent mutation (24/30, 80%). Conditional overexpression of panD from M. tuberculosis, M. smegmatis or E. coli, or of M. tuberculosis mutant PanD M117I, all conferred resistance to POA and PZA in M. tuberculosis. β-alanine and pantothenate, which are downstream products of PanD, were found to antagonize the antituberculosis activity of POA. In addition, the activity of the M. tuberculosis PanD enzyme was inhibited by POA at therapeutically relevant concentrations in a concentration-dependent manner but was not inhibited by the prodrug PZA or the control compound nicotinamide. These findings suggest that PanD represents a new target of PZA/POA. These results have implications for a better understanding of this peculiar persister drug and for the design of new drugs targeting M. tuberculosis persisters for improved treatment.

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.

In vitro infection with Mycobacterium tuberculosis induces a distinct immunological pattern in blood from healthy relatives of tuberculosis patients.

PubMed

Juan-García, Javier; García-García, Silvia; Guerra-Laso, José Manuel; Raposo-García, Sara; Diez-Tascón, Cristina; Nebreda-Mayoral, Teresa; López-Fidalgo, Eduardo; López-Medrano, Ramiro; Fernández-Maraña, Araceli; Rivero-Lezcano, Octavio Miguel

2017-11-30

Part of the susceptibility to tuberculosis has a genetic basis, which is clear in primary immunodeficiencies, but is less evident in apparently immunocompetent subjects. Immune responses were analysed in blood samples from tuberculosis patients and their healthy first-degree relatives who were infected in vitro with mycobacteria (either Mycobacterium tuberculosis or M. bovis BCG). The antimicrobial activity against M. tuberculosis in blood from relatives was significantly lower than that observed in healthy controls. Tuberculosis patients exhibited a higher number of neutrophils, and monocyte phagocytosis was inhibited in both relatives and tuberculosis patients. A remarkable finding was that the production of reactive oxygen species by infected neutrophils was higher in relatives than in healthy controls. A higher production of TNFα in infected blood from relatives was also observed. These results may indicate that relatives display a stronger inflammatory response and that their immune response to M. tuberculosis is different from those of unrelated controls. First-degree relatives may represent a highly informative group for the analysis of tuberculosis susceptibility. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Pilot study to detect airborne Mycobacterium tuberculosis exposure in a South African public healthcare facility outpatient clinic.

PubMed

Matuka, O; Singh, T S; Bryce, E; Yassi, A; Kgasha, O; Zungu, M; Kyaw, K; Malotle, M; Renton, K; O'Hara, L

2015-03-01

Airborne transmission of Mycobacterium tuberculosis remains an occupational health hazard, particularly in crowded and resource-limited healthcare settings. To quantify airborne M. tuberculosis in a busy outpatient clinic in Gauteng, South Africa. Stationary air samples and samples from healthcare workers (HCWs) were collected in the polyclinic and administrative block. Quantitative real-time polymerase chain reaction (PCR) was used to detect airborne M. tuberculosis. Walkthrough observations and work practices of HCWs were also recorded. In total, M. tuberculosis was detected in 11 of 49 (22.4%) samples: nine of 25 (36%) HCW samples and two of 24 (8.3%) stationary air samples. Samples from five of 10 medical officers (50%) and three of 13 nurses (23%) were positive. Repeat measurements on different days showed variable results. Most of the HCWs (87.5%) with positive results had been in contact with coughing patients and had not worn respiratory masks despite training. The use of air sampling coupled with quantitative real-time PCR is a simple and effective tool to demonstrate the risk of M. tuberculosis exposure. The findings provide an impetus for hospital management to strengthen infection prevention and control measures for tuberculosis. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Neutral-red reaction is related to virulence and cell wall methyl-branched lipids in Mycobacterium tuberculosis.

PubMed

Cardona, P-J; Soto, C Y; Martín, C; Giquel, B; Agustí, G; Andreu, Núria; Guirado, E; Sirakova, T; Kolattukudy, P; Julián, E; Luquin, M

2006-01-01

Searching for virulence marking tests for Mycobacterium tuberculosis, Dubos and Middlebrook reported in 1948 that in an alkaline aqueous solution of neutral-red, the cells of the virulent H37Rv M. tuberculosis strain fixed the dye and became red in color, whereas the cells of the avirulent H37Ra M. tuberculosis strain remained unstained. In the 1950 and 1960s, fresh isolates of M. tuberculosis were tested for this neutral-red cytochemical reaction and it was reported that they were neutral-red positive, whereas other mycobacteria of diverse environmental origins that were non-pathogenic for guinea pigs were neutral-red negative. However, neutral-red has not really been proven to be a virulence marker. To test if virulence is in fact correlated to neutral-red, we studied a clinical isolate of M. tuberculosis that was originally neutral-red positive but, after more than 1 year passing through culture mediums, turned neutral-red negative. We found that, in comparison to the original neutral-red positive strain, this neutral-red negative variant was attenuated in two murine models of experimental tuberculosis. Lipid analysis showed that this neutral-red negative natural mutant lost the capacity to synthesize pthiocerol dimycocerosates, a cell wall methyl-branched lipid that has been related to virulence in M. tuberculosis. We also studied the neutral-red of different gene-targeted M. tuberculosis mutants unable to produce pthiocerol dimycocerosates or other cell wall methyl-branched lipids such as sulfolipids, and polyacyltrehaloses. We found a negative neutral-red reaction in mutants that were deficient in more than one type of methyl-branched lipids. We conclude that neutral-red is indeed a marker of virulence and it indicates important perturbations in the external surface of M. tuberculosis cells.

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

Cost-effectiveness of adding novel or group 5 interventions to a background regimen for the treatment of multidrug-resistant tuberculosis in Germany.

PubMed

Wirth, Daniel; Dass, Ramesh; Hettle, Robert

2017-03-08

Treatment of multidrug-resistant tuberculosis (MDR-TB) is complex, lengthy, and involves a minimum of four drugs termed a background regimen (BR), that have not previously been prescribed or that have proven susceptible to patient sputum culture isolates. In recent years, promising new treatment options have emerged as add-on therapies to a BR. The aim of this study was to evaluate the long-term costs and effectiveness of adding the novel or group 5 interventions bedaquiline, delamanid, and linezolid to a background regimen (BR) of drugs for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis (MDR-TB), within their marketing authorisations, from a German healthcare cost-effectiveness perspective. A cohort-based Markov model was developed to simulate the incremental cost-effectiveness ratio of bedaquiline plus BR, delamanid plus BR, or linezolid plus BR versus BR alone in the treatment of MDR-TB, over a 10-year time horizon. Effectiveness of treatment was evaluated in Quality-Adjusted Life-Years (QALYs) and Life-Years Gained (LYG), using inputs from clinical trials for bedaquiline and delamanid and from a German observational study for linezolid. Cost data were obtained from German Drug Directory costs (€/2015), published literature, and expert opinion. A 3% yearly discount rate was applied. Probabilistic and deterministic sensitivity analyses were conducted. The total discounted costs per-patient were €85,575 for bedaquiline plus BR, €81,079 for delamanid plus BR, and €80,460 for linezolid plus BR, compared with a cost of €60,962 for BR alone. The total discounted QALYs per-patient were 5.95 for bedaquiline plus BR, 5.36 for delamanid plus BR, and 3.91 for linezolid plus BR, compared with 3.68 for BR alone. All interventions were therefore associated with higher QALYs and higher costs than BR alone, with incremental costs per QALY gained of €22,238 for bedaquiline, €38,703 for delamanid, and €87,484 for linezolid, versus

Recent mouse models and vaccine candidates for preventing chronic/latent tuberculosis infection and its reactivation.

PubMed

Pedroza-Roldán, César; Flores-Valdez, Mario Alberto

2017-08-31

Tuberculosis (TB) remains a major challenge in public health worldwide. Until today, the only widely used and approved vaccine is the Mycobacterium bovis bacille Calmette-Guerin (BCG). This vaccine provides a highly variable level of protection against the active, pulmonary form of tuberculosis, and practically none against the latent form of TB infection. This disparity in protection has been extensively studied, and for this reason, several groups have focused their research on the quest for attenuated vaccines based on M. tuberculosis or on the identification of latency-associated antigens that can be incorporated into modified BCG, or that can be used as adjuvanted subunit vaccines. In order to seek new potential antigens relevant for infection, some researchers have performed experiments with highly sensitive techniques such as transcriptomic and proteomic analyses using sputum samples from humans or by using mouse models resembling several aspects of TB. In this review, we focus on reports of new mouse models or mycobacterial antigens recently tested for developing vaccine candidates against chronic/latent tuberculosis and its reactivation.

Human tuberculosis predates domestication in ancient Syria.

PubMed

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

2015-06-01

The question of pre-neolithic tuberculosis is still open in paleopathological perspective. One of the major interests is to explore what type of infection could have existed around the early stage of animal domestication. Paleopathological lesions evoking skeletal TB were observed on five human skeletons coming from two PPNB sites in Syria, which belongs to the geographical cradle of agriculture. These sites represent respectively pre-domestication phase (Dja'de el Mughara, Northern Syria, 8800-8300 BCE cal.) and early domestication phase (Tell Aswad, Southern Syria, 8200-7600 BCE cal.). MicroCT scan analyses were performed on two specimens (one per site) and revealed microscopic changes in favor of TB infection. Detection of lipid biomarkers is positive for two specimens (one per site). Initial molecular analysis further indicates the presence of TB in one individual from Dja'de. Interestingly, no morphological evidence of TB was observed on animal remains of wild and newly domesticated species, discovered in these sites. These observations strongly suggest the presence of human tuberculosis before domestication and at its early stages. Copyright © 2015 Elsevier Ltd. All rights reserved.