Primary tuberculosis of the glans penis.

PubMed

Jimenez Parra, Jose David; Alvarez Bandres, Silvia; Garcia Garcia, Diego; Torres Varas, Lorena; Sotil Arrieta, Amaia; Jimenez Calvo, Jesus

2014-03-01

Tuberculosis of the penis is an extremely rare disease with few cases reported in the literature. We present the case of a 64 year-old man with a whitish papular-ampullary eruption in the glans penis. After antibiotic/antimycotic therapy and several topical ointments for 3 months without response he was referred to our Department. Biopsy of the ulceration edge was performed and pathology result showed a chronic granulomatous inflammatory necrotizing lesion with granulomatous vasculitis lesions, without tumor infiltration. Systemic examination to rule out other tuberculosis foci was negative. With de suspicion of primary tuberculosis of the glans penis, anti tuberculosis therapy with Isoniazid and Piridoxine was started. Within a period of five months the ulceration healed significantly. Currently, the patient is still asymptomatic without glans penis lesions. Primary glans penis tuberculosis is a rare disease, but we must consider it (both primary and secondary forms) to try to avoid diagnostic delays that may cause prejudice for the patient. This condition promptly responds to anti tuberculosis therapy as evidenced by our case and many other reports.

Offer of primary care services and detection of tuberculosis incidence in Brazil

PubMed Central

Pelissari, Daniele Maria; Bartholomay, Patricia; Jacobs, Marina Gasino; Arakaki-Sanchez, Denise; dos Anjos, Davllyn Santos Oliveira; Costa, Mara Lucia dos Santos; Cavalcanti, Pauline Cristine da Silva; Diaz-Quijano, Fredi Alexander

2018-01-01

ABSTRACT OBJECTIVE To evaluate the association between the health services offered by primary care teams and the detection of new tuberculosis cases in Brazil. METHODS This was an ecological study covering all Brazilian municipalities that registered at least one new tuberculosis case (diagnosed between 2012 to 2014 and notified in the Information System of Notifiable Diseases) and with at least one primary care team evaluated by the second cycle of the National Program for Improving Access and Quality of Primary Care (PMAQ-AB). The variables of the PMAQ-AB were classified as proximal or distal, according to their relation with the tuberculosis diagnosis. Then, they were tested hierarchically in multiple models (adjusted by States) using negative binomial regression. RESULTS An increase of 10% in the primary health care coverage was associated with a decrease of 2.24% in the tuberculosis detection rate (95%CI -3.35– -1.11). Regarding the proximal variables in relation to diagnosis, in the multiple model, the detection of tuberculosis was associated with the proportion of teams that conduct contact investigation (increase in Incidence Rate Ratio [IRR] = 2.97%, 95%CI 2.41–3.53), carry out tuberculosis active case finding (increase in IRR = 2.17%, 95%CI 1.48–2.87), and request culture for mycobacteria (increase in IRR = 1.87%, 95%CI 0.98–2.76). CONCLUSIONS The variables related to the search actions were positively associated with the detection of new tuberculosis cases, which suggests a significant contribution to the strengthening of the sensitivity of the surveillance system. On the other hand, primary care coverage was inversely associated with the tuberculosis detection rate, which could represent the overall effect of the primary care on transmission control, probably from the identification and early treatment of cases. PMID:29791528

Non-healing gastro-duodenal ulcer: A rare presentation of primary abdominal tuberculosis

PubMed Central

Merali, Nabeel; Chandak, Pankaj; Doddi, Sudeendra; Sinha, Prakash

2014-01-01

INTRODUCTION We present a case of primary gastrointestinal tuberculosis that has culminated in ulcer formation, in the absence of pulmonary involvement in an immunocompetent patient. PRESENTATION OF CASE A 28-year-old Asian male presented to casualty with a 1-week history of epigastric cramping abdominal pain and several episodes of non-bilious vomiting. The patient deteriorated clinically, becoming more cachectic and given his unexplained weight loss, an oesophageal-gastro-duodenal endoscopic imaging confirmed a duodenal ulcer. The biopsy of the non-healing ulcer was the hallmark of the disease, revealing evidence of granulomatous inflammation consistent with tuberculosis bacilli. DISCUSSION Gastrointestinal tuberculosis with ulceration is rare with respect to the oesophagus, stomach and duodenum. This case proves to be unique, as our patient had experienced primary isolated gastric tuberculosis in the absence of pulmonary tuberculosis in a healthy individual. Immunohistochemical staining, histopathology and radiological investigations have demonstrated their importance in confirming abdominal tuberculosis and the extent of bowel involvement. CONCLUSION This case has illustrated the difficulties associated with a prompt diagnosis of an unusual case of primary duodenal tuberculosis from chronic peptic ulcer disease in an immunocompetent patient. PMID:25506841

Non-healing gastro-duodenal ulcer: A rare presentation of primary abdominal tuberculosis.

PubMed

Merali, Nabeel; Chandak, Pankaj; Doddi, Sudeendra; Sinha, Prakash

2015-01-01

We present a case of primary gastrointestinal tuberculosis that has culminated in ulcer formation, in the absence of pulmonary involvement in an immunocompetent patient. A 28-year-old Asian male presented to casualty with a 1-week history of epigastric cramping abdominal pain and several episodes of non-bilious vomiting. The patient deteriorated clinically, becoming more cachectic and given his unexplained weight loss, an oesophageal-gastro-duodenal endoscopic imaging confirmed a duodenal ulcer. The biopsy of the non-healing ulcer was the hallmark of the disease, revealing evidence of granulomatous inflammation consistent with tuberculosis bacilli. Gastrointestinal tuberculosis with ulceration is rare with respect to the oesophagus, stomach and duodenum. This case proves to be unique, as our patient had experienced primary isolated gastric tuberculosis in the absence of pulmonary tuberculosis in a healthy individual. Immunohistochemical staining, histopathology and radiological investigations have demonstrated their importance in confirming abdominal tuberculosis and the extent of bowel involvement. This case has illustrated the difficulties associated with a prompt diagnosis of an unusual case of primary duodenal tuberculosis from chronic peptic ulcer disease in an immunocompetent patient. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Feasibility of achieving the 2025 WHO global tuberculosis targets in South Africa, China, and India: a combined analysis of 11 mathematical models.

PubMed

Houben, Rein M G J; Menzies, Nicolas A; Sumner, Tom; Huynh, Grace H; Arinaminpathy, Nimalan; Goldhaber-Fiebert, Jeremy D; Lin, Hsien-Ho; Wu, Chieh-Yin; Mandal, Sandip; Pandey, Surabhi; Suen, Sze-Chuan; Bendavid, Eran; Azman, Andrew S; Dowdy, David W; Bacaër, Nicolas; Rhines, Allison S; Feldman, Marcus W; Handel, Andreas; Whalen, Christopher C; Chang, Stewart T; Wagner, Bradley G; Eckhoff, Philip A; Trauer, James M; Denholm, Justin T; McBryde, Emma S; Cohen, Ted; Salomon, Joshua A; Pretorius, Carel; Lalli, Marek; Eaton, Jeffrey W; Boccia, Delia; Hosseini, Mehran; Gomez, Gabriela B; Sahu, Suvanand; Daniels, Colleen; Ditiu, Lucica; Chin, Daniel P; Wang, Lixia; Chadha, Vineet K; Rade, Kiran; Dewan, Puneet; Hippner, Piotr; Charalambous, Salome; Grant, Alison D; Churchyard, Gavin; Pillay, Yogan; Mametja, L David; Kimerling, Michael E; Vassall, Anna; White, Richard G

2016-11-01

The post-2015 End TB Strategy proposes targets of 50% reduction in tuberculosis incidence and 75% reduction in mortality from tuberculosis by 2025. We aimed to assess whether these targets are feasible in three high-burden countries with contrasting epidemiology and previous programmatic achievements. 11 independently developed mathematical models of tuberculosis transmission projected the epidemiological impact of currently available tuberculosis interventions for prevention, diagnosis, and treatment in China, India, and South Africa. Models were calibrated with data on tuberculosis incidence and mortality in 2012. Representatives from national tuberculosis programmes and the advocacy community provided distinct country-specific intervention scenarios, which included screening for symptoms, active case finding, and preventive therapy. Aggressive scale-up of any single intervention scenario could not achieve the post-2015 End TB Strategy targets in any country. However, the models projected that, in the South Africa national tuberculosis programme scenario, a combination of continuous isoniazid preventive therapy for individuals on antiretroviral therapy, expanded facility-based screening for symptoms of tuberculosis at health centres, and improved tuberculosis care could achieve a 55% reduction in incidence (range 31-62%) and a 72% reduction in mortality (range 64-82%) compared with 2015 levels. For India, and particularly for China, full scale-up of all interventions in tuberculosis-programme performance fell short of the 2025 targets, despite preventing a cumulative 3·4 million cases. The advocacy scenarios illustrated the high impact of detecting and treating latent tuberculosis. Major reductions in tuberculosis burden seem possible with current interventions. However, additional interventions, adapted to country-specific tuberculosis epidemiology and health systems, are needed to reach the post-2015 End TB Strategy targets at country level. Bill and Melinda Gates Foundation. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Primary tuberculosis clinically presenting as gingival enlargement: a case report.

PubMed

Sharma, C G Dileep; Pradeep, A R; Karthikeyan, B V

2006-11-01

Tuberculosis is a chronic systemic granulomatous disease which rarely affects the oral cavity. Oral lesions can be either primary or secondary to systemic tuberculosis, the former being rare. This is a never-before reported case of primary tuberculosis presenting as a localized diffuse gingival enlargement in an 11-year-old Indian female patient. The diagnosis was reached through identification of positive histopathological features, Tuberculin test results, presence of anti-tubercular antibodies confirmed by a polymerase chain reaction. In view of the recent increase in the incidence of tuberculosis and the prevalence of the same, it is reasonable to include tuberculosis in the differential diagnosis of gingival enlargements. This is essential to avoid any serious complications for both the clinician and patient due to a delay in the diagnosis of such a rare but plausible oral condition.

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 deployment of new TB vaccines in malaria endemic areas. PMID:22205939

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

PubMed Central

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

2008-01-01

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

Mycobacterium tuberculosis multistage antigens confer comprehensive protection against pre- and post-exposure infections by driving Th1-type T cell immunity

PubMed Central

Fan, Xionglin; Yu, Qi; Jing, Yukai; Wang, Weihua; Li, Li; Zhou, Zijie

2016-01-01

There is an urgent need for a vaccine against tuberculosis (TB) that is more effective than the current sole licensed option. However, target antigens of Mycobacterium tuberculosis with the vaccine potential remain elusive. Five immunodominant antigens with characteristic expressions at the stages of primary infection (Ag85A), the regulation of nutrition and metabolism when transferring from rapid growth to latency (PhoY2 and Rv3407), latency (Rv2626c), and reactivation (RpfB) were selected to construct the fusion polyprotein WH121, which has better immunogenicity and protection than each multistage antigen. DMT adjuvanted WH121 vaccinated C57BL/6 mice could confer persistent and significant protection against the respiratory challenge with 80 CFU of virulent M. tuberculosis H37Rv at 9 and 18 weeks after immunization, as the BCG vaccine did. Moreover, WH121/DMT could boost the BCG primed mice against post-exposure infection, and more significantly inhibit the growth of M. tuberculosis in the spleen than BCG repeat vaccination. The protection elicited by WH121/DMT is attributed to the WH121-specific Th1-type biased immune responses, characterized by increased antigen-specific IgG2a/IgG1 ratio and high levels of IFN-γ secreted by the splenocytes of vaccinated mice. In particular, high levels of IFN-γ+ TEM cells in the spleen are an effective biomarker for the vaccine-induced early protection, and the persistent protection mainly depends on the increasing IL-2+IFN-γ+CD4+ and CD8+ T cells, especially IL-2+ TCM cells. These findings demonstrate that multistage-specific antigens might be promising targets for the next generation TB vaccine, and a combination of these antigens such as WH121/DMT is required for further preclinical evaluation. PMID:27566581

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

Primary tubercular abscess of the breast--an unusual entity.

PubMed

Gupta, R; Singal, R P; Gupta, A; Singal, S; Shahi, S R; Singal, R

2012-02-22

Primary breast tuberculosis manifested as abscess is a rare entity. We are reporting a case of primary breast tuberculosis, which presented as breast abscess. Abscess was drained and tissue sent for histopathology. To our surprise, diagnosis came as breast tuberculosis. Aspiration cytology was not done, as it is not a routine test for abscess cases. Patient was put on anti- tubercular drugs. In the follow-up of 6 months, she was asymptomatic and advised to continue medicine.

Primary breast tuberculosis: diagnostic and therapeutic dilemmas.

PubMed

Hiremath, Bharati V; Subramaniam, Narayana

2015-01-01

To review the diagnostic and therapeutic challenges associated with treating isolated primary breast tuberculosis through discussion of our series of seven cases. Although breast is an uncommon site of occurrence of tuberculosis and isolated primary breast tuberculosis is an even rarer entity, its importance lies in distinguishing it from more common pathologies like abscesses or malignancy and avoiding unnecessary erroneous surgical intervention. The spectrum and presentation is wide and varied and we present our experience in managing seven such cases. A retrospective analysis of all the cases of histopathologically proven primary breast tuberculosis in the last three years at M.S. Ramaiah Hospital (2012-2014) was done. Analysis was in terms of mode of presentation, clinical features, diagnostic modalities used for evaluation and confirmation of the diagnosis, medical treatment and surgical intervention, if any. Special emphasis was placed on dilemmas in diagnosis and difficulties encountered during treatment. All cases were followed up till cure. Patients most commonly presented with a breast abscess, painful breast lumps and recurrent abscesses. Other foci of tuberculosis were ruled out in all of these patients. Majority were treated exclusively with anti-tubercular therapy (although regimens varied), but those with abscesses underwent incision and drainage. All cases were treated and followed up till cure. The challenges associated with primary breast tuberculosis are multiple, including which anti-tubercular therapy regimen to use, when to surgically intervene (as the breast is a cosmetically important area) and treating atypical mycobacteria. We provide a detailed discussion of the challenges we faced and review of literature.

Primary tubercular abscess of the breast – an unusual entity

PubMed Central

Gupta, R; Singal, RP; Gupta, A; Singal, S; Shahi, SR; Singal, R

2012-01-01

Primary breast tuberculosis manifested as abscess is a rare entity. We are reporting a case of primary breast tuberculosis, which presented as breast abscess. Abscess was drained and tissue sent for histopathology. To our surprise, diagnosis came as breast tuberculosis. Aspiration cytology was not done, as it is not a routine test for abscess cases. Patient was put on anti- tubercular drugs. In the follow-up of 6 months, she was asymptomatic and advised to continue medicine. PMID:22574095

Tuberculosis Prevention in College Students

ERIC Educational Resources Information Center

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

2004-01-01

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

Primary tuberculosis of the eustachian tube causing otitis media with effusion.

PubMed

Oh, Se-Joon; Yi, Keun-Ik; Lee, Chang-Hoon; Cho, Kyu-Sup

2015-01-01

Eustachian tube (ET) dysfunction may cause pathological changes in the middle ear, including recurrent acute otitis media and otitis media with effusion (OME). Mechanical obstruction of the ET may be caused by primary tumor-like lesions arising from ET or secondary ET infiltration due to nasopharyngeal and parapharyngeal space tumor. Tuberculosis is known to affect almost every organ in the body, and it should be a concern of each and every medical practitioner. However, tuberculosis of the ET has not been reported in the literature previously. This article reports primary tuberculosis arising in the ET that presented as aural fullness and hearing disturbance in a patient with OME. Copyright © 2015 Elsevier Inc. All rights reserved.

Multiple hepatic lesions in a case of isolated hepatic tuberculosis simulating metastases on 18F-FDG PET/CT imaging.

PubMed

Karunanithi, Sellam; Sharma, Punit; Jain, Tarun Kumar; Vijay, Maneesh Kumar; Kumar, Rakesh

2014-01-01

Hepatic tuberculosis is an unusual form of extrapulmonary tuberculosis and constitutes less than 1% of all cases of tuberculosis. Imaging studies for hepatic tuberculosis are nonspecific and mimic primary or metastatic carcinoma. Here we present ¹⁸F-FDG PET/CT images of a 25-year-old male patient with isolated hepatic tuberculosis.

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.

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.

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.

Primary Papillary Mucinous Adenocarcinoma of the Ureter Mimicking Genitourinary Tuberculosis

PubMed Central

Gulwani, Hanni; Jain, Aruna

2010-01-01

Primary adenocarcinomas of the renal pelvis and ureter are rare and account for less than 1% of all malignancies at this site. We report a case of primary papillary mucinous adenocarcinoma of the ureter that clinically mimicked genitourinary tuberculosis. Early diagnosis is important for the better outcome. PMID:21151719

9 CFR 77.34 - Official tuberculosis tests.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Official tuberculosis tests. 77.34... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS TUBERCULOSIS Captive Cervids § 77.34 Official tuberculosis tests. (a) Primary tests. (1) Single cervical tuberculin (SCT) test...

Primary and acquired drug resistance in Mycobacterium tuberculosis strains in western region of Libyan Arab Jamahiriya.

PubMed

Elghoul, M T; Joshi, R M; Rizghalla, T

1989-10-01

Drug resistance in Mycobacterium tuberculosis strains prevalent in the Western Region of Libyan Arab Jamahiriya was studied for the years 1984, 1985 and 1986 at the regional tuberculosis control centre at Gurgi, Tripoli. Records of resistance to streptomycin, isoniazid, ethambutol and rifampicin were analysed. Whereas primary drug resistance was observed in 5.1%, 19.5% and 3.8%, acquired drug resistance was found in 12.2%, 34.0% and 15.3% of the strains in 1984, 1985 and 1986 respectively. Only 3 out of 598 strains (1.2%) were found to show acquired resistance to rifampicin. No primary resistance to rifampicin was observed. The situation of drug resistance in pulmonary tuberculosis in the Jamahiriya is discussed.

A primary intestinal lymphangiectasia hiding the diagnosis of pleural and pericardial tuberculosis: a clinical observation

PubMed Central

Hammi, Sanaa; Berrani, Hajar; Benouchen, Thami; Lamlami, Naima; Elkhiyat, Imane; Bourkadi, Jamal Eddine

2017-01-01

Primary intestinal lymphangiectasia (Waldmann’s disease) is an exudative enteropathy characterized by lymph leakage into the small bowel lumen leading to hypoalbuminemia, hypogammaglobulinemia and lymphopenia (particularly T-cell). The diagnosis is based on viewing the duodenal lymphangiectasia. A 20 years old female patient, treated for a primary intestinal lymphangiectasia, has consulted for anasarca. Etiological work-up reveals pleural and pericardial tuberculosis. The clinical aggravation of an enteropathy, particularly in adulthood, requires a search for a secondary etiology. Tuberculosis should be sought systematically. PMID:28491220

A primary intestinal lymphangiectasia hiding the diagnosis of pleural and pericardial tuberculosis: a clinical observation.

PubMed

Hammi, Sanaa; Berrani, Hajar; Benouchen, Thami; Lamlami, Naima; Elkhiyat, Imane; Bourkadi, Jamal Eddine

2017-01-01

Primary intestinal lymphangiectasia (Waldmann's disease) is an exudative enteropathy characterized by lymph leakage into the small bowel lumen leading to hypoalbuminemia, hypogammaglobulinemia and lymphopenia (particularly T-cell). The diagnosis is based on viewing the duodenal lymphangiectasia. A 20 years old female patient, treated for a primary intestinal lymphangiectasia, has consulted for anasarca. Etiological work-up reveals pleural and pericardial tuberculosis. The clinical aggravation of an enteropathy, particularly in adulthood, requires a search for a secondary etiology. Tuberculosis should be sought systematically.

Prevalence of post-traumatic stress symptoms and associated factors in tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa.

PubMed

Peltzer, Karl; Naidoo, Pamela; Matseke, Gladys; Louw, Julia; McHunu, Gugu; Tutshana, Bomkazi

2013-01-01

High rates of tuberculosis (TB) and TB/HIV co-infection is often linked with mental health issues such as post-traumatic stress disorder (PTSD) symptoms, which is further associated with poor health outcomes. In a country such as South Africa where rates of these infectious diseases are high, it is concerning that there is limited/no data on prevalence rates of mental disorders such as PTSD and its associated factors. Therefore, the aim of this study was to establish the prevalence of PTSD symptoms and associated factors in TB, TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa. Brief screening self-report tools were used to measure: PTSD symptoms, psychological distress (anxiety and depression) and alcohol misuse. Other relevant measures, such as adherence to medication, stressful life events and sexual risk-taking behaviours, were obtained through structured questions. A total of 4900 public primary care adult patients from clinics in high TB burden districts from three provinces in South Africa participated. All the patients screened positive for TB (either new or retreatment cases). The prevalence of PTSD symptoms was 29.6%. Patients who screened positive for PTSD symptoms and psychological distress were more likely to be on antidepressant medication. Factors that predicted PTSD symptoms were poverty, residing in an urban area, psychological distress, suicide attempt, alcohol and/or drug use before sex, unprotected sex, TB-HIV co-infected and the number of other chronic conditions. Health-care systems should be strengthened to improve delivery of mental health care, by focusing on existing programmes and activities, such as those which address the prevention and treatment of TB and HIV.

Parascapular mass revealing primary tuberculosis of the posterior arch

PubMed Central

Arbault, Anais; Ornetti, Paul; Chevallier, Olivier; Avril, Julien; Pottecher, Pierre

2016-01-01

We report the case of a parascapular abscess revealing primary tuberculosis of the posterior arch in a 31-year-old man. Sectional imaging is essential in order to detect the different lesions of this atypical spinal tuberculosis as osteolysis of the posterior arch extendible to vertebral body, osteocondensation, epidural extension which is common in this location, and high specificity of a zygapophysial, costo-vertebral or transverse arthritis. PMID:27709081

The primary fallopian tube carcinoma: a rare association with pelvic nodal tuberculosis

PubMed Central

Mamouni, Nisrine; Saadi, Hanane; belfatemi, Hinde; Erraghay, Sanaa; Bouchikhi, Chahrazade; Banani, Abdelaziz

2017-01-01

The primary carcinoma of fallopian tube is a rare entity. It represents 0.14 to 1.81% of genital cancers in women. It is a cancer of older women. Its association with tuberculosis is exceptional. We report a rare case of bilateral serous adenocarcinoma of the fallopian tube in a patient aged 42 years, multiparous, whose characteristic is the unexpected association with peritoneal tuberculosis. PMID:29541309

An unusual surgical indication for cerebral tuberculosis: status dystonicus. Case report.

PubMed

Franzini, Andrea; Franzini, Angelo; Levi, Vincenzo; Cordella, Roberto; Messina, Giuseppe

2018-05-15

Actual indications for surgery in tuberculosis are limited to obtaining a diagnosis, acquiring tissue for culture studies, treating hydrocephalus, aspiring a brain abscess, and reducing intracranial pressure in patients with multiple tuberculomas. Tuberculosis-related movement disorders are usually treated pharmacologically. We report on a child affected by post-tubercular generalized dystonia, who progressed to status dystonicus (SD) and underwent stereotactic bilateral pallidotomy. After surgery, SD resolved, and drugs were rapidly tapered. The successful reversal of SD and the motor improvement observed in our patient demonstrate the safety, feasibility, and clinical efficacy of pallidotomy in post-tuberculous-meningoencephalitis dystonia and SD.

Primary Nasopharyngeal Tuberculosis Combined with Tuberculous Otomastoiditis and Facial Nerve Palsy

PubMed Central

Choi, Hee Young; Jang, Ji Hye; Lee, Kyung Mi; Choi, Woo Suk; Kim, Sang Hoon; Yeo, Seung Geun; Kim, Eui Jong

2016-01-01

Primary nasopharyngeal tuberculosis (TB) without pulmonary involvement is rare, even in endemic areas. Herein, we present a rare complication of primary nasopharyngeal TB accompanied with tuberculous otomastoiditis (TOM) and ipsilateral facial nerve palsy, in a 24-year-old female patient, with computed tomography and magnetic resonance imagery findings. PMID:27127580

Immunotherapy with fragmented Mycobacterium tuberculosis cells increases the effectiveness of chemotherapy against a chronical infection in a murine model of tuberculosis.

PubMed

Cardona, Pere-Joan; Amat, Isabel; Gordillo, Sergi; Arcos, Virginia; Guirado, Evelyn; Díaz, Jorge; Vilaplana, Cristina; Tapia, Gustavo; Ausina, Vicenç

2005-02-03

Reduction of colony forming units by rifampicin-isoniazid therapy given 9-17 weeks post-infection was made more pronounced by immunotherapy with a vaccine made of fragmented Mycobacterium tuberculosis cells detoxified and liposomed (RUTI), given on weeks 17, 19 and 21 post-infection, in the murine model of tuberculosis in C57BL/6 and DBA/2 inbred strains. RUTI triggered a Th1/Th2 response, as demonstrated by the production of IgG1, IgG2a and IgG3 antibodies against a wide range of peptides. The histological analysis did not show neither eosinophilia nor necrosis, and granulomatous infiltration was only slightly increased in C57BL/6 mice when RUTI was administered intranasally.

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

Extra-pulmonary primary multidrug-resistant tubercular lymphadenitis in an HIV negative patient

PubMed Central

Kant, Surya; Saheer, S; Hassan, Ghulam; Parengal, Jabeed

2012-01-01

A 28-year-old woman without any history of prior antituberculosis treatment presented with cervical lymphadenopathy and a cold abscess near medial end of clavicle of 5 months duration. Pus culture and sensitivity revealed Mycobacterium tuberculosis resistant to rifampicin and isoniazid. Thus she was diagnosed as a case of primary multidrug-resistant tuberculosis and treated with second line drugs according to culture susceptibility pattern. On completion of therapy, patent showed good clinical response. This case highlights the observation that even extra-pulmonary primary multidrug-resistant tuberculosis can be successfully treated with currently available second line drugs. PMID:22605844

Primary Conjunctival Tuberculosis Presenting as Dry Eye: A Rare Case Report and Review of the Literature.

PubMed

Brar, Rupinder Kaur; Singh, Ashok; Deshpande, Archana Hemant; Gargade, Chitrawati Bal; Das, Sujit

2017-11-01

Primary conjunctival tuberculosis is very rare in the developed countries. In an endemic country like India, it should be considered in the differential diagnosis of any unusual conjunctival lesion with unilaterality, chronicity, and nonresolution of symptoms after steroid use. We present the case of a 52-year-old female who presented with unilateral itching and blurring of vision for 20 days. There were irregular nodular elevated areas with shrinkage of the lower palpebral conjunctiva. A biopsy of the lesion revealed necrotizing epithelioid cell granulomas along with Langhans type of giant cells. However, no acid-fast bacilli were seen on Ziehl-Neelsen stain. Systemic examination of the patient was normal, and there was no evidence of pulmonary tuberculosis. Polymerase chain reaction of conjunctival scrapings was positive for Mycobacterium tuberculosis . The patient was started on antitubercular drugs. We present this very rare case of primary tuberculosis of the conjunctiva presenting with dryness of the eye.

Chronic symptoms and pulmonary dysfunction in post-tuberculosis Brazilian patients.

PubMed

Nihues, Simone de Sousa Elias; Mancuzo, Eliane Viana; Sulmonetti, Nara; Sacchi, Flávia Patussi Correia; Viana, Vanessa de Souza; Netto, Eduardo Martins; Miranda, Silvana Spindola; Croda, Julio

2015-01-01

Questionnaire and spirometry were applied to post-tuberculosis indigenous and non-indigenous individuals from Dourados, Brazil, to investigate the prevalence of chronic respiratory symptoms and pulmonary dysfunction. This was a cross-sectional study in cured tuberculosis individuals as reported in the National System on Reportable Diseases (SINAN) from 2002 to 2012. One hundred and twenty individuals were included in the study and the prevalence of chronic respiratory symptoms was 45% (95% CI, 34-59%). Respiratory symptoms included cough (28%), sputum (23%), wheezing (22%) and dyspnea (8%). These symptoms were associated with alcoholism, AOR: 3.1 (1.2-8.4); less than 4 years of schooling, AOR: 5.0 (1.4-17.7); and previous pulmonary diseases, AOR: 5.4 (1.7-17.3). Forty-one percent (95% CI, 29-56) had pulmonary disorders, of which the most prevalent were obstructive disorders (49%), followed by obstructive disorder with reduced forced vital capacity disorders (46%) and restrictive disorders (5%). The lifestyle difference could not explain differences in chronic symptoms and/or the prevalence of pulmonary dysfunction. The high prevalence of chronic respiratory symptoms and pulmonary dysfunction in post-tuberculosis patients indicates a need for further interventions to reduce social vulnerability of patients successfully treated for tuberculosis. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Laser-heat puncturing as highly effective method of post-tuberculous cystalgia treatment

NASA Astrophysics Data System (ADS)

Koultchavenia, Ekaterina V.

1999-07-01

The tuberculosis of an urine bladder in men develops is authentic less often, and recovery is authentic more often, than in the women. In 39,1 percent of the women with nephrotuberculosis and urocystis and urocystis tuberculosis a specific cystitides is finished in development of post- tuberculous cystalgia. One of starting mechanism of dysuria after the transferred urocystis tuberculosis in the women in menopause is hormonal insufficiency. The method of laser heat puncturing, developed by us, for the treatment this complication is highly effective, does not require additional introduction of medicines, can be executed as in hospitals, and in our-patient.

Is there a rationale for pulmonary rehabilitation following successful chemotherapy for tuberculosis?

PubMed Central

Muñoz-Torrico, Marcela; Rendon, Adrian; Centis, Rosella; D'Ambrosio, Lia; Fuentes, Zhenia; Torres-Duque, Carlos; Mello, Fernanda; Dalcolmo, Margareth; Pérez-Padilla, Rogelio; Spanevello, Antonio; Migliori, Giovanni Battista

2016-01-01

ABSTRACT The role of tuberculosis as a public health care priority and the availability of diagnostic tools to evaluate functional status (spirometry, plethysmography, and DLCO determination), arterial blood gases, capacity to perform exercise, lesions (chest X-ray and CT), and quality of life justify the effort to consider what needs to be done when patients have completed their treatment. To our knowledge, no review has ever evaluated this topic in a comprehensive manner. Our objective was to review the available evidence on this topic and draw conclusions regarding the future role of the "post-tuberculosis treatment" phase, which will potentially affect several million cases every year. We carried out a non-systematic literature review based on a PubMed search using specific keywords (various combinations of the terms "tuberculosis", "rehabilitation", "multidrug-resistant tuberculosis", "pulmonary disease", "obstructive lung disease", and "lung volume measurements"). The reference lists of the most important studies were retrieved in order to improve the sensitivity of the search. Manuscripts written in English, Spanish, and Russian were selected. The main areas of interest were tuberculosis sequelae following tuberculosis diagnosis and treatment; "destroyed lung"; functional evaluation of sequelae; pulmonary rehabilitation interventions (physiotherapy, long-term oxygen therapy, and ventilation); and multidrug-resistant tuberculosis.The evidence found suggests that tuberculosis is definitively responsible for functional sequelae, primarily causing an obstructive pattern on spirometry (but also restrictive and mixed patterns), and that there is a rationale for pulmonary rehabilitation. We also provide a list of variables that should be discussed in future studies on pulmonary rehabilitation in patients with post-tuberculosis sequelae. PMID:27812638

Cytological Diagnosis of Primary Thyroid Tuberculosis.

PubMed

Goyal, P; Mittal, D; Ghosh, S; Agrawal, D; Sehgal, S; Singh, S

2015-01-01

Primary thyroid tuberculosis is an extremely rare disease, even in countries where other forms of tuberculosis are abundant. TT has no age bar but usually affects women in fourth and fifth decade. Hereby, we report a case of 16-years-old girl presented with complaint of progressively increasing, painful thyroid swelling. Diagnosis of TT was made on cytology and there was no evidence of involvement of any other organ by tuberculosis. Despite of its rarity, TT is usually misdiagnosed. So, a clinician should always consider this entity in the differential diagnosis of thyroid swelling. Fine needle aspiration cytology is the best diagnostic method and can result in the avoidance of unnecessary thyroid surgeries.

In vivo induction of neutrophil extracellular traps by Mycobacterium tuberculosis in a guinea pig model.

PubMed

Filio-Rodríguez, Georgina; Estrada-García, Iris; Arce-Paredes, Patricia; Moreno-Altamirano, María M; Islas-Trujillo, Sergio; Ponce-Regalado, M Dolores; Rojas-Espinosa, Oscar

2017-10-01

In 2004, a novel mechanism of cellular death, called 'NETosis', was described in neutrophils. This mechanism, different from necrosis and apoptosis, is characterized by the release of chromatin webs admixed with microbicidal granular proteins and peptides (NETs). NETs trap and kill a variety of microorganisms. Diverse microorganisms, including Mycobacterium tuberculosis, are NET inducers in vitro. The aim of this study was to examine whether M. tuberculosis can also induce NETs in vivo and if the NETs are bactericidal to the microorganism. Guinea pigs were intradermally inoculated with M. tuberculosis H37Rv, and the production of NETs was investigated at several time points thereafter. NETs were detected as early as 30 min post-inoculation and were clearly evident by 4 h post-inoculation. NETs produced in vivo contained DNA, myeloperoxidase, elastase, histones, ROS and acid-fast bacilli. Viable and heat-killed M. tuberculosis, as well as Mycobacterium bovis BCG were efficient NET inducers, as were unilamellar liposomes prepared with lipids from M. tuberculosis. In vitro, guinea pig neutrophils also produced NETs in response to M. tuberculosis. However, neither the in vivo nor the in vitro-produced NETs were able to kill M. tuberculosis. Nevertheless, in vivo, neutrophils might propitiate recruitment and activation of more efficient microbicidal cells.

[Tuberculosis incidence and primary drug resistance rates in young soldiers: data from 14 military hospitals in Turkey].

PubMed

Taş, Dilaver; Taşçı, Cantürk; Demirer, Ersin; Sezer, Ogün; Okutan, Oğuzhan; Kartaloğlu, Zafer

2012-01-01

Tuberculosis is an important health care problem worldwide as well as in Turkey and the control programmes are still in progress. Epidemiological data are necessary to conduct control studies related to the disease. Tuberculosis incidence and drug resistance rates are two necessary parameters which should be monitored for the effective establishment of tuberculosis control. In this objective, tuberculosis incidence and drug resistance rates were studied in young subjects performing their compulsory military service in Turkish Armed Forces. The study was performed in 14 military hospitals which served for the country-wide soldier patients. Based on the computerized medical database of these military hospitals, conscripts diagnosed with tuberculosis between January 01, 2009 and December 31, 2009 were retrospectively evaluated. Drug sensitivity tests of the Mycobacterium tuberculosis complex isolates were done prior to the treatment in the two military medical training hospitals of the two big cities of Turkey (Ankara and Istanbul). There were a total of 259 new tuberculosis cases in 2009 and they were all male with a mean age of 22.51 ± 4.63 years. The number of patients with pulmonary, extrapulmonary (pleuresia, lymphadenitis, others) and both pulmonary and extrapulmonary involvements were 175 (67.5%), 72 (27.8%) and 12 (4.6%), respectively. The total rate of pulmonary tuberculosis cases was 72.2% (187/259) and 64.7% (121/187) of them were smear positive. Since the number of soldiers in Turkish army in the midyear was 537.200; total tuberculosis, pulmonary tuberculosis and smear-positive pulmonary tuberculosis incidences were estimated as 48.2/100.000, 34.8/100.000 and 22.5/100.000, respectively. Drug sensitivity tests was performed for the M.tuberculosis complex strains isolated from 104 cases. Primary resistance rate to at least one drug was detected as 16.3% (n= 17), while the rates of resistance for isoniazid, rifampicin, ethambutol and streptomycin were 12.5% (n= 13), 7.7% (n= 8), 5.8% (n= 6) and 0.9% (n= 1), respectively. Multidrug resistant tuberculosis (isoniazid + rifampicin resistance) was detected in 6 (5.8%) patients. Our data indicated that although tuberculosis incidence among young soldiers was moderately high, a decreasing trend was observed when compared to the previous years. However, the rates of primary anti-tuberculosis drug resistance and multi-drug resistance were found to be high in our study. To decrease the incidence of tuberculosis and multidrug resistant tuberculosis, drug sensitivity tests should be performed for each patient and national tuberculosis programme should be established effectively.

[A rare cause of anosmia: nasosinusal tuberculosis].

PubMed

Hemmaoui, B; Fejjal, N; Errami, N; Temsamani, H; Benchafai, I; Jahidi, A; Benariba, F

2014-10-01

We report the case of a 46-year-old-woman who presented with anosmia and nasal obstruction. Primary nasal tuberculosis was discovered. Primary nasal tuberculosis is very rare. Women are more touched than men. Symptomatology is often unilateral with nasal obstruction, anterior rhinorrhea or epistaxis. Diagnosis relies on the anatomopathologic and bacteriological examinations. The treatment is mainly medical based on antituberculosis drugs. In the light of this case report, a review of the literature was made. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

An Unusual Gross Appearance of Vulval Tuberculosis Masquerading as Tumor

PubMed Central

Arakeri, Surekha U.

2014-01-01

Tuberculosis of the vulva is very rare. It is found in about 0.2% of the cases of genital tract tuberculosis. It usually presents as small shallow ulcers and multiple sinus tracts or rarely as elephantiasis of vulva. Except for very rare cases of primary tuberculosis in the vulva, it is usually associated with tuberculosis elsewhere in the body leading to secondary tuberculosis. Here, we report a case of secondary vulval tuberculosis which presented as a vulval mass in a 40-year-old female patient. The rarity of this presentation in the female genital tract is emphasized. PMID:25298898

An unusual gross appearance of vulval tuberculosis masquerading as tumor.

PubMed

Arakeri, Surekha U; Sinkar, Prachi

2014-01-01

Tuberculosis of the vulva is very rare. It is found in about 0.2% of the cases of genital tract tuberculosis. It usually presents as small shallow ulcers and multiple sinus tracts or rarely as elephantiasis of vulva. Except for very rare cases of primary tuberculosis in the vulva, it is usually associated with tuberculosis elsewhere in the body leading to secondary tuberculosis. Here, we report a case of secondary vulval tuberculosis which presented as a vulval mass in a 40-year-old female patient. The rarity of this presentation in the female genital tract is emphasized.

Early onset primary pulmonary cryptococcosis in a renal transplant patient.

PubMed

Tarai, B; Kher, V; Kotru, P; Sabhikhi, A; Barman, P; Rattan, A

2010-01-01

We report a case of primary pulmonary cryptococcosis in a post-renal transplant patient. A 65-year-old male renal transplant patient was admitted to the hospital with a low grade fever of 1 month, radiologically mimicking tuberculosis (TB). Broncho-alveolar fluid (BAL) shows capsulated yeast, and Cryptococcus neoformans was grown on culture supported by cytology and histopathological examination. Cryptococcal antigen was positive (32-fold) in serum and was negative in cerebrospinal fluid (CSF). The patient was given amphotericin B and 5-flucytosine and clinical improvement was seen on a weekly follow up. The serum cryptococcal antigen test might contribute to the early detection and treatment of pulmonary cryptococcosis. The results of antifungal susceptibility were aid in selecting the drug of choice for treatment.

Progressive Primary Pulmonary Tuberculosis Presenting as the Sudden Unexpected Death in Infancy: A Case Report

PubMed Central

Dempers, Johan; Sens, Mary Ann; Wadee, Shabbir Ahmed; Kinney, Hannah C.; Odendaal, Hein J.; Wright, Colleen A.

2010-01-01

The classification of an unexpected infant death as the sudden infant death syndrome (SIDS) depends upon a complete autopsy and death scene investigation to exclude known causes of death. Here we report the death of a four-month-old infant in a tuberculosis endemic area that presented as a sudden unexpected death in infancy (SUDI) with no apparent explanation based on the death scene characteristics. The autopsy, however, revealed progressive primary pulmonary tuberculosis with intrathoracic adenopathy, compression of the tracheobronchial tree and miliary lesions in the liver. This case underscores the clinical difficulties in the diagnosis of infantile tuberculosis, as well as the possibility of sudden death as part of its protean manifestations. The pathology and clinical progression of tuberculosis in infants differs from older children and adults due to the immature immune response in infants. This case dramatically highlights the need for complete autopsies in all sudden and unexpected infant deaths, as well as the public health issues in a sentinel infant tuberculosis diagnosis. PMID:20705406

Antro-duodenal tuberculosis causing gastric outlet obstruction--a rare presentation of a protean disease.

PubMed

Gheorghe, Liana; Băncilă, Ion; Gheorghe, Cristian; Herlea, Vlad; Vasilescu, Cătălin; Aposteanu, Gabriela

2002-06-01

Gastroduodenal tuberculosis is a rare location of abdominal tuberculosis. It usually occurs secondary to pulmonary tuberculosis. We report a case of a 63-year-old woman admitted to the referral center for symptoms of upper gastrointestinal obstruction caused by ulcerohypertrophic antroduodenal tuberculosis. The lesion was misdiagnosed as malignancy at endoscopy. Even at surgery, the lesion was considered gastric cancer and imposed an oncologic resection. The diagnosis was established in the presence of giant-cell granulomas with caseating necrosis in the surgical resected specimens. In our case, the rare gastroduodenal location of abdominal tuberculosis occurred as primary tuberculosis, in the absence of other identifiable locations.

Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy.

PubMed

Mieras, Liesbeth; Anthony, Richard; van Brakel, Wim; Bratschi, Martin W; van den Broek, Jacques; Cambau, Emmanuelle; Cavaliero, Arielle; Kasang, Christa; Perera, Geethal; Reichman, Lee; Richardus, Jan Hendrik; Saunderson, Paul; Steinmann, Peter; Yew, Wing Wai

2016-06-08

Post-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where SDR is currently being implemented under routine programme conditions in defined areas, questions were raised by health authorities and professional bodies about the possible risk of inducing rifampicin resistance among the M. tuberculosis strains circulating in these areas. This issue has not been addressed in scientific literature to date. To produce an authoritative consensus statement about the risk that SDR would induce rifampicin-resistant tuberculosis, a meeting was convened with tuberculosis (TB) and leprosy experts. The experts carefully reviewed and discussed the available evidence regarding the mechanisms and risk factors for the development of (multi) drug-resistance in M. tuberculosis with a view to the special situation of the use of SDR as PEP for leprosy. They concluded that SDR given to contacts of leprosy patients, in the absence of symptoms of active TB, poses a negligible risk of generating resistance in M. tuberculosis in individuals and at the population level. Thus, the benefits of SDR prophylaxis in reducing the risk of developing leprosy in contacts of new leprosy patients far outweigh the risks of generating drug resistance in M. tuberculosis.

Tuberculosis Outbreak in a Primary School, Milan, Italy

PubMed Central

Faccini, Marino; Codecasa, Luigi Ruffo; Ciconali, Giorgio; Cammarata, Serafina; Borriello, Catia Rosanna; De Gioia, Costanza; Za, Alessandro; Marino, Andrea Filippo; Ferrarese, Maurizio; Gesu, Giovanni; Mazzola, Ester; Castaldi, Silvana

2013-01-01

Investigation of an outbreak of tuberculosis (TB) in a primary school in Milan, Italy, found 15 schoolchildren had active TB disease and 173 had latent TB infection. TB was also identified in 2 homeless men near the school. Diagnostic delay, particularly in the index case-patient, contributed to the transmission of infection. PMID:23621942

Recent developments in the diagnosis and management of tuberculosis.

PubMed

Sulis, Giorgia; Centis, Rosella; Sotgiu, Giovanni; D'Ambrosio, Lia; Pontali, Emanuele; Spanevello, Antonio; Matteelli, Alberto; Zumla, Alimuddin; Migliori, Giovanni Battista

2016-11-03

Tuberculosis (TB) is a major public health issue worldwide, with ~9.6 million new incident cases and 1.5 million deaths in 2014. The End-TB Strategy launched by the World Health Organization in the context of the post-2015 agenda aims to markedly abate the scourge of TB towards global elimination, by improving current diagnostic and therapeutic practices, promoting preventative interventions, stimulating government commitment and increased financing, and intensifying research and innovation. The emergence and spread of multidrug-resistant strains is currently among the greatest concerns, which may hinder the achievement of future goals. It is crucial that primary healthcare providers are sufficiently familiar with the basic principles of TB diagnosis and care, to ensure early case detection and prompt referral to specialised centres for treatment initiation and follow-up. Given their special relationship with patients, they are in the best position to promote educational interventions and identify at-risk individuals as well as to improve adherence to treatment.

Defining the Needs for Next Generation Assays for Tuberculosis

PubMed Central

Denkinger, Claudia M.; Kik, Sandra V.; Cirillo, Daniela Maria; Casenghi, Martina; Shinnick, Thomas; Weyer, Karin; Gilpin, Chris; Boehme, Catharina C.; Schito, Marco; Kimerling, Michael; Pai, Madhukar

2015-01-01

To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets. PMID:25765104

[Morphological signs of inflammatory activity in different clinical forms of drug-resistant pulmonary tuberculosis].

PubMed

Elipashev, A A; Nikolsky, V O; Shprykov, A S

to determine whether the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant pulmonary tuberculosis. The material taken from 310 patients operated on in 2010-2015 were retrospectively examined. The patients underwent economical lung resections of limited extent (typical and atypical ones of up to 3 segments) for circumscribed forms of tuberculosis with bacterial excretion. A study group consisted of 161 (51.9%) patients with drug-resistant variants of pulmonary tuberculosis. A control group included 149 (48.1%) patients with preserved susceptibility of Mycobacterium tuberculosis to anti-TB drugs. The activity of specific changes in tuberculosis was morphologically evaluated in accordance with the classification proposed by B.M. Ariel in 1998. The highest activity of fourth-to-fifth degree specific inflammation, including that outside the primary involvement focus, was obtained in the drug-resistant pulmonary tuberculosis group due to the predominance of patients with cavernous and fibrous-cavernous tuberculosis versus those in whom the susceptibility to chemotherapeutic agents was preserved. A macroscopic study showed that the primary lesion focus had a median size in one-half of the all the examinees; but large tuberculomas, caverns, and fibrous caverns over 4 cm in diameter were multiple and detected in the drug-resistant pulmonary tuberculosis group. Multidrug resistance was observed in more than 60% of the patients with fibrous-cavernous pulmonary tuberculosis, extensive drug resistance was seen in those with cavernous tuberculosis, which is an aggravating factor. The data obtained from the morphological study of the intraoperative material can specify the clinical form of tuberculosis and evaluate the efficiency of preoperative specific therapy. The highest activity of specific inflammation was observed in patients with multiple drug-resistant pulmonary tuberculosis, the prevalence of third-to-fourth degree specific changes was seen in those with multiple and extensively drug-resistant tuberculosis. The findings suggest that the activity of tuberculous inflammation is associated with different clinical forms of drug-resistant tuberculosis and with a spectrum of drug resistance.

Prospects in Mycobacterium bovis Bacille Calmette et Guérin (BCG) Vaccine Diversity and Delivery: Why does BCG fail to protect against Tuberculosis?

PubMed Central

Moliva, Juan I.; Turner, Joanne; Torrelles, Jordi B.

2015-01-01

Mycobacterium tuberculosis (M.tb) infection leads to active tuberculosis (TB), a disease that kills one human every 18 seconds. Current therapies available to combat TB include chemotherapy and the preventative vaccine Mycobacterium bovis Bacille Calmette et Guérin (BCG). Increased reporting of drug resistant M.tb strains worldwide indicates that drug development cannot be the primary mechanism for eradication. BCG vaccination has been used globally for protection against childhood and disseminated TB, however, its efficacy at protecting against pulmonary TB in adult and aging populations is highly variable. In this regard, the immune response generated by BCG vaccination is incapable of sterilizing the lung post M.tb infection as indicated by the large proportion of individuals with latent TB infection that have received BCG. Although many new TB vaccine candidates have entered the development pipeline, only a few have moved to human clinical trials; where they showed no efficacy and/or were withdrawn due to safety regulations. These trials highlight our limited understanding of protective immunity against the development of active TB. Here, we discuss current vaccination strategies and their impact on the generation and sustainability of protective immunity against TB. PMID:26319069

Primary Pulmonary Mucinous (Colloid) Adenocarcinoma that Arose in the Cavernomyoplasty Area in a Patient with Tuberculosis: A Rare Case Report.

PubMed

Yener, Neşe A; Sariman, Nesrin; Atasoy, Mehmet M; Midi, Ahmet; Örki, Alpay

2017-01-01

Primary pulmonary mucinous (colloid) adenocarcinoma is a rare type of lung cancer. Its arising in the cavernomyoplasty area has not been reported before. We here describe a sixty-year-old man with a previous history of multidrug-resistant and surgically-treated tuberculosis who was diagnosed as primary mucinous adenocarcinoma in the cavernomyoplasty site. We discuss the relevant literature on this rare entity.

Impact of type of calcineurin inhibitor on post-transplant tuberculosis: Single-center study from India.

PubMed

Agarwal, Sanjay K; Bhowmik, Dipankar; Mahajan, Sandeep; Bagchi, Soumita

2017-02-01

Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients. Immunosuppressive drugs are one of the most important risk factor for post-transplant tuberculosis (PTTB). A paucity of data exists about the impact of the type of calcineurin inhibitor on PTTB. In this retrospective study, all adult patients on calcineurin inhibitor-based immunosuppression were included. Patients receiving TB chemoprophylaxis were excluded. Diabetes, duration of dialysis, hepatitis B and C, past treated TB, induction therapy, type of antimetabolite, acute rejection, new onset of diabetes after renal transplantation (RT) (NODAT) and cytomegalovirus (CMV) were analyzed in tacrolimus (Tac) and cyclosporine (CsA) groups. Primary outcome was incidence of TB and secondary outcomes were timeline of development of TB after RT and pattern of TB in the two groups. Of the 1664 patients included, 582 patients received CsA-based immunosuppression while 1082 received Tac-based immunosuppression. Duration of dialysis, positive tuberculin skin test, use of induction, mycophenolate mofetil use, CMV infection, and NODAT were significantly more, and hepatitis B infection, past treated TB, and acute rejection episodes were significantly less in the Tac group. At the end of follow-up, incidence of TB in the Tac group was significantly less than in the CsA group (6.1% vs 19.9%, P<.001). Mean time for development of TB after RT was similar in both the groups and nodal and disseminated TB were more common in the Tac group. In conclusion, our study shows that use of Tac as compared to CsA significantly decreases incidence of PTTB. Time of infection since transplant was similar in both the groups. However, nodal and disseminated TB were more common in the Tac group. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Increasing Incidence of Tuberculosis Infection in the Coastal Region of Northern Miyagi after the Great East Japan Earthquake.

PubMed

Sakurai, Masahiro; Takahashi, Tatsuya; Ohuchi, Miyako; Terui, Yuki; Kiryu, Kouji; Shikano, Kazuo

2016-03-01

On March 11, 2011, the Great East Japan Earthquake struck off the northeast coast of Japan. Within an hour of the earthquake, devastating tsunamis swept over the coastal region of the Miyagi Prefecture, facing Pacific Ocean. Accordingly, more than 400,000 residents were forced to stay at evacuation shelters. We investigated the changes in tuberculosis prevalence after the disaster. Annual data for all tuberculosis patients between April 1, 2009 and March 31, 2013 were extracted from the database of the Miyagi Prefectural Government. In the coastal region of Northern Miyagi, the number of tuberculosis patients increased in the post-disaster period (p < 0.001, 9.6 vs.19.1 per 100,000 people), compared to the pre-disaster period. In contrast, its prevalence did not change in the inland region of Northern Miyagi and the coastal and inland regions of Southern Miyagi. Importantly, in the inland and coastal regions of Northern Miyagi, the number of patients with latent tuberculosis infection (LTBI) increased in the post-disaster period (p < 0.001). Furthermore, in the coastal shelters, 11 evacuees with the history of contacting tuberculosis patients were diagnosed with LTBI, whereas no cases of LTBI patients were observed in the inland shelters. Thus, staying in the coastal shelters was a risk factor for contracting tuberculosis (OR: 19.31, 95% CI: 1.11-334.80); indeed, twice as many evacuees visited each coastal shelter on April 1, 2011, compared to the inland region. We should prepare the shelters to avoid overcrowding, and long-term observation is required to detect the prevalence of tuberculosis infection.

Innate myeloid cell TNFR1 mediates first line defence against primary Mycobacterium tuberculosis infection.

PubMed Central

Segueni, Noria; Benmerzoug, Sulayman; Rose, Stéphanie; Gauthier, Amandine; Bourigault, Marie-Laure; Reverchon, Flora; Philippeau, Amandine; Erard, François; Le Bert, Marc; Bouscayrol, Hélène; Wachter, Thierry; Garcia, Irène; Kollias, George; Jacobs, Muazzam; Ryffel, Bernhard; Quesniaux, Valerie F.J.

2016-01-01

TNF is crucial for controlling Mycobacterium tuberculosis infection and understanding how will help immunomodulating the host response. Here we assessed the contribution of TNFR1 pathway from innate myeloid versus T cells. We first established the prominent role of TNFR1 in haematopoietic cells for controlling M. tuberculosis in TNFR1 KO chimera mice. Further, absence of TNFR1 specifically on myeloid cells (M-TNFR1 KO) recapitulated the uncontrolled M. tuberculosis infection seen in fully TNFR1 deficient mice, with increased bacterial burden, exacerbated lung inflammation, and rapid death. Pulmonary IL-12p40 over-expression was attributed to a prominent CD11b+ Gr1high cell population in infected M-TNFR1 KO mice. By contrast, absence of TNFR1 on T-cells did not compromise the control of M. tuberculosis infection over 6-months. Thus, the protective TNF/TNFR1 pathway essential for controlling primary M. tuberculosis infection depends on innate macrophage and neutrophil myeloid cells, while TNFR1 pathway in T cells is dispensable. PMID:26931771

Mycobacterium tuberculosis nitrogen assimilation and host colonization require aspartate

PubMed Central

Gouzy, Alexandre; Larrouy-Maumus, Gérald; Wu, Ting-Di; Peixoto, Antonio; Levillain, Florence; Lugo-Villarino, Geanncarlo; Gerquin-Kern, Jean-Luc; de Carvalho, Luiz Pedro Sório; Poquet, Yannick; Neyrolles, Olivier

2013-01-01

Here we identify the amino acid transporter AnsP1 as the unique aspartate importer in the human pathogen Mycobacterium tuberculosis. Metabolomic analysis of a mutant inactivated in AnsP1 revealed the transporter is essential for M. tuberculosis to assimilate nitrogen from aspartate. Virulence of the AnsP1 mutant is impaired in vivo, revealing aspartate is a primary nitrogen source required for host colonization by the tuberculosis bacillus. PMID:24077180

Trends of Mycobacterium bovis Isolation and First-Line Anti-tuberculosis Drug Susceptibility Profile: A Fifteen-Year Laboratory-Based Surveillance.

PubMed

Bobadilla-del Valle, Miriam; Torres-González, Pedro; Cervera-Hernández, Miguel Enrique; Martínez-Gamboa, Areli; Crabtree-Ramirez, Brenda; Chávez-Mazari, Bárbara; Ortiz-Conchi, Narciso; Rodríguez-Cruz, Luis; Cervantes-Sánchez, Axel; Gudiño-Enríquez, Tomasa; Cinta-Severo, Carmen; Sifuentes-Osornio, José; Ponce de León, Alfredo

2015-09-01

Mycobacterium tuberculosis causes the majority of tuberculosis (TB) cases in humans; however, in developing countries, human TB caused by M. bovis may be frequent but undetected. Human TB caused by M. bovis is considered a zoonosis; transmission is mainly through consumption of unpasteurized dairy products, and it is less frequently attributed to animal-to-human or human-to-human contact. We describe the trends of M. bovis isolation from human samples and first-line drug susceptibility during a 15-year period in a referral laboratory located in a tertiary care hospital in Mexico City. Data on mycobacterial isolates from human clinical samples were retrieved from the laboratory's database for the 2000-2014 period. Susceptibility to first-line drugs: rifampin, isoniazid, streptomycin (STR) and ethambutol was determined. We identified 1,165 isolates, 73.7% were M. tuberculosis and 26.2%, M. bovis. Among pulmonary samples, 16.6% were M. bovis. The proportion of M. bovis isolates significantly increased from 7.8% in 2000 to 28.4% in 2014 (X(2)trend, p<0.001). Primary STR resistance was higher among M. bovis compared with M. tuberculosis isolates (10.9% vs.3.4%, p<0.001). Secondary multidrug resistance (MDR) rates were 38.5% and 34.4% for M. bovis and M. tuberculosis, respectively (p = 0.637). A rising trend of primary STR monoresistance was observed for both species (3.4% in 2000-2004 vs. 7.6% in 2010-2014; p = 0.02). There is a high prevalence and a rising trend of M. bovis isolates in our region. The proportion of pulmonary M. bovis isolates is higher than in previous reports. Additionally, we report high rates of primary anti-tuberculosis resistance and secondary MDR in both M. tuberculosis and M. bovis. This is one of the largest reports on drug susceptibility of M. bovis from human samples and shows a significant proportion of first-line anti-tuberculosis drug resistance.

Decline of common mental disorders over time in public primary care tuberculosis patients in South Africa.

PubMed

Peltzer, Karl

2016-04-01

The relationship between tuberculosis and common mental disorders over time is under researched. The aim of this investigation was to estimate the prevalence of common mental disorders and its predictors among tuberculosis patients over a period of six months. A longitudinal investigation was carried out with new tuberculosis and tuberculosis retreatment patients systematically selected from 40 primary health care facilities and had screened positive for hazardous or harmful alcohol use in South Africa. Common mental disorders were measured with the Kessler-10 scale and the Primary Care Posttraumatic Stress Disorder Screen at baseline and at six months. At six months, 710 tuberculosis patients had completed the follow up. At baseline, 34.1% had severe psychological distress with a higher cut-off score (≥28), 81.1% had moderate psychological distress with a lower cut-off score (≥16), and 29.4% had posttraumatic stress disorder symptoms (two or more). At the six-month follow-up, severe psychological stress significantly reduced by 12.3%, moderate psychological distress reduced by 24.9%, and PTSD reduced by 20.0%. Multivariate logistic regression analysis using generalized estimation equation modeling across the three mental conditions found that moderate psychological distress and PTSD symptoms but not severe psychological distress significantly reduced over time. Having chronic conditions, including HIV, and sociodemographic factors (lower education and poverty) were associated with common mental disorders. The prevalence of moderate psychological distress and posttraumatic stress disorder symptoms significantly reduced over a period of six months. Mental health services should be integrated into tuberculosis treatment programs. © The Author(s) 2016.

Tracheal Wall Thickening Is Associated with the Granulation Tissue Formation Around Silicone Stents in Patients with Post-Tuberculosis Tracheal Stenosis

PubMed Central

Eom, Jung Seop; Jeon, Kyeongman; Um, Sang-Won; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kwon, O Jung

2013-01-01

Purpose Tracheal restenosis due to excessive granulation tissue around a silicone stent requires repeated bronchoscopic interventions in patients with post-tuberculosis tracheal stenosis (PTTS). The current study was conducted to identify the risk factors for granulation tissue formation after silicone stenting in PTTS patients. Materials and Methods A retrospective study was conducted between January 1998 and December 2010. Forty-two PTTS patients with silicone stenting were selected. Clinical and radiological variables were retrospectively collected and analyzed. Results Tracheal restenosis due to granulation tissue formation were found in 20 patients (47.6%), and repeated bronchoscopic interventions were conducted. In multivariate analysis, tracheal wall thickness, measured on axial computed tomography scan, was independently associated with granulation tissue formation after silicone stenting. Furthermore, the degree of tracheal wall thickness was well correlated with the degree of granulation tissue formation. Conclusion Tracheal wall thickening was associated with granulation tissue formation around silicone stents in patients with post-tuberculosis tracheal stenosis. PMID:23709431

Tracheal wall thickening is associated with the granulation tissue formation around silicone stents in patients with post-tuberculosis tracheal stenosis.

PubMed

Eom, Jung Seop; Kim, Hojoong; Jeon, Kyeongman; Um, Sang-Won; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kwon, O Jung

2013-07-01

Tracheal restenosis due to excessive granulation tissue around a silicone stent requires repeated bronchoscopic interventions in patients with post-tuberculosis tracheal stenosis (PTTS). The current study was conducted to identify the risk factors for granulation tissue formation after silicone stenting in PTTS patients. A retrospective study was conducted between January 1998 and December 2010. Forty-two PTTS patients with silicone stenting were selected. Clinical and radiological variables were retrospectively collected and analyzed. Tracheal restenosis due to granulation tissue formation were found in 20 patients (47.6%), and repeated bronchoscopic interventions were conducted. In multivariate analysis, tracheal wall thickness, measured on axial computed tomography scan, was independently associated with granulation tissue formation after silicone stenting. Furthermore, the degree of tracheal wall thickness was well correlated with the degree of granulation tissue formation. Tracheal wall thickening was associated with granulation tissue formation around silicone stents in patients with post-tuberculosis tracheal stenosis.

[Tuberculosis in cattle - surprisingly re-emerging or continuously present?].

PubMed

Moser, I; Köhler, H; Menge, C

2014-01-01

Tuberculosis in cattle, caused by Mycobacterium (M.) bovis/M. caprae, is globally one of the most important zoonotic diseases in cattle. It was widespread in Germany until the second half of the 20th century. Due to the effective control and eradication campaigns in Germany, the epidemic was almost eradicated. Consequently, Germany was regarded as essentially tuberculosis free since the end of 1961 (West) and the end of 1978 (East). By declaring the unified Germany "officially free of tuberculosis" (OTF) in 1996, freedom from tuberculosis was officially ratified by the European Commission. The prerequisite was the detection of tuberculosis in less than 0.1% of the cattle holdings per year in Germany. This status has been steadily maintained hitherto, thus resulting in some loss of awareness of bovine tuberculosis by veterinarians, farmers and the public over many decades. After 1996, the number of notified outbreaks had been on average less than 10 per 200,000 cattle holdings per year for many years. It was the year 2008 when the numbers increased. Based in part on subsequently enhanced ante mortem testing efforts, 46 outbreaks were notified in 2013. Bavaria and Lower Saxony were the federal states with the highest number of cases. Consequently, the national tuberculosis regulation was revised in 2009, 2012 and 2013 to form the basis for a modification of tuberculosis surveillance. Regionally, an improvement of the control strategy was considered necessary. In addition to the traditionally applied examination and detection methods of the tuberculin skin test (ante mortem) and bacteriological culture (post mortem), the gamma-interferon-release assay (ante mortem) and the molecular detection of the causative pathogen (post mortem) were introduced into the official collection of recommended methods. Consequently, the diagnostic procedure of tuberculosis has been accelerated. However, in many cases the increase in the range of available test systems did not increase the ease in the interpretation of results.

High prevalence of multidrug resistant tuberculosis in Djibouti: a retrospective study.

PubMed

Boyer-Cazajous, Géraldine; Martinaud, Christophe; Déhan, Céline; Hassan, Mohammed Osman; Gaas, Yassin; Chenilleau-Vidal, Marie-Caroline; Soler, Charles

2014-02-13

The Republic of Djibouti is an African country that exhibits one of the highest incidence rate of tuberculosis in the world. The aim of this study was to evaluate the prevalence of multidrug-resistant tuberculosis among new cases. We studied retrospectively every tuberculosis case diagnosed over a 12-month period in patients hospitalized at the French Military Hospital of Bouffard. During this period, 1,274 samples from 675 patients were tested. We isolated 266 mycobacteria corresponding to 180 cases of tuberculosis. Thirty-three were fully susceptible and 57% met the tuberculosis criteria, with 46% primary resistance. No extensively-drug-resistant tuberculosis was found. Our results highlight a major concern about the situation in this part of the world.

Effect of Video-Assisted Teaching Module (VATM) on Knowledge of ASHAs regarding RNTCP in Kuchinda Block of Sambalpur (Odisha).

PubMed

Pradhan, Malati; Dash, Bijayalakshmi

2015-05-01

Infectious disease is a major public health issue for both developed and developing countries. Among infectious diseases, tuberculosis (TB) is most prevalent in the develop- ing countries. India is the highest TB burden country in the world and accounts for nearly one fifth (20%) of global burden of tuberculosis. A pre-experimental design where pre- and post-test without control group with experimental approach was undertaken in Kuchinda block of Sambalpur district (Odisha) with the objectives to assess effectiveness of Video-assisted Teaching Module (VATM) on knowledge of Accredited Social Health Activists (ASHAs) regarding Revised National Tuberculosis Control Programme (RNTCP) Data were collected from 52 ASHAs, selected by systematic random sampling technique through structured questionnaire. The overall mean score in pre-test was 23.31±3.07 which is 58.27 percent of maximum score and good knowledge whereas it was 34.35±3.56 while post-test it was 85.87 percent of maximum score during post-test showing a difference of 27.6 percent effectiveness. Highly significant (p<0.01) differ- ence was found between pre- and post-test knowledge score and no significant (>0.05) association was found between post-test knowledge score when compared to all the demographic variables of ASHAs.

Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results.

PubMed

Jacomelli, Márcia; Silva, Priscila Regina Alves Araújo; Rodrigues, Ascedio Jose; Demarzo, Sergio Eduardo; Seicento, Márcia; Figueiredo, Viviane Rossi

2012-01-01

To evaluate the diagnostic accuracy of bronchoscopy in patients with clinical or radiological suspicion of tuberculosis who were unable to produce sputum or with negative sputum smear microscopy results. A prospective cross-sectional study involving 286 patients under clinical or radiological suspicion of having pulmonary tuberculosis and submitted to bronchoscopy-BAL and transbronchial biopsy (TBB). The BAL specimens were submitted to direct testing and culture for AFB and fungi, whereas the TBB specimens were submitted to histopathological examination. Of the 286 patients studied, 225 (79%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary tuberculosis, in 127 (44%); nonspecific chronic inflammation, in 51 (18%); pneumocystis, fungal infections, or nocardiosis, in 20 (7%); bronchiolitis obliterans organizing pneumonia, alveolites, or pneumoconiosis, in 14 (5%); lung or metastatic neoplasms, in 7 (2%); and nontuberculous mycobacterium infections, in 6 (2%). For the diagnosis of tuberculosis, BAL showed a sensitivity and a specificity of 60% and 100%, respectively. Adding the TBB findings significantly increased this sensitivity (to 84%), as did adding the post-bronchoscopy sputum smear microscopy results (total sensitivity, 94%). Minor post-procedure complications occurred in 5.6% of the cases. Bronchoscopy is a reliable method for the diagnosis of pulmonary tuberculosis, with low complication rates. The combination of TBB and BAL increases the sensitivity of the method and facilitates the differential diagnosis with other diseases.

In routine UK hospital practice T-SPOT.TB™ is useful in some patients with a modest pre-test probability of active tuberculosis.

PubMed

Turtle, Lance; Kemp, Tim; Davies, Geraint R; Squire, S Bertie; Beeching, Nick J; Beadsworth, Michael B J

2012-06-01

to assess the usefulness of the T-SPOT.TB™ interferon-gamma release assay (IGRA), as used in a regional hospital infectious diseases unit in Northwest England, for the diagnosis of active tuberculosis. Retrospective case series. T-SPOT.TB™ test was applied to a group of 64 patients, 20 of whom had tuberculosis (mostly extra-pulmonary tuberculosis). The T-SPOT.TB™ test had a sensitivity of 83.3% and a specificity of 75% for the diagnosis of active tuberculosis, compared with culture. A positive IGRA approximately doubled the pre-test probability of disease from 0.23 to 0.5. This doubling of probability was true regardless of HIV status, though for HIV+ patients the sensitivity was lower (sensitivity 66.7%, post test probability 0.4 for a positive IGRA result). When extrapolated to the local population the test was most useful for exclusion of disease; post test probability 0.006 (or 1 in 167) for a negative IGRA result. Although it can add weight to a clinical diagnosis, T-SPOT.TB™ assay is not reliable for the diagnosis of active tuberculosis in a real world setting where the test is often used in patients with smear negative or extra-pulmonary disease. The test is useful for ruling out disease in HIV negative patients. Copyright © 2012. Published by Elsevier B.V.

Use of immunochromatographic assay for rapid identification of Mycobacterium tuberculosis complex from liquid culture

PubMed Central

Považan, Anika; Vukelić, Anka; Savković, Tijana; Kurucin, Tatjana

2012-01-01

A new, simple immunochromatographic assay for rapid identification of Mycobacterium tuberculosis complex in liquid cultures has been developed. The principle of the assay is binding of the Mycobacterium tuberculosis complex specific antigen to the monoclonal antibody conjugated on the test strip. The aim of this study is evaluation of the performance of immunochromatographic assay in identification of Mycobacterium tuberculosis complex in primary positive liquid cultures of BacT/Alert automated system. A total of 159 primary positive liquid cultures were tested using the immunochromatographic assay (BD MGIT TBc ID) and the conventional subculture, followed by identification using biochemical tests. Of 159 positive liquid cultures, using the conventional method, Mycobacterium tuberculos is was identified in 119 (74.8%), nontuberculous mycobacteria were found in 4 (2.5%), 14 (8.8%) cultures were contaminated and 22 (13.8%) cultures were found to be negative. Using the immunochromatographic assay, Mycobacterium tuberculosis complex was detected in 118 (74.2%) liquid cultures, and 41 (25.8%) tests were negative. Sensitivity, specificity, positive and negative predictive values of the test were 98.3%; 97.5%; 99.15%; 95.12%, respectively. The value of kappa test was 0.950, and McNemar test was 1.00. The immunochromatographic assay is a simple and rapid test which represents a suitable alternative to the conventional subculture method for the primary identification of Mycobacterium tuberculosis complex in liquid cultures of BacT/Alert automated system. PMID:22364301

Misdiagnosis of primary pleural DLBCL as tuberculosis: A case report and literature review.

PubMed

Yang, Xinmei; Xu, Xiaofang; Song, Binbin; Zhou, Qiang; Zheng, Ying

2018-06-01

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). DLBCL presents with pleural involvement at an advanced stage; however, primary pleural lymphomas without any other site of involvement are rare, and the possibility of misdiagnosis is high, particularly in developing countries, where tuberculosis or other severe pulmonary infections remain a major health concern. Furthermore, lymphoma and tuberculosis share a number of common clinical characteristics, such as fever, night sweats, feeling of satiety after a small meal, fatigue and unexplained weight loss, among others. We herein describe a case of misdiagnosis of primary pleural lymphoma as tuberculosis in a 49-year-old male patient who presented with pleural effusion and high adenosine deaminase (ADA) level in the pleural fluid. Anti-tuberculosis treatment was administered for 1 month, but the patient's condition deteriorated. A surgical biopsy was performed and was diagnostic of DLBCL. CHOP chemotherapy was administered with a significant delay due to the misdiagnosis, and it was not efficient, as rituximab was not added to the regimen. The therapeutic efficacy was monitored by computed tomography scans, which revealed that the lesion had shrunk slightly. The overall survival of the patient was ~1 year and he eventually succumbed to severe thoracic infection and pleural effusion. Suspicion should be raised when a patient presents with pleural effusion and extremely high ADA levels, as ADA activity of >250 U/L should raise the suspicion of empyema or lymphoma rather than tuberculosis.

[A case of tuberculous otitis media associated with meningoencephalitis in the Bangui paediatric institution (Central African Republic)].

PubMed

Gody, J-C; Kassa-Kelembho, E; Bobossi-Serengbe, G; Beyam, E-N; Bercion, R

2006-03-01

The authors report a case of fatal tuberculous meningoencephalitis following chronic bilateral otitis media in a child. Mycobacterium tuberculosis was identified in the CSF and in the otitis secretions. There were no pulmonary tuberculosis signs, thus the tuberculous otitis was considered as primary. In high tuberculosis endemic areas like Central African Republic it is important to consider tuberculosis, in chronic otitis media resistant to non specific therapy, and to reinforce the immunization programs for children.

CE: Tuberculosis: A New Screening Recommendation and an Expanded Approach to Elimination in the United States.

PubMed

Parmer, John; Allen, Leeanna; Walton, Wanda

2017-08-01

: Nurses play a critical role in the diagnosis and treatment of tuberculosis and in the prevention of tuberculosis transmission through infection control practices. To eliminate tuberculosis in the United States, however, an expanded approach to testing and treating people with latent tuberculosis infection must be implemented. Recently, the U.S. Preventive Services Task Force (USPSTF) issued a new recommendation statement on latent tuberculosis infection testing that expands nurses' opportunities to identify at-risk populations for tuberculosis prevention. In combination with newer testing methodologies and shorter treatment regimens, implementation of the USPSTF recommendation has the potential to remove previously existing barriers to screening and treatment of both patients and health care providers. This article provides a general overview of tuberculosis transmission, pathogenesis, and epidemiology; presents preventive care recommendations for targeted testing among high-risk groups; and discusses the USPSTF recommendation's applicability to public health and primary care practice in the United States.

Mycobacterium tuberculosis manipulates pulmonary APCs subverting early immune responses.

PubMed

Garcia-Romo, Gina S; Pedroza-Gonzalez, Alexander; Lambrecht, Bart N; Aguilar-Leon, Diana; Estrada-Garcia, Iris; Hernandez-Pando, Rogelio; Flores-Romo, Leopoldo

2013-03-01

Alveolar macrophages (AM) and dendritic cells (DCs) are the main antigen presenting cells (APCs) in the respiratory tract. Whereas macrophages have been extensively studied in tuberculosis, in situ interactions of DC with Mycobacterium tuberculosis (Mtb) are poorly explored. We aimed to characterize lung APCs during pulmonary tuberculosis in Balb/C mice infected with Mtb H37Rv. Mtb-infection via the airways induced a delayed and continuous accumulation of DCs and AM in the lungs. While lung DCs increased after day 3 post-infection, macrophages increased after 2-3 weeks. Although both populations accumulated in lungs during the infection, DCs decreased in the late stages. Infection induced differential expression of co-stimulatory molecules in these lung APCs, decreasing to basal levels in both APCs in the late stages. A remarkable segregation was found regarding bacillary burden. Many macrophages contained numerous bacilli, but DC contained scarce mycobacteria or none. Mtb-infection also induced delayed accumulation of DC in draining lymph nodes. This delayed recruitment was not associated with a lack of IL-12p40, which was detected from day 3 post-infection. Although AM and lung DCs behave differently during pulmonary tuberculosis, Mtb apparently manipulates both lung APCs subverting early protective responses resulting in disease progression. Copyright © 2012 Elsevier GmbH. All rights reserved.

Immunogenicity and protective efficacy of the Mycobacterium tuberculosis fadD26 mutant

PubMed Central

Infante, E; Aguilar, L D; Gicquel, B; Pando, R Hernandez

2005-01-01

The Mycobacterium tuberculosis fadD26 mutant has impaired synthesis of phthiocerol dimycocerosates (DIM) and is attenuated in BALB/c mice. Survival analysis following direct intratracheal infection confirmed the attenuation: 60% survival at 4 months post-infection versus 100% mortality at 9 weeks post-infection with the wild-type strain. The fadD26 mutant induced less pneumonia and larger DTH reactions. It induced lower but progressive production of interferon (IFN)-γ, interleukin (IL)-4 and tumour necrosis factor (TNF)-α. Used as a subcutaneous vaccine 60 days before intratracheal challenge with a hypervirulent strain of M. tuberculosis (Beijing code 9501000), the mutant induced a higher level of protection than did Bacille Calmette–Guérin (BCG). Seventy per cent of the mice vaccinated with the fadD26 mutant survived at 16 weeks after challenge compared to 30% of those vaccinated with BCG. Similarly, there was less tissue damage (pneumonia) and lower colony-forming units (CFU) in the mice vaccinated with the fadD26 mutant compared to the findings in mice vaccinated with BCG. These data suggest that DIM synthesis is important for the pathogenicity of M. tuberculosis, and that inactivation of DIM synthesis can increase the immunogenicity of live vaccines, and increase their ability to protect against tuberculosis. PMID:15958066

Evaluation of the efficiency of nested q-PCR in the detection of Mycobacterium tuberculosis complex directly from tuberculosis-suspected lesions in post-mortem macroscopic inspections of bovine carcasses slaughtered in the state of Mato Grosso, Brazil.

PubMed

Carvalho, Ricardo César Tavares; Furlanetto, Leone Vinícius; Maruyama, Fernanda Harumy; Araújo, Cristina Pires de; Barros, Sílvia Letícia Bomfim; Ramos, Carlos Alberto do Nascimento; Dutra, Valéria; Araújo, Flábio Ribeiro de; Paschoalin, Vânia Margaret Flosi; Nakazato, Luciano; Figueiredo, Eduardo Eustáquio de Souza

2015-08-01

Bovine tuberculosis (BTB) is a zoonotic disease caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC). The quick and specific detection of this species is of extreme importance, since BTB may cause economic impacts, in addition to presenting imminent risks to human health. In the present study a nested real-time PCR test (nested q-PCR) was used in post-mortem evaluations to assess cattle carcasses with BTB-suspected lesions. A total of 41,193 cattle slaughtered in slaughterhouses located in the state of Mato Grosso, were examined. Of the examined animals, 198 (0.48%) showed BTB-suspected lesions. M. bovis was isolated in 1.5% (3/198) of the samples. Multiplex-PCR detected MTC in 7% (14/198) of the samples. The nested q-PCR test detected MTC in 28% (56/198) of the BTB-suspected lesions, demonstrating higher efficiency when compared to the multiplex-PCR and conventional microbiology. Nested q-PCR can therefore be used as a complementary test in the national program for control and eradication of bovine tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Trends of Mycobacterium bovis Isolation and First-Line Anti-tuberculosis Drug Susceptibility Profile: A Fifteen-Year Laboratory-Based Surveillance

PubMed Central

Bobadilla-del Valle, Miriam; Torres-González, Pedro; Cervera-Hernández, Miguel Enrique; Martínez-Gamboa, Areli; Crabtree-Ramirez, Brenda; Chávez-Mazari, Bárbara; Ortiz-Conchi, Narciso; Rodríguez-Cruz, Luis; Cervantes-Sánchez, Axel; Gudiño-Enríquez, Tomasa; Cinta-Severo, Carmen; Sifuentes-Osornio, José; Ponce de León, Alfredo

2015-01-01

Background Mycobacterium tuberculosis causes the majority of tuberculosis (TB) cases in humans; however, in developing countries, human TB caused by M. bovis may be frequent but undetected. Human TB caused by M. bovis is considered a zoonosis; transmission is mainly through consumption of unpasteurized dairy products, and it is less frequently attributed to animal-to-human or human-to-human contact. We describe the trends of M. bovis isolation from human samples and first-line drug susceptibility during a 15-year period in a referral laboratory located in a tertiary care hospital in Mexico City. Methodology/Principal Findings Data on mycobacterial isolates from human clinical samples were retrieved from the laboratory’s database for the 2000–2014 period. Susceptibility to first-line drugs: rifampin, isoniazid, streptomycin (STR) and ethambutol was determined. We identified 1,165 isolates, 73.7% were M. tuberculosis and 26.2%, M. bovis. Among pulmonary samples, 16.6% were M. bovis. The proportion of M. bovis isolates significantly increased from 7.8% in 2000 to 28.4% in 2014 (X 2 trend, p<0.001). Primary STR resistance was higher among M. bovis compared with M. tuberculosis isolates (10.9% vs.3.4%, p<0.001). Secondary multidrug resistance (MDR) rates were 38.5% and 34.4% for M. bovis and M. tuberculosis, respectively (p = 0.637). A rising trend of primary STR monoresistance was observed for both species (3.4% in 2000–2004 vs. 7.6% in 2010–2014; p = 0.02). Conclusions/Significance There is a high prevalence and a rising trend of M. bovis isolates in our region. The proportion of pulmonary M. bovis isolates is higher than in previous reports. Additionally, we report high rates of primary anti-tuberculosis resistance and secondary MDR in both M. tuberculosis and M. bovis. This is one of the largest reports on drug susceptibility of M. bovis from human samples and shows a significant proportion of first-line anti-tuberculosis drug resistance. PMID:26421930

Primary tuberculous gingival enlargement - A rare clinical entity: Case report and brief review of the literature.

PubMed

Jan, Suhail Majid; Khan, Fayiza Youqoob; Bhat, Muzafar Ahmad; Behal, Roobal

2014-09-01

Tuberculosis (TB) is a chronic specific granulomatous disease and a major cause of death in developing countries. The clinical presentation of TB lesions of the oral cavity varies widely and can manifest as ulcerations, diffuse inflammatory lesions, granulomas and fissures. Oral lesions generally appear secondary to primary TB infection elsewhere, although primary infection of the oral mucosa by Mycobacterium tuberculosis has also been described. We hereby report a case of primary TB of the gingiva manifesting as gingival enlargement. Diagnosis was based on histopathological examination, complete blood count, X-ray chest and immunological investigations with detection of antibodies against M. tuberculosis. Anti-tuberculous therapy was carried out for over 6 months and was followed by surgical excision of the residual enlargement under local anesthesia. After 1-year follow-up, there was no recurrence of the disease. This case report emphasizes the need for dentists to include TB in the differential diagnosis of various types of gingival enlargements.

Defining the needs for next generation assays for tuberculosis.

PubMed

Denkinger, Claudia M; Kik, Sandra V; Cirillo, Daniela Maria; Casenghi, Martina; Shinnick, Thomas; Weyer, Karin; Gilpin, Chris; Boehme, Catharina C; Schito, Marco; Kimerling, Michael; Pai, Madhukar

2015-04-01

To accelerate the fight against tuberculosis, major diagnostic challenges need to be addressed urgently. Post-2015 targets are unlikely to be met without the use of novel diagnostics that are more accurate and can be used closer to where patients first seek care in affordable diagnostic algorithms. This article describes the efforts by the stakeholder community that led to the identification of the high-priority diagnostic needs in tuberculosis. Subsequently target product profiles for the high-priority diagnostic needs were developed and reviewed in a World Health Organization (WHO)-led consensus meeting. The high-priority diagnostic needs included (1) a sputum-based replacement test for smear-microscopy; (2) a non-sputum-based biomarker test for all forms of tuberculosis, ideally suitable for use at levels below microscopy centers; (3) a simple, low cost triage test for use by first-contact care providers as a rule-out test, ideally suitable for use by community health workers; and (4) a rapid drug susceptibility test for use at the microscopy center level. The developed target product profiles, along with complimentary work presented in this supplement, will help to facilitate the interaction between the tuberculosis community and the diagnostics industry with the goal to lead the way toward the post-2015 global tuberculosis targets. © 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.

A review of eleven cases of tuberculosis presenting as sternal wound abscess after open heart surgery.

PubMed

Tabaja, Hussam; Hajar, Zeina; Kanj, Souha S

2017-10-01

Sternal wound infection with Mycobacterium tuberculosis is an uncommon yet highly challenging disease that can be quite insidious with various presentations. We hereby provide a review of 10 cases in current literature and describe an additional case which illustrates the difficulties associated with diagnosis. We used PubMed and Google search engine to search the literature for all published papers reporting on cases of sternal M. tuberculosis infections post open-heart surgeries. A total of 11 cases were presented, including a case of our own. The majority were males and were exposed to endemic areas. The average age was 59.6 ± 15.5 years. Coronary artery bypass surgery accounted for 73% of procedures and the average time to symptoms onset was 12.2 ± 16.6 months. Diabetes was the most reported non-cardiac comorbidity. Presenting symptoms varied and only 5 patients had other organs involved. Blood tests and radiographic studies were neither sensitive nor specific. M. tuberculosis culture on debrided tissues was the most sensitive test but often forgotten initially. Diagnostic delay was seen in almost all cases, often leading to unnecessary courses of antibiotics and aggressive surgical interventions. Finally, all patients responded well to anti-tuberculosis treatment, with reported treatment duration ranging from 9 to 12 months. M. tuberculosis infection of the sternum should be suspected in late-onset sternal wound infections post open-heart surgery especially when the course is chronic and indolent.

Primary Multidrug Resistant Tuberculosis and Utility of Line Probe Assay for Its Detection in Smear-Positive Sputum Samples in a Tertiary Care Hospital in South India.

PubMed

Yacoob, Fahmiya Leena; Philomina Jose, Beena; Karunakaran Lelitha, Sarada Devi; Sreenivasan, Sreelatha

2016-01-01

In a high tuberculosis burdened country like India, rapid, cost-effective, and reliable diagnostic tools for tuberculosis are an urgent need of the hour to prevent inappropriate treatment strategies and further spread of resistance. This study aimed to estimate the proportion of new smear-positive tuberculosis cases with primary resistance to rifampicin and/or isoniazid as well as identify the common mutations associated with it. Sputum of 200 newly diagnosed smear-positive cases of 1+ score and above was directly subjected to Line Probe Assay using the GenoType MTBDRplus assay kit. All samples were inoculated onto solid media and 61 samples were inoculated in automated liquid culture also. The Line Probe Assay gave hundred percent interpretable results with 2.5% of the study population showing resistant pattern. Only 1% of the cases were primary multidrug resistant tuberculosis and 1.5% showed isoniazid monoresistance. S531L and C15T were the most common genetic mutations seen for rifampicin and isoniazid resistance, respectively. 40% had absent rpoB wild type 8 band indicating probable silent mutation after clinical correlation. The average turnaround time for Line Probe Assay was far less (3.8 days) as compared to solid and liquid cultures (35.6 days and 13.5 days, resp.).

Tuberculosis non-communicable disease comorbidity and multimorbidity in public primary care patients in South Africa.

PubMed

Peltzer, Karl

2018-04-11

 Little is known about the prevalence of non-communicable disease (NCD) multimorbidity among tuberculosis (TB) patients in Africa.Aim and setting: The aim of this study was to assess the prevalence of NCD multimorbidity, its pattern and impact on adverse health outcomes among patients with TB in public primary care in three selected districts of South Africa.  In a cross-sectional survey, new TB and TB retreatment patients were interviewed, and medical records assessed in consecutive sampling within 1 month of anti-TB treatment. The sample included 4207 (54.5% men and 45.5% women) TB patients from 42 primary care clinics in three districts. Multimorbidity was measured as the simultaneous presence of two or more of 10 chronic conditions, including myocardial infarction or angina pectoris, arthritis, asthma, chronic lung disease, diabetes mellitus, hypertension, dyslipidaemia, malignant neoplasms, tobacco and alcohol-use disorder.  The prevalence of comorbidity (with one NCD) was 26.9% and multimorbidity (with two or more NCDs) was 25.3%. We identified three patterns of multimorbidity: (1) cardio-metabolic disorders; (2) respiratory disorders, arthritis and cancer; and (3) substance-use disorders. The likelihood of multimorbidity was higher in older age, among men, and was lower in those with higher education and socio-economic status. The prevalence of physical health decreased, and common mental disorders and post-traumatic stress disorder increased with an increase in the number of chronic conditions.  High NCD comorbidity and multimorbidity were found among TB patients predicted by socio-economic disparity.

Urine colorimetry for therapeutic drug monitoring of pyrazinamide during tuberculosis treatment.

PubMed

Zentner, Isaac; Modongo, Chawangwa; Zetola, Nicola M; Pasipanodya, Jotam G; Srivastava, Shashikant; Heysell, Scott K; Mpagama, Stellah; Schlect, Hans P; Gumbo, Tawanda; Bisson, Gregory P; Vinnard, Christopher

2018-03-01

Pyrazinamide is a key drug in the first-line treatment regimen for tuberculosis, with a potent sterilizing effect. Although low pyrazinamide peak serum concentrations (C max ) are associated with poor treatment outcomes, many resource-constrained settings do not have sufficient laboratory capacity to support therapeutic drug monitoring (TDM). The objective of this study was to determine whether a colorimetric test of urine can identify tuberculosis patients with adequate pyrazinamide exposures, as defined by serum C max above a target threshold. In the derivation study of healthy volunteers, three dose sizes of pyrazinamide were evaluated, and intensive pharmacokinetic blood sampling was performed over an 8-h period, with a timed urine void at 4h post-dosing. Pyrazinamide in urine was isolated by spin column centrifugation with an exchange resin, followed by colorimetric analysis; the absorbance peak at 495nm was measured. The urine assay was then evaluated in a study of 39 HIV/tuberculosis patients in Botswana enrolled in an intensive pharmacokinetic study. Receiver operating characteristics (ROC) curves were used to measure diagnostic accuracy. The guideline-recommended pyrazinamide serum C max target of 35mg/l was evaluated in the primary analysis; this target was found to be predictive of favorable outcomes in a clinical study. Following this, a higher serum C max target of 58mg/l was evaluated in the secondary analysis. At the optimal cut-off identified in the derivation sample, the urine colorimetric assay was 97% sensitive and 50% specific to identify 35 of 39 HIV/tuberculosis patients with pharmacokinetic target attainment, with an area under the ROC curve of 0.81 (95% confidence interval 0.60-0.97). Diagnostic accuracy was lower at the 58mg/l serum C max target, with an area under the ROC curve of 0.68 (95% confidence interval 0.48-0.84). Men were less likely than women to attain either serum pharmacokinetic target. The urine colorimetric assay was sensitive but not specific for the detection of adequate pyrazinamide pharmacokinetic exposures among HIV/tuberculosis patients in a high-burden setting. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Household crowding as a potential mediator of socioeconomic determinants of tuberculosis incidence in Brazil

PubMed Central

Pelissari, Daniele Maria; Diaz-Quijano, Fredi Alexander

2017-01-01

Although many studies have identified social conditions associated with tuberculosis, contextual and individual factors have rarely been analysed simultaneously. Consequently, we aimed to identify contextual and individual factors associated with tuberculosis incidence in general population in Brazil in 2010. We also assessed whether household crowding mediates the association between socioeconomic determinants and tuberculosis incidence. Individual data of tuberculosis cases were obtained from 5,565 municipalities in Brazil in 2010 (last year of national census), and merged with contextual variables. The associations were evaluated in a multilevel analysis using negative binomial regression. After adjusting for individual factors (age, sex and race) and geographic region, the following contextual factors were associated with tuberculosis incidence rate: AIDS incidence rate [incidence rate ratio (IRR), 1.21; 95% confidence interval (CI), 1.18–1.24], unemployment rate (IRR, 1.16; 95% CI, 1.13–1.19), Gini coefficient (IRR, 1.05; 95% CI, 1.02–1.08), proportion of inmates (IRR, 1.11; 95% CI, 1.09–1.14), mean per capita household income (IRR, 0.94; 95% CI, 0.91–0.97) and primary care coverage (IRR, 0.94; 95% CI, 0.92–0.96). Inclusion of household crowding in the multivariate model led to a loss of the associations of both Gini coefficient and mean per capita household income. In conclusion, our findings suggest that income inequality and poverty, as determinants of tuberculosis incidence, can be mediated by household crowding. Moreover, prison population can represent a potential social reservoir of tuberculosis in Brazil and should be addressed as a priority for disease control. Finally, the negative association between primary health coverage and tuberculosis incidence highlights the importance of this level of care as a strategy to control this disease. PMID:28419146

Prostatic tuberculosis and AIDS.

PubMed

Lanjewar, D N; Maheshwari, M B

1994-01-01

Tuberculosis of the prostate is rare and is thought to be either due to haematogenous dissemination or secondary to renal infection. We describe, possibly for the first time, two male patients with the acquired immunodeficiency syndrome who had tuberculous abscesses in the prostate discovered at post-mortem examination. Only one of them had mild urinary symptoms and neither had evidence of urogenital tuberculosis before death. We suggest that in a patient with acquired immunodeficiency syndrome tuberculous infection of the prostate should be sought by microscopic examination of the urine, semen and prostatic fluid obtained after massage.

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.

Tuberculosis of the middle ear with post auricular abscess.

PubMed

Arya, Manoj; Dixit, Ramakant; Paramez, A R; Sharma, Sidharth; Rathore, Dilip Singh

2009-07-01

A case of tuberculous otitis media with post auricular abscess is being described in a 14-year-old female patient in view of its rare occurrence. The diagnosis was made on demonstration of acid fast bacilli (AFB) in the ear discharge and characteristic cytological features of post auricular abscess aspirate.

Implementation and Operational Research: Clinical Impact of the Xpert MTB/RIF Assay in Patients With Multidrug-Resistant Tuberculosis.

PubMed

Padayatchi, Nesri; Naidu, Naressa; Yende-Zuma, Nonhlanhla; OʼDonnell, Max Roe; Naidoo, Kogieleum; Augustine, Stanton; Zumla, Alimuddin; Loveday, Marian

2016-09-01

The Xpert MTB/RIF assay has been widely implemented in South Africa for rapid tuberculosis (TB) screening. However, its usefulness in management and improving treatment outcomes in patients with multidrug-resistant TB (MDR-TB) remains undefined. The aim of this study was to evaluate the clinical impact of introduction of the Xpert MTB/RIF assay in patients with MDR-TB. We enrolled 921 patients with MDR-TB, who presented to a specialist drug-resistant TB facility in KwaZulu-Natal, South Africa, pre- and post-rollout and implementation of the Xpert MTB/RIF assay. Clinical, laboratory, chest radiograph, and follow-up data from 108 patients with MDR-TB, post-introduction of the Xpert MTB/RIF assay (Xpert group) in November 2010, were analyzed and compared with data from 813 MDR-TB patients from the pre-MTB/RIF assay period (Conventional group), July 2008-2010. Primary impact measure was "treatment success" (World Health Organization definition) at 24 months. Secondary outcomes were time to treatment initiation and disease morbidity. There were no significant differences in treatment success rates between the pre-Xpert MTB/RIF and post-Xpert MTB/RIF groups (54% versus 56.5%, P = 0.681). Median time to treatment initiation was 20 days (interquartile range, 13-31) in the Xpert group versus 92 days (interquartile range, 69-120) in the Conventional group (P < 0.001). Although use of Xpert MTB/RIF assay significantly reduces the time to initiation of MDR-TB treatment, it had no significant impact on treatment outcomes of patients with MDR-TB. Studies on the impact of the Xpert MTB/RIF assay usage on transmission of MDR-TB are required.

Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis

PubMed Central

Lerner, Thomas R.; de Souza Carvalho-Wodarz, Cristiane; Repnik, Urska; Russell, Matthew R.G.; Borel, Sophie; Diedrich, Collin R.; Rohde, Manfred; Wainwright, Helen; Collinson, Lucy M.; Wilkinson, Robert J.; Griffiths, Gareth; Gutierrez, Maximiliano G.

2016-01-01

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes. PMID:26901813

Low serum vitamin D levels in type 2 diabetes patients are associated with decreased mycobacterial activity.

PubMed

Herrera, María Teresa; Gonzalez, Yolanda; Hernández-Sánchez, Fernando; Fabián-San Miguel, Guadalupe; Torres, Martha

2017-09-07

Concurrent diabetes mellitus and tuberculosis represent a significant health problem worldwide. Patients with diabetes mellitus have a high risk of tuberculosis, which may be mediated by an abnormal innate immune response due to hyperglycaemia or low vitamin D levels. In the present study, we evaluated inactive vitamin D serum levels and the monocyte response to infection with M. tuberculosis, including phagocytosis of M. tuberculosis, antimycobacterial activity, LL-37, human β defensin-2 and IL-10 gene expression and nitric oxide production, between type 2 diabetes mellitus patients (n = 51) and healthy volunteers (n = 38). Twenty-seven type 2 diabetes mellitus patients had inadequate inactive vitamin D levels (<50 nM). The percentages of M. tuberculosis phagocytosis between monocytes were similar across groups according to microscopy. Intracellular mycobacterial growth was similar in infected monocytes from both groups. However, M. tuberculosis growth was significantly higher in monocytes obtained from type 2 diabetes mellitus patients and lower vitamin D levels after 1-h (D0) and 72-h (D3) post-infection (p ≤ 0.05). LL-37, human β defensin-2 and IL-10 mRNA expression were similar between monocytes across groups; vitamin D serum levels and LL-37, human β defensin-2 and IL-10 expression were not correlated. Nitric oxide production was significantly higher in healthy volunteers than in type 2 diabetes mellitus patients with low vitamin D serum levels at D3 post-infection (p ≤ 0.05). Our results show that monocytes from type 2 diabetes mellitus patients and low vitamin D serum levels show an impaired ability to control the intracellular growth of M. tuberculosis, which is not associated with significant decrease of LL-37 or human β defensin-2 expression. Vitamin D could be the link between diabetes and tuberculosis susceptibility.

Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

PubMed

Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

2017-11-01

Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

Obstructive lung disease as a complication in post pulmonary TB

NASA Astrophysics Data System (ADS)

Tarigan, A. P.; Pandia, P.; Eyanoer, P.; Tina, D.; Pratama, R.; Fresia, A.; Tamara; Silvanna

2018-03-01

The case of post TB is a problem that arises in the community. Pulmonary tuberculosis (TB) can affect lung function. Therefore, we evaluated impaired pulmonary function in subjects with diagnosed prior pulmonary TB. A Case Series study, pulmonary function test was performed in subjects with a history of pulmonary tuberculosis; aged ≥18 years were included. Exclusion criteria was a subject who had asthma, obesity, abnormal thorax and smoking history. We measured FEV1 and FVC to evaluate pulmonary function. Airflow obstruction was FEV1/FVC%<75 and restriction was FVC<80% according to Indonesia’s pneumomobile project. This study was obtained from 23 patients with post pulmonary TB, 5 subjects (23%) had airflow obstruction with FEV1/FVC% value <75%, 15 subjects (71.4%) had abnormalities restriction with FVC value <80% and 3 subjects (5.6%) had normal lung function. Obstructive lung disease is one of the complications of impaired lung function in post pulmonary TB.

Pre-Columbian mycobacterial genomes reveal seals as a source of New World human tuberculosis

PubMed Central

Bos, Kirsten I.; Harkins, Kelly M.; Herbig, Alexander; Coscolla, Mireia; Weber, Nico; Comas, Iñaki; Forrest, Stephen A.; Bryant, Josephine M.; Harris, Simon R.; Schuenemann, Verena J.; Campbell, Tessa J.; Majander, Kerrtu; Wilbur, Alicia K.; Guichon, Ricardo A.; Wolfe Steadman, Dawnie L.; Cook, Della Collins; Niemann, Stefan; Behr, Marcel A.; Zumarraga, Martin; Bastida, Ricardo; Huson, Daniel; Nieselt, Kay; Young, Douglas; Parkhill, Julian; Buikstra, Jane E.; Gagneux, Sebastien; Stone, Anne C.; Krause, Johannes

2015-01-01

Modern strains of Mycobacterium tuberculosis from the Americas are closely related to those from Europe, supporting the assumption that human tuberculosis was introduced post-contact1. This notion, however, is incompatible with archaeological evidence of pre-contact tuberculosis in the New World2. Comparative genomics of modern isolates suggests that M. tuberculosis attained its worldwide distribution following human dispersals out of Africa during the Pleistocene epoch3, although this has yet to be confirmed with ancient calibration points. Here we present three 1,000-year-old mycobacterial genomes from Peruvian human skeletons, revealing that a member of the M. tuberculosis complex caused human disease before contact. The ancient strains are distinct from known human-adapted forms and are most closely related to those adapted to seals and sea lions. Two independent dating approaches suggest a most recent common ancestor for the M. tuberculosis complex less than 6,000 years ago, which supports a Holocene dispersal of the disease. Our results implicate sea mammals as having played a role in transmitting the disease to humans across the ocean. PMID:25141181

The hidden harm of home-based care: pulmonary tuberculosis symptoms among children providing home medical care to HIV/AIDS-affected adults in South Africa.

PubMed

Cluver, Lucie; Orkin, Mark; Moshabela, Mosa; Kuo, Caroline; Boyes, Mark

2013-01-01

Millions of children in sub-Saharan Africa undertake personal and medical care for family members who are unwell with AIDS. To date, no research has investigated whether such care provision places children at heightened risk for pulmonary tuberculosis. This study aimed to address this gap by identifying risk factors for paediatric pulmonary tuberculosis symptomatology. In 2009-2011, 6002 children aged 10-17 years were surveyed using door-to-door household sampling of census enumeration areas. These were randomly sampled from six urban and rural sites with over 30% HIV prevalence, within South Africa's three highest tuberculosis-burden provinces. Validated scales and clinical tuberculosis symptom checklists were modelled in multivariate logistic regressions, controlling for socio-demographic co-factors. Findings showed that, among children, severe pulmonary tuberculosis symptomatology was predicted by primary caregiver HIV/AIDS-illness [odds ratio (OR): 1.63, confidence interval (CI): 1.23-2.15, p<0.001], and AIDS-orphanhood (OR: 1.44, CI: 1.04-2.00, p<0.029). Three-fold increases in severe tuberculosis symptoms were predicted by the child's exposure to body fluids through providing personal or medical care to an ill adult (OR: 3.12, CI: 1.96-4.95, p<0.001). Symptoms were also predicted by socio-economic factors of food insecurity (OR: 1.52, CI: 1.15-2.02, p<0.003) and household overcrowding (OR: 1.35, CI: 1.06-1.72, p<0.017). Percentage probability of severe tuberculosis symptoms rose from 1.4% amongst least-exposed children, to 18.1% amongst those exposed to all above-stated risk factors, independent of biological relationship of primary caregiver-child and other socio-demographics. Amongst symptomatic children, 75% had never been tested for tuberculosis. These findings identify the risk of tuberculosis among children providing home medical care to their unwell caregivers, and suggest that there are gaps in the health system to screen and detect these cases of paediatric tuberculosis. There is a need for effective interventions to reduce childhood risk, as well as further support for community-based contact-tracing, tuberculosis screening and anti-tuberculosis treatment for children caring for ill adults in contexts with a high burden of HIV and tuberculosis.

A comprehensive review on Primary gallbladder tuberculosis.

PubMed

Gupta, Ashish; Gupta, Amit; Anjum, Rohik; Agrawal, Saumya; Mallik, Dhiraj

2018-04-30

Tuberculosis (TB) is an infectious disease that can affect any organ system of the body. Abdominal TB can be gastrointestinal, lymph nodal, visceral or peritoneal. The gallbladder (GB) is rarely involved in abdominal TB as a primary organ. Extensive research literature on gallbladder TB is limited to case reports. There has been no review on this rare abdominal pathology. GB tuberculosis is a difficult diagnosis preoperatively. It is a rare differential among the more common gallbladder pathologies such as cholelithiasis, or a gallbladder malignancy. Typical histopathology of the resected specimen helps to establish this rare diagnosis. Subjecting every specimen to histopathological examination followed by medical treatment offers the chance of cure. Through this review, the authors attempt to provide an insight into this disease entity.

Assessment of vaccine testing at three laboratories using the guinea pig model of tuberculosis.

PubMed

Grover, Ajay; Troudt, Jolynn; Arnett, Kimberly; Izzo, Linda; Lucas, Megan; Strain, Katie; McFarland, Christine; Hall, Yper; McMurray, David; Williams, Ann; Dobos, Karen; Izzo, Angelo

2012-01-01

The guinea pig model of tuberculosis is used extensively in different locations to assess the efficacy of novel tuberculosis vaccines during pre-clinical development. Two key assays are used to measure protection against virulent challenge: a 30 day post-infection assessment of mycobacterial burden and long-term post-infection survival and pathology analysis. To determine the consistency and robustness of the guinea pig model for testing vaccines, a comparative assessment between three sites that are currently involved in testing tuberculosis vaccines from external providers was performed. Each site was asked to test two "subunit" type vaccines in their routine animal model as if testing vaccines from a provider. All sites performed a 30 day study, and one site also performed a long-term survival/pathology study. Despite some differences in experimental approach between the sites, such as the origin of the Mycobacterium tuberculosis strain and the type of aerosol exposure device used to infect the animals and the source of the guinea pigs, the data obtained between sites were consistent in regard to the ability of each "vaccine" tested to reduce the mycobacterial burden. The observations also showed that there was good concurrence between the results of short-term and long-term studies. This validation exercise means that efficacy data can be compared between sites. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dramatic reduction of culture time of Mycobacterium tuberculosis

NASA Astrophysics Data System (ADS)

Ghodbane, Ramzi; Raoult, Didier; Drancourt, Michel

2014-02-01

Mycobacterium tuberculosis culture, a critical technique for routine diagnosis of tuberculosis, takes more than two weeks. Here, step-by-step improvements in the protocol including a new medium, microaerophlic atmosphere or ascorbic-acid supplement and autofluorescence detection dramatically shortened this delay. In the best case, primary culture and rifampicin susceptibility testing were achieved in 72 hours when specimens were inoculated directly on the medium supplemented by antibiotic at the beginning of the culture.

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

Shorter treatment for minimal tuberculosis (TB) in children (SHINE): a study protocol for a randomised controlled trial.

PubMed

Chabala, Chishala; Turkova, Anna; Thomason, Margaret J; Wobudeya, Eric; Hissar, Syed; Mave, Vidya; van der Zalm, Marieke; Palmer, Megan; Kapasa, Monica; Bhavani, Perumal K; Balaji, Sarath; Raichur, Priyanka A; Demers, Anne-Marie; Hoddinott, Graeme; Owen-Powell, Ellen; Kinikar, Aarti; Musoke, Philippa; Mulenga, Veronica; Aarnoutse, Rob; McIlleron, Helen; Hesseling, Anneke; Crook, Angela M; Cotton, Mark; Gibb, Diana M

2018-04-19

Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug-susceptible TB in children, regardless of HIV status, is efficacious and safe. The trial will also fill existing gaps in knowledge on dosing and acceptability of new anti-tuberculosis formulations and commonly used HIV drugs in settings with a high burden of TB. A positive result from this trial could simplify and shorten treatment, improve adherence and be cost-saving for many children with TB. Recruitment to the SHINE trial begun in July 2016; results are expected in 2020. International Standard Randomised Controlled Trials Number: ISRCTN63579542 , 14 October 2014. Pan African Clinical Trials Registry Number: PACTR201505001141379 , 14 May 2015. Clinical Trial Registry-India, registration number: CTRI/2017/07/009119, 27 July 2017.

Pulmonary Bovine-Type Tuberculosis in Rabbits: Bacillary Virulence, Inhaled Dose Effects, Tuberculin Sensitivity, and Mycobacterium vaccae Immunotherapy

PubMed Central

Converse, P. J.; Dannenberg, A. M.; Shigenaga, T.; McMurray, D. N.; Phalen, S. W.; Stanford, J. L.; Rook, G. A. W.; Koru-Sengul, T.; Abbey, Helen; Estep, J. E.; Pitt, M. L. M.

1998-01-01

This report elucidates four aspects of the immunology of pulmonary tuberculosis produced in rabbits: (i) the virulence of bovine-type tubercle bacilli, strain Ravenel S, (ii) systemic factors influencing the generation of visible primary pulmonary tubercles, (iii) differences in tuberculin sensitivity of rabbits and humans, and (iv) the effect of Mycobacterium vaccae immunotherapy on cavitary tuberculosis. Laboratory strain Ravenel S (ATCC 35720) was not fully virulent. Fully virulent strains produce one visible primary pulmonary tubercle for each three bacillary units inhaled. Strain ATCC 35720 produced one such tubercle for each 18 to 107 bacillary units inhaled, indicating that its virulence was reduced by 6- to 36-fold. When a low dose of this Ravenel S strain was inhaled, the host resistance (measured by the number of inhaled bacilli needed to generate one visible primary pulmonary tubercle) was increased at least 3.5-fold compared to the host resistance when a high dose was inhaled. Rabbits and humans differ in the degree and in the maintenance of their dermal sensitivities to tuberculin. Compared to rabbits, humans are 100 times more sensitive to tuberculin. Also, at 33 weeks rabbits with well-controlled cavitary tuberculosis usually showed a decrease in their tuberculin reactions of about 50% from peak values, whereas humans with such well-controlled tuberculosis are thought to maintain strong reactions for many years. These species differences may be due to desensitization to group II mycobacterial antigens in the rabbits because they have a different diet and a different type of digestive tract. M. vaccae immunotherapy of rabbits with cavitary tuberculosis produced no statistically significant effects. Experiments with many more rabbits would be required to prove whether or not such immunotherapy is beneficial. PMID:9801350

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.

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.

Clinical information systems for the management of tuberculosis in primary health care.

PubMed

Medeiros, Eliabe Rodrigues de; Silva, Sandy Yasmine Bezerra E; Ataide, Cáthia Alessandra Varela; Pinto, Erika Simone Galvão; Silva, Maria de Lourdes Costa da; Villa, Tereza Cristina Scatena

2017-12-11

to analyze the clinical information systems used in the management of tuberculosis in Primary Health Care. descriptive, quantitative cross-sectional study with 100 health professionals with data collected through a questionnaire to assess local institutional capacity for the model of attention to chronic conditions, as adapted for tuberculosis care. The analysis was performed through descriptive and inferential statistics. Nurses and the Community Health Agents were classified as having fair capacity with a mean of 6.4 and 6.3, respectively. The city was classified as having fair capacity, with a mean of 6.0 and standard deviation of 1.5. Family Health Units had higher capacity than Basic Health Units and Mixed Units, although not statistically relevant. Clinical records and data on tuberculosis patients, items of the clinical information systems, had a higher classification than the other items, classified as having fair capacity, with a mean of 7.3 and standard deviation of 1.6, and the registry of TB patients had a mean of 6.6 and standard deviation of 2.0. clinical information systems are present in the city, mainly in clinical records and patient data, and they have the contribution of professionals linked with tuberculosis patients.

Coexistence of breast cancer metastases and tuberculosis in axillary lymph nodes--a rare association and review of the literature.

PubMed

Salemis, Nikolaos S; Razou, Anna

2010-05-01

The coexistence of metastatic breast cancer and tuberculosis in axillary lymph nodes is very rare. We present the case of a 57-year-old woman with multifocal invasive ductal breast carcinoma in whom the resected axillary nodes were found to harbor both metastatic cancer and tuberculous lymphadenitis. Thorough investigation revealed no evidence of primary tuberculosis elsewhere. A quantiFERON TB-Gold test was positive, indicating latent tuberculosis. The patient was treated with adjuvant chemotherapy antituberculous therapy, radiation and hormonal therapy with aromatase inhibitors. We conclude the possibility of coexistent latent tuberculosis should be kept in mind when granulomatous lesions are identified in axillary lymph nodes with metastatic breast cancer, especially in patients from endemic regions.

Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis.

PubMed

Williams, Ann; Hatch, Graham J; Clark, Simon O; Gooch, Karen E; Hatch, Kim A; Hall, Graham A; Huygen, Kris; Ottenhoff, Tom H M; Franken, Kees L M C; Andersen, Peter; Doherty, T Mark; Kaufmann, Stefan H E; Grode, Leander; Seiler, Peter; Martin, Carlos; Gicquel, Brigitte; Cole, Stewart T; Brodin, Priscille; Pym, Alexander S; Dalemans, Wilfried; Cohen, Joe; Lobet, Yves; Goonetilleke, Nilu; McShane, Helen; Hill, Adrian; Parish, Tanya; Smith, Debbie; Stoker, Neil G; Lowrie, Douglas B; Källenius, Gunilla; Svenson, Stefan; Pawlowski, Andrzej; Blake, Karen; Marsh, Philip D

2005-01-01

The TB Vaccine Cluster project funded by the EU Fifth Framework programme aims to provide novel vaccines against tuberculosis that are suitable for evaluation in humans. This paper describes the studies of the protective efficacy of vaccines in a guinea pig aerosol-infection model of primary tuberculosis. The objective was to conduct comparative evaluations of vaccines that had previously demonstrated efficacy in other animal models. Groups of 6 guinea pigs were immunized with vaccines provided by the relevant EU Vaccine Cluster partners. Survival over 17 or 26 weeks was used as the principal measure of vaccine efficacy following aerosol challenge with H37Rv. Counts of mycobacteria in lungs and spleens, and histopathological changes in the lungs, were also used to provide evidence of protection. A total of 24 vaccines were evaluated in 4 experiments each of a different design. A heterologous prime-boost strategy of DNA and MVA, each expressing Ag85A and a fusion protein of ESAT-6 and Ag85B in adjuvant, protected the guinea pigs to the same extent as BCG. Genetically modified BCG vaccines and boosted BCG strategies also protected guinea pigs to the same extent as BCG but not statistically significantly better. A relatively high aerosol-challenge dose and evaluation over a protracted time post-challenge allowed superior protection over BCG to be demonstrated by BCG boosted with MVA and fowl pox vectors expressing Ag85A.

Cost Analysis of Tuberculosis Diagnosis in Cambodia with and without Xpert® MTB/RIF for People Living with HIV/AIDS and People with Presumptive Multidrug-resistant Tuberculosis.

PubMed

Pallas, Sarah Wood; Courey, Marissa; Hy, Chhaily; Killam, Wm Perry; Warren, Dora; Moore, Brittany

2018-06-04

The Xpert ® MTB/RIF (Xpert) test has been shown to be effective and cost-effective for diagnosing tuberculosis (TB) under conditions with high HIV prevalence and HIV-TB co-infection but less is known about Xpert's cost in low HIV prevalence settings. Cambodia, a country with low HIV prevalence (0.7%), high TB burden, and low multidrug-resistant (MDR) TB burden (1.4% of new TB cases, 11% of retreatment cases) introduced Xpert into its TB diagnostic algorithms for people living with HIV (PLHIV) and people with presumptive MDR TB in 2012. The study objective was to estimate these algorithms' costs pre- and post-Xpert introduction in four provinces of Cambodia. Using a retrospective, ingredients-based microcosting approach, primary cost data on personnel, equipment, maintenance, supplies, and specimen transport were collected at four sites through observation, records review, and key informant consultations. Across the sample facilities, the cost per Xpert test was US$33.88-US$37.11, clinical exam cost US$1.22-US$1.84, chest X-ray cost US$2.02-US$2.14, fluorescent microscopy (FM) smear cost US$1.56-US$1.93, Ziehl-Neelsen (ZN) smear cost US$1.26, liquid culture test cost US$11.63-US$22.83, follow-on work-up for positive culture results and Mycobacterium tuberculosis complex (MTB) identification cost US$11.50-US$14.72, and drug susceptibility testing (DST) cost US$44.26. Specimen transport added US$1.39-US$5.21 per sample. Assuming clinician adherence to the algorithms and perfect test accuracy, the normative cost per patient correctly diagnosed under the post-Xpert algorithms would be US$25-US$29 more per PLHIV and US$34-US$37 more per person with presumptive MDR TB (US$41 more per PLHIV when accounting for variable test sensitivity and specificity). Xpert test unit costs could be reduced through lower cartridge prices, longer usable life of GeneXpert ® (Cepheid, USA) instruments, and increased test volumes; however, epidemiological and test eligibility conditions in Cambodia limit the number of specimens received at laboratories, leading to sub-optimal utilization of current instruments. Improvements to patient referral and specimen transport could increase test volumes and reduce Xpert test unit costs in this setting.

Mycobacterium tuberculosis infection within parotid gland Warthin tumor.

PubMed

Ozcan, Cengiz; Apa, Duygu Düşmez; Aslan, Gönül; Gülhan, Stk; Görür, Kemal

2008-11-01

Tuberculosis of the parotid gland is extremely unusual. Tuberculosis comprises 2.5% to 10% of parotid gland lesions. Two clinical forms of parotid gland tuberculosis infection exist. One is a diffuse parenchymatous disease (either primary or secondary to nodal disease), resembling common infection. The second is a chronic, slow-growing, painless, and firm parotid mass mimicking a neoplasm. Most of these patients were diagnosed after parotid gland surgery and histopathologic evaluation. Warthin tumor is a well-known benign neoplasm of the salivary glands. It is the second most common tumor of the parotid gland. Mycobacterium tuberculosis within Warthin tumor is also unusual. Five cases with parotid gland tuberculosis within Warthin tumor were reported in the literature. In this report, we present a new patient with parotid gland tuberculosis within the Warthin tumor. This type parotid gland pathology is an extremely rare entity, and to the best of our knowledge, this is the second documented case using polymerase chain reaction. We also discussed the possible mechanisms of development of infection within Warthin tumor.

Extra-Pulmonary Tuberculosis and Its Surgical Treatment.

PubMed

Fry, Donald E

2016-08-01

Tuberculous infection has declined in the United States but remains a major infectious disease with morbidity and death for millions of people. Although the primary therapy is drugs, complications of the disease require surgical interventions. The published literature on tuberculosis was reviewed to provide a current understanding of the medical treatment of the disease and to define those areas where surgical intervention continues to be necessary. Multi-drug therapy for tuberculosis has become the standard and has reduced the complications of the disease necessitating surgical intervention. However, multi-drug resistance and extensively drug-resistant tuberculosis continue to be major problems and require effective initial therapy with surveillance to define resistant infections. The roles of surgery in tuberculosis are in establishing the diagnosis in extra-pulmonary infection and in the management of complications of disseminated disease. Tuberculosis remains an occupational risk for surgeons and surgical personnel. Tuberculosis is still a global problem, mandating recognition and treatment. Surgeons should have an understanding of the diverse presentation and complications of the disease.

Engaging adolescents in tuberculosis and clinical trial research through drama.

PubMed

Schmidt, Bey-Marrié; Abrams, Amber; Tameris, Michele

2016-04-06

The South African Tuberculosis Vaccine Initiative is based in Worcester where tuberculosis (TB) is endemic, and incidence rates are amongst the highest nationally. In high TB burden settings after an early childhood peak, incidence rates start to rise again in adolescents, therefore they are an important target group for tuberculosis vaccine research. In 2012, learners from a local school developed a one-off theatrical production out of an educational comic book Carina's Choice, developed by the South African Tuberculosis Vaccine Initiative in 2010. A Wellcome Trust International Engagement grant allowed for this one-off production to be further developed, with input from university students and staff, and rolled out to schools in the Worcester area as an engagement and education intervention. Focus group feedback was used to identify key messages and to develop the play's script. Qualitative methods were used to collect and analyse relevant data. Interviews were conducted with learner-actors, pre- and post-focus group feedback was obtained from a sample of school-going adolescents, and pre- and post-questionnaires were administered to adolescent audience members. From the pre-drama focus group discussions, topics such as TB symptoms, stigma and transmission were identified as areas that needed attention. After the performances, adolescents showed improved knowledge on the identified topics and they discussed TB prevention measures. They highlighted transmission of TB during pregnancy as a further topic to be addressed in future iterations of the drama. Although stigma is a difficult phenomenon to interpret, post-drama participants understood that TB transmission could occur in all individuals. Learner-actors agreed with focus group participants that the play could impact the wider community if it were rolled out. Feedback from the South African Tuberculosis Vaccine Initiative staff verified that recruitment for an upcoming trial was facilitated by the preparedness that the play provided in recruitment areas. The study showed that before and after evaluations provide data on the usefulness of the play as an education tool. Theatre, presented and motivated by adolescent peers, can raise awareness of TB, and assist clinical trial preparedness and further engagement between trial staff and their trial community.

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

PubMed

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

2015-10-01

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. The objective of the present study was to assess the association between a history of tuberculosis and airflow obstruction and spirometric abnormalities in adults.The study was performed in adults, aged 40 years and above, who took part in the multicentre, cross-sectional, general population-based Burden of Obstructive Lung Disease study, and 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.A self-reported history of tuberculosis was associated with airflow obstruction (adjusted odds ratio 2.51, 95% CI 1.83-3.42) and spirometric restriction (adjusted odds ratio 2.13, 95% CI 1.42-3.19).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. Copyright ©ERS 2015.

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

Vitamin C supplementation improve the sputum conversion culture rate in pulmonary tuberculosis treatment while rifampicin susceptible

NASA Astrophysics Data System (ADS)

Susanto, L.; Siregar, Y.; Kusumawati, L.

2018-03-01

The failure of first-line tuberculosis treatment greatly affects multiple drug-resistant tuberculosis. In vitro study of vitamin C induces the death of M. tuberculosis bacteria and accelerates healing of tuberculosis, so the multiple drug-resistant tuberculosis can be avoided. This research aimed to identify the effect of vitamin C as a supportive treatment on the sputum conversion rate. The randomizedand double group with a parallel design by matching pair method was used to collect samples. The first group was treated with standard tuberculosis treatment, and the other was given vitamin C supplementation. Vitamin C plasma level analyzation was performed before and after two months of treatment. Sputum conversion was evaluated every week for eight weeks. The comparison of vitamin C plasma level in pre and post-treatment group was significant (p=0.03) but not in the other group. There was no significant difference in vitamin C plasma level between two groups (p=0.21). The proportion of sputum conversion rate in both group in the first week was 0% vs. 9.6% (p=0.83) and the last week of study was 83.9% vs. 100% (p=0.02). In conclusion, vitamin C supplementation has effects in improving the healing process of tuberculosis patients as indicated by higher in sputum conversion rate.

The management of infection with Mycobacterium tuberculosis in young children post-2015: an opportunity to close the policy-practice gap.

PubMed

Graham, Stephen M

2017-01-01

The treatment of infection with Mycobacterium tuberculosis in young children is supported by universal policy based on strong rationale and evidence of effectiveness, but has rarely been implemented in tuberculosis endemic countries. Areas covered: This review highlights a number of important recent developments that provide an unprecedented opportunity to close the policy-practice gap, as well as ongoing needs to facilitate implementation under programmatic conditions and scale-up. Expert commentary: The WHO's End TB Strategy and Stop TB Partnership's Plan to End TB provide ambitious targets for prevention at a time when National Tuberculosis Programs in tuberculosis endemic countries are increasing attention to the challenges of management and prevention of tuberculosis disease in children. This opportunity is greatly enhanced by recent evidence of the effectiveness of shorter, simpler and safer regimens to treat tuberculosis infection. The scale of the challenge for implementation will require a decentralized, integrated, community-based approach. An accurate and low-cost point-of-care test for tuberculous infection would be a major advance to support such implementation. Specific guidance for the treatment of infection in young child contacts of multidrug-resistant tuberculosis cases is a major current need while awaiting further evidence.

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

Managing a case of extensively drug-resistant (XDR) pulmonary tuberculosis in Singapore.

PubMed

Phua, Chee Kiang; Chee, Cynthia B E; Chua, Angeline P G; Gan, Suay Hong; Ahmed, Aneez D B; Wang, Yee Tang

2011-03-01

Extensively drug-resistant tuberculosis (XDR-TB) is an emerging global health risk. We present the first case report of XDR-TB in Singapore. A 41-year-old Indonesian lady with previously treated pulmonary tuberculosis presented with chronic cough. Her sputum was strongly acid-fast bacilli positive and grew Mycobacterium tuberculosis complex resistant to first and second-line TB medications. She received 5 months of intensive multidrug treatment without sputum smear conversion. She then underwent resection of the diseased lung. The total cost incurred amounted to over S$100,000. She achieved sputum smear/culture conversion post-surgery, but will require further medical therapy for at least 18 months. XDRTB is poorly responsive to therapy and extremely expensive to manage. Its prevention by strict compliance to therapy is paramount.

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.

Absorption, distribution and excretion of the anti-tuberculosis drug delamanid in rats: Extensive tissue distribution suggests potential therapeutic value for extrapulmonary tuberculosis.

PubMed

Shibata, Masakazu; Shimokawa, Yoshihiko; Sasahara, Katsunori; Yoda, Noriaki; Sasabe, Hiroyuki; Suzuki, Mitsunari; Umehara, Ken

2017-05-01

Delamanid (OPC-67683, Deltyba™, nitro-dihydro-imidazooxazoles derivative) is approved for the treatment of adult pulmonary multidrug-resistant tuberculosis. The absorption, distribution and excretion of delamanid-derived radioactivity were investigated after a single oral administration of 14 C-delamanid at 3 mg/kg to rats. In both male and female rats, radioactivity in blood and all tissues reached peak levels by 8 or 24 h post-dose, and thereafter decreased slowly. Radioactivity levels were 3- to 5-fold higher in lung tissue at time to maximum concentration compared with plasma. In addition, radioactivity was broadly distributed in various tissues, including the central nervous system, eyeball, placenta and fetus, indicating that 14 C-delamanid permeated the brain, retinal and placental blood barriers. By 168 h post-dose, radioactivity in almost all the tissues was higher than that in the plasma. Radioactivity was also transferred into the milk of lactating rats. Approximately 6% and 92% of radioactivity was excreted in the urine and feces, respectively, indicating that the absorbed radioactivity was primarily excreted via the biliary route. No significant differences in the absorption, distribution and excretion of 14 C-delamanid were observed between male and female rats. The pharmacokinetic results suggested that delamanid was broadly distributed to the lungs and various tissues for a prolonged duration of time at concentrations expected to effectively target tuberculosis bacteria. These data indicate that delamanid, in addition to its previously demonstrated efficacy in pulmonary tuberculosis, might be an effective therapeutic approach to treating extrapulmonary tuberculosis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

Long-term tolerance of airway silicone stent in patients with post-tuberculosis tracheobronchial stenosis.

PubMed

Verma, Akash; Um, Sang-Won; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kwon, O Jung; Kim, Hojoong

2012-01-01

Surgery is a well-recognized modality of treatment for benign tracheobronchial stenosis. However, in some benign disease groups, such as tuberculosis, sarcoidosis, war gas exposure, and inhalation burns, multiplicity of involvement or long length of stenosed segment heightens surgical challenge. We investigated the outcomes and long-term tolerability of the Natural stent (N-stent) in such patients with post-tuberculosis tracheobronchial stenosis. A retrospective review was done for 17 patients who underwent silicone stenting (N-stent) for post-tuberculosis tracheobronchial stenosis during January 2000-December 2003 but needed persistent stent placement and still require the stent. Significant increase in the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), expressed as FEV1%, as well as in forced percentual vital capacity (FVC%) (Δ24% and Δ11%, respectively) in the short term and sustained increase in the FEV1% and FVC% (Δ26.5% and Δ16.5%, respectively) in the long term were noted at a median (range) interval of 1 (0.5-72) month and 72 (12-114) months, respectively, along with symptomatic relief. No procedure-related death occurred. Stent-related late complications included granulation tissue formation (76%), migration (70%), and mucostasis (17%). The median duration for which N-stents were tolerated was 7.9 (range, 3-11) years. N-stents are well-tolerated for a prolonged period. Stent-related complications occur, but are easily managed. These results might carry medical implications for those who have airway lesions difficult to correct surgically.

Tuberculin skin test, Interferon gamma release assays or just chest X-ray to study latent tuberculosis before solid organ transplantation?

PubMed

Guirao-Arrabal, Emilio; Torre-Cisneros, Julián

2018-05-24

We have read with great interest the article entitled 'Tuberculosis (TB) after liver transplantation in a large center in New York City: QuantiFERON ® -TB Gold-based pre-transplant screening performance and active TB post transplant' by Hand et al. 1 The authors' results are in accordance with our previously published data in lung transplantation, in which we reported that radiologic findings in pretransplant chest computed tomography (CT) compatible with residual TB are an independent risk factor for post-transplant TB. 2 This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Brain tuberculomas: a case report.

PubMed

Saleh, Maryam; Saeedi, Ali Asghar; Ali Pooran, Ali

2014-07-01

An unusual incidence of tuberculosis in different parts of the body is called tuberculomas. The rate of brain tuberculosis is rare. The following case of tuberculamas of the brain, presented by enhancing rings of meninges, is reported because of its rarity. It was a case of brain tuberculomas in a 15-year-old girl with primary symptoms of headache and general weakness, and no signs of primary pulmonary infection. The subject underwent computerized tomography (CT) and magnetic resonance imaging (MRI) of the brain. Microbiological tests (acid fast bacilli smear-AFB, and culture of biopsy specimen) were applied subsequently. According to the results, the problem was diagnosed as brain tuberculomas. After operation she was completely treated with anti-TB drugs. Although brain tuberculosis is rare, it was diagnosed on the basis of histopathology and the patient's successful response to anti-tuberculous drug treatment.

Emerging tuberculosis pathogen hijacks social communication behavior in the group-living banded mongoose (Mungos mungo)

USDA-ARS?s Scientific Manuscript database

Mycobacterium mungi, a novel M. tuberculosis complex pathogen (MtbC), has emerged in wild banded mongoose (Mungos mungo) in Northern Botswana, causing significant mortality. Unlike other members of the MtbC, M. mungi is not transmitted through a primary aerosol route. Rather, pathogen invasion occur...

Strengthening health human resources and improving clinical outcomes through an integrated guideline and educational outreach in resource-poor settings: a cluster-randomized trial.

PubMed

Schull, Michael J; Banda, Hastings; Kathyola, Damson; Fairall, Lara; Martiniuk, Alexandra; Burciul, Barry; Zwarenstein, Merrick; Sodhi, Sumeet; Thompson, Sandy; Joshua, Martias; Mondiwa, Martha; Bateman, Eric

2010-12-03

In low-income countries, only about a third of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) patients eligible for anti-retroviral treatment currently receive it. Providing decentralized treatment close to where patients live is crucial to a faster scale up, however, a key obstacle is limited health system capacity due to a shortage of trained health-care workers and challenges of integrating HIV/AIDS care with other primary care services (e.g. tuberculosis, malaria, respiratory conditions). This study will test an adapted primary care health care worker training and guideline intervention, Practical Approach to Lung Health and HIV/AIDS Malawi (PALM PLUS), on staff retention and satisfaction, and quality of patient care. A cluster-randomized trial design is being used to compare usual care with a standardized clinical guideline and training intervention, PALM PLUS. The intervention targets middle-cadre health care workers (nurses, clinical officers, medical assistants) in 30 rural primary care health centres in a single district in Malawi. PALM PLUS is an integrated, symptom-based and user-friendly guideline consistent with Malawian national treatment protocols. Training is standardized and based on an educational outreach approach. Trainers will be front-line peer healthcare workers trained to provide outreach training and support to their fellow front-line healthcare workers during focused (1-2 hours), intermittent, interactive sessions on-site in health centers. Primary outcomes are health care worker retention and satisfaction. Secondary outcomes are clinical outcomes measured at the health centre level for HIV/AIDS, tuberculosis, prevention-of-mother-to-child-transmission of HIV and other primary care conditions. Effect sizes and 95% confidence intervals for outcomes will be presented. Assessment of outcomes will occur at 1 year post- implementation. The PALM PLUS trial aims to address a key problem: strengthening middle-cadre health care workers to support the broader scale up of HIV/AIDS services and their integration into primary care. The trial will test whether the PALM PLUS intervention improves staff satisfaction and retention, as well as the quality of patient care, when compared to usual practice. Controlled Clinical Trials ISRCTN47805230.

High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis

PubMed Central

Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P.; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter

2018-01-01

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world’s population with latent Mtb infection (LTBI), and 5–10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection. PMID:29379507

High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against Tuberculosis.

PubMed

Billeskov, Rolf; Lindenstrøm, Thomas; Woodworth, Joshua; Vilaplana, Cristina; Cardona, Pere-Joan; Cassidy, Joseph P; Mortensen, Rasmus; Agger, Else Marie; Andersen, Peter

2017-01-01

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB leaving 25% of the world's population with latent Mtb infection (LTBI), and 5-10% of these people will reactivate and develop active TB. An efficient therapeutic vaccine targeting LTBI could have an enormous impact on global TB incidence, and could be an important aid in fighting multidrug resistance, which is increasing globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB vaccine candidate that post-exposure, but not preventive, vaccine protection requires low vaccine antigen doses for optimal protection. Loss of protection from high dose post-exposure vaccination was not associated with a loss of overall vaccine response magnitude, but rather with greater differentiation and lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen dose also led to a decreased ability of vaccine-specific CD4 T cells to home into the Mtb-infected lung parenchyma, a recently discovered important feature of T cell protection in mice. These results underscore the importance of T cell quality rather than magnitude in TB-vaccine protection, and the significant role that antigen dosing plays in vaccine-mediated protection.

Difficulties in the accessibility to health services for tuberculosis diagnoses in Brazilian municipalities.

PubMed

Scatena, Lúcia Marina; Villa, Tereza Cristina Scatena; Netto, Antonio Ruffino; Kritski, Afrânio Lineu; Figueiredo, Tânia Maria Ribeiro Monteiro de; Vendramini, Silvia Helena Figueiredo; Assis, Marluce Maria de Araújo; Motta, Maria Catarina Salvador da

2009-06-01

To assess difficulties in the accessibility to tuberculosis diagnoses in the health services in Brazil. The study was carried out in 2007 and surveyed tuberculosis patients treated in the primary care services in the cities of Ribeirão Preto, São José do Rio Preto, Itaboraí (these three in Southeastern Brazil), Campina Grande and Feira de Santana (these two in Northeastern Brazil). The instrument 'Primary Care Assessment Tool' was used, adapted to assess tuberculosis care in Brazil. Tuberculosis diagnosis in the health services was assessed by means of multiple correspondence factor analysis. The accessibility to the diagnosis was represented by the dimensions 'locomotion to the health service' and 'assistance service' in the factorial plan. The patients from Ribeirão Preto and Itaboraí were associated with more favorable conditions to the dimension 'locomotion to the health service' and the patients from Campina Grande and Feira de Santana were associated with less favorable conditions. Ribeirão Preto presented more favorable conditions to the dimension 'assistance service', followed by Itaboraí, Feira de Santana and Campina Grande. São José do Rio Preto presented less favorable conditions to both dimensions, 'locomotion to the health service' and 'assistance service', compared to the other cities. The factor analysis enabled the visualization of the organizational characteristics of the services that provide tuberculosis care. The decentralization of the actions to the family health program and reference centers seems not to present a satisfactory performance regarding accessibility to the tuberculosis diagnosis, as the form of services organization was not a determinant factor to guarantee the accessibility to the early diagnosis of the illness.

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

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

HIV infection and tuberculosis in South Africa: an urgent need to escalate the public health response

PubMed Central

Abdool Karim, Salim S.; Churchyard, Gavin J.; Abdool Karim, Quarraisha; Lawn, Stephen D.

2009-01-01

One of the greatest challenges facing post-apartheid South Africa is the control of the concomitant HIV and tuberculosis epidemics. HIV continues to spread relentlessly, and tuberculosis has been declared a national emergency. In 2007, South Africa, with 0·7% of the world’s population, had 17% of the global burden of HIV infection, and one of the world’s worst tuberculosis epidemics, compounded by rising drug resistance and HIV co-infection. Until recently, the South African Government’s response to these diseases has been marked by denial, lack of political will, and poor implementation of policies and programmes. Nonetheless, there have been notable achievements in disease management, including substantial improvements in access to condoms, expansion of tuberculosis control efforts, and scale-up of free antiretroviral therapy (ART). Care for acutely ill AIDS patients and long-term provision of ART are two issues that dominate medical practice and the health-care system. Decisive action is needed to implement evidence-based priorities for the control of the HIV and tuberculosis epidemics. By use of the framework of the Strategic Plans for South Africa for tuberculosis and HIV/AIDS, we provide prioritised four-step approaches for tuberculosis control, HIV prevention, and HIV treatment. Strong leadership, political will, social mobilisation, adequate human and financial resources, and sustainable development of health-care services are needed for successful implementation of these approaches. PMID:19709731

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.

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 pattern will secure the long-term success of the program. PMID:28766465

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.

Passive serum therapy with polyclonal antibodies against Mycobacterium tuberculosis protects against post-chemotherapy relapse of tuberculosis infection in SCID mice.

PubMed

Guirado, Evelyn; Amat, Isabel; Gil, Olga; Díaz, Jorge; Arcos, Virginia; Caceres, Neus; Ausina, Vicenç; Cardona, Pere-Joan

2006-04-01

We investigated the protective role of immune-sera against reactivation of Mycobacterium tuberculosis infection in SCID mice and found that passive immunization with sera obtained from mice treated with detoxified M. tuberculosis extracts (delivered in liposomes in a composition known as RUTI) exerted significant protection. Our SCID mouse model consisted of aerosol infection by M. tuberculosis, followed by 3 to 8weeks of chemotherapy with isoniazid+rifampicin (INH+RIF) (25 and 10mg/kg, respectively). After infection and antibiotic administration, two groups of mice were treated for up to 10weeks with intraperitoneal passive immunization using hyperimmune serum (HS) obtained from mice infected with M. tuberculosis, treated with chemotherapy (INH+RIF) for 8weeks and inoculated with RUTI (HS group) or with normal serum (CT group). Significant differences were found between HS and CT groups in the number of bacilli in the lungs (3.68+/-2.02 vs. 5.72+/-1.41log(10) c.f.u.), extent of pulmonary granulomatomous infiltration (10.33+/-0.67 vs. 31.2+/-1.77%), and percentage of animals without pulmonary abscesses (16.7% vs. 45.5%). These data strongly suggest a protective role of specific antibodies against lung dissemination of M. tuberculosis infection.

The safety, effectiveness and cost-effectiveness of cytisine in achieving six-month continuous smoking abstinence in tuberculosis patients - protocol for a double-blind, placebo-controlled randomised trial.

PubMed

Dogar, Omara; Barua, Deepa; Boeckmann, Melanie; Elsey, Helen; Fatima, Razia; Gabe, Rhian; Huque, Rumana; Keding, Ada; Khan, Amina; Kotz, Daniel; Kralikova, Eva; Newell, James N; Nohavova, Iveta; Parrott, Steve; Readshaw, Anne; Renwick, Lottie; Sheikh, Aziz; Siddiqi, Kamran

2018-04-20

Tuberculosis (TB) patients who quit smoking have much better disease outcomes than those who continue to smoke. Behavioural support combined with pharmacotherapy is the most effective strategy in helping people to quit, in general populations. However, there is no evidence for the effectiveness of this strategy in TB patients who smoke. We will assess the safety, effectiveness and cost-effectiveness of cytisine - a low-cost plant-derived nicotine substitute - for smoking cessation in TB patients compared with placebo, over and above brief behavioural support. Two-arm, parallel, double-blind, placebo-controlled, multi-centre (30 sites in Bangladesh and Pakistan), individually randomised trial. TB treatment centres integrated into public health care systems in Bangladesh and Pakistan. Newly diagnosed (in the last four weeks) adult pulmonary TB patients who are daily smokers (with or without dual smokeless tobacco use) and are interested in quitting (n= 2,388). The primary outcome measure is biochemically verified continuous abstinence from smoking at six months post-randomization, assessed using Russell Standard criteria. The secondary outcome measures include continuous abstinence at 12 months, lapses and relapses; clinical TB outcomes; nicotine dependency and withdrawal; and adverse events. This is the first smoking cessation trial of cytisine in low- and middle-income countries evaluating both cessation and tuberculosis (TB) outcomes. If found effective, cytisine could become the most affordable cessation intervention to help TB patients who smoke. This article is protected by copyright. All rights reserved.

Whole genome sequencing of clinical strains of Mycobacterium tuberculosis from Mumbai, India: A potential tool for determining drug-resistance and strain lineage.

PubMed

Chatterjee, Anirvan; Nilgiriwala, Kayzad; Saranath, Dhananjaya; Rodrigues, Camilla; Mistry, Nerges

2017-12-01

Amplification of drug resistance in Mycobacterium tuberculosis (M.tb) and its transmission are significant barriers in controlling tuberculosis (TB) globally. Diagnostic inaccuracies and delays impede appropriate drug administration, which exacerbates primary and secondary drug resistance. Increasing affordability of whole genome sequencing (WGS) and exhaustive cataloguing of drug resistance mutations is poised to revolutionise TB diagnostics and facilitate personalized drug therapy. However, application of WGS for diagnostics in high endemic areas is yet to be demonstrated. We report WGS of 74 clinical TB isolates from Mumbai, India, characterising genotypic drug resistance to first- and second-line anti-TB drugs. A concordance analysis between phenotypic and genotypic drug susceptibility of a subset of 29 isolates and the sensitivity of resistance prediction to the 4 drugs was calculated, viz. isoniazid-100%, rifampicin-100%, ethambutol-100% and streptomycin-85%. The whole genome based phylogeny showed almost equal proportion of East Asian (27/74) and Central Asian (25/74) strains. Interestingly we also found a clonal group of 9 isolates, of which 7 patients were found to be from the same geographical location and accessed the same health post. This provides the first evidence of epidemiological linkage for tracking TB transmission in India, an approach which has the potential to significantly improve chances of End-TB goals. Finally, the use of Mykrobe Predictor, as a standalone drug resistance and strain typing tool, requiring just few minutes to analyse raw WGS data into tabulated results, implies the rapid clinical applicability of WGS based TB diagnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.

PubMed

Bloom, Chloe I; Graham, Christine M; Berry, Matthew P R; Rozakeas, Fotini; Redford, Paul S; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A; Wilkinson, Robert J; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Valeyre, Dominique; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-Pei; Lipman, Marc; O'Garra, Anne

2013-01-01

New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.

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.

Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9.

PubMed

Ordonez, Alvaro A; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J; Klunk, Mariah H; Mollura, Daniel J; Nuermberger, Eric L; Jain, Sanjay K

2016-07-01

Cavitation is a key pathological feature of human tuberculosis (TB), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. Despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. Although cavitation does not occur in conventional mouse strains after infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally been observed in C3HeB/FeJ mice. However, to date, there has been no demonstration that cavitation can be produced consistently enough to support C3HeB/FeJ mice as a new and useful model of cavitary TB. We utilized serial computed tomography (CT) imaging to detect pulmonary cavitation in C3HeB/FeJ mice after aerosol infection with M. tuberculosis Post-mortem analyses were performed to characterize lung lesions and to localize matrix metalloproteinases (MMPs) previously implicated in cavitary TB in situ A total of 47-61% of infected mice developed cavities during primary disease or relapse after non-curative treatments. Key pathological features of human TB, including simultaneous presence of multiple pathologies, were noted in lung tissues. Optical imaging demonstrated increased MMP activity in TB lesions and MMP-9 was significantly expressed in cavitary lesions. Tissue MMP-9 activity could be abrogated by specific inhibitors. In situ, three-dimensional analyses of cavitary lesions demonstrated that 22.06% of CD11b+ signal colocalized with MMP-9. C3HeB/FeJ mice represent a reliable, economical and tractable model of cavitary TB, with key similarities to human TB. This model should provide an excellent tool to better understand the pathogenesis of cavitation and its effects on TB treatments. © 2016. Published by The Company of Biologists Ltd.

Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9

PubMed Central

Ordonez, Alvaro A.; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J.; Klunk, Mariah H.; Mollura, Daniel J.; Nuermberger, Eric L.

2016-01-01

ABSTRACT Cavitation is a key pathological feature of human tuberculosis (TB), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. Despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. Although cavitation does not occur in conventional mouse strains after infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally been observed in C3HeB/FeJ mice. However, to date, there has been no demonstration that cavitation can be produced consistently enough to support C3HeB/FeJ mice as a new and useful model of cavitary TB. We utilized serial computed tomography (CT) imaging to detect pulmonary cavitation in C3HeB/FeJ mice after aerosol infection with M. tuberculosis. Post-mortem analyses were performed to characterize lung lesions and to localize matrix metalloproteinases (MMPs) previously implicated in cavitary TB in situ. A total of 47-61% of infected mice developed cavities during primary disease or relapse after non-curative treatments. Key pathological features of human TB, including simultaneous presence of multiple pathologies, were noted in lung tissues. Optical imaging demonstrated increased MMP activity in TB lesions and MMP-9 was significantly expressed in cavitary lesions. Tissue MMP-9 activity could be abrogated by specific inhibitors. In situ, three-dimensional analyses of cavitary lesions demonstrated that 22.06% of CD11b+ signal colocalized with MMP-9. C3HeB/FeJ mice represent a reliable, economical and tractable model of cavitary TB, with key similarities to human TB. This model should provide an excellent tool to better understand the pathogenesis of cavitation and its effects on TB treatments. PMID:27482816

Evaluation of a standardized treatment regimen of anti-tuberculosis drugs for patients with multi-drug-resistant tuberculosis (STREAM): study protocol for a randomized controlled trial.

PubMed

Nunn, Andrew J; Rusen, I D; Van Deun, Armand; Torrea, Gabriela; Phillips, Patrick P J; Chiang, Chen-Yuan; Squire, S Bertel; Madan, Jason; Meredith, Sarah K

2014-09-09

In contrast to drug-sensitive tuberculosis, the guidelines for the treatment of multi-drug-resistant tuberculosis (MDR-TB) have a very poor evidence base; current recommendations, based on expert opinion, are that patients should be treated for a minimum of 20 months. A series of cohort studies conducted in Bangladesh identified a nine-month regimen with very promising results. There is a need to evaluate this regimen in comparison with the currently recommended regimen in a randomized controlled trial in a variety of settings, including patients with HIV-coinfection. STREAM is a multi-centre randomized trial of non-inferiority design comparing a nine-month regimen to the treatment currently recommended by the World Health Organization in patients with MDR pulmonary TB with no evidence on line probe assay of fluoroquinolone or kanamycin resistance. The nine-month regimen includes clofazimine and high-dose moxifloxacin and can be extended to 11 months in the event of delay in smear conversion. The primary outcome is based on the bacteriological status of the patients at 27 months post-randomization. Based on the assumption that the nine-month regimen will be slightly more effective than the control regimen and, given a 10% margin of non-inferiority, a total of 400 patients are required to be enrolled. Health economics data are being collected on all patients in selected sites. The results from the study in Bangladesh and cohorts in progress elsewhere are encouraging, but for this regimen to be recommended more widely than in a research setting, robust evidence is needed from a randomized clinical trial. Results from the STREAM trial together with data from ongoing cohorts should provide the evidence necessary to revise current recommendations for the treatment for MDR-TB. This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010.

Brain Tuberculomas: A Case Report

PubMed Central

Saleh, Maryam; Saeedi, Ali Asghar; Ali Pooran, Ali

2014-01-01

Introduction: An unusual incidence of tuberculosis in different parts of the body is called tuberculomas. The rate of brain tuberculosis is rare. Case Presentation: The following case of tuberculamas of the brain, presented by enhancing rings of meninges, is reported because of its rarity. It was a case of brain tuberculomas in a 15-year-old girl with primary symptoms of headache and general weakness, and no signs of primary pulmonary infection. Discussion: The subject underwent computerized tomography (CT) and magnetic resonance imaging (MRI) of the brain. Microbiological tests (acid fast bacilli smear-AFB, and culture of biopsy specimen) were applied subsequently. According to the results, the problem was diagnosed as brain tuberculomas. After operation she was completely treated with anti-TB drugs. Although brain tuberculosis is rare, it was diagnosed on the basis of histopathology and the patient's successful response to anti-tuberculous drug treatment. PMID:25368795

Surveillance of drug resistance for tuberculosis control: why and how?

PubMed

Chaulet, P; Boulahbal, F; Grosset, J

1995-12-01

The resistance of Mycobacterium tuberculosis to antibiotics, which reflects the quality of the chemotherapy applied in the community, is one of the elements of epidemiological surveillance used in national tuberculosis programmes. Measurement of drug resistance poses problems for biologists in standardization of laboratory methods and quality control. The definition of rates of acquired and primary drug resistance also necessitates standardization in the methods used to collect information transmitted by clinicians. Finally, the significance of the rates calculated depends on the choice of the patients sample on which sensitivity tests have been performed. National surveys of drug resistance therefore require multidisciplinary participation in order to select the only useful indicators: rates of primary resistance and of acquired resistance. These indicators, gathered in representative groups of patients over a long period, are a measurement of the impact of modern chemotherapy regimens on bacterial ecology.

Fluorescent microscopy and Ziehl-Neelsen staining of bronchoalveolar lavage, bronchial washings, bronchoscopic brushing and post bronchoscopic sputum along with cytological examination in cases of suspected tuberculosis.

PubMed

Bodal, Vijay Kumar; Bal, Manjit S; Bhagat, Sunita; Kishan, Jai; Brar, Rupinder K

2015-01-01

Ever since the discovery of Mycobacterium tuberculosis in 1882, many diagnostic methods have been developed. However "The gold standard" for the diagnosis of tuberculosis (TB) is still the demonstration of acid fast Bacilli (AFB) by microscopic examination of smear or bacteriological confirmation by culture method. In suspected 75 patients with active pulmonary TB, the materials obtained bronchoscopically, were bronchoalveolar lavage (BAL), bronchial brushings, bronchial washings and post bronchoscopic sputum. Four smears were made from each of the specimen. Fluorescent Staining, Ziehl-Neelsen (ZN), Pap and May Grunwald-Giemsa (MGG) stains were carried out for cytological examination. Fluorescent stain yielded maximum AFB positivity in all the methods, that is 36 (48%) in post fibre-optic bronchoscopy (FOB) sputum and 19 (25.33%) by fluorescence microscopy in both bronchial brushings and bronchial washings. Maximum yield of AFB with ZN staining 12 (16%) was equal to the post FOB sputum and bronchial brushings samples. It was followed by 6 cases (8%) in BAL and 4 (5.3%) in bronchial washings. The cytological examination was suggestive of TB in only 8 (10.66%) cases in bronchial washings and 6 (8%) cases in post FOB collection. It was equal in BAL and Bronchial brushings each that is 5 (6.67%). Bronchoscopy is a useful diagnostic tool and fluorescent microscopy is more sensitive than ZN and cytology. On X-ray examination, other diseases like malignancy or fungus can also mimick TB. So apart from ZN staining or fluorescence microscopy, Pap and MGG stain will be worthwhile to identify other microorganisms.

Label-free nano-biosensing on the road to tuberculosis detection.

PubMed

Golichenari, Behrouz; Velonia, Kelly; Nosrati, Rahim; Nezami, Alireza; Farokhi-Fard, Aref; Abnous, Khalil; Behravan, Javad; Tsatsakis, Aristidis M

2018-08-15

Tuberculosis, an ailment caused by the bacterium Mycobacterium tuberculosis (Mtb) complex, is one of the catastrophic transmittable diseases that affect human. Reports published by WHO indicate that in 2017 about 6.3 million people progressed to TB and 53 million TB patients died from 2000 to 2016. Therefore, early diagnosis of the disease is of great importance for global health care programs. Common diagnostics like the traditional PPD test and antibody-assisted assays suffer the lack of sensitivity, long processing time and cumbersome post-test proceedings. These shortcomings restrict their use and encourage innovations in TB diagnostics. In recent years, the biosensor concept opened up new horizons in sensitive and fast detection of the disease, reducing the interval time between sampling and diagnostic result. Among new diagnostics, label-free nano-biosensors are highly promising for sensitive and accessible detection of tuberculosis. Various specific label-free nano-biosensors have been recently reported detecting the whole cell of M. tuberculosis, mycobacterial proteins and IFN-γ as crucial markers in early diagnosis of TB. This article provides a focused overview on nanomaterial-based label-free biosensors for tuberculosis detection. Copyright © 2018 Elsevier B.V. All rights reserved.

The potential role of lung epithelial cells and beta-defensins in experimental latent tuberculosis.

PubMed

Rivas-Santiago, B; Contreras, J C L; Sada, E; Hernández-Pando, R

2008-05-01

Mycobacterium tuberculosis is a facultative intracellular pathogen capable of producing both progressive disease and latent infection. Latent infection is clinically asymptomatic and is manifested only by a positive tuberculin test or a chest radiograph that shows scars or calcified nodules indicative of resolved primary tuberculosis infection. In this study, we used a well-characterized model of latent tuberculosis infection in B6D2F1 mice to compare the production of beta-defensin-3 by infected bronchial epithelial cells and macrophages. We demonstrated by immunolectronmicroscopy that M. tuberculosis can actually infect epithelial cells and induce significant higher production of beta-defensin-3 associated to mycobacteria than infected macrophages. These results demonstrate that lung epithelium harbour mycobacteria during experimental chronic infection; being a possible reservoir of latent mycobacteria in vivo, beta-defensins might participate in bacilli killing or dormancy induction.

On the nature of Mycobacterium tuberculosis-latent bacilli.

PubMed

Cardona, P-J; Ruiz-Manzano, J

2004-12-01

Mycobacterium tuberculosis-latent bacilli are microorganisms that adapt to stressful conditions generated by the infected host against them. By slowing metabolism or becoming dormant, they may counterbalance these conditions and appear as silent to the immune system. Moreover, the dynamic turnover of the infected cells provokes a constant reactivation of the latent bacilli when the environmental conditions are favourable, or an activation after being dormant in necrotic and fibrotic lesions for a long period of time. Since there is no in vivo nor in vitro evidence for quick resuscitation of dormant bacilli, the current authors strongly favour the possibility that latent tuberculosis infection can be maintained for no longer than approximately 10 yrs, which is, nowadays, a time period very close to that considered for "primary" tuberculosis. This concept may also be helpful for newer epidemiological considerations regarding the real impact of reinfection in tuberculosis.

What's new in tuberculosis vaccines?

PubMed Central

Ginsberg, Ann M.

2002-01-01

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

Structure of Rv1848 (UreA), the Mycobacterium tuberculosis urease γ subunit

PubMed Central

Habel, Jeff E.; Bursey, Evan H.; Rho, Beom-Seop; Kim, Chang-Yub; Segelke, Brent W.; Rupp, Bernhard; Park, Min S.; Terwilliger, Thomas C.; Hung, Li-Wei

2010-01-01

The crystal structure of the urease γ subunit (UreA) from Mycobacterium tuberculosis, Rv1848, has been determined at 1.8 Å resolution. The asymmetric unit contains three copies of Rv1848 arranged into a homotrimer that is similar to the UreA trimer in the structure of urease from Klebsiella aerogenes. Small-angle X-ray scattering experiments indicate that the Rv1848 protein also forms trimers in solution. The observed homotrimer and the organization of urease genes within the M. tuberculosis genome suggest that M. tuberculosis urease has the (αβγ)3 composition observed for other bacterial ureases. The γ subunit may be of primary importance for the formation of the urease quaternary structure. PMID:20606272

O-mannosylation of the Mycobacterium tuberculosis Adhesin Apa Is Crucial for T Cell Antigenicity during Infection but Is Expendable for Protection

PubMed Central

Dobos, Karen M.; Lucas, Megan; Spencer, John S.; Fang, Sunan; McDonald, Melissa A.; Pohl, Jan; Birkness, Kristin; Chamcha, Venkateswarlu; Ramirez, Melissa V.; Plikaytis, Bonnie B.; Posey, James E.; Amara, Rama Rao

2013-01-01

Glycosylation is the most abundant post-translational polypeptide chain modification in nature. Although carbohydrate modification of protein antigens from many microbial pathogens constitutes important components of B cell epitopes, the role in T cell immunity is not completely understood. Here, using ELISPOT and polychromatic flow cytometry, we show that O-mannosylation of the adhesin, Apa, of Mycobacterium tuberculosis (Mtb) is crucial for its T cell antigenicity in humans and mice after infection. However, subunit vaccination with both mannosylated and non-mannosylated Apa induced a comparable magnitude and quality of T cell response and imparted similar levels of protection against Mtb challenge in mice. Both forms equally improved waning BCG vaccine-induced protection in elderly mice after subunit boosting. Thus, O-mannosylation of Apa is required for antigenicity but appears to be dispensable for its immunogenicity and protective efficacy in mice. These results have implications for the development of subunit vaccines using post-translationally modified proteins such as glycoproteins against infectious diseases like tuberculosis. PMID:24130497

O-mannosylation of the Mycobacterium tuberculosis adhesin Apa is crucial for T cell antigenicity during infection but is expendable for protection.

PubMed

Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Fang, Sunan; McDonald, Melissa A; Pohl, Jan; Birkness, Kristin; Chamcha, Venkateswarlu; Ramirez, Melissa V; Plikaytis, Bonnie B; Posey, James E; Amara, Rama Rao; Sable, Suraj B

2013-01-01

Glycosylation is the most abundant post-translational polypeptide chain modification in nature. Although carbohydrate modification of protein antigens from many microbial pathogens constitutes important components of B cell epitopes, the role in T cell immunity is not completely understood. Here, using ELISPOT and polychromatic flow cytometry, we show that O-mannosylation of the adhesin, Apa, of Mycobacterium tuberculosis (Mtb) is crucial for its T cell antigenicity in humans and mice after infection. However, subunit vaccination with both mannosylated and non-mannosylated Apa induced a comparable magnitude and quality of T cell response and imparted similar levels of protection against Mtb challenge in mice. Both forms equally improved waning BCG vaccine-induced protection in elderly mice after subunit boosting. Thus, O-mannosylation of Apa is required for antigenicity but appears to be dispensable for its immunogenicity and protective efficacy in mice. These results have implications for the development of subunit vaccines using post-translationally modified proteins such as glycoproteins against infectious diseases like tuberculosis.

Revisiting Host Preference in the Mycobacterium tuberculosis Complex: Experimental Infection Shows M. tuberculosis H37Rv to Be Avirulent in Cattle

PubMed Central

Whelan, Adam O.; Coad, Michael; Cockle, Paul J.; Hewinson, Glyn; Vordermeier, Martin; Gordon, Stephen V.

2010-01-01

Experiments in the late 19th century sought to define the host specificity of the causative agents of tuberculosis in mammals. Mycobacterium tuberculosis, the human tubercle bacillus, was independently shown by Smith, Koch, and von Behring to be avirulent in cattle. This finding was erroneously used by Koch to argue the converse, namely that Mycobacterium bovis, the agent of bovine tuberculosis, was avirulent for man, a view that was subsequently discredited. However, reports in the literature of M. tuberculosis isolation from cattle with tuberculoid lesions suggests that the virulence of M. tuberculosis for cattle needs to be readdressed. We used an experimental bovine infection model to test the virulence of well-characterized strains of M. tuberculosis and M. bovis in cattle, choosing the genome-sequenced strains M. tuberculosis H37Rv and M. bovis 2122/97. Cattle were infected with approximately 106 CFU of M. tuberculosis H37Rv or M. bovis 2122/97, and sacrificed 17 weeks post-infection. IFN-γ and tuberculin skin tests indicated that both M. bovis 2122 and M. tuberculosis H37Rv were equally infective and triggered strong cell-mediated immune responses, albeit with some indication of differential antigen-specific responses. Postmortem examination revealed that while M. bovis 2122/97–infected animals all showed clear pathology indicative of bovine tuberculosis, the M. tuberculosis–infected animals showed no pathology. Culturing of infected tissues revealed that M. tuberculosis was able to persist in the majority of animals, albeit at relatively low bacillary loads. In revisiting the early work on host preference across the M. tuberculosis complex, we have shown M. tuberculosis H37Rv is avirulent for cattle, and propose that the immune status of the animal, or genotype of the infecting bacillus, may have significant bearing on the virulence of a strain for cattle. This work will serve as a baseline for future studies into the genetic basis of host preference, and in particular the molecular basis of virulence in M. bovis. PMID:20049086

Reactivation or reinfection in adult tuberculosis: Is that the question?

PubMed

Cardona, Pere-Joan

2016-12-01

Looking at the chapter on "natural history" in any tuberculosis (TB) reference book, there is a kind of certainty regarding TB in adults. That is the concept of "post-primary" TB described as the reactivation of dormant bacilli hidden in an old lesion developed during infancy due to a type of local immunosuppression. Intriguingly, this concept involves at least two major uncertainties: how can dormant bacilli remain for such a long period, almost a lifetime, in an old lesion, taking into account granuloma dynamism; and what sort of local immunosuppression is the one that facilitates reactivation? The controversy between reactivation and exogenous reinfection as the cause of active TB started very soon in TB research. Interestingly, this "balance" was disturbed in the 1960s when the "Unitary Concept" became very successful in supporting the reactivation dogma. The "Unitary Concept" was mainly based on the data of tuberculin surveillance during the pre-antibiotic era as well as the data obtained from experimental modelling in animals. At the same time, the "Three-risks model" appeared to explain the relationship between the risk of infection and TB incidence, granting reinfection a key role in adult TB together with primary infection. This role was reinforced by the studies of recurrence based on molecular epidemiology, and a better knowledge of the immune response, granuloma dynamics, and lung physiology. Now it is a matter of taking it into account when designing new prophylactic and therapeutic strategies and also reflecting it in text books to better illustrate to our students. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Addressing the double-burden of diabetes and tuberculosis: lessons from Kyrgyzstan.

PubMed

Skordis-Worrall, Jolene; Round, Jeff; Arnold, Matthias; Abdraimova, Aida; Akkazieva, Baktygul; Beran, David

2017-03-15

The incidence of diabetes and tuberculosis co-morbidity is rising, yet little work has been done to understand potential implications for health systems, healthcare providers and individuals. Kyrgyzstan is a priority country for tuberculosis control and has a 5% prevalence of diabetes in adults, with many health system challenges for both conditions. Patient exit interviews collected data on demographic and socio-economic characteristics, health spending and care seeking for people with diabetes, tuberculosis and both diabetes and tuberculosis. Qualitative data were collected through semi-structured interviews with healthcare workers involved in diabetes and tuberculosis care, to understand delivery of care and how providers view effectiveness of care. The experience of co-affected individuals within the health system is different than those just with tuberculosis or diabetes. Co-affected patients do not receive more care and also have different care for their tuberculosis than people with only tuberculosis. Very high levels of catastrophic spending are found among all groups despite these two conditions being included in the Kyrgyz state benefit package especially for medicines. This study highlights that different patterns of service provision by disease group are found. Although Kyrgyzstan has often been cited as an example in terms of health reforms and developing Primary Health Care, this study highlights the challenge of managing conditions that are viewed as "too complicated" for non-specialists and the impact this has on costs and management of individuals.

Individual and social vulnerabilities upon acquiring tuberculosis: a literature systematic review

PubMed Central

2014-01-01

Tuberculosis is a contagious infectious disease mainly caused by the bacteria Mycobacterium tuberculosis that still meets the priority criteria - high magnitude, transcendence and vulnerability - due to the threat it poses to public health. When taking into consideration the vulnerability conditions that favor the onset of the disease, this article aimed to investigate the implications originated from individual and social vulnerability conditions in which tuberculosis patients are inserted. Databases like MEDLINE, LILACS and SciELO were searched in Portuguese, Spanish and English using the descriptors tuberculosis and vulnerability, and 183 articles were found. After the selection criterion was applied, there were 22 publications left to be discussed. Some of the aspects that characterize the vulnerability to tuberculosis are: low-income and low-education families, age, poor living conditions, chemical dependency, pre-existing conditions/aggravations like diabetes mellitus and malnutrition, indigenous communities, variables related to health professionals, intense border crossings and migration, difficulty in accessing information and health services and lack of knowledge on tuberculosis. Much as such aspects are present and favor the onset of the disease, several reports show high incidence rates of tuberculosis in low vulnerability places, suggesting that some factors related to the disease are still unclear. In conclusion, health promotion is important in order to disfavor such conditions or factors of vulnerability to tuberculosis, making them a primary target in the public health planning process and disease control. PMID:25067955

Individual and social vulnerabilities upon acquiring tuberculosis: a literature systematic review.

PubMed

Nadjane Batista Lacerda, Sheylla; Cristina de Abreu Temoteo, Rayrla; Maria Ribeiro Monteiro de Figueiredo, Tânia; Darliane Tavares de Luna, Fernanda; Alves Nunes de Sousa, Milena; Carlos de Abreu, Luiz; Luiz Affonso Fonseca, Fernando

2014-01-01

Tuberculosis is a contagious infectious disease mainly caused by the bacteria Mycobacterium tuberculosis that still meets the priority criteria - high magnitude, transcendence and vulnerability - due to the threat it poses to public health. When taking into consideration the vulnerability conditions that favor the onset of the disease, this article aimed to investigate the implications originated from individual and social vulnerability conditions in which tuberculosis patients are inserted. Databases like MEDLINE, LILACS and SciELO were searched in Portuguese, Spanish and English using the descriptors tuberculosis and vulnerability, and 183 articles were found. After the selection criterion was applied, there were 22 publications left to be discussed. Some of the aspects that characterize the vulnerability to tuberculosis are: low-income and low-education families, age, poor living conditions, chemical dependency, pre-existing conditions/aggravations like diabetes mellitus and malnutrition, indigenous communities, variables related to health professionals, intense border crossings and migration, difficulty in accessing information and health services and lack of knowledge on tuberculosis. Much as such aspects are present and favor the onset of the disease, several reports show high incidence rates of tuberculosis in low vulnerability places, suggesting that some factors related to the disease are still unclear. In conclusion, health promotion is important in order to disfavor such conditions or factors of vulnerability to tuberculosis, making them a primary target in the public health planning process and disease control.

Atypical extraspinal musculoskeletal tuberculosis in immunocompetent patients: part II, tuberculous myositis, tuberculous bursitis, and tuberculous tenosynovites.

PubMed

Abdelwahab, Ibrahim Fikry; Bianchi, Stefano; Martinoli, Carlo; Klein, Michael; Hermann, George

2006-12-01

Tuberculosis involving the soft tissue from adjacent bone or joint is well recognized. However, primary tuberculous pyomyositis, tuberculous bursitis, and tuberculous tenosynovitis are rare entities constituting 1% of skeletal tuberculosis. Tuberculous tenosynovitis involves most commonly the tendon sheaths of the hand and wrist, and tuberculous bursitis occurs most commonly around the hip. The greater trochanteric bursa and the greater trochanter are the most frequent sites of tuberculous bursitis. Cases of primary tuberculous pyomyositis and tenosynovitis of the tendons of the ankle and foot are seldom reported in the radiology literature. All imaging modalities-plain radiography, bone scan, computed tomography, and magnetic resonance imaging (MRI)--provide information that is helpful in determining therapy. MRI in particular, with its multiplanar capabilities and superb contrast of soft tissue, can demonstrate the extent of the soft tissue mass and access the adjacent bones and joints. However, MRI has no diagnostic specificity in regard to tuberculosis, and in nonendemic areas, biopsy is strongly recommended. All patients in this review were permanent residents of North America or Western Europe and were immunocompetent. Examples of atypical presentations of the above entities are demonstrated.

Imaging of thoracic tuberculosis in children: current and future directions.

PubMed

Sodhi, Kushaljit Singh; Bhalla, Ashu S; Mahomed, Nasreen; Laya, Bernard F

2017-09-01

Tuberculosis continues to be an important cause of morbidity and mortality worldwide. It is the leading cause of infection-related deaths worldwide. Children are amongst the high-risk groups for developing tuberculosis and often pose a challenge to the clinicians in making a definitive diagnosis. The newly released global tuberculosis report from World Health Organization reveals a 50% increase in fatality from tuberculosis in children. Significantly, diagnostic and treatment algorithms of tuberculosis for children differ from those of adults. Bacteriologic confirmation of the disease is often difficult in children; hence radiologists have an important role to play in early diagnosis of this disease. Despite advancing technology, the key diagnostic imaging modalities for primary care and emergency services, especially in rural and low-resource areas, are chest radiography and ultrasonography. In this article, we discuss various diagnostic imaging modalities used in diagnosis and treatment of tuberculosis and their indications. We highlight the use of US as point-of-care service along with mediastinal US and rapid MRI protocols, especially in mediastinal lymphadenopathy and thoracic complications. MRI is the ideal modality in high-resource areas when adequate infrastructure is available. Because the prevalence of tuberculosis is highest in lower-resource countries, we also discuss global initiatives in low-resource settings.

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.

Mycobacterium tuberculosis GroEL2 Modulates Dendritic Cell Responses.

PubMed

Georgieva, Maria; Sia, Jonathan Kevin; Bizzell, Erica; Madan-Lala, Ranjna; Rengarajan, Jyothi

2018-02-01

Mycobacterium tuberculosis successfully subverts the host immune response to promote disease progression. In addition to its known intracellular niche in macrophages, M. tuberculosis interferes with the functions of dendritic cells (DCs), which are the primary antigen-presenting cells of the immune system. We previously showed that M. tuberculosis dampens proinflammatory responses and impairs DC functions through the cell envelope-associated serine protease Hip1. Here we present data showing that M. tuberculosis GroEL2, a substrate of Hip1, modulates DC functions. The full-length GroEL2 protein elicited robust proinflammatory responses from DCs and promoted DC maturation and antigen presentation to T cells. In contrast, the cleaved form of GroEL2, which predominates in M. tuberculosis , was poorly immunostimulatory and was unable to promote DC maturation and antigen presentation. Moreover, DCs exposed to full-length, but not cleaved, GroEL2 induced strong antigen-specific gamma interferon (IFN-γ), interleukin-2 (IL-2), and IL-17A cytokine responses from CD4 + T cells. Moreover, the expression of cleaved GroEL2 in the hip1 mutant restored the robust T cell responses to wild-type levels, suggesting that proteolytic cleavage of GroEL2 allows M. tuberculosis to prevent optimal DC-T cell cross talk during M. tuberculosis infection. Copyright © 2018 American Society for Microbiology.

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 the assay, and few were tested under more than one condition imposing nonreplication. That nonreplicating mycobacteria are metabolically active was corroborated by their susceptibility to several antibiotics and tool compounds that target the synthesis of lipids, RNA, DNA, proteins, and peptidoglycan. PMID:28233509

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.

Transcriptional Blood Signatures Distinguish Pulmonary Tuberculosis, Pulmonary Sarcoidosis, Pneumonias and Lung Cancers

PubMed Central

Bloom, Chloe I.; Graham, Christine M.; Berry, Matthew P. R.; Rozakeas, Fotini; Redford, Paul S.; Wang, Yuanyuan; Xu, Zhaohui; Wilkinson, Katalin A.; Wilkinson, Robert J.; Kendrick, Yvonne; Devouassoux, Gilles; Ferry, Tristan; Miyara, Makoto; Bouvry, Diane; Dominique, Valeyre; Gorochov, Guy; Blankenship, Derek; Saadatian, Mitra; Vanhems, Phillip; Beynon, Huw; Vancheeswaran, Rama; Wickremasinghe, Melissa; Chaussabel, Damien; Banchereau, Jacques; Pascual, Virginia; Ho, Ling-pei; Lipman, Marc; O’Garra, Anne

2013-01-01

Rationale New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. Objectives To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. Methods We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. Measurements and Main Results An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Conclusions Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment. PMID:23940611

Recent transmission of Mycobacterium tuberculosis in China: the implication of molecular epidemiology for tuberculosis control.

PubMed

Yang, Chongguang; Gao, Qian

2018-02-01

Tuberculosis (TB) has remained an ongoing concern in China. The national scale-up of the Directly Observed Treatment, Short Course (DOTS) program has accelerated the fight against TB in China. Nevertheless, many challenges still remain, including the spread of drug-resistant strains, high disease burden in rural areas, and enormous rural-to-urban migrations. Whether incident active TB represents recent transmission or endogenous reactivation has helped to prioritize the strategies for TB control. Evidence from molecular epidemiology studies has delineated the recent transmission of Mycobacterium tuberculosis (M. tuberculosis) strains in many settings. However, the transmission patterns of TB in most areas of China are still not clear. Studies carried out to date could not capture the real burden of recent transmission of the disease in China because of the retrospective study design, incomplete sampling, and use of low-resolution genotyping methods. We reviewed the implementations of molecular epidemiology of TB in China, the estimated disease burden due to recent transmission of M. tuberculosis strains, the primary transmission of drug-resistant TB, and the evaluation of a feasible genotyping method of M. tuberculosis strains in circulation.

[Storage and transport of isolated M. tuberculosis at public and private health institutions in Japan].

PubMed

Ohkado, Akihiro; Takahashi, Chieko; Horiba, Masahide; Murase, Yoshiro; Mitarai, Satoshi

2008-08-01

To obtain basic data about the present practices on storage and transport of isolated M. tuberculosis at public and private health institutions in Japan. Survey forms regarding the practices on storage and transport of isolated M. tuberculosis were distributed and collected by post-mail in January 2007 to 76 local public health institutions, 145 public health centres, and 150 public or private hospitals. The questionnaire was adopted from the guidelines proposed by the Ministry of Health, Labour, and Welfare in 2006 on storage and transport of isolated M. tuberculosis. The respondents of the survey were as follows: 96.1% (73/76) from local public health institutions, 93.8% (136/145) from public health centres, and 73.3% (110/150) from hospitals. In general, local public health institutions conformed well to the proposed standards, however public health centres and hospitals were not compliant to some standards. Based on the survey conducted on the practice of storage and transport of isolated M. tuberculosis, certain discrepancy was found among public health centres and hospitals.

Insights from the docking and molecular dynamics simulation of the Phosphopantetheinyl transferase (PptT) structural model from Mycobacterium tuberculosis.

PubMed

Rohini, Karunakaran; Srikumar, Padmalayam Sadanandan

2013-01-01

A great challenge is posed to the treatment of tuberculosis due to the evolution of multidrug-resistant (MDR) and extensively drugresistant (XDR) strains of Mycobacterium tuberculosis in recent times. The complex cell envelope of the bacterium contains unusual structures of lipids which protects the bacterium from host enzymes and escape immune response. To overcome the drug resistance, targeting "drug targets" which have a critical role in growth and virulence factor is a novel approach for better tuberculosis treatment. The enzyme Phosphopantetheinyl transferase (PptT) is an attractive drug target as it is primarily involved in post translational modification of various types-I polyketide synthases and assembly of mycobactin, which is required for lipid virulence factors. Our in silico studies reported that the structural model of M.tuberculosis PptT characterizes the structure-function activity. The refinement of the model was carried out with molecular dynamics simulations and was analyzed with root mean square deviation (RMSD), and radius of gyration (Rg). This confirmed the structural behavior of PptT in dynamic system. Molecular docking with substrate coenzyme A (CoA) identified the binding pocket and key residues His93, Asp114 and Arg169 involved in PptT-CoA binding. In conclusion, our results show that the M.tuberculosis PptT model and critical CoA binding pocket initiate the inhibitor design of PptT towards tuberculosis treatment.

Bacteriological diagnosis and molecular strain typing of Mycobacterium bovis and Mycobacterium caprae.

PubMed

Gormley, E; Corner, L A L; Costello, E; Rodriguez-Campos, S

2014-10-01

The primary isolation of a Mycobacterium sp. of the Mycobacterium tuberculosis complex from an infected animal provides a definitive diagnosis of tuberculosis. However, as Mycobacterium bovis and Mycobacterium caprae are difficult to isolate, particularly for animals in the early stages of disease, success is dependent on the optimal performance of all aspects of the bacteriological process, from the initial choice of tissue samples at post-mortem examination or clinical samples, to the type of media and conditions used to cultivate the microorganism. Each step has its own performance characteristics, which can contribute to sensitivity and specificity of the procedure, and may need to be optimized in order to achieve the gold standard diagnosis. Having isolated the slow-growing mycobacteria, species identification and fine resolution strain typing are keys to understanding the epidemiology of the disease and to devise strategies to limit transmission of infection. New technologies have emerged that can now even discriminate different isolates from the same animal. In this review we highlight the key factors that contribute to the accuracy of bacteriological diagnosis of M. bovis and M. caprae, and describe the development of advanced genotyping techniques that are increasingly used in diagnostic laboratories for the purpose of supporting detailed epidemiological investigations. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Prevalence of tobacco smoking among phthisio-pulmonological inpatients].

PubMed

Ugriumov, A I

2001-01-01

A questionnaire survey of 222 phthisiopulmonological inpatients has indicated that 21.7 of the males and 4.05% of the females are smokers. Among clinical and morphological forms of tuberculosis, fibrocavernous tuberculosis is prevalent in smokers. Tuberculoma and post tuberculous fibrosis of varying severity are common in never smokers. Smokers are at high risk for lung cancer and at less risk for sarcoidosis with the equal incidence of chronic obstructive lung disease. The paper states that hospital physicians pay little attention to smoking among their patients.

Changing epidemiology of non-cystic fibrosis bronchiectasis.

PubMed

Bahçeci, Semiha; Karaman, Sait; Nacaroğlu, Hikmet Tekin; Yazıcı, Selçuk; Girit, Saniye; Ünsal-Karkıner, Şule; Can, Demet

2016-01-01

Non-cystic fibrosis bronchiectasis again becomes a major health problem due to inappropriate antibiotic use and increasing frequency of protracted bacterial bronchitis. The aim was to determine the changes in etiology of bronchiectasis. Patients who admitted to Behçet Uz Children Hospital between 2005 and 2015 (n=110) were retrospectively examined. The etiology of bronchiectasis was detected as; primary ciliary dyskinesia 26.4%, protracted bacterial bronchitis 22.8%, primary immune deficiency 11.8%, bronchiolitis obliterans 8.2%, lung disease secondary to gastro-esophageal reflux 3.7%, foreign body aspiration 2.7%, tuberculosis %2.7, congenital malformation 1.8% and asthma 1.8%, respectively. In 15.4% of cases, etiology was not identified clearly. 91% of the patients were medically treated. In ten years, the frequency of asthma and tuberculosis in etiology had decreased but primary ciliary dyskinesia and primary immune deficiency had increased. Non-cystic fibrosis bronchiectasis can be followed up for a long time with medical treatment.

Infection rate and tissue localization of murine IL-12p40-producing monocyte-derived CD103(+) lung dendritic cells during pulmonary tuberculosis.

PubMed

Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus

2013-01-01

Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naïve donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103(+) dendritic cells (αE-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that αE-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of αE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of αE-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that αE-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung αE-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that αE-DC contain the highest frequency of IL-12p40(+) cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive αE-DC phenotype.

Infection Rate and Tissue Localization of Murine IL-12p40-Producing Monocyte-Derived CD103+ Lung Dendritic Cells during Pulmonary Tuberculosis

PubMed Central

Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D.; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus

2013-01-01

Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naïve donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103+ dendritic cells (αE-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that αE-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of αE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of αE-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that αE-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung αE-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that αE-DC contain the highest frequency of IL-12p40+ cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive αE-DC phenotype. PMID:23861965

Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial.

PubMed

Abate, E; Elias, D; Getachew, A; Alemu, S; Diro, E; Britton, S; Aseffa, A; Stendahl, O; Schön, T

2015-02-01

Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6±2.9 for albendazole versus 5.9±2.5 for placebo, P=0.59). The albendazole-treated group showed a decline in eosinophil cells (P=0.001) and IL-10 (P=0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2±8.5 kg versus 8.2±8.7 kg, P=0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Preparation, validation and user-testing of pictogram-based patient information leaflets for tuberculosis.

PubMed

Shrestha, Anmol; Rajesh, V; Dessai, Sneha Shamrao; Stanly, Sharon Mary; Mateti, Uday Venkat

2018-05-25

Patient education is of paramount importance with regard to the condition of the disease and the treatment given besides lifestyle remodelling in order to get the desired therapeutic outcome. When verbal information is provided to the patients, they often tend to forget it. Pictorial aids or pictograms, as they are commonly known, are tools that are widely used for imparting knowledge to the patients. The aim of the study is to prepare and validate a Pictogram-based Patient Information Leaflet (P-PILs) on Tuberculosis (TB). P-PILs have been prepared from tertiary, secondary and primary sources. The knowledge-based questions are prepared with respect to the P-PILs. The baseline knowledge of the volunteers and patients have been analyzed before administering the P-PILs by using the validated questionnaire. The post-knowledge of the volunteers and patients has been analyzed after administering the P-PILs (20 min) by using the same questionnaire and the user-opinion has also been obtained at the end. The study results show that the mean scores of the overall user-testing knowledge assessment are found to have improved significantly from the pre-P-PILs administration score of 62.67 to the post-P-PILs administration score of 91. The overall user-opinion about the P-PILs has been found to be good (75%) followed by average (25%). The present study shows that there is significant improvement in the knowledge levels of the patients and volunteers after reading the validated leaflets. The Pictogram-based Patient Information Leaflets are found to be an effective educational tool for TB patients. Copyright © 2018. Published by Elsevier Ltd.

Investigation of bovine tuberculosis outbreaks by using a trace-back system and molecular typing in Korean Hanwoo beef cattle.

PubMed

Ku, Bok Kyung; Jeon, Bo-Young; Kim, Jae Myung; Jang, Young-Boo; Lee, Hyeyoung; Choi, Jae Young; Jung, Suk Chan; Nam, Hyang-Mi; Park, Hun; Cho, Sang-Nae

2018-01-31

Bovine tuberculosis is a chronic contagious disease responsible for major agricultural economic losses. Abattoir monitoring and trace-back systems are an appropriate method to control bovine tuberculosis, particularly in beef cattle. In the present study, a trace-back system was applied to bovine tuberculosis cases in Korean native Hanwoo beef cattle. Bovine tuberculosis was detected in three index beef cattle during abattoir monitoring in Jeonbuk Province, Korea, and the original herds were traced back from each index cow. All cattle in each original herd were subjected to tuberculin skin test. The positive rates in the tuberculin skin test were 64.6% (62 of 96), 4.8% (2 of 42), and 8.1% (3 of 37) at farms A, B, and C, respectively. On post-mortem examination of 56 tuberculin-positive cattle, 62% had granulomatous lesions, and Mycobacterium bovis was cultured from 40 (71.4%) of the cattle. Molecular typing by spoligotyping and the mycobacterial interspersed repetitive unit-variable-number tandem repeat assay revealed the genotype of the M. bovis strains from the index cattle were same as the M. bovis genotype in each original herd. The results suggest that tracing back from index cattle to the original herd is an effective method to control bovine tuberculosis in beef cattle.

Drug-resistant tuberculosis in subjects included in the Second National Survey on Antituberculosis Drug Resistance in Porto Alegre, Brazil*, **

PubMed Central

Micheletti, Vania Celina Dezoti; Moreira, José da Silva; Ribeiro, Marta Osório; Kritski, Afranio Lineu; Braga, José Ueleres

2014-01-01

OBJECTIVE: To describe the prevalence of multidrug-resistant tuberculosis (MDR-TB) among tuberculosis patients in a major Brazilian city, evaluated via the Second National Survey on Antituberculosis Drug Resistance, as well as the social, demographic, and clinical characteristics of those patients. METHODS: Clinical samples were collected from tuberculosis patients seen between 2006 to 2007 at three hospitals and five primary health care clinics participating in the survey in the city of Porto Alegre, Brazil. The samples were subjected to drug susceptibility testing. The species of mycobacteria was confirmed using biochemical methods. RESULTS: Of the 299 patients included, 221 (73.9%) were men and 77 (27.3%) had a history of tuberculosis. The mean age was 36 years. Of the 252 patients who underwent HIV testing, 66 (26.2%) tested positive. The prevalence of MDR-TB in the sample as a whole was 4.7% (95% CI: 2.3-7.1), whereas it was 2.2% (95% CI: 0.3-4.2) among the new cases of tuberculosis and 12.0% (95% CI: 4.5-19.5) among the patients with a history of tuberculosis treatment. The multivariate analysis showed that a history of tuberculosis and a longer time to diagnosis were both associated with MDR-TB. CONCLUSIONS: If our results are corroborated by other studies conducted in Brazil, a history of tuberculosis treatment and a longer time to diagnosis could be used as predictors of MDR-TB. PMID:24831400

Alternation of Gut Microbiota in Patients with Pulmonary Tuberculosis.

PubMed

Luo, Mei; Liu, Yong; Wu, Pengfei; Luo, Dong-Xia; Sun, Qun; Zheng, Han; Hu, Richard; Pandol, Stephen J; Li, Qing-Feng; Han, Yuan-Ping; Zeng, Yilan

2017-01-01

One-third of the world's population has been infected with Mycobacterium tuberculosis ( M. tuberculosis ), a primary pathogen of the mammalian respiratory system, while about 10% of latent infections progress to active tuberculosis (TB), indicating that host and environmental factors may determine the outcomes such as infection clearance/persistence and treatment prognosis. The gut microbiota is essential for development of host immunity, defense, nutrition and metabolic homeostasis. Thus, the pattern of gut microbiota may contribute to M. tuberculosis infection and prognosis. In current study we characterized the differences in gut bacterial communities in new tuberculosis patients (NTB), recurrent tuberculosis patients (RTB), and healthy control. The abundance-based coverage estimator (ACE) showed the diversity index of the gut microbiota in the patients with recurrent tuberculosis was increased significantly compared with healthy controls ( p < 0.05). At the phyla level, Actinobacteria and Proteobacteria, which contain many pathogenic species, were significantly enriched in the feces RTB patients. Conversely, phylum Bacteroidetes, containing a variety of beneficial commensal organisms, was reduced in the patients with the recurrent tuberculosis compared to healthy controls. The Gram-negative genus Prevotella of oral origin from phylum of Bacteroidetes and genus Lachnospira from phylum of Firmicutes were significantly decreased in both the new and recurrent TB patient groups, compared with the healthy control group ( p < 0.05). We also found that there was a positive correlation between the gut microbiota and peripheral CD4+ T cell counts in the patients. This study, for the first time, showed associations between gut microbiota with tuberculosis and its clinical outcomes. Maintaining eubiosis, namely homeostasis of gut microbiota, may be beneficial for host recovery and prevention of recurrence of M. tuberculosis infection.

Insights into the Origin, Emergence, and Current Spread of a Successful Russian Clone of Mycobacterium tuberculosis

PubMed Central

2013-01-01

SUMMARY Mycobacterium tuberculosis variant Beijing B0/W148 is regarded as a successful clone of M. tuberculosis that is widespread in the former Soviet Union and respective immigrant communities. Understanding the pathobiology and phylogeography of this notorious strain may help to clarify its origin and evolutionary history and the driving forces behind its emergence and current dissemination. I present the first review and analysis of all available data on the subject. In spite of the common perception of the omnipresence of B0/W148 across post-Soviet countries, its geographic distribution shows a peculiar clinal gradient. Its frequency peaks in Siberian Russia and, to a lesser extent, in the European part of the former Soviet Union. In contrast, the frequency of B0/W148 is sharply decreased in the Asian part of the former Soviet Union, and it is absent in autochthonous populations elsewhere in the world. Placing the molecular, clinical, and epidemiological features in a broad historical, demographic, and ecological context, I put forward two interdependent hypotheses. First, B0/W148 likely originated in Siberia, and its primary dispersal was driven by a massive population outflow from Siberia to European Russia in the 1960s to 1980s. Second, a historically recent, phylogenetically demonstrated successful dissemination of the Beijing B0/W148 strain was triggered by the advent and wide use of modern antituberculosis (anti-TB) drugs and was due to the remarkable capacity of this strain to acquire drug resistance. In contrast, there is some indication, but not yet systematic proof, of an enhanced virulence of this strain. PMID:23554420

Risk factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil

PubMed Central

Fregona, Geisa; Cosme, Lorrayne Belique; Moreira, Cláudia Maria Marques; Bussular, José Luis; Dettoni, Valdério do Valle; Dalcolmo, Margareth Pretti; Zandonade, Eliana; Maciel, Ethel Leonor Noia

2017-01-01

ABSTRACT OBJECTIVE To analyze the prevalence and factors associated with multidrug-resistant tuberculosis in Espírito Santo, Brazil. METHODS This is a cross-sectional study of cases of tuberculosis tested for first-line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin) in Espírito Santo between 2002 and 2012. We have used laboratory data and registration of cases of tuberculosis – from the Sistema Nacional de Agravos de Notificação and Sistema para Tratamentos Especiais de Tuberculose. Individuals have been classified as resistant and non-resistant and compared in relation to the sociodemographic, clinical, and epidemiological variables. Some variables have been included in a logistic regression model to establish the factors associated with resistance. RESULTS In the study period, 1,669 individuals underwent anti-tuberculosis drug susceptibility testing. Of these individuals, 10.6% showed resistance to any anti-tuberculosis drug. The rate of multidrug resistance observed, that is, to rifampicin and isoniazid, has been 5%. After multiple analysis, we have identified as independent factors associated with resistant tuberculosis: history of previous treatment of tuberculosis [recurrence (OR = 7.72; 95%CI 4.24–14.05) and re-entry after abandonment (OR = 3.91; 95%CI 1.81–8.43)], smoking (OR = 3.93; 95%CI 1.98–7.79), and positive culture for Mycobacterium tuberculosis at the time of notification of the case (OR = 3.22; 95%CI 1.15–8.99). CONCLUSIONS The partnership between tuberculosis control programs and health teams working in the network of Primary Health Care needs to be strengthened. This would allow the identification and monitoring of individuals with a history of previous treatment of tuberculosis and smoking. Moreover, the expansion of the offer of the culture of tuberculosis and anti-tuberculosis drug susceptibility testing would provide greater diagnostic capacity for the resistant types in Espírito Santo. PMID:28489185

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.

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.

Thymoquinone (TQ) inhibits the replication of intracellular Mycobacterium tuberculosis in macrophages and modulates nitric oxide production.

PubMed

Mahmud, Hafij Al; Seo, Hoonhee; Kim, Sukyung; Islam, Md Imtiazul; Nam, Kung-Woo; Cho, Hyun-Deuk; Song, Ho-Yeon

2017-05-25

Human tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. Thymoquinone (TQ), an essential compound of Nigella sativa, was previously reported as an active anti-tuberculosis agent. In this study, the effects of TQ on intracellular mycobacterial replication are examined in macrophages. In addition, its effect on mycobacteria-induced NO production and pro-inflammatory responses were investigated in Mycobacterium tuberculosis (MTB)-infected Type II human alveolar and human myeloid cell lines. TQ at concentrations ranging from 12.5 to 25 μg/mL and 6.25 to 12.5 μg/mL reduced intracellular M. tuberculosis H37Rv and extensively drug-resistant tuberculosis (XDR-TB) 72 h post-infection in RAW 264.7 cells. TQ treatment also produced a concentration-dependent reduction in nitric oxide production in both H37Rv and XDR-TB infected RAW 264.7 cells. Furthermore, TQ reduced the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory molecules such as tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6) in H37Rv-infected cells and eventually reduced pathogen-derived stress in host cells. TQ inhibits intracellular H37Rv and XDR-TB replication and MTB-induced production of NO and pro-inflammatory molecules. Therefore, along with its anti-inflammatory effects, TQ represents a prospective treatment option to combat Mycobacterium tuberculosis infection.

Primary drug resistance in a region with high burden of tuberculosis. A critical problem.

PubMed

Villa-Rosas, Cecilia; Laniado-Laborín, Rafael; Oceguera-Palao, Lorena

2015-01-01

To determine rates of drug resistance in new cases of pulmonary tuberculosis in a region with a high burden of the disease. New case suspects were referred for drug susceptibility testing. 28.9% of new cases were resistant to at least one first line drug; 3.9% had a multidrug-resistant strain, 15.6% a monoresistant strain and 9.4% a polyresistant strain. Our rate of drug resistant tuberculosis in new cases is very high; this has important clinical implications, since even monoresistance can have a negative impact on the outcome of new cases treated empirically with a six month regimen.

Angulated Stents-A Novel Stent Improvisation to Manage Difficult Post-tuberculosis Bronchial Stenosis.

PubMed

Tay, Chee Kiang; Jeong, Byeong-Ho; Kim, Hojoong

2017-10-18

Post-tuberculosis bronchostenosis (PTBS), a complication of endobronchial tuberculosis is currently treated by bronchial stenting. However, in cases of angulated bronchial stenoses, difficulty is often encountered in stent insertion and maintenance, resulting in stent migration, granulation tissue overgrowth, and restenosis. To accommodate the angulated alignment of the stenosis, we devised an "angulated stent"-a novel improvisation of the conventional stent via splicing and suturing to achieve a resultant angulated shape. A retrospective review was undertaken to evaluate the performance of this stent. Among 283 PTBS patients who underwent interventional bronchoscopy at our center from 2004 to 2014, 21 were treated with at least one angulated stent. Clinical outcomes, including the stenting duration were investigated. After a median follow-up of 26 months, stent removal was successful in 7 (33.3%) out of 21 patients. In patients managed with angulated stents, the median duration to stent change or eventual removal was longer than those treated with straight tube stents (392 days vs. 86 days; p < 0.05). Angulated stents are a feasible treatment option in patients with angulated PTBS by reducing complications and prolonging the stent-changing interval.

The hbhA Gene of Mycobacterium tuberculosis Is Specifically Upregulated in the Lungs but Not in the Spleens of Aerogenically Infected Mice

PubMed Central

Delogu, Giovanni; Sanguinetti, Maurizio; Posteraro, Brunella; Rocca, Stefano; Zanetti, Stefania; Fadda, Giovanni

2006-01-01

We report that hbhA is differentially regulated during Mycobacterium tuberculosis infection. Upregulation was observed in epithelial cell infection but not in macrophage infection and in the lungs but not in the spleens of infected mice, and it was greater during the early steps of infection, when bacilli disseminate from the site of primary infection. PMID:16622240

Delays in diagnosis and treatment of extrapulmonary tuberculosis in Guatemala.

PubMed

Shah, Pooja Ajay; Coj, Merida; Rohloff, Peter

2017-10-09

A 23-year-old indigenous Guatemalan man presented in 2016 to our clinic in Sololá, Guatemala, with 10 months of recurrent neck swelling, fevers, night sweats and weight loss. Previously, he had sought care in three different medical settings, including a private physician-run clinic, a tertiary private cancer treatment centre and, finally, a rural government health post. With assistance from our institution's accompaniment staff, the patient was admitted to a public tertiary care hospital for work-up. Rifampin-susceptible tuberculosis was diagnosed, and appropriate treatment was begun. The case illustrates how low tuberculosis recognition among community health workers and health system segmentation creates obstacles to appropriate care, especially for patients with limited means. As a result, significant diagnostic and treatment delays can occur, increasing the public health burden of tuberculosis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Safety assessment in primary Mycobacterium tuberculosis smear microscopy centres in Blantyre Malawi: a facility based cross sectional survey.

PubMed

Majamanda, J; Ndhlovu, P; Shawa, I T

2013-12-01

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is transmitted mainly through aerosolization of infected sputum which puts laboratory workers at risk in spite of the laboratory workers' risk of infection being at 3 to 9 times higher than the general public. Laboratory safety should therefore be prioritized and optimized to provide sufficient safety to laboratory workers. To assess the safety for the laboratory workers in TB primary microscopy centres in Blantyre urban. TB primary microscopy centers in Blantyre urban were assessed in aspects of equipment availability, facility layout, and work practice, using a standardized WHO/AFRO ISO 15189 checklist for the developing countries which sets the minimum safety score at ≥80%. Each center was graded according to the score it earned upon assessment. Only one (1) microscopy center out nine (9) reached the minimum safety requirement. Four (4) centers were awarded 1 star level, four (4) centers were awarded 2 star level and only one (1) center was awarded 3 star level. In Blantyre urban, 89% of the Tuberculosis microscopy centers are failing to provide the minimum safety to the laboratory workers. Government and other stake holders should be committed in addressing the safety challenges of TB microscopy centres in the country to ensure safety for the laboratory workers. It is recommended that the study be conducted at the regional or national level for both public and private laboratories in order to have a general picture of safety in Tb microscopy centres possibly across the country.

Epidemiologic and Demographic Attributes of Primary Spondylodiscitis in a Middle Eastern Population Sample.

PubMed

Menon, K Venugopal; Sorour, Tamer Malak Moawad

2016-11-01

The prevalence and characteristics of spontaneous spondylodiscitis in the Middle East are unknown. There seems to be an emerging dominance of pyogenic infections over tuberculosis and brucellosis. We conducted a retrospective observational study based on electronic case records of 4 years from a tertiary reference facility in Oman. Case records, microbiology reports, blood reports, imaging studies, and histopathology, and surgical reports of all spinal infection cases were studied. Patients with secondary infections after invasive spinal interventions and expatriate patients were excluded. Risk factors and comorbidities were also analyzed. Sixty-two cases of primary spondylodiscitis of the spine were identified in this cohort, including 10 cases of tuberculosis, 1 of brucellosis, and 1 of tuberculosis with pyogenic infection. Of the 50 pyogenic infections, 4 were in children; among the adults, the mean age was 49.5 years and 63.8% were male. Thirty-three patients had no medical comorbidities. Common ailments associated were 18 patients with diabetes mellitus, 13 hypertensives, 6 with renal insufficiency, 2 with liver cirrhosis, 3 with alcoholism, 5 with hepatitis C virus, and 2 with immunosuppression. More than 69% involvement was in the lumbar spine. Fourteen patients were infected with Staphylococcus aureus and 9 with Pseudomonas aeruginosa, whereas 35.4% were culture negative. Spontaneous infective spondylodiscitis affects older men with and without medical comorbidities equally. It often involves the lumbar spine and a third of patients are culture negative. Tuberculosis constitutes only about 17% of primary infections in the spine in this population sample. Copyright © 2016 Elsevier Inc. All rights reserved.

Reduced importation of tuberculosis after the implementation of an enhanced pre-immigration screening protocol.

PubMed

Lowenthal, P; Westenhouse, J; Moore, M; Posey, D L; Watt, J P; Flood, J

2011-06-01

Importation of infectious tuberculosis (TB) threatens TB control in California and the United States. To assess the effectiveness of an enhanced pre-immigration screening and treatment protocol to prevent the importation of infectious TB. Retrospective analysis of immigrants ≥ 15 years of age with TB suspect classifications who were screened for TB in their countries of origin before (pre-intervention cohort) and after (post-intervention cohort) implementation of enhanced pre-immigration screening. Enhanced pre-immigration screening added sputum cultures to the existing screening system based on sputum smears for persons with abnormal chest radiographs. The pre- and post-intervention cohorts included respectively 2049 and 1430 immigrants. The occurrence of tuberculosis ≤ 6 months after US arrival in this population decreased following the intervention, from 4.2% (86 cases) to 1.5% (22 cases, P < 0.001). Among pre-intervention cohort cases, 14% were sputum acid-fast bacilli (AFB) smear-positive and 81% were sputum culture-positive for TB, compared with 5% sputum AFB smear-positive (P = 0.46) and 68% sputum culture-positive (P = 0.18) among the post-intervention cohort cases. The enhanced pre-immigration screening was associated with a decline in the proportion of immigrants with TB suspect classifications identified with TB within 6 months of arrival in the United States. Continued state and national surveillance is critical to monitor the effectiveness of the revised pre-immigration screening as it is implemented in additional countries.

Tuberculous otitis media: clinical aspects of 12 cases.

PubMed

Nishiike, Suetaka; Irifune, Morihiro; Doi, Katsumi; Osaki, Yasuhiro; Kiuchi, Nobuo

2003-11-01

The clinical features of tuberculous otitis media (TOM) have changed. This study was performed to evaluate changing trends in the clinical manifestations of TOM. We reviewed a series of 12 cases of TOM (13 ears) recently treated at Osaka Prefectural Habikino Hospital. The results showed a mean age of 41 years and a male predominance of 1.4 to 1. Central or total perforations of the tympanic membrane were observed in most cases, but none of the patients had multiple perforations. Nine patients (75%) had active pulmonary tuberculosis. Normal lung status or inactive pulmonary tuberculosis was significantly more frequent in the older age group. Diagnosis of primary TOM required more time than that of secondary TOM. Most cases of primary TOM had high infectiousness of the primary lesion. We summarize the clinical features of patients who should be evaluated for TOM.

Preventive chemotherapy for HIV-associated tuberculosis in Uganda: an operational assessment at a voluntary counselling and testing centre.

PubMed

Aisu, T; Raviglione, M C; van Praag, E; Eriki, P; Narain, J P; Barugahare, L; Tembo, G; McFarland, D; Engwau, F A

1995-03-01

To assess the operational aspects of isoniazid preventive chemotherapy (IPT) for tuberculosis in persons dually infected with HIV and Mycobacterium tuberculosis identified at an independent HIV voluntary counselling and testing centre in Kampala, Uganda. HIV-infected persons were counselled, had active tuberculosis excluded by medical examination, and were offered purified protein derivative (PPD) skin testing. PPD-positive persons were offered isoniazid 300 mg daily for 6 months. Drugs were supplied, and toxicity and compliance were assessed monthly. Utilization of service, cost, and sustainability were also assessed. Between 14 June 1991 and 30 September 1992, 9862 persons tested HIV-positive. Of 5594 HIV-infected clients who returned to collect test results, only 1524 (27%) were enrolled. Of those, 1344 were tuberculin-tested (88%); 180 were not tested because of active tuberculosis, serious illnesses, refusal, and other reasons. Of the 1344, 250 (19%) did not return for test reading and 515 were negative (47% of tests read). Of 579 tuberculin-positive persons, 59 (10%) were excluded from preventive chemotherapy because of tuberculosis and other respiratory illnesses. Of 520 persons given isoniazid, 62% collected at least 80% of their drug supplies. No major toxicity was observed. One case of tuberculosis occurred in the first month of treatment. Cost of HIV counselling and testing was US $18.54 per person and cost of follow-up counselling and social support was US $7.89. Important factors were identified which caused attrition, such as limited motivation by counsellors to discuss tuberculosis issues during HIV pre- and post-test counselling, insufficient availability of medical screening, shifting of sites to collect pills, and frequent tuberculin-negative tests. Active tuberculosis among 6% of persons screened suggests that voluntary counselling and testing sites may be important for tuberculosis case finding and underscores the need to exclude tuberculosis carefully before starting IPT. In developing countries, further studies assessing the feasibility of IPT within tuberculosis and HIV/AIDS programme conditions are needed. Cost-effectiveness of IPT, compared with passive case finding, and its sustainability should be assessed before national policies are established.

Reassessment of the positive predictive value and specificity of Xpert MTB/RIF: a diagnostic accuracy study in the context of community-wide screening for tuberculosis.

PubMed

Ho, Jennifer; Nguyen, Phuong Thi Bich; Nguyen, Thu Anh; Tran, Khoa Hien; Van Nguyen, Son; Nguyen, Nhung Viet; Nguyen, Hoa Binh; Luu, Khanh Boi; Fox, Greg J; Marks, Guy B

2016-09-01

Community-wide screening for tuberculosis with Xpert MTB/RIF as a primary screening tool overcomes some of the limitations of conventional screening. However, concerns exist about the low positive predictive value of this test in screening settings. We did a cross-sectional assessment of this diagnostic test to directly estimate the actual positive predictive value of Xpert MTB/RIF when used in the setting of community-wide screening for tuberculosis, and to draw an inference about the specificity of the test for tuberculosis detection. Field staff visited households in 60 randomly selected villages in Ca Mau province, Vietnam. We included people aged 15 years or older who provided written informed consent and were able to produce 0·5 mL or more of sputum, irrespective of reported symptoms. Participants were tested with Xpert MTB/RIF, then those with positive results had two further sputum samples tested for smear microscopy and culture, and underwent chest radiography at the provincial TB Health Center. The positive predictive value of Xpert MTB/RIF was compared against two reference standards for tuberculosis diagnosis-a positive sputum culture for Mycobacterium tuberculosis, and a positive sputum culture or a chest radiograph consistent with active pulmonary tuberculosis. We then calculated the specificity of Xpert MTB/RIF for tuberculosis detection on the basis of these positive predictive values and disease prevalence in this setting. 43 435 adults consented to screening with Xpert MTB/RIF. Sputum samples of 0·5 mL or greater were collected from 23 202 participants, producing 22 673 valid results. 169 participants had positive Xpert MTB/RIF results (0·39% of those screened and 0·75% of those with valid sputum results). The positive predictive value of Xpert MTB/RIF was 61·0% (95% CI 52·8-68·7) when compared against a positive sputum culture and 83·9% (76·8-89·2) when compared against a positive sputum culture or chest radiograph consistent with active tuberculosis. On the basis of these positive predictive values, the specificity of Xpert MTB/RIF was determined to be between 99·78% (95% CI 99·71-99·84) and 99·93% (99·88-99·96). The positive predictive value and specificity of Xpert MTB/RIF in the context of community-wide screening for tuberculosis is substantially higher than that predicted in previous studies. Our findings support the potential role of Xpert MTB/RIF as a primary screening tool to detect prevalent cases of tuberculosis in the community. Australian National Health and Medical Research Council. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fatal Disseminated Tuberculosis during Treatment with Ruxolitinib Plus Prednisolone in a Patient with Primary Myelofibrosis: A Case Report and Review of the Literature.

PubMed

Tsukamoto, Yasuhiro; Kiyasu, Junichi; Tsuda, Mariko; Ikeda, Motohiko; Shiratsuchi, Motoaki; Ogawa, Yoshihiro; Yufu, Yuji

2018-05-01

A 73-year-old man with primary myelofibrosis (PMF) was being treated with hydroxyurea, which was changed to ruxolitinib treatment because of worsening constitutional symptoms. Although ruxolitinib rapidly induced relief, he developed a high-grade fever. A comprehensive fever work-up found no apparent cause of the fever, except for PMF. Therefore, we increased the dose of ruxolitinib and added prednisolone, which was gradually withdrawn with resolution of the fever. However, the patient subsequently developed disseminated tuberculosis and died eight months after initiation of ruxolitinib. Our case highlights the importance of assessing and monitoring the immune status of patients receiving ruxolitinib.

Laser heat puncturing as highly effective method of post-tuberculous cystalgia treatment

NASA Astrophysics Data System (ADS)

Koultchavenia, Ekaterina V.; Krasnov, Vladimir A.

1999-09-01

The tuberculosis of an urine bladder in men develops less often, and recovery is authentic more often, than in women. In 39.1% of the female patients with nephrotuberculosis, a specific cystitis is finished in postturberculous cystalgia. One of starting mechanisms of disuria after urocystis tuberculosis in the women in menopause is hormonal insufficiency. The method of laserheatpuncturing, developed by us, for the treatment this complication is highly effective, does not require additional introduction of medicines, can be executed as in hospitals, and in out-patient.

Childhood bone tuberculosis from Roman Pécs, Hungary.

PubMed

Hlavenková, L; Teasdale, M D; Gábor, O; Nagy, G; Beňuš, R; Marcsik, A; Pinhasi, R; Hajdu, T

2015-02-01

A child from a Roman necropolis in Pécs, Hungary (4th century CE) was initially diagnosed with severe spinal osteomyelitis. The post-cranial skeleton displayed bone alterations in the lower thoracic and upper lumbar segments, including vertebral body destruction, collapse and sharp kyphosis, and additional multiple rib lesions, suggesting a most likely diagnosis of pulmonary and spinal tuberculosis. This study discusses a number of selected diagnoses in the context of our pathological findings, complementing the macroscopic examination with radiological and biomolecular analyses. Copyright © 2014 Elsevier GmbH. All rights reserved.

Mycobacterium tuberculosis impairs dendritic cell functions through the serine hydrolase Hip1.

PubMed

Madan-Lala, Ranjna; Sia, Jonathan Kevin; King, Rebecca; Adekambi, Toidi; Monin, Leticia; Khader, Shabaana A; Pulendran, Bali; Rengarajan, Jyothi

2014-05-01

Mycobacterium tuberculosis is a highly successful human pathogen that primarily resides in host phagocytes, such as macrophages and dendritic cells (DCs), and interferes with their functions. Although multiple strategies used by M. tuberculosis to modulate macrophage responses have been discovered, interactions between M. tuberculosis and DCs are less well understood. DCs are the primary APCs of the immune system and play a central role in linking innate and adaptive immune responses to microbial pathogens. In this study, we show that M. tuberculosis impairs DC cytokine secretion, maturation, and Ag presentation through the cell envelope-associated serine hydrolase, Hip1. Compared to wild-type, a hip1 mutant strain of M. tuberculosis induced enhanced levels of the key Th1-inducing cytokine IL-12, as well as other proinflammatory cytokines (IL-23, IL-6, TNF-α, IL-1β, and IL-18) in DCs via MyD88- and TLR2/9-dependent pathways, indicating that Hip1 restricts optimal DC inflammatory responses. Infection with the hip1 mutant also induced higher levels of MHC class II and costimulatory molecules CD40 and CD86, indicating that M. tuberculosis impairs DC maturation through Hip1. Further, we show that M. tuberculosis promotes suboptimal Ag presentation, as DCs infected with the hip1 mutant showed increased capacity to present Ag to OT-II- and early secreted antigenic target 6-specific transgenic CD4 T cells and enhanced Th1 and Th17 polarization. Overall, these data show that M. tuberculosis impairs DC functions and modulates the nature of Ag-specific T cell responses, with important implications for vaccination strategies.

Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma.

PubMed

Jian, Zhi-Hong; Huang, Jing-Yang; Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

2016-01-01

To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22-5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73-2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84-6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57-2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63-1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05-2.32; p = 0.261) for pneumonia+ TB, respectively. Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB.

Bilateral adrenal masses: a single-centre experience

PubMed Central

Bandgar, Tushar; Khare, Shruti; Jadhav, Swati; Lila, Anurag; Goroshi, Manjunath; Kasaliwal, Rajeev; Khadilkar, Kranti; Shah, Nalini S

2016-01-01

Background Bilateral adrenal masses may have aetiologies like hyperplasia and infiltrative lesions, besides tumours. Hyperplastic and infiltrative lesions may have coexisting hypocortisolism. Bilateral tumours are likely to have hereditary/syndromic associations. The data on clinical profile of bilateral adrenal masses are limited. Aims To analyse clinical, biochemical and radiological features, and management outcomes in patients with bilateral adrenal masses. Methods Retrospective analysis of 70 patients with bilateral adrenal masses presenting to a single tertiary care endocrine centre from western India (2002–2015). Results The most common aetiology was pheochromocytoma (40%), followed by tuberculosis (27.1%), primary adrenal lymphoma (PAL) (10%), metastases (5.7%), non-functioning adenomas (4.3%), primary bilateral macronodular adrenal hyperplasia (4.3%), and others (8.6%). Age at presentation was less in patients with pheochromocytoma (33 years) and tuberculosis (41 years) compared with PAL (48 years) and metastases (61 years) (P<0.001). The presenting symptoms for pheochromocytoma were hyperadrenergic spells (54%) and abdominal pain (29%), whereas tuberculosis presented with adrenal insufficiency (AI) (95%). The presenting symptoms for PAL were AI (57%) and abdominal pain (43%), whereas all cases of metastasis had abdominal pain. Mean size of adrenal masses was the largest in lymphoma (5.5cm) followed by pheochromocytoma (4.8cm), metastasis (4cm) and tuberculosis (2.1cm) (P<0.001). Biochemically, most patients with pheochromocytoma (92.8%) had catecholamine excess. Hypocortisolism was common in tuberculosis (100%) and PAL (71.4%) and absent with metastases (P<0.001). Conclusion In evaluation of bilateral adrenal masses, age at presentation, presenting symptoms, lesion size, and biochemical features are helpful in delineating varied underlying aetiologies. PMID:27037294

A Multistage Subunit Vaccine Effectively Protects Mice Against Primary Progressive Tuberculosis, Latency and Reactivation.

PubMed

Ma, Jilei; Teng, Xindong; Wang, Xiaochun; Fan, Xionglin; Wu, Yaqi; Tian, Maopeng; Zhou, Zijie; Li, Longmeng

2017-08-01

Adult tuberculosis (TB) is the main cause of TB epidemic and death. The infection results mainly by endogenous reactivation of latent TB infection and secondarily transmitted by exogenous infection. There is no vaccine for adult TB. To this end, we first chose antigens from a potential antigenic reservoir. The antigens strongly recognized T cells from latent and active TB infections that responded to antigens expressed by Mycobacterium tuberculosis cultured under different metabolic states. Fusions of single-stage polyprotein CTT3H, two-stage polyprotein A1D4, and multistage CMFO were constructed. C57BL/6 mice vaccinated with DMT adjuvant ed CMFO (CMFO-DMT) were protected more significantly than by CTT3H-DMT, and efficacy was similar to that of the only licensed vaccine, Bacillus Calmette-Guérin (BCG) and A1D4-DMT in the M. tuberculosis primary infection model. In the setting of BCG priming and latent TB infection, M. tuberculosis in the lung and spleen was eliminated more effectively in mice boosted with CMFO-DMT rather than with BCG, A1D4-DMT, or CTT3H-DMT. In particular, sterile immunity was only conferred by CMFO-DMT, which was associated with expedited homing of interferon-gamma + CD4 + T EM and interleukin-2 + T CM cells from the spleen to the infected lung. CMFO-DMT represents a promising candidate to prevent the occurrence of adult TB through both prophylactic and therapeutic methods, and warrants assessment in preclinical and clinical trials. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

An attenuated quadruple gene mutant of Mycobacterium tuberculosis imparts protection against tuberculosis in guinea pigs

PubMed Central

Chauhan, Priyanka

2018-01-01

ABSTRACT Previously we had developed a triple gene mutant of Mycobacterium tuberculosis (MtbΔmms) harboring disruption in three genes, namely mptpA, mptpB and sapM. Though vaccination with MtbΔmms strain induced protection in the lungs of guinea pigs, the mutant strain failed to control the hematogenous spread of the challenge strain to the spleen. Additionally, inoculation with MtbΔmms resulted in some pathological damage to the spleens in the early phase of infection. In order to generate a strain that overcomes the pathology caused by MtbΔmms in spleen of guinea pigs and controls dissemination of the challenge strain, MtbΔmms was genetically modified by disrupting bioA gene to generate MtbΔmmsb strain. Further, in vivo attenuation of MtbΔmmsb was evaluated and its protective efficacy was assessed against virulent M. tuberculosis challenge in guinea pigs. MtbΔmmsb mutant strain was highly attenuated for growth and virulence in guinea pigs. Vaccination with MtbΔmmsb mutant generated significant protection in comparison to sham-immunized animals at 4 and 12 weeks post-infection in lungs and spleen of infected animals. However, the protection imparted by MtbΔmmsb was significantly less in comparison to BCG immunized animals. This study indicates the importance of attenuated multiple gene deletion mutants of M. tuberculosis for generating protection against tuberculosis. PMID:29242198

Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD.

PubMed

Guiedem, Elise; Ikomey, George Mondinde; Nkenfou, Céline; Walter, Pefura-Yone Eric; Mesembe, Martha; Chegou, Novel Njweipi; Jacobs, Graeme Brendon; Okomo Assoumou, Marie Claire

2018-03-27

The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy. We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 10 6 /ml and 2.48 × 10 6 /ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.

Executive Summary of the Guidelines for the Use of interferon-gamma Release Assays in the Diagnosis of Tuberculosis Infection.

PubMed

Santin, Miguel; García-García, José-María; Rigau, David; Altet, Neus; Anibarro, Luis; Casas, Irma; Díez, Nuria; García-Gasalla, Mercedes; Martínez-Lacasa, Xavier; Penas, Antón; Pérez-Escolano, Elvira; Sánchez, Francisca; Domínguez, José

2016-09-01

Interferon-gamma release assays are widely used for the diagnosis of tuberculosis infection in Spain. However, there is no consensus on their application in specific clinical scenarios. To develop a guide-line for their use, a panel of experts comprising specialists in infectious diseases, respiratory diseases, microbiology, pediatrics and preventive medicine, together with a methodologist, conducted a systematic literature search, summarized the findings, rated the quality of the evidence, and formulated recommendations following the Grading of Recommendations of Assessment Development and Evaluations methodology. This document provides evidence-based guidance on the use of interferon-gamma release assays for the diagnosis of tuberculosis infection in patients at risk of tuberculosis or suspected of having active disease. The guidelines will be applicable to specialist and primary care, and public health. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Isolated splenic tuberculosis diagnosed by endoscopic ultrasound-guided fine needle aspiration.

PubMed

Nasa, Mukesh; Choudhary, Narendra S; Guleria, Mridula; Puri, Rajesh

2017-04-01

Our patient was a 48-year-old female, who presented with history of persistent low-grade fever and weight loss. The CT scan of the abdomen revealed multiple hypodense lesions in spleen. No primary focus of infection was detected in any other organs. Endoscopic ultrasound-guided fine needle aspiration of splenic lesion revealed granulomatous inflammation. The patient was started on anti-tuberculous therapy. There is a diagnostic possibility of splenic tuberculosis even in immunocompetent individuals and we chose a combination anti-tuberculous therapy as the first line treatment with consideration of splenectomy depending on the response. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Resistant and sensitive strains of Mycobacterium tuberculosis found in repeated surveys among a South Indian rural population*

PubMed Central

Narain, Raj; Chandrasekhar, P.; Satyanarayanachar, R. A.; Lal, Pyare

1968-01-01

The findings in a highly selected group of patients, such as those attending clinics or sanatoria, cannot be used as the basis for assessing the true prevalence of strains of Mycobacterium tuberculosis with acquired or primary resistance or of sensitive strains in a community. The present report describes the prevalence of such strains as found in 3 successive surveys in a sizeable random sample of villages in a South Indian district. Changes in the status of cases with such strains from an earlier survey to a later one and the status at an earlier round of cases found at a later one are also described. The prevalence of tuberculous infection among household contacts of cases with acquired resistance to isoniazid was significantly higher than that among contacts of cases with primary resistance or of those with sensitive cultures. This is probably due to the longer duration of sputum positivity of the former at the time of diagnosis. But infectivity, as judged by the incidence of new infections among household contacts, was generally less for cases with acquired or primary resistance than for cases with sensitive cultures, though the difference was not statistically significant. A large number of culture-positive cases, especially those with primary resistance, had no radiological evidence of active pulmonary tuberculosis. The prevalence of primary resistance was very high among certain categories of cases, and the differences between cases with primary resistance and those with acquired resistance were many and large. It is suggested that this could be due to some of the primary resistant cultures being those of atypical mycobacteria, despite positivity in the niacin test. There was a significant increase in the number of cases with acquired resistance to isoniazid at the third survey round owing to irregular treatment with that drug after the second round. The prevalence of primary resistance at the 3 rounds was almost the same. PMID:4978410

A cross-sectional study to assess the stigma associated with tuberculosis among tuberculosis patients in Udupi district, Karnataka.

PubMed

Shivapujimath, R; Rao, A P; Nilima, A R; Shilpa, D M

2017-10-01

For decades, tuberculosis and other communicable diseases like human immunodeficiency virus/acquired immune deficiency syndrome, leprosy, etc., have been associated with stigma and discrimination by the society; this can interfere with the lifestyle and disease management among these patients. To assess the stigma experienced by tuberculosis patients and to find the factors associated with stigma. A cross-sectional study was conducted among 209 sputum-positive and sputum-negative tuberculosis patients. Convenient sampling was used to identify the patients. A predesigned, pretested proforma from Explanatory Model Interview Catalogue developed by World Health Organization was used for data collection. The study revealed that out of 209 respondents, 51.2% of the respondents experienced some form of stigma. Majority of the patients have received only primary education and 71.3% of the respondents were males. Most of the patients were under category 1 of Directly Observed Treatment Short course. Age, education, and smear status of the patient were found to be associated with stigmatization (P<0.05), whereas factors like gender, income, occupation, family history, and marital status were found to be not significantly associated with stigmatization. Effective counseling measures are recommended for tuberculosis patients with advancing age and education which can help reduce stigmatization and thereby improve quality of life. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Assessment of post-vaccination tuberculin sensitivity in Lagos-Nigeria.

PubMed

Odujinrin, O M; Ogunmekan, D A

1992-01-01

An increase in the number of cases of tuberculosis, especially in children, has been observed recently. Post-vaccination conversion rate in babies immunised with BCG was assessed. Sensitization was detected as early as 4 weeks after BCG inoculation. Although 84.2% had physical evidence of BCG inoculation only 69.8% had developed detectable sensitization to the tubercle bacilli as shown by the Mantoux test.

Therapeutic vaccination against relevant high virulence clinical isolates of Mycobacterium tuberculosis.

PubMed

Shanley, Crystal A; Ireton, Gregory C; Baldwin, Susan L; Coler, Rhea N; Reed, Steven G; Basaraba, Randall J; Orme, Ian M

2014-03-01

The purpose of this study was to attempt to develop therapeutic or post-exposure vaccines that could slow progressive disease in guinea pigs infected by low dose aerosol with very high virulence Beijing isolates of Mycobacterium tuberculosis, currently classified as Category C biodefense pathogens by the NIH and CDC. After screening several candidates we focused on the use of three candidates; these were a pool of bacterial iron acquisition proteins, a pool of antigens recognized by T cells from chronically infected mice thought to represent proteins made by the bacillus in response to decreases in local oxygen tension, and a bacterial lipoprotein that is a potent TLR2 agonist. When delivered in a potent GLA-based adjuvant [targeting TLR4 and TLR9], in most cases we were unable to reduce the bacterial load in the lungs. However, the pathologic appearance of lungs from these animals showed that, while primary lesions were most unaffected and had become necrotic, the development of large, lung consolidating secondary lesions seemed to have been mostly prevented. In animals given both a priming vaccination and a boost the effects were prominent, and almost certainly contributed to significantly prolonged survival in these animals. In a biodefense situation, this prolonged survival would be potentially long enough to allow for the organism to be identified and a drug susceptibility profile determined. Copyright © 2013 Elsevier Ltd. All rights reserved.

N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions.

PubMed

Amaral, Eduardo P; Conceição, Elisabete L; Costa, Diego L; Rocha, Michael S; Marinho, Jamocyr M; Cordeiro-Santos, Marcelo; D'Império-Lima, Maria Regina; Barbosa, Theolis; Sher, Alan; Andrade, Bruno B

2016-10-28

Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria. Oxidative stress status in plasma was compared between pulmonary TB (PTB) patients and those with latent M. tuberculosis infection (LTBI) or healthy uninfected individuals. Lipid peroxidation, DNA oxidation and cell death, as well as accumulation of reactive oxygen species (ROS) were measured in cultures of primary human monocyte-derived macrophages infected with M. tuberculosis and treated or not with NAC. M. tuberculosis, M. avium and M. bovis BCG cultures were also exposed to different doses of NAC with or without medium pH adjustment to control for acidity. The anti-mycobacterial effect of NAC was assessed in M. tuberculosis infected human THP-1 cells and bone marrow-derived macrophages from mice lacking a fully functional NADPH oxidase system. The capacity of NAC to control M. tuberculosis infection was further tested in vivo in a mouse (C57BL/6) model. PTB patients exhibited elevated levels of oxidation products and a reduction of anti-oxidants compared with LTBI cases or uninfected controls. NAC treatment in M. tuberculosis-infected human macrophages resulted in a decrease of oxidative stress and cell death evoked by mycobacteria. Importantly, we observed a dose-dependent reduction in metabolic activity and in vitro growth of NAC treated M. tuberculosis, M. avium and M. bovis BCG. Furthermore, anti-mycobacterial activity in infected macrophages was shown to be independent of the effects of NAC on the host NADPH oxidase system in vitro. Short-term NAC treatment of M. tuberculosis infected mice in vivo resulted in a significant reduction of mycobacterial loads in the lungs. NAC exhibits potent anti-mycobacterial effects and may limit M. tuberculosis infection and disease both through suppression of the host oxidative response and through direct antimicrobial activity.

Rapid diagnosis of pulmonary tuberculosis in African children in a primary care setting by use of Xpert MTB/RIF on respiratory specimens: a prospective study.

PubMed

Zar, Heather J; Workman, Lesley; Isaacs, Washiefa; Dheda, Keertan; Zemanay, Widaad; Nicol, Mark P

2013-08-01

In children admitted to hospital, rapid, accurate diagnosis of pulmonary tuberculosis with the Xpert MTB/RIF assay is possible, but no paediatric studies have been done in the primary care setting, where most children are given care, and where microbiological diagnosis is rarely available. We assessed the diagnostic accuracy of Xpert MTB/RIF in children in primary care. For this prospective study, we obtained repeat induced sputum and nasopharyngeal aspirate specimens from children (<15 years) with suspected pulmonary tuberculosis at a clinic in Khayeliwtsha, Cape Town, South Africa. We compared the diagnostic accuracy of Xpert MTB/RIF with a reference standard of culture and smear microscopy on induced sputum specimens. For the main analysis, specificity of Xpert MTB/RIF versus liquid culture, we included only children with two interpretable Xpert MTB/RIF and induced sputum culture results. Between Aug 1, 2010, and July 30, 2012, we enrolled 384 children (median age 38·3 months, IQR 21·2-56·5) who had one paired induced sputum and nasopharyngeal specimen, 309 (81%) of whom had two paired specimens. Five children (1%) tested positive for tuberculosis by smear microscopy, 26 (7%) tested positive by Xpert MTB/RIF, and 30 (8%) tested positive by culture. Xpert MTB/RIF on two induced sputum specimens detected 16 of 28 culture-confirmed cases (sensitivity of 57·1%, 95% CI 39·1-73·5) and on two nasopharyngeal aspirates detected 11 of 28 culture-confirmed cases (sensitivity of 39·3, 23·6-57·6; p=0·18). The specificity of Xpert MTB/RIF on induced sputum was 98·9% (95% CI 96·9-99·6) and on nasopharyngeal aspirates was 99·3% (97·4-99·8). Our findings suggest that Xpert MTB/RIF on respiratory secretions is a useful test for rapid diagnosis of paediatric pulmonary tuberculosis in primary care. National Institutes of Health, National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, the National Research Foundation South Africa, the European and Developing Countries Clinical Trials Partnership. Copyright © 2013 Zar et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.

Comparative 'omics analyses differentiate Mycobacterium tuberculosis and Mycobacterium bovis and reveal distinct macrophage responses to infection with the human and bovine tubercle bacilli

PubMed Central

Malone, Kerri M.; Rue-Albrecht, Kévin; Magee, David A.; Conlon, Kevin; Schubert, Olga T.; Nalpas, Nicolas C.; Browne, John A.; Smyth, Alicia; Gormley, Eamonn; Aebersold, Ruedi; MacHugh, David E.; Gordon, Stephen V.

2018-01-01

Members of the Mycobacterium tuberculosis complex (MTBC) are the causative agents of tuberculosis in a range of mammals, including humans. A key feature of MTBC pathogens is their high degree of genetic identity yet distinct host tropism. Notably, while Mycobacterium bovis is highly virulent and pathogenic for cattle, the human pathogen M. tuberculosis is attenuated in cattle. Previous research also suggests that host preference amongst MTBC members has a basis in host innate immune responses. To explore MTBC host tropism, we present in-depth profiling of the MTBC reference strains M. bovis AF2122/97 and M. tuberculosis H37Rv at both the global transcriptional and the translational level via RNA-sequencing and SWATH MS. Furthermore, a bovine alveolar macrophage infection time course model was used to investigate the shared and divergent host transcriptomic response to infection with M. tuberculosis H37Rv or M. bovis AF2122/97. Significant differential expression of virulence-associated pathways between the two bacilli was revealed, including the ESX-1 secretion system. A divergent transcriptional response was observed between M. tuberculosis H37Rv and M. bovis AF2122/97 infection of bovine alveolar macrophages, in particular cytosolic DNA-sensing pathways at 48 h post-infection, and highlights a distinct engagement of M. bovis with the bovine innate immune system. The work presented here therefore provides a basis for the identification of host innate immune mechanisms subverted by virulent host-adapted mycobacteria to promote their survival during the early stages of infection. PMID:29557774

Global health diplomacy in Iraq: international relations outcomes of multilateral tuberculosis programmes.

PubMed

Kevany, Sebastian; Jaf, Payman; Workneh, Nibretie Gobezie; Abu Dalod, Mohammad; Tabena, Mohammed; Rashid, Sara; Al Hilfi, Thamer Kadum Yousif

2014-01-01

International development programmes, including global health interventions, have the capacity to make important implicit and explicit benefits to diplomatic and international relations outcomes. Conversely, in the absence of awareness of these implications, such programmes may generate associated threats. Due to heightened international tensions in conflict and post-conflict settings, greater attention to diplomatic outcomes may therefore be necessary. We examine related 'collateral' effects of Global Fund-supported tuberculosis programmes in Iraq. During site visits to Iraq conducted during 2012 and 2013 on behalf of the Global Fund to Fight AIDS, Tuberculosis and Malaria, on-site service delivery evaluations, unstructured interviews with clinical and operational staff, and programme documentary review of Global Fund-supported tuberculosis treatment and care programmes were conducted. During this process, a range of possible external or collateral international relations and diplomatic effects of global health programmes were assessed according to predetermined criteria. A range of positive diplomatic and international relations effects of Global Fund-supported programmes were observed in the Iraq setting. These included (1) geo-strategic accessibility and coverage; (2) provisions for programme sustainability and alignment; (3) contributions to nation-building and peace-keeping initiatives; (4) consistent observation of social, cultural and religious norms in intervention selection; and (5) selection of the most effective and cost-effective tuberculosis treatment and care interventions. Investments in global health programmes have valuable diplomatic, as well as health-related, outcomes, associated with their potential to prevent, mitigate or reverse international tension and hostility in conflict and post-conflict settings, provided that they adhere to appropriate criteria. The associated international presence in such regions may also contribute to peace-keeping efforts. Global health programmes may frequently produce a wider range of 'collateral benefits' that conventional monitoring and evaluation systems should be expanded to assess, in keeping with contemporary efforts to leverage development programmes from a 'global health diplomacy' perspective.

[Drug resistance profile of Mycobacterium tuberculosis in the state of Mato Grosso do Sul, Brazil, 2000-2006].

PubMed

Marques, Marli; Cunha, Eunice Atsuko Totumi; Ruffino-Netto, Antonio; Andrade, Sonia Maria de Oliveira

2010-01-01

To determine the drug resistance profile of Mycobacterium tuberculosis in the state of Mato Grosso do Sul, Brazil, between 2000 and 2006. Descriptive study of reported tuberculosis cases in the Brazilian Case Registry Database. We included only those cases in which M. tuberculosis culture was positive and sensitivity to drugs (rifampicin, isoniazid, streptomycin and ethambutol) was tested. Löwenstein-Jensen and Ogawa-Kudoh solid media were used for cultures, as was an automated liquid medium system. Sensitivity tests were based on the proportion method. Among the 783 cases evaluated, males predominated (69.7%), as did patients in the 20-49 year age bracket (70%), a diagnosis of pulmonary tuberculosis (94.4%) and positive HIV serology (8.6%); 645 (82.4%) were new cases, and 138 (17.6%) had previously been treated. Resistance to at least one drug was found in 143 cases (18.3%). The primary resistance (PR) rate was, respectively, 8.1%, 1.6%, 2.8% and 12.4%, for monoresistance, multidrug resistance (MDR), other patterns of resistance and resistance to at least one drug, whereas the acquired resistance (AR) rate was 14.5%, 20.3%, 10.9% and 45.7%, respectively, and the combined resistance (CR) rate was 9.2%, 4.9%, 4.2% and 18.3%, respectively. In PR, streptomycin was the most common drug, whereas isoniazid was the most common in AR and CR (7.2% and 3.7%, respectively). These high levels of resistance undermine the efforts for tuberculosis control in Mato Grosso do Sul. Acquired MDR was 12.7 times more common than was primary MDR, demonstrating that the previous use of drug therapy is an indicator of resistance. These levels reflect the poor quality of the health care provided to these patients, showing the importance of using the directly observed treatment, short course strategy, as well as the need to perform cultures and sensitivity tests for the early diagnosis of drug resistance.

Transmission of Mycobacterium tuberculosis between Farmers and Cattle in Central Ethiopia

PubMed Central

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

2013-01-01

Background Transmission of Mycobacterium tuberculosis (M. tuberculosis) complex could be possible between farmers and their cattle in Ethiopia. Methodology/Principal Findings A study was conducted in mixed type multi-purposes cattle raising region of Ethiopia on 287 households (146 households with case of pulmonary tuberculosis (TB) and 141 free of TB) and 287 herds consisting of 2,033 cattle belonging to these households to evaluate transmission of TB between cattle and farmers. Interview, bacteriological examinations and molecular typing were used for human subjects while comparative intradermal tuberculin (CIDT) test, post mortem and bacteriological examinations, and molecular typing were used for animal studies. Herd prevalence of CIDT reactors was 9.4% and was higher (p<0.01) in herds owned by households with TB than in herds owned by TB free households. Animal prevalence was 1.8% and also higher (p<0.01) in cattle owned by households with TB case than in those owned by TB free households. All mycobacteria (141) isolated from farmers were M. tuberculosis, while only five of the 16 isolates from cattle were members of the M. tuberculosis complex (MTC) while the remaining 11 were members of non-tuberculosis mycobacteria (NTM). Further speciation of the five MTC isolates showed that three of the isolates were M. bovis (strain SB1176), while the remaining two were M. tuberculosis strains (SIT149 and SIT53). Pathology scoring method described by “Vordermeier et al. (2002)” was applied and the average severity of pathology in two cattle infected with M. bovis, in 11 infected with NTM and two infected with M. tuberculosis were 5.5, 2.1 and 0.5, respectively. Conclusions/Significance The results showed that transmission of TB from farmers to cattle by the airborne route sensitizes the cows but rarely leads to TB. Similarly, low transmission of M. bovis between farmers and their cattle was found, suggesting requirement of ingestion of contaminated milk from cows with tuberculous mastitis. PMID:24130804

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.

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

[Treatment duration of extra-pulmonary tuberculosis: 6 months or more? TB-INFO database analysis].

PubMed

Bouchikh, S; Stirnemann, J; Prendki, V; Porcher, R; Kesthmand, H; Morin, A-S; Cruaud, P; Rouaghe, S; Farge, D; Fain, O

2012-12-01

The recommended duration of pulmonary tuberculosis therapy is 6 months. For extrapulmonary tuberculosis, treatment duration depends on tuberculosis involvement and HIV status. The objective of this study was to describe the main characteristics of a cohort of extrapulmonary tuberculosis patients, to compare patients with a 6-month treatment to those with more than a 6-month treatment, and to analyze the compliance of medical centres with recommended duration of treatment. A retrospective cohort study of 210 patients with extrapulmonary tuberculosis was carried from January 1999 to December 2006 in two hospitals in the north-east of Paris. These patients were treated with quadruple therapy during two months, followed by dual therapy during 4 months (n=77) or more (n=66). The characteristics of each group were compared by uni- and multivariate analysis. The primary endpoint was the rate of relapse or treatment failure at 24-month follow-up after treatment completion. No relapse was observed after 24 months of follow-up after the end of treatment in the two groups. In univariate analysis, patients with lymph node tuberculosis were more often treated for 6 months than at other sites of tuberculosis (respectively 61% versus 40.9%; P=0.02); the decision of treatment duration was related to medical practices (79.2% treated 6 months in one hospital versus 20.7% in the other, P<0.001); patients living in private residence were more often treated during 6 months than patients living in residence (24.2% versus 10.3%, P=0.042). In multivariate analysis, only hospital (P=0.046), sex (P=0.007) and private residence were significantly different in each group. A period of 6 months seems to be sufficient to treat extrapulmonary tuberculosis (except for neuromeningeal localization). Copyright © 2012. Published by Elsevier SAS.

Tuberculosis screening prior to anti-tumor necrosis factor therapy among patients with immune-mediated inflammatory diseases in Japan: a longitudinal study using a large-scale health insurance claims database.

PubMed

Tomio, Jun; Yamana, Hayato; Matsui, Hiroki; Yamashita, Hiroyuki; Yoshiyama, Takashi; Yasunaga, Hideo

2017-11-01

Tuberculosis screening is recommended for patients with immune-mediated inflammatory diseases (IMIDs) prior to anti-tumor necrosis factor (TNF) therapy. However, adherence to the recommended practice is unknown in the current clinical setting in Japan. We used a large-scale health insurance claims database in Japan to conduct a longitudinal observational study. Of more than two million beneficiaries in the database between 2013 and 2014, we enrolled those with IMIDs aged 15-69 years who had initiated anti-TNF therapy. We defined tuberculosis screening primarily as tuberculin skin test and/or interferon-gamma release assay (TST/IGRA) within 2 months before commencing anti-TNF therapy. We analyzed the proportions of the patients who had undergone tuberculosis screening and the associations with primary disease, type of anti-TNF agent, methotrexate prescription prior to anti-TNF therapy, and treatment for latent tuberculosis infection (LTBI). Of 385 patients presumed to have initiated anti-TNF therapy, 252 (66%) had undergone tuberculosis screening by TST/IGRA (22% TST, 56% IGRA, and 12% both TST and IGRA), and 231 (60%) had undergone TST/IGRA and radiography. Patients with psoriasis tended to be more likely to undergo tuberculosis screening than those with other diseases; however, this association was not statistically significant. Treatment for LTBI was provided to 43 (11%) patients; 123 (32%) received neither TST/IGRA nor LTBI treatment. Tuberculosis screening was often not performed prior to anti-TNF therapy despite the guidelines' recommendations; thus, patients could be put at unnecessary risk of reactivation of tuberculosis. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Primary Pancreatic Head Tuberculosis: Great Masquerader of Pancreatic Adenocarcinoma

PubMed Central

Gupta, Dhaval; Patel, Jatin; Rathi, Chetan; Ingle, Meghraj; Sawant, Prabha

2015-01-01

Isolated pancreatic tuberculosis (TB) is considered an extremely rare condition, even in the developing countries. Most reported cases of pancreatic TB are diagnosed after exploratory laparotomy or autopsy. Pancreatic TB is a potential mimic of invasive pancreatic malignancy and the presence of vascular invasion does not distinguish one condition from the other. Every effort should be made for the earliest diagnosis of this condition as TB is a treatable condition and it avoids unnecessary management of pancreatic carcinoma. Here we report a rare case of primary pancreatic head TB in a 58-year-old male who presented with hypodense lesion in head of pancreas with double duct sign and portal vein invasion mimicking non-resectable pancreatic carcinoma. PMID:27785295

Addison's disease presenting with muscle spasm.

PubMed

Bhattacharjee, Rana; Sharma, A; Rays, A; Thakur, I; Sarkar, D; Mandal, B; Mookerjee, S K; Chatterjee, S K; Chowdhury, Pradip Roy

2013-09-01

Primary hypoadrenalism has various causes and protean manifestation. We report a young female patient who presented with severe muscle spasm as her primary complaint. On evaluation she was found to be a case of Addison's disease secondary to adrenal tuberculosis. Her muscle spasm disappeared rapidly with replacement dose of glucocorticoid.

Prevalence and Associated Factors of Alcoholism among Tuberculosis Patients in Udupi Taluk, Karnataka, India: A Cross Sectional Study.

PubMed

Thapa, P; Kamath, R; Shetty, B K; Monteiro, A; Sekaran, V C

2014-01-01

Tuberculosis (TB) is a major public health problem in India. Several studies carried out in India have shown alcoholism as a risk factor for tuberculosis mortality, factor for default in TB and reason for non-compliance under the Revised National Tuberculosis Control Program (RNTCP). The aim of this study was to assess the prevalence, pattern and associated factors of alcohol use among tuberculosis patients in Udupi taluk, Karnataka, India. A cross-sectional study was conducted with the complete enumeration of all the cases undergoing Directly Observed Treatment Short-course (DOTS) treatment in Primary Health Centre and Community Health Centre of Udupi taluk from March to April 2013. Interview was conducted to obtain the socio-demographic and health information and participants were screened using WHO developed Alcohol Use Disorders Identification Test (AUDIT) for alcohol use. Out of 123 participants, 78% were males, 86.2% were Hindu, 79.7% were married and 88.6% were from low socio-economic status. About 20.3% (n=25) participants were alcoholic. Among them, 44% were low risk drinkers, 32% were hazardous drinkers, 4% were harmful drinkers and 20% were alcohol dependent. Age, sex, occupation, tobacco use, perceived health status and discrimination due to tuberculosis positive status were significantly associated with alcohol use. On logistic regression sex, tobacco use, perceived health status and facing discrimination due infection with tuberculosis were found to be factors associated with alcohol use. This study found a high prevalence of alcoholism among tuberculosis patients which is of concern and has to be addressed.

Aspergillus epidural abscess in a patient with obstructive airway disease.

PubMed Central

Chee, Y. C.; Poh, S. C.

1983-01-01

A 54-year-old Chinese man with episodic bronchial asthma since 25 years of age was treated for pulmonary tuberculosis in 1976 because of left upper lobe lesions on chest radiograph. In 1981 he presented with an extradural mass compressing the thoracic spinal cord, thought to be tuberculosis but which on biopsy was found to be aspergillosis. Sputum culture, type on skin-prick reactivity and serum precipitating antibodies were positive for Aspergillus. Amphotericin B intravenously, then ketoconazole orally did not substantially improve his clinical course. He died about four months post-laminectomy. PMID:6866873

Use of the 1 tuberculin unit (TU) Mantoux test in the assessment of tuberculous infection in children following neonatal BCG vaccination.

PubMed

Hoskyns, E W; Simpson, H; Monk, P

1994-10-01

BCG vaccination alters the response to tuberculin testing and influences the potential validity of the Heaf test in the diagnosis of tuberculosis. This study used a purified protein derivative 1 tuberculin unit (TU) Mantoux test with a cut off of 5 mm induration as an indicator of tuberculous infection in high risk children to determine whether this would distinguish infection from previous neonatal BCG vaccination. Children at high risk of tuberculosis on chest radiography, Heaf test, or contact history who had been screened in the contact tracing clinic and referred for further assessment were included in the study. After clinical examination, chest radiography, and Mantoux testing they were assigned to three groups (tuberculous disease, chemoprophylaxis, or no treatment) and followed up for 6-24 months in the outpatient clinic and subsequently by postal questionnaire. Comparison of the Heaf and Mantoux tests showed a difference in the results with 82% of cases positive by the Heaf test and 59% positive by the Mantoux test. Using the Mantoux test result in combination with clinical and radiographic findings 194 children were allocated to the three groups as follows: primary tuberculosis (5), chemoprophylaxis (101), no treatment (88). During follow up for a mean (range) time of 46 (11-102) months four additional cases received treatment for primary tuberculosis, two in the chemoprophylaxis group and two in the untreated group. The use of the 1 TU Mantoux test after neonatal BCG vaccination reduced the number of children receiving treatment from 129 to 93-that is, by 36%. Although the numbers are small, there was no increase in the later development of tuberculosis.

Impact of nursing interventions on adherence to treatment with antituberculosis drugs in children and young people: A non-randomized controlled trial.

PubMed

Guix-Comellas, Eva Maria; Rozas-Quesada, Librada; Velasco-Arnaiz, Eneritz; Ferres-Canals, Ariadna; Estrada-Masllorens, Joan Maria; Force-Sanmartín, Enriqueta; Noguera-Julian, Antoni

2018-05-03

To evaluate the association of a new nursing intervention on the adherence to antituberculosis treatment in a pediatric cohort (<18 years). Tuberculosis remains a public health problem worldwide. The risk of developing tuberculosis after primary infection and its severity are higher in children. Proper adherence to antituberculosis treatment is critical for disease control. Non-randomized controlled trial; Phase 1, retrospective (2011-2013), compared with Phase 2, prospective with intervention (2015-2016), in a referral center for pediatric tuberculosis in Spain (NCT03230409). A total of 359 patients who received antituberculosis drugs after close contact with a smear-positive patient (primary chemoprophylaxis) or were treated for latent tuberculosis infection or tuberculosis disease were included, 261 in Phase 1 and 98 in Phase 2. In phase 2, a new nurse-led intervention was implemented in all patients and included two educational steps (written information in the child's native language and follow-up telephone calls) and two monitoring steps (Eidus-Hamilton test and follow-up questionnaire) that were exclusively carried out by nurses. Adherence to antituberculosis treatment increased from 74.7% in Phase 1 to 87.8% in Phase 2 (p=0.014; Chi-square test), after the implementation of the nurse-led intervention. In Phase 2, non-adherence was only associated with being born abroad (28.6% versus 7.8%; p=0.019; Chi-square test) and with foreign origin families (27.3% versus 0%; p<0.0001; Chi-square test). The nurse-led intervention was associated to an increase in adherence to antituberculosis treatment. Immigrant-related variables remained major risk factors for sub-optimal adherence in a low-endemic setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The double burden.

PubMed

Faurholt-Jepsen, Daniel

2013-07-01

One third of the world's population is latently infected with Mycobacterium tuberculosis, and with the lifestyle changes succeeding the on-going urbanization, populations already burdened by tuberculosis are experiencing a dramatic increase in chronic diseases, with diabetes being a serious challenge. Tuberculosis and diabetes are not only becoming co-existing diseases. In fact, the diseases interact, and there is evidence to suggest that especially diabetes disease increases the susceptibility for developing active tuberculosis disease. Furthermore, it is plausible that tuberculosis leads to, either transient or permanent, impairment of the glucose metabolism, which ultimately will turn into diabetes. A number of studies from the Americas, Europe, Asia, and, most lately, from sub-Saharan Africa have reported strong association between tuberculosis and diabetes; on average, the estimated risk of active tuberculosis is thrice as high among people with diabetes. The study from sub-Saharan Africa was conducted in Tanzania and is the basis of this thesis. Based on available evidence on the association between tuberculosis and diabetes, the primary aim of the study was to assess the role of diabetes for tuberculosis risk, manifestations, treatment outcomes and survival in a Tanzanian population of tuberculosis patients and non-tuberculosis neighbourhood controls. The study was conducted in Mwanza City in northern Tanzania, with a population exceeding half a million inhabitants, with tuberculosis and HIV being common infections in the region, but with little knowledge about the prevalence of diabetes. We recruited newly diagnosed pulmonary tuberculosis patients from spring 2006 and continuously till the fall 2009, with all participating in a nutritional intervention running in parallel with the medical tuberculosis treatment. All participants underwent diabetes and HIV testing as well as a series of measurements such as anthropometric, clinical and paraclinical parameters. The population was followed up during treatment (2 and 5 months) to assess treatment outcome as well as after one year to assess their survival status. Based on data from 1,250 tuberculosis patients and 350 neighbourhood controls, we found that 38 and 21%, respectively, had impaired glycaemia, and that the prevalence of diabetes was 17 and 9% among tuberculosis patients and controls, respectively. This difference in prevalence between patients and controls was equivalent to an adjusted odds ratio of more than four, indicating a strong association between tuberculosis and diabetes. Furthermore, we found that diabetes was associated with tuberculosis among both participants with or without HIV co-infection. Despite the strong association, diabetes had only moderate clinical implications when the tuberculosis patients initiated the tuberculosis treatment; the patients with diabetes co-morbidity had a minor elevation in the immune response and more frequently reported to have fever. Furthermore, diabetes did not seem to delay time to sputum conversion during treatment. Nevertheless, diabetes co-morbidity led to impaired treatment outcome with slower recovery of weight and haemoglobin and a more than four times higher mortality rate within the initial phase of tuberculosis treatment. In conclusion, in the African region, the double burden of tuberculosis and diabetes is becoming a major health problem. Although the tuberculosis incidence has stabilized during the last decade, the increasing incidence of diabetes will possibly interfere with tuberculosis control and may, consequently, make the tuberculosis incidence increase again. Future research strategies should focus on enhanced diagnostic tools to identify tuberculosis patients with diabetes co-morbidity, and on the role of disease-disease, drug-disease and drug-drug interactions between tuberculosis and diabetes diseases and treatments.

The Diagnosis and Treatment of Tuberculosis of the Breast

PubMed Central

Wilson, T. S.; Macgregor, J. W.

1963-01-01

Tuberculosis of the breast is a rare disease. It may be primary—confined to the breast, or secondary to tuberculosis elsewhere. Five cases are reported of which three were primary. The clinician confuses the disease with pyogenic breast abscess and cancer. The pathologist may confuse the disease with comedomastitis. Definite diagnosis must rest on bacteriological proof, that is, positive tuberculous culture and guinea-pig inoculation. Treatment of the disease may be either medical or surgical. Medical treatment in our hands has been long and expensive, and the disease tends to reappear in further pregnancies. Surgical treatment, which usually consists of simple mastectomy, is preferable. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7 PMID:14079137

Post-Inhaled Corticosteroid Pulmonary Tuberculosis Increases Lung Cancer in Patients with Asthma

PubMed Central

Lin, Frank Cheau-Feng; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Wu, Min-Chen; Wu, Ming-Fang; Liaw, Yung-Po

2016-01-01

Purpose To evaluate the association between post-inhaled corticosteroid (ICS) pulmonary tuberculosis (TB), pneumonia and lung cancer in patients with asthma. Methods The study samples were collected from the National Health Insurance Database. Asthmatic patients who were first-time users of ICS between 2003 and 2005 were identified as cases. For each case, 4 control individuals were randomly matched for sex, age and date of ICS use. Cases and matched controls were followed up until the end of 2010. Cox proportional hazard regression was used to determine the hazard ratio for pulmonary infections and lung cancer risk in the ICS users and non-users. Results A total of 10,904 first-time users of ICS were matched with 43,616 controls. The hazard ratios for lung cancer were: 2.52 (95% confidence interval [CI], 1.22–5.22; p = 0.012) for individuals with post-ICS TB, 1.28 (95%CI, 0.73–2.26; p = 0.389) for post-ICS pneumonia, 2.31(95%CI, 0.84–6.38; p = 0.105) for post-ICS pneumonia+TB, 1.08 (95%CI, 0.57–2.03; p = 0.815) for TB, 0.99 (95%CI, 0.63–1.55; p = 0.970) for pneumonia, and 0.32 (95%CI, 0.05–2.32; p = 0.261) for pneumonia+ TB, respectively. Conclusions Post-ICS TB increased lung cancer risk in patients with asthma. Because of the high mortality associated with lung cancer, screening tests are recommended for patients with post-ICS TB. PMID:27448321

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial.

PubMed

Hosseinipour, Mina C; Bisson, Gregory P; Miyahara, Sachiko; Sun, Xin; Moses, Agnes; Riviere, Cynthia; Kirui, Fredrick K; Badal-Faesen, Sharlaa; Lagat, David; Nyirenda, Mulinda; Naidoo, Kogieleum; Hakim, James; Mugyenyi, Peter; Henostroza, German; Leger, Paul D; Lama, Javier R; Mohapi, Lerato; Alave, Jorge; Mave, Vidya; Veloso, Valdilea G; Pillay, Sandy; Kumarasamy, Nagalingeswaran; Bao, Jing; Hogg, Evelyn; Jones, Lynne; Zolopa, Andrew; Kumwenda, Johnstone; Gupta, Amita

2016-03-19

Mortality within the first 6 months after initiating antiretroviral therapy is common in resource-limited settings and is often due to tuberculosis in patients with advanced HIV disease. Isoniazid preventive therapy is recommended in HIV-positive adults, but subclinical tuberculosis can be difficult to diagnose. We aimed to assess whether empirical tuberculosis treatment would reduce early mortality compared with isoniazid preventive therapy in high-burden settings. We did a multicountry open-label randomised clinical trial comparing empirical tuberculosis therapy with isoniazid preventive therapy in HIV-positive outpatients initiating antiretroviral therapy with CD4 cell counts of less than 50 cells per μL. Participants were recruited from 18 outpatient research clinics in ten countries (Malawi, South Africa, Haiti, Kenya, Zambia, India, Brazil, Zimbabwe, Peru, and Uganda). Individuals were screened for tuberculosis using a symptom screen, locally available diagnostics, and the GeneXpert MTB/RIF assay when available before inclusion. Study candidates with confirmed or suspected tuberculosis were excluded. Inclusion criteria were liver function tests 2·5 times the upper limit of normal or less, a creatinine clearance of at least 30 mL/min, and a Karnofsky score of at least 30. Participants were randomly assigned (1:1) to either the empirical group (antiretroviral therapy and empirical tuberculosis therapy) or the isoniazid preventive therapy group (antiretroviral therapy and isoniazid preventive therapy). The primary endpoint was survival (death or unknown status) at 24 weeks after randomisation assessed in the intention-to-treat population. Kaplan-Meier estimates of the primary endpoint across groups were compared by the z-test. All participants were included in the safety analysis of antiretroviral therapy and tuberculosis treatment. This trial is registered with ClinicalTrials.gov, number NCT01380080. Between Oct 31, 2011, and June 9, 2014, we enrolled 850 participants. Of these, we randomly assigned 424 to receive empirical tuberculosis therapy and 426 to the isoniazid preventive therapy group. The median CD4 cell count at baseline was 18 cells per μL (IQR 9-32). At week 24, 22 (5%) participants from each group died or were of unknown status (95% CI 3·5-7·8) for empirical group and for isoniazid preventive therapy (95% CI 3·4-7·8); absolute risk difference of -0·06% (95% CI -3·05 to 2·94). Grade 3 or 4 signs or symptoms occurred in 50 (12%) participants in the empirical group and 46 (11%) participants in the isoniazid preventive therapy group. Grade 3 or 4 laboratory abnormalities occurred in 99 (23%) participants in the empirical group and 97 (23%) participants in the isoniazid preventive therapy group. Empirical tuberculosis therapy did not reduce mortality at 24 weeks compared with isoniazid preventive therapy in outpatient adults with advanced HIV disease initiating antiretroviral therapy. The low mortality rate of the trial supports implementation of systematic tuberculosis screening and isoniazid preventive therapy in outpatients with advanced HIV disease. National Institutes of Allergy and Infectious Diseases through the AIDS Clinical Trials Group. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Tuberculosis of the lung bases].

PubMed

Elkard, I; Zaghba, N; Benjelloun, H; Bakhatar, A; Yassine, N

2016-05-01

Tuberculosis is a major public health problem in Morocco. Tuberculosis of the lung bases is a rare and atypical form and raises real diagnostic problems. We report a retrospective study of 21 cases of basal pulmonary tuberculosis, collected at the service of respiratory diseases in Ibn Rushd hospital in Casablanca between 2004 and 2015 (11 years). From a total of 21 patients having basal pulmonary tuberculosis, 13 (62%) were women versus eight men (48%), the average age was 33 years. The average time of diagnosis was 25 days. The disease was unilateral in 20 cases (95%). The right lower lobe was the most frequently affected (71%). Inhomogeneous opacities (66%) and consolidation (28%) were the main radiological findings. Associated comorbidities were dominated by diabetes in six cases (28%). Bronchoscopy had recovered thickening spurs in eight cases, endobronchial granules in seven cases and bronchial inflammation in six cases. Bronchial biopsies had found a necrotizing granulomatous inflammation tuberculoide in seven cases (33%). The smear was positive in sputum in three cases (14%), in the bronchial aspirate in four cases (19%), in induced sputum in one case (4.7%) and in post-bronchoscopic sputum in six cases (28%). The antituberculous treatment was started in all patients with good clinical and radiological evolution. The basal localization of the pulmonary tuberculosis is misleading; source of diagnostic delay, hence the need to think about it especially in patients with comorbidities. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis.

PubMed

Yamshchikov, Alexandra V; Kurbatova, Ekaterina V; Kumari, Meena; Blumberg, Henry M; Ziegler, Thomas R; Ray, Susan M; Tangpricha, Vin

2010-09-01

Vitamin D insufficiency is common in industrialized and developing nations. Recent studies have shown that vitamin D insufficiency is associated with a higher risk of active tuberculosis. Laboratory studies provided a mechanism for this link on the basis of findings that vitamin D metabolites regulate the expression of cathelicidin (LL-37), which is an endogenous antimicrobial peptide with activity against Mycobacterium tuberculosis. Little information is available on the clinical relation between vitamin D, LL-37 concentrations, and disease severity in patients with tuberculosis. The primary objective of the study was to evaluate the relation between vitamin D nutriture, serum LL-37 concentrations, and tuberculosis by using samples stored in the Tuberculosis Trials Consortium serum repository. We measured 25-hydroxyvitamin D [25(OH)D] and LL-37 concentrations in 95 serum specimens from patients with culture-confirmed pulmonary tuberculosis and correlated these concentrations to clinical and demographic variables. The prevalence of vitamin D insufficiency [serum 25(OH)D concentration lt 30 ng/mL] in patients with active tuberculosis was 86% (n = 95) with a mean baseline serum 25(OH)D concentration of 20.4 ng/mL. Factors associated with vitamin D insufficiency were black race and indoor lifestyle. The mean ( plusmn SD) baseline LL-37 concentration was 49.5 plusmn 23.8 ng/mL. Higher LL-37 concentrations correlated with acid fast bacilli sputum smear positivity and weight gt 10% below ideal body weight. Serum vitamin D status of the study subjects did not correlate with serum LL-37 concentrations. More prospectively designed studies are needed to evaluate the clinical implications of vitamin D insufficiency in patients with tuberculosis and the utility of circulating LL-37 as a potential biomarker in patients with active tuberculosis disease. The parent trial was registered at clinicaltrials.gov as NCT00023335.

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.

Acid-fast bacilli culture positivity and drug resistance in abdominal tuberculosis in Mumbai, India.

PubMed

Samant, Hrishikesh; Desai, Devendra; Abraham, Philip; Joshi, Anand; Gupta, Tarun; Rodrigues, Camilla; George, Siji

2014-09-01

Culture positivity for Mycobacterium tuberculosis complex (MTB) in abdominal tuberculosis (TB) using Lowenstein Jensen medium and Bactec system varies from 25 % to 36 %. Data on the prevalence of drug resistance in primary abdominal TB is scant. Our aim was to study the acid-fast bacilli (AFB) culture positivity rate in primary abdominal TB using Bactec Mycobacterial Growth Indicator Tubes (MGIT) system and the prevalence of drug resistance in these patients. Records of patients with abdominal TB (diagnosed on clinical features, endoscopy, histology, microbiology) seen during the period 2008 to 2013 were retrieved from the Gastroenterology and Microbiology departments. Patients with extra-abdominal TB (five pulmonary, two nodal), adnexal (one), and HIV (one) were excluded from analysis. Of 61 patients, 31 (50.8 %) had a positive AFB culture. In the 30 culture-negative patients, histology showed non-caseating granulomas in 25 patients. Drug sensitivity pattern was analyzed in 18 patients; resistance was detected in eight (14.3 % of all patients and 44.4 % of patients in whom drug sensitivity was done) including three (5.4 % of all subjects and 16.6 % in whom drug sensitivity was available) who were multidrug-resistant. The rate of AFB culture positivity in primary abdominal TB was 50.8 % using Bactec MGIT. Likelihood of drug resistance was seen in 14.3 %, of whom 5.4 % were multidrug-resistant.

Hemothorax

MedlinePlus

... pulmonary infarction) Lung or pleural cancer -- primary or secondary (metastatic, or from another site) Tear in a blood vessel when placing a central venous catheter or when associated with severe high blood pressure Tuberculosis

Predictors of tuberculosis (TB) and antiretroviral (ARV) medication non-adherence in public primary care patients in South Africa: a cross sectional study.

PubMed

Naidoo, Pamela; Peltzer, Karl; Louw, Julia; Matseke, Gladys; McHunu, Gugu; Tutshana, Bomkazi

2013-04-26

Despite the downward trend in the absolute number of tuberculosis (TB) cases since 2006 and the fall in the incidence rates since 2001, the burden of disease caused by TB remains a global health challenge. The co-infection between TB and HIV adds to this disease burden. TB is completely curable through the intake of a strict anti-TB drug treatment regimen which requires an extremely high and consistent level of adherence.The aim of this study was to investigate factors associated with adherence to anti-TB and HIV treatment drugs. A cross-sectional survey method was used. Three study districts (14 primary health care facilities in each) were selected on the basis of the highest TB caseload per clinic. All new TB and new TB retreatment patients were consecutively screened within one month of anti-tuberculosis treatment. The sample comprised of 3107 TB patients who had been on treatment for at least three weeks and a sub-sample of the total sample were on both anti-TB treatment and anti-retro-viral therapy(ART) (N = 757). Data collection tools included: a Socio-Demographic Questionnaire; a Post-Traumatic-Stress-Disorder (PTSD) Screen; a Psychological Distress Scale; the Alcohol Use Disorder Identification Test (AUDIT); and self-report measures of tobacco use, perceived health status and adherence to anti-TB drugs and ART. The majority of the participants (N = 3107) were new TB cases with a 55.9% HIV co-infection rate in this adult male and female sample 18 years and older. Significant predictors of non-adherence common to both anti-TB drugs and to dual therapy (ART and anti-TB drugs) included poverty, having one or more co-morbid health condition, being a high risk for alcohol mis-use and a partner who is HIV positive. An additional predictor for non-adherence to anti-TB drugs was tobacco use. A comprehensive treatment programme addressing poverty, alcohol mis-use, tobacco use and psycho-social counseling is indicated for TB patients (with and without HIV). The treatment care package needs to involve not only the health sector but other relevant government sectors, such as social development.

Primary resistence of mycobacteria in tuberculosis patients.

PubMed

Daddi, G; Giobbi, A; Lucchesi, M

1976-03-01

Primary mycobactria resistance especially in some countries may be a serious obstacle to a successful therapy and the number of patients carrier of primary resistant mycobacteria remains almost at the same level in spite of the chemotherapeutic treatments and the usually rapid recover of the newly diagnosed cases. This may probably be attributed to the fact that the number of chronic patients, spitting resistant tubercle bacilli has remained almost the same, because these patients are eliminated little by little. In our country there is a constant regression of the morbidity, but not so rapid as expected, The newly diagnosed patients are generally young and, if well treated, they heal quickly and well; moreover, they are usually not so richly bacillised as they used to be once and the severity of their disease, globally evaluated, appears also reduced. The cultural positivity at the first admission into hospital is also diminishing. From all the above facts it is obvious that in order to eradicate tuberculosis it is necessary: First - to avoid creatin chronic patients; in order to reach this goal the treatment must be the most effective possible from the very beginning: INH and Rifampin. Second - to try to cure the chronic patients and to render them abacillary of, at least, to treat them intensively, with the purpose of inducing in the infecting flora a polyresistance which reners the mycobacteria hypovirulent, especially if it includes a R/AMP resistance over 40-gamma. Third - the role of the primary resistance in the epidemiology and the evolution of tuberculosis in the various countries and in the single patients, may be very different.

Intestinal tuberculosis complicated with perforation during anti-tuberculous treatment in a 13-year-old girl with defective mitogen-induced IL-12 production.

PubMed

Law, Siu-Tong; Chiu, Sin-Chuen; Li, Kin Kong

2014-10-01

Interleukin-12 (IL-12) is a cytokine which is secreted by activated phagocytes and dendritic cells and promotes cell-mediated immunity to intracellular pathogens, by inducing type 1 helper T cell (TH1) responses and interferon- γ (IFN- γ) production. Defects in the IL-12 may cause selective susceptibility to intracellular pathogens, such as mycobacteria. We herein report on a 13-year-old girl with defective mitogen-induced IL-12 production, who developed intestinal tuberculosis with wide dissemination involving the lung and urinary tract. She improved gradually, but developed terminal ileal perforation approximately 6.1 months following initiation of anti-tuberculous treatment. The paradoxical response phenomenon was suspected. The girl subsequently underwent surgical resection of the affected bowel segment with a temporary double barrel stoma, and ileocolonic anastomosis was performed after the completion of the anti-tuberculous therapy. The patient remained well, with no evidence of recurrent tuberculosis in the past 5 years. This case illustrates the possibility of underlying primary immunodeficiency in a patient with disseminated tuberculosis; delayed tuberculous intestinal perforation can develop during chemotherapy for tuberculosis. Copyright © 2012. Published by Elsevier B.V.

A Rare, Unusual Presentation of Primary Tuberculosis in the Temporomandibular Joint.

PubMed

Towdur, Geetha N; Upasi, Amarnath P; Veerabhadrappa, Umashankara Kagathur; Rai, Kirthikumar

2018-04-01

Tuberculosis (TB) is a very common health problem in developing nations such as India. It can present as its primary form or as secondary forms (extrapulmonary TB). Maxillofacial manifestations of TB compose nearly 10% of all extrapulmonary manifestations of the disease. Extrapulmonary TB involving the maxillofacial region is very rare and can present in any tissues in this region. These infections generally involve the head and neck through hematogenous or lymphatic routes. Very few cases of primary TB of the temporomandibular joint (TMJ) have been reported in the literature. The presentation of TB infection of the TMJ can resemble arthritis, osteomyelitis, or any other kind of chronic joint disease. It is very important to diagnose this disease at an early stage. If left untreated, it can prove fatal within 5 years in more than half the cases. Therefore, early diagnosis and management of these cases is critical. This article describes a case of primary TB of the TMJ that presented as a preauricular swelling. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Food baskets given to tuberculosis patients at a primary health care clinic in the city of Duque de Caxias, Brazil: effect on treatment outcomes.

PubMed

Cantalice Filho, João Paulo

2009-10-01

To evaluate the effect that the distribution of food baskets to tuberculosis (TB) patients has on treatment outcomes at a primary health care clinic. Retrospective comparative study of the medical and social aspects of 142 patients at a primary health care clinic in the city of Duque de Caxias, Brazil. The patients were divided into two groups: the first group included 68 patients treated with standard regimens (between September of 2001 and December of 2003); and the second group included 74 patients treated with the same regimens but also receiving food baskets on a monthly basis (between January of 2004 and July of 2006). The statistical comparison between the two groups revealed that the cure rate was higher in the group receiving the food baskets (87.1% vs. 69.7%), whereas the rate of noncompliance was markedly lower (12.9% vs. 30.3%). The results indicate that the distribution of food baskets can be a useful strategy to improve compliance with TB treatment at primary health care clinics.

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 (Brazil and Colombia); which are all high tuberculosis prevalence areas. Tuberculosis outreach screening, using house-to-house visits, sometimes combined with printed information about going to clinic, may increase tuberculosis case detection (RR 1.24, 95% CI 0.86 to 1.79; 4 trials, 6,458,591 participants in 297 clusters, low-certainty evidence); and probably increases case detection in areas with tuberculosis prevalence of 5% or more (RR 1.52, 95% CI 1.10 to 2.09; 3 trials, 155,918 participants, moderate-certainty evidence; prespecified stratified analysis). These interventions may lower the early default (prior to starting treatment) or default during treatment (RR 0.67, 95% CI 0.47 to 0.96; 3 trials, 849 participants, low-certainty evidence). However, this intervention may have may have little or no effect on treatment success (RR 1.07, 95% CI 1.00 to 1.15; 3 trials, 849 participants, low-certainty evidence), and we do not know if there is an effect on treatment failure or mortality. One study investigated long-term prevalence in the community, but with no clear effect due to imprecision and differences in care between the two groups (RR 1.14, 95% CI 0.65 to 2.00; 1 trial, 556,836 participants, very low-certainty evidence). Four studies examined health promotion activities to encourage people to attend for screening, including mass media strategies and more locally organized activities. There was some increase, but this could have been related to temporal trends, with no corresponding increase in case notifications, and no evidence of an effect on long-term tuberculosis prevalence. Two studies examined the effects of two to six nurse practitioner educational sessions in tuberculosis diagnosis, with no clear effect on tuberculosis cases detected. One trial compared mobile clinics every five days with house-to-house screening every six months, and showed an increase in tuberculosis cases. There was also insufficient evidence to determine if sustained improvements in case detection impact on long-term tuberculosis prevalence; this was evaluated in one study, which indicated little or no effect after four years of either contact tracing, extensive health promotion activities, or both (RR 1.31, 95% CI 0.75 to 2.30; 1 study, 405,788 participants in 12 clusters, very low-certainty evidence). Authors' conclusions The available evidence demonstrates that when used in appropriate settings, active case-finding approaches may result in increase in tuberculosis case detection in the short term. The effect of active case finding on treatment outcome needs to be further evaluated in sufficiently powered studies. Interventions to increase the number of tuberculosis cases being diagnosed This review summarized trials evaluating the effects of interventions aiming to increase the diagnosis of tuberculosis and reduce the number of undiagnosed tuberculosis cases in communities. After searching for relevant trials up to 19 December 2016, we included 17 studies conducted in sub-Saharan Africa (nine studies), Asia (six studies), and South America (two studies). Why does tuberculosis go undiagnosed and how might programmes improve this? Tuberculosis is a chronic infectious disease that affects over 10 million people worldwide, with an estimated four million tuberculosis patients remaining undiagnosed each year. Interventions such as outreach tuberculosis screening with or without health promotion that actively screen for tuberculosis among individuals presenting with symptoms of tuberculosis, may increase detection of microbiologically confirmed tuberculosis cases. These interventions may improve treatment outcomes by increasing the number of tuberculosis patients who are cured and complete treatment. However, we do not know if these interventions reduce either tuberculosis treatment failure, or tuberculosis-associated death or long-term tuberculosis burden in moderate- and high-tuberculosis settings. What the research says House-to-house screening for active tuberculosis, and organizing tuberculosis diagnostic clinics nearer to where people live and work, may increase tuberculosis case detection in settings where the prevalence of undiagnosed disease is high (low-certainty evidence). These people may have higher levels of treatment success and lower levels of default from treatment (low-certainty evidence). There was insufficient evidence to determine if health promotion activities alone increase tuberculosis case detection (very low-certainty evidence). There was also insufficient evidence to determine if sustained improvements in case detection impact on long-term tuberculosis prevalence, as the only study to evaluate this found no effect after four years (very low-certainty evidence). PMID:29182800

Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial.

PubMed

Sudfeld, Christopher R; Mugusi, Ferdinand; Aboud, Said; Nagu, Tumaini J; Wang, Molin; Fawzi, Wafaie W

2017-02-10

HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D 3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART. The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D 3 (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D 3 supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D 3 regimen consists of oral supplements containing 50,000 IU vitamin D 3 taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D 3 taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D 3 regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers. The ToV4 will provide causal evidence on the effect of vitamin D 3 supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D 3 supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations. ClinicalTrials.gov, NCT01798680 . Registered on 21 February 2013.

Interferon-gamma and interleukin-10 profile of children with tuberculosis in North Sumatera, Indonesia

NASA Astrophysics Data System (ADS)

Daulay, R. S.; Daulay, R. M.

2018-03-01

Cellular immunity was mediated the host immune response against Mycobacterium tuberculosis, in which cytokine and T-helper (Th) 1 cells play an important role. Interferon-gamma (IFN-γ) is a leading cytokine involved in the immune response of tuberculosis (TB).The primary function of IFN-γ is to activate macrophages in opposition Mycobacterium tuberculosis. Contrast from IFN-γ, interleukin-10 (IL-10) is considered inhibitory cytokine, important to an adequate balance between inflammatory responses. To analyze cytokine profile, particularly IFN-γ and IL-10 of the children with TB in Indonesia, a cross-sectional study was conducted at two general hospitals and seven primary health care located in Medan and Batubara, North Sumatera, Indonesia. Among 51 children with TB disease and 51 healthy children, found that IFN-γ and IL-10 levels were lower in TB patients compared to healthy children. Statistically significant decreased production of the IFN-γ levels (p=0.042) were found in TB patients 9.41 (1.10-28.06) pg/ml contrast to healthy children 6.30 (1.30-89.76) pg/ml. Homologue finding of the IL-10 levels were also found in TB patients 4.93 (0.22-48.01) pg/ml and 4.93 (0.07-81.60) pg/ml in healthy children, but not statistically significant (p=0.784). High levels of IL-10 were not proven to suppress the levels production of IFN-γ in TB patients.

Tuberculosis in hospitalized patients: clinical characteristics of patients receiving treatment within the first 24 h after admission*

PubMed Central

Silva, Denise Rossato; da Silva, Larissa Pozzebon; Dalcin, Paulo de Tarso Roth

2014-01-01

Objective: To evaluate clinical characteristics and outcomes in patients hospitalized for tuberculosis, comparing those in whom tuberculosis treatment was started within the first 24 h after admission with those who did not. Methods: This was a retrospective cohort study involving new tuberculosis cases in patients aged ≥ 18 years who were hospitalized after seeking treatment in the emergency room. Results: We included 305 hospitalized patients, of whom 67 (22.0%) received tuberculosis treatment within the first 24 h after admission ( ≤24h group) and 238 (88.0%) did not (>24h group). Initiation of tuberculosis treatment within the first 24 h after admission was associated with being female (OR = 1.99; 95% CI: 1.06-3.74; p = 0.032) and with an AFB-positive spontaneous sputum smear (OR = 4.19; 95% CI: 1.94-9.00; p < 0.001). In the ≤24h and >24h groups, respectively, the ICU admission rate was 22.4% and 15.5% (p = 0.258); mechanical ventilation was used in 22.4% and 13.9% (p = 0.133); in-hospital mortality was 22.4% and 14.7% (p = 0.189); and a cure was achieved in 44.8% and 52.5% (p = 0.326). Conclusions: Although tuberculosis treatment was initiated promptly in a considerable proportion of the inpatients evaluated, the rates of in-hospital mortality, ICU admission, and mechanical ventilation use remained high. Strategies for the control of tuberculosis in primary care should consider that patients who seek medical attention at hospitals arrive too late and with advanced disease. It is therefore necessary to implement active surveillance measures in the community for earlier diagnosis and treatment. PMID:25029651

Diabetes Reduces the Rate of Sputum Culture Conversion in Patients With Newly Diagnosed Multidrug-Resistant Tuberculosis

PubMed Central

Salindri, Argita D.; Kipiani, Maia; Kempker, Russell R.; Gandhi, Neel R.; Darchia, Lasha; Tukvadze, Nestani; Blumberg, Henry M.; Magee, Matthew J.

2016-01-01

Background. Diabetes is a risk factor for active tuberculosis (TB), but little is known about the relationship between diabetes and multidrug-resistant (MDR) TB. We aimed to assess risk factors for primary MDR TB, including diabetes, and determine whether diabetes reduced the rate of sputum culture conversion among patients with MDR TB. Methods. From 2011 to 2014, we conducted a cohort study at the National Center for Tuberculosis and Lung Diseases in Tbilisi, Georgia. Adult (≥35 years) patients with primary TB were eligible. Multidrug-resistant TB was defined as resistance to at least rifampicin and isoniazid. Patients with capillary glycosylated hemoglobin (HbA1c) ≥ 6.5% or previous diagnosis were defined to have diabetes. Polytomous regression was used to estimate the association of patient characteristics with drug resistance. Cox regression was used to compare rates of sputum culture conversion in patients with and without diabetes. Results. Among 318 patients with TB, 268 had drug-susceptibility test (DST) results. Among patients with DST results, 19.4% (52 of 268) had primary MDR TB and 13.4% (36 of 268) had diabetes. In multivariable analyses, diabetes (adjusted odds ratio [aOR], 2.51; 95% confidence interval [CI], 1.00–6.31) and lower socioeconomic status (aOR, 3.51; 95% CI, 1.56–8.20) were associated with primary MDR TB. Among patients with primary MDR TB, 44 (84.6%) converted sputum cultures to negative. The rate of sputum culture conversion was lower among patients with diabetes (adjusted hazard ratio [aHR], 0.34; 95% CI, .13–.87) and among smokers (aHR, 0.16; 95% CI, .04–.61). Conclusions. We found diabetes was associated with an increased risk of primary MDR TB; both diabetes and smoking were associated with a longer time to sputum culture conversion. PMID:27419188

Factors associated with length of hospital stay among HIV positive and HIV negative patients with tuberculosis in Brazil.

PubMed

Gonçalves, Maria Jacirema Ferreira; Ferreira, Alaidistania A

2013-01-01

Identify and analyze the factors associated to length of hospital stay among HIV positive and HIV negative patients with tuberculosis in Manaus city, state of Amazonas, Brazil, in 2010. Epidemiological study with primary data obtained from monitoring of hospitalized patients with tuberculosis in Manaus. Data were collected by interviewing patients and analyzing medical records, according to the following study variables age, sex, co-morbidities, education, race, income, lifestyle, history of previous treatment or hospitalization due to tuberculosis, treatment regimen, adverse reactions, smear test, clinical form, type of discharge, and length of hospital stay. The associated factors were identified through chi-square or t-Student test at a 5% significance level. Income from 1 to 3 minimum wages (P = 0.028), pulmonary tuberculosis form (P = 0.011), negative smear test or no information in this regard (P = 0.014), initial 6-month treatment scheme (P = 0.029), and adverse drug reactions (P = 0.021) were associated to prolonged hospital stay in HIV positive patients. We found out that although there were no significant differences in the length of hospital stay in HIV positive patients, all factors significantly associated to prolonged hospital stay occurred in this group of patients. This finding corroborates other studies indicating the severity of tuberculosis in HIV patients, which may also contribute to lengthen their hospital stay.

Theory-Informed Interventions to Improve the Quality of Tuberculosis Evaluation at Ugandan Health Centers: A Quasi-Experimental Study.

PubMed

Chaisson, Lelia H; Katamba, Achilles; Haguma, Priscilla; Ochom, Emmanuel; Ayakaka, Irene; Mugabe, Frank; Miller, Cecily; Vittinghoff, Eric; Davis, J Lucian; Handley, Margaret A; Cattamanchi, Adithya

2015-01-01

Tuberculosis (TB) remains under-diagnosed in many countries, in part due to poor evaluation practices at health facilities. Theory-informed strategies are needed to improve implementation of TB evaluation guidelines. We aimed to evaluate the impact of performance feedback and same-day smear microscopy on the quality of TB evaluation at 6 health centers in rural Uganda. We tested components of a multi-faceted intervention to improve adherence to the International Standards for Tuberculosis Care (ISTC): performance feedback and same-day smear microscopy. The strategies were selected based on a qualitative assessment guided by the Theory of Planned Behavior and the PRECEDE model. We collected patient data 6 months before and after the introduction of each intervention component, and compared ISTC adherence in the pre- and post-intervention periods for adults with cough ≥ 2 weeks' duration. The performance feedback evaluation included 1,446 adults; 838 (58%) were evaluated during the pre-intervention period and 608 (42%) during the post-intervention period. Performance feedback resulted in a 15% (95%CI +10% to +20%, p<0.001) increase in the proportion of patients receiving ISTC-adherent care. The same-day microscopy evaluation included 1,950 adults; 907 (47%) were evaluated during the pre-intervention period and 1,043 (53%) during the post-intervention period. Same-day microscopy was associated with a 14% (95%CI +10% to +18%, p<0.001) increase in the proportion of patients receiving ISTC-adherent care. Performance feedback and same-day microscopy should be considered along with ISTC training as part of a multi-faceted intervention to improve the quality of TB evaluation in other high TB burden countries.

Theory-Informed Interventions to Improve the Quality of Tuberculosis Evaluation at Ugandan Health Centers: A Quasi-Experimental Study

PubMed Central

Haguma, Priscilla; Ochom, Emmanuel; Ayakaka, Irene; Mugabe, Frank; Miller, Cecily; Vittinghoff, Eric; Davis, J. Lucian; Handley, Margaret A.; Cattamanchi, Adithya

2015-01-01

Background Tuberculosis (TB) remains under-diagnosed in many countries, in part due to poor evaluation practices at health facilities. Theory-informed strategies are needed to improve implementation of TB evaluation guidelines. We aimed to evaluate the impact of performance feedback and same-day smear microscopy on the quality of TB evaluation at 6 health centers in rural Uganda. Methods We tested components of a multi-faceted intervention to improve adherence to the International Standards for Tuberculosis Care (ISTC): performance feedback and same-day smear microscopy. The strategies were selected based on a qualitative assessment guided by the Theory of Planned Behavior and the PRECEDE model. We collected patient data 6 months before and after the introduction of each intervention component, and compared ISTC adherence in the pre- and post-intervention periods for adults with cough ≥ 2 weeks’ duration. Results The performance feedback evaluation included 1,446 adults; 838 (58%) were evaluated during the pre-intervention period and 608 (42%) during the post-intervention period. Performance feedback resulted in a 15% (95%CI +10% to +20%, p<0.001) increase in the proportion of patients receiving ISTC-adherent care. The same-day microscopy evaluation included 1,950 adults; 907 (47%) were evaluated during the pre-intervention period and 1,043 (53%) during the post-intervention period. Same-day microscopy was associated with a 14% (95%CI +10% to +18%, p<0.001) increase in the proportion of patients receiving ISTC-adherent care. Conclusions Performance feedback and same-day microscopy should be considered along with ISTC training as part of a multi-faceted intervention to improve the quality of TB evaluation in other high TB burden countries. PMID:26172948

Primary thyroid tuberculosis: a rare etiology of hypothyroidism and anterior cervical mass mimicking carcinoma.

PubMed

Silva, Bradley Paulino da; Amorim, Erico Gurgel; Pavin, Elizabeth João; Martins, Antonio Santos; Matos, Patrícia Sabino de; Zantut-Wittmann, Denise Engelbrecht

2009-06-01

The involvement of the thyroid by tuberculosis (TB) is rare. Hypothyroidism caused by tissue destruction is an extremely rare report. Our aim was to report a patient with primary thyroid TB emphasizing the importance of diagnosis, despite the rarity of the occurrence. Women, 62 years old, showing extensive cervical mass since four months, referring lack of appetite, weight loss, dysphagia and dysphonia. Laboratorial investigation revealed primary hypothyroidism. Cervical ultrasound: expansive lesion in left thyroid lobe, involving adjacent muscle. Computed tomography scan: 13 cm diameter cervical mass with central necrosis. Fine needle biopsy: hemorrhagic material. total thyroidectomy, left radical neck dissection and protective tracheotomy. The pathological examination showed chronic granulomatous inflammatory process with areas of caseous necrosis and lymph node involvement. The thyroid baciloscopy was positive. Pulmonary disease was absent. The patient was treated with antituberculosis drugs. Thyroid TB is not frequent, and should be considered as differential diagnosis of hypothyroidism and anterior cervical mass.

Primary gingival tuberculosis in pregnancy: A rare combination.

PubMed

Sharma, Shweta; Ahad, Abdul; Gupta, Narinder Dev; Sharma, Vivek Kumar

2018-01-01

Tuberculosis (TB), a common chronic-specific granulomatous disease, has become rare in the developed countries. However, it is still a common cause of morbidity and mortality in India. Although it commonly involves the lungs, its presentation in the oral cavity is quite uncommon. The very rare incidence of primary gingival TB, particularly in the absence of active pulmonary involvement often leads to misdiagnosis. Clinical features of oral lesions may include ulceration, nodules, granulomas, and fissures. TB in pregnant women is a major cause of obstetric complications and increased risk of maternal and child mortality. This report highlights a rare case of primary TB of gingiva, presenting as severe gingival overgrowth in a patient with 4 th month of pregnancy. This case strongly suggests the importance of suspecting TB as the differential diagnosis of gingival overgrowth and therefore, playing a critical role in the early detection and treatment. Interdisciplinary collaboration for diagnosis and management resulted in the successful outcome and prevented the obstetric complications in this case.

Methodology and preliminary results of a systematic literature review of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis.

PubMed

Downs, Sara H; Parry, Jessica E; Upton, Paul A; Broughan, Jennifer M; Goodchild, Anthony V; Nuñez-Garcia, Javier; Greiner, Matthias; Abernethy, Darrell A; Cameron, Angus R; Cook, Alasdair J; de la Rua-Domenech, Ricardo; Gunn, Jane; Pritchard, Elizabeth; Rhodes, Shelley; Rolfe, Simon; Sharp, Michael; Vordermeier, H Martin; Watson, Eamon; Welsh, Michael; Whelan, Adam O; Woolliams, John A; More, Simon J; Clifton-Hadley, Richard S

2018-05-01

A systematic review was conducted to identify studies with data for statistical meta-analyses of sensitivity (Se) and specificity (Sp) of ante-mortem and post-mortem diagnostic tests for bovine tuberculosis (bTB) in cattle. Members of a working group (WG) developed and tested search criteria and developed a standardised two-stage review process, to identify primary studies with numerator and denominator data for test performance and an agreed range of covariate data. No limits were applied to year, language, region or type of test in initial searches of electronic databases. In stage 1, titles and available abstracts were reviewed. References that complied with stage 1 selection criteria were reviewed in entirety and agreed data were extracted from references that complied with stage 2 selection criteria. At stage 1, 9782 references were reviewed and 261 (2.6%) passed through to stage 2 where 215 English language references were each randomly allocated to two of 18 WG reviewers and 46 references in other languages were allocated to native speakers. Agreement regarding eligibility between reviewers of the same reference at stage 2 was moderate (Kappa statistic = 0.51) and a resolution procedure was conducted. Only 119 references (published 1934-2009) were identified with eligible performance estimates for one or more of 14 different diagnostic test types; despite a comprehensive search strategy and the global impact of bTB. Searches of electronic databases for diagnostic test performance data were found to be nonspecific with regard to identifying references with diagnostic test Se or Sp data. Guidelines for the content of abstracts to research papers reporting diagnostic test performance are presented. The results of meta-analyses of the sensitivity and specificity of the tests, and of an evaluation of the methodological quality of the source references, are presented in accompanying papers (Nuñez-Garcia et al., 2017; Downs et al., 2017). Copyright © 2017. Published by Elsevier B.V.

Evaluation of the Tuberculosis Infection Control Training Center, Tajikistan, 2014–2015

PubMed Central

Scott, C.; Mangan, J.; Tillova, Z.; Jensen, P. A.; Ahmedov, S.; Ismoilova, J.; Trusov, A.

2017-01-01

SUMMARY SETTING Training center on tuberculosis (TB) infection control (IC) for health care workers in the Central Asian Republics region. OBJECTIVE To assess the effects of TB IC training courses conducted at the Tuberculosis Infection Control Training Center in Machiton, Tajikistan. DESIGN Participants who participated in training (n = 89) during the first year of operation (April 2014–February 2015) were invited to participate in a post-training interview. RESULTS Of the 89 participants, 84 (94%) completed the interview and expressed satisfaction with the training. Eighty (95%) participants reported meeting with workplace leadership to discuss the training. Of these, 69 (85%) reported discussing changes required to meet TB IC standards. Self-reported changes in TB IC practices at work facilities post training included the creation of TB IC committees, designation of a TB IC focal person, TB IC planning, policies to separate infectious patients in waiting rooms, provision of masks for infectious patients, development of cough etiquette policies, improved glove availability, hand hygiene programs, and TB IC posters in waiting rooms. CONCLUSIONS Participant satisfaction and reported changes in TB IC activities illustrate the potential of these training courses to improve TB IC in the region. Future training courses may be tailored to specific audiences using a structured conceptual framework to impact administration, budgeting, and facilities management of TB IC practices. PMID:28399974

Longitudinal whole genome analysis of pre and post drug treatment Mycobacterium tuberculosis isolates reveals progressive steps to drug resistance.

PubMed

Datta, Gargi; Nieto, Luisa M; Davidson, Rebecca M; Mehaffy, Carolina; Pederson, Caroline; Dobos, Karen M; Strong, Michael

2016-05-01

Tuberculosis (TB) is one of the leading causes of death due to an infectious disease in the world. Understanding the mechanisms of drug resistance has become pivotal in the detection and treatment of newly emerging resistant TB cases. We have analyzed three pairs of Mycobacterium tuberculosis strains pre- and post-drug treatment to identify mutations involved in the progression of resistance to the drugs rifampicin and isoniazid. In the rifampicin resistant strain, we confirmed a mutation in rpoB (S450L) that is known to confer resistance to rifampicin. We discovered a novel L101R mutation in the katG gene of an isoniazid resistant strain, which may directly contribute to isoniazid resistance due to the proximity of the mutation to the katG isoniazid-activating site. Another isoniazid resistant strain had a rare mutation in the start codon of katG. We also identified a number of mutations in each longitudinal pair, such as toxin-antitoxin mutations that may influence the progression towards resistance or may play a role in compensatory fitness. These findings improve our knowledge of drug resistance progression during therapy and provide a methodology to monitor longitudinal strains using whole genome sequencing, polymorphism comparison, and functional annotation. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Tuberculin reactivity and tuberculosis epidemiology in the Pakaanóva (Wari') Indians of Rondônia, south-western Brazilian Amazon.

PubMed

Escobar, A L; Coimbra, C E A; Camacho, L A B; Santos, R V

2004-01-01

To investigate the characteristics of tuberculin skin test reactivity in the Pakaanóva Indians, in Amazonia, Brazil, after revaccination of all study participants with bacille Calmette-Guerin (BCG). The investigation was designed as a post-BCG vaccination purified protein derivative (PPD) survey. Data included PPD readings, age, sex, nutritional status, place of residence, previous tuberculosis, physical examinations and BCG status. Bivariate and multivariate logistic regression analyses were conducted. About 90% (n = 505) of the total population participated. One third (32.1%) of the subjects presented induration > or = 10 mm at 72 h. Induration sizes showed weak linear correlation with age; differences between sexes were not observed. Skin reaction was not associated with nutritional status. Individuals with a history of tuberculosis were six times more likely to test positive. History of tuberculosis, age, and previous BCG vaccination were significantly associated with PPD reactivity in the multivariate analyses. The Pakaanóva showed a high proportion (58.4%) of non-reactors, even with a recent BCG booster. Sex differences in PPD reactivity were either not present or could not be demonstrated. The association between age and PPD reactivity resembles that observed in other Amazonian populations. The authors discuss the potential of PPD testing as a screening tool to enhance tuberculosis detection, especially in indigenous populations in Amazonia with limited access to health services.

[Therapeutic principles of bronchopulmonary infections in the aged].

PubMed

Kummer, F

1983-05-01

Airways and lungs are equipped with a highly effective defense mechanism. These can bei found damaged in the aged: Cough is weaker, mucociliary clearance and mucous production are irregular. This damage can bei caused and increased by smoking, recurrent infection, and some sorts of air pollution (SO2). We call it a primary infection, when the organ has been intact as well as the general condition (immune defense etc), and where the causative agent is a virus or virus-like organism. A secondary infection is conditioned by previous disease, and when the causative agents are bacilli. Finally, a tertiary infection is dependent on a defense failure of the body and on opportunistic organisms. For elderly patients, secondary infections outweight the others (recurrent purulent bronchitits). However, tertiary infections must also bei considered in bedridden or post-operative patients or in those with metabolic disease. Finally, pneumonia in the aged must be differentiated in terms of underlying carcinoma, infarction, aspiration and tuberculosis. Therapy of primary (viral)infection consists mainly in prophylaxis of bacterial secondary infection. The choice of drug, dosage and duration of treatment depends on the degree of previous damage to the organ, of complications and status of the whole body and it's defense mechanisms.

Inability of immunomorphometric assessment of angiogenesis to distinguish primary versus secondary myelofibrosis.

PubMed

Sharma, Prashant; Pati, Hara Prasad; Mishra, Pravas Chandra; Dinda, Amit Kumar; Gupta, Ruchika; Sharma, Alok; Jacob, Tony George

2011-08-01

To explore the utility of bone marrow (BM) angiogenesis in differentiating primary myelofibrosis (PMF) from secondary myelofibrosis (MF). CD34 immunostaining was performed on BM biopsies from 21 PMFs, 23 non-PMF myeloproliferative neoplasms (MPN) with associated MF, 20 secondary MF samples, and 10 nonfibrotic controls. Microvessel density (MVD) and microvessel surface area (MSA), along with blood and BM findings were compared between the groups. The post-MPN MF cases included chronic myeloid leukemia-MF and polycythemia vera-MF. Etiologies of secondary MF were metastatic carcinomas, non-MPN hematologic malignancies, tuberculosis, autoimmune MF, and osteopetrosis. Megakaryocytic clustering was the most frequent and intrasinusoidal hematopoiesis the most specific feature of PMF. Higher reticulin grade, collagenization, and osteomyelosclerosis were commoner in PMF. MVD and MSA were significantly increased in fibrotic marrows regardless of etiology. Although mean MVD as well as MSA were highest in PMF, extensive overlaps among groups and marked heterogeneity in the secondary MF group rendered them of limited utility in the differential diagnosis. Enhanced angiogenesis is not entirely specific for PMF. Overlaps with secondary MF limits its differential diagnostic utility. Pathogenetically, our findings suggest that enhanced angiogenesis is a secondary paraneoplastic stromal response shared by various unrelated conditions.

The influence of sex steroid hormones in the immunopathology of experimental pulmonary tuberculosis.

PubMed

Bini, Estela Isabel; Mata Espinosa, Dulce; Marquina Castillo, Brenda; Barrios Payán, Jorge; Colucci, Darío; Cruz, Alejandro Francisco; Zatarain, Zyanya Lucía; Alfonseca, Edgar; Pardo, Marta Romano; Bottasso, Oscar; Hernández Pando, Rogelio

2014-01-01

The relation between men and women suffering pulmonary tuberculosis is 7/3 in favor to males. Sex hormones could be a significant factor for this difference, considering that testosterone impairs macrophage activation and pro-inflammatory cytokines production, while estrogens are proinflammatory mediator's inducer. The aim of this work was to compare the evolution of tuberculosis in male and female mice using a model of progressive disease. BALB/c mice, male and female were randomized into two groups: castrated or sham-operated, and infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and in their lungs were determined bacilli loads, inflammation, cytokines expression, survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female and castrated male animals. Compared to males, females and castrated males exhibited significant higher inflammation in all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females there were not significant differences. Females and castrated males expressed significant higher TNF-α, IFN γ, IL12, iNOS and IL17 than non-castrated males during the first month of infection. Serum Testosterone of males showed higher concentration during late infection. Orchidectomy at day 60 post-infection produced a significant decrease of bacilli burdens in coexistence with higher expression of TNFα, IL-12 and IFNγ. Thus, male mice are more susceptible to tuberculosis than females and this was prevented by castration suggesting that testosterone could be a tuberculosis susceptibility factor.

The Influence of Sex Steroid Hormones in the Immunopathology of Experimental Pulmonary Tuberculosis

PubMed Central

Bini, Estela Isabel; Mata Espinosa, Dulce; Marquina Castillo, Brenda; Barrios Payán, Jorge; Colucci, Darío; Cruz, Alejandro Francisco; Zatarain, Zyanya Lucía; Alfonseca, Edgar; Pardo, Marta Romano; Bottasso, Oscar; Pando, Rogelio Hernández

2014-01-01

The relation between men and women suffering pulmonary tuberculosis is 7/3 in favor to males. Sex hormones could be a significant factor for this difference, considering that testosterone impairs macrophage activation and pro-inflammatory cytokines production, while estrogens are proinflammatory mediator’s inducer. The aim of this work was to compare the evolution of tuberculosis in male and female mice using a model of progressive disease. BALB/c mice, male and female were randomized into two groups: castrated or sham-operated, and infected by the intratracheal route with a high dose of Mycobacterium tuberculosis strain H37Rv. Mice were euthanized at different time points and in their lungs were determined bacilli loads, inflammation, cytokines expression, survival and testosterone levels in serum. Non-castrated male mice showed significant higher mortality and bacilli burdens during late disease than female and castrated male animals. Compared to males, females and castrated males exhibited significant higher inflammation in all lung compartments, earlier formation of granulomas and pneumonia, while between castrated and non-castrated females there were not significant differences. Females and castrated males expressed significant higher TNF-α, IFN γ, IL12, iNOS and IL17 than non-castrated males during the first month of infection. Serum Testosterone of males showed higher concentration during late infection. Orchidectomy at day 60 post-infection produced a significant decrease of bacilli burdens in coexistence with higher expression of TNFα, IL-12 and IFNγ. Thus, male mice are more susceptible to tuberculosis than females and this was prevented by castration suggesting that testosterone could be a tuberculosis susceptibility factor. PMID:24722144

[Comparative diagnosis of bacterial pneumonia and pulmonary tuberculosis in HIV positive patients].

PubMed

Horo, K; Koné, A; Koffi, M-O; Ahui, J M B; Brou-Godé, C V; Kouassi, A B; N'Gom, A; Koffi, N G; Aka-Danguy, E

2016-01-01

Immunodepression induced by the human immunodeficiency virus (HIV) modifies the clinical, radiological and microbiological manifestations of pulmonary tuberculosis; leading to similarities between pulmonary tuberculosis and acute community-acquired bacterial pneumonia. A consequence is the high proportion of discordant pre- and post-mortem diagnoses of pneumonia. The aim of our study was to contribute to the improvement in the diagnosis of acute bacterial pneumonia in HIV positive patients in areas where tuberculosis is endemic. This retrospective study in HIV positive patients has compared 94 cases of positive smear cases pulmonary tuberculosis and 78 cases of acute community-acquired bacterial pneumonia. Using logistic regression, the following features were positively associated with bacterial pneumonia: the sudden onset of signs (OR=8.48 [CI 95% 2.50-28.74]), a delay in the evolution of symptoms of less than 15 days (OR=3.70 [CI 95% 1.11-12.35]), chest pain (OR=2.81 [CI 95% 1.10-7.18]), radiological alveolar shadowing (OR=12.98 [CI 95% 4.66-36.12) and high leukocytosis (OR=3.52 [CI 95% 1.19-10.44]). These five variables allowed us to establish a diagnostic score for bacterial pneumonia ranging from 0 to 5. The area under the ROC curve was 0.886 [CI 95% 0.84-0.94, P<0.001]). Its specificity was >96.8% for a score of greater than or equal to 4. The diagnostic score for acute community-acquired pneumonia may improve the management of bacterial pneumonia in areas where tuberculosis is endemic. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Population Genomics of Mycobacterium tuberculosis in Ethiopia Contradicts the Virgin Soil Hypothesis for Human Tuberculosis in Sub-Saharan Africa

PubMed Central

Comas, Iñaki; Hailu, Elena; Kiros, Teklu; Bekele, Shiferaw; Mekonnen, Wondale; Gumi, Balako; Tschopp, Rea; Ameni, Gobena; Hewinson, R. Glyn; Robertson, Brian D.; Goig, Galo A.; Stucki, David; Gagneux, Sebastien; Aseffa, Abraham; Young, Douglas; Berg, Stefan

2015-01-01

Summary Colonial medical reports claimed that tuberculosis (TB) was largely unknown in Africa prior to European contact, providing a “virgin soil” for spread of TB in highly susceptible populations previously unexposed to the disease [1, 2]. This is in direct contrast to recent phylogenetic models which support an African origin for TB [3, 4, 5, 6]. To address this apparent contradiction, we performed a broad genomic sampling of Mycobacterium tuberculosis in Ethiopia. All members of the M. tuberculosis complex (MTBC) arose from clonal expansion of a single common ancestor [7] with a proposed origin in East Africa [3, 4, 8]. Consistent with this proposal, MTBC lineage 7 is almost exclusively found in that region [9, 10, 11]. Although a detailed medical history of Ethiopia supports the view that TB was rare until the 20th century [12], over the last century Ethiopia has become a high-burden TB country [13]. Our results provide further support for an African origin for TB, with some genotypes already present on the continent well before European contact. Phylogenetic analyses reveal a pattern of serial introductions of multiple genotypes into Ethiopia in association with human migration and trade. In place of a “virgin soil” fostering the spread of TB in a previously naive population, we propose that increased TB mortality in Africa was driven by the introduction of European strains of M. tuberculosis alongside expansion of selected indigenous strains having biological characteristics that carry a fitness benefit in the urbanized settings of post-colonial Africa. PMID:26687624

Population Genomics of Mycobacterium tuberculosis in Ethiopia Contradicts the Virgin Soil Hypothesis for Human Tuberculosis in Sub-Saharan Africa.

PubMed

Comas, Iñaki; Hailu, Elena; Kiros, Teklu; Bekele, Shiferaw; Mekonnen, Wondale; Gumi, Balako; Tschopp, Rea; Ameni, Gobena; Hewinson, R Glyn; Robertson, Brian D; Goig, Galo A; Stucki, David; Gagneux, Sebastien; Aseffa, Abraham; Young, Douglas; Berg, Stefan

2015-12-21

Colonial medical reports claimed that tuberculosis (TB) was largely unknown in Africa prior to European contact, providing a "virgin soil" for spread of TB in highly susceptible populations previously unexposed to the disease [1, 2]. This is in direct contrast to recent phylogenetic models which support an African origin for TB [3-6]. To address this apparent contradiction, we performed a broad genomic sampling of Mycobacterium tuberculosis in Ethiopia. All members of the M. tuberculosis complex (MTBC) arose from clonal expansion of a single common ancestor [7] with a proposed origin in East Africa [3, 4, 8]. Consistent with this proposal, MTBC lineage 7 is almost exclusively found in that region [9-11]. Although a detailed medical history of Ethiopia supports the view that TB was rare until the 20(th) century [12], over the last century Ethiopia has become a high-burden TB country [13]. Our results provide further support for an African origin for TB, with some genotypes already present on the continent well before European contact. Phylogenetic analyses reveal a pattern of serial introductions of multiple genotypes into Ethiopia in association with human migration and trade. In place of a "virgin soil" fostering the spread of TB in a previously naive population, we propose that increased TB mortality in Africa was driven by the introduction of European strains of M. tuberculosis alongside expansion of selected indigenous strains having biological characteristics that carry a fitness benefit in the urbanized settings of post-colonial Africa. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mycobacterium tuberculosis Whole Genome Sequences From Southern India Suggest Novel Resistance Mechanisms and the Need for Region-Specific Diagnostics.

PubMed

Manson, Abigail L; Abeel, Thomas; Galagan, James E; Sundaramurthi, Jagadish Chandrabose; Salazar, Alex; Gehrmann, Thies; Shanmugam, Siva Kumar; Palaniyandi, Kannan; Narayanan, Sujatha; Swaminathan, Soumya; Earl, Ashlee M

2017-06-01

India is home to 25% of all tuberculosis cases and the second highest number of multidrug resistant cases worldwide. However, little is known about the genetic diversity and resistance determinants of Indian Mycobacterium tuberculosis, particularly for the primary lineages found in India, lineages 1 and 3. We whole genome sequenced 223 randomly selected M. tuberculosis strains from 196 patients within the Tiruvallur and Madurai districts of Tamil Nadu in Southern India. Using comparative genomics, we examined genetic diversity, transmission patterns, and evolution of resistance. Genomic analyses revealed (11) prevalence of strains from lineages 1 and 3, (11) recent transmission of strains among patients from the same treatment centers, (11) emergence of drug resistance within patients over time, (11) resistance gained in an order typical of strains from different lineages and geographies, (11) underperformance of known resistance-conferring mutations to explain phenotypic resistance in Indian strains relative to studies focused on other geographies, and (11) the possibility that resistance arose through mutations not previously implicated in resistance, or through infections with multiple strains that confound genotype-based prediction of resistance. In addition to substantially expanding the genomic perspectives of lineages 1 and 3, sequencing and analysis of M. tuberculosis whole genomes from Southern India highlight challenges of infection control and rapid diagnosis of resistant tuberculosis using current technologies. Further studies are needed to fully explore the complement of diversity and resistance determinants within endemic M. tuberculosis populations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial12

PubMed Central

Tukvadze, Nestan; Sanikidze, Ekaterina; Kipiani, Maia; Hebbar, Gautam; Easley, Kirk A; Shenvi, Neeta; Kempker, Russell R; Frediani, Jennifer K; Mirtskhulava, Veriko; Alvarez, Jessica A; Lomtadze, Nino; Vashakidze, Lamara; Hao, Li; Del Rio, Carlos; Tangpricha, Vin; Blumberg, Henry M; Ziegler, Thomas R

2015-01-01

Background: Tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), is a major global health problem. Individuals with tuberculosis disease commonly exhibit vitamin D deficiency, which may adversely affect immunity and the response to therapy. Objective: We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease. Design: The study was a double-blind, randomized, placebo-controlled, intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi, Georgia. Subjects were randomly assigned to receive oral vitamin D3 [50,000 IUs (1.25 mg) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk] or a placebo concomitant with standard first-line antituberculosis drugs. The primary outcome was the time for the conversion of a Mycobacterium tuberculosis (Mtb) sputum culture to negative. Results: Baseline characteristics between groups were similar. Most subjects (74%) were vitamin D deficient (plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/L). With vitamin D3, plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16. Adverse events and plasma calcium concentrations were similar between groups. In 192 subjects with culture-confirmed tuberculosis, an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [29 and 27 d, respectively; HR: 0.86; 95% CI: 0.63, 1.18; P = 0.33). Eight-week culture-conversion rates were also similar (84.0% and 82.1% for vitamin D3 and placebo, respectively; P = 0.99). Conclusion: A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort. This trial was registered at clinicaltrials.gov at NCT00918086. PMID:26399865

High-dose vitamin D3 in adults with pulmonary tuberculosis: a double-blind randomized controlled trial.

PubMed

Tukvadze, Nestan; Sanikidze, Ekaterina; Kipiani, Maia; Hebbar, Gautam; Easley, Kirk A; Shenvi, Neeta; Kempker, Russell R; Frediani, Jennifer K; Mirtskhulava, Veriko; Alvarez, Jessica A; Lomtadze, Nino; Vashakidze, Lamara; Hao, Li; Del Rio, Carlos; Tangpricha, Vin; Blumberg, Henry M; Ziegler, Thomas R

2015-11-01

Tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), is a major global health problem. Individuals with tuberculosis disease commonly exhibit vitamin D deficiency, which may adversely affect immunity and the response to therapy. We determined whether adjunctive high-dose vitamin D3 supplementation improves outcomes in individuals with pulmonary tuberculosis disease. The study was a double-blind, randomized, placebo-controlled, intent-to-treat trial in 199 individuals with pulmonary tuberculosis disease in Tbilisi, Georgia. Subjects were randomly assigned to receive oral vitamin D3 [50,000 IUs (1.25 mg) thrice weekly for 8 wk and 50,000 IU every other week for 8 wk] or a placebo concomitant with standard first-line antituberculosis drugs. The primary outcome was the time for the conversion of a Mycobacterium tuberculosis (Mtb) sputum culture to negative. Baseline characteristics between groups were similar. Most subjects (74%) were vitamin D deficient (plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/L). With vitamin D3, plasma 25(OH)D concentrations peaked at ∼250 nmol/L by 8 wk and decreased to ∼125 nmol/L at week 16. Adverse events and plasma calcium concentrations were similar between groups. In 192 subjects with culture-confirmed tuberculosis, an adjusted efficacy analysis showed similar median culture-conversion times between vitamin D3 and placebo groups [29 and 27 d, respectively; HR: 0.86; 95% CI: 0.63, 1.18; P = 0.33). Eight-week culture-conversion rates were also similar (84.0% and 82.1% for vitamin D3 and placebo, respectively; P = 0.99). A high-dose vitamin D3 regimen safely corrected vitamin D deficiency but did not improve the rate of sputum Mtb clearance over 16 wk in this pulmonary tuberculosis cohort. This trial was registered at clinicaltrials.gov at NCT00918086. © 2015 American Society for Nutrition.

Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection.

PubMed

Xu, Zheng Zhong; Chen, Xiang; Hu, Ting; Meng, Chuang; Wang, Xiao Bo; Rao, Yan; Zhang, Xiao Ming; Yin, Yue Lan; Pan, Zhi Ming; Jiao, Xin An

2016-01-01

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is currently the only vaccine available for preventing tuberculosis (TB), however, BCG has varying success in preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A) strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. Our results indicated that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, and the Ag85A peptide-MHC complexes on draining lymph node dendritic cells of C57BL/6 mice infected with rBCG::Ag85A were detectable 4 h post-infection. The C57BL/6 mice infected with this strain had stronger antigen-specific interferon-gamma (IFN-γ) responses and higher antibody titers than those immunized with BCG, and the protective experiments showed that rBCG::Ag85A can enhance protection against Mycobacterium tuberculosis (M. tuberculosis) H37Rv infection compared to the BCG vaccine alone. Our results demonstrate the potential of rBCG::Ag85A as a candidate vaccine against TB.

[Childhood tuberculosis].

PubMed

Hamzaoui, A

2015-01-01

Childhood TB is an indication of failing TB control in the community. It allows disease persistence in the population. Mortality and morbidity due to TB is high in children. Moreover, HIV co-infection and multidrug-resistant diseases are as frequent in children as in adults. Infection is more frequent in younger children. Disease risk after primary infection is greatest in infants younger than 2 years. In case of exposure, evidence of infection can be obtained using the tuberculin skin test (TST) or an interferon-gamma assay (IGRA). There is no evidence to support the use of IGRA over TST in young children. TB suspicion should be confirmed whenever possible, using new available tools, particularly in case of pulmonary and lymph node TB. Induced sputum, nasopharyngeal aspiration and fine needle aspiration biopsy provide a rapid and definitive diagnosis of mycobacterial infection in a large proportion of patients. Analysis of paediatric samples revealed higher sensitivity and specificity values of molecular techniques in comparison with the ones originated from adults. Children require higher drugs dosages than adults. Short courses of steroids are associated with TB treatment in case of respiratory distress, bronchoscopic desobstruction is proposed for severe airways involvement and antiretroviral therapy is mandatory in case of HIV infection. Post-exposure prophylaxis in children is a highly effective strategy to reduce the risk of TB disease. The optimal therapy for treatment of latent infection with a presumably multidrug-resistant Mycobacterium tuberculosis strain is currently not known. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Tuberculosis and the role of war in the modern era.

PubMed

Drobniewski, F A; Verlander, N Q

2000-12-01

Tuberculosis (TB) remains a major global health problem; historically, major wars have increased TB notifications. This study evaluated whether modern conflicts worldwide affected TB notifications between 1975 and 1995. Dates of conflicts were obtained and matched with national TB notification data reported to the World Health Organization. Overall notification rates were calculated pre and post conflict. Poisson regression analysis was applied to all conflicts with sufficient data for detailed trend analysis. Thirty-six conflicts were identified, for which 3-year population and notification data were obtained. Overall crude TB notification rates were 81.9 and 105.1/100,000 pre and post start of conflict in these countries. Sufficient data existed in 16 countries to apply Poisson regression analysis to model 5-year pre and post start of conflict trends. This analysis indicated that the risk of presenting with TB in any country 2.5 years after the outbreak of conflict relative to 2.5 years before the outbreak was 1.016 (95%CI 0.9435-1.095). The modelling suggested that in the modern era war may not significantly damage efforts to control TB in the long term. This might be due to the limited scale of most of these conflicts compared to the large-scale civilian disruption associated with 'world wars'. The management of TB should be considered in planning post-conflict refugee and reconstruction programmes.

PA-824 Kills Nonreplicating Mycobacterium tuberculosis by Intracellular NO Release

PubMed Central

Singh, Ramandeep; Manjunatha, Ujjini; Boshoff, Helena I. M.; Ha, Young Hwan; Niyomrattanakit, Pornwaratt; Ledwidge, Richard; Dowd, Cynthia S.; Lee, Ill Young; Kim, Pilho; Zhang, Liang; Kang, Sunhee; Keller, Thomas H.; Jiricek, Jan; Barry, Clifton E.

2009-01-01

Bicyclic nitroimidazoles, including PA-824, are exciting candidates for the treatment of tuberculosis. These prodrugs require intracellular activation for their biological function. We found that Rv3547 is a deazaflavin-dependent nitroreductase (Ddn) that converts PA-824 into three primary metabolites; the major one is the corresponding des-nitroimidazole (des-nitro). When derivatives of PA-824 were used, the amount of des-nitro metabolite formed was highly correlated with anaerobic killing of Mycobacterium tuberculosis (Mtb). Des-nitro metabolite formation generated reactive nitrogen species, including nitric oxide (NO), which are the major effectors of the anaerobic activity of these compounds. Furthermore, NO scavengers protected the bacilli from the lethal effects of the drug. Thus, these compounds may act as intracellular NO donors and could augment a killing mechanism intrinsic to the innate immune system. PMID:19039139

Protecting health care workers from tuberculosis: a 10-year experience.

PubMed

Welbel, Sharon F; French, Audrey L; Bush, Patricia; DeGuzman, Delia; Weinstein, Robert A

2009-10-01

Cook County Hospital (CCH) is an inner-city, large public hospital. Twenty-five percent of Chicago's tuberculosis (TB) cases are diagnosed at CCH. We wanted to review and analyze interventions implemented over a 10-year period at CCH to prevent TB infection in health care workers. We performed a retrospective review of interventions to prevent health care-associated tuberculosis. We collated and analyzed tuberculin skin test conversions in our employees for the same time period. From 1990 to 2002, we cared for over 1800 in-patients with tuberculosis. During 1992-1997, multiple interventions to eliminate health care-associated spread of tuberculosis were implemented. Tuberculin skin test conversions in our employees decreased markedly from January 1994 through December 2002. Two drops in tuberculin skin test conversion rates occurred: one after introduction of basic administrative and engineering controls and a second after we experienced a decrease in missed TB cases and the introduction of N-95 personal respirators with 1-time qualitative fit testing. Our annual health care worker skin test conversion rate fell significantly when our primary interventions were relatively simple administrative and engineering controls. Educating health care workers to promptly recognize patients with TB and placing exhaust fans to create negative-pressure respiratory isolation rooms were probably our 2 most potent infection control measures.

A comparative study of tuberculosis patients initiated on ART and receiving different models of TB-HIV care.

PubMed

Schulz, S A; Draper, H R; Naidoo, P

2013-12-01

Although health policy in South Africa calls for the integration of services, the effectiveness of different models of integration on patient outcomes has not been well demonstrated. To evaluate the outcomes of coinfected patients starting antiretroviral treatment (ART) in a tuberculosis (TB) hospital who received different models of ongoing care. This cohort study compared outcomes for 271 coinfected patients who started ART in a TB hospital in the Western Cape. After discharge, one group of patients received anti-tuberculosis treatment and ART from different providers, in the same or in different clinics (vertical care). The other group received anti-tuberculosis treatment and ART at the same visit from the same service provider (integrated care). Demographic and clinical data and TB and ART outcomes were compared. The vertical care model had more unfavourable outcomes for anti-tuberculosis treatment (28.7% vs. 5.9%, P < 0.001) and ART (30.1% vs. 7.4%, P < 0.001) than the integrated care model. The vertical care model showed no difference whether services were provided by two service providers in the same or in geographically separate primary health care clinics. Patient outcomes were better when TB and HIV care was received from the same service provider at the same visit.

Community-based outbreaks of tuberculosis.

PubMed

Raffalli, J; Sepkowitz, K A; Armstrong, D

1996-05-27

Numerous recent reports have detailed outbreaks of tuberculosis in hospitals and other congregate settings. The characteristics of such settings, including high concentrations of infectious patients and immunocompromised hosts, the potential for sustained daily contact for weeks and often months, and improper precautions taken for protection, make them well suited for tuberculosis transmission. However, community-based outbreaks, which are the source of much public concern, have not been reviewed since 1964, when 109 community outbreaks were examined. Since few of the characteristics of institutional settings are present in the community, the lessons learned may not be applicable to community-based outbreaks. Furthermore, recent studies with analysis by restriction fragment length polymorphisms have documented unexpectedly high rates of primary disease in certain urban communities, suggesting that our understanding of community-based transmission may be incomplete. We reviewed all reported community-based outbreaks of tuberculosis occurring in the last 30 years to assess the basis of our current understanding of community-based transmission. More than 70 outbreaks were identified, with schools being the most common site. In most, a delay in diagnosis, sustained contact with the index case, inadequate ventilation, or overcrowding was contributory. We conclude that community-based outbreaks of tuberculosis continue to occur and that well-established risks contribute to most outbreaks. Many outbreaks can be prevented or limited by attention to basic infection control principles.

The impact of nutritional deficit on mortality of in-patients with pulmonary tuberculosis.

PubMed

Kim, H-J; Lee, C-H; Shin, S; Lee, J H; Kim, Y W; Chung, H S; Han, S K; Shim, Y-S; Kim, D K

2010-01-01

A metropolitan governmental medical centre, Seoul, Republic of Korea. To elucidate the impact of the nutritional deficit assessed by the Nutritional Risk Score (NRS) on the outcomes of in-patients with pulmonary tuberculosis (PTB). All hospitalised patients with microbiologically confirmed PTB were enrolled. A four-point NRS included low body mass index (<18.5 kg/m(2)), hypoalbuminaemia (<30.0 g/l), hypocholesterolaemia (<2.33 mmol/l) and severe lymphocytopaenia (<7 x 10(5) cells/l). The primary outcome was overall in-hospital mortality. The degree of radiographical resolution after anti-tuberculosis treatment was also evaluated. In a total of 156 patients, the male to female ratio was 1.6:1. The overall mortality was 13.5% and tuberculosis-specific fatality was 3.9%. Predisposing factors and high NRS (> or = 3 points) were independent risk factors for in-hospital death after adjusting for the severity of PTB. High NRS (OR = 16.8, P < 0.001) and predisposing factors (OR = 5.4, P = 0.032) were independent risk factors for 30-day survival. The NRS was not associated with radiographic improvement. Regardless of disease severity, the high NRS was a significant negative predictor among in-patients with PTB; this finding should therefore be considered in the management of PTB despite the current era of effective anti-tuberculosis chemotherapy.

Effect of Lagerstroemia tomentosa and Diospyros virginiana methanolic extracts on different drug-resistant strains of Mycobacterium tuberculosis

PubMed Central

Esfahani, B. Nasr; Hozoorbakhsh, F.; Rashed, Kh.; Havaei, S.A.; Heidari, K.; Moghim, Sh.

2014-01-01

Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis. The increasing incidence of multi drug resistance tuberculosis (MDR-TB) and extensively drug resistance tuberculosis (XDR-TB) worldwide highlighted the urgent need to search for alternative antimycobacterial agents. More and more people in developing countries utilize traditional medicine for their major primary health care needs. It has been determined that pharmaceutical plant, Lagerstroemia tomentosa and Diospyros virginiana, possesses some antibacterial effect. In this study, the antimycobacterial effects of L. tomentosa and D. virginiana methanolic extracts on sensitive and resistant isolates of MTB were examined. Leaf methanolic extract was prepared using methanol 70%. Sensitivity and resistance of isolates was determined by proportion method. The effects of two different methonolic extract concentrations (20 and 40 μg/ml) of the plants were examined against 6 sensitive and resistant strains of MTB with different patterns of drug resistance. MTB H37Rv (ATCC 27294) was set as control in all culturing and sensitivity testing processes. The results showed that L. tomentosa and D. virginiana methanolic extracts had weak inhibitory effect on different strains of MTB. The highest percentage of inhibition for L. tomentosa and D. virginiana was observed 38% and 33.3%, respectively. PMID:25657789

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

PubMed Central

Walker, Naomi F.; Clark, Simon O.; Oni, Tolu; Andreu, Nuria; Tezera, Liku; Singh, Shivani; Saraiva, Luísa; Pedersen, Bernadette; Kelly, Dominic L.; Tree, Julia A.; D'Armiento, Jeanine M.; Meintjes, Graeme; Mauri, Francesco A.; Williams, Ann; Wilkinson, Robert J.; Friedland, Jon S.

2012-01-01

Rationale: Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage. Objectives: To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology. Methods: Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. Measurements and Main Results: HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation. Conclusions: HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB. PMID:22345579

[The results of an active screening program for tuberculosis in immigrants from the Maghreb: acceptability and adherence].

PubMed

Rivas-Clemente, F P; Nácher-Conches, M; Corrillero-Martín, J; Vélez-Reyes, S; Huerta-Galindo, L

1999-10-31

To assess acceptability and adherence to a tuberculosis screening programme (TSP) in Maghrebi immigrants (MI). A descriptive crossover study. Primary health care service. MI residing in a periurban health district. All people who attended clinic for consultation at a primary care center were systematically recommended to be screened for tuberculosis. Individuals accomplished a questionnaire in arabic (with interpreter assistance) and were subjected to tuberculosis infection/illness screening tests till they were assigned one of the definitive diagnostic classes of the American Thoracic Society. 219 individuals were offered the TSP (sex ratio 6.2:1). 166 individuals (76.1%) accepted the test and kept their first appointment: 147 males (78.2%) versus 19 females (63.3%); difference in acceptance by gender was not significant (chi 2 = 3.14; p = 0.07). Fourteen individuals did not complete the study (8.6%): one did not attend clinic for Mantoux reading, four did not have the chest X-ray, three did not present themselves on their Mantoux reading, nor did they have the chest X-ray and, six did not deliver sputum samples (11.1% of the required samples). Six cases of TB were diagnosed. Given the special features of the MI (communication difficulties, illegal status, no fixed abode ...) acceptance and adherence to TSP are considered to be high. The diagnostic effectiveness, though considerable, was affected by the high number of individuals which did not deliver sputum samples. TSP directed to MI must have a specific design in order to facilitate acceptance and adherence.

A tuberculin skin test survey among Ghanaian school children.

PubMed

Addo, Kennedy Kwasi; van den Hof, Susan; Mensah, Gloria Ivy; Hesse, Adukwei; Bonsu, Christian; Koram, Kwadwo Ansah; Afutu, Felix Kwami; Bonsu, Frank Adae

2010-01-26

Ghana has not conducted a national tuberculin survey or tuberculosis prevalence survey since the establishment of the National Tuberculosis Control Programme. The primary objective of this study was therefore to determine the prevalence of tuberculin skin sensitivity in Ghanaian school children aged 6-10 years in 8 out of 10 regions of Ghana between 2004 and 2006. Tuberculin survey was conducted in 179 primary schools from 21 districts in 8 regions. Schools were purposively selected so as to reflect the proportion of affluent private and free tuition public schools as well as the proportion of small and large schools. Of the 24,778 children registered for the survey, 23,600 (95.2%) were tested of which 21,861 (92.6%) were available for reading. The age distribution showed an increase in numbers of children towards older age: 11% of the children were 6 years and 25%, 10 years. Females were 52.5% and males 47.5%. The proportion of girls was higher in all age groups (range 51.4% to 54.0%, p < 0.001). BCG scar was visible in 89.3% of the children. The percentage of children with a BCG scar differed by district and by age. The percentage of children with a BCG scar decreased with increasing age in all districts, reflecting increasing BCG vaccination coverage in Ghana in the last ten years. The risk of tuberculosis infection was low in the northern savannah zones compared to the southern coastal zones. Using a cut-off of 15 mm, the prevalence of infection ranged from 0.0% to 5.4% and the Annual Risks of Tuberculosis Infection 0.0% to 0.6%. There was an increase in the proportion of infected children after the age of 7 years. Children attending low and middle-class schools had a higher risk of infection than children attending upper-class schools. Tuberculosis infection is still a public health problem in Ghana and to monitor the trend, the survey needs to be repeated at 5 years interval.

Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial.

PubMed

Daley, Peter; Jagannathan, Vijayakumar; John, K R; Sarojini, Joy; Latha, Asha; Vieth, Reinhold; Suzana, Shirly; Jeyaseelan, Lakshmanan; Christopher, Devasahayam J; Smieja, Marek; Mathai, Dilip

2015-05-01

Vitamin D has immunomodulatory effects that might aid clearance of mycobacterial infection. We aimed to assess whether vitamin D supplementation would reduce time to sputum culture conversion in patients with active tuberculosis. We did this randomised, double-blind, placebo-controlled, superiority trial at 13 sites in India. Treatment-naive patients who were sputum-smear positive, HIV negative, and had pulmonary tuberculosis were randomly assigned (1:1), with centrally labelled, serially numbered bottles, to receive standard active tuberculosis treatment with either supplemental high-dose oral vitamin D3 (four doses of 2·5 mg at weeks 0, 2, 4, and 6) or placebo. Neither the patients nor the clinical and laboratory investigators and personnel were aware of treatment assignment. The primary efficacy outcome was time to sputum culture conversion. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00366470. Between Jan 20, 2010, and Aug 23, 2011, we randomly assigned 247 participants to the vitamin D group (n=121) or the placebo group (n=126), of whom 211 participants (n=101 and n=110, respectively) were included in the primary efficacy analysis. Median time to culture conversion in the vitamin D group was 43·0 days (95% CI 33·3-52·8) versus 42·0 days (33·9-50·1) in the placebo group (log-rank p=0·95). Three (2%) patients died in the vitamin D group and one (1%) patient died in the placebo group; no death was considered attributable to the study intervention. No patients had hypercalcaemia. Our findings show that vitamin D supplementation did not reduce time to sputum culture conversion. Further studies should investigate the role of vitamin D in prevention or reactivation of tuberculosis infection. Dalhousie University and Infectious Diseases Training and Research Centre. Copyright © 2015 Elsevier Ltd. All rights reserved.

Factors Associated with Length of Hospital Stay among HIV Positive and HIV Negative Patients with Tuberculosis in Brazil

PubMed Central

Gonçalves, Maria Jacirema Ferreira; Ferreira, Alaidistania A.

2013-01-01

Objective Identify and analyze the factors associated to length of hospital stay among HIV positive and HIV negative patients with tuberculosis in Manaus city, state of Amazonas, Brazil, in 2010. Methods Epidemiological study with primary data obtained from monitoring of hospitalized patients with tuberculosis in Manaus. Data were collected by interviewing patients and analyzing medical records, according to the following study variables age, sex, co-morbidities, education, race, income, lifestyle, history of previous treatment or hospitalization due to tuberculosis, treatment regimen, adverse reactions, smear test, clinical form, type of discharge, and length of hospital stay. The associated factors were identified through chi-square or t-Student test at a 5% significance level. Results Income from 1 to 3 minimum wages (P = 0.028), pulmonary tuberculosis form (P = 0.011), negative smear test or no information in this regard (P = 0.014), initial 6-month treatment scheme (P = 0.029), and adverse drug reactions (P = 0.021) were associated to prolonged hospital stay in HIV positive patients. Conclusion We found out that although there were no significant differences in the length of hospital stay in HIV positive patients, all factors significantly associated to prolonged hospital stay occurred in this group of patients. This finding corroborates other studies indicating the severity of tuberculosis in HIV patients, which may also contribute to lengthen their hospital stay. PMID:23593227

Pulmonary tuberculosis treatment regimen recommended by the Brazilian National Ministry of Health: predictors of treatment noncompliance in the city of Porto Alegre, Brazil.

PubMed

Campani, Simone Teresinha Aloise; Moreira, José da Silva; Tietbohel, Carlos Nunes

2011-01-01

To determine the predictors of noncompliance with the pulmonary tuberculosis treatment regimen recommended by the Brazilian National Ministry of Health, in previously treatment-naïve patients with active tuberculosis treated in the city of Porto Alegre, Brazil. This was a case-control study involving six referral primary health care clinics for tuberculosis in Porto Alegre. We reviewed the medical charts of all previously treatment-naïve patients with active pulmonary tuberculosis who were noncompliant with the treatment between 2004 and 2006. Those were paired with other patients having similar characteristics and having been cured. We conducted univariate and multivariate analyses. Of the 2,098 patients included, 218 (10.4%) became noncompliant with the treatment. In the multivariate analysis, the factors most strongly associated with treatment noncompliance were being an alcoholic (with or without concomitant use of illicit drugs), being HIV-infected, not residing with family members, and having a low level of education. In the univariate analysis, treatment noncompliance was also significantly associated with being younger and with being non-White. Gender was not significantly associated with treatment noncompliance; nor was the occurrence of adverse effects of the drugs included in the regimen. In the population studied, being an alcoholic, being HIV-infected, and not residing with family members were the major predictors of noncompliance with treatment for pulmonary tuberculosis among previously treatment-naïve patients.

[Epidemiology of resistance to antituberculosis drugs in Mycobacterium tuberculosis complex strains isolated from adenopathies in Djibouti. Prospective study carried out in 1999].

PubMed

Koeck, J L; Bernatas, J J; Gerome, P; Fabre, M; Houmed, A; Herve, V; Teyssou, R

2002-01-01

Tuberculosis is a major cause of death in the Republic of Djibouti. Tuberculous lymphadenitis represents about 25% of the clinical forms of tuberculosis in this country. Between January 1999 and April 1999, 196 lymph node specimens were consecutively collected from 153 patients living in Djibouti. Testing of susceptibility to the major anti-tuberculosis drugs was performed by the proportion method. Growth of Mycobacterium tuberculosis complex strains was obtained from specimens of 85 patients including 9 with prior treatment. Strains were identified as Mycobacterium tuberculosis in 78 cases, Mycobacterium canetti in 3, Mycobacterium africanum in 3, and Mycobacterium bovis in 1. Prevalence of HIV infection was 15%. Assessment of primary resistance demonstrated that the overall resistance rate, i.e., resistance to 1 or more drugs, was 18 (21.2%). Results showed resistance to isoniazid (H) in 6 cases (7.1%), rifampicin (R) in 3 (3.5%), ethambutol (E) in 1 (1.2%), streptomycin (S) in 13 (15.3%) and pyrazinamide (Z) in 1 (1.2%). Multidrug resistance (MDR) was found in 2 cases (2.4%). Assessment of acquired resistance demonstrated resistance to H in 4 cases (44%), R in 2 (22%), S in 2 (22%), E in 0, Z in 0 and MDR in 1 (11%). These findings were not significantly different from data obtained from sputum samples analysed between 1997 and 2000 or from those described in a study conducted in 1985.

Burden of Multidrug Resistant Mycobacterium tuberculosis Among New Cases in Al-Madinah Al-Monawarah, Saudi Arabia.

PubMed

Elhassan, Mogahid M; Hemeg, Hassan A; Elmekki, Miskelyemen A; Turkistani, Khalid A; Abdul-Aziz, Ahmed A

2017-01-01

The pattern of Mycobacterium tuberculosis susceptibility to first line drugs and multidrug resistance in Al-Madinah Al-Munawarah, a seasonally overcrowded are during Hajj and Omrah, is not well studied. This study aimed to investigate anti-tuberculosis drug resistance and its distribution among new cases in Al-Madinah Al-Monawarah. Study subjects included 622 patients with first time confirmed TB referred to the central tuberculosis laboratory in Al-Madinah between January 2012 and December 2014. Out of the 622 isolates, 99 (15.9%) were Mycobacteria Other Than Tuberculosis (MOTTS) and 25 (4.0%), three of which (12%) were children under five years of age, revealed multidrug resistance (MDR). Monoresistance to isoniazid (H) was (1.8%), to rifampin (R) was (1.4%), to streptomycin (S) was (1.9 %) to ethambutol (E) was (1.1 %) and to pyrazinamide (Z) was (2.1%). Being among the new cases, multidrug resistant tuberculosis (MDR TB) is supposed to be caused by strains which are originally multidrug resistant. Neither nationality nor gender was found to be associated with MDR TB. Since 12% of MDR cases were among children, a probability of primary infection with MDR strains is to be considered. Moreover, mass gathering during Hajj and Omrah seasons does not seem to increase the burden of MDR in the region. However, further investigation is needed to molecularly characterize MDR isolates and their phylogenetics and geographical origin. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The role of B cells and humoral immunity in Mycobacterium tuberculosis infection.

PubMed

Chan, John; Mehta, Simren; Bharrhan, Sushma; Chen, Yong; Achkar, Jacqueline M; Casadevall, Arturo; Flynn, JoAnne

2014-12-01

Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of B cells and humoral immunity in Mycobacterium tuberculosis infection

PubMed Central

Chan, John; Mehta, Simren; Bharrhan, Sushma; Chen, Yong; Achkar, Jacqueline M.; Casadevall, Arturo; Flynn, JoAnne

2014-01-01

Mycobacterium tuberculosis remains a major public health burden. It is generally thought that while B cell- and antibody-mediated immunity plays an important role in host defense against extracellular pathogens, the primary control of intracellular microbes derives from cellular immune mechanisms. Studies on the immune regulatory mechanisms during infection with M. tuberculosis, a facultative intracellular organism, has established the importance of cell-mediated immunity in host defense during tuberculous infection. Emerging evidence suggest a role for B cell and humoral immunity in the control of intracellular pathogens, including obligatory species, through interactions with the cell-mediated immune compartment. Recent studies have shown that B cells and antibodies can significantly impact on the development of immune responses to the tubercle bacillus. In this review, we present experimental evidence supporting the notion that the importance of humoral and cellular immunity in host defense may not be entirely determined by the niche of the pathogen. A comprehensive approach that examines both humoral and cellular immunity could lead to better understanding of the immune response to M. tuberculosis. PMID:25458990

Tuberculous Otitis Media Leading to Sequentialib Bilateral Facial Nerve Paralysis.

PubMed

Gupta, Nitin; Dass, Arjun; Goel, Neha; Tiwari, Sandeep

2015-05-01

Tuberculous otitis media (TOM) is an uncommon, insidious, and frequently misdiagnosed form of tuberculosis (TB). In particular, TOM is usually secondary to direct transmission from adjacent organs, while the primary form has been rarely reported. The main aim of treatment is to start the patient on an antitubercular regime and early surgical intervention to decompress the facial nerve if involved. The case report of a twenty year-old male with bilateral tuberculous otitis media, who presented himself with fever followed by sequential bilateral facial nerve paralysis, bilateral profound hearing loss, and abdominal tuberculosis leading to intestinal perforation, is presented. To the best available knowledge and after researching literature, no such case depicting the extensive otological complications of tuberculosis has been reported till date. Tuberculosis of the ear is a rare entity and in most cases the clinical features resemble that of chronic otitis media. The diagnosis is often delayed due to varied clinical presentations and this can lead to irreversible complications. Early diagnosis is essential for prompt administration of antitubercular therapy and to prevent complications.

Tuberculous Otitis Media Leading to Sequentialib Bilateral Facial Nerve Paralysis

PubMed Central

Gupta, Nitin; Dass, Arjun; Goel, Neha; Tiwari, Sandeep

2015-01-01

Introduction: Tuberculous otitis media (TOM) is an uncommon, insidious, and frequently misdiagnosed form of tuberculosis (TB). In particular, TOM is usually secondary to direct transmission from adjacent organs, while the primary form has been rarely reported. The main aim of treatment is to start the patient on an antitubercular regime and early surgical intervention to decompress the facial nerve if involved. Case Report: The case report of a twenty year-old male with bilateral tuberculous otitis media, who presented himself with fever followed by sequential bilateral facial nerve paralysis, bilateral profound hearing loss, and abdominal tuberculosis leading to intestinal perforation, is presented. To the best available knowledge and after researching literature, no such case depicting the extensive otological complications of tuberculosis has been reported till date. Conclusion: Tuberculosis of the ear is a rare entity and in most cases the clinical features resemble that of chronic otitis media. The diagnosis is often delayed due to varied clinical presentations and this can lead to irreversible complications. Early diagnosis is essential for prompt administration of antitubercular therapy and to prevent complications. PMID:26082906

Mycobacterium tuberculosis exploits the formation of new blood vessels for its dissemination

PubMed Central

Polena, Helena; Boudou, Frédéric; Tilleul, Sylvain; Dubois-Colas, Nicolas; Lecointe, Cécile; Rakotosamimanana, Niaina; Pelizzola, Mattia; Andriamandimby, Soa Fy; Raharimanga, Vaomalala; Charles, Patricia; Herrmann, Jean-Louis; Ricciardi-Castagnoli, Paola; Rasolofo, Voahangy; Gicquel, Brigitte; Tailleux, Ludovic

2016-01-01

The mechanisms by which the airborne pathogen Mycobacterium tuberculosis spreads within the lung and leaves its primary niche to colonize other organs, thus inducing extrapulmonary forms of tuberculosis (TB) in humans, remains poorly understood. Herein, we used a transcriptomic approach to investigate the host cell gene expression profile in M. tuberculosis–infected human macrophages (ΜΦ). We identified 33 genes, encoding proteins involved in angiogenesis, for which the expression was significantly modified during infection, and we show that the potent angiogenic factor VEGF is secreted by M. tuberculosis-infected ΜΦ, in an RD1-dependent manner. In vivo these factors promote the formation of blood vessels in murine models of the disease. Inhibiting angiogenesis, via VEGF inactivation, abolished mycobacterial spread from the infection site. In accordance with our in vitro and in vivo results, we show that the level of VEGF in TB patients is elevated and that endothelial progenitor cells are mobilized from the bone marrow. These results strongly strengthen the most recent data suggesting that mycobacteria take advantage of the formation of new blood vessels to disseminate. PMID:27616470

Influence of diabetes mellitus on immunity to human tuberculosis.

PubMed

Kumar Nathella, Pavan; Babu, Subash

2017-09-01

Type 2 diabetes mellitus(DM) is a major risk factor for the development of active pulmonary tuberculosis (TB), with development of DM pandemic in countries where TB is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility. One possible mechanism is that an impaired immune response in patients with DM facilitates either primary infection with Mycobacterium tuberculosis or reactivation of latent TB. Diabetes is associated with immune dysfunction and alterations in the components of the immune system, including altered levels of specific cytokines and chemokines. Some effects of DM on adaptive immunity that are potentially relevant to TB defence have been identified in humans. In this review, we summarize current findings regarding the alterations in the innate and adaptive immune responses and immunological mechanisms of susceptibility of patients with DM to M. tuberculosis infection and disease. © 2017 John Wiley & Sons Ltd.

Hematemesis: Unusual presentation of isolated gastric tuberculosis.

PubMed

Nasa, Mukesh; Kumar, Arvind; Phadke, Aniruddha; Sawant, Prabha

2016-01-01

A 25-year-old male presented with hematemesis, epigastric pain, and melena. He had dyspepsia with significant weight loss for 3 months period. On clinical examination, he was pale with no organomegaly or lymphadenopathy. The X-ray chest was normal, and ultrasound abdomen was normal. Upper GI endoscopy revealed nodularity and ulceration along proximal part of lesser curvature of the stomach. CT scan abdomen showed thickening of lesser curvature just below gastro-esophageal junction. The biopsies were negative for malignancy. Repeat upper GI endoscopy showed a nonhealing ulcer, on repeat well biopsies taken from the base of ulcer primary gastric tuberculosis was diagnosed. It showed many epithelioid cell granulomas and multinucleated giant cells with caseous necrosis on histology. Acid-fast bacilli on Zeil Neelsen staining and TB PCR were positive for Mycobacterium tuberculosis. He was put on four-drug anti-tuberculous treatment. On follow-up, the patient gradually improved and regained weight. Repeat upper GI endoscopy done after 8 weeks showed healing of the ulcer with decrease in nodularity. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

[Multidrug-Resistant Tuberculosis by Strains of Beijing Family, in Patients from Lisbon, Portugal: Preliminary Report].

PubMed

Maltez, Fernando; Martins, Teresa; Póvoas, Diana; Cabo, João; Peres, Helena; Antunes, Francisco; Perdigão, João; Portugal, Isabel

2017-03-31

Beijing family strains of Mycobacterium tuberculosis are associated with multidrug-resistance. Although strains of the Lisboa family are the most common among multidrug-resistant and extensively drug-resistant patients in the region, several studies have reported the presence of the Beijing family. However, the features of patients from whom they were isolated, are not yet known. Retrospective study involving 104 multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, from the same number of patients, isolated and genotyped between 1993 and 2015 in Lisbon. We assessed the prevalence of strains of both families and the epidemiologic and clinical features of those infected with Beijing family strains. Seventy-four strains (71.2%) belonged to the Lisboa family, 25 (24.0%) showed a unique genotypic pattern and five (4.8%) belonged to the Beijing family, the latter identified after 2009. Those infected with Beijing family strains were angolan (n = 1), ukrainian (n = 2) and portuguese (n = 2), mainly young-aged and, four of five immunocompetent and with no past history of tuberculosis. All had multidrug-resistant tuberculosis. We did not find any distinctive clinical or radiological features, neither a predominant resistance pattern. Cure rate was high (four patients). Although the number of infected patients with Beijing strains was small, it suggests an important proportion of primary tuberculosis, a potential for transmission in the community but also a better clinical outcome when compared to other reported strains, such as W-Beijing and Lisboa. Although Lisboa family strains account for most of the multidrug and extensively drug-resistant tuberculosis cases in Lisbon area, Beijing strains are transmitted in the city and might change the local characteristics of the epidemics.

Three months of rifapentine and isoniazid for latent tuberculosis infection.

PubMed

Sterling, Timothy R; Villarino, M Elsa; Borisov, Andrey S; Shang, Nong; Gordin, Fred; Bliven-Sizemore, Erin; Hackman, Judith; Hamilton, Carol Dukes; Menzies, Dick; Kerrigan, Amy; Weis, Stephen E; Weiner, Marc; Wing, Diane; Conde, Marcus B; Bozeman, Lorna; Horsburgh, C Robert; Chaisson, Richard E

2011-12-08

Treatment of latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control and elimination. The current standard regimen of isoniazid for 9 months is efficacious but is limited by toxicity and low rates of treatment completion. We conducted an open-label, randomized noninferiority trial comparing 3 months of directly observed once-weekly therapy with rifapentine (900 mg) plus isoniazid (900 mg) (combination-therapy group) with 9 months of self-administered daily isoniazid (300 mg) (isoniazid-only group) in subjects at high risk for tuberculosis. Subjects were enrolled from the United States, Canada, Brazil, and Spain and followed for 33 months. The primary end point was confirmed tuberculosis, and the noninferiority margin was 0.75%. In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P=0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001). The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.).

[Genome instability in pulmonary tuberculosis before and after treatment].

PubMed

Dzhokhadze, T A; Buadze, T Zh; Rubanov, K Dzh; Kiriia, N A; Lezhava, T A

2013-11-01

Pulmonary tuberculosis is classified as a disease with a genetic predisposition, and therefore, as with other pathologies related to this group of diseases, by pulmonary tuberculosis, special importance is given to finding those markers that enable early identification of risk groups, such as skrinnig in general population and relatives of patients with tuberculosis, which in turn can provide the basis for preventive measures. One of this markers is the level of genome stability. The aim of this study was a comparative evaluation of the functional parameters of the genome variability in patients with sensitive form of pulmonary tuberculosis before and after treatment, and the possibility of its correction with anti-stress peptide bioregulator - epitalon. The studies were conducted using short-term mitoge -stimulated cell cultures of TB patients, before and after treatment. As an indicator of genome stability has been studied the frequency of structural and numerical chromosome aberrations and fragile sites. It is shown, that in intact cultures from patients with pulmonary tuberculosis, before treatment was significantly higher level of frequency of cells with structural chromosome aberrations, that still retained after the treatment. As for epithalon, it appears that was shown a pronounced protective effect after treatment, on the test of chromosome aberrations, by reducing both overall mean frequency aberrant cells and indicators for all individuals. In the study of fragility of chromosomes in patients with primary tuberculosis was found, that in intact cultures, the proportion of cells with chromosomal fragile sites was higher than in control group of healthy individuals, befor and after treatment. High frequency of chromosome fragility persisted by treatment with peptide bioregulator in both cases - before and after treatment. It is suggested that the identified patterns can be correlated with a high incidence of re- TB.

Macrophage defense mechanisms against intracellular bacteria

PubMed Central

Weiss, Günter; Schaible, Ulrich E

2015-01-01

Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

A live attenuated BCG vaccine overexpressing multistage antigens Ag85B and HspX provides superior protection against Mycobacterium tuberculosis infection.

PubMed

Yuan, Xuefeng; Teng, Xindong; Jing, Yukai; Ma, Jilei; Tian, Maopeng; Yu, Qi; Zhou, Lei; Wang, Ruibo; Wang, Weihua; Li, Li; Fan, Xionglin

2015-12-01

Tuberculosis (TB) remains one of the most menacing infectious diseases, although attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine has been widely used to protect children against primary TB. There are increasing evidences that rapid growing and dormant Mycobacterium tuberculosis (M. tuberculosis) coexist in vivo after infection. However, BCG vaccine only elicits cell-mediated immune responses to secretory antigens expressed by rapid growing pathogen. BCG vaccine is thus unable to thwart the reactivation of latent tuberculosis infection (LTBI), and its protection wanes over age after neonatal immunization. In order to extend its ability for a durable protection, a novel recombinant BCG (rBCG) strain, named rBCG::XB, was constructed by overexpressing immunodominant multistage antigens of Ag85B and HspX, which are expressed by both rapid replicating and dormant M. tuberculosis. Long-term protective effect and immunogenicity of rBCG::XB were compared with the parental BCG in vaccinated C57BL/6 mice. Our results demonstrated that rBCG::XB provided the stronger and long-lasting protection against M. tuberculosis H37Rv intranasal infection than BCG. The rBCG::XB not only elicited the more durable multistage antigen-specific CD4(+)Th1-biased immune responses and specific polyfunctional CD4(+)T cells but also augmented the CD8(+) CTL effects against Ag85B in vivo. In particular, higher levels of CD4(+) TEM and CD8(+) TCM cells, dominated by IL2(+) CD4(+) and CD8(+) TCM cells, were obtained in the spleen of rBCG::XB vaccinated mice. Therefore, our findings indicate that rBCG::XB is a promising candidate to improve the efficacy of BCG.

Feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing for tuberculosis in primary-care settings in Africa: a multicentre, randomised, controlled trial.

PubMed

Theron, Grant; Zijenah, Lynn; Chanda, Duncan; Clowes, Petra; Rachow, Andrea; Lesosky, Maia; Bara, Wilbert; Mungofa, Stanley; Pai, Madhukar; Hoelscher, Michael; Dowdy, David; Pym, Alex; Mwaba, Peter; Mason, Peter; Peter, Jonny; Dheda, Keertan

2014-02-01

The Xpert MTB/RIF test for tuberculosis is being rolled out in many countries, but evidence is lacking regarding its implementation outside laboratories, ability to inform same-day treatment decisions at the point of care, and clinical effect on tuberculosis-related morbidity. We aimed to assess the feasibility, accuracy, and clinical effect of point-of-care Xpert MTB/RIF testing at primary-care health-care facilities in southern Africa. In this pragmatic, randomised, parallel-group, multicentre trial, we recruited adults with symptoms suggestive of active tuberculosis from five primary-care health-care facilities in South Africa, Zimbabwe, Zambia, and Tanzania. Eligible patients were randomly assigned using pregenerated tables to nurse-performed Xpert MTB/RIF at the clinic or sputum smear microscopy. Participants with a negative test result were empirically managed according to local WHO-compliant guidelines. Our primary outcome was tuberculosis-related morbidity (measured with the TBscore and Karnofsky performance score [KPS]) in culture-positive patients who had begun anti-tuberculosis treatment, measured at 2 months and 6 months after randomisation, analysed by intention to treat. This trial is registered with Clinicaltrials.gov, number NCT01554384. Between April 12, 2011, and March 30, 2012, we randomly assigned 758 patients to smear microscopy (182 culture positive) and 744 to Xpert MTB/RIF (185 culture positive). Median TBscore in culture-positive patients did not differ between groups at 2 months (2 [IQR 0-3] in the smear microscopy group vs 2 [0·25-3] in the MTB/RIF group; p=0·85) or 6 months (1 [0-3] vs 1 [0-3]; p=0·35), nor did median KPS at 2 months (80 [70-90] vs 90 [80-90]; p=0·23) or 6 months (100 [90-100] vs 100 [90-100]; p=0·85). Point-of-care MTB/RIF had higher sensitivity than microscopy (154 [83%] of 185 vs 91 [50%] of 182; p=0·0001) but similar specificity (517 [95%] 544 vs 540 [96%] of 560; p=0·25), and had similar sensitivity to laboratory-based MTB/RIF (292 [83%] of 351; p=0·99) but higher specificity (952 [92%] of 1037; p=0·0173). 34 (5%) of 744 tests with point-of-care MTB/RIF and 82 (6%) of 1411 with laboratory-based MTB/RIF failed (p=0·22). Compared with the microscopy group, more patients in the MTB/RIF group had a same-day diagnosis (178 [24%] of 744 vs 99 [13%] of 758; p<0·0001) and same-day treatment initiation (168 [23%] of 744 vs 115 [15%] of 758; p=0·0002). Although, by end of the study, more culture-positive patients in the MTB/RIF group were on treatment due to reduced dropout (15 [8%] of 185 in the MTB/RIF group did not receive treatment vs 28 [15%] of 182 in the microscopy group; p=0·0302), the proportions of all patients on treatment in each group by day 56 were similar (320 [43%] of 744 in the MTB/RIF group vs 317 [42%] of 758 in the microscopy group; p=0·6408). Xpert MTB/RIF can be accurately administered by a nurse in primary-care clinics, resulting in more patients starting same-day treatment, more culture-positive patients starting therapy, and a shorter time to treatment. However, the benefits did not translate into lower tuberculosis-related morbidity, partly because of high levels of empirical-evidence-based treatment in smear-negative patients. European and Developing Countries Clinical Trials Partnership, National Research Foundation, and Claude Leon Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Laparoscopic Reconstruction in Post-Tubercular Urinary Tract Strictures: Technical Challenges.

PubMed

Ghosh, Bastab; Sridhar, Kartik; Pal, Dilip Kumar

2017-11-01

Genitourinary tuberculosis still continues to plague developing countries and is a significant cause of morbidity as well as mortality in the developing world. At present, nearly 55% of the patients of genitourinary tuberculosis (GUTB) need surgical management. Owing to the presence of dense adhesions and loss of normal anatomical planes, GUTB was considered to be a contraindication to laparoscopic surgery. However, recent literature shows laparoscopy to be feasible in GUTB. Our study aimed at identifying the challenges in laparoscopic urinary tract reconstructive surgery in genitourinary tuberculosis-related urinary tract obstruction. The details of 6 patients who underwent different types of laparoscopic reconstructive surgery for genitourinary tuberculosis-related urinary tract obstruction from January 2014 to December 2015 were reviewed. Baseline characteristics, indications of surgery, type of surgery, operative duration, blood loss, and follow-up details were noted. All patients received antitubercular treatment before surgery as per the direct observed treatment short-course regimen followed in our country. We performed one bilateral laparoscopic pyeloplasty, one unilateral laparoscopic pyeloplasty, two laparoscopic ureteroneocystostomies, and two ureteroureterostomies. Difficulty was encountered during dissection owing to the presence of adhesions, but conversion to open surgery was not done in five cases. Dense adhesions adjacent to the common iliac vessels necessitated conversion to open surgery in one of the ureteroureterostomies. Stenting was done in all the patients. All patients had uneventful postoperative recovery. Functional imaging following stent removal showed unobstructed tracer flow, showing successful operative outcome. Our study showed that laparoscopic reconstructive surgery is feasible in genitourinary tuberculosis despite the presence of adhesions that may pose a challenge to dissection. This is in contrast to the previous studies which conclude that genitourinary tuberculosis is a relative contraindication to laparoscopic surgery.

Direct detection of Mycobacterium tuberculosis complex in bovine and bubaline tissues through nested-PCR.

PubMed

Araújo, Cristina P; Osório, Ana Luiza A R; Jorge, Klaudia S G; Ramos, Carlos A N; Souza Filho, Antonio F; Vidal, Carlos E S; Vargas, Agueda P C; Roxo, Eliana; Rocha, Adalgiza S; Suffys, Philip N; Fonseca, Antônio A; Silva, Marcio R; Barbosa Neto, José D; Cerqueira, Valíria D; Araújo, Flábio R

2014-01-01

Post-mortem bacterial culture and specific biochemical tests are currently performed to characterize the etiologic agent of bovine tuberculosis. Cultures take up to 90 days to develop. A diagnosis by molecular tests such as PCR can provide fast and reliable results while significantly decreasing the time of confirmation. In the present study, a nested-PCR system, targeting rv2807, with conventional PCR followed by real-time PCR, was developed to detect Mycobacterium tuberculosis complex (MTC) organisms directly from bovine and bubaline tissue homogenates. The sensitivity and specificity of the reactions were assessed with DNA samples extracted from tuberculous and non-tuberculous mycobacteria, as well as other Actinomycetales species and DNA samples extracted directly from bovine and bubaline tissue homogenates. Regarding the analytical sensitivity, DNA of the M. bovis AN5 strain was detected up to 1.5 pg by nested-PCR, whereas DNA of M. tuberculosis H37Rv strain was detected up to 6.1 pg. The nested-PCR system showed 100% analytical specificity for MTC when tested with DNA of reference strains of non-tuberculous mycobacteria and closely-related Actinomycetales. A clinical sensitivity level of 76.7% was detected with tissues samples positive for MTC by means of the culture and conventional PCR. A clinical specificity of 100% was detected with DNA from tissue samples of cattle with negative results in the comparative intradermal tuberculin test. These cattle exhibited no visible lesions and were negative in the culture for MTC. The use of the nested-PCR assay to detect M. tuberculosis complex in tissue homogenates provided a rapid diagnosis of bovine and bubaline tuberculosis.

Direct detection of Mycobacterium tuberculosis complex in bovine and bubaline tissues through nested-PCR

PubMed Central

Araújo, Cristina P.; Osório, Ana Luiza A.R.; Jorge, Klaudia S.G.; Ramos, Carlos A.N.; Souza Filho, Antonio F.; Vidal, Carlos E.S.; Vargas, Agueda P.C.; Roxo, Eliana; Rocha, Adalgiza S.; Suffys, Philip N.; Fonseca, Antônio A.; Silva, Marcio R.; Barbosa Neto, José D.; Cerqueira, Valíria D.; Araújo, Flábio R.

2014-01-01

Post-mortem bacterial culture and specific biochemical tests are currently performed to characterize the etiologic agent of bovine tuberculosis. Cultures take up to 90 days to develop. A diagnosis by molecular tests such as PCR can provide fast and reliable results while significantly decreasing the time of confirmation. In the present study, a nested-PCR system, targeting rv2807, with conventional PCR followed by real-time PCR, was developed to detect Mycobacterium tuberculosis complex (MTC) organisms directly from bovine and bubaline tissue homogenates. The sensitivity and specificity of the reactions were assessed with DNA samples extracted from tuberculous and non-tuberculous mycobacteria, as well as other Actinomycetales species and DNA samples extracted directly from bovine and bubaline tissue homogenates. Regarding the analytical sensitivity, DNA of the M. bovis AN5 strain was detected up to 1.5 pg by nested-PCR, whereas DNA of M. tuberculosis H37Rv strain was detected up to 6.1 pg. The nested-PCR system showed 100% analytical specificity for MTC when tested with DNA of reference strains of non-tuberculous mycobacteria and closely-related Actinomycetales. A clinical sensitivity level of 76.7% was detected with tissues samples positive for MTC by means of the culture and conventional PCR. A clinical specificity of 100% was detected with DNA from tissue samples of cattle with negative results in the comparative intradermal tuberculin test. These cattle exhibited no visible lesions and were negative in the culture for MTC. The use of the nested-PCR assay to detect M. tuberculosis complex in tissue homogenates provided a rapid diagnosis of bovine and bubaline tuberculosis. PMID:25242951

Alteration of serum inflammatory cytokines in active pulmonary tuberculosis following anti-tuberculosis drug therapy.

PubMed

Chowdhury, Imran Hussain; Ahmed, Albin Mostaque; Choudhuri, Subhadip; Sen, Aditi; Hazra, Avijit; Pal, Nishith Kumar; Bhattacharya, Basudev; Bahar, Bojlul

2014-11-01

Active pulmonary tuberculosis (APTB) is associated with a failure of the host immune system to control the invading Mycobacterium tuberculosis (Mtb). The objective of this study was to quantify and assess the role of serum inflammatory cytokines in active pulmonary tuberculosis patients following anti-tuberculosis drug (ATD) therapy. Blood samples were collected from APTB patients and normal healthy subjects (NHS) (total n=204) at baseline and 2, 4 and 6 months post-therapy and the abundance of serum inflammatory cytokines were measured by cytokine specific ELISA. Compared to NHS, APTB patients at baseline had higher levels of serum pro-inflammatory cytokines IL-12p40 (P<0.001), IFN-γ (P<0.001), TNF-α (P<0.01), IL-1β (P<0.001) and IL-6 (P<0.001) and anti-inflammatory cytokines IL-10 (P<0.001) and TGF-β1 (P<0.001) while there was no change in the level of IL-4. In APTB patients, the serum levels of IFN-γ, TNF-α, IL-6 and TGF-β1 directly relate to the bacterial load while the TNF-α, IL-1β, IL-6 and TGF-β1 relate to radiological severity. At baseline, the IL-6 level in NHS and APTB patients differed most and following ATD therapy, this level rapidly decreased and stabilized by 4-month in APTB patients. It is concluded that a subtle reduction in the serum level of IL-6 of the APTB patients following ATD therapy might play a vital role in immune-protection of the host against Mtb infection and hence the serum IL-6 level can be a useful marker to diagnose the effectiveness of therapy in the patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bovine tuberculosis at the human-livestock-wildlife interface: is it a public health problem in Tanzania? A review.

PubMed

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

2012-06-20

Despite the apparent public health concern about Bovine tuberculosis (BTB) in Tanzania, little has been done regarding the zoonotic importance of the disease and raising awareness of the community to prevent the disease. Bovine tuberculosis is a potential zoonotic disease that can infect a variety of hosts, including humans. The presence of multiple hosts including wild animals, inefficient diagnostic techniques, absence of defined national controls and eradication programs could impede the control of bovine TB. In Tanzania, the diagnosis of Mycobacterium bovis in animals is mostly carried out by tuberculin skin testing, meat inspection in abattoirs and only rarely using bacteriological techniques. The estimated prevalence of BTB in animals in Tanzania varies and ranges across regions from 0.2% to 13.3%, which is likely to be an underestimate if not confirmed by bacteriology or molecular techniques. Mycobacterium bovis has been detected and isolated from different animal species and has been recovered in 10% of apparently healthy wildebeest that did not show lesions at post-mortem. The transmission of the disease from animals to humans can occur directly through the aerosol route and indirectly by consumption of raw milk. This poses an emerging disease threat in the current era of HIV confection in Tanzania and elsewhere. Mycobacterium bovis is one of the causative agents of human extra pulmonary tuberculosis. In Tanzania there was a significant increase (116.6%) of extrapulmonary cases reported between 1995 and 2009, suggesting the possibility of widespread M. bovis and Mycobacterium tuberculosis infection due to general rise of Human Immunodeficiency virus (HIV). This paper aims to review the potential health and economic impact of bovine tuberculosis and challenges to its control in order to safeguard human and animal population in Tanzania.

Risk to police officers from biohazards encountered in police work.

PubMed

Trottier, A; Brown, J

1995-06-01

The risk of contracting infectious disease in the course of police work is reviewed. The specific focus is on Acquired Immune Deficiency Syndrome (AIDS), hepatitis and tuberculosis. A review of the relevant literature and an assessment of the biohazard risk specific to police work is provided. The risk of AIDS and hepatitis C is seen to be less than the risk of hepatitis B. For these blood borne diseases, universal precautions are recommended. The application of such precautions to policing is outlined. Immunisation against hepatitis B is recommended. Tuberculosis is seen as a possibly increasing risk. A programme of surveillance is recommended. A review of post-exposure management is provided.

Cost-effectiveness of a comprehensive programme for drug-resistant tuberculosis in China.

PubMed

Fitzpatrick, Christopher; Hui, Zhang; Lixia, Wang; Renzhong, Li; Yunzhou, Ruan; Mingting, Chen; Yanlin, Zhao; Jin, Zhao; Wei, Su; Caihong, Xu; Cheng, Chen; Alston, Timothy; Yan, Qu; Chengfei, Lv; Yunting, Fu; Shitong, Huan; Qiang, Sun; Scano, Fabio; Chin, Daniel P; Floyd, Katherine

2015-11-01

To investigate the cost-effectiveness of a comprehensive programme for drug-resistant tuberculosis launched in four sites in China in 2011. In 2011-2012, we reviewed the records of 172 patients with drug-resistant tuberculosis who enrolled in the comprehensive programme and we collected relevant administrative data from hospitals and China's public health agency. For comparison, we examined a cohort of 81 patients who were treated for drug-resistant tuberculosis in 2006-2009. We performed a cost-effectiveness analysis, from a societal perspective, that included probabilistic uncertainty. We measured early treatment outcomes based on three-month culture results and modelled longer-term outcomes to facilitate estimation of the comprehensive programme's cost per disability-adjusted life-year (DALY) averted. The comprehensive programme cost 8837 United States dollars (US$) per patient treated. Low enrolment rates meant that some fixed costs were higher, per patient, than expected. Although the comprehensive programme appeared 30 times more costly than the previous one, it resulted in greater health benefits. The comprehensive programme, which cost US$ 639 (95% credible interval: 112 to 1322) per DALY averted, satisfied the World Health Organization's criterion for a very cost-effective intervention. The comprehensive programme, which included rapid screening, standardized care and financial protection, improved individual outcomes for MDR tuberculosis in a cost-effective manner. To support post-2015 global heath targets, the comprehensive programme should be expanded to non-residents and other areas of China.

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.

Unique Chemokine Profiles of Lung Tissues Distinguish Post-chemotherapeutic Persistent and Chronic Tuberculosis in a Mouse Model.

PubMed

Park, Soomin; Baek, Seung-Hun; Cho, Sang-Nae; Jang, Young-Saeng; Kim, Ahreum; Choi, In-Hong

2017-01-01

There is a substantial need for biomarkers to distinguish latent stage from active Mycobacterium tuberculosis infections, for predicting disease progression. To induce the reactivation of tuberculosis, we present a new experimental animal model modified based on the previous model established by our group. In the new model, the reactivation of tuberculosis is induced without administration of immunosuppressive agents, which might disturb immune responses. To identify the immunological status of the persistent and chronic stages, we analyzed immunological genes in lung tissues from mice infected with M. tuberculosis . Gene expression was screened using cDNA microarray analysis and confirmed by quantitative RT-PCR. Based on the cDNA microarray results, 11 candidate cytokines genes, which were obviously up-regulated during the chronic stage compared with those during the persistent stage, were selected and clustered into three groups: (1) chemokine genes, except those of monocyte chemoattractant proteins (MCPs; CXCL9, CXCL10, CXCL11, CCL5, CCL19); (2) MCP genes (CCL2, CCL7, CCL8, CCL12); and (3) TNF and IFN-γ genes. Results from the cDNA microarray and quantitative RT-PCR analyses revealed that the mRNA expression of the selected cytokine genes was significantly higher in lung tissues of the chronic stage than of the persistent stage. Three chemokines (CCL5, CCL19, and CXCL9) and three MCPs (CCL7, CCL2, and CCL12) were noticeably increased in the chronic stage compared with the persistent stage by cDNA microarray ( p < 0.01, except CCL12) or RT-PCR ( p < 0.01). Therefore, these six significantly increased cytokines in lung tissue from the mouse tuberculosis model might be candidates for biomarkers to distinguish the two disease stages. This information can be combined with already reported potential biomarkers to construct a network of more efficient tuberculosis markers.

Performance of the National Tuberculosis Control Program in the post conflict Liberia.

PubMed

Desta, Kassaye Tekie; Masango, T E; Nkosi, Zerish Zethu

2018-01-01

Tuberculosis is a major public health problem in Liberia. According to the World Health Organization (WHO), the incidence of tuberculosis in Liberia is significantly increasing from year to year. However, little is known about the performance of the programme and the challenges after the 14 years of civil war which ended in 2003.The purpose of the study was to evaluate the performance of the TB programme of Liberia. The study utilised mixed research design; both quantitative and qualitative methods were used in this study conducted from 2013 to 2014. For the quantitative part of the study, a questionnaire, laboratory performance and eleven years TB programme data (2003-2013) were used. For the performance of tuberculosis laboratory testing, all the 107 functional tuberculosis microscopy centers in Liberia were included. For the qualitative part of the study, an interview of 10 informants and two focus group discussions (FGDs) were also conducted, each comprising of eight people. Themes and subthemes emerged from the two FGDs. Data was analysed in line with the Donabedian model. Quantitative findings were analysed and presented using both descriptive and inferential statistics. The study findings pointed out that there was overall improvement in the performance of the tuberculosis control programme in Liberia from 2003 to 2013. The percentage of cured patients was 60% in 2005 and 62% in 2013. Percentage of treatment completed was 16% in 2005 and 21% in 2013. The case detection rate was 57% and treatment success rate 80% in 2013. The default rate was 11% in 2013. Of the 139 participants, 120 (86%) completed TB treatment while 19 (14%) did not. Between 2003 and 2013, the National Leprosy and Tuberculosis Control Programme (NLTCP) succeeded in restoring the TB services and improving some of the TB treatment outcomes including the Directly observed treatment short courses(DOTS) coverage. Despite these improvements, the TB treatment, laboratory services and human resource capacity lagged behind. The TB programme of Liberia needs to develop new strategies to address its challenges.

Burden of tuberculosis in intensive care units in Cape Town, South Africa, and assessment of the accuracy and effect on patient outcomes of the Xpert MTB/RIF test on tracheal aspirate samples for diagnosis of pulmonary tuberculosis: a prospective burden of disease study with a nested randomised controlled trial.

PubMed

Calligaro, Gregory L; Theron, Grant; Khalfey, Hoosain; Peter, Jonathan; Meldau, Richard; Matinyenya, Brian; Davids, Malika; Smith, Liezel; Pooran, Anil; Lesosky, Maia; Esmail, Aliasgar; Miller, Malcolm G; Piercy, Jenna; Michell, Lancelot; Dawson, Rodney; Raine, Richard I; Joubert, Ivan; Dheda, Keertan

2015-08-01

There are few prospective data about the incidence and mortality associated with pulmonary tuberculosis in intensive care units (ICUs), and none on the accuracy and clinical effect of the Xpert-MTB/RIF assay in this setting. We aimed to measure the frequency of culture-positive tuberculosis in ICUs in Cape Town, South Africa and to assess the performance and effect on patient outcomes of Xpert MTB/RIF versus smear microscopy for diagnosis of tuberculosis. We did a prospective burden of disease study with a randomised controlled substudy at the ICUs of four hospitals in Cape Town. Mechanically ventilated adults (≥18 years) with suspected pulmonary tuberculosis admitted between Aug 1, 2010, and July 31, 2013 (irrespective of the reason for admission), were prospectively investigated by culture, and by Xpert-MTB/RIF testing or smear microscopy, of tracheal aspirate samples. In the substudy, patients were randomly assigned (1:1), via a computer-generated allocation list, to smear microscopy or Xpert MTB/RIF. Participants, caregivers, and outcome assessors were not masked to group assignment. Only the laboratory staff were blinded to the clinical details of the participants. In November, 2012, Xpert MTB/RIF was adopted as the initial diagnostic test for respiratory samples in Western Cape province. Thereafter, patients received Xpert MTB/MIF and culture as standard of care. For the whole study cohort, the primary outcome was the frequency of bacteriologically confirmed tuberculosis. The primary endpoint of the randomised substudy was the proportion of culture-positive patients on treatment at 48 h after enrolment. The randomised substudy is registered with ClinicalTrials.gov, number NCT01530568. We investigated 341 patients for suspected pulmonary tuberculosis out of a total of 2309 ICU admissions. 46 (15%) of 317 patients included in the final analysis had a positive test for tuberculosis (Xpert MTB/RIF or culture). Culture-positive patients who failed to initiate treatment (adjusted HR 4·49, 95% CI 1·45-13·89) or who received inotropes (4·33, 1·49-12·60) were more likely to die. However, tuberculosis status was not associated with 28-day or 90-day mortality. In the substudy, we randomly assigned 115 patients to smear microscopy and 111 to Xpert MTB/RIF. Smear microscopy detected six (43%) of 14 culture-positive patients, and Xpert MTB/RIF detected 11 (100%) of 11 culture-positive patients (p=0·002). The proportion of culture-positive patients on treatment at 48 h was higher in the Xpert MTB/RIF group than in the smear microscopy group (11 [92%] of 12 vs nine [53%] of 17; p=0·043), although use of Xpert MTB/RIF had no effect on mortality or other patient outcomes. Tuberculosis is fairly common in ICUs in high-burden settings, and clinicians should screen and test patients for tuberculosis with Xpert MTB/RIF where available. This test improves diagnostic yield and rates of treatment initiation, and reduces unnecessary treatment, but might not increase the total number of patients on treatment when empirical treatment is widely used. A suspected diagnosis of pulmonary tuberculosis should not exclude patients from ICU care in resource-limited settings because mortality is unaffected by the presence of this disease. European and Developing Countries Clinical Trials Partnership, South African Medical Research Council, and the Discovery Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pulmonary tuberculosis and non-recent immigrants in Japan - some issues for post-entry interventions.

PubMed

Kawatsu, Lisa; Uchimura, Kazuhiro; Ohkado, Akihiro; Kato, Seiya

2017-01-01

Foreign-born persons are considered one of the high-risk populations for tuberculosis (TB), and numerous studies have discussed the potential role of pre-entry TB screening for immigrants. However, rates of TB disease among immigrants can remain high several years after entry. In Japan, approximately 50% of TB among foreign-born persons occurs among those who have entered Japan more than five years before being diagnosed, i.e. non-recent immigrants. However, little attention has been paid so far to the issue of TB control among the non-recent immigrants. A detailed analysis of the Japan Tuberculosis Surveillance data was therefore conducted to describe the characteristics of TB among non-recent immigrants and discuss policy implications in terms of post-entry interventions in Japan. The main findings were as follows: 1) the proportion of pulmonary TB cases aged 65 years and older was higher among non-recent than recent immigrants (9.8% vs 1.2%); 2) the proportion of those with social risk factors including homelessness and and being on social welfare assistance was higher among non-recent than recent immigrants; and 3) the proportion of those detected via routine screening at school or workplace was significantly lower among non-recent immigrants aged between 25 and 64 than among recent immigrants in the same age group (15.4% vs 28.7%). Our results suggested the need to increase the opportunities for and simultaneously improve the take-up rate of community-based screening for non-recent immigrants.

Feasibility of a combined camp approach for vector control together with active case detection of visceral leishmaniasis, post kala-azar dermal leishmaniasis, tuberculosis, leprosy and malaria in Bangladesh, India and Nepal: an exploratory study.

PubMed

Banjara, Megha R; Kroeger, Axel; Huda, Mamun M; Kumar, Vijay; Gurung, Chitra K; Das, Murari L; Rijal, Suman; Das, Pradeep; Mondal, Dinesh

2015-06-01

We assessed the feasibility and results of active case detection (ACD) of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and other febrile diseases as well as of bednet impregnation for vector control. Fever camps were organized and analyzed in twelve VL endemic villages in Bangladesh, India, and Nepal. VL, PKDL, tuberculosis, malaria and leprosy were screened among the febrile patients attending the camps, and existing bednets were impregnated with a slow release insecticide. Among the camp attendees one new VL case and two PKDL cases were detected in Bangladesh and one VL case in Nepal. Among suspected tuberculosis cases two were positive in India but none in the other countries. In India, two leprosy cases were found. No malaria cases were detected. Bednet impregnation coverage during fever camps was more than 80% in the three countries. Bednet impregnation led to a reduction of sandfly densities after 2 weeks by 86% and 32%, and after 4 weeks by 95% and 12% in India and Nepal respectively. The additional costs for the control programmes seem to be reasonable. It is feasible to combine ACD camps for VL and PKDL along with other febrile diseases, and vector control with bednet impregnation. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Low rates of recurrence after successful treatment of multidrug-resistant tuberculosis in Tomsk, Russia.

PubMed

Gelmanova, I Y; Ahmad Khan, F; Becerra, M C; Zemlyanaya, N A; Unakova, I A; Andreev, Y G; Berezina, V I; Pavlova, V E; Shin, S; Yedilbayev, A B; Krasnov, V A; Keshavjee, S

2015-04-01

Tomsk, Russia, where multidrug-resistant tuberculosis (MDR-TB) is prevalent. To report rates of recurrence following successful treatment of MDR-TB in a program providing individualized treatment regimens designed according to the current global standard of care. A retrospective cohort study of 408 adults successfully treated for pulmonary MDR-TB from 10 September 2000 to 1 November 2004, and followed for up to 6 years post-treatment. We used Poisson regression with generalized estimating equations to assess whether recurrence rates changed significantly with time. We analyzed 399 (97.5%) patients with at least one follow-up visit (15 850 person-months of observation [PMO]). Baseline resistance to second-line drugs was common (65.2%); 398 patients (99.7%) were human immunodeficiency virus (HIV) negative. In the first year of post-treatment follow-up, there were six episodes of recurrence (1.4/1000 PMO, 95%CI 0.5-3.0). After the first post-treatment year, there were 21 episodes of recurrence (1.8/1000 PMO, 95%CI 1.1-2.8). The rate did not change significantly with time. Individualized regimens designed according to the current global standard of care achieved low rates of MDR-TB recurrence among non-HIV-infected persons treated in a programmatic setting.

Detection and differentiation of Mycobacterium tuberculosis and nontuberculous mycobacterial isolates by real-time PCR.

PubMed

Shrestha, Nabin K; Tuohy, Marion J; Hall, Gerri S; Reischl, Udo; Gordon, Steven M; Procop, Gary W

2003-11-01

Mycobacteria cause a variety of illnesses that differ in severity and public health implications. The differentiation of Mycobacterium tuberculosis from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of antimicrobial therapy. Despite advances in molecular diagnostics, the ability to rapidly diagnose M. tuberculosis infections by PCR is still inadequate, largely because of the possibility of false-negative reactions. We designed and validated a real-time PCR for mycobacteria by using the LightCycler system with 18 reference strains and 168 clinical mycobacterial isolates. All clinically significant mycobacteria were detected; the mean melting temperatures (with 99.9% confidence intervals [99.9% CI] in parentheses) for the different mycobacteria were as follows: M. tuberculosis, 64.35 degrees C (63.27 to 65.42 degrees C); M. kansasii, 59.20 degrees C (58.07 to 60.33 degrees C); M. avium, 57.82 degrees C (57.05 to 58.60 degrees C); M. intracellulare, 54.46 degrees C (53.69 to 55.23 degrees C); M. marinum, 58.91 degrees C (58.28 to 59.55 degrees C); rapidly growing mycobacteria, 53.09 degrees C (50.97 to 55.20 degrees C) or 43.19 degrees C (42.19 to 44.49 degrees C). This real-time PCR assay with melting curve analysis consistently accurately detected and differentiated M. tuberculosis from NTM. Detection of an NTM helps ensure that the negative result for M. tuberculosis is a true negative. The specific melting temperature also provides a suggestion of the identity of the NTM present, when the most commonly encountered mycobacterial species are considered. In a parallel comparison, both the LightCycler assay and the COBAS Amplicor M. tuberculosis assay correctly categorized 48 of 50 specimens that were proven by culture to contain M. tuberculosis, and the LightCycler assay correctly characterized 3 of 3 specimens that contained NTM.

Detection and Differentiation of Mycobacterium tuberculosis and Nontuberculous Mycobacterial Isolates by Real-Time PCR

PubMed Central

Shrestha, Nabin K.; Tuohy, Marion J.; Hall, Gerri S.; Reischl, Udo; Gordon, Steven M.; Procop, Gary W.

2003-01-01

Mycobacteria cause a variety of illnesses that differ in severity and public health implications. The differentiation of Mycobacterium tuberculosis from nontuberculous mycobacteria (NTM) is of primary importance for infection control and choice of antimicrobial therapy. Despite advances in molecular diagnostics, the ability to rapidly diagnose M. tuberculosis infections by PCR is still inadequate, largely because of the possibility of false-negative reactions. We designed and validated a real-time PCR for mycobacteria by using the LightCycler system with 18 reference strains and 168 clinical mycobacterial isolates. All clinically significant mycobacteria were detected; the mean melting temperatures (with 99.9% confidence intervals [99.9% CI] in parentheses) for the different mycobacteria were as follows: M. tuberculosis, 64.35°C (63.27 to 65.42°C); M. kansasii, 59.20°C (58.07 to 60.33°C); M. avium, 57.82°C (57.05 to 58.60°C); M. intracellulare, 54.46°C (53.69 to 55.23°C); M. marinum, 58.91°C (58.28 to 59.55°C); rapidly growing mycobacteria, 53.09°C (50.97 to 55.20°C) or 43.19°C (42.19 to 44.49°C). This real-time PCR assay with melting curve analysis consistently accurately detected and differentiated M. tuberculosis from NTM. Detection of an NTM helps ensure that the negative result for M. tuberculosis is a true negative. The specific melting temperature also provides a suggestion of the identity of the NTM present, when the most commonly encountered mycobacterial species are considered. In a parallel comparison, both the LightCycler assay and the COBAS Amplicor M. tuberculosis assay correctly categorized 48 of 50 specimens that were proven by culture to contain M. tuberculosis, and the LightCycler assay correctly characterized 3 of 3 specimens that contained NTM. PMID:14605148

Development of an Intracellular Screen for New Compounds Able To Inhibit Mycobacterium tuberculosis Growth in Human Macrophages.

PubMed

Sorrentino, Flavia; Gonzalez del Rio, Ruben; Zheng, Xingji; Presa Matilla, Jesus; Torres Gomez, Pedro; Martinez Hoyos, Maria; Perez Herran, Maria Esther; Mendoza Losana, Alfonso; Av-Gay, Yossef

2016-01-01

Here we describe the development and validation of an intracellular high-throughput screening assay for finding new antituberculosis compounds active in human macrophages. The assay consists of a luciferase-based primary identification assay, followed by a green fluorescent protein-based secondary profiling assay. Standard tuberculosis drugs and 158 previously recognized active antimycobacterial compounds were used to evaluate assay robustness. Data show that the assay developed is a short and valuable tool for the discovery of new antimycobacterial compounds. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Evolution of granulomas in lungs of mice infected aerogenically with Mycobacterium tuberculosis.

PubMed

Cardona, P J; Llatjós, R; Gordillo, S; Díaz, J; Ojanguren, I; Ariza, A; Ausina, V

2000-08-01

Aerogenous infection of C57Bl/6 mice with a virulent strain of Mycobacterium tuberculosis (CL 511) leads to the formation of primary granulomas in the lung where neutrophils, macrophages and subsequently, lymphocytes accumulate progressively around an initial cluster of infected macrophages. The spread of infection through the lung parenchyma gives rise to secondary granulomas featuring numerous lymphocytes that surround a small number of infected macrophages. Afterwards, foamy macrophages add an outer layer to the granulomas, which characteristically respect the pulmonary interstitium and remain confined within the alveolar spaces. This feature, in conjunction with the constant presence of M. tuberculosis in the products of broncho-alveolar lavage, suggests that the upward bronchial migration of infected macrophages may contribute significantly to pulmonary dissemination of mycobacterial infection. The latter would be in agreement with the persistence of chronic pulmonary infection in spite of a concomitant strong T helper 1 cell response.

Knowledge about anti-tuberculosis treatment among nurses at tuberculosis clinics.

PubMed

Yükseltürk, Neriman; Dinç, Leyla

2013-02-01

Nurses are primary responsible for Direct Observation Therapy Strategy and administration of anti-tuberculosis (TB) medications. Lack of knowledge might result with medication errors and ineffective TB control. The purpose of this study was to assess knowledge of nurses about anti-TB treatment. A descriptive cross-sectional study was conducted in Turkey with 208 nurses employed at TB and lung disease clinics of health-care settings in Ankara. Data were collected through a questionnaire, which included questions about demographics and a knowledge test with true-false questions related to TB treatment. Overall scores were high with a mean score of 18.5 out of 24, but there was knowledge deficiency in effects and side-effects of anti-TB drugs. Knowledge is foundational for any practice and for TB control. Clinical experience and continuing education after graduation influence the level of knowledge. © 2013 Wiley Publishing Asia Pty Ltd.

Three cases of donor-derived pulmonary tuberculosis in lung transplant recipients and review of 12 previously reported cases: opportunities for early diagnosis and prevention.

PubMed

Mortensen, E; Hellinger, W; Keller, C; Cowan, L S; Shaw, T; Hwang, S; Pegues, D; Ahmedov, S; Salfinger, M; Bower, W A

2014-02-01

Solid organ transplant recipients have a higher frequency of tuberculosis (TB) than the general population, with mortality rates of approximately 30%. Although donor-derived TB is reported to account for <5% of TB in solid organ transplants, the source of Mycobacterium tuberculosis infection is infrequently determined. We report 3 new cases of pulmonary TB in lung transplant recipients attributed to donor infection, and review the 12 previously reported cases to assess whether cases could have been prevented and whether any cases that might occur in the future could be detected and investigated more quickly. Specifically, we evaluate whether opportunities existed to determine TB risk on the basis of routine donor history, to expedite diagnosis through routine mycobacterial smears and cultures of respiratory specimens early post transplant, and to utilize molecular tools to investigate infection sources epidemiologically. On review, donor TB risk was present among 7 cases. Routine smears and cultures diagnosed 4 asymptomatic cases. Genotyping was used to support epidemiologic findings in 6 cases. Validated screening protocols, including microbiological testing and newer technologies (e.g., interferon-gamma release assays) to identify unrecognized M. tuberculosis infection in deceased donors, are warranted. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Establishment of a Neonatal Rhesus Macaque Model to Study Mycobacterium tuberculosis Infection

PubMed Central

Cepeda, Magdalena; Salas, Mary; Folwarczny, Jessica; Leandro, Ana C.; Hodara, Vida L.; de la Garza, Melissa A.; Dick, Edward J.; Owston, Michael; Armitige, Lisa Y.; Gauduin, Marie-Claire

2014-01-01

Summary Mycobacterium tuberculosis (Mtb) is the causative agent of human tuberculosis (TB) with an estimated 8.8 million new TB cases and 1.4 million deaths annually. Tuberculosis is the leading cause of death in AIDS patients worldwide but very little is known about early TB infection or TB/HIV co-infection in infants. A clinically relevant newborn animal model to study TB infection is urgently needed. We have successfully established an aerosol newborn/infant model in neonatal nonhuman primates (NHPs) that mimics clinical and bacteriological characteristics of Mtb infection as seen in human newborns/infants. Further, this model will allow the establishment of a TB coinfection model of pediatric AIDS. Aerosol versus intra broncho-alveolar Mtb infection was studied. Interestingly, 42 days post infection specific lesions were detected suggestive of the classic Ghon focus in human children. Concurrently, specific cellular immune responses developed 4–6 weeks after Mtb infection. Using the enzyme-linked immunospot (ELISPOT) assays, we found that IL-12 production correlated with early Mtb infection lesions seen by routine thoracic radiographs. Overall, this work represents the first example of early Mtb infection of newborn macaques. This study gives us a unique opportunity to further characterize immunopathogenesis and establish a TB/SIV co-infection model for pediatric AIDS. PMID:24388650

Age, nutritional status and INH acetylator status affect pharmacokinetics of anti-tuberculosis drugs in children.

PubMed

Ramachandran, G; Hemanth Kumar, A K; Bhavani, P K; Poorana Gangadevi, N; Sekar, L; Vijayasekaran, D; Banu Rekha, V V; Ramesh Kumar, S; Ravichandran, N; Mathevan, G; Swaminathan, S

2013-06-01

The currently recommended dosages of rifampicin (RMP), isoniazid (INH), pyrazinamide (PZA) and ethambutol in children are extrapolated from adult pharmacokinetic studies, and have not been adequately evaluated in children. To describe the pharmacokinetics of RMP, INH and PZA given thrice weekly in children with tuberculosis (TB), and to relate pharmacokinetics to treatment outcomes. Eighty-four human immunodeficiency virus negative children with TB aged 1-12 years in Chennai and Madurai, India, were recruited. Phenotypic INH acetylator status was determined. Nutritional status was assessed using Z scores. During the intensive phase of anti-tuberculosis treatment, a complete pharmacokinetic study was performed after directly observed administration of drugs. At 2 and 6 months, drug levels were measured 2 h post-dose. Drug concentrations were measured using high performance liquid chromatography and pharmacokinetic variables were calculated. Multivariable regression analysis was performed to explore factors impacting drug levels and treatment outcomes. Children aged <3 years had significantly lower RMP, INH and PZA concentrations than older children, and 90% of all children had sub-therapeutic RMP Cmax (<8 μg/ml). Age, nutritional status and INH acetylator status influenced drug levels. Peak RMP and INH concentrations were important determinants of treatment outcome. Recommendations for anti-tuberculosis treatment in children should take these factors into consideration.

Evaluation of the Mycobacterium tuberculosis SO2 vaccine using a natural tuberculosis infection model in goats.

PubMed

Bezos, J; Casal, C; Álvarez, J; Roy, A; Romero, B; Rodríguez-Bertos, A; Bárcena, C; Díez, A; Juste, R; Gortázar, C; Puentes, E; Aguiló, N; Martín, C; de Juan, L; Domínguez, L

2017-05-01

The development of new vaccines against animal tuberculosis (TB) is a priority for improving the control and eradication of this disease, particularly in those species not subjected to compulsory eradication programmes. In this study, the protection conferred by the Mycobacterium tuberculosis SO 2 experimental vaccine was evaluated using a natural infection model in goats. Twenty-six goats were distributed in three groups: (1) 10 goats served as a control group; (2) six goats were subcutaneously vaccinated with BCG; and (3) 10 goats were subcutaneously vaccinated with SO 2 . Four months after vaccination, all groups were merged with goats infected with Mycobacterium bovis or Mycobacterium caprae, and tested over a 40 week period using a tuberculin intradermal test and an interferon-γ assay for mycobacterial reactivity. The severity of lesions was determined at post-mortem examination and the bacterial load in tissues were evaluated by culture. The two vaccinated groups had significantly lower lesion and bacterial culture scores than the control group (P<0.05); at the end of the study, the SO 2 vaccinated goats had the lowest lesion and culture scores. These results suggest that the SO 2 vaccine provides some protection against TB infection acquired from natural exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Internal migration and transmission dynamics of tuberculosis in Shanghai, China: an epidemiological, spatial, genomic analysis.

PubMed

Yang, Chongguang; Lu, Liping; Warren, Joshua L; Wu, Jie; Jiang, Qi; Zuo, Tianyu; Gan, Mingyu; Liu, Mei; Liu, Qingyun; DeRiemer, Kathryn; Hong, Jianjun; Shen, Xin; Colijn, Caroline; Guo, Xiaoqin; Gao, Qian; Cohen, Ted

2018-04-19

Massive internal migration from rural to urban areas poses new challenges for tuberculosis control in China. We aimed to combine genomic, spatial, and epidemiological data to describe the dynamics of tuberculosis in an urban setting with large numbers of migrants. We did a population-based study of culture-positive Mycobacterium tuberculosis isolates in Songjiang, Shanghai. We used whole-genome sequencing to discriminate apparent genetic clusters of M tuberculosis sharing identical variable-number-tandem-repeat (VNTR) patterns, and analysed the relations between proximity of residence and the risk of genomically clustered M tuberculosis. Finally, we used genomic, spatial, and epidemiological data to estimate time of infection and transmission links among migrants and residents. Between Jan 1, 2009, and Dec 31, 2015, 1620 cases of culture-positive tuberculosis were recorded, 1211 (75%) of which occurred among internal migrants. 150 (69%) of 218 people sharing identical VNTR patterns had isolates within ten single-nucleotide polymorphisms (SNPs) of at least one other strain, consistent with recent transmission of M tuberculosis. Pairs of strains collected from individuals living in close proximity were more likely to be genetically similar than those from individuals who lived far away-for every additional km of distance between patients' homes, the odds that genotypically matched strains were within ten SNPs of each other decreased by about 10% (OR 0·89 [95% CI 0·87-0·91]; p<0·0001). We inferred that transmission from residents to migrants occurs as commonly as transmission from migrants to residents, and we estimated that more than two-thirds of migrants in genomic clusters were infected locally after migration. The primary mechanism driving local incidence of tuberculosis in urban centres is local transmission between both migrants and residents. Combined analysis of epidemiological, genomic, and spatial data contributes to a richer understanding of local transmission dynamics and should inform the design of more effective interventions. National Natural Science Foundation of China, National Science and Technology Major Project of China, and US National Institutes of Health. Copyright © 2018 Elsevier Ltd. All rights reserved.

Changing prevalence and resistance patterns in children with drug-resistant tuberculosis in Mumbai.

PubMed

Shah, Ira; Shah, Forum

2017-05-01

The prevalence of drug-resistant (DR) tuberculosis (TB) in children is increasing. Although, in India, multi-drug-resistant (MDR) TB rates have been relatively stable, the number of children with pre-extensively drug-resistant and extensively drug-resistant (XDR) TB is increasing. To determine whether the prevalence of DR TB in children in Mumbai is changing and to study the evolving patterns of resistance. A retrospective study was undertaken in 1311 paediatric patients referred between April 2007 and March 2013 to the Paediatric TB clinic at B. J. Wadia Hospital for Children, Mumbai. Children were defined as having DR TB on the basis of drug susceptibility testing (DST) of Mycobacterium tuberculosis grown on culture of body fluids (in the case of extra pulmonary TB) or from gastric lavage/bronchi-alveolar lavage/sputum in patients with pulmonary TB or from DST of the contacts. The prevalence of DR TB was calculated and the type of DR was evaluated yearly and in the pre-2010 and post-2010 eras. The overall prevalence of DR TB was 86 (6.6%) with an increase from 23 (5.6%) patients pre-2010 to 63 (7%) post-2010 (P = 0.40). Nine (10.4%) patients were diagnosed on the basis of contact with a parent with DR TB. Overall fluoroquinolone resistance increased from 9 (39.1%) pre-2010 to 59 (93.7%) post-2010 (P = 0.0001): moxifloxacin resistance increased from 2 (8.7%) to 29 (46%) (P = 0.0018) and ofloxacin resistance increased from 7 (30.4%) to 30 (47.6%) (P = 0.14). Ethionamide resistance also increased from 6 (26.1%) to 31 (49.2%) (P = 0.04), aminoglycoside resistance was one (4.3%) pre-2010 and 12 (19%) post-2010 (P = 0.17) and resistance remained virtually the same for both amikacin [0 pre-2010 and 6 (9.5%) after 2010] and kanamycin [one (4.3%) pre- and 6 (9.5%) post-2010]. Of the first-line drugs, resistance remained the same for isoniazid [23 (100%) to 61 (96.8%)], rifampicin [22 (95.7%) to 51 (80.9%),P = 0.17], pyrazinamide [15 (65.2%) to 35 (55.6%), P = 0.47], ethambutol [14 (60.9%) to 38 (60.3%), P = 1.00] and streptomycin [19 (82.6%) to 50 (79.4%), P = 1.00]. Resistance to PAS remained unchanged [2 (8.7%) to 5 (7.9%), P = 1.00]. There is increasing resistance to second-line anti-tuberculosis (ATT) drugs, particularly flouroquinolones and ethionamide. Hence, there is an urgent need to avoid the use of ATT drugs for non-tuberculous infection and to increase surveillance for DR TB in adults as MDR TB in children is usually through contact with an adult with infectious MDR TB.

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.

Transcriptional Profiling of Mycobacterium tuberculosis Exposed to In Vitro Lysosomal Stress

PubMed Central

Lin, Wenwei; de Sessions, Paola Florez; Teoh, Garrett Hor Keong; Mohamed, Ahmad Naim Nazri; Zhu, Yuan O.; Koh, Vanessa Hui Qi; Ang, Michelle Lay Teng; Dedon, Peter C.; Hibberd, Martin Lloyd

2016-01-01

Increasing experimental evidence supports the idea that Mycobacterium tuberculosis has evolved strategies to survive within lysosomes of activated macrophages. To further our knowledge of M. tuberculosis response to the hostile lysosomal environment, we profiled the global transcriptional activity of M. tuberculosis when exposed to the lysosomal soluble fraction (SF) prepared from activated macrophages. Transcriptome sequencing (RNA-seq) analysis was performed using various incubation conditions, ranging from noninhibitory to cidal based on the mycobacterial replication or killing profile. Under inhibitory conditions that led to the absence of apparent mycobacterial replication, M. tuberculosis expressed a unique transcriptome with modulation of genes involved in general stress response, metabolic reprogramming, respiration, oxidative stress, dormancy response, and virulence. The transcription pattern also indicates characteristic cell wall remodeling with the possible outcomes of increased infectivity, intrinsic resistance to antibiotics, and subversion of the host immune system. Among the lysosome-specific responses, we identified the glgE-mediated 1,4 α-glucan synthesis pathway and a defined group of VapBC toxin/anti-toxin systems, both of which represent toxicity mechanisms that potentially can be exploited for killing intracellular mycobacteria. A meta-analysis including previously reported transcriptomic studies in macrophage infection and in vitro stress models was conducted to identify overlapping and nonoverlapping pathways. Finally, the Tap efflux pump-encoding gene Rv1258c was selected for validation. An M. tuberculosis ΔRv1258c mutant was constructed and displayed increased susceptibility to killing by lysosomal SF and the antimicrobial peptide LL-37, as well as attenuated survival in primary murine macrophages and human macrophage cell line THP-1. PMID:27324481

Characterization of bovine gamma delta T cells phenotype during post-natal development and following Mycobacterium bovis vaccination or virulent infection

USDA-ARS?s Scientific Manuscript database

Bovine tuberculosis caused by Mycobacterium bovis is a globally significant veterinary health problem. Gamma delta T cells are known to participate in the immune control of mycobacterial infections. Data in human and non-human primates suggest that mycobacterial infection regulates memory/effector p...

Screening prior to biological therapy in Crohn's disease: adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study.

PubMed

van der Have, Mike; Belderbos, Tim D G; Fidder, Herma H; Leenders, Max; Dijkstra, Gerard; Peters, Charlotte P; Eshuis, Emma J; Ponsioen, Cyriel Y; Siersema, Peter D; van Oijen, Martijn G H; Oldenburg, Bas

2014-10-01

Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. A multicentre retrospective study was conducted in Crohn's disease patients in whom infliximab or adalimumab was started between 2000 and 2010. Screening included tuberculin skin test, interferon-gamma release assay or chest X-ray for tuberculosis. Extended screening included screening for tuberculosis and viral infections. Patients were followed until three months after ending treatment. Primary endpoints were opportunistic and serious infections. 611 patients were included, 91% on infliximab. 463 (76%) patients were screened for tuberculosis, of whom 113 (24%) underwent extended screening. Screening for tuberculosis and hepatitis B increased to, respectively, 90-97% and 36-49% in the last two years. During a median follow-up of two years, 64/611 (9%, 3.4/100 patient-years) opportunistic infections and 26/611 (4%, 1.6/100 patient-years) serious infections were detected. Comorbidity was significantly associated with serious infections (hazard ratio 3.94). Although screening rates for tuberculosis and hepatitis B increased, screening for hepatitis B was still suboptimal. More caution is required when prescribing biologicals in patients with comorbid conditions. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Implementing a successful tuberculosis programme within primary care services in a conflict area using the stop TB strategy: Afghanistan case study

PubMed Central

2014-01-01

Introduction Afghanistan has faced health consequences of war including those due to displacement of populations, breakdown of health and social services, and increased risks of disease transmission for over three decades. Yet it was able to restructure its National Tuberculosis Control Programme (NTP), integrate tuberculosis treatment into primary health care and achieve most of its targets by the year 2011. What were the processes that enabled the programme to achieve its targets? More importantly, what were the underpinning factors that made this success possible? We addressed these important questions through a case study. Case description We adopted a processes and outcomes framework for this study, which began with examining the change in key programme indicators, followed by backwards tracing of the processes and underlying factors, responsible for this change. Methods included review of the published and grey literature along with in-depth interviews of 15 key informants involved with the care of tuberculosis patients in Afghanistan. Discussion and evaluation TB incidence and mortality per 100,000 decreased from 325 and 92 to 189 and 39 respectively, while case notification and treatment success improved during the decade under study. Efficient programme structures were enabled through high political commitment from the Government, strong leadership from the programme, effective partnership and coordination among stakeholders, and adequate technical and financial support from the development partners. Conclusions The NTP Afghanistan is an example that public health programmes can be effectively implemented in fragile states. High political commitment and strong local leadership are essential factors for such programmes. To ensure long-term effectiveness of the NTP, the international support should be withdrawn in a phased manner, coupled with a sequential increase in resources allocated to the NTP by the Government of Afghanistan. PMID:24507446

Tuberculosis-related mortality in people living with HIV in Europe and Latin America: an international cohort study.

PubMed

Podlekareva, Daria N; Efsen, Anne Marie W; Schultze, Anna; Post, Frank A; Skrahina, Alena M; Panteleev, Alexander; Furrer, Hansjakob; Miller, Robert F; Losso, Marcelo H; Toibaro, Javier; Miro, Jose M; Vassilenko, Anna; Girardi, Enrico; Bruyand, Mathias; Obel, Niels; Lundgren, Jens D; Mocroft, Amanda; Kirk, Ole

2016-03-01

Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study. Consecutive HIV-positive patients aged 16 years or older with a diagnosis of tuberculosis between Jan 1, 2011, and Dec 31, 2013, were enrolled from 62 HIV and tuberculosis clinics in 19 countries in eastern Europe, western Europe, and Latin America. The primary endpoint was death within 12 months after starting tuberculosis treatment; all deaths were classified according to whether or not they were tuberculosis related. Follow-up was either until death, the final visit, or 12 months after baseline, whichever occurred first. Risk factors for all-cause and tuberculosis-related deaths were assessed using Kaplan-Meier estimates and Cox models. Of 1406 patients (834 in eastern Europe, 317 in western Europe, and 255 in Latin America), 264 (19%) died within 12 months. 188 (71%) of these deaths were tuberculosis related. The probability of all-cause death was 29% (95% CI 26-32) in eastern Europe, 4% (3-7) in western Europe, and 11% (8-16) in Latin America (p<0·0001) and the corresponding probabilities of tuberculosis-related death were 23% (20-26), 1% (0-3), and 4% (2-8), respectively (p<0·0001). Patients receiving care outside eastern Europe had a 77% decreased risk of death: adjusted hazard ratio (aHR) 0·23 (95% CI 0·16-0·31). In eastern Europe, compared with patients who started a regimen with at least three active antituberculosis drugs, those who started fewer than three active antituberculosis drugs were at a higher risk of tuberculosis-related death (aHR 3·17; 95% CI 1·83-5·49) as were those who did not have baseline drug-susceptibility tests (2·24; 1·31-3·83). Other prognostic factors for increased tuberculosis-related mortality were disseminated tuberculosis and a low CD4 cell count. 18% of patients were receiving ART at tuberculosis diagnosis in eastern Europe compared with 44% in western Europe and 39% in Latin America (p<0·0001); 12 months later the proportions were 67% in eastern Europe, 92% in western Europe, and 85% in Latin America (p<0·0001). Patients with HIV and tuberculosis in eastern Europe have a risk of death nearly four-times higher than that in patients from western Europe and Latin America. This increased mortality rate is associated with modifiable risk factors such as lack of drug susceptibility testing and suboptimal initial antituberculosis treatment in settings with a high prevalence of drug resistance. Urgent action is needed to improve tuberculosis care for patients living with HIV in eastern Europe. EU Seventh Framework Programme. Copyright © 2016 Elsevier Ltd. All rights reserved.

Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection

PubMed Central

Belknap, Robert; Holland, David; Feng, Pei-Jean; Millet, Joan-Pau; Caylà, Joan A.; Martinson, Neil A.; Wright, Alicia; Chen, Michael P.; Moro, Ruth N.; Scott, Nigel A.; Arevalo, Bert; Miró, José M.; Villarino, Margarita E.; Weiner, Marc; Borisov, Andrey S.

2017-01-01

Background Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials.gov: NCT01582711) Setting Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa. Participants 1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection. Intervention Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring. Measurements The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication event–monitoring devices for self-administration. The main secondary outcome was adverse events. Results Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U.S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the direct-observation group, 74.0% (CI, 68.9% to 78.6%) in the self-administration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration–with–reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met noninferiority criteria. A few drug-related adverse events occurred and were similar across groups. Limitation Persons with latent tuberculosis infection enrolled in South Africa would not routinely be treated programmatically. Conclusion These results support using self-administered, once-weekly isoniazid and rifapentine to treat latent tuberculosis infection in the United States, and such treatment could be considered in similar settings when direct observation is not feasible. Primary Funding Source Centers for Disease Control and Prevention. PMID:29114781

[Evaluation of primary health care activities at the Albert Schweitzer hospital in Lambarene, Gabon].

PubMed

Diallo, M; Ninteretse, B

2007-06-01

In 1999 the Albert Schweitzer Hospital in Lambrene, Gabon set up a community health care service that provides immunization campaigns and mother/child health care and manages 9 village health care centers in a district with a population of approximately 64000 inhabitants. An evaluation conducted in April 2006 showed that collection of a consultation charge (15 euros) could cover the basic costs of operating these centers and purchasing necessary medicines. Three of the four centers evaluated demonstrated good quality indicators including properly kept records, posting of information bulletins for patients, appropriate referrals, and good relations with village authorities. At the center that performed poorly, the nurse apparently received no pay or lodging. Analysis of data about pediatric activity showed that diagnosis of diarrhea, malnutrition and anemia has fallen while hospitalization for tuberculosis and urinary schistomiasis is now being recorded. At the same time, village health centers are increasingly concerned with problems related to management and prevention of AIDS, malaria and urinary schistomiasis. This service shows that with good supervision it is possible to improve the quality of primary health care with partial but adequate recovery of costs and that basic health care workers are able to provide overall management for complicated patients, facilitate the work of reference hospital, and report new health problems.

Multidrug-resistant pulmonary tuberculosis in Los Altos, Selva and Norte regions, Chiapas, Mexico.

PubMed

Sánchez-Pérez, H J; Díaz-Vázquez, A; Nájera-Ortiz, J C; Balandrano, S; Martín-Mateo, M

2010-01-01

To analyse the proportion of multidrug-resistant tuberculosis (MDR-TB) in cultures performed during the period 2000-2002 in Los Altos, Selva and Norte regions, Chiapas, Mexico, and to analyse MDR-TB in terms of clinical and sociodemographic indicators. Cross-sectional study of patients with pulmonary tuberculosis (PTB) from the above regions. Drug susceptibility testing results from two research projects were analysed, as were those of routine sputum samples sent in by health personnel for processing (n = 114). MDR-TB was analysed in terms of the various variables of interest using bivariate tests of association and logistic regression. The proportion of primary MDR-TB was 4.6% (2 of 43), that of secondary MDR-TB was 29.2% (7/24), while among those whose history of treatment was unknown the proportion was 14.3% (3/21). According to the logistic regression model, the variables most highly associated with MDR-TB were as follows: having received anti-tuberculosis treatment previously, cough of >3 years' duration and not being indigenous. The high proportion of MDR cases found in the regions studied shows that it is necessary to significantly improve the control and surveillance of PTB.

Tuberculous Otitis with Proteus mirabilis Co-Infection: An Unsuspected Presentation Encountered in Clinical Practice.

PubMed

Rajesh Gandham, Nageswari; Sardar, Moumita; Jadhav, Savita Vivek; Vyawahare, Chanda; Misra, Rabindranath

2014-05-01

Tuberculosis, a contagious bacterial disease which is caused by Mycobacterium tuberculosis, primarily involves the lungs.Though Pulmonary tuberculosis (PTB) is the commonest clinical presentation, there is a need for alertness towards uncommon presentations which involve other organs. Tuberculous otitis media (TOM) is one such rare presentation seen in paediatric practice. It is characterized by painless otorrhoea which fails to respond to the routine antibacterial treatment. TOM usually occurs secondary to PTB. Here is a case of tuberculous otitis media with Proteus mirabilis co-infection, with no evidence of PTB. In the sample of ear discharge obtained from the patient, acid fast bacilli were demonstrated on direct microscopy after Ziehl-Neelsen staining. Culture done on Lowenstein-Jensen medium demonstrated slow-growing Mycobacterium. Bacteriological culture and identification helped in isolating Proteus mirabilis. PCR, followed by Line- Probe Assay for early identification and susceptibility testing to primary drugs, was done. Further, patient tested negative for the Mantoux test. Patient was enrolled in National Tuberculosis programme- RNTCP. This case emphasizes on one of the less common presentations of a common disease. A high clinical suspicion and laboratory confirmation are required for appropriate patient management.

Tuberculous Otitis with Proteus mirabilis Co-Infection: An Unsuspected Presentation Encountered in Clinical Practice

PubMed Central

Sardar, Moumita; Jadhav, Savita Vivek; Vyawahare, Chanda; Misra, Rabindranath

2014-01-01

Tuberculosis, a contagious bacterial disease which is caused by Mycobacterium tuberculosis, primarily involves the lungs.Though Pulmonary tuberculosis (PTB) is the commonest clinical presentation, there is a need for alertness towards uncommon presentations which involve other organs. Tuberculous otitis media (TOM) is one such rare presentation seen in paediatric practice. It is characterized by painless otorrhoea which fails to respond to the routine antibacterial treatment. TOM usually occurs secondary to PTB. Here is a case of tuberculous otitis media with Proteus mirabilis co-infection, with no evidence of PTB. In the sample of ear discharge obtained from the patient, acid fast bacilli were demonstrated on direct microscopy after Ziehl-Neelsen staining. Culture done on Lowenstein-Jensen medium demonstrated slow-growing Mycobacterium. Bacteriological culture and identification helped in isolating Proteus mirabilis. PCR, followed by Line- Probe Assay for early identification and susceptibility testing to primary drugs, was done. Further, patient tested negative for the Mantoux test. Patient was enrolled in National Tuberculosis programme- RNTCP. This case emphasizes on one of the less common presentations of a common disease. A high clinical suspicion and laboratory confirmation are required for appropriate patient management. PMID:24995225

[The clinical manifestations and diagnostics of otitis media caused by tuberculosis].

PubMed

Kryukov, A I; Garov, E V; Ivoilov, A Yu; Shadrin, G B; Sidorina, N G; Lavrova, A S

2015-01-01

The objective of the present study was to clarify the characteristic pathognomonic features of middle ear lesions associated with tuberculosis and the approaches to their diagnostics under the present-day conditions. The study included 11 cases (18 ears) of tuberculosis otitis media and the related lesions of the mastoid process diagnosed with the use of clinical, roentgenological, cytological, bacteriological, pathomorphological, and molecular-genetic methods (including PCR diagnostics). The primary localization of tuberculosis in the middle ear was documented in 6 patients; in 5 patients, it was associated with pulmonary involvement. Five patients presented with smoldering exudative otitis media and the remaining six ones with suppurative perforating otitis media. The tuberculous process was diagnosed with the use of various methods including clinical examination, bacteriological (9%), cytological (27.3%), pathomorphological (18%) studies, and PCR diagnostics (55%). Diagnosis was made within a period from 1 month to 1.5 years after the application of the patients for medical assistance which suggests the difficulty of verification of tuberculous etiology of the disease of the middle ear. It is concluded that the high index of suspicion in the case of smoldering middle ear pathology facilitates its early diagnostics and successful treatment.

Vitamin D supplementation promotes macrophages' anti-mycobacterial activity in type 2 diabetes mellitus patients with low vitamin D receptor expression.

PubMed

Lopez-Lopez, Nallely; Gonzalez-Curiel, Irma; Castañeda-Delgado, Julio; Montoya-Rosales, Alejandra; Gandara-Jasso, Benjamin; Enciso-Moreno, Jose Antonio; Rivas-Santiago, Bruno

2014-09-01

The increasing number of people with type 2 diabetes (DM2) is alarming and if it is taken into account that the relative odds of developing tuberculosis in diabetic patients ranges from 2.44 to 8.33 compared with non-diabetic patients, thus in developing countries where these two diseases are encountering face to face, there is a need for prophylaxis strategies. The role of vitamin D has been widely implicated in growth control of Mycobacterium tuberculosis (Mtb) during primary infection mainly through the induction of certain antimicrobial peptides (AMPs). In this study we evaluated the vitamin D serum levels, CYP27B1-hydroxylase enzyme, vitamin D receptor (VDR) and AMPs gene expression in Healthy donors, DM2 and TB patients. Results showed that DM2 group has lower VDR and AMPs expression levels. When Monocytes Derived Macrophages (MDM) from DM2 patients with low VDR expression were supplemented with vitamin D, MDMs eliminate efficiently M. tuberculosis. This preliminary study suggests the use of vitamin D as prophylaxis for tuberculosis in high DM2 endemic countries. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Social and environmental factors associated with the hospitalization of tuberculosis patients.

PubMed

de Oliveira, Nathália França; Gonçalves, Maria Jacirema Ferreira

2013-01-01

to identify social and environmental factors associated with hospitalization of tuberculosis (TB) patients in Manaus, Amazonas, during 2010. this is a quantitative cross-sectional epidemiological study, with primary data collection and analysis of human immunodeficiency virus (HIV), based on seropositive status. Among social factors for TB-HIV co-infection, the association between alcohol use and dependence was significant for employed workers; among non-co-infections, the association between income less than one minimum wage (U.S. $200) and retired people, Bolsa Família Program [Family Allowance]/other social benefits was significant. Regarding environmental factors, the association was significant for TB-HIV co-infection among those not having their own house, having masonry housing and daily garbage collection; and among non-co-infection, owning their own house, no masonry housing and lack of daily garbage collection was significant. The findings indicated that not only social factors, but also environmental ones are associated with hospitalization of tuberculosis patients, and such associations differ according to TB-HIV co-infection. Findings revealed that the non-biological factors associated with hospitalization of tuberculosis patients should be considered when caring patients with this disease.

Perspectives on the History of Bovine TB and the Role of Tuberculin in Bovine TB Eradication

PubMed Central

Good, Margaret; Duignan, Anthony

2011-01-01

Tuberculosis remains a significant disease of animals and humans worldwide. Bovine tuberculosis is caused by Mycobacteria with an extremely wide host range and serious, although currently probably underdiagnosed, zoonotic potential. Where bovine tuberculosis controls are effective, human zoonotic TB, due to Mycobacterium bovis or M. caprae, is uncommon and clinical cases are infrequent in cattle. Therefore, the control and ultimate eradication of bovine tuberculosis is desirable. Tuberculin tests are the primary screening tool used in bovine eradication. The choice of tuberculin test is dependent on the environment in which it is to be used. Tuberculin potency is critical to test performance, and the accurate determination of potency is therefore particularly important. The design of a control or eradication programme should take into consideration the fundamental scientific knowledge, the epidemiological profile of disease, the experience of other eradication programmes, and the presence, in the same ecosystem, of maintenance hosts, in which infection is self-sustaining and which are capable of transmitting infection. A control or eradication programme will necessarily require modification as it progresses and must be under constant review to identify the optimal desirable goals, the efficacy of policy, and constraints to progress. PMID:21547209

The Role of ESX-1 in Mycobacterium tuberculosis Pathogenesis.

PubMed

Wong, Ka-Wing

2017-05-01

In this article, we have described several cellular pathological effects caused by the Mycobacterium tuberculosis ESX-1. The effects include induction of necrosis, NOD2 signaling, type I interferon production, and autophagy. We then attempted to suggest that these pathological effects are mediated by the cytosolic access of M. tuberculosis -derived materials as a result of the phagosome-disrupting activity of the major ESX-1 substrate ESAT-6. Such activity of ESAT-6 is most likely due to its pore-forming activity at the membrane. The amyloidogenic characteristic of ESAT-6 is reviewed here as a potential mechanism of membrane pore formation. In addition to ESAT-6, the ESX-1 substrate EspB interferes with membrane-mediated innate immune mechanisms such as efferocytosis and autophagy, most likely through its ability to bind phospholipids. Overall, the M. tuberculosis ESX-1 secretion system appears to be a specialized system for the deployment of host membrane-targeting proteins, whose primary function is to interrupt key steps in innate immune mechanisms against pathogens. Inhibitors that block the ESX-1 system or block host factors critical for ESX-1 toxicity have been identified and should represent attractive potential new antituberculosis drugs.

Kinetics and cellular sources of cathelicidin during the course of experimental latent tuberculous infection and progressive pulmonary tuberculosis.

PubMed

Castañeda-Delgado, J; Hernández-Pando, R; Serrano, C J; Aguilar-León, D; León-Contreras, J; Rivas-Santiago, C; Méndez, R; González-Curiel, I; Enciso-Moreno, A; Rivas-Santiago, B

2010-09-01

In spite of advances in immunology on mycobacterial infection, there are few studies on the role of anti-microbial peptides in tuberculosis. The cathelin-related anti-microbial peptide (CRAMP) is the only cathelicidin isolated from mice. In this work we investigated the cellular sources and the production kinetics of this molecule during experimental tuberculosis, using two well-characterized models of latent or chronic infection and progressive disease. The lung of non-infected control mice expressed CRAMP at very low levels. In both models of experimental tuberculosis the main cells immunolabelled for CRAMP were bronchial epithelial cells, macrophages and pneumocytes types II and I. After intratracheal infection with a high bacilli dose (H37Rv strain) in Balb/c mice to produce progressive disease, a high CRAMP gene expression was induced showing three peaks: very early after 1 day of infection, at day 21 when the peak of protective immunity in this model is raised, and at day 28 when the progressive phase starts and the immunoelectronmicroscopy study showed intense immunolabelling in the cell wall and cytoplasm of intracellular bacilli, as well as in cytoplasmic vacuoles. Interestingly, at day 60 post-infection, when advanced progressive disease is well established, characterized by high bacillary loads and extensive tissue damage, CRAMP gene expression decreased but strong CRAMP immunostaining was detected in vacuolated macrophages filled with bacilli. Thus, cathelicidin is highly produced during experimental pulmonary tuberculosis from diverse cellular sources and could have significant participation in its pathogenesis. © 2010 British Society for Immunology.

Modulation of Roquin function in myeloid cells reduces Mycobacterium tuberculosis induced inflammation

PubMed Central

Nagalingam, Gayathri; Vinuesa, Carola G.; Britton, Warwick J; Saunders, Bernadette M.

2017-01-01

Damaging inflammation is a hallmark of Mycobacterium tuberculosis infection, and understanding how this is regulated is important for the development of new therapies to limit excessive inflammation. The E3 ubiquitin ligase, Roquin, is involved in immune regulation, however its role in immunity to M. tuberculosis is unknown. To address this we infected mice with a point mutation in Roquin1/Rc3h1 (sanroque). Aerosol-infected sanroque mice showed enhanced control of M. tuberculosis infection associated with delayed bacterial dissemination and upregulated TNF production in the lung after 2 weeks. However, this early control of infection was not maintained, and by 8 weeks post-infection sanroque mice demonstrated increased bacterial burden and dysregulated inflammation in the lung. As the inflammation in the lung of the sanroque mice could have been influenced by emerging autoimmune conditions that are characteristic of aging sanroque mice, the function of Roquin was examined in immune cell subsets in the absence of autoimmune complications. Mycobacterium bovis BCG-primed sanroque T cells transferred into Rag1-/- mice provided equivalent protection in the spleen and liver. Interestingly, the transfer of mycobacteria-specific (P25 CD4+ TCR transgenic) wild-type spleen cells into sanroque.Rag1-/- mice actually led to enhanced protection with reduced bacterial load, decreased chemokine expression and reduced inflammation in the lung compared with transfers into Rag1-/- mice expressing intact Roquin. These studies suggest that modulation of Roquin in myeloid cells may reduce both inflammation and bacterial growth during the chronic phase of M. tuberculosis infection. PMID:28747346

Multiple Inflammatory Cytokines Converge to Regulate CD8+ T cell Expansion and Function During Tuberculosis

PubMed Central

Booty, Matthew G.; Nunes-Alves, Cláudio; Carpenter, Stephen M.; Jayaraman, Pushpa; Behar, Samuel M.

2015-01-01

The differentiation of effector CD8+ T cells is a dynamically regulated process that varies during different infections and is influenced by the inflammatory milieu of the host. Here, we define three signals regulating CD8+ T cell responses during tuberculosis by focusing on cytokines known to affect disease outcome: IL-12, type I IFN, and IL-27. Using mixed bone marrow chimeras, we compared wild type and cytokine receptor knockout CD8+ T cells within the same mouse following aerosol infection with Mycobacterium tuberculosis. Four weeks post-infection, IL-12, type 1 IFN, and IL-27 were all required for efficient CD8+ T cell expansion in the lungs. We next determined if these cytokines directly promote CD8+ T cell priming or are required only for expansion in the lungs. Utilizing retrogenic CD8+ T cells specific for the Mtb antigen TB10.4 (EsxH), we observed that IL-12 is the dominant cytokine driving both CD8+ T cell priming in the lymph node and expansion in the lungs; however, type I IFN and IL-27 have non-redundant roles supporting pulmonary CD8+ T cell expansion. Thus, IL-12 is a major signal promoting priming in the lymph node, but a multitude of inflammatory signals converge in the lung to promote continued expansion. Furthermore, these cytokines regulate the differentiation and function of CD8+ T cells during tuberculosis. These data demonstrate distinct and overlapping roles for each of the cytokines examined and underscore the complexity of CD8+ T cell regulation during tuberculosis. PMID:26755819

Estimation of the relative sensitivity of the comparative tuberculin skin test in tuberculous cattle herds subjected to depopulation.

PubMed

Karolemeas, Katerina; de la Rua-Domenech, Ricardo; Cooper, Roderick; Goodchild, Anthony V; Clifton-Hadley, Richard S; Conlan, Andrew J K; Mitchell, Andrew P; Hewinson, R Glyn; Donnelly, Christl A; Wood, James L N; McKinley, Trevelyan J

2012-01-01

Bovine tuberculosis (bTB) is one of the most serious economic animal health problems affecting the cattle industry in Great Britain (GB), with incidence in cattle herds increasing since the mid-1980s. The single intradermal comparative cervical tuberculin (SICCT) test is the primary screening test in the bTB surveillance and control programme in GB and Ireland. The sensitivity (ability to detect infected cattle) of this test is central to the efficacy of the current testing regime, but most previous studies that have estimated test sensitivity (relative to the number of slaughtered cattle with visible lesions [VL] and/or positive culture results) lacked post-mortem data for SICCT test-negative cattle. The slaughter of entire herds ("whole herd slaughters" or "depopulations") that are infected by bTB are occasionally conducted in GB as a last-resort control measure to resolve intractable bTB herd breakdowns. These provide additional post-mortem data for SICCT test-negative cattle, allowing a rare opportunity to calculate the animal-level sensitivity of the test relative to the total number of SICCT test-positive and negative VL animals identified post-mortem (rSe). In this study, data were analysed from 16 whole herd slaughters (748 SICCT test-positive and 1031 SICCT test-negative cattle) conducted in GB between 1988 and 2010, using a bayesian hierarchical model. The overall rSe estimate of the SICCT test at the severe interpretation was 85% (95% credible interval [CI]: 78-91%), and at standard interpretation was 81% (95% CI: 70-89%). These estimates are more robust than those previously reported in GB due to inclusion of post-mortem data from SICCT test-negative cattle.

Estimation of the Relative Sensitivity of the Comparative Tuberculin Skin Test in Tuberculous Cattle Herds Subjected to Depopulation

PubMed Central

Karolemeas, Katerina; de la Rua-Domenech, Ricardo; Cooper, Roderick; Goodchild, Anthony V.; Clifton-Hadley, Richard S.; Conlan, Andrew J. K.; Mitchell, Andrew P.; Hewinson, R. Glyn; Donnelly, Christl A.; Wood, James L. N.; McKinley, Trevelyan J.

2012-01-01

Bovine tuberculosis (bTB) is one of the most serious economic animal health problems affecting the cattle industry in Great Britain (GB), with incidence in cattle herds increasing since the mid-1980s. The single intradermal comparative cervical tuberculin (SICCT) test is the primary screening test in the bTB surveillance and control programme in GB and Ireland. The sensitivity (ability to detect infected cattle) of this test is central to the efficacy of the current testing regime, but most previous studies that have estimated test sensitivity (relative to the number of slaughtered cattle with visible lesions [VL] and/or positive culture results) lacked post-mortem data for SICCT test-negative cattle. The slaughter of entire herds (“whole herd slaughters” or “depopulations”) that are infected by bTB are occasionally conducted in GB as a last-resort control measure to resolve intractable bTB herd breakdowns. These provide additional post-mortem data for SICCT test-negative cattle, allowing a rare opportunity to calculate the animal-level sensitivity of the test relative to the total number of SICCT test-positive and negative VL animals identified post-mortem (rSe). In this study, data were analysed from 16 whole herd slaughters (748 SICCT test-positive and 1031 SICCT test-negative cattle) conducted in GB between 1988 and 2010, using a Bayesian hierarchical model. The overall rSe estimate of the SICCT test at the severe interpretation was 85% (95% credible interval [CI]: 78–91%), and at standard interpretation was 81% (95% CI: 70–89%). These estimates are more robust than those previously reported in GB due to inclusion of post-mortem data from SICCT test-negative cattle. PMID:22927952

Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study.

PubMed

Dorman, Susan E; Schumacher, Samuel G; Alland, David; Nabeta, Pamela; Armstrong, Derek T; King, Bonnie; Hall, Sandra L; Chakravorty, Soumitesh; Cirillo, Daniela M; Tukvadze, Nestani; Bablishvili, Nino; Stevens, Wendy; Scott, Lesley; Rodrigues, Camilla; Kazi, Mubin I; Joloba, Moses; Nakiyingi, Lydia; Nicol, Mark P; Ghebrekristos, Yonas; Anyango, Irene; Murithi, Wilfred; Dietze, Reynaldo; Lyrio Peres, Renata; Skrahina, Alena; Auchynka, Vera; Chopra, Kamal Kishore; Hanif, Mahmud; Liu, Xin; Yuan, Xing; Boehme, Catharina C; Ellner, Jerrold J; Denkinger, Claudia M

2018-01-01

The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (-2·7%, -3·9 to -1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Primary Intestinal Lymphangiectasia (Waldmann's Disease) Presenting with Chylous Effusions in a 15-Year-Old.

PubMed

Surampalli, Vijay; Ramaswamy, Srinath; Surendran, Deepanjali; Bammigatti, Chanaveerappa; Swaminathan, Rathinam Palamalai

2017-08-01

Primary Intestinal Lymphangiectasia (PIL) is a rare disease of unknown aetiology which presents in the paediatric age group with anasarca, diarrhoea, hypoproteinaemia, lymphoedema and chylous effusions. Tuberculosis, filariasis, chest trauma, malignancies and haematological disorders usually contribute to most cases of secondary lymphangiectasia and chylous effusions. We hereby describe a case of PIL presenting with chylous effusions which remained undiagnosed for eight years.

Preparing patients for biologic medications for dermatologic and rheumatic diseases.

PubMed

Smith, Benjamin J; Nuccio, Brigitta C; Graves, Katelyn Y; McMillan, Victor M

2018-06-01

Psoriasis, psoriatic arthritis, and rheumatoid arthritis are prevalent conditions that often require a team of primary care and specialist healthcare professionals for the most optimum patient outcomes. Primary care providers can facilitate referrals to dermatology and rheumatology specialists by obtaining the needed screening workup for patients who need treatment with immunosuppressive therapies. This article reviews tuberculosis screening, hepatitis screening, and vaccinations to be administered before patients begin biologic medications.

Influence of Ebola on tuberculosis case finding and treatment outcomes in Liberia

PubMed Central

Cambell, C. L.; Ade, S.; Bhat, P.; Harries, A. D; Wilkinson, E.; Cooper, C. T.

2017-01-01

Setting: National Leprosy and Tuberculosis (TB) Control Programme, Liberia. Objectives: To assess TB case finding, including human immunodeficiency virus (HIV) associated interventions and treatment outcomes, before (January 2013–March 2014), during (April 2014–June 2015) and after (July–December 2015) the Ebola virus disease outbreak. Design: A cross-sectional study and retrospective cohort analysis of outcomes. Results: The mean quarterly numbers of individuals with presumptive TB and the proportion diagnosed as smear-positive were: pre-Ebola (n = 7032, 12%), Ebola (n = 6147, 10%) and post-Ebola (n = 6795, 8%). For all forms of TB, stratified by category and age group, there was a non-significant decrease in the number of cases from the pre-Ebola to the Ebola and post-Ebola periods. There were significant decreases in numbers of cases with smear-positive pulmonary TB (PTB) from the pre-Ebola period (n = 855), to the Ebola (n = 640, P < 0.001) and post-Ebola (n = 568, P < 0.001) periods. The proportions of patients tested for HIV, found to be HIV-positive and started on antiretroviral therapy decreased as follows: pre-Ebola (respectively 72%, 15% and 34%), Ebola (69%, 14% and 30%) and post-Ebola (68%, 12% and 26%). Treatment success rates among TB patients were: 80% pre-Ebola, 69% Ebola (P < 0.001) and 73% post-Ebola (P < 0.001). Loss to follow-up was the main contributing adverse outcome. Conclusion: The principal negative effects of Ebola were the significant decreases in diagnoses of smear-positive PTB, the declines in HIV testing and antiretroviral therapy uptake and poor treatment success. Ways to prevent these adverse effects from recurring in the event of another Ebola outbreak need to be found. PMID:28744441

Influence of Ebola on tuberculosis case finding and treatment outcomes in Liberia.

PubMed

Konwloh, P K; Cambell, C L; Ade, S; Bhat, P; Harries, A D; Wilkinson, E; Cooper, C T

2017-06-21

Setting: National Leprosy and Tuberculosis (TB) Control Programme, Liberia. Objectives: To assess TB case finding, including human immunodeficiency virus (HIV) associated interventions and treatment outcomes, before (January 2013-March 2014), during (April 2014-June 2015) and after (July-December 2015) the Ebola virus disease outbreak. Design: A cross-sectional study and retrospective cohort analysis of outcomes. Results: The mean quarterly numbers of individuals with presumptive TB and the proportion diagnosed as smear-positive were: pre-Ebola ( n = 7032, 12%), Ebola ( n = 6147, 10%) and post-Ebola ( n = 6795, 8%). For all forms of TB, stratified by category and age group, there was a non-significant decrease in the number of cases from the pre-Ebola to the Ebola and post-Ebola periods. There were significant decreases in numbers of cases with smear-positive pulmonary TB (PTB) from the pre-Ebola period ( n = 855), to the Ebola ( n = 640, P < 0.001) and post-Ebola ( n = 568, P < 0.001) periods. The proportions of patients tested for HIV, found to be HIV-positive and started on antiretroviral therapy decreased as follows: pre-Ebola (respectively 72%, 15% and 34%), Ebola (69%, 14% and 30%) and post-Ebola (68%, 12% and 26%). Treatment success rates among TB patients were: 80% pre-Ebola, 69% Ebola ( P < 0.001) and 73% post-Ebola ( P < 0.001). Loss to follow-up was the main contributing adverse outcome. Conclusion: The principal negative effects of Ebola were the significant decreases in diagnoses of smear-positive PTB, the declines in HIV testing and antiretroviral therapy uptake and poor treatment success. Ways to prevent these adverse effects from recurring in the event of another Ebola outbreak need to be found.

"Not a shack in the woods": architecture for tuberculosis in Muskoka and Toronto.

PubMed

Adams, Annmarie; Burke, Stacie

2006-01-01

This paper explores architecture as a primary source in the history of tuberculosis. In comparing five Ontario sanatoria built between 1897 and 1923, we identify a range of types and a growing resemblance of ex-urban TB sanatoria to urban hospitals. Existing literature on Canadian TB hospital architecture suggests the endurance of picturesque architecture, but the cottage plan was only one of the types deemed appropriate for consumptives in the early 20th century, even in Muskoka. Furthermore we argue that urban and ex-urban TB ideologies actually coalesce about 1923, best illustrated in the boldly modern architecture of Muskoka's new Gage pavilion.

Is there a rationale for pulmonary rehabilitation following successful chemotherapy for tuberculosis?

PubMed

Muñoz-Torrico, Marcela; Rendon, Adrian; Centis, Rosella; D'Ambrosio, Lia; Fuentes, Zhenia; Torres-Duque, Carlos; Mello, Fernanda; Dalcolmo, Margareth; Pérez-Padilla, Rogelio; Spanevello, Antonio; Migliori, Giovanni Battista

2016-01-01

The role of tuberculosis as a public health care priority and the availability of diagnostic tools to evaluate functional status (spirometry, plethysmography, and DLCO determination), arterial blood gases, capacity to perform exercise, lesions (chest X-ray and CT), and quality of life justify the effort to consider what needs to be done when patients have completed their treatment. To our knowledge, no review has ever evaluated this topic in a comprehensive manner. Our objective was to review the available evidence on this topic and draw conclusions regarding the future role of the "post-tuberculosis treatment" phase, which will potentially affect several million cases every year. We carried out a non-systematic literature review based on a PubMed search using specific keywords (various combinations of the terms "tuberculosis", "rehabilitation", "multidrug-resistant tuberculosis", "pulmonary disease", "obstructive lung disease", and "lung volume measurements"). The reference lists of the most important studies were retrieved in order to improve the sensitivity of the search. Manuscripts written in English, Spanish, and Russian were selected. The main areas of interest were tuberculosis sequelae following tuberculosis diagnosis and treatment; "destroyed lung"; functional evaluation of sequelae; pulmonary rehabilitation interventions (physiotherapy, long-term oxygen therapy, and ventilation); and multidrug-resistant tuberculosis.The evidence found suggests that tuberculosis is definitively responsible for functional sequelae, primarily causing an obstructive pattern on spirometry (but also restrictive and mixed patterns), and that there is a rationale for pulmonary rehabilitation. We also provide a list of variables that should be discussed in future studies on pulmonary rehabilitation in patients with post-tuberculosis sequelae. RESUMO O papel da tuberculose como uma prioridade de saúde pública e a disponibilidade de ferramentas diagnósticas para avaliar o estado funcional (espirometria, pletismografia e DLCO), a gasometria arterial, a capacidade de realizar exercícios, as lesões (radiografia de tórax e TC) e a qualidade de vida justificam o esforço de se considerar o que deve ser feito quando os pacientes completam seu tratamento. Até onde sabemos, nenhuma revisão avaliou esse tópico de forma abrangente. Nosso objetivo foi revisar as evidências disponíveis e obter algumas conclusões sobre o futuro papel da fase de "tratamento pós-tuberculose", que irá potencialmente impactar milhões de casos todos os anos. Realizou-se uma revisão não sistemática da literatura tendo como base uma pesquisa no PubMed usando palavras-chave específicas (várias combinações dos termos "tuberculose", "reabilitação", "tuberculose multirresistente", "doença pulmonar", "doença pulmonar obstrutiva", e "medidas de volume pulmonar"). As listas de referências dos artigos principais foram recuperadas para melhorar a sensibilidade da busca. Foram selecionados manuscritos escritos em inglês, espanhol e russo. As principais áreas de interesse foram sequelas de tuberculose após diagnóstico e tratamento; "pulmão destruído"; avaliação funcional das sequelas; intervenções de reabilitação pulmonar (fisioterapia, oxigenoterapia de longo prazo e ventilação); e tuberculose multirresistente. As evidências encontradas sugerem que a tuberculose é definitivamente responsável por sequelas funcionais, principalmente causando um padrão obstrutivo na espirometria (mas também padrões restritivos e mistos) e que há razão para a reabilitação pulmonar. Fornecemos também uma lista de variáveis a serem discutidas em futuros estudos sobre reabilitação pulmonar em pacientes com sequelas pós-tuberculose.

Whole-animal imaging of bacterial infection using endoscopic excitation of β-lactamase (BlaC)-specific fluorogenic probe

NASA Astrophysics Data System (ADS)

Nooshabadi, Fatemeh; Yang, Hee-Jeong; Cheng, Yunfeng; Xie, Hexin; Rao, Jianghong; Cirillo, Jeffrey D.; Maitland, Kristen C.

2016-03-01

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains one of the most frequent causes of death worldwide. The slow growth rate of Mtb limits progress toward understanding tuberculosis including diagnosis of infections and evaluating therapeutic efficacy. Development of near-infrared (NIR) β-lactamase (BlaC)-specific fluorogenic substrate has made a significant breakthrough in the whole-animal imaging to detect Mtb infection. The reporter enzyme fluorescence (REF) system using a BlaC-specific fluorogenic substrate has improved the detection sensitivity in whole-animal optical imaging down to ~104 colony forming units (CFU) of bacteria, about 100-fold improvement over recombinant strains. However, improvement of detection sensitivity is strongly needed for clinical diagnosis of early stage infection at greater tissue depth. In order to improve detection sensitivity, we have integrated a fiber-based microendoscpe into a whole-animal imaging system to transmit the excitation light from the fiber bundle to the fluorescent target directly and measure fluorescent level using BlaC-specific REF substrate in the mouse lung. REF substrate, CNIR800, was delivered via aerosol route to the pulmonary infected mice with M. bovis BCG strain at 24 hours post-infection and groups of mice were imaged at 1-4 hours post-administration of the substrate using the integrated imaging system. In this study we evaluated the kinetics of CNIR800 substrate using REF technology using the integrated imaging system. Integration of these technologies has great promise for improved detection sensitivity allowing pre-clinical imaging for evaluation of new therapeutic agents.

Pulmonary tuberculosis and non-recent immigrants in Japan – some issues for post-entry interventions

PubMed Central

Uchimura, Kazuhiro; Ohkado, Akihiro; Kato, Seiya

2017-01-01

Foreign-born persons are considered one of the high-risk populations for tuberculosis (TB), and numerous studies have discussed the potential role of pre-entry TB screening for immigrants. However, rates of TB disease among immigrants can remain high several years after entry. In Japan, approximately 50% of TB among foreign-born persons occurs among those who have entered Japan more than five years before being diagnosed, i.e. non-recent immigrants. However, little attention has been paid so far to the issue of TB control among the non-recent immigrants. A detailed analysis of the Japan Tuberculosis Surveillance data was therefore conducted to describe the characteristics of TB among non-recent immigrants and discuss policy implications in terms of post-entry interventions in Japan. The main findings were as follows: 1) the proportion of pulmonary TB cases aged 65 years and older was higher among non-recent than recent immigrants (9.8% vs 1.2%); 2) the proportion of those with social risk factors including homelessness and and being on social welfare assistance was higher among non-recent than recent immigrants; and 3) the proportion of those detected via routine screening at school or workplace was significantly lower among non-recent immigrants aged between 25 and 64 than among recent immigrants in the same age group (15.4% vs 28.7%). Our results suggested the need to increase the opportunities for and simultaneously improve the take-up rate of community-based screening for non-recent immigrants. PMID:29487759

Systematic Survey of Serine Hydrolase Activity in Mycobacterium tuberculosis Defines Changes Associated with Persistence

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

Ortega, Corrie; Anderson, Lindsey N.; Frando, Andrew

The transition between replication and non-replication underlies much of Mycobacterium tuberculosis (Mtb) pathogenicity, as non- or slowly replicating Mtb are responsible for persistence and poor treatment outcomes. Therapeutic targeting of non-replicating, persistent populations is a priority for tuberculosis treatment, but only few drug targets in non-replicating Mtb are currently known. Here, we directly measure the activity of the highly diverse and druggable serine hydrolases (SHs) during active replication and non-replication by activity-based proteomics. We predict serine hydrolase activity for 78 proteins, including 27 proteins with previously unknown function, and identify 37 SHs that remain active even in the absence ofmore » replication, providing a set of candidate persistence targets. Non-replication was associated with large shifts in the activity of the majority of SHs. These activity changes were largely independent of SH abundance, indicating extensive post-translational regulation. By probing a large cross-section of druggable Mtb enzyme space during replication and non-replication, we identify new SHs and suggest new persistence targets.« less

Inherited and acquired immunodeficiencies underlying tuberculosis in childhood

PubMed Central

Boisson-Dupuis, Stéphanie; Bustamante, Jacinta; El-Baghdadi, Jamila; Camcioglu, Yildiz; Parvaneh, Nima; Azbaoui, Safaa El; Agader, Aomar; Hassani, Amal; Hafidi, Naima El; Mrani, Nidal Alaoui; Jouhadi, Zineb; Ailal, Fatima; Najib, Jilali; Reisli, Ismail; Zamani, Adil; Yosunkaya, Sebnem; Gulle-Girit, Saniye; Yildiran, Alisan; Cipe, Funda Erol; Torun, Selda Hancerli; Metin, Ayse; Atikan, Basak Yildiz; Hatipoglu, Nevin; Aydogmus, Cigdem; Kilic, Sara Sebnem; Dogu, Figen; Karaca, Neslihan; Aksu, Guzide; Kutukculer, Necil; Keser-Emiroglu, Melike; Somer, Ayper; Tanir, Gonul; Aytekin, Caner; Adimi, Parisa; Mahdaviani, Seyed Alireza; Mamishi, Setareh; Bousfiha, Aziz; Sanal, Ozden; Mansouri, Davood; Casanova, Jean-Laurent; Abel, Laurent

2015-01-01

Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey. PMID:25703555

Sex disparities in tuberculosis suspect evaluation: a cross-sectional analysis in rural Uganda.

PubMed

Miller, C R; Davis, J L; Katamba, A; Sserwanga, A; Kakeeto, S; Kizito, F; Cattamanchi, A

2013-04-01

Six primary health care centers in rural Uganda. To compare the quality of tuberculosis (TB) evaluation for men and women presenting to primary health care facilities in high-burden settings. Cross-sectional study using indicators derived from the International Standards of Tuberculosis Care (ISTC) to compare the quality of TB evaluation services provided to men and women. Of 161 230 patient visits between January 2009 and December 2010, 112 329 (69.7%) were women. We considered 3308 (2.1%) patients with cough ≥2 weeks as TB suspects, of whom 1871 (56.6%) were women. Female TB suspects were less likely to be referred for sputum smear examination (45.9% vs. 61.6%, P < 0.001), to complete sputum smear examination if referred (73.7% vs. 78.3%, P = 0.024) and to receive comprehensive evaluation and care as defined by the ISTC (33.0% vs. 45.6%, P < 0.001). After adjusting for age, clinic site and visit date, women remained less likely to be referred for sputum smear examination (risk ratio [RR] 0.81, 95%CI 0.74-0.89, P < 0.001) and to receive ISTC-recommended care (RR 0.79, 95%CI 0.72-0.86, P < 0.001). Strategies to ensure that women receive appropriate TB evaluation could provide a valuable opportunity for increasing case detection while also promoting equitable and universal access to care.

Proteome analysis of ofloxacin and moxifloxacin induced mycobacterium tuberculosis isolates by proteomic approach.

PubMed

Lata, Manju; Sharma, Divakar; Kumar, Bhavnesh; Deo, Nirmala; Tiwari, Pramod Kumar; Bisht, Deepa; Venkatesan, Krishnamurthy

2015-01-01

Ofloxacin (OFX) and moxifloxacin (MOX) are the most promising second line drugs for tuberculosis treatment. Although the primary mechanism of action of OFX and MOX is gyrase inhibition, other possible mechanisms cannot be ruled out. Being the functional moiety of cell, the proteins act as primary targets for developing drugs, diagnostics and therapeutics. In this study we have investigated the proteomic changes of Mycobacterium tuberculosis isolates induced by OFX and MOX by applying comparative proteomic approaches based on two-dinensional gel electrophoresis (2DE) along with matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI TOF/TOF-MS) and bioinformatic tools. The findings are likely to provide new understanding of OFX and MOX mechanisms that might be helpful in exploring new diagnostics and drug targets. Our study explored eleven proteins (Rv2889c, Rv2623, Rv0952, Rv1827, Rv1932, Rv0054, Rv1080c, Rv3418c, Rv3914, Rv1636 and Rv0009) that were overexpressed in the presence of drugs. Among them, Rv2623, Rv1827 and Rv1636 were identified as proteins with unknown function. InterProScan and molecular docking revealed that the conserved domain of hypothetical proteins interact with OFX and MOX which indicate a probable inhibition/modulation of the functioning of these proteins by both drugs, which might be overexpressed to overcome this effect.

Health care workers' gender bias in testing could contribute to missed tuberculosis among women in South Africa.

PubMed

Smith, A; Burger, R; Claassens, M; Ayles, H; Godfrey-Faussett, P; Beyers, N

2016-03-01

Eight communities with high tuberculosis (TB) prevalence, Western Cape, South Africa. To identify sex differences in TB health-seeking behaviour and diagnosis in primary health care facilities and how this influences TB diagnosis. We used data from a prevalence survey among 30,017 adults conducted in 2010 as part of the Zambia, South Africa Tuberculosis and AIDS Reduction (ZAMSTAR) trial. A total of 1670 (5.4%) adults indicated they had a cough of ⩾2 weeks, 950 (56.9%) of whom were women. Women were less likely to report a cough of ⩾2 weeks (5.1% vs. 6.4%, P < 0.001), but were more likely to seek care for their cough (32.6% vs. 26.9%, P = 0.012). Of all adults who sought care, 403 (80.0%) sought care for their cough at a primary health care (PHC) facility (79.0% women vs. 81.4% men, P = 0.511). Women were less likely to be asked for a sputum sample at the PHC facility (63.3% vs. 77.2%, P = 0.003) and less likely to have a positive sputum result (12.6% vs. 20.7%, P = 0.023). The attainment of sex equity in the provision of TB health services requires adherence to testing protocols. Everyone, irrespective of sex, who seeks care for a cough of ⩾2 weeks should be tested.

Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification

PubMed Central

Wareham, Alice; Lewandowski, Kuiama S.; Williams, Ann; Dennis, Michael J.; Sharpe, Sally; Vipond, Richard; Silman, Nigel; Ball, Graham

2016-01-01

A temporal study of gene expression in peripheral blood leukocytes (PBLs) from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides. Data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time course study. Further data refinements identified groups of key markers showing group-specific expression patterns, with a substantial reprogramming event evident at the four to six week interval. Selected statistically-significant gene entities from this study and other immune and apoptotic markers were validated using qPCR, which confirmed many of the results obtained using microarray hybridisation. These showed evidence of a step-change in gene expression from an ‘early’ FOS-associated response, to a ‘late’ predominantly type I interferon-driven response, with coincident reduction of expression of other markers. Loss of T-cell-associate marker expression was observed in responsive animals, with concordant elevation of markers which may be associated with a myeloid suppressor cell phenotype e.g. CD163. The animals in the study were of different lineages and these Chinese and Mauritian cynomolgous macaque lines showed clear evidence of differing susceptibilities to Tuberculosis challenge. We determined a number of key differences in response profiles between the groups, particularly in expression of T-cell and apoptotic makers, amongst others. These have provided interesting insights into innate susceptibility related to different host `phenotypes. Using a combination of parametric and non-parametric artificial neural network analyses we have identified key genes and regulatory pathways which may be important in early and adaptive responses to TB. Using comparisons between data outputs of each analytical pipeline and comparisons with previously published Human TB datasets, we have delineated a subset of gene entities which may be of use for biomarker diagnostic test development. PMID:27228113

Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste

PubMed Central

Martins, Nelson; Morris, Peter

2009-01-01

Objective To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis. Design Parallel group randomised controlled trial. Setting Three primary care clinics in Dili, Timor-Leste. Participants 270 adults aged ≥18 with previously untreated newly diagnosed pulmonary tuberculosis. Main outcome measures Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes. Results Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3). Conclusion Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required. Trial registration Clinical Trials NCT0019256. PMID:19858174

Determining the lymphadenopathy characteristics of the mediastinum in lung CT scan of children with tuberculosis.

PubMed

Mehrian, Payam; Moghaddam, Amin Momeni; Tavakkol, Elham; Amini, Afshin; Moghimi, Mehrdad; Kabir, Ali; Velayati, Aliakbar

2016-09-01

Most tuberculosis cases in children are primary infection, with difficult and imprecise diagnosis mainly based on the existence of mediastinal lymphadenopathy. Here, we investigated the characteristics of mediastinal lymphadenopathy in lung computed tomography (CT) scans of children with tuberculosis. This cross-sectional study was performed on 75 children with tuberculosis referred to Masih Daneshvari Hospital in Tehran, Iran, from 2009 to 2013. Their medical records were investigated, and CT-scan characteristics were extracted by a radiologist. Mean±standard deviation age of cases was 11.2±4.6years. CT-scan results indicated 94.7% of cases had lymphadenopathy, with lower paratracheal, upper paratracheal, hilar, and subcarinal forms observed in 81.7%, 69.1%, 53.5%, and 47.9% of cases as the most involved stations in lymph nodes, respectively. In 74.6% of patients with mediastinal lymphadenopathy, perilymph node fat inflammation (matting) was observed, with 52.11% exhibiting conglomeration. Bronchial pressure was observed in 4.23% of children with tuberculosis, and bilateral-, right-, and left-parenchymal involvement was observed in 42.7%, 25.3%, and 8% of these cases, respectively. Left- and right-pleural effusion and calcification was reported in 6.7%, 12%, and 5.6% of patients, respectively. Additionally, nearly 80% of patients exhibited mediastinal lymphadenopathy and lung-parenchyma involvement simultaneously. Lung-parenchyma involvement was significantly correlated with subcarinal (p<.001), hilar (p<.001), subaortic (p=.030), lower paratracheal (p=.037), and axillary (p=.006) stations. Situation of mediastinal lymphadenopathy and its synchronicity with lung-parenchyma involvement can help in differential diagnosis of pulmonary tuberculosis from other lung diseases. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Quantitative Comparison of Active and Latent Tuberculosis in the Cynomolgus Macaque Model▿ †

PubMed Central

Lin, Philana Ling; Rodgers, Mark; Smith, Le'kneitah; Bigbee, Matthew; Myers, Amy; Bigbee, Carolyn; Chiosea, Ion; Capuano, Saverio V.; Fuhrman, Carl; Klein, Edwin; Flynn, JoAnne L.

2009-01-01

We previously described that low-dose Mycobacterium tuberculosis infection in cynomolgus macaques results in a spectrum of disease similar to that of human infection: primary disease, latent infection, and reactivation tuberculosis (S. V. Capuano III, D. A. Croix, S. Pawar, A. Zinovik, A. Myers, P. L. Lin, S. Bissel, C. Fuhrman, E. Klein, and J. L. Flynn, Infect. Immun. 71:5831-5844, 2003). This is the only established model of latent infection, and it provides a unique opportunity to understand host and pathogen differences across of range of disease states. Here, we provide a more extensive and detailed characterization of the gross pathology, microscopic histopathology, and immunologic characteristics of monkeys in each clinical disease category. The data underscore the similarities between human and nonhuman primate M. tuberculosis infection. Furthermore, we describe novel methods of quantifying gross pathology and bacterial burden that distinguish between active disease and latent infection, and we extend the usefulness of this model for comparative studies. Early in infection, an abnormal chest X ray, M. tuberculosis growth by gastric aspirate, and increased mycobacterium-specific gamma interferon (IFN-γ) in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage (BAL) cells were associated with the development of active disease. At necropsy, disease was quantified with respect to pathology and bacterial numbers. Microscopically, a spectrum of granuloma types are seen and differ with disease type. At necropsy, monkeys with active disease had more lung T cells and more IFN-γ from PBMC, BAL, and mediastinal lymph nodes than monkeys with latent infection. Finally, we have observed a spectrum of disease not only in monkeys with active disease but also in those with latent infection that provides insight into human latent tuberculosis. PMID:19620341

8-Hydroxyquinolines Are Boosting Agents of Copper-Related Toxicity in Mycobacterium tuberculosis.

PubMed

Shah, Santosh; Dalecki, Alex G; Malalasekera, Aruni P; Crawford, Cameron L; Michalek, Suzanne M; Kutsch, Olaf; Sun, Jim; Bossmann, Stefan H; Wolschendorf, Frank

2016-10-01

Copper (Cu) ions are likely the most important immunological metal-related toxin utilized in controlling bacterial infections. Impairment of bacterial Cu resistance reduces viability within the host. Thus, pharmacological enhancement of Cu-mediated antibacterial toxicity may lead to novel strategies in drug discovery and development. Screening for Cu toxicity-enhancing antibacterial molecules identified 8-hydroxyquinoline (8HQ) to be a potent Cu-dependent bactericidal inhibitor of Mycobacterium tuberculosis The MIC of 8HQ in the presence of Cu was 0.16 μM for replicating and nonreplicating M. tuberculosis cells. We found 8HQ's activity to be dependent on the presence of extracellular Cu and to be related to an increase in cell-associated labile Cu ions. Both findings are consistent with 8HQ acting as a Cu ionophore. Accordingly, we identified the 1:1 complex of 8HQ and Cu to be its active form, with Zn, Fe, or Mn neither enhancing nor reducing its Cu-specific action. This is remarkable, considering that the respective metal complexes have nearly identical structures and geometries. Finally, we found 8HQ to kill M. tuberculosis selectively within infected primary macrophages. Given the stark Cu-dependent nature of 8HQ activity, this is the first piece of evidence that Cu ions within macrophages may bestow antibacterial properties to a Cu-dependent inhibitor of M. tuberculosis In conclusion, our findings highlight the metal-binding ability of the 8-hydroxyquinoline scaffold to be a potential focus for future medicinal chemistry and highlight the potential of innate immunity-inspired screening platforms to reveal molecules with novel modes of action against M. tuberculosis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Human Granuloma In Vitro Model, for TB Dormancy and Resuscitation

PubMed Central

Kapoor, Nidhi; Pawar, Santosh; Sirakova, Tatiana D.; Deb, Chirajyoti; Warren, William L.; Kolattukudy, Pappachan E.

2013-01-01

Tuberculosis (TB) is responsible for death of nearly two million people in the world annually. Upon infection, Mycobacterium tuberculosis (Mtb) causes formation of granuloma where the pathogen goes into dormant state and can live for decades before resuscitation to develop active disease when the immune system of the host is weakened and/or suppressed. In an attempt to better understand host-pathogen interactions, several groups have been developing in vitro models of human tuberculosis granuloma. However, to date, an in vitro granuloma model in which Mtb goes into dormancy and can subsequently resuscitate under conditions that mimic weakening of the immune system has not been reported. We describe the development of a biomimetic in vitro model of human tuberculosis granuloma using human primary leukocytes, in which the Mtb exhibited characteristics of dormant mycobacteria as demonstrated by (1) loss of acid-fastness, (2) accumulation of lipid bodies (3) development of rifampicin-tolerance and (4) gene expression changes. Further, when these micro granulomas were treated with immunosuppressant anti-tumor necrosis factor-alpha monoclonal antibodies (anti-TNFα mAbs), resuscitation of Mtb was observed as has been found in humans. In this human in vitro granuloma model triacylglycerol synthase 1deletion mutant (Δtgs1) with impaired ability to accumulate triacylglycerides (TG), but not the complemented mutant, could not go into dormancy. Deletion mutant of lipY, with compromised ability to mobilize the stored TG, but not the complemented mutant, was unable to come out of dormancy upon treatment with anti-TNFα mAbs. In conclusion, we have developed an in vitro human tuberculosis granuloma model that largely exhibits functional features of dormancy and resuscitation observed in human tuberculosis. PMID:23308269

Food incentives to improve completion of tuberculosis treatment: randomised controlled trial in Dili, Timor-Leste.

PubMed

Martins, Nelson; Morris, Peter; Kelly, Paul M

2009-10-26

To determine the effectiveness of the provision of whole food to enhance completion of treatment for tuberculosis. Parallel group randomised controlled trial. Three primary care clinics in Dili, Timor-Leste. 270 adults aged >or=18 with previously untreated newly diagnosed pulmonary tuberculosis. Completion of treatment (including cure). Secondary outcomes included adherence to treatment, weight gain, and clearance of sputum smears. Outcomes were assessed remotely, blinded to allocation status. Interventions Participants started standard tuberculosis treatment and were randomly assigned to intervention (nutritious, culturally appropriate daily meal (weeks 1-8) and food package (weeks 9-32) (n=137) or control (nutritional advice, n=133) groups. Randomisation sequence was computer generated with allocation concealment by sequentially numbered, opaque, sealed envelopes. Most patients with tuberculosis were poor, malnourished men living close to the clinics; 265/270 (98%) contributed to the analysis. The intervention had no significant beneficial or harmful impact on the outcome of treatment (76% v 78% completion, P=0.7) or adherence (93% for both groups, P=0.7) but did lead to improved weight gain at the end of treatment (10.1% v 7.5% improvement, P=0.04). Itch was more common in the intervention group (21% v 9%, P<0.01). In a subgroup analysis of patients with positive results on sputum smears, there were clinically important improvements in one month sputum clearance (85% v 67%, P=0.13) and completion of treatment (78% v 68%, P=0.3). Provision of food did not improve outcomes with tuberculosis treatment in these patients in Timor-Leste. Further studies in different settings and measuring different outcomes are required. Clinical Trials NCT00192556.

Feasibility of using teleradiology to improve tuberculosis screening and case management in a district hospital in Malawi

PubMed Central

Panunzi, Isabella; Spijker, Saskia; Brant, William E; Duran, Laura Triviño; Kosack, Cara S; Murowa, Michael Mitchell

2012-01-01

Abstract Problem Malawi has one of the world’s highest rates of human immunodeficiency virus (HIV) infection (10.6%), and southern Malawi, where Thyolo district is located, bears the highest burden in the country (14.5%). Tuberculosis, common among HIV-infected people, requires radiologic diagnosis, yet Malawi has no radiologists in public service. This hinders rapid and accurate diagnosis and increases morbidity and mortality. Approach Médecins Sans Frontières, in collaboration with Malawi’s Ministry of Health, implemented teleradiology in Thyolo district to assist clinical staff in radiologic image interpretation and diagnosis. Local setting Thyolo district’s 600 000 inhabitants are mostly subsistence-level or migrant farmers living in extreme poverty. Health facilities include one public hospital and 38 primary health centres. Understaffing and the absence of a radiologist make the diagnosis of tuberculosis difficult in a population where this disease affects 66% of patients with HIV infection. Relevant changes From September 2010–2011, 159 images (from 158 patients) were reviewed by teleradiology. Teleradiology changed patient management in 36 cases (23.5%). Two (1.3%) of them were cases of pulmonary tuberculosis not previously suspected by clinical staff. In addition, the radiologist’s review corrected the misdiagnosis of tuberculosis and averted inappropriate treatment in 16 patients (10.5%). Lessons learnt Teleradiology can improve tuberculosis diagnosis and case management, especially if criteria to identify the patients most suitable for referral are developed and the radiologist is conversant with local resources and health problems. Designating a clinical focal point for teleradiology ensures sustainability. Staff need time to adapt to a new teleradiology programme. PMID:22984316

Impact of a Daily SMS Medication Reminder System on Tuberculosis Treatment Outcomes: A Randomized Controlled Trial.

PubMed

Mohammed, Shama; Glennerster, Rachel; Khan, Aamir J

2016-01-01

The rapid uptake of mobile phones in low and middle-income countries over the past decade has provided public health programs unprecedented access to patients. While programs have used text messages to improve medication adherence, there have been no high-powered trials evaluating their impact on tuberculosis treatment outcomes. To measure the impact of Zindagi SMS, a two-way SMS reminder system, on treatment success of people with drug-sensitive tuberculosis. We conducted a two-arm, parallel design, effectiveness randomized controlled trial in Karachi, Pakistan. Individual participants were randomized to either Zindagi SMS or the control group. Zindagi SMS sent daily SMS reminders to participants and asked them to respond through SMS or missed (unbilled) calls after taking their medication. Non-respondents were sent up to three reminders a day. Public and private sector tuberculosis clinics in Karachi, Pakistan. Newly-diagnosed patients with smear or bacteriologically positive pulmonary tuberculosis who were on treatment for less than two weeks; 15 years of age or older; reported having access to a mobile phone; and intended to live in Karachi throughout treatment were eligible to participate. We enrolled 2,207 participants, with 1,110 randomized to Zindagi SMS and 1,097 to the control group. The primary outcome was clinically recorded treatment success based upon intention-to-treat. We found no significant difference between the Zindagi SMS or control groups for treatment success (719 or 83% vs. 903 or 83%, respectively, p = 0·782). There was no significant program effect on self-reported medication adherence reported during unannounced visits during treatment. In this large-scale randomized controlled effectiveness trial of SMS medication reminders for tuberculosis treatment, we found no significant impact. The trial was registered with ClinicalTrials.gov, NCT01690754.

Isoniazid plus antiretroviral therapy to prevent tuberculosis: a randomised double-blind placebo-controlled trial

PubMed Central

Rangaka, Molebogeng X; Wilkinson, Robert J; Boulle, Andrew; Glynn, Judith R; Fielding, Katherine; van Cutsem, Gilles; Wilkinson, Katalin A; Goliath, Rene; Mathee, Shaheed; Goemaere, Eric; Maartens, Gary

2014-01-01

Background Antiretroviral therapy (ART) reduces the risk of tuberculosis, but the incidence still exceeds that in HIV-uninfected people. Isoniazid preventive therapy (IPT), which decreases the risk of tuberculosis in people not on ART, may offer additional protection. Methods Pragmatic randomized double-blind placebo-controlled trial to evaluate the effect of 12 months IPT among participants established on or newly starting ART, in Khayelitsha, South Africa (NCT00463086, Lancet D-09-02885). Tuberculosis was excluded at screening by sputum culture. Incident tuberculosis was the primary endpoint. Findings 1,329 participants contributed 3,227 person-years (PY) of follow up in the modified intention-to-treat analysis; 662 on IPT and 667 on placebo. There were 95 incident tuberculosis cases: 2.3 (95%CI 1.6-3.1) versus 3.6 (95%CI 2.8-4.7) per 100 PY in the IPT and placebo arms respectively (hazard ratio 0.63, 95%CI 0.41-0.94). Study drug was discontinued due to grade 3 or 4 raised ALT in 19/662 in the IPT and 10/667 in the placebo arm, risk ratio=1.9 (95%CI 0.90-4.09). In secondary analyses, there was no evidence that the effect of IPT was restricted to those who were positive on tuberculin skin test (TST) or interferon gamma release assay (IGRA): adjusted hazard ratio for those with negative tests 0.43 (95%CI 0.21-0.86) and 0.43 (95%CI 0.20-0.96); for positive tests 0.86 (95%CI 0.37-2.00) and 0.55 (95%CI 0.26-1.24) respectively. No all cause mortality benefit of IPT was demonstrated Interpretation IPT reduced the incidence of tuberculosis in HIV-infected individuals on ART. In this high incidence setting, individuals on ART who have TST or IGRA negative results may also benefit from IPT. IPT can easily be implemented in ART clinics. PMID:24835842

Fragment-Based Whole Cell Screen Delivers Hits against M. tuberculosis and Non-tuberculous Mycobacteria.

PubMed

Moreira, Wilfried; Lim, Jia Jie; Yeo, Si Ying; Ramanujulu, Pondy M; Dymock, Brian W; Dick, Thomas

2016-01-01

Reactive multi-target 'fragment drugs' represent critical components of current tuberculosis regimens. These compounds, such as pyrazinamide, are old synthetic antimycobacterials that are activated inside Mycobacterium tuberculosis bacilli and are smaller than the usual drug-like, single-target molecules. Based on the success of small 'dirty' drugs in the chemotherapy of tuberculosis, we suggested previously that fragment-based whole cell screens should be introduced in our current antimycobacterial drug discovery efforts. Here, we carried out such a screen and characterized bactericidal activity, selectivity and spectrum of hits we obtained. A library of 1725 fragments was tested at a single concentration for growth inhibitory activity against M. bovis BCG as screening strain and 38 of 116 primary hits were confirmed in dose response analyses to be active against virulent M. tuberculosis. Bacterial kill experiments showed that most hits displayed bactericidal activity at their minimal inhibitory concentration. Cytotoxicity assays established that a large proportion of hits displayed a favorable selectivity index for mammalian cells. Importantly, one third of M. tuberculosis active fragments were also active against M. abscessus and M. avium, two emerging non-tuberculous mycobacterial (NTM) pathogens, opening the opportunity to develop broad spectrum antimycobacterials. Activity determination against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa) bacteria, as well as fungi (Candida albicans, Cryptococcus neoformans) showed only a small overlap indicating a generally narrow spectrum of these novel antimicrobial hits for mycobacteria. In conclusion, we carried out the first fragment-based whole cell screen against bacteria and identified a substantial number of hits with excellent physicochemical properties and dual activity against M. tuberculosis and NTM pathogens. These hits will now be evaluated in animal models of mycobacterial infection to determine whether any of them can be moved forward as a new antimycobacterial fragment drug candidate.

QuantiFERON-TB Gold In-Tube as a Confirmatory Test for Tuberculin Skin Test in Tuberculosis Contact Tracing: A Noninferiority Clinical Trial.

PubMed

Muñoz, Laura; Santin, Miguel; Alcaide, Fernando; Ruíz-Serrano, Maria Jesús; Gijón, Paloma; Bermúdez, Elena; Domínguez-Castellano, Angel; Navarro, María Dolores; Ramírez, Encarnación; Pérez-Escolano, Elvira; López-Prieto, María Dolores; Gutiérrez-Rodriguez, José; Anibarro, Luis; Calviño, Laura; Trigo, Matilde; Cifuentes, Carmen; García-Gasalla, Mercedes; Payeras, Antoni; Gasch, Oriol; Espasa, Mateu; Agüero, Ramon; Ferrer, Diego; Casas, Xavier; González-Cuevas, Araceli; García-Zamalloa, Alberto; Bikuña, Edurne; Lecuona, María; Galindo, Rosa; Ramírez-Lapausa, Marta; Carrillo, Raquel

2018-01-18

Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. NCT01223534. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Mycobacterium tuberculosis Genotypes Determined by Spoligotyping to Be Circulating in Colombia between 1999 and 2012 and Their Possible Associations with Transmission and Susceptibility to First-Line Drugs

PubMed Central

Puerto, Gloria; Erazo, Lina; Wintaco, Maira; Castro, Claudia; Ribón, Wellman; Guerrero, Martha Inírida

2015-01-01

Introduction Tuberculosis (TB) remains a primary public health problem worldwide. The number of multidrug-resistant tuberculosis (MDR TB) cases has increased in recent years in Colombia. Knowledge of M. tuberculosis genotypes defined by spoligotyping can help determine the circulation of genotypes that must be controlled to prevent the spread of TB. Objective To describe the genotypes of M. tuberculosis using spoligotyping in resistant and drug-sensitive isolates and their possible associations with susceptibility to first-line drugs. Methods An analytical observational study was conducted that included 741 isolates of M. tuberculosis from patients. The isolates originated from 31 departments and were obtained by systematic surveillance between 1999 and 2012. Results In total 61.94% of the isolates were resistant to 1 or more drugs, and 147 isolates were MDR. In total, 170 genotypes were found in the population structure of Colombian M. tuberculosis isolates. The isolates were mainly represented by four families: LAM (39.9%), Haarlem (19%), Orphan (17%) and T (9%). The SIT42 (LAM 9) was the most common genotype and contained 24.7% of the isolates, followed by the genotypes SIT62 (Haarlem1), SIT53 (T1), and SIT50 (H3). A high clustering of isolates was evident with 79.8% of the isolates classified into 32 groups. The Beijing family was associated with resistant isolates, whereas the Haarlem and T families were associated with sensitive isolates. The Haarlem family was also associated with grouped isolates (p = 0.031). Conclusions A high proportion (approximately 80%) of isolates was found in clusters; these clusters were not associated with resistance to first-line drugs. The Beijing family was associated with drug resistance, whereas the T and Haarlem families were associated with susceptibility in the Colombian isolates studied. PMID:26066494

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

PubMed

Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

2016-05-13

Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

New insights into the transposition mechanisms of IS6110 and its dynamic distribution between Mycobacterium tuberculosis Complex lineages

PubMed Central

Uranga, Santiago; Picó, Ana; Lampreave, Carlos; Cebollada, Alberto; Otal, Isabel

2018-01-01

The insertion Sequence IS6110, only present in the pathogens of the Mycobacterium tuberculosis Complex (MTBC), has been the gold-standard epidemiological marker for TB for more than 25 years, but biological implications of IS6110 transposition during MTBC adaptation to humans remain elusive. By studying 2,236 clinical isolates typed by IS6110-RFLP and covering the MTBC, we remarked a lineage-specific content of IS6110 being higher in modern globally distributed strains. Once observed the IS6110 distribution in the MTBC, we selected representative isolates and found a correlation between the normalized expression of IS6110 and its abundance in MTBC chromosomes. We also studied the molecular regulation of IS6110 transposition and we found a synergistic action of two post-transcriptional mechanisms: a -1 ribosomal frameshift and a RNA pseudoknot which interferes translation. The construction of a transcriptionally active transposase resulted in 20-fold increase of the transposition frequency. Finally, we examined transposition in M. bovis and M. tuberculosis during laboratory starvation and in a mouse infection model of TB. Our results shown a higher transposition in M. tuberculosis, that preferably happens during TB infection in mice and after one year of laboratory culture, suggesting that IS6110 transposition is dynamically adapted to the host and to adverse growth conditions. PMID:29649213

Socio-economic gradients in prevalent tuberculosis in Zambia and the Western Cape of South Africa.

PubMed

Yates, Tom A; Ayles, Helen; Leacy, Finbarr P; Schaap, A; Boccia, Delia; Beyers, Nulda; Godfrey-Faussett, Peter; Floyd, Sian

2018-04-01

To describe the associations between socio-economic position and prevalent tuberculosis in the 2010 ZAMSTAR Tuberculosis Prevalence Survey, one of the first large tuberculosis prevalence surveys in Southern Africa in the HIV era. The main analyses used data on 34 446 individuals in Zambia and 30 017 individuals in South Africa with evaluable tuberculosis culture results. Logistic regression was used to estimate adjusted odds ratios for prevalent TB by two measures of socio-economic position: household wealth, derived from data on assets using principal components analysis, and individual educational attainment. Mediation analysis was used to evaluate potential mechanisms for the observed social gradients. The quartile with highest household wealth index in Zambia and South Africa had, respectively, 0.55 (95% CI 0.33-0.92) times and 0.70 (95% CI 0.54-0.93) times the adjusted odds of prevalent TB of the bottom quartile. College or university-educated individuals in Zambia and South Africa had, respectively, 0.25 (95% CI 0.12-0.54) and 0.42 (95% CI 0.25-0.70) times the adjusted odds of prevalent TB of individuals who had received only primary education. We found little evidence that these associations were mediated via several key proximal risk factors for TB, including HIV status. These data suggest that social determinants of TB remain important even in the context of generalised HIV epidemics. © 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Decentralized care for multidrug-resistant tuberculosis: a systematic review and meta-analysis.

PubMed

Ho, Jennifer; Byrne, Anthony L; Linh, Nguyen N; Jaramillo, Ernesto; Fox, Greg J

2017-08-01

To assess the effectiveness of decentralized treatment and care for patients with multidrug-resistant (MDR) tuberculosis, in comparison with centralized approaches. We searched ClinicalTrials.gov, the Cochrane library, Embase®, Google Scholar, LILACS, PubMed®, Web of Science and the World Health Organization's portal of clinical trials for studies reporting treatment outcomes for decentralized and centralized care of MDR tuberculosis. The primary outcome was treatment success. When possible, we also evaluated, death, loss to follow-up, treatment adherence and health-system costs. To obtain pooled relative risk (RR) estimates, we performed random-effects meta-analyses. Eight studies met the eligibility criteria for review inclusion. Six cohort studies, with 4026 participants in total, reported on treatment outcomes. The pooled RR estimate for decentralized versus centralized care for treatment success was 1.13 (95% CI: 1.01-1.27). The corresponding estimate for loss to follow-up was RR: 0.66 (95% CI: 0.38-1.13), for death RR: 1.01 (95% CI: 0.67-1.52) and for treatment failure was RR: 1.07 (95% CI: 0.48-2.40). Two of three studies evaluating health-care costs reported lower costs for the decentralized models of care than for the centralized models. Treatment success was more likely among patients with MDR tuberculosis treated using a decentralized approach. Further studies are required to explore the effectiveness of decentralized MDR tuberculosis care in a range of different settings.

Outbreak of primary inoculation tuberculosis in an acupuncture clinic in southeastern China.

PubMed

Wang, J; Zhu, M Y; Li, C; Zhang, H B; Zuo, G B; Wang, M H; Teng, H L

2015-04-01

Outbreak of Mycobacterium tuberculosis infections associated with acupuncture has not been reported. Thirteen patients with a painful swollen lump were referred to our hospital. The index patient received acupuncture and paraspinal muscular injection at a local acupuncture clinic in April 2011 and was diagnosed with M. tuberculosis 1 month later. From May 2011 to August 2011, 12 more patients with a swollen lump on the nuchal region or in the lower back or the buttocks region were referred to our hospital. Tuberculin skin test (TST), T-SPOT.TB, acid-fast stain, M. tuberculosis culture, chest radiograph, and lump magnetic resonance imaging (MRI) were performed and the patients were diagnosed with tuberculous abscess of the lump. All 13 patients received intramuscular injection at the paraspinal muscle by two acupuncturists at a local clinic and reported a swollen lump at the injection site. The needles and syringes were reused after autoclave sterilization. The TST was positive in all patients. Twelve patients had positive acid-fast stains. Mycobacterial cultures of abscess specimens were positive in all 13 patients. T-SPOT.TB tests were positive in all patients who underwent the test. The lesions and biopsies were subjected to polymerase chain reaction (PCR) and gene sequencing by the Disease Control Center of Zhejiang Province, China and the causative agent was identified as M. tuberculosis, Beijing type. In conclusion, physicians should consider the possibility of mycobacterial infections, apart from other bacterial agents, in patients with a swollen paraspinal lump following intramuscular injection.

Decentralized care for multidrug-resistant tuberculosis: a systematic review and meta-analysis

PubMed Central

Byrne, Anthony L; Linh, Nguyen N; Jaramillo, Ernesto; Fox, Greg J

2017-01-01

Abstract Objective To assess the effectiveness of decentralized treatment and care for patients with multidrug-resistant (MDR) tuberculosis, in comparison with centralized approaches. Methods We searched ClinicalTrials.gov, the Cochrane library, Embase®, Google Scholar, LILACS, PubMed®, Web of Science and the World Health Organization’s portal of clinical trials for studies reporting treatment outcomes for decentralized and centralized care of MDR tuberculosis. The primary outcome was treatment success. When possible, we also evaluated, death, loss to follow-up, treatment adherence and health-system costs. To obtain pooled relative risk (RR) estimates, we performed random-effects meta-analyses. Findings Eight studies met the eligibility criteria for review inclusion. Six cohort studies, with 4026 participants in total, reported on treatment outcomes. The pooled RR estimate for decentralized versus centralized care for treatment success was 1.13 (95% CI: 1.01–1.27). The corresponding estimate for loss to follow-up was RR: 0.66 (95% CI: 0.38–1.13), for death RR: 1.01 (95% CI: 0.67–1.52) and for treatment failure was RR: 1.07 (95% CI: 0.48–2.40). Two of three studies evaluating health-care costs reported lower costs for the decentralized models of care than for the centralized models. Conclusion Treatment success was more likely among patients with MDR tuberculosis treated using a decentralized approach. Further studies are required to explore the effectiveness of decentralized MDR tuberculosis care in a range of different settings. PMID:28804170

Tuberculous Dactylitis: An Uncommon Presentation of Skeletal Tuberculosis.

PubMed

Abebe, Workeabeba; Abebe, Betel; Molla, Kebede; Alemayehu, Tinsae

2016-05-01

Skeletal involvement accounts 1-5% of all cases of Tuberculosis. The vertebrae are more commonly affected. The bones of the hands are more affected than the bones of the feet. The term "spina ventosa" has been used to describe this disorder because of its radiographic features of cystic expansion of the involved short tubular bones. Tuberculous dactylitis mainly occurs through lympho-hematogenous spread. The lung is the primary focus in 75% of cases. A 4 years old female child developed a painless swelling on her left index finger two months prior to her presentation. Following an unsuccessful treatment as a case of osteomyelitis with antibiotics, imaging showed an expansile lytic lesion with sclerosis, and fine needle aspiration confirmed tuberculous dactylitis. The child was initiated on anti-tubercular treatment with subsequent marked clinical and radiologic improvement. Presence of longstanding finger swelling and pain should alert a clinician to consider active disseminated tuberculosis. Furthermore, proper interpretation of imaging and use of fine needle aspiration has been highlighted.

Intracellular growth of Mycobacterium tuberculosis after macrophage cell death leads to serial killing of host cells

PubMed Central

Mahamed, Deeqa; Boulle, Mikael; Ganga, Yashica; Mc Arthur, Chanelle; Skroch, Steven; Oom, Lance; Catinas, Oana; Pillay, Kelly; Naicker, Myshnee; Rampersad, Sanisha; Mathonsi, Colisile; Hunter, Jessica; Wong, Emily B; Suleman, Moosa; Sreejit, Gopalkrishna; Pym, Alexander S; Lustig, Gila; Sigal, Alex

2017-01-01

A hallmark of pulmonary tuberculosis is the formation of macrophage-rich granulomas. These may restrict Mycobacterium tuberculosis (Mtb) growth, or progress to central necrosis and cavitation, facilitating pathogen growth. To determine factors leading to Mtb proliferation and host cell death, we used live cell imaging to track Mtb infection outcomes in individual primary human macrophages. Internalization of Mtb aggregates caused macrophage death, and phagocytosis of large aggregates was more cytotoxic than multiple small aggregates containing similar numbers of bacilli. Macrophage death did not result in clearance of Mtb. Rather, it led to accelerated intracellular Mtb growth regardless of prior activation or macrophage type. In contrast, bacillary replication was controlled in live phagocytes. Mtb grew as a clump in dead cells, and macrophages which internalized dead infected cells were very likely to die themselves, leading to a cell death cascade. This demonstrates how pathogen virulence can be achieved through numbers and aggregation states. DOI: http://dx.doi.org/10.7554/eLife.22028.001 PMID:28130921

Modeling the spread of tuberculosis in semiclosed communities.

PubMed

Herrera, Mauricio; Bosch, Paul; Nájera, Manuel; Aguilera, Ximena

2013-01-01

We address the problem of long-term dynamics of tuberculosis (TB) and latent tuberculosis (LTB) in semiclosed communities. These communities are congregate settings with the potential for sustained daily contact for weeks, months, and even years between their members. Basic examples of these communities are prisons, but certain urban/rural communities, some schools, among others could possibly fit well into this definition. These communities present a sort of ideal conditions for TB spread. In order to describe key relevant dynamics of the disease in these communities, we consider a five compartments SEIR model with five possible routes toward TB infection: primary infection after a contact with infected and infectious individuals (fast TB), endogenous reactivation after a period of latency (slow TB), relapse by natural causes after a cure, exogenous reinfection of latently infected, and exogenous reinfection of recovered individuals. We discuss the possible existence of multiple endemic equilibrium states and the role that the two types of exogenous reinfections in the long-term dynamics of the disease could play.

Tuberculosis masked by immunodeficiency: a review of two cases diagnosed with chronic granulomatous disease.

PubMed

Nacaroğlu, Hikmet Tekin; Bahçeci Erdem, Semiha; Gülez, Nesrin; Ünsal Karkıner, Canan Şule; Devrim, İlker; Genel, Ferah; Köker, Mustafa Yavuz; Can, Demet

2017-03-01

Chronic granulomatous disease (CGD) is a genetically heterogeneous primary immunodeficiency that is characterized by recurrent and life-threatening infections resulting from defects in phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system and granuloma formation due to increased inflammatory response. The most commonly involved organs are the lungs, skin, lymph nodes, and liver due to infection. It may present with recurrent pneumonia, hilar lymphadenopathy, empyema, abscess, reticulonodular patterns, and granulomas due to lung involvement. In recent years, mycobacterial disease susceptibility has been reported in CGD cases. This article presents two male cases, one of whom is aged 18 months and the other is aged 5 years, who were diagnosed with CGD and tuberculosis during examination due to extended pneumonia. This report is presented because CGD should be considered not only in the presence of skin abscesses and Aspergillus infections, but also in the differential diagnosis for cases with BCG-itis and/or tuberculosis. It should be kept in mind that mycobacterial infections can occur during the course of the disease.

The SS x-ray unit as an instrument for "total registration" and "race selection".

PubMed

Schmidt, Mathias; Winzen, Tina; Gross, Dominik

2015-05-01

The aim of this article is to show that, after the onset of World War II at the latest, the central task of the x-ray unit of the Nazi-SS (Schutzstaffel) led by Prof. Hans Holfelder was by no means the early diagnosis of tuberculosis. Its primary purpose, rather, was to serve the various "racial" and inhuman aims of the SS itself. Main historical sources and information about the SS x-ray unit are surveyed and analyzed. Clearly, the significance of the x-ray storm unit was increasingly subordinated to the necessities of the war until its original objectives disappeared from focus completely. The main purpose of operation of the x-ray storm unit thus by no means lay in the early detection of tuberculosis and did not therefore serve tuberculosis control. The actual objective lay, rather, in the implementation of SS aims in terms of Volk politics, genetics, and "racial hygiene".

Genital tuberculosis in females

PubMed Central

Grace, G. Angeline; Devaleenal, D. Bella; Natrajan, Mohan

2017-01-01

The morbidity and mortality due to tuberculosis (TB) is high worldwide, and the burden of disease among women is significant, especially in developing countries. Mycobacterium tuberculosis bacilli reach the genital tract primarily by haematogenous spread and dissemination from foci outside the genitalia with lungs as the common primary focus. Genital TB in females is a chronic disease with low-grade symptoms. The fallopian tubes are affected in almost all cases of genital TB, and along with endometrial involvement, it causes infertility in patients. Many women present with atypical symptoms which mimic other gynaecological conditions. A combination of investigations is needed to establish the diagnosis of female genital TB (FGTB). Multidrug anti-TB treatment is the mainstay of management and surgery may be required in advanced cases. Conception rates are low among infertile women with genital TB even after multidrug therapy for TB, and the risk of complications such as ectopic pregnancy and miscarriage is high. More research is needed on the changing trends in the prevalence and on the appropriate methods for diagnosis of FGTB. PMID:28862174

The development, evaluation and performance of molecular diagnostics for detection of Mycobacterium tuberculosis.

PubMed

Bates, Matthew; Zumla, Alimuddin

2016-01-01

The unique pathogenesis of tuberculosis (TB) poses several barriers to the development of accurate diagnostics: a) the establishment of life-long latency by Mycobacterium tuberculosis (M.tb) after primary infection confounds the development of classical antibody or antigen based assays; b) our poor understanding of the molecular pathways that influence progression from latent to active disease; c) the intracellular nature of M.tb infection in tissues means that M.tb and/or its components, are not readily detectable in peripheral specimens; and d) the variable presence of M.tb bacilli in specimens from patients with extrapulmonary TB or children. The literature on the current portfolio of molecular diagnostics tests for TB is reviewed here and the developmental pipeline is summarized. Also reviewed are data from recently published operational research on the GeneXpert MTB/RIF assay and discussed are the lessons that can be taken forward for the design of studies to evaluate the impact of TB diagnostics.

Isoniazid Preventive Therapy and Risk for Resistant Tuberculosis

PubMed Central

Balcells, Maria Elvira; Thomas, Sara L.; Godfrey-Faussett, Peter

2006-01-01

In the context of tuberculosis (TB) resurgence, isoniazid preventive therapy (IPT) is increasingly promoted, but concerns about the risk for development of isoniazid-resistant tuberculosis may hinder its widespread implementation. We conducted a systematic review of data published since 1951 to assess the effect of primary IPT on the risk for isoniazid-resistant TB. Different definitions of isoniazid resistance were used, which affected summary effect estimates; we report the most consistent results. When all 13 studies (N = 18,095 persons in isoniazid groups and N = 17,985 persons in control groups) were combined, the summary relative risk for resistance was 1.45 (95% confidence interval 0.85–2.47). Results were similar when studies of HIV-uninfected and HIV-infected persons were considered separately. Analyses were limited by small numbers and incomplete testing of isolates, but findings do not exclude an increased risk for isoniazid-resistant TB after IPT. The diagnosis of active TB should be excluded before IPT. Continued surveillance for isoniazid resistance is essential. PMID:16704830

Modeling the Spread of Tuberculosis in Semiclosed Communities

PubMed Central

Herrera, Mauricio; Bosch, Paul; Nájera, Manuel; Aguilera, Ximena

2013-01-01

We address the problem of long-term dynamics of tuberculosis (TB) and latent tuberculosis (LTB) in semiclosed communities. These communities are congregate settings with the potential for sustained daily contact for weeks, months, and even years between their members. Basic examples of these communities are prisons, but certain urban/rural communities, some schools, among others could possibly fit well into this definition. These communities present a sort of ideal conditions for TB spread. In order to describe key relevant dynamics of the disease in these communities, we consider a five compartments SEIR model with five possible routes toward TB infection: primary infection after a contact with infected and infectious individuals (fast TB), endogenous reactivation after a period of latency (slow TB), relapse by natural causes after a cure, exogenous reinfection of latently infected, and exogenous reinfection of recovered individuals. We discuss the possible existence of multiple endemic equilibrium states and the role that the two types of exogenous reinfections in the long-term dynamics of the disease could play. PMID:23762194

Tuberculosis elimination in the post Millennium Development Goals era.

PubMed

Wejse, Christian

2015-03-01

The Millennium Development Goal for tuberculosis (TB) is to stop the increase in incidence and halve the mortality of TB between 1990 and 2015. This goal has now been reached on a global scale, although not in the most affected region of Africa. The new target is TB elimination, defined as one case of active TB per one million population per year, which is to be reached before 2050. This review will discuss the main tools in play, namely case-finding and new diagnostics, increased access and effectiveness of anti-TB therapy (directly observed therapy, short course (DOTS)), preventive therapy for latent infection, and vaccination. Each approach is discussed and a way forward in research and management is suggested. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

[Biologics and mycobacterial diseases].

PubMed

Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

2013-03-01

Various biologics such as TNF-alpha inhibitor or IL-6 inhibitor are now widely used for treatment of rheumatoid arthritis. Many reports suggested that one of the major issues is high risk of developing tuberculosis (TB) associated with using these agents, which is especially important in Japan where tuberculosis still remains endemic. Another concern is the risk of development of nontuberculous mycobacterial (NTM) diseases and we have only scanty information about it. The purpose of this symposium is to elucidate the role of biologics in the development of mycobacterial diseases and to establish the strategy to control them. First, Dr. Tohma showed the epidemiologic data of TB risks associated with using biologics calculated from the clinical database on National Database of Rheumatic Diseases by iR-net in Japan. He estimated TB risks in rheumatoid arthritis (RA) patients to be about four times higher compared with general populations and to become even higher by using biologics. He also pointed out a low rate of implementation of QuantiFERON test (QFT) as screening test for TB infection. Next, Dr. Tokuda discussed the issue of NTM disease associated with using biologics. He suggested the airway disease in RA patients might play some role in the development of NTM disease, which may conversely lead to overdiagnosis of NTM disease in RA patients. He suggested that NTM disease should not be uniformly considered a contraindication to treatment with biologics, considering from the results of recent multicenter study showing relatively favorable outcome of NTM patients receiving biologics. Patients with latent tuberculosis infection (LTBI) should receive LTBI treatment before starting biologics. Dr. Kato, a chairperson of the Prevention Committee of the Japanese Society for Tuberculosis, proposed a new LTBI guideline including active implementation of LTBI treatment, introducing interferon gamma release assay, and appropriate selection of persons at high risk for developing TB. Lastly, Dr. Matsumoto stressed the risk of discontinuing TNF-alpha inhibitor during treatment for tuberculosis. He showed from his clinical experience that TNF-alpha inhibitor can be safely used in active TB patient receiving effective antituberculosis chemotherapy and it is even more effective for prevention of paradoxical response. Active discussion was done about the four topics, including the matter beyond present guidelines. We hope these discussions will form the basis for the establishment of new guideline for the management of mycobacterial disease when using immunosuppressive agents including biologics. 1. The risk of developing tuberculosis (TB) and situations of screening for TB risk at administration of biologics-the case of rheumatoid arthritis: Shigeto TOHMA (Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital) We calculated the standardized incidence ratio (SIR) of TB from the clinical data on National Database of Rheumatic Diseases by iR-net in Japan (NinJa) and compared with the SIR of TB from the data of the post-marketing surveillances of five biologics. Among 43584 patient-years, forty patients developed TB. The SIR of TB in NinJa was 4.34 (95%CI: 3.00-5.69). According to the post-marketing surveillances of 5 biologics, the SIR of TB were 3.62-34.4. The incidence of TB in patients with RA was higher than general population in Japan, and was increased more by some biologics. We have to recognize the risk of TB when we start biologics therapy to patients with RA. Although the frequency of implementation of QuantiFERON test (QFT) had gradually increased, it was still limited to 41%. In order to predict the risk of developing TB and to prevent TB, it might be better to check all RA patients by QFT at time time of biologics administration. 2. Biologics and nontuberculous mycobacterial diseases: Hitoshi TOKUDA (Social Insurance Central General Hospital) Several topics about the relationship between RA and nontuberculous mycobacterial (NTM) diseases were discussed, which is still poorly understood. It is well known that airway diseases often accompany RA, which may be considered as a possible etiology for development of NTM diseases, but conversely it may lead to overdiagnosis of NTM disease. Next, we evaluated justification for the contraindication of biologics in patients with NTM diseases. Recent multicenter study showed that prognosis of patients developing NTM diseases during treatment with biologics were not always poor, which throws doubt on uniform prohibition of biologics in NTM diseases. 3. Future guideline for treating latent tuberculosis infection: Seiya KATO (Research Institute of Tuberculosis, Japan AntiTuberculosis Association) The Japanese Society for Tuberculosis issued a joint statement on chemoprophylaxis with the Japan College of Rheumatology in 2004. However, issues and challenges due to changing circumstance indicate application of interferon gamma release assay (IGRA), increased variety and indication of biologics, dissemination of knowledge on strategy and system for latent tuberculosis infection (LTBI), etc. Future guideline should include 1) promoting LTBI treatment to achieve low incidence, 2) updated information on IGRAs, 3) treatment strategy and target: contact to infectious cases, immunosuppressive cases (especially HIV and patients treated with biologics), high risk groups, etc. 4) fundamental information on tuberculosis control strategies, especially DOTS. 4. Therapy for RA and tuberculosis in patients with RA and TB activated by anti-TNF treatment: Tomoshige MATSUMOTO (Osaka Prefectural Medical Center for Respiratory and Allergic Diseases) Biologics targeting TNF, including infliximab, have brought about a paradigm shift in the treatment of rheumatoid arthritis (RA). In 2001, tuberculosis, an ancient and also modem scourge, became spotlighted again, because Keane reported in the New England Journal of Medicine that infliximab administration induced reactivation of tuberculosis. How should we treat RA after we successfully treated tuberculosis? Decisions regarding the treatment of patients with refractory RA in the setting of active tuberculosis remain difficult. We successfully treated RA in patients with tuberculosis by anti-TNF therapy. These demonstrate that anti-TNF therapy can be considered for patients with refractory RA who have tuberculosis and in whom antituberculosis therapy can be maintained.

[Analysis of clinical features and treatment outcomes of patients with tuberculous otitis media and mastoiditis].

PubMed

Hao, Xin-ping; Gong, Shu-sheng; Li, Yong-xin; Xia, Yin; Zhao, Shou-qin; Zheng, Jun; Zheng, Ya-li; Zhao, Yan-ling; Ma, Xiao-bo

2010-11-01

To analyze the clinical features and the surgical treatment outcomes of patients with tuberculous otitis media and mastoiditis. The medical records of 16 patients (18 ears) with tuberculous otitis media and mastoiditis, who received surgery in Beijing Tongren hospital, were reviewed. The common symptoms were otorrhea and hearing loss, and 3 patients demonstrated severe sensorineural hearing loss. Three patients demonstrated a peripheral-type facial palsy. Temporal bone high resolution CT scans demonstrated the entire tympanum and mastoid air cells were occupied by soft tissue. Eleven patients demonstrated bone destruction and sequestra was found in 7 temporal bones. Contemporary pulmonary tuberculosis were diagnosed in 7 of the 16 patients. Surgical removal of disease lesions in combination with anti-tuberculosis treatment were given to 15 patients. Other than 2 cases of tuberculous otitis media and mastoiditis diagnosed by pre-operational biopsy through the perforated tympanic membrane, the remaining 14 cases were diagnosed intra-operatively or post-operatively. No relapse of tuberculosis in the middle ear and mastoid were found after follow-up for more than 1 year, except for the one case that was lost to follow-up. The 3 cases of facial nerve palsy almost recovered to normal. Clinicians should suspect tuberculous otitis media and mastoiditis if clinical findings include refractory otorrhea, total occupation of the tympanic cavity and mastoid ari cells by soft tissue, and erosion of the bone or sequestra as shown by CT. A history of tuberculosis should be asked carefully in order to differentiate tuberculous otitis media and mastoiditis. The patients who received surgery and anti-tuberculosis chemotherapy achieved more rapid healing of the ear.

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.

PubMed

Menzies, Nicolas A; Gomez, Gabriela B; Bozzani, Fiammetta; Chatterjee, Susmita; Foster, Nicola; Baena, Ines Garcia; Laurence, Yoko V; Qiang, Sun; Siroka, Andrew; Sweeney, Sedona; Verguet, Stéphane; Arinaminpathy, Nimalan; Azman, Andrew S; Bendavid, Eran; Chang, Stewart T; Cohen, Ted; Denholm, Justin T; Dowdy, David W; Eckhoff, Philip A; Goldhaber-Fiebert, Jeremy D; Handel, Andreas; Huynh, Grace H; Lalli, Marek; Lin, Hsien-Ho; Mandal, Sandip; McBryde, Emma S; Pandey, Surabhi; Salomon, Joshua A; Suen, Sze-Chuan; Sumner, Tom; Trauer, James M; Wagner, Bradley G; Whalen, Christopher C; Wu, Chieh-Yin; Boccia, Delia; Chadha, Vineet K; Charalambous, Salome; Chin, Daniel P; Churchyard, Gavin; Daniels, Colleen; Dewan, Puneet; Ditiu, Lucica; Eaton, Jeffrey W; Grant, Alison D; Hippner, Piotr; Hosseini, Mehran; Mametja, David; Pretorius, Carel; Pillay, Yogan; Rade, Kiran; Sahu, Suvanand; Wang, Lixia; Houben, Rein M G J; Kimerling, Michael E; White, Richard G; Vassall, Anna

2016-11-01

The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. Bill & Melinda Gates Foundation. Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

Spot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosis.

PubMed

Murphy, Michael E; Phillips, Patrick P J; Mendel, Carl M; Bongard, Emily; Bateson, Anna L C; Hunt, Robert; Murthy, Saraswathi; Singh, Kasha P; Brown, Michael; Crook, Angela M; Nunn, Andrew J; Meredith, Sarah K; Lipman, Marc; McHugh, Timothy D; Gillespie, Stephen H

2017-10-27

The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. Patients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses. Data from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24-41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/μL (IQR 318-535). Pre-treatment spot samples had a higher yield of positive Ziehl-Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P < 0.001). There were no differences in time to positivity in pre-treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan-Meier analyses in either EMS or spot samples. Our data do not support the hypothesis that EMS samples are superior to spot sputum samples in a clinical trial of patients with smear positive pulmonary TB. Observed small differences in mycobacterial burden are of uncertain significance and EMS samples do not detect post-treatment positives any sooner than spot samples.

Enhancing Effects of Carbon Dioxide on the Primary Isolation of Acid-Fast Bacilli in a Modified Lowenstein-Jensen Medium

PubMed Central

Gruft, Howard; Loder, Arthur

1971-01-01

Specimens inoculated on modified Lowenstein-Jensen medium were incubated aerobically and in an atmosphere of 8% CO2. Sixteen per cent of the positive specimens grew Mycobacterium tuberculosis only after incubation in CO2. PMID:5002315

Interventions to improve adherence to tuberculosis treatment: systematic review and meta-analysis.

PubMed

Müller, A M; Osório, C S; Silva, D R; Sbruzzi, G; de Tarso, P; Dalcin, Roth

2018-07-01

One of the most serious problems in tuberculosis (TB) control is non-adherence to treatment. Several strategies have been developed to improve adherence and increase the cure rate. To systematically review interventions to improve adherence to anti-tuberculosis treatment. We performed a systematic review and meta-analysis of 22 randomised clinical trials (RCTs) to ascertain whether providing directly observed treatment, short-course (DOTS), financial incentives, food incentives and/or patient education/counselling improved adherence to anti-tuberculosis treatment. The primary outcome was cure rate; secondary outcomes were default and mortality rates. Sources used were Medline (accessed via PubMed), Cochrane Central, LILACS (Literatura Latino Americana em Ciências da Saúde, Latin American and Caribbean Health Sciences Literature) and Embase from inception to October 2015. A significant increase in cure rates, by 18% with DOTS and by 16% with patient education and counselling, was observed. In addition, the default rate decreased by 49% with DOTS, by 26% with financial incentives and by 13% with patient education and counselling. There was no statistically significant reduction in mortality rates with these interventions. Use of DOTS and patient education/counselling significantly improved cure rates; DOTS, patient education/counselling and financial incentives led to a reduction in the default rate.

Dehalogenation of Haloalkanes by Mycobacterium tuberculosis H37Rv and Other Mycobacteria

PubMed Central

Jesenská, Andrea; Sedlác̆ek, Ivo; Damborský, Jir̆í

2000-01-01

Haloalkane dehalogenases convert haloalkanes to their corresponding alcohols by a hydrolytic mechanism. To date, various haloalkane dehalogenases have been isolated from bacteria colonizing environments that are contaminated with halogenated compounds. A search of current databases with the sequences of these known haloalkane dehalogenases revealed the presence of three different genes encoding putative haloalkane dehalogenases in the genome of the human parasite Mycobacterium tuberculosis H37Rv. The ability of M. tuberculosis and several other mycobacterial strains to dehalogenate haloaliphatic compounds was therefore studied. Intact cells of M. tuberculosis H37Rv were found to dehalogenate 1-chlorobutane, 1-chlorodecane, 1-bromobutane, and 1,2-dibromoethane. Nine isolates of mycobacteria from clinical material and four strains from a collection of microorganisms were found to be capable of dehalogenating 1,2-dibromoethane. Crude extracts prepared from two of these strains, Mycobacterium avium MU1 and Mycobacterium smegmatis CCM 4622, showed broad substrate specificity toward a number of halogenated substrates. Dehalogenase activity in the absence of oxygen and the identification of primary alcohols as the products of the reaction suggest a hydrolytic dehalogenation mechanism. The presence of dehalogenases in bacterial isolates from clinical material, including the species colonizing both animal tissues and free environment, indicates a possible role of parasitic microorganisms in the distribution of degradation genes in the environment. PMID:10618227

[Tuberculoma mimicking the tumor of ponto-cerebellum angle as complication after postvaccinated tuberculous otitis media].

PubMed

Niemczyk, Kazimierz; Jamróz, Barbara; Bartoszewicz, Robert; Bruzgielewicz, Antoni

2014-01-01

Tuberculosis is a major problem of constant importance all over the world. Notably, in the developed countries it is due to immunosuppressive therapy and AIDS. Primary otological tuberculosis constitutes a very small share of cases of this disease. Moreover, the appearance of tuberculomas remains unique to even greater extent. Clinical history of a patient who has already been infected tuberculosis for 60 years in result of the BCG vaccination. Ponto-cerebellum angle tumour appeared in his brain as complication ensuing the disease. The first therapeutic method used was based on antituberculous drugs, subsequent surgical intervention (cerebello-pontine angle tumor removal via translabirynthin approche) was necessary however. We suspected another cause of this lesion - cholesteatoma or facial nerve neurinoma. Correct diagnosis give only histopatological examination. Because of facial nerve palsy, facial nerve reconstruction was necessary (connection of n. VII and n. This case reminds us that correct diagnosis of tuberculosis remains a serious problem despite the long experience and the development of diagnostics and treatment methods. Nowadays we observe the unusual clinical manifestations of the disease (e.g. such as ear pain, tinnitus, rapid hearing loss) more frequently. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth of Mycobacterium tuberculosis

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

Molle, Virginie; Gulten, Gulcin; Vilchèze, Catherine

The remarkable survival ability of Mycobacterium tuberculosis in infected hosts is related to the presence of cell wall-associated mycolic acids. Despite their importance, the mechanisms that modulate expression of these lipids in response to environmental changes are unknown. Here we demonstrate that the enoyl-ACP reductase activity of InhA, an essential enzyme of the mycolic acid biosynthetic pathway and the primary target of the anti-tubercular drug isoniazid, is controlled via phosphorylation. Thr-266 is the unique kinase phosphoacceptor, both in vitro and in vivo. The physiological relevance of Thr-266 phosphorylation was demonstrated using inhA phosphoablative (T266A) or phosphomimetic (T266D/E) mutants. Enoyl reductasemore » activity was severely impaired in the mimetic mutants in vitro, as a consequence of a reduced binding affinity to NADH. Importantly, introduction of inhA{_}T266D/E failed to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment. This study suggests that phosphorylation of InhA may represent an unusual mechanism that allows M. tuberculosis to regulate its mycolic acid content, thus offering a new approach to future anti-tuberculosis drug development.« less

Phosphorylation of InhA inhibits mycolic acid biosynthesis and growth of Mycobacterium tuberculosis.

PubMed

Molle, Virginie; Gulten, Gulcin; Vilchèze, Catherine; Veyron-Churlet, Romain; Zanella-Cléon, Isabelle; Sacchettini, James C; Jacobs, William R; Kremer, Laurent

2010-12-01

The remarkable survival ability of Mycobacterium tuberculosis in infected hosts is related to the presence of cell wall-associated mycolic acids. Despite their importance, the mechanisms that modulate expression of these lipids in response to environmental changes are unknown. Here we demonstrate that the enoyl-ACP reductase activity of InhA, an essential enzyme of the mycolic acid biosynthetic pathway and the primary target of the anti-tubercular drug isoniazid, is controlled via phosphorylation. Thr-266 is the unique kinase phosphoacceptor, both in vitro and in vivo. The physiological relevance of Thr-266 phosphorylation was demonstrated using inhA phosphoablative (T266A) or phosphomimetic (T266D/E) mutants. Enoyl reductase activity was severely impaired in the mimetic mutants in vitro, as a consequence of a reduced binding affinity to NADH. Importantly, introduction of inhA_T266D/E failed to complement growth and mycolic acid defects of an inhA-thermosensitive Mycobacterium smegmatis strain, in a similar manner to what is observed following isoniazid treatment. This study suggests that phosphorylation of InhA may represent an unusual mechanism that allows M. tuberculosis to regulate its mycolic acid content, thus offering a new approach to future anti-tuberculosis drug development. © 2010 Blackwell Publishing Ltd.

Tuberculous Otomastoiditis.

PubMed

Hand, Jonathan M; Pankey, George A

2016-12-01

Tuberculous otitis media and mastoiditis, or tuberculous otomastoiditis, is a rare but well-described infectious process occasionally affecting individuals in the United States but more frequently seen in countries where tuberculosis is endemic. Infection may be primary and occur through mucus aspirated through the Eustachian tube. Alternatively, organisms may secondarily infect the nasopharynx when expectorated from the lungs and, less frequently, may be hematogenously spread. Chronic otorrhea and hearing loss are common symptoms, and extensive perforation of the tympanic membranes and facial nerve paralysis are routinely described. Diagnosis is made by direct culture of Mycobacterium tuberculosis, although more recently, molecular techniques have been used. Successful treatment of tuberculous otomastoiditis routinely involves surgical intervention combined with prolonged antituberculosis therapy.

Risk of Mycobacterium tuberculosis infection in Somalia: national tuberculin survey 2006.

PubMed

Munim, A; Rajab, Y; Barker, A; Daniel, M; Williams, B

2008-01-01

To estimate the annual risk of tuberculosis (TB) infection (ARTI) in Somalia a tuberculin survey was conducted in February/March 2006. Stratified cluster sampling was carried out within the 18 regions and 101 randomly selected primary schools. Tuberculin testing was done in 10 680 grade 1 schoolchildren. Transverse tuberculin reaction size was measured 72 hours later. The number of children with a satisfactory test read was 10 364. The overall BCG coverage was 54%. Based on frequency distribution of tuberculin reaction sizes, the ARTI in Somalia was estimated at 2.2% (confidence interval: 1.5%-3.2%). There was an annual decline of 2.6% comparing with a previous study in 1956.

A rare cause of hypophysitis: tuberculosis.

PubMed

Ates, Ihsan; Katipoglu, B; Copur, B; Yilmaz, N

2017-10-26

Hypophysitis is a heterogeneous inflammatory disease of pituitary gland. As it causes headache and visual defects, it mimics sellar tumors in clinical and radiological aspects. It may occur due to primary or secondary causes. Tuberculosis is one of the rare secondary causes of the hypophysitis. Subject and Results. A 30-year-old male patient presented with fatigue and headache. Panhypopituitarism was considered due to the results and the diagnostic magnetic resonance (MR) imaging revealed sagittal section diamater of pituitary gland higher than normal. Biopsy of the pituitary gland was concordant with the granulomatous hypophysitis. Other possible diagnosis was excluded. The tubercular hypophysitis, as a result of performed tests, is discussed hereby, in the case report.

The Haiti research-based model of international public health collaboration: the GHESKIO Centers.

PubMed

Pape, Jean W; Severe, Patrice D; Fitzgerald, Daniel W; Deschamps, Marie M; Joseph, Patrice; Riviere, Cynthia; Rouzier, Vanessa; Johnson, Warren D

2014-01-01

For 3 decades, GHESKIO (the Groupe Haitien d'Etude du Sarcome de Kaposi et des Infections Opportunistes), the Haitian Ministry of Health, and Weill Cornell have pursued a tripartite mission of service, training, and translational research. The initial focus was on AIDS and tuberculosis. The mission has expanded to include the local community and now provides maternal-child health, family planning, cancer prevention and treatment, immunizations (including human papillomavirus, cholera), and primary education through vocational and microcredit programs. Outcome measures include a reduction in HIV prevalence from 6.2% to the current 2.2%, extensive tuberculosis and cholera prevention and treatment programs, and national training programs for biomedical and community health workers.

Ossified ligamentum flavum causing neurological deficit above the level of post-tuberculous kyphotic deformity.

PubMed

Subramani, Suresh; Shetty, Ajoy Prasad; Kanna, Rishi Mugesh; Shanmuganathan, Rajasekaran

2017-01-01

Late onset paraplegia is a rare complication of spinal tuberculosis. Disease reactivation and cord compression by internal gibbus are the common causes for neurological deficit. We report a patient with post-tubercular kyphotic deformity in whom the late onset paraplegia is caused by ossified ligamentum flavum above the level of kyphotic deformity. The deficit was attributable to the ossified ligamentum flavum and she recovered completely following posterior decompression and instrumented posterolateral fusion. To the best of our knowledge, this is the first report of this unusual cause of late onset paraplegia.

Spirometry is underused in the diagnosis and monitoring of patients with chronic obstructive pulmonary disease (COPD)

PubMed Central

Yu, Wai Cho; Fu, Sau Nga; Tai, Emily Lai-bun; Yeung, Yiu Cheong; Kwong, Kwok Chu; Chang, Yui; Tam, Cheuk Ming; Yiu, Yuk Kwan

2013-01-01

Spirometry is important in the diagnosis and management of chronic obstructive pulmonary disease (COPD), yet it is a common clinical observation that it is underused though the extent is unclear. This survey aims to examine the use of spirometry in the diagnosis and management of COPD patients in a district in Hong Kong. It is a cross-sectional survey involving four clinic settings: hospital-based respiratory specialist clinic, hospital-based mixed medical specialist clinic, general outpatient clinic (primary care), and tuberculosis and chest clinic. Thirty physician-diagnosed COPD patients were randomly selected from each of the four clinic groups. All of them had a forced expiratory volume in 1 second (FEV1) to forced vital capacity ratio less than 0.70 and had been followed up at the participating clinic for at least 6 months for COPD treatment. Of 126 patients who underwent spirometry, six (4.8%) did not have COPD. Of the 120 COPD patients, there were 111 males and mean post-bronchodilator FEV1 was 46.2% predicted. Only 22 patients (18.3%) had spirometry done during diagnostic workup, and 64 patients (53.3%) had spirometry done ever. The only independent factor predicting spirometry done ever was absence of old pulmonary tuberculosis and follow-up at respiratory specialist clinic. Age, sex, smoking status, comorbidities, duration of COPD, percentage predicted FEV1, body mass index, 6-minute walking distance, and Medical Research Council dyspnea score were not predictive. We conclude that spirometry is underused in general but especially by nonrespiratory physicians and family physicians in the management of COPD patients. More effort at educating the medical community is urgently needed. PMID:24009418

Demographic and socioeconomic disparity in knowledge about tuberculosis in Inner Mongolia, China.

PubMed

Ma, Enbo; Ren, Liping; Wang, Wensheng; Takahashi, Hideto; Wagatsuma, Yukiko; Ren, Yulin; Gao, Fei; Gao, Fangfang; Wang, Wenrui; Bi, Lifu

2015-01-01

The aim of this study is to evaluate the awareness status, attitudes, and care-seeking behaviors concerning tuberculosis (TB) and associated factors among the public in Inner Mongolia, China. A five-stage sampling was conducted, in which counties as the primary survey units and towns, villages, and households as sub-survey units were selected progressively. A standardized questionnaire was used to collect TB information. Complex survey analysis methods, including the procedures of survey frequency and survey logistic regression, were applied for analysis of TB knowledge and associated factors. The sample was weighted by survey design, non-respondent, and post-stratification adjustment. Among 10 581 respondents, awareness that TB is an infectious disease was 86.7%. Knowing that a cough lasting ≥3 weeks is suggestive of TB was 26.9%. Knowledge about TB dispensaries in county administrative areas was reported by 68.3% of respondents, and knowledge about the free TB detection/treatment policy was reported by 57.5% of respondents. About 52.5% of participants would stigmatize TB patients. Compared with the majority Han ethnic group, Mongolians and other minorities were 1.52-2.18 times more likely to know about TB curability, TB symptoms, the free detection/treatment policy, and TB dispensaries' locations, but were less likely to know about the TB transmission mode (odds ratio, 0.74; 95% confidence interval, 0.65-0.84). The main sources of TB information were TV (65.6%) and other persons (47.2%). In the past year, 19.7% of TB knowledge was from acquaintances, and 16.1% was from TB institutes. Improvement in knowledge about TB risk (symptoms and transmission), the free treatment policy, and facilities is necessary and should be provided through effective multimedia for different target populations.

Demographic and Socioeconomic Disparity in Knowledge About Tuberculosis in Inner Mongolia, China

PubMed Central

Ma, Enbo; Ren, Liping; Wang, Wensheng; Takahashi, Hideto; Wagatsuma, Yukiko; Ren, Yulin; Gao, Fei; Gao, Fangfang; Wang, Wenrui; Bi, Lifu

2015-01-01

Background The aim of this study is to evaluate the awareness status, attitudes, and care-seeking behaviors concerning tuberculosis (TB) and associated factors among the public in Inner Mongolia, China. Methods A five-stage sampling was conducted, in which counties as the primary survey units and towns, villages, and households as sub-survey units were selected progressively. A standardized questionnaire was used to collect TB information. Complex survey analysis methods, including the procedures of survey frequency and survey logistic regression, were applied for analysis of TB knowledge and associated factors. The sample was weighted by survey design, non-respondent, and post-stratification adjustment. Results Among 10 581 respondents, awareness that TB is an infectious disease was 86.7%. Knowing that a cough lasting ≥3 weeks is suggestive of TB was 26.9%. Knowledge about TB dispensaries in county administrative areas was reported by 68.3% of respondents, and knowledge about the free TB detection/treatment policy was reported by 57.5% of respondents. About 52.5% of participants would stigmatize TB patients. Compared with the majority Han ethnic group, Mongolians and other minorities were 1.52–2.18 times more likely to know about TB curability, TB symptoms, the free detection/treatment policy, and TB dispensaries’ locations, but were less likely to know about the TB transmission mode (odds ratio, 0.74; 95% confidence interval, 0.65–0.84). The main sources of TB information were TV (65.6%) and other persons (47.2%). In the past year, 19.7% of TB knowledge was from acquaintances, and 16.1% was from TB institutes. Conclusions Improvement in knowledge about TB risk (symptoms and transmission), the free treatment policy, and facilities is necessary and should be provided through effective multimedia for different target populations. PMID:25797599

Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study.

PubMed

Semvua, Hadija H; Mtabho, Charles M; Fillekes, Quirine; van den Boogaard, Jossy; Kisonga, Riziki M; Mleoh, Liberate; Ndaro, Arnold; Kisanga, Elton R; van der Ven, Andre; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Burger, David M

2013-01-01

To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients. This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART). A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported. Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

Effect of universal MODS access on pulmonary tuberculosis treatment outcomes in new patients in Peru

PubMed Central

Alarcón, E.; Alarcón, V.; Bissell, K.; Castillo, E.; Sabogal, I.; Mora, J.; Moore, D.; Harries, A. D.

2012-01-01

Setting: Primary health care centres in Callao, Peru. Objectives: To evaluate the effect of universal access to the microscopic-observation drug susceptibility (MODS) assay on treatment outcomes in new and primary multidrug-resistant tuberculosis (MDR-TB) patients and on the process of drug susceptibility testing (DST). Design: Retrospective review of tuberculosis (TB) registers and clinical records before (2007) and after (2009) the introduction of MODS in 2008. Results: There were 281 patients in each cohort. Favourable treatment outcomes for 2007 (81%) and 2009 (77%) cohorts were similar. There was an increase in loss to follow-up (from 6% to 10%, P = 0.04) and a reduction in failure rates (from 4% to 0.4%, P = 0.01) in the 2009 compared with the 2007 cohort. In new MDR-TB cases (n = 22), a favourable treatment outcome was improved (from 46% to 82%, P = 0.183) in the 2009 cohort. DST coverage improved (from 24% to 74%, P < 0.001), and a significant reduction in time to diagnosis of drug-susceptible (from 118 to 33 days, P < 0.001) and MDR-TB (from 158 to 52 days, P = 0.003) was observed in the 2009 cohort. Conclusion: Universal access to MODS increased DST coverage, reduced the time required to obtain DST results and was associated with reduced failure rates. MODS can make an important contribution to TB management and control in Peru. PMID:24579063

Sex disparities in tuberculosis suspect evaluation: a cross-sectional analysis in rural Uganda

PubMed Central

Miller, C. R.; Davis, J. L.; Katamba, A.; Sserwanga, A.; Kakeeto, S.; Kizito, F.; Cattamanchi, A.

2013-01-01

SUMMARY SETTING Six primary health care centers in rural Uganda. OBJECTIVE To compare the quality of tuberculosis (TB) evaluation for men and women presenting to primary health care facilities in high-burden settings. DESIGN Cross-sectional study using indicators derived from the International Standards of Tuberculosis Care (ISTC) to compare the quality of TB evaluation services provided to men and women. RESULTS Of 161 230 patient visits between January 2009 and December 2010, 112 329 (69.7%) were women. We considered 3308 (2.1%) patients with cough ≥ 2 weeks as TB suspects, of whom 1871 (56.6%) were women. Female TB suspects were less likely to be referred for sputum smear examination (45.9% vs. 61.6%, P < 0.001), to complete sputum smear examination if referred (73.7% vs. 78.3%, P = 0.024) and to receive comprehensive evaluation and care as defined by the ISTC (33.0% vs. 45.6%, P < 0.001). After adjusting for age, clinic site and visit date, women remained less likely to be referred for sputum smear examination (risk ratio [RR] 0.81, 95%CI 0.74–0.89, P < 0.001) and to receive ISTC-recommended care (RR 0.79, 95%CI 0.72–0.86, P < 0.001). CONCLUSION Strategies to ensure that women receive appropriate TB evaluation could provide a valuable opportunity for increasing case detection while also promoting equitable and universal access to care. PMID:23485382

Primary tuberculosis of glans penis after intravesical Bacillus Calmette Guerin immunotherapy.

PubMed

Sharma, V K; Sethy, P K; Dogra, P N; Singh, Urvashi; Das, P

2011-01-01

A 55-year-old male with carcinoma in situ of urinary bladder was treated with weekly intravesical injections of Bacillus Calmette Guerin (BCG) vaccine. Three days after the sixth injection, he developed low grade fever and multiple grouped punched out, 2-3 mm ulcers around meatus and corona glandis. In addition, multiple, firm, indurated, nontender papules and few deeper nodules were present on the proximal part of glans penis, along with bilateral enlarged, matted and nontender inguinal lymph nodes. There was no history suggestive of sexually transmitted diseases and high risk behavior. Chest X-ray was within normal limits, and Mantoux, Venereal Disease Research Laboratory (VDRL) and HIV antibody tests were negative. The biopsy from the penile ulcer revealed epithelioid cell granuloma with Langhans giant cells. Fine needle aspiration cytology from the lymph node also revealed epithelioid cell granuloma and acid fast bacilli on Ziehl Neelsen's stain. The tissue biopsy grew Mycobacterium tuberculosis. The BCG immunotherapy was stopped and patient was treated with four drug antitubercular therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide in standard daily doses along with pyridoxine. The edema resolved and the ulcers started healing within 2 weeks, and at 6 weeks after starting antitubercular therapy almost complete healing occurred. To the best of our knowledge, we describe the first case of an Indian patient with BCG induced primary tuberculosis of penis after immunotherapy for carcinoma urinary bladder and review the previously described cases to increase awareness of this condition in dermatologists and venereologists.

Daily Rifapentine for Treatment of Pulmonary Tuberculosis. A Randomized, Dose-Ranging Trial

PubMed Central

Savic, Radojka M.; Goldberg, Stefan; Stout, Jason E.; Schluger, Neil; Muzanyi, Grace; Johnson, John L.; Nahid, Payam; Hecker, Emily J.; Heilig, Charles M.; Bozeman, Lorna; Feng, Pei-Jean I.; Moro, Ruth N.; MacKenzie, William; Dooley, Kelly E.; Nuermberger, Eric L.; Vernon, Andrew; Weiner, Marc

2015-01-01

Rationale: Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. Objectives: We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. Methods: Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. Measurements and Main Results: A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration–time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). Conclusions: Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629). PMID:25489785

Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial.

PubMed

Dorman, Susan E; Savic, Radojka M; Goldberg, Stefan; Stout, Jason E; Schluger, Neil; Muzanyi, Grace; Johnson, John L; Nahid, Payam; Hecker, Emily J; Heilig, Charles M; Bozeman, Lorna; Feng, Pei-Jean I; Moro, Ruth N; MacKenzie, William; Dooley, Kelly E; Nuermberger, Eric L; Vernon, Andrew; Weiner, Marc

2015-02-01

Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629).

Multidrug-resistant tuberculosis in Lisbon, Portugal: a molecular epidemiological perspective.

PubMed

Perdigão, João; Macedo, Rita; João, Inês; Fernandes, Elisabete; Brum, Laura; Portugal, Isabel

2008-06-01

Portugal has the fourth highest tuberculosis (TB) incidence rate in the European Union (EU). Thirty-nine percent of all cases originate in Lisbon Health Region. Portugal also presents high levels of multidrug-resistant tuberculosis (MDR-TB) (1.5%, primary rate and 2.4%, in retreatment cases). In the present study we have characterized 58 MDR-TB clinical isolates by: (i) determining the resistance profile to first- and second-line drugs used in the treatment of tuberculosis; (ii) genotyping all isolates by MIRU-VNTR; (iii) analyzing mutations conferring resistance to isoniazid, rifampicin, streptomycin, and ethambutol, in katG, mabA-inhA, rpoB, rpsL, rrs, and pncA genes. We have therefore established the prevalence of the most common mutations associated with drug resistance in the Lisbon Health Region: C-15T in mabA-inhA for isoniazid; S531L in rpoB for rifampicin; K43R in rpsL for streptomycin; and V125G in pncA for pyrazinamide. By genotyping all isolates and combining with the mutational results, we were able to assess the isolates' genetic relatedness and determine possible transmission events. Strains belonging to family Lisboa, characterized several years ago, are still responsible for the majority of the MDR-TB. Even more alarming is the high prevalence of extensive drug-resistant tuberculosis (XDR-TB) among the MDR-TB isolates, which was found to be 53%. The TB status in Portugal therefore requires urgent attention to contain the strains continuously responsible for MDR-TB and now, XDR-TB.

Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries

PubMed Central

2012-01-01

Background Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries. Methods Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE). Results CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (P < 0.0001 and P = 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement. Conclusions CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading. PMID:22296612

Partial reconstitution of the CD4+-T-cell compartment in CD4 gene knockout mice restores responses to tuberculosis DNA vaccines.

PubMed

D'Souza, Sushila; Romano, Marta; Korf, Johanna; Wang, Xiao-Ming; Adnet, Pierre-Yves; Huygen, Kris

2006-05-01

Reactivation tuberculosis (TB) is a serious problem in immunocompromised individuals, especially those with human immunodeficiency virus (HIV) coinfection. The adaptive immune response mediated by CD4+ and CD8+ T cells is known to confer protection against TB. Hence, vaccines against TB are designed to activate these two components of the immune system. Anti-TB DNA vaccines encoding the immunodominant proteins Ag85A, Ag85B, and PstS-3 from Mycobacterium tuberculosis are ineffective in mice lacking CD4+ T cells (CD4-/- mice). In this study, we demonstrate that reconstitution of the T-cell compartment in CD4-/- mice restores vaccine-specific antibody and gamma interferon (IFN-gamma) responses to these DNA vaccines. The magnitude of the immune responses correlated with the extent of reconstitution of the CD4+-T-cell compartment. Reconstituted mice vaccinated with DNA encoding PstS-3, known to encode a dominant D(b)-restricted CD8+-T-cell epitope, displayed CD8+-T-cell responses not observed in CD4-/- mice. M. tuberculosis challenge in reconstituted mice led to the extravasation of IFN-gamma-producing CD4+ and CD8+ T cells into lungs, the primary site of bacterial replication. Importantly, a reconstitution of 12 to 15% of the CD4+-T-cell compartment resulted in Ag85B plasmid DNA-mediated protection against a challenge M. tuberculosis infection. Our findings provide evidence that anti-TB DNA vaccines could be effective in immunodeficient individuals after CD4+-T-lymphocyte reconstitution, as may occur following antiretroviral therapy in HIV+ patients.

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis

PubMed Central

Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M.; Lucas, Megan; Spencer, John S.; Amara, Rama Rao; Plikaytis, Bonnie B.; Posey, James E.; Sable, Suraj B.

2016-01-01

Heterologous prime–boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32–52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime–Apa-subunit-boost strategy compared to Apa-subunit-prime–BCG-boost approach. However, parenteral BCG-prime–Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime–boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime–boost regimens against tuberculosis in humans. PMID:27173443

Chronic airway obstruction after successful treatment of tuberculosis and its impact on quality of life.

PubMed

de la Mora, I Laniado; Martínez-Oceguera, D; Laniado-Laborín, R

2015-07-01

Tuberculosis (TB) clinic in Tijuana, México. Chronic airway obstruction (CAO) can be a sequella of pulmonary tuberculosis (PTB), independently of smoking history. To determine the prevalence of CAO in subjects recently recorded as cured after treatment of PTB, and its impact on quality of life. Cross-sectional study. Overall, 34.3% of patients with a history of PTB had non-reversible CAO, defined as FEV1 <70% post-bronchodilator. Subjects with CAO had significantly more radiographic fibrocavitary sequellae on chest X-rays, more extensive changes (1.8 ± 0.8 affected quadrants vs. 1.3 ± 0.6, P = 0.04), more residual lung cavities (1.4 ± 0.8 vs. 0.5 ± 0.7, P = 0.002), and greater mediastinal retraction (42.4% vs. 16.7%, P = 0.026). The mean COPD Assessment Test score for subjects with CAO was 15.1 ± 10.4. The prevalence of irreversible CAO using the lower limit of normal criteria was higher (40%) than that calculated with fixed ratio criteria (34.3%). Functional abnormalities are frequently already present at the end of treatment for PTB; patients with CAO are often symptomatic and experience a significant impact on quality of life.

Attomolar quantitation of Mycobacterium tuberculosis by asymmetric helicase-dependent isothermal DNA-amplification and electrochemical detection.

PubMed

Barreda-García, Susana; González-Álvarez, María José; de-Los-Santos-Álvarez, Noemí; Palacios-Gutiérrez, Juan José; Miranda-Ordieres, Arturo J; Lobo-Castañón, María Jesús

2015-06-15

A highly sensitive and robust method for the quantification of specific DNA sequences based on coupling asymmetric helicase-dependent DNA amplification to electrochemical detection is described. This method relies on the entrapment of the amplified ssDNA sequences on magnetic beads followed by a post-amplification hybridization assay to provide an added degree of specificity. As a proof-of-concept a 84-bases long sequence specific of Mycobacterium tuberculosis is amplified at 65°C, providing 3×10(6) amplification after 90 min. Using this system 0.5 aM, corresponding to 15 copies of the target gene in 50 µL of sample, can be successfully detected and reliably quantified under isothermal conditions in less than 4h. The assay has been applied to the detection of M. tuberculosis in sputum, pleural fluid and urine samples. Besides this application, the proposed assays is a powerful and general tool for molecular diagnostic that can be applied to the detection of other specific DNA sequences, taking full advantage of the plethora of genomic information now available. Copyright © 2014 Elsevier B.V. All rights reserved.

Tuberculous otitis media: a resurgence?

PubMed

Kameswaran, M; Natarajan, K; Parthiban, M; Krishnan, P V; Raghunandhan, S

2017-09-01

Tuberculosis is a global health problem that is especially prevalent in developing countries such as India. Recently, atypical presentation has become more common and a high index of suspicion is essential. This study analysed the various presenting symptoms and signs of tuberculous otitis media and the role of diagnostic tests, with the aim of formulating criteria for the diagnosis. A total of 502 patients underwent tympanomastoidectomy over a two-year period. Microbiological and histopathological examinations and polymerase chain reaction analysis of tissue taken during tympanomastoidectomy were performed. A total of 25 patients (5 per cent) were diagnosed with tuberculous otitis media. Severe mixed hearing loss, facial palsy, labyrinthine fistula, post-aural fistula, perichondritis and extradural abscess were noted. There seems to be a resurgence in tuberculous otitis media in India. Microbiological, histopathological and polymerase chain reaction tests for tuberculosis are helpful for its diagnosis.

Tuberculous spondylitis in Haji Adam Malik hospital, Medan

NASA Astrophysics Data System (ADS)

Dharmajaya, R.

2018-03-01

Ankylosing tuberculosis is an infection caused by Mycobacterium tuberculosis in one or more components of the vertebrae; it is Pott disease or tuberculous spondylitis. It might become a potential cause of morbidity, including neurological deficits and permanent deformity of the spine. Management of TB Spondylitis, in general, is chemotherapy with antituberculosis drugs (ATG), immobilization, and spine surgical interventions. A retrospective study was conducted to analyze the patients of TB Spondylitis who had undergone surgery at Haji Adam Malik hospital from June 2015 to June 2017. The most common location is thoracal (10%), lumbal (3%), and thoracolumbal junction (3%). Decompression laminectomy with fusion (18%) is the most suitable option for surgical management. The majority, pre- operation ASIA scale is D (8%), and post operation is E (8%). It means that surgical plays an important role in themanagement of tuberculous spondylitis.

Multiple intracranial space-occupying lesions in a renal transplant recipient from an area endemic for tuberculosis (TB): TB vs. toxoplasmosis.

PubMed

Bagchi, S; Sachdev, S S; Nalwa, A; Das, C J; Sinha, S; Suri, V; Mahajan, S; Bhowmik, D; Agarwal, S

2014-10-01

Renal transplant recipients may present with intracranial space-occupying lesions (SOLs) due to infections as well as a post-transplant lymphoproliferative disorder (PTLD). Here, we discuss a renal transplant recipient who presented with neurologic symptoms and magnetic resonance imaging (MRI) of the brain showed multiple focal SOLs. Tuberculosis (TB), toxoplasmosis, nocardiosis, fungal infections, and PTLD were considered in the differential diagnosis. MRI spectroscopy was suggestive of an infectious cause, such as toxoplasmosis or TB. Serologic tests using Toxoplasma were negative. A brain biopsy followed by immunohistochemical staining using Toxoplasma antibody demonstrated multiple intravascular cysts of toxoplasma. This case highlights the diagnostic dilemma in an immunocompromised patient with multiple focal brain lesions, especially in areas where TB is endemic. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Tuberculin-Specific T Cells Are Reduced in Active Pulmonary Tuberculosis Compared to LTBI or Status Post BCG Vaccination

PubMed Central

Streitz, Mathias; Fuhrmann, Stephan; Powell, Fiona; Quassem, Ali; Nomura, Laurel; Maecker, Holden; Martus, Peter; Volk, Hans-Dieter

2011-01-01

Functional characteristics of tuberculosis (TB)–specific CD4 T cells were studied in clinically active pulmonary TB (n = 21) and high TB exposure including LTBI (n = 17). Following tuberculin stimulation, activated CD4 T cells were identified by flow-cytometry (CD154 up-regulation, degranulation, interferon γ [IFN-γ], tumor necrosis factor α [TNF-α], and interleukin 2 [IL-2\\ production). Interestingly, CD154 up-regulation accounted for ∼80% of activated CD4 T cells in the active TB group but just 40% in the controls, whereas IFN-γ accounted for only ∼50% of activated cells in each group. The frequencies of CD4 T cells displaying at least 1 activation marker discriminated better between the groups than those displaying degranulation or IFN-γ production alone. PMID:21186260

Ambulatory tuberculosis treatment in post-Semashko health care systems needs supportive financing mechanisms.

PubMed

Kohler, S; Asadov, D A; Bründer, A; Healy, S; Khamraev, A K; Sergeeva, N; Tinnemann, P

2014-12-01

The tuberculosis (TB) control strategy in the Republic of Karakalpakstan, Uzbekistan, is being changed to decentralised out-patient care for most TB patients by the Government of Uzbekistan, in collaboration with the international medical humanitarian organisation Médecins Sans Frontières. Ambulatory treatment of both drug-susceptible and drug-resistant TB from the first day of treatment has been recommended since 2011. Out-patient treatment of TB from the beginning of treatment was previously prohibited. However, the current Uzbek health financing system, which evolved from the Soviet Semashko model, offers incentives that work against the adoption of ambulatory TB treatment. Based on the 'Comprehensive TB Care for All' programme implemented in Karakalpakstan, we describe how existing policies for the allocation of health funds complicate the scale-up of ambulatory-based management of TB.

Immunoendocrine abnormalities in the male reproductive system during experimental pulmonary tuberculosis.

PubMed

Ramos Robles, Brenda; Valdez, Ricardo A; Hernández, Uriel Juárez; Marquina Castillo, Brenda; Mata Espinosa, Dulce; Barrios Payan, Jorge; Hernández Pando, Rogelio; Romano, Marta C

2018-03-01

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that mainly affects the lungs. Along the course of pulmonary TB there are remarkable changes in the production of cytokines that cause endocrine changes. So far, it is not known the physiological and histological changes in the male reproductive system during pulmonary TB. To investigate whether pulmonary TB produces histological alterations of the BALB/c mice reproductive organs, as well as abnormalities in spermatogenesis, serum testosterone concentrations and expression of testicular cytokines. BALB/c mice were infected intratracheally with high dose Mtb strain H37Rv. Groups of six non infected and infected animals were euthanized on days 1, 3, 7, 14, 21, 28, 60, 90 and 120 post-infection. Bacillary loads were determined by counting colony forming units (CFUs) in lungs, testes, prostate and seminal vesicles. Histological sections were obtained from the same organs. Spermatozoids number and quality were assessed by spermatobioscopy. Serum testosterone concentrations were determined by radioimmunoanalysis (RIA) in control and infected mice in each time of sacrifice. Mtb only grew in lung tissue. Serum androgens showed a trend to decrease in the infected mice compared to the healthy animals, the difference turn into statistically significance at post infection day 120. The weight of the testis was not modified throughout the study, and no histopathological changes were found. However, we detected a significant decrease in the weight of the seminal vesicles and prostate starting at 28 days post-infection. Atrophy of the seminal vesicles and prostate epithelia were significant, beginning after 60 days of infection. Spermatobioscopy revealed hypospermia in the later stages of the disease. We have observed in the testes a local significant disbalance on the cytokine profile (increase of IL-6 and decrease of IL-10 and TGF-b levels) together with a very significant reduction of the body weight during late pulmonary TB. Pulmonary TB affects the histophysiology of the male reproductive system due to hormonal changes, an imbalance of pro-inflammatory cytokine profile, and a wasting syndrome during late disease. Copyright © 2018. Published by Elsevier Ltd.

An Unusual Presentation of Addison's Disease-A Case Report.

PubMed

Choudhary, Sandeep; Alam, Anwer; Dewan, Vivek; Yadav, Dinesh; Dubey, N K

2011-07-01

Addison's disease is most commonly due to autoimmune adrenalitis and tuberculosis and refers to primary hypoadrenalism caused by a total or near total destruction or dysfunction of both adrenal cortices. Usual manifestations involve chronic fatigue, muscle weakness, loss of appetite, nausea, vomiting, diarrhea, hypotension and hyperpigmentation of skin. We herein report a case of primary adrenal insufficiency presenting with fever and seizures in an 11-yr-old boy. His symptoms resolved after starting specific therapy. This kind of presentation of Addison's disease is rather unusual.

Measuring workload for tuberculosis service provision at primary care level: a methodology

PubMed Central

2012-01-01

We developed and piloted a methodology to establish TB related work load at primary care level for clinical and laboratory staff. Workload is influenced by activities to be implemented, time to perform them, their frequency and patient load. Of particular importance is the patient pathway for diagnosis and treatment and the frequency of clinic visits. Using observation with checklists, clocking, interviews and review of registers, allows assessing the contribution of different factors on the workload. PMID:22640406

Stringent homology-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions.

PubMed

Zhou, Hufeng; Gao, Shangzhi; Nguyen, Nam Ninh; Fan, Mengyuan; Jin, Jingjing; Liu, Bing; Zhao, Liang; Xiong, Geng; Tan, Min; Li, Shijun; Wong, Limsoon

2014-04-08

H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are essential for understanding the infection mechanism of the formidable pathogen M. tuberculosis H37Rv. Computational prediction is an important strategy to fill the gap in experimental H. sapiens-M. tuberculosis H37Rv PPI data. Homology-based prediction is frequently used in predicting both intra-species and inter-species PPIs. However, some limitations are not properly resolved in several published works that predict eukaryote-prokaryote inter-species PPIs using intra-species template PPIs. We develop a stringent homology-based prediction approach by taking into account (i) differences between eukaryotic and prokaryotic proteins and (ii) differences between inter-species and intra-species PPI interfaces. We compare our stringent homology-based approach to a conventional homology-based approach for predicting host-pathogen PPIs, based on cellular compartment distribution analysis, disease gene list enrichment analysis, pathway enrichment analysis and functional category enrichment analysis. These analyses support the validity of our prediction result, and clearly show that our approach has better performance in predicting H. sapiens-M. tuberculosis H37Rv PPIs. Using our stringent homology-based approach, we have predicted a set of highly plausible H. sapiens-M. tuberculosis H37Rv PPIs which might be useful for many of related studies. Based on our analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent homology-based approach, we have discovered several interesting properties which are reported here for the first time. We find that both host proteins and pathogen proteins involved in the host-pathogen PPIs tend to be hubs in their own intra-species PPI network. Also, both host and pathogen proteins involved in host-pathogen PPIs tend to have longer primary sequence, tend to have more domains, tend to be more hydrophilic, etc. And the protein domains from both host and pathogen proteins involved in host-pathogen PPIs tend to have lower charge, and tend to be more hydrophilic. Our stringent homology-based prediction approach provides a better strategy in predicting PPIs between eukaryotic hosts and prokaryotic pathogens than a conventional homology-based approach. The properties we have observed from the predicted H. sapiens-M. tuberculosis H37Rv PPI network are useful for understanding inter-species host-pathogen PPI networks and provide novel insights for host-pathogen interaction studies.

Clinicopathological profile and surgical treatment of abdominal tuberculosis: a single centre experience in northwestern Tanzania

PubMed Central

2013-01-01

Background Abdominal tuberculosis continues to be a major public health problem worldwide and poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. This study was conducted to describe the clinicopathological profile and outcome of surgical treatment of abdominal tuberculosis in our setting and compare with what is described in literature. Methods A prospective descriptive study of patients who presented with abdominal tuberculosis was conducted at Bugando Medical Centre (BMC) in northwestern Tanzania from January 2006 to February 2012. Ethical approval to conduct the study was obtained from relevant authorities. Statistical data analysis was performed using SPSS version 17.0. Results Out of 256 patients enrolled in the study, males outnumbered females. The median age was 28 years (range = 16–68 years). The majority of patients (77.3%) had primary abdominal tuberculosis. A total of 127 (49.6%) patients presented with intestinal obstruction, 106 (41.4%) with peritonitis, 17 (6.6%) with abdominal masses and 6 (2.3%) patients with multiple fistulae in ano. Forty-eight (18.8%) patients were HIV positive. A total of 212 (82.8%) patients underwent surgical treatment for abdominal tuberculosis. Bands /adhesions (58.5%) were the most common operative findings. Ileo-caecal region was the most common bowel involved in 122 (57.5%) patients. Release of adhesions and bands was the most frequent surgical procedure performed in 58.5% of cases. Complication and mortality rates were 29.7% and 18.8% respectively. The overall median length of hospital stay was 32 days and was significantly longer in patients with complications (p < 0.001). Advanced age (age ≥ 65 years), co-morbid illness, late presentation, HIV positivity and CD4+ count < 200 cells/μl were statistically significantly associated with mortality (p < 0.0001). The follow up of patients were generally poor as only 37.5% of patients were available for follow up at twelve months after discharge. Conclusion Abdominal tuberculosis constitutes a major public health problem in our environment and presents a diagnostic challenge requiring a high index of clinical suspicion. Early diagnosis, early anti-tuberculous therapy and surgical treatment of the associated complications are essential for survival. PMID:23758837

Rifampicin-induced adrenal crisis in a patient with tuberculosis: a therapeutic challenge.

PubMed

Denny, Nicholas; Raghunath, Sarika; Bhatia, Praveen; Abdelaziz, Muntasir

2016-11-29

A 55-year-old Indian man presented with productive cough and a large left pleural effusion. Pleural fluid culture grew Mycobacterium tuberculosis, and he was started on antituberculosis therapy. One week later, the patient presented to hospital with drowsiness, dehydration and hypotension. He was transferred to critical care and only improved after starting hydrocortisone and stopping rifampicin. His short synACTHen test subsequently confirmed primary adrenal insufficiency, and a CT of the abdomen showed bilateral adrenal enlargement. Rifampicin is known to accelerate cortisol metabolism. We report the rare case of a rifampicin-induced adrenal crisis as a first presentation of Addison's disease in a patient with tuberculous infiltration of the adrenal glands. 2016 BMJ Publishing Group Ltd.

Acquisition of second-line drug resistance and extensive drug resistance during recent transmission of Mycobacterium tuberculosis in rural China.

PubMed

Hu, Y; Mathema, B; Zhao, Q; Chen, L; Lu, W; Wang, W; Kreiswirth, B; Xu, B

2015-12-01

Multidrug-resistant tuberculosis (MDR-TB) is prevalent in countries with a high TB burden, like China. As little is known about the emergence and spread of second-line drug (SLD) -resistant TB, we investigate the emergence and transmission of SLD-resistant Mycobacterium tuberculosis in rural China. In a multi-centre population-based study, we described the bacterial population structure and the transmission characteristics of SLD-resistant TB using Spoligotyping in combination with genotyping based on 24-locus MIRU-VNTR (mycobacterial interspersed repetitive unit-variable-number tandem repeat) plus four highly variable loci for the Beijing family, in four rural Chinese regions with diverse geographic and socio-demographic characteristics. Transmission networks among genotypically clustered patients were constructed using social network analysis. Of 1332 M. tuberculosis patient isolates recovered, the Beijing family represented 74.8% of all isolates and an association with MDR and simultaneous resistance between first-line drugs and SLDs. The genotyping analysis revealed that 189 isolates shared MIRU-VNTR patterns in 78 clusters with clustering rate and recent transmission rate of 14.2% and 8.3%, respectively. Fifty-three SLD-resistant isolates were observed in 31 clusters, 30 of which contained the strains with different drug susceptibility profiles and genetic mutations. In conjunction with molecular data, socio-network analysis indicated a key role of Central Township in the transmission across a highly interconnected network where SLD resistance accumulation occurred during transmission. SLD-resistant M. tuberculosis has been spreading in rural China with Beijing family being the dominant strains. Primary transmission of SLD-resistant strains in the population highlights the importance of routine drug susceptibility testing and effective anti-tuberculosis regimens for drug-resistant TB. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Characterization of Antibacterial and Hemolytic Activity of Synthetic Pandinin 2 Variants and Their Inhibition against Mycobacterium tuberculosis

PubMed Central

Rodríguez, Alexis; Villegas, Elba; Montoya-Rosales, Alejandra; Rivas-Santiago, Bruno; Corzo, Gerardo

2014-01-01

The contention and treatment of Mycobacterium tuberculosis and other bacteria that cause infectious diseases require the use of new type of antibiotics. Pandinin 2 (Pin2) is a scorpion venom antimicrobial peptide highly hemolytic that has a central proline residue. This residue forms a structural “kink” linked to its pore-forming activity towards human erythrocytes. In this work, the residue Pro14 of Pin2 was both substituted and flanked using glycine residues (P14G and P14GPG) based on the low hemolytic activities of antimicrobial peptides with structural motifs Gly and GlyProGly such as magainin 2 and ponericin G1, respectively. The two Pin2 variants showed antimicrobial activity against E. coli, S. aureus, and M. tuberculosis. However, Pin2 [GPG] was less hemolytic (30%) than that of Pin2 [G] variant. In addition, based on the primary structure of Pin2 [G] and Pin2 [GPG], two short peptide variants were designed and chemically synthesized keeping attention to their physicochemical properties such as hydrophobicity and propensity to adopt alpha-helical conformations. The aim to design these two short antimicrobial peptides was to avoid the drawback cost associated to the synthesis of peptides with large sequences. The short Pin2 variants named Pin2 [14] and Pin2 [17] showed antibiotic activity against E. coli and M. tuberculosis. Besides, Pin2 [14] presented only 25% of hemolysis toward human erythrocytes at concentrations as high as 100 µM, while the peptide Pin2 [17] did not show any hemolytic effect at the same concentration. Furthermore, these short antimicrobial peptides had better activity at molar concentrations against multidrug resistance M. tuberculosis than that of the conventional antibiotics ethambutol, isoniazid and rifampicin. Therefore, Pin2 [14] and Pin2 [17] have the potential to be used as an alternative antibiotics and anti-tuberculosis agents with reduced hemolytic effects. PMID:25019413

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

PubMed

Nliwasa, Marriott; MacPherson, Peter; Chisala, Palesa; Kamdolozi, Mercy; Khundi, McEwen; Kaswaswa, Kruger; Mwapasa, Mphatso; Msefula, Chisomo; Sohn, Hojoon; Flach, Clare; Corbett, Elizabeth L

2016-01-01

Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi

PubMed Central

Nliwasa, Marriott; MacPherson, Peter; Chisala, Palesa; Kamdolozi, Mercy; Khundi, McEwen; Kaswaswa, Kruger; Mwapasa, Mphatso; Msefula, Chisomo; Sohn, Hojoon; Flach, Clare; Corbett, Elizabeth L.

2016-01-01

Background Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. Objective To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. Methods Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. Results Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). Conclusion The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis. PMID:27171380

Evaluation of Xpert MTB/RIF assay in children with presumed pulmonary tuberculosis in Papua New Guinea.

PubMed

Kasa Tom, Sharon; Welch, Henry; Kilalang, Cornelia; Tefuarani, Nakapi; Vince, John; Lavu, Evelyn; Johnson, Karen; Magaye, Ruth; Duke, Trevor

2018-05-01

The Gene Xpert MTB/ RIF assay (Xpert) is used for rapid, simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin resistance. This study examined the accuracy of Xpert in children with suspected pulmonary tuberculosis (PTB). Children admitted to Port Moresby General Hospital with suspected PTB were prospectively enrolled between September 2014 and March 2015. They were classified into probable, possible and TB-unlikely groups. Sputum or gastric aspirates were tested by Xpert and smear microscopy; mycobacterial culture was undertaken on a subset. Children were diagnosed with TB on the basis of standard criteria which were used as the primary reference standard. Xpert, smear for acid-fast bacilli (AFB) and the Edwards TB score were compared with the primary reference standard. A total of 93 children ≤14 years with suspected PTB were enrolled; 67 (72%) were classified as probable, 21 (22%) possible and 5 (5.4%) TB-unlikely. Eighty were treated for TB based on the primary reference standard. Xpert was positive in 26/93 (28%) MTB cases overall, including 22/67 (33%) with probable TB and 4/21 (19%) with possible TB. Three (13%) samples identified rifampicin resistance. Xpert confirmed more cases of TB than AFB smear (26 vs 13, p = 0.019). The sensitivity of Xpert, AFB smear and an Edwards TB score of ≥7 was 31% (25/80), 16% (13/80) and 90% (72/80), respectively, and the specificity was 92% (12/13), 100% (13/13) and 31% (4/13), respectively, when compared with the primary reference standard. Xpert sensitivity is sub-optimal and cannot be relied upon for diagnosing TB, although a positive result is confirmatory. A detailed history and examination, standardised clinical criteria, radiographs and available tests remain the most appropriate way of diagnosing TB in children in resource-limited countries. Xpert helps confirm PTB better than AFB smear, and identifies rifampicin resistance. Practical guidelines should be used to identify children who will benefit from an Xpert assay.

Hypoxia promotes Mycobacterium tuberculosis-specific up-regulation of granulysin in human T cells.

PubMed

Zenk, Sebastian F; Vollmer, Michael; Schercher, Esra; Kallert, Stephanie; Kubis, Jan; Stenger, Steffen

2016-06-01

Oxygen tension affects local immune responses in inflammation and infection. In tuberculosis mycobacteria avoid hypoxic areas and preferentially persist and reactivate in the oxygen-rich apex of the lung. Oxygen restriction activates antimicrobial effector mechanisms in macrophages and restricts growth of intracellular Mycobacterium tuberculosis (M.Tb). The effect of oxygen restriction on T cell-mediated antimicrobial effector mechanisms is unknown. Therefore we determined the influence of hypoxia on the expression of granulysin, an antimicrobial peptide of lymphocytes. Hypoxia increased the antigen-specific up-regulation of granulysin mRNA and protein in human CD4(+) and CD8(+) T lymphocytes. This observation was functionally relevant, because oxygen restriction supported the growth-limiting effect of antigen-specific T cells against virulent M.Tb residing in primary human macrophages. Our results provide evidence that oxygen restriction promotes the expression of granulysin and suggest that this effect-in conjunction with additional T cell-mediated immune responses-supports protection against mycobacteria. The therapeutic modulation of oxygen availability may offer a new strategy for the host-directed therapy of infectious diseases with intracellular pathogens.

Oxidative Phosphorylation as a Target Space for Tuberculosis: Success, Caution, and Future Directions.

PubMed

Cook, Gregory M; Hards, Kiel; Dunn, Elyse; Heikal, Adam; Nakatani, Yoshio; Greening, Chris; Crick, Dean C; Fontes, Fabio L; Pethe, Kevin; Hasenoehrl, Erik; Berney, Michael

2017-06-01

The emergence and spread of drug-resistant pathogens, and our inability to develop new antimicrobials to combat resistance, have inspired scientists to seek out new targets for drug development. The Mycobacterium tuberculosis complex is a group of obligately aerobic bacteria that have specialized for inhabiting a wide range of intracellular and extracellular environments. Two fundamental features in this adaptation are the flexible utilization of energy sources and continued metabolism in the absence of growth. M. tuberculosis is an obligately aerobic heterotroph that depends on oxidative phosphorylation for growth and survival. However, several studies are redefining the metabolic breadth of the genus. Alternative electron donors and acceptors may provide the maintenance energy for the pathogen to maintain viability in hypoxic, nonreplicating states relevant to latent infection. This hidden metabolic flexibility may ultimately decrease the efficacy of drugs targeted against primary dehydrogenases and terminal oxidases. However, it may also open up opportunities to develop novel antimycobacterials targeting persister cells. In this review, we discuss the progress in understanding the role of energetic targets in mycobacterial physiology and pathogenesis and the opportunities for drug discovery.

Management and outcome of chemotherapy for childhood tuberculosis. Medical Research Council Tuberculosis and Chest Diseases Unit.

PubMed Central

1989-01-01

The management and outcome of chemotherapy is reported for 393 children with tuberculosis notified in 1983 (191 (49%) of white, 155 (39%) of Indian, Pakistani, or Bangladeshi, and 47 (12%) of other ethnic origins). Most (313) had respiratory disease, 65 had extrathoracic lymph node disease, and 15 had both. Only 15 (4%) of the 390 children for whom information was available did not complete chemotherapy, 10 because of default. All except 23 (6%) of the children known to have completed chemotherapy received isoniazid and rifampicin, 194 (52%) without additional drugs, 126 (34%) with ethambutol, eight (2%) with pyrazinamide, and seven (2%) with both drugs in the initial phase. The median duration of treatment was nine months. At the time they were last seen, all except six of the 375 children who completed chemotherapy were classified by the clinician as cured either on the primary course of chemotherapy (348, 93%) or after modification for failure or relapse (11.3%), or toxicity (10.3%). The remaining children were still on treatment for relapse (n = 2) or had defaulted from follow up (n = 4). PMID:2629621

Physiological and Molecular Pathology of Aminoglycoside Ototoxicity

ERIC Educational Resources Information Center

Sha, Su-Hua

2005-01-01

The problem of aminoglycoside-induced ototoxicity, which was recognized within a year of the discovery of streptomycin to combat tuberculosis in 1944, is still of great concern due to the widespread use of these powerful antibacterial agents. These drugs can damage to varying degrees the cochlea and vestibular system. Their primary targets are the…

Primary School Nutrition and Tuck Shops in Hhoho, Swaziland

ERIC Educational Resources Information Center

Wojcicki, Janet M.; Elwan, Deena

2014-01-01

Background: Obesity and associated chronic diseases are increasing in frequency in African populations that also have a high burden of disease from infectious diseases such as HIV/AIDS and tuberculosis. Obesity and diabetes mellitus are common in Swaziland, Southern Africa, where >10% of children under the age of five are already obese.…

Etiology of pleural effusions: analysis of more than 3,000 consecutive thoracenteses.

PubMed

Porcel, José M; Esquerda, Aureli; Vives, Manuel; Bielsa, Silvia

2014-05-01

To investigate the etiology of pleural effusions (PE) in adults and the accuracy of pleural fluid (PF) cytology and cultures in malignant and infectious PE, respectively. Retrospective analysis of all consecutive patients with PE undergoing diagnostic thoracentesis during the last 19 years in a university hospital. The leading causes of PE among the 3,077 patients were: cancer (27%), heart failure (21%), pneumonia (19%), tuberculosis (9%), abdominal surgery (4%), pericardial diseases (4%) and cirrhosis (3%). Tuberculosis was the most common etiology in patients <34 years of age (52%), whereas heart failure predominated in octogenarians (45%). The most common primary tumors in malignant PE were lung (37%) and breast (16%). The overall accuracy of PF cytology was 59%, although it was significantly lower in mesotheliomas (27%) and squamous cell lung cancer (25%). In infectious PE, only 30% of cultures yielded positive results, a percentage which increased two-fold (66%) in purulent fluids (empyemas). Viridans streptococci were the most commonly isolated pathogens (25.5%). The sensitivity of solid media cultures of PF for Mycobacterium tuberculosis was low (18.5%). Three-quarters of patients with PE in whom a diagnostic thoracentesis was indicated had cancer, heart failure, pneumonia or tuberculosis. PF cytology and cultures give false negative results in a significant number of cases. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Laboratory diagnosis of tuberculosis: Advances in technology and drug susceptibility testing.

PubMed

Oommen, Seema; Banaji, Nandita

2017-01-01

There have been rapid technological advances in the detection of Mycobacterium tuberculosis and its drug susceptibility in clinical samples. These include advances in microscopic examination, in vitro culture and application of molecular techniques. The World Health Organization (WHO) has played a large role in evaluating these technologies for their efficacy and feasibility, especially in the developing countries. Amongst these, the Revised National Tuberculosis Control Programme (RNTCP), through its national network of designated microscopy centres and intermediate reference laboratories, has adopted certain technologies that are currently implemented in India. Advances in microscopy technology include fluorescent microscopy using light-emitting diode source, sodium hypochlorite microscopy and vital fluorescent staining of sputum smears. Automation of in vitro culture has markedly reduced the turnaround time (TAT), even in smear-negative samples, and permits simultaneous detection of resistant mutants. Molecular detection of drug resistance has further reduced the TAT, and the cartridge-based nucleic acid amplification test with its performance convenience and rapid results, appears poised to become the future of tuberculosis (TB) diagnosis in all settings, provided the cost of testing is reduced especially for use in private diagnostic settings. This article reviews technologies currently available for the diagnosis of TB, keeping in mind the WHO recommendations and the RNTCP practices. This is a thematic synthesis of data available on diagnosis in literature, preserving the conclusions of the primary studies.

MUBII-TB-DB: a database of mutations associated with antibiotic resistance in Mycobacterium tuberculosis.

PubMed

Flandrois, Jean-Pierre; Lina, Gérard; Dumitrescu, Oana

2014-04-14

Tuberculosis is an infectious bacterial disease caused by Mycobacterium tuberculosis. It remains a major health threat, killing over one million people every year worldwide. An early antibiotic therapy is the basis of the treatment, and the emergence and spread of multidrug and extensively drug-resistant mutant strains raise significant challenges. As these bacteria grow very slowly, drug resistance mutations are currently detected using molecular biology techniques. Resistance mutations are identified by sequencing the resistance-linked genes followed by a comparison with the literature data. The only online database is the TB Drug Resistance Mutation database (TBDReaM database); however, it requires mutation detection before use, and its interrogation is complex due to its loose syntax and grammar. The MUBII-TB-DB database is a simple, highly structured text-based database that contains a set of Mycobacterium tuberculosis mutations (DNA and proteins) occurring at seven loci: rpoB, pncA, katG; mabA(fabG1)-inhA, gyrA, gyrB, and rrs. Resistance mutation data were extracted after the systematic review of MEDLINE referenced publications before March 2013. MUBII analyzes the query sequence obtained by PCR-sequencing using two parallel strategies: i) a BLAST search against a set of previously reconstructed mutated sequences and ii) the alignment of the query sequences (DNA and its protein translation) with the wild-type sequences. The post-treatment includes the extraction of the aligned sequences together with their descriptors (position and nature of mutations). The whole procedure is performed using the internet. The results are graphs (alignments) and text (description of the mutation, therapeutic significance). The system is quick and easy to use, even for technicians without bioinformatics training. MUBII-TB-DB is a structured database of the mutations occurring at seven loci of major therapeutic value in tuberculosis management. Moreover, the system provides interpretation of the mutations in biological and therapeutic terms and can evolve by the addition of newly described mutations. Its goal is to provide easy and comprehensive access through a client-server model over the Web to an up-to-date database of mutations that lead to the resistance of M. tuberculosis to antibiotics.

Treatment outcomes of TB-infected individuals attending public sector primary care clinics in rural Liberia from 2015 to 2017: a retrospective cohort study.

PubMed

Wickett, Eugene; Peralta-Santos, André; Beste, Jason; Micikas, Mary; Toe, Foriest; Rogers, Julia; Jabateh, Lassana; Wagenaar, Bradley H

2018-05-01

In June 2015, Partners in Health (PIH) and the Liberian Ministry of Health began a community health worker (CHW) programme containing food support, reimbursement of transport and social assistance to address gaps in tuberculosis (TB) treatment exacerbated by the 2014-2015 Ebola virus disease (EVD) epidemic. The purpose of this article was to analyse the performance of routine clinical TB care and the effects of this CHW programme. Retrospective cohort study utilising data from TB patient registers at a census of all health facilities treating TB in the south-east region of Liberia from January 2015 - April 2017. Competing risks Cox regression analyses were used to generate subhazard ratios (sHR) analysing factors associated with rates of TB cure (smear negative), treatment completion (no smear), lost to follow-up (LTFU) and death. LTFU rates decreased 76% pre- vs. post-CHW intervention, from 14.6% in pre-intervention to 3.4% post-intervention (P < 0.001). Although the post-intervention had better cure rates (sHR 1.07, CI 0.58-1.9), treatment completion (sHR 1.53, CI 1.00 2.39) and lower death rates (sHR 0.64, CI 0.34-1.2), statistical significance was not reached. Younger patients had significantly lower death and cure rates, while older patients had higher LTFU and cure rates. Overall, 31% of patients were cured, 44% completed treatment without a confirmatory smear, 5% were LTFU, 9% died, 0.5% failed treatment, and 10% transferred out. In challenging environments, LTFU can be reduced by CHW accompaniment and socio-economic assistance to patients with TB. Approaches are needed to improve cure verification in young patients and reduce mortality. © 2018 John Wiley & Sons Ltd.

[Multicenter transversal study of tuberculosis and drug resistance in Madrid (October 1993-April 1994)].

PubMed

1996-01-13

The aim of this study was to know the demographic profile of the new cases of tuberculosis (TB) and evaluate the current status of resistance to antituberculous drugs in Madrid, Spain. A transversal study was carried out in 8 hospitals (6 general hospitals) during 6 months. The clinical data of patients over 14 years old who presented a positive culture for Mycobacterium tuberculosis were collected in a protocolized method; the study on sensitivity to 5 drugs was independently and centrally performed (proportions method). 467 patients (339 from general hospitals), were included. In respect to the latter patients, 71% were under the age of 45 years and 36% presented coinfection with the human immunodeficiency virus (HIV). A sensitivity study was performed in 419 strains. Forty strains showed resistance to one or more of the antituberculous drugs; 13 were from the same center (CIC) in which a nosocomial outbreak of multiresistent TB had been detected among HIV infected patients. Resistence to more than one drug was observed in 29 cases (6.9%) and to rifampicine (RIF) and isoniacide (INH) in 24 patients (5.7%). On excluding the patients from the CIC these values were 16 (4.1%) and 13 (3.3%), respectively. Ninety-two percent of the strains with resistence to RIF + INH were from HIV positive patients. The rate of primary resistence to iNH in the patients with TB without HIV infection was 2.7%. This rate was 9.3% in those with HIV infection, and was 5.7% on excluding CIC cases. In patients with HIV infection most of the strains with primary resistence to INH also presented primary resistance to RIF. More than one third of the patients with TB diagnosed in the general hospitals in Madrid, presented coinfection with HIV. In this population, the initial treatment for TB should probably begin with 4 drugs while awaiting the obliged sensitivity study.

Mycobacterium tuberculosis Infection and Innate Responses in a New Model of Lung Alveolar Macrophages.

PubMed

Woo, Minjeong; Wood, Connor; Kwon, Doyoon; Park, Kyu-Ho Paul; Fejer, György; Delorme, Vincent

2018-01-01

Lung alveolar macrophages (AMs) are in the first line of immune defense against respiratory pathogens and play key roles in the pathogenesis of Mycobacterium tuberculosis ( Mtb ) in humans. Nevertheless, AMs are available only in limited amounts for in vitro studies, which hamper the detailed molecular understanding of host- Mtb interactions in these macrophages. The recent establishment of the self-renewing and primary Max Planck Institute (MPI) cells, functionally very close to lung AMs, opens unique opportunities for in vitro studies of host-pathogen interactions in respiratory diseases. Here, we investigated the suitability of MPI cells as a host cell system for Mtb infection. Bacterial, cellular, and innate immune features of MPI cells infected with Mtb were characterized. Live bacteria were readily internalized and efficiently replicated in MPI cells, similarly to primary murine macrophages and other cell lines. MPI cells were also suitable for the determination of anti-tuberculosis (TB) drug activity. The primary innate immune response of MPI cells to live Mtb showed significantly higher and earlier induction of the pro-inflammatory cytokines TNFα, interleukin 6 (IL-6), IL-1α, and IL-1β, as compared to stimulation with heat-killed (HK) bacteria. MPI cells previously showed a lack of induction of the anti-inflammatory cytokine IL-10 to a wide range of stimuli, including HK Mtb . By contrast, we show here that live Mtb is able to induce significant amounts of IL-10 in MPI cells. Autophagy experiments using light chain 3B immunostaining, as well as LysoTracker labeling of acidic vacuoles, demonstrated that MPI cells efficiently control killed Mtb by elimination through phagolysosomes. MPI cells were also able to accumulate lipid droplets in their cytoplasm following exposure to lipoproteins. Collectively, this study establishes the MPI cells as a relevant, versatile host cell model for TB research, allowing a deeper understanding of AMs functions in this pathology.

Care production for tuberculosis cases:analysis according to the elements of the Chronic Care Model.

PubMed

Silva, Daiane Medeiros da; Farias, Hérika Brito Gomes de; Villa, Tereza Cristina Scatena; Sá, Lenilde Duarte de; Brunello, Maria Eugênia Firmino; Nogueira, Jordana de Almeida

2016-04-01

To analyze the care provided to tuberculosis cases in primary health care services according to the elements of the Chronic Care Model. Cross-sectional study conducted in a capital city of the northeastern region of Brazil involving 83 Family Health Strategy professionals.A structured tool adapted to tuberculosis-related care in Brazil was applied.Analysis was based on the development of indicators with capacity to produce care varying between limited and optimum. The organization of care for tuberculosis and supported self-care presented reasonable capacity.In the coordination with the community, the presence of the community agent presented optimum capacity.Partnership with organizations of the community and involvement of experts presented limited capacity.The qualification of professionals, the system for scheduling and monitoring tuberculosis in the community, and the clinical information system presented basic capacity. The capacity of the primary health care services to produce tuberculosis-related care according to the elements of the Chronic Care Model is still limited.Overcoming the fragmentation of care and prioritizing a systemic operation between actions and services of the health care network remains as a major challenge. Analisar,segundo os elementos doChronicCareModel,a produção do cuidado aos casos de tuberculose nos serviços de Atenção Primária à Saúde. Estudo transversal, realizado em capital do nordeste brasileiro, envolvendo 83 profissionais da Estratégia Saúde da Família. Aplicou-se um instrumento estruturado, adaptado para atenção à tuberculose no Brasil. A análise pautou-se na construção de indicadores, cujacapacidade para produção de cuidados variou entre limitada a ótima. A organização da atenção à tuberculose e o autocuidado apoiado apresentaram capacidade razoável. Na articulação com a comunidade, a presençadoagente comunitário de saúde apresentou capacidade ótima. A parceria com organizações da comunidade e o envolvimento de especialistas obtiveram capacidade limitada. A capacitação dos profissionais, o sistema de agendamento e monitoramento da tuberculose na comunidade e o sistema de informação clínica alcançaram capacidade básica. A capacidade dos serviços da Atenção Primária à Saúde para produção do cuidado aos casos de tuberculose,segundo os elementos doChronicCareModel,ainda é limitada.Superar a fragmentação do cuidado e priorizar um funcionamento sistêmico entre ações e serviços da rede de atenção à saúde é ainda um grande desafio.

Increased adolescent knowledge and behavior following a one-time educational intervention about tuberculosis.

PubMed

Hatzenbuehler, Lindsay A; Starke, Jeffrey R; Smith, E O'Brian; Turner, Teri L; Balmer, Doreen F; Arif, Zainab; Guzman, Francisco; Cruz, Andrea T

2017-05-01

To evaluate the impact of a tuberculosis (TB) educational intervention (EI) on change in adolescent student knowledge and participation in a TB prevention program. From 2/2013-5/2015, students from 2 high schools in Houston, TX participated. The 25-min EI discussed TB bacteriology, epidemiology, symptoms, and indications for TB testing/treatment. Students completed pre- and post-quizzes. Immediately after the EI, students were invited to participate in voluntary TB risk-factor screening, testing and treatment. At 6 months, focus groups were conducted. 895 students attended the EI. 827 students (92%) completed the EI quizzes. Knowledge improved by 12% (pre: 70%; post: 82%, p<0.001); 78% shared their TB knowledge. Following the EI, 671/827 (81%) enrolled in a TB prevention program. Focus groups indicated that the EI stimulated student learning about TB and increased their willingness to participate. A brief, one-time, TB EI is an effective method to encourage adolescents to learn about TB and motivate their uptake of TB risk-factor screening, testing and treatment. Similar EIs should accompany TB prevention programs targeting adolescents. The study's procedures could be considered for incorporation into school-based TB prevention programs to improve the identification, testing and treatment of adolescents at risk for TB. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.

PubMed

Braian, Clara; Svensson, Mattias; Brighenti, Susanna; Lerm, Maria; Parasa, Venkata R

2015-10-05

Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

Mycobacterial disease in patients with chronic granulomatous disease: A retrospective analysis of 71 cases.

PubMed

Conti, Francesca; Lugo-Reyes, Saul Oswaldo; Blancas Galicia, Lizbeth; He, Jianxin; Aksu, Güzide; Borges de Oliveira, Edgar; Deswarte, Caroline; Hubeau, Marjorie; Karaca, Neslihan; de Suremain, Maylis; Guérin, Antoine; Baba, Laila Ait; Prando, Carolina; Guerrero, Gloria G; Emiroglu, Melike; Öz, Fatma Nur; Yamazaki Nakashimada, Marco Antonio; Gonzalez Serrano, Edith; Espinosa, Sara; Barlan, Isil; Pérez, Nestor; Regairaz, Lorena; Guidos Morales, Héctor Eduardo; Bezrodnik, Liliana; Di Giovanni, Daniela; Dbaibo, Ghassan; Ailal, Fatima; Galicchio, Miguel; Oleastro, Matias; Chemli, Jalel; Danielian, Silvia; Perez, Laura; Ortega, Maria Claudia; Soto Lavin, Susana; Hertecant, Joseph; Anal, Ozden; Kechout, Nadia; Al-Idrissi, Eman; ElGhazali, Gehad; Bondarenko, Anastasia; Chernyshova, Liudmyla; Ciznar, Peter; Herbigneaux, Rose-Marie; Diabate, Aminata; Ndaga, Stéphanie; Konte, Barik; Czarna, Ambre; Migaud, Mélanie; Pedraza-Sánchez, Sigifredo; Zaidi, Mussaret Bano; Vogt, Guillaume; Blanche, Stéphane; Benmustapha, Imen; Mansouri, Davood; Abel, Laurent; Boisson-Dupuis, Stéphanie; Mahlaoui, Nizar; Bousfiha, Ahmed Aziz; Picard, Capucine; Barbouche, Ridha; Al-Muhsen, Saleh; Espinosa-Rosales, Francisco J; Kütükçüler, Necil; Condino-Neto, Antonio; Casanova, Jean-Laurent; Bustamante, Jacinta

2016-07-01

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. Our objective was to assess the effect of mycobacterial disease in patients with CGD. We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Rapid and accurate identification of Mycobacterium tuberculosis complex and common non-tuberculous mycobacteria by multiplex real-time PCR targeting different housekeeping genes.

PubMed

Nasr Esfahani, Bahram; Rezaei Yazdi, Hadi; Moghim, Sharareh; Ghasemian Safaei, Hajieh; Zarkesh Esfahani, Hamid

2012-11-01

Rapid and accurate identification of mycobacteria isolates from primary culture is important due to timely and appropriate antibiotic therapy. Conventional methods for identification of Mycobacterium species based on biochemical tests needs several weeks and may remain inconclusive. In this study, a novel multiplex real-time PCR was developed for rapid identification of Mycobacterium genus, Mycobacterium tuberculosis complex (MTC) and the most common non-tuberculosis mycobacteria species including M. abscessus, M. fortuitum, M. avium complex, M. kansasii, and the M. gordonae in three reaction tubes but under same PCR condition. Genetic targets for primer designing included the 16S rDNA gene, the dnaJ gene, the gyrB gene and internal transcribed spacer (ITS). Multiplex real-time PCR was setup with reference Mycobacterium strains and was subsequently tested with 66 clinical isolates. Results of multiplex real-time PCR were analyzed with melting curves and melting temperature (T (m)) of Mycobacterium genus, MTC, and each of non-tuberculosis Mycobacterium species were determined. Multiplex real-time PCR results were compared with amplification and sequencing of 16S-23S rDNA ITS for identification of Mycobacterium species. Sensitivity and specificity of designed primers were each 100 % for MTC, M. abscessus, M. fortuitum, M. avium complex, M. kansasii, and M. gordonae. Sensitivity and specificity of designed primer for genus Mycobacterium was 96 and 100 %, respectively. According to the obtained results, we conclude that this multiplex real-time PCR with melting curve analysis and these novel primers can be used for rapid and accurate identification of genus Mycobacterium, MTC, and the most common non-tuberculosis Mycobacterium species.

Surgery as an Adjunctive Treatment for Multidrug-Resistant Tuberculosis: An Individual Patient Data Metaanalysis.

PubMed

Fox, Gregory J; Mitnick, Carole D; Benedetti, Andrea; Chan, Edward D; Becerra, Mercedes; Chiang, Chen-Yuan; Keshavjee, Salmaan; Koh, Won-Jung; Shiraishi, Yuji; Viiklepp, Piret; Yim, Jae-Joon; Pasvol, Geoffrey; Robert, Jerome; Shim, Tae Sun; Shin, Sonya S; Menzies, Dick; Ahuja, S; Ashkin, D; Avendaño, M; Banerjee, R; Bauer, M; Burgos, M; Centis, R; Cobelens, F; Cox, H; D'Ambrosio, L; de Lange, W C M; DeRiemer, K; Enarson, D; Falzon, D; Flanagan, K; Flood, J; Gandhi, N; Garcia-Garcia, L; Granich, R M; Hollm-Delgado, M G; Holtz, T H; Hopewell, P; Iseman, M; Jarlsberg, L G; Kim, H R; Lancaster, J; Lange, C; Leimane, V; Leung, C C; Li, J; Menzies, D; Migliori, G B; Narita, M; Nathanson, E; Odendaal, R; O'Riordan, P; Pai, M; Palmero, D; Park, S K; Pena, J; Pérez-Guzmán, C; Ponce-de-Leon, A; Quelapio, M I D; Quy, H T; Riekstina, V; Royce, S; Salim, M; Schaaf, H S; Seung, K J; Shah, L; Shean, K; Sifuentes-Osornio, J; Sotgiu, G; Strand, M J; Sung, S W; Tabarsi, P; Tupasi, T E; Vargas, M H; van Altena, R; van der Walt, M; van der Werf, T S; Westenhouse, J; Yew, W W

2016-04-01

Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy. © 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.

Structural Basis for Catalysis of a Tetrameric Class IIa Fructose 1,6-Bisphosphate Aldolase from Mycobacterium tuberculosis

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

Pegan, Scott D.; Ruskseree, Kamolchanok; Franzblau, Scott G.

2009-03-04

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), currently infects one-third of the world's population in its latent form. The emergence of multidrug-resistant and extensive drug-resistant strains has highlighted the need for new pharmacological targets within M. tuberculosis. The class IIa fructose 1,6-bisphosphate aldolase (FBA) enzyme from M. tuberculosis (MtFBA) has been proposed as one such target since it is upregulated in latent TB. Since the structure of MtFBA has not been determined and there is little information available on its reaction mechanism, we sought to determine the X-ray structure of MtFBA in complex with its substrates. By lowering themore » pH of the enzyme in the crystalline state, we were able to determine a series of high-resolution X-ray structures of MtFBA bound to dihydroxyacetone phosphate, glyceraldehyde 3-phosphate, and fructose 1,6-bisphosphate at 1.5, 2.1, and 1.3 {angstrom}, respectively. Through these structures, it was discovered that MtFBA belongs to a novel tetrameric class of type IIa FBAs. The molecular details at the interface of the tetramer revealed important information for better predictability of the quaternary structures among the FBAs based on their primary sequences. These X-ray structures also provide interesting and new details on the reaction mechanism of class II FBAs. Substrates and products were observed in geometries poised for catalysis; in addition, unexpectedly, the hydroxyl-enolate intermediate of dihydroxyacetone phosphate was also captured and resolved structurally. These concise new details offer a better understanding of the reaction mechanisms for FBAs in general and provide a structural basis for inhibitor design efforts aimed at this class of enzymes.« less

Structural basis for catalysis of a tetrameric, class IIa fructose 1,6-bisphosphate aldolase from M. tuberculosis

PubMed Central

Pegan, Scott D.; Rukseree, Kamolchanok; Franzblau, Scott G.; Mesecar, Andrew D.

2009-01-01

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), currently infects one third of the world’s population in its latent form. The emergence of multidrug resistant strains, MDR-TB and XDR-TB has highlighted the need for new pharmacological targets within M. tuberculosis. The Class IIa fructose 1,6-bisphosphate aldolase (FBA) enzyme from M. tuberculosis (MtFBA) has been proposed as one such target since its upregulated in latent TB. Since the structure of MtFBA had not been determined and since there was little information available on its reaction mechanism, we sought to determine the X-ray structure of MtFBA in complex with its substrates. By lowering the pH of the enzyme in the crystalline state, we were able to determine a series of high-resolution X-ray structures of MtFBA bound to dihydroxyacetonephosphate (DHAP), glyceraldehyde-3-phosphate (G3P), and fructose 1,6-bisphosphate (FBP) at 1.5 Å, 2.1 Å, and 1.3 Å respectively. Through these structures it was discovered that MtFBA belongs to a novel tetrameric class of the type IIa FBAs. The molecular details at the interface of the tetramer revealed important information for being able to better predict the quaternary structures among the FBAs based on their primary sequences. These X-ray structures also provide interesting and new details on the reaction mechanism of class II FBAs. Not only were the substrates and products observed in geometries poised for catalysis, but unexpectedly the hydroxyl enolate intermediate of DHAP was also captured and resolved structurally. These concise new details provide a better understanding of the reaction mechanisms for FBAs in general and provide a structural basis for inhibitor design efforts aimed at this class of enzymes. PMID:19167403

The effect of vitamin A and zinc supplementation on treatment outcomes in pulmonary tuberculosis: a randomized controlled trial.

PubMed

Visser, Marianne E; Grewal, Harleen Ms; Swart, Elizabeth C; Dhansay, Muhammad A; Walzl, Gerhard; Swanevelder, Sonja; Lombard, Carl; Maartens, Gary

2011-01-01

Low serum concentrations of vitamin A and zinc are common in tuberculosis and may have an adverse effect on host cell-mediated responses. The role of adjunctive micronutrient supplementation on treatment outcomes is uncertain. The objective was to assess the efficacy of vitamin A and zinc supplementation on sputum smear and culture conversion and time to culture detection in adults with sputum smear-positive pulmonary tuberculosis. Participants attending a primary care tuberculosis clinic in Cape Town, South Africa, were randomly assigned to receive micronutrients (single dose of 200,000 IU retinyl palmitate plus 15 mg Zn/d for 8 wk) or matching placebo. Sputum was collected weekly for 8 wk for auramine staining and culture on liquid media (BACTEC MGIT 960; Becton Dickinson, Sparks, MD). Performance status, chest radiographs, and anthropometric measures were assessed at baseline and again at 8 wk. The participants (n = 154) were randomly assigned to the micronutrient (n = 77) or placebo (n = 77) group. Twenty participants were HIV infected (13%), and 12 participants had an unknown HIV status (8%). No differences in time to smear or culture conversion were observed between the treatment groups by Kaplan-Meier analysis (P = 0.15 and P = 0.38, respectively; log-rank test). Log-logistic regression analysis found no significant group interaction effect in time to culture detection over the 8-wk period (P = 0.32). No significant differences in weight gain (2.3 ± 3.5 compared with 2.2 ± 2.4 kg, P = 0.68) or radiologic resolution were observed between the treatment groups. Supplementation with vitamin A and zinc did not affect treatment outcomes in participants with pulmonary tuberculosis at 8 wk. This trial was registered at controlled-trials.com as ISRCTN80852505.

Efficient activation of human T cells of both CD4 and CD8 subsets by urease-deficient recombinant Mycobacterium bovis BCG that produced a heat shock protein 70-M. tuberculosis-derived major membrane protein II fusion protein.

PubMed

Mukai, Tetsu; Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Makino, Masahiko

2014-01-01

For the purpose of obtaining Mycobacterium bovis bacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed of Mycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8(+) T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8(+) T cells and perforin-producing effector CD8(+) T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive to in vitro secondary stimulation with HSP70, MMP-II, and M. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challenged M. tuberculosis more efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.

Pre- and post-diagnosis costs of tuberculosis to patients on Directly Observed Treatment Short course in districts of southwestern Ethiopia: a longitudinal study.

PubMed

Asres, Abyot; Jerene, Degu; Deressa, Wakgari

2018-05-21

Financial burden on tuberculosis (TB) patients results in delayed treatment and poor compliance. We assessed pre- and post-diagnosis costs to TB patients. A longitudinal study among 735 new TB cases was conducted from January 2015 through June 2016 in 10 woredas (districts) of southwestern Ethiopia. Direct out-of-pocket, payments, and lost income (indirect cost) were solicited from patients during the first 2 months and at the end of treatment. Thus, we ascertained direct medical, nonmedical, and indirect costs incurred by patients during pre- and post-diagnosis periods. We categorized costs incurred from onset of illness until TB diagnosis as pre-diagnosis and that incurred after diagnosis through treatment completion as post-diagnosis. Pre- and post-diagnosis costs constitute total cost incurred by the patients. We fitted linear regression model to identify predictors of cost. Between onset of illness and anti-TB treatment course, patients incurred a median (inter-quartile range (IQR)) of US$201.48 (136.7-318.94). Of the total cost, the indirect and direct costs respectively constituted 70.6 and 29.4%. TB patients incurred a median (IQR) of US$97.62 (6.43-184.22) and US$93.75 (56.91-141.54) during the pre- and post-diagnosis periods, respectively. Thus, patients incurred 53.6% of the total cost during the pre-diagnosis period. Direct out-of-pocket expenses during the pre- and post-diagnosis periods respectively amount to median (IQR) of US$21.64 (10.23-48.31) and US$35.02 (0-70.04). Patient delay days (p < 0.001), provider delay days (p < 0.001), number of healthcare facilities visited until TB diagnosis (p < 0.001), and TB diagnosis at private facilities (p = 0.02) independently predicted increased pre-diagnosis cost. Similarly, rural residence (p < 0.001), hospitalization during anti-TB treatment (p < 0.001), patient delay days (p < 0.001), and provider delay days (p < 0.001) predicted increased post-diagnosis costs. TB patients incur substantial cost for care seeking and treatment despite "free service" for TB. Therefore, promoting early care seeking, decentralizing efficient diagnosis, and treatment services within reach of peoples, and introducing reimbursement system for direct costs can help minimize financial burden to the patient.

Tackling both the player and the ball: lessons from crystallographic studies on the N-utilization substance B (NusB) from Mycobacterium tuberculosis

NASA Astrophysics Data System (ADS)

Haire, L. F.; Gopal, B.

2001-11-01

The N-utilization substance B (NusB) from Mycobacterium tuberculosis is an important element in a complex assembly of other proteins and ribonucleic acid effecting transcription antitermination in this organism. The cloning and overexpression of the protein in E. coli, followed by the purification, crystallization, and use of selenomethionine samples to obtain phase information by anomalous dispersion techniques, allows us to investigate the fine interplay of sample engineering and modification of crystallization parameters leading to successful structure determination. Knowledge of the crystal structure and the surface properties of the protein allows an analysis of the packing of the NusB dimers in the crystal lattice. This exercise, albeit post facto, helps to demonstrate how biophysical and functional information could help 'rationalize' the course of obtaining protein crystals suitable for structural studies.

Long-Term Assessment of Wild Boar Harvesting and Cattle Removal for Bovine Tuberculosis Control in Free Ranging Populations

PubMed Central

Mentaberre, Gregorio; Romero, Beatriz; de Juan, Lucía; Navarro-González, Nora; Velarde, Roser; Mateos, Ana; Marco, Ignasi; Olivé-Boix, Xavier; Domínguez, Lucas; Lavín, Santiago; Serrano, Emmanuel

2014-01-01

Wild boar is a recognized reservoir of bovine tuberculosis (TB) in the Mediterranean ecosystems, but information is scarce outside of hotspots in southern Spain. We describe the first high-prevalence focus of TB in a non-managed wild boar population in northern Spain and the result of eight years of TB management. Measures implemented for disease control included the control of the local wild boar population through culling and stamping out of a sympatric infected cattle herd. Post-mortem inspection for detection of tuberculosis-like lesions as well as cultures from selected head and cervical lymph nodes was done in 745 wild boar, 355 Iberian ibexes and five cattle between 2004 and 2012. The seasonal prevalence of TB reached 70% amongst adult wild boar and ten different spoligotypes and 13 MIRU-VNTR profiles were detected, although more than half of the isolates were included in the same clonal complex. Only 11% of infected boars had generalized lesions. None of the ibexes were affected, supporting their irrelevance in the epidemiology of TB. An infected cattle herd grazed the zone where 168 of the 197 infected boars were harvested. Cattle removal and wild boar culling together contributed to a decrease in TB prevalence. The need for holistic, sustained over time, intensive and adapted TB control strategies taking into account the multi-host nature of the disease is highlighted. The potential risk for tuberculosis emergence in wildlife scenarios where the risk is assumed to be low should be addressed. PMID:24558435

The impact of migration on tuberculosis epidemiology and control in high-income countries: a review.

PubMed

Pareek, Manish; Greenaway, Christina; Noori, Teymur; Munoz, Jose; Zenner, Dominik

2016-03-23

Tuberculosis (TB) causes significant morbidity and mortality in high-income countries with foreign-born individuals bearing a disproportionate burden of the overall TB case burden in these countries. In this review of tuberculosis and migration we discuss the impact of migration on the epidemiology of TB in low burden countries, describe the various screening strategies to address this issue, review the yield and cost-effectiveness of these programs and describe the gaps in knowledge as well as possible future solutions.The reasons for the TB burden in the migrant population are likely to be the reactivation of remotely-acquired latent tuberculosis infection (LTBI) following migration from low/intermediate-income high TB burden settings to high-income, low TB burden countries.TB control in high-income countries has historically focused on the early identification and treatment of active TB with accompanying contact-tracing. In the face of the TB case-load in migrant populations, however, there is ongoing discussion about how best to identify TB in migrant populations. In general, countries have generally focused on two methods: identification of active TB (either at/post-arrival or increasingly pre-arrival in countries of origin) and secondly, conditionally supported by WHO guidance, through identifying LTBI in migrants from high TB burden countries. Although health-economic analyses have shown that TB control in high income settings would benefit from providing targeted LTBI screening and treatment to certain migrants from high TB burden countries, implementation issues and barriers such as sub-optimal treatment completion will need to be addressed to ensure program efficacy.

Lipidated promiscuous peptide augments the expression of MHC-II molecules on dendritic cells and activates T cells

PubMed Central

Gowthaman, Uthaman; Rai, Pradeep K.; Zeng, Weiguang; Jackson, David C.; Agrewala, Javed N.

2013-01-01

Background & objectives: In spite of the fact that BCG is the most widely used vaccine, tuberculosis (TB) continues to be a major killer disease in TB-endemic regions. Recently, many emerging evidences from the published literature indicate the role of environmental mycobacteria in blocking the processing and presentation of BCG antigens and thereby impairing with suboptimal generation of protective T cells. To surmount this problem associated with BCG, we constructed a novel lipopeptide (L91) by conjugating a promiscuous peptide consisting of CD4+ T-helper epitope of sequence of 91-110 of 16 kDa antigen of Mycobacterium tuberculosis to Pam2Cys, an agonist of Toll-like receptor-2. Methods: Mice were immunized subcutaneously with 20 nmol of L91, followed by a booster with 10 nmol, after an interval of 21 days of primary immunization. Animals were sacrificed after seven days of post-booster immunization. L91 induced immune response was characterized by the expression of MHC-II and CD74 on the surface of dendritic cells (DCs) by flowcytometry. Cytokines (IL-4, IL-10, IFN-γ) secretion and anti-peptide antibodies were measured by ELISA. Results: Self-adjuvanting lipopeptide vaccine (L91) was directly bound to MHC-II molecules and without requiring extensive processing for its presentation to T cells. It stimulated and activated dendritic cells and augmented the expression of MHC-II molecules. Further, it activated effector CD4 T cells to mainly secrete interferon (IFN)-γ but not interleukin (IL)-4 and IL-10. L91 did not elicit anti-peptide antibodies. Interpretation & conclusions: The findings suggest that L91 evokes maturation and upregulation of MHC class II molecules and promotes better antigen presentation and, therefore, optimum activation of T cells. L91 mainly induces effector Th1 cells, as evidenced by predominant release of IFN-γ, consequently can mount favourable immune response against M. tuberculosis. As L91 does not provoke the generation of anti-peptide antibodies, there is no fear of the efficacy of the vaccine being neutralized by pre-existing anti-mycobacterial antibodies in TB-endemic population. In conclusion, L91 may be considered as a future potential candidate vaccine against TB. PMID:24434326

Mycobacterium tuberculosis strains induce strain-specific cytokine and chemokine response in pulmonary epithelial cells.

PubMed

Mvubu, Nontobeko E; Pillay, Balakrishna; McKinnon, Lyle R; Pillay, Manormoney

2018-04-01

M. tuberculosis F15/LAM4/KZN has been associated with high transmission rates of drug resistant tuberculosis in the KwaZulu-Natal province of South Africa. The current study elucidated the cytokine/chemokine responses induced by representatives of the F15/LAM4/KZN and other dominant strain families in pulmonary epithelial cells. Multiplex cytokine analyses were performed at 24, 48 and 72h post infection of the A549 pulmonary epithelial cell line with the F15/LAM4/KZN, F28, F11, Beijing, Unique and H37Rv strains at an MOI of ∼10:1. Twenty-three anti- and pro-inflammatory cytokines/chemokines were detected at all-time intervals. Significantly high concentrations of IL-6, IFN-γ, TNF-α and G-CSF at 48h, and IL-8, IFN-γ, TNF-α, G-CSF and GM-CSF at 72h, were induced by the F28 and F15/LAM4/KZN strains, respectively. Lower levels of cytokines/chemokines were induced by either the Beijing or Unique strains at all three time intervals. All strains induced up-regulation of pathogen recognition receptors (PRRs) (TLR3 and TLR5) while only the F15/LAM4/KZN, F11 and F28 strains induced significant differential expression of TLR2 compared to the Beijing, Unique and H37Rv strains. The low induction of cytokines in epithelial cells by the Beijing strain correlates with its previously reported hypervirulent properties. High concentrations of cytokines and chemokines required for early protection against M. tuberculosis infections induced by the F15/LAM4/KZN and F28 strains suggests a lower virulence of these genotypes compared to the Beijing strain. These findings demonstrate the high diversity in host cytokine/chemokine response to early infection of pulmonary epithelial cells by different strains of M. tuberculosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Secondary lymphangiectasia of the small bowel: utility of double balloon enteroscopy for diagnosis and management.

PubMed

Safatle-Ribeiro, Adriana Vaz; Iriya, Kiyoshi; Couto, Décio Sampaio; Kawaguti, Fábio Shiguehiss; Retes, Felipe; Ribeiro, Ulysses; Sakai, Paulo

2008-01-01

Sporadic lymphangiectasias are commonly found throughout the small bowel and are considered to be normal. Not uncommonly, lymphangiectasias are pathologic and can lead to mid-gastrointestinal bleeding, abdominal pain and protein-losing enteropathy. Pathologic lymphangiectasias of the small bowel include primary lymphangiectasia, secondary lymphangiectasia and lymphaticovenous malformations. In this report we present three different cases of small bowel lymphangiectasia detected by double balloon enteroscopy. The patients were diagnosed with South American blastomycosis, tuberculosis and primary small bowel lymphangioma. 2009 S. Karger AG, Basel

[Reccurent mycobacterial diseases in patients with impaired axis IL-12/INF-gamma].

PubMed

Strach, Magdalena; Nalepa, Piotr; Sulicka-Grodzicka, Joanna; Kierzkowska, Izabella; Siedlar, Maciej; Grodzicki, Tomasz

2013-01-01

Mycobacteria is a large group of pathogens that are common in environment, in soil and tap water. Although mycobacteria [non tuberculosis mycobacteria] can inhabit body surface without causing any disease in the circumstances of primary or secondary immunodeficiency can cause clinically significant organ or systemic damage. Defect of IL-12/INFgamma axis is an example of primary immunodeficiency that predispose to mycobacterial infections while protection against other microorganisms is not damaged. We present review of known defects of IL-12/IFNgamma axis and brief presentation of our own experience.

Feasibility of tuberculosis treatment monitoring by video directly observed therapy: a binational pilot study.

PubMed

Garfein, R S; Collins, K; Muñoz, F; Moser, K; Cerecer-Callu, P; Raab, F; Rios, P; Flick, A; Zúñiga, M L; Cuevas-Mota, J; Liang, K; Rangel, G; Burgos, J L; Rodwell, T C; Patrick, K

2015-09-01

Although directly observed therapy (DOT) is recommended worldwide for monitoring anti-tuberculosis treatment, transportation and personnel requirements limit its use. To evaluate the feasibility and acceptability of 'video DOT' (VDOT), which allows patients to record and transmit medication ingestion via videos watched remotely by health care providers to document adherence. We conducted a single-arm trial among tuberculosis (TB) patients in San Diego, California, USA, (n = 43) and Tijuana, Mexico (n = 9) to represent high- and low-resource settings. Pre-/post-treatment interviews assessed participant characteristics and experiences. Adherence was defined as the proportion of observed doses to expected doses. The mean age was 37 years (range 18-86), 50% were male, and 88% were non-Caucasian. The mean duration of VDOT use was 5.5 months (range 1-11). Adherence was similar in San Diego (93%) and Tijuana (96%). Compared to time on in-person DOT, 92% preferred VDOT, 81% thought VDOT was more confidential, 89% never/rarely had problems recording videos, and 100% would recommend VDOT to others. Seven (13%) participants were returned to in-person DOT and six (12%) additional participants had their phones lost, broken or stolen. VDOT was feasible and acceptable, with high adherence in both high- and low-resource settings. Efficacy and cost-effectiveness studies are needed.

Reactivation of Latent Tuberculosis in Cynomolgus Macaques Infected with SIV Is Associated with Early Peripheral T Cell Depletion and Not Virus Load

PubMed Central

Klein, Edwin; Janssen, Chris; Phuah, Jiayao; Sturgeon, Timothy J.; Montelaro, Ronald C.; Lin, Philana Ling; Flynn, JoAnne L.

2010-01-01

HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb) infection are at significantly greater risk of reactivation tuberculosis (TB) than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV). Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks) had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection. PMID:20224771

Epidemiological situation of tuberculosis in Poland: part II. What are the causes of the different epidemiological situation in various regions of Poland?

PubMed

Rowińska-Zakrzewska, Ewa; Korzeniewska-Koseła, Maria; Roszkowski-Śliż, Kazimierz

2014-01-01

The different epidemiological situation of tuberculosis in various regions of Poland (higher and lower notification rates) was described previously by our group. The patients diagnosed with tuberculosis in the higher notification rate areas were younger and there were more cases of primary tuberculosis (tuberculous pleurisy and tuberculosis of chest lymph nodes) than in the patients diagnosed in the lower notification areas. The aim of the present study was to assess the possible causes of the different epidemiological situation of tuberculosis in various regions of Poland. Analysis was done at the same regions as in the previous paper. A comparison was made between two groups: Group I, which included three voivodeships with higher rates of notification, from 23.7 to 32.3/100,000 (mean rates in the analysed period of time); and Group II, which included five voivodeships with lower notification rates (mean rates from 12.2 to 18.6/100,000). The wealth of the regions (GDP, gross domestic product per capita), the level of unemployment, and social status of the patients were analysed. We compared the population density in both regions. The results of treatment in both regions were also analysed. We did not find any differences in GDP and unemployment rates between the compared regions. The results of treatment were different in particular regions, but there was no clear tendency for worse results in voivodeships in Group I compared to voivodeships in Group II. However, the number of patients lost from observation was significantly higher in the regions from Group I than in those from Group II. There was also a significantly higher death rate from tuberculosis in younger patients (£ 59 years) from Group I than from Group II. This is additional proof that the epidemiological situation in the two regions was different. Finally, we found that the mean density of population in the regions from Group I was higher than that from Group II. The density of population may influence transmission of tuberculosis. There is also the possibility that the differences in the epidemiological situation in various regions of Poland are caused by historical events. In the past the epidemiological situation of tuberculosis was much worse in the east of Europe than in the west. Just after the Second World War, according to the changes of the Polish territory, many Polish citizens (mainly ancestors of those from Group I) were displaced from the east to the west. In conclusion, the greater number of patients lost from observation, together with the higher density of population in the regions from Group I in comparison with those from Group II, seems to be partly responsible for the difference in the epidemiological situation in the two regions. It is also possible that some patients from Group I are more susceptible to infection and disease caused by Mycobacterium tuberculosis due to their ancestors, who lived in the east of Europe.

A systematic assessment of the concept and practice of public-private mix for tuberculosis care and control

PubMed Central

2011-01-01

Introduction The STOP TB Partnership aims to improve global tuberculosis (TB) control through expanding access to the directly observed treatment short course (DOTS) strategy. One approach to this is 'Engaging all Care Providers', which evolved from 'Public-Private Mix (PPM) DOTS'. The overall aim of this study was to systematically assess whether and to what degree the STOP TB Partnership's four global objectives of engaging all care providers are met through existing PPM interventions. These four objectives are; 1) Increase TB case detection; 2) Improve TB treatment outcomes; 3) Enhance access and equity; 4) Reduce financial burden on patients. The specific objectives of this assessment were to 1) Understand what PPM means to the STOP TB Partnership's PPM Subgroup and to National Tuberculosis Programme managers; 2) Scope the nature of existing country-level PPM interventions and 3) Review PPM practice against the global PPM objectives. Methods We undertook a systematic, multi-facetted assessment. The methods included interviews with National Tuberculosis Programme managers from high burden countries, clarification of key issues with the STOP TB Partnership PPM secretariat and a review of publicly accessible reports and published articles on PPM projects. Both the literature review and interviews with the National Tuberculosis Programme managers yielded data on project characteristics; PPM models at country level; National Tuberculosis Programme partners; and mechanisms for engagement. Matrices were developed from the literature review and the interviews to show the relationship between services and service providers for different PPM projects. Data from the literature were assessed against each of the four global PPM objectives. Results Twelve National Tuberculosis Programme managers from high burden countries were interviewed about the scope of PPM partnerships. Understanding of PPM and types of engaged providers varied considerably; 'private-for-profit qualified clinical providers' were the dominant category. The literature review yielded information on 22 projects in which 'private-for-profit qualified clinical providers' were again the dominant category. The contributions made by 'private-for-profit qualified clinical providers' and 'Non Governmental Organisation qualified clinical providers', were assessed against the four global PPM objectives. Reporting on tuberculosis case detection and treatment outcomes was generally good and demonstrated important PPM contributions in these areas. Reporting on equity, access and reduced patient costs was often lacking or inconclusive. Conclusions PPM has improved case detection and treatment outcomes among patients seeking care with private providers. Evidence on reducing patient costs is inconclusive, and there is scope for increasing equity in access to care by systematically engaging those providers who are the primary agents for poor people seeking health care. Guidelines outlining which types of providers best contribute to achieving the four global objectives, along with the resources required by National Tuberculosis Programs for such engagement is needed. PMID:22074377

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

PubMed Central

2011-01-01

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

Multidrug-resistant tuberculosis of the spine--is it the beginning of the end? A study of twenty-five culture proven multidrug-resistant tuberculosis spine patients.

PubMed

Pawar, Uday M; Kundnani, Vishal; Agashe, Vikas; Nene, Amita; Nene, Abhay

2009-10-15

Prospective cohort study. We report the first study of multidrug-resistant tuberculosis (MDR-TB) in the spine. The aim was to determine the clinical, radiologic, and drug resistance profile as well as the factors associated with treatment outcome of MDR-TB in the spine. Tuberculosis of the spine is the most common extrapulmonary form of tuberculosis in the Asian subcontinent. The disease in few cases is resistant to the primary anti-Koch's medications and the number of cases detected is on the rise. Multidrug resistant form of tuberculosis of the spine is ill reported in the literature. The diagnosis, management thus remains a challenge to the treating surgeon. This study tries to assess these critical issues of this "new" disease. Described here are the clinical characteristics of 25 MDR-TB spine patients identified in the study and their drug susceptibility patterns. They were followed up clinically, radiologically after a biopsy, culture, and Drug Susceptibility Testing. According to their Drug Susceptibility Testing pattern and previous history of Anti-Tubercular Treatment (ATT), individualized treatment regimens were tailored for each patient by an expert physician. Majority of the patients seen in the present study were in the productive years of their life. (Males (9) mean age: 38.5 years and females (16) mean age: 34.3 years. Four patients were defaulters of the ATT. The average number of drugs used was 6, including 4 second line drugs. Average treatment duration was 24 months. Almost 50% of the patients had adverse drug effects. Of the 25 patients, 19 achieved healed status and 6 are still on treatment. Four patients required surgery for mechanical instability of the spine. Radiologic improvement was observed in all the cases after a mean treatment of 6 months. Five predictors were identified for successful outcome of MDR-TB. They include progressive clinical improvement at 6 months, radiologic improvement during treatment and disease with Mycobacterium tuberculosis strains exhibiting resistance to less than or up to 3 antitubercular drugs, use of less than or up to 4 second-line drugs in treatment, and no change of regimen during treatment. MDR-TB of the spine is a different disease and is here to stay. There is an urgent need to include culture and drug susceptibility testing in the protocol for the treatment of tuberculosis of the spine.

Stringent homology-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions

PubMed Central

2014-01-01

Background H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are essential for understanding the infection mechanism of the formidable pathogen M. tuberculosis H37Rv. Computational prediction is an important strategy to fill the gap in experimental H. sapiens-M. tuberculosis H37Rv PPI data. Homology-based prediction is frequently used in predicting both intra-species and inter-species PPIs. However, some limitations are not properly resolved in several published works that predict eukaryote-prokaryote inter-species PPIs using intra-species template PPIs. Results We develop a stringent homology-based prediction approach by taking into account (i) differences between eukaryotic and prokaryotic proteins and (ii) differences between inter-species and intra-species PPI interfaces. We compare our stringent homology-based approach to a conventional homology-based approach for predicting host-pathogen PPIs, based on cellular compartment distribution analysis, disease gene list enrichment analysis, pathway enrichment analysis and functional category enrichment analysis. These analyses support the validity of our prediction result, and clearly show that our approach has better performance in predicting H. sapiens-M. tuberculosis H37Rv PPIs. Using our stringent homology-based approach, we have predicted a set of highly plausible H. sapiens-M. tuberculosis H37Rv PPIs which might be useful for many of related studies. Based on our analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent homology-based approach, we have discovered several interesting properties which are reported here for the first time. We find that both host proteins and pathogen proteins involved in the host-pathogen PPIs tend to be hubs in their own intra-species PPI network. Also, both host and pathogen proteins involved in host-pathogen PPIs tend to have longer primary sequence, tend to have more domains, tend to be more hydrophilic, etc. And the protein domains from both host and pathogen proteins involved in host-pathogen PPIs tend to have lower charge, and tend to be more hydrophilic. Conclusions Our stringent homology-based prediction approach provides a better strategy in predicting PPIs between eukaryotic hosts and prokaryotic pathogens than a conventional homology-based approach. The properties we have observed from the predicted H. sapiens-M. tuberculosis H37Rv PPI network are useful for understanding inter-species host-pathogen PPI networks and provide novel insights for host-pathogen interaction studies. Reviewers This article was reviewed by Michael Gromiha, Narayanaswamy Srinivasan and Thomas Dandekar. PMID:24708540

[Life-threatening hypophosphatemia in 74-year-old woman with recurrent pneumonia and progressive muscular atrophy].

PubMed

Shahnazaryan, Urszula; Popow, Michał; Rosłon, Marek

2016-02-01

Although hypophosphatemia can be a serious threat to health and life, it is a problem rarely taken into consideration in the differential diagnosis in the current clinical practice. The aim of the study was to present the description of hypophosphatemia issues in the context of the threat they may pose to the health and life when undiagnosed. 74-year-old internal charged woman , with progressive destruction for a few years, recurrent pneumonia, and a compression fracture of the spine, was admitted to hospital because of fainting and general deterioration. In the course of the performed diagnostics primary hyperparathyroidism was diagnosed with pre-existing inadequate severe hypophosphatemia. Because the presented clinical picture, only partially tie in symptomatology of primary hiperparathyroidism, the diagnostic process was targeted to search for other causes of both hypophosphatemia and symptoms reported by the patient. Finally, in addition to PHPT ( primary hyperparathyroidism) also vitamin D deficiency and tuberculosis was found. The fact that the treatment of infectious disease led to the phosphatemia standardization , and thus to significant improvement of the overall demonstrates, shows the significant contribution of tuberculosis in the pathogenesis of phosphate deficiency in this case. Our case is an example of confirming the need for a thorough and multidirectional analysis of the clinical picture, which is a prerequisite for a correct diagnosis. © 2016 MEDPRESS.

Management of children exposed to Mycobacterium tuberculosis: a public health evaluation in West Java, Indonesia.

PubMed

Rutherford, Merrin E; Ruslami, Rovina; Anselmo, Melissa; Alisjahbana, Bachti; Yulianti, Neti; Sampurno, Hedy; van Crevel, Reinout; Hill, Philip C

2013-12-01

To investigate qualitatively and quantitatively the performance of a programme for managing the child contacts of adult tuberculosis patients in Indonesia. A public health evaluation framework was used to assess gaps in a child contact management programme at a lung clinic. Targets for programme performance indicators were derived from established programme indicator targets, the scientific literature and expert opinion. Compliance with tuberculosis screening, the initiation of isoniazid preventive therapy in children younger than 5 years, the accuracy of tuberculosis diagnosis and adherence to preventive therapy were assessed in 755 child contacts in two cohorts. In addition, 22 primary caregivers and 34 clinic staff were interviewed to evaluate knowledge and acceptance of child contact management. The cost to caregivers was recorded. Gaps between observed and target indicator values were quantified. THE GAPS BETWEEN OBSERVED AND TARGET PERFORMANCE INDICATORS WERE: 82% for screening compliance; 64 to 100% for diagnostic accuracy, 50% for the initiation of preventive therapy, 54% for adherence to therapy and 50% for costs. Many staff did not have adequate knowledge of, or an appropriate attitude towards, child contact management, especially regarding isoniazid preventive therapy. Caregivers had good knowledge of screening but not of preventive therapy and had difficulty travelling to the clinic and paying costs. The study identified widespread gaps in the performance of a child contact management system in Indonesia, all of which appear amenable to intervention. The public health evaluation framework used could be applied in other settings where child contact management is failing.

Tuberculosis caseload in children with severe acute malnutrition related with high hospital based mortality in Lusaka, Zambia.

PubMed

Munthali, Tendai; Chabala, Chishala; Chama, Elson; Mugode, Raider; Kapata, Nathan; Musonda, Patrick; Michelo, Charles

2017-06-12

Tuberculosis and severe acute malnutrition (SAM) in children pose a major treatment and care challenge in high HIV burden countries in Africa. We investigated the prevalence of Tuberculosis notifications among hospitalised under-five children with severe acute malnutrition. A retrospective review of medical records for all children aged 0-59 months admitted to the University Teaching Hospital from 2009 to 2013 was performed. Descriptive statistics were employed to estimate TB caseload. Logistic regression was used to identify predictors of the TB caseload. A total of (n = 9540) under-five children with SAM were admitted over the period reviewed. The median age was 16 months (IQR 11-24) and the proportion diagnosed with TB was 1.58% (95% CI 1.3, 1.8) representing 151 cases. Of these, only 37 (25%) were bacteriologically confirmed cases. The HIV seroprevalence of children with SAM and TB was 46.5%. Children with SAM and TB were 40% more likely to die than children with SAM and without TB. Tuberculosis contributes to mortality among children with SAM in high TB and HIV prevalence settings. The under detection of cases and association of TB with HIV infection in malnutrition opens up opportunities to innovate integrative case finding approaches beyond just HIV counselling and testing within existing mother and child health service areas to include TB screening and prevention interventions, as these are critical primary care elements.

Urgent Implementation in a Hospital Setting of a Strategy To Rule Out Secondary Cases Caused by Imported Extensively Drug-Resistant Mycobacterium tuberculosis Strains at Diagnosis

PubMed Central

Pérez-Lago, Laura; Martínez-Lirola, Miguel; García, Sergio; Herranz, Marta; Mokrousov, Igor; Comas, Iñaki; Martínez-Priego, Llúcia; Bouza, Emilio

2016-01-01

Current migratory movements require new strategies for rapidly tracking the transmission of high-risk imported Mycobacterium tuberculosis strains. Whole-genome sequencing (WGS) enables us to identify single-nucleotide polymorphisms (SNPs) and therefore design PCRs to track specific relevant strains. However, fast implementation of these strategies in the hospital setting is difficult because professionals working in diagnostics, molecular epidemiology, and genomics are generally at separate institutions. In this study, we describe the urgent implementation of a system that integrates genomics and molecular tools in a genuine high-risk epidemiological alert involving 2 independent importations of extensively drug resistant (XDR) and pre-XDR Beijing M. tuberculosis strains from Russia into Spain. Both cases involved commercial sex workers with long-standing tuberculosis (TB). The system was based on strain-specific PCRs tailored from WGS data that were transferred to the local node that was managing the epidemiological alert. The optimized tests were available for prospective implementation in the local node 33 working days after receiving the primary cultures of the XDR strains and were applied to all 42 new incident cases. An interpretable result was obtained in each case (directly from sputum for 27 stain-positive cases) and corresponded to the amplification profiles for strains other than the targeted pre-XDR and XDR strains, which made it possible to prospectively rule out transmission of these high-risk strains at diagnosis. PMID:27682128

Urgent Implementation in a Hospital Setting of a Strategy To Rule Out Secondary Cases Caused by Imported Extensively Drug-Resistant Mycobacterium tuberculosis Strains at Diagnosis.

PubMed

Pérez-Lago, Laura; Martínez-Lirola, Miguel; García, Sergio; Herranz, Marta; Mokrousov, Igor; Comas, Iñaki; Martínez-Priego, Llúcia; Bouza, Emilio; García-de-Viedma, Darío

2016-12-01

Current migratory movements require new strategies for rapidly tracking the transmission of high-risk imported Mycobacterium tuberculosis strains. Whole-genome sequencing (WGS) enables us to identify single-nucleotide polymorphisms (SNPs) and therefore design PCRs to track specific relevant strains. However, fast implementation of these strategies in the hospital setting is difficult because professionals working in diagnostics, molecular epidemiology, and genomics are generally at separate institutions. In this study, we describe the urgent implementation of a system that integrates genomics and molecular tools in a genuine high-risk epidemiological alert involving 2 independent importations of extensively drug resistant (XDR) and pre-XDR Beijing M. tuberculosis strains from Russia into Spain. Both cases involved commercial sex workers with long-standing tuberculosis (TB). The system was based on strain-specific PCRs tailored from WGS data that were transferred to the local node that was managing the epidemiological alert. The optimized tests were available for prospective implementation in the local node 33 working days after receiving the primary cultures of the XDR strains and were applied to all 42 new incident cases. An interpretable result was obtained in each case (directly from sputum for 27 stain-positive cases) and corresponded to the amplification profiles for strains other than the targeted pre-XDR and XDR strains, which made it possible to prospectively rule out transmission of these high-risk strains at diagnosis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Efficacy of isoniazid prophylactic therapy in prevention of tuberculosis in children: a meta–analysis

PubMed Central

2014-01-01

Background Children are highly susceptible to tuberculosis; thus, there is need for safe and effective preventive interventions. Our objective was to evaluate the efficacy of isoniazid in prevention of tuberculosis morbidity and mortality in children aged 15 years or younger by performing a meta-analysis of randomized controlled trials. To our knowledge, this is the first meta-analysis evaluating efficacy of isoniazid prophylaxis in prevention of tuberculosis in children. Methods A systematic search of the literature was done to identify randomized controlled trials evaluating isoniazid prophylaxis efficacy among children. Each study was evaluated for relevance and validity for inclusion in the analysis. Subgroup analyses were conducted based on study quality, HIV status, tuberculosis endemicity, type of prophylaxis and age of participants. Results Eight studies comprising 10,320 participants were included in this analysis. Upon combining data from all eight studies, isoniazid prophylaxis was found to be efficacious in preventing development of tuberculosis, with a pooled RR of 0.65 (95% CI 0.47, 0.89) p = 0.004 , with confidence intervals adjusted for heterogeneity. Among the sub-group analyses conducted, only age of the participants yielded dramatic differences in the summary estimate of efficacy, suggesting that age might be an effect modifier of the efficacy of isoniazid among children, with no effect realised in children initiating isoniazid at four months of age or earlier and an effect being present in older children. Excluding studies in which isoniazid was initiated at four months of age or earlier yielded an even stronger effect (RR = 0.41 (95% CI 0.31, 0.55) p <0.001). Data on the effect of isoniazid on all-cause mortality, excluding studies in which isoniazid was initiated in infants, yielded an imprecise estimate of mortality benefit (RR = 0.58 (95% CI 0.31, 1.09) p = 0.092). Conclusion Isoniazid prophylaxis reduces the risk of developing tuberculosis by 59% among children aged 15 years or younger excluding children initiated during early infancy for primary prophylaxis (RR = 0.41, 95% CI 0.31, 0.55 p < 0.001) . However, further studies are needed to assess effects on mortality and to determine prophylaxis effectiveness in very young children and among HIV-infected children. PMID:24555539

Tuberculosis Containment among the Homeless in Metropolitan Jackson, Mississippi.

PubMed

Azevedo, Mario J; Conwill, David E; Lawrence, Shonda; Jackson, Ann; Bhuiyan, Azad R; Hall, Dianne; Anderson, Brian; Franklin, Donald; Brown, David; Wilkerson, Patricia; Beckett, Gloria

2015-08-01

Preventing tuberculosis among the homeless has emerged as an especially difficult challenge. We assessed a 2008-2009 tuberculosis (TB) outbreak ad subsequent prevention strategies among homeless persons in metropolitan Jackson, Hinds County, Mississippi. We compared data about cases and subclinical TB infections (LTBI) among homeless persons during the outbreak and post-outbreak years, interviewed involved homeless persons, compiled observations from visits to Jackson homeless shelters and conducted literature reviews on homelessness and infectious diseases. We reviewed homeless shelter TB prevention methods adopted by other municipalities, guidelines developed by the Centers for Disease Control and Prevention (CDC), and recommendations from other official and ad hoc groups and considered their applicability to metropolitan Jackson. The Mississippi State Department of Health TB Program assisted by the CDC and other agencies, contained the Jackson-area outbreak by the end of 2009 as reflected by progressively lower TB rates among homeless persons thereafter. However, some follow-up activities and enforcement of shelter preventive measures have not been consistently maintained. Resources to prevent further outbreaks continue to be inadequate, and over-reliance on private organizations has continued. In the process, appreciation of the dynamic interaction enhancing TB risk among the homeless and incarcerated persons has emerged. Major outbreak contributors were lack of periodic TB screening among homeless shelter clients, preventive treatment compliance and follow-up difficulties among those with subclinical tuberculosis infections, interrupted preventive measures among infected persons incarcerated in local correctional facilities who disproportionately re-join Jackson's homeless community when released, inadequate attention to shelter environmental preventive strategies such as ultraviolet light germicidal irradiators and proper air-exchange/ventilation, costs of isolation housing for homeless people with full-blown tuberculosis (especially those co-infected with HIV and other infections and those with alcohol and/or other chemical dependencies), lack of adequate transportation which impacts access to evaluation and care, lack of mandated ongoing training among shelter and correctional facility staff, and inadequate attention to the societal problem of homelessness itself. Sustained adherence to local shelter and correctional facility TB prevention measures based on standards and policies proved effective in other settings is most crucial. These include requirements for periodic tuberculosis prevention and awareness training for shelter and correctional facility staff, ongoing tuberculosis screening and follow-up among homeless shelter clients and inmates of local correctional facilities, and attention to shelter and correctional facility environmental sanitation, proper ventilation, ultraviolet light fixtures and capacity/bed alignment standards.

A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania

PubMed Central

2011-01-01

Background Children with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately. Methods 255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin. Results There was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n = 22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI = 0.12, 1.10; p = 0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p < 0.01). HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n = 48; 2 cm, compared to 1 cm in the placebo group; 95% CI = 0.20, 1.70; p = 0.01; p for interaction by age group = 0.01). Conclusions Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure. Clinicaltrials.gov Identifier NCT00145184 PMID:22039966

[Investigation analysis on public awareness of tuberculosis knowledge in Zhejiang province, 2010].

PubMed

Huang, Yu; Zhong, Jie-ming; Chen, Song-hua; Chen, Bin; Wang, Xiao-meng

2012-04-01

To investigate the status of awareness on tuberculosis (TB) in the public and its impact factors in Zhejiang province. A multi-stage sampling was applied. Around 6600 subjects were enrolled for questionnaire survey from December 2010 to January 2011 in Zhejiang province. Survey data were input by EpiData 3.0 software, and the the status of awareness on tuberculosis (TB) in the public and impact factors were analyzed by SPSS 13.0 software package. A total of 6546 subjects were investigated, the response rate was 99.18% (6546/6600), 3306 were male and 3240 were female, the age of subjects was (44.90 ± 12.40) year-old. The total key information awareness rate of TB was 45.66% (14 944/32 730). 65.70% (4301/6546) knowing the transmission route, 33.30% (2180/6546) knowing the symptom of TB, 39.21% (2567/6546) knowing where to go when suspected suffering TB, 38.28% (2506, 6546) knowing national free anti-TB drug supply and examination of infectious TB patients, 51.79% (3390/6546) knowing TB is curable in most case. As for the the key information awareness rate, among senior high school or above, primary high school, primary school or below were 57.19% (3257/5695), 52.07% (6 066/11 650), 36.54% (5 621/15 385), respectively; among birthplace in city, rural areas were 54.70 (1745/3190), 44.68% (13 199/29 540), respectively; Amone male, female were 47.11% (7 788/16 530), 44.17% (7 156/16 200); among different occupations, cadre or staff was highest (59.43%, 1 563/2 630), whereas students was lowest (40.33%, 492/1220); among different age groups, subjects aged beyond 50 years was lowest (39.75%, 5 189/13 055). The total key information awareness rate among above different population groups showed statistically difference (all P values < 0.01). Awareness of knowledge for prevention and therapy of tuberculosis in Zhejiang public was insufficient and imbalanced among subjects with different social demographic characteristics.

A randomized trial of multivitamin supplementation in children with tuberculosis in Tanzania.

PubMed

Mehta, Saurabh; Mugusi, Ferdinand M; Bosch, Ronald J; Aboud, Said; Chatterjee, Anirban; Finkelstein, Julia L; Fataki, Maulidi; Kisenge, Rodrick; Fawzi, Wafaie W

2011-10-31

Children with tuberculosis often have underlying nutritional deficiencies. Multivitamin supplementation has been proposed as a means to enhance the health of these children; however, the efficacy of such an intervention has not been examined adequately. 255 children, aged six weeks to five years, with tuberculosis were randomized to receive either a daily multivitamin supplement or a placebo in the first eight weeks of anti-tuberculous therapy in Tanzania. This was only 64% of the proposed sample size as the trial had to be terminated prematurely due to funding constraints. They were followed up for the duration of supplementation through clinic and home visits to assess anthropometric indices and laboratory parameters, including hemoglobin and albumin. There was no significant effect of multivitamin supplementation on the primary endpoint of the trial: weight gain after eight weeks. However, significant differences in weight gain were observed among children aged six weeks to six months in subgroup analyses (n=22; 1.08 kg, compared to 0.46 kg in the placebo group; 95% CI=0.12, 1.10; p=0.01). Supplementation resulted in significant improvement in hemoglobin levels at the end of follow-up in children of all age groups; the median increase in children receiving multivitamins was 1.0 g/dL, compared to 0.4 g/dL in children receiving placebo (p<0.01). HIV-infected children between six months and three years of age had a significantly higher gain in height if they received multivitamins (n=48; 2 cm, compared to 1 cm in the placebo group; 95% CI=0.20, 1.70; p=0.01; p for interaction by age group=0.01). Multivitamin supplementation for a short duration of eight weeks improved the hematological profile of children with tuberculosis, though it didn't have any effect on weight gain, the primary outcome of the trial. Larger studies with a longer period of supplementation are needed to confirm these findings and assess the effect of multivitamins on clinical outcomes including treatment success and growth failure. CLINICALTRIALS.GOV IDENTIFIER: NCT00145184.

Validity and reliability of a health care service evaluation instrument for tuberculosis

PubMed Central

Scatena, Lucia Marina; Wysocki, Anneliese Domingues; Beraldo, Aline Ale; Magnabosco, Gabriela Tavares; Brunello, Maria Eugênia Firmino; Netto, Antonio Ruffino; Nogueira, Jordana de Almeida; Silva, Reinaldo Antonio; Brito, Ewerton William Gomes; Alexandre, Patricia Borges Dias; Monroe, Aline Aparecida; Villa, Tereza Cristina Scatena

2015-01-01

OBJECTIVE To evaluate the validity and reliability of an instrument that evaluates the structure of primary health care units for the treatment of tuberculosis. METHODS This cross-sectional study used simple random sampling and evaluated 1,037 health care professionals from five Brazilian municipalities (Natal, state of Rio Grande do Norte; Cabedelo, state of Paraíba; Foz do Iguaçu, state of Parana; Sao José do Rio Preto, state of Sao Paulo, and Uberaba, state of Minas Gerais) in 2011. Structural indicators were identified and validated, considering different methods of organization of the health care system in the municipalities of different population sizes. Each structure represented the organization of health care services and contained the resources available for the execution of health care services: physical resources (equipment, consumables, and facilities); human resources (number and qualification); and resources for maintenance of the existing infrastructure and technology (deemed as the organization of health care services). The statistical analyses used in the validation process included reliability analysis, exploratory factor analysis, and confirmatory factor analysis. RESULTS The validation process indicated the retention of five factors, with 85.9% of the total variance explained, internal consistency between 0.6460 and 0.7802, and quality of fit of the confirmatory factor analysis of 0.995 using the goodness-of-fit index. The retained factors comprised five structural indicators: professionals involved in the care of tuberculosis patients, training, access to recording instruments, availability of supplies, and coordination of health care services with other levels of care. Availability of supplies had the best performance and the lowest coefficient of variation among the services evaluated. The indicators of assessment of human resources and coordination with other levels of care had satisfactory performance, but the latter showed the highest coefficient of variation. The performance of the indicators “training” and “access to recording instruments” was inferior to that of other indicators. CONCLUSIONS The instrument showed feasibility of application and potential to assess the structure of primary health care units for the treatment of tuberculosis. PMID:25741651

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

Impact of the pretransplant dialysis modality on kidney transplantation outcomes: a nationwide cohort study.

PubMed

Lin, Huan-Tang; Liu, Fu-Chao; Lin, Jr-Rung; Pang, See-Tong; Yu, Huang-Ping

2018-06-04

Most patients with uraemia must undergo chronic dialysis while awaiting kidney transplantation; however, the role of the pretransplant dialysis modality on the outcomes of kidney transplantation remains obscure. The objective of this study was to clarify the associations between the pretransplant dialysis modality, namely haemodialysis (HD) or peritoneal dialysis (PD), and the development of post-transplant de novo diseases, allograft failure and all-cause mortality for kidney-transplant recipients. Retrospective nationwide cohort study. Data retrieved from the Taiwan National Health Insurance Research Database. The National Health Insurance database was explored for patients who received kidney transplantation in Taiwan during 1998-2011 and underwent dialysis >90 days before transplantation. The pretransplant characteristics, complications during kidney transplantation and post-transplant outcomes were statistically analysed and compared between the HD and PD groups. Cox regression analysis was used to evaluate the HR of the dialysis modality on graft failure and all-cause mortality. The primary outcomes were long-term post-transplant death-censored allograft failure and all-cause mortality started after 90 days of kidney transplantation until the end of follow-up. The secondary outcomes were events during kidney transplantation and post-transplant de novo diseases adjusted by propensity score in log-binomial model. There were 1812 patients included in our cohort, among which 1209 (66.7%) and 603 (33.3%) recipients received pretransplant HD and PD, respectively. Recipients with chronic HD were generally older and male, had higher risks of developing post-transplant de novo ischaemic heart disease, tuberculosis and hepatitis C after adjustment. Pretransplant HD contributed to higher graft failure in the multivariate analysis (HR 1.38, p<0.05) after adjustment for the recipient age, sex, duration of dialysis and pretransplant diseases. There was no significant between-group difference in overall survival. Pretransplant HD contributed to higher risks of death-censored allograft failure after kidney transplantation when compared with PD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Peritonitis: 10 years' experience in a single surgical unit.

PubMed

Agarwal, Nitin; Saha, Sudipta; Srivastava, Anurag; Chumber, Sunil; Dhar, Anita; Garg, Sanket

2007-01-01

Peritonitis secondary to gut perforation is still one of the commonest surgical emergencies in India and is associated with high morbidity and mortality. The present study examines the aetiology and outcome of peritonitis cases operated on in our surgical unit, and compares our findings with those of previous studies performed between 1981 and 1991. A retrospective study of 260 peritonitis patients operated on in a single surgical unit from 1995 to 2006 was done and data involving clinical presentation, operative findings and post-operative course were studied and analysed. Causes of peritonitis were small bowel perforation (96 ileal, 17 jejunal), peptic perforation (45 duodenal, 16 gastric), appendicular perforation (36), primary peritonitis (8), and others (42). The incidence of major complications was 25% (burst-11%, leak-5%, intraabdominal abscess-5%, multi-organ failure-6.5%). The overall mortality was 10%. High mortality was observed in jejunal, gall bladder and liver abscess perforation cases (> 20%). Histopathological evaluation (143 specimens) revealed tuberculosis in 42 (mostly small bowel), malignancy in 8, and inflammation in the rest. Comparisons with a similar study carried out in the same unit and published in 1995 revealed similar demographic features and mortality, but a change in the most common cause (peptic ulcer perforation to small bowel perforation), and an increased performance of enterostomy compared with primary repair in small bowel perforation and a decrease in the leak rate (13% to 4%). Small bowel perforation is the commonest form of perforation and the mortality rate associated with peritonitis remains unchanged.

Innovative Tuberculosis Symposium held during Cuba Salud 2015.

PubMed

Chapman, Helena J; Armas Pérez, Luisa

2016-12-01

The fourth Tuberculosis (TB) Symposium, held during the Cuba Salud 2015 International Convention, highlighted advancements in research on TB and Mycobacterium tuberculosis (Mtb) by interdisciplinary teams from academic and federal institutions in Cuba, Colombia, Mexico, and the Dominican Republic. Delegates focused on the targets presented in the World Health Organization End TB Strategy for 2016-2035 and elaborated on four primary themes: 1) attention to vulnerable populations such as immunocompromised individuals, health care workers, and residents of long-term institutions such as prisons and nursing homes; 2) identification of active and latent TB cases through contact investigations; 3) spread and control of drug-resistant Mtb strains; and 4) advancements in the development of novel vaccines or "booster" immunizations. This international TB forum served as a platform for experts in diverse disciplines in these Latin American countries to discuss challenges faced by TB research and control programs, proposing novel research initiatives and promoting collaborative teamwork strategies for TB elimination. In solidarity, collaborative efforts in TB control require identification of symptomatic individuals, rapid diagnostic testing for TB, drug susceptibility assays on Mtb strains, and management that provide universal and gratuitous access to directly observed short-course therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

The Role of MGIT 960 Culture Medium in Resolving the Diagnostic Dilemma for Genital Tuberculosis Patients Presenting with Infertility.

PubMed

Jindal, Nidhi; Gainder, Shalini; Dhaliwal, Lakhbir Kaur; Sethi, Sunil

2018-04-01

The purpose of this study was to assess the utility of Mycobacteria Growth Indicator Tube (MGIT) 960 culture medium for the diagnosis of genital tuberculosis (GTB) in women presenting with infertility. The premenstrual endometrial biopsy samples in 300 women presenting with primary and secondary infertility were subjected to AFB smear method, histopathological examination and culture on LJ and MGIT 960 media. Detection rates were compared for diagnostic modalities and their combinations. In total, 30 cases were positive for genital tuberculosis by either of the four tests employed. The detection rates for AFB smear, MGIT culture, LJ culture and HPE were 50, 46.7, 3.3 and 33.3%, respectively. A combination of smear examination for AFB, MGIT 960 culture and histopathological examination was able to detect all the positive cases. A combination of MGIT and LJ media provided no added advantage over MGIT alone since the only case where LJ culture was positive had been detected by positive MGIT culture. In as many as five positive cases (16.7%), only MGIT culture was positive. The addition of MGIT 960 culture medium to routine battery of investigations in infertility patients significantly improves the diagnosis.

Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion

PubMed Central

Schiebler, Mark; Brown, Karen; Hegyi, Krisztina; Newton, Sandra M; Renna, Maurizio; Hepburn, Lucy; Klapholz, Catherine; Coulter, Sarah; Obregón-Henao, Andres; Henao Tamayo, Marcela; Basaraba, Randall; Kampmann, Beate; Henry, Katherine M; Burgon, Joseph; Renshaw, Stephen A; Fleming, Angeleen; Kay, Robert R; Anderson, Karen E; Hawkins, Phillip T; Ordway, Diane J; Rubinsztein, David C; Floto, Rodrigo Andres

2015-01-01

Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection. PMID:25535254

Breast tuberculosis: Diagnosis, management and treatment

PubMed Central

Marinopoulos, Spyridon; Lourantou, Dionysia; Gatzionis, Thomas; Dimitrakakis, Constantine; Papaspyrou, Irini; Antsaklis, Aris

2012-01-01

INTRODUCTION Mammary (breast) tuberculosis is a rare manifestation of extra-pulmonary localization of the disease which accounts for less than 0.1% of breast conditions in developed countries, but reaches 3–4% in regions where the disease presents with high incidence (India, Africa). It appears mostly in women of reproductive age, multiparous, lactating. It has been scarcely reported to infect male patients, mainly before puberty, as well as women of older age. The most common presentation is that of a tumor in the middle or upper-outer quadrant of the breast, with multifocal involvement being rarely documented. The differential diagnosis includes breast cancer and abscess formation. PRESENTATION OF CASE We report a case of breast tuberculosis that was treated in the Breast Unit of our hospital. Differential diagnosis, imaging methods, operative diagnostic approach and surgical treatment, histological verification of the disease and further therapeutic management are described. DISCUSSION High risk population is identified, primary and secondary disease is described and clinical presentations are analyzed. Evaluation of diagnostic workup and limitations are reported. CONCLUSION In accordance with the present worldwide revival of the disease, mainly because of massive numbers of migrating population, this subject is reviewed, reminding us of a rather uncommon clinical entity. PMID:22918083

Lessons learned during the successful eradication of bovine tuberculosis from Australia

PubMed Central

More, S. J.; Radunz, B.; Glanville, R. J.

2015-01-01

There are very few international examples of the successful eradication of bovine tuberculosis (TB, caused by infection with Mycobacterium bovis) from a national cattle population. This paper presents a brief overview of the successful TB eradication programme in Australia from 1970, with primary emphasis on lessons of international relevance that were learned from the Australian experience. The national brucellosis and tuberculosis eradication campaign ran for 27 years from 1970 to 1997 and has been followed by ongoing abattoir surveillance. Rapid progress towards eradication was made in southern Australia, but proved much more challenging in extensive pastoral areas of northern Australia. Declaration of TB freedom was made on December 31, 1997. A range of factors were critical to this success, including a compelling rationale for eradication, an agreed final outcome, industry commitment and financial support, a business model for programme planning, implementation and review, consistent and transparent technical standards underpinned by a strict regulatory regime and applied research, the critical role of abattoir surveillance, effective elimination of residual infection and objective measures of programme progress. Although direct translation of some of these experiences may not be possible, many of the lessons learned from the Australian experience may be relevant to other countries. PMID:26338937

Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.

PubMed

Schiebler, Mark; Brown, Karen; Hegyi, Krisztina; Newton, Sandra M; Renna, Maurizio; Hepburn, Lucy; Klapholz, Catherine; Coulter, Sarah; Obregón-Henao, Andres; Henao Tamayo, Marcela; Basaraba, Randall; Kampmann, Beate; Henry, Katherine M; Burgon, Joseph; Renshaw, Stephen A; Fleming, Angeleen; Kay, Robert R; Anderson, Karen E; Hawkins, Phillip T; Ordway, Diane J; Rubinsztein, David C; Floto, Rodrigo Andres

2015-02-01

Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

[Primary mucosal tuberculosis of head and neck region: a clinicopathologic analysis of 47 cases].

PubMed

Wang, Shu-yi; Zhu, Jia-xing

2013-10-01

To study the clinicopathologic features, histologic diagnosis and differential diagnosis of primary mucosal tuberculosis (TB) in the head and neck region. Forty-seven cases of primary mucosal TB of the head and neck region were studied by hematoxylin-eosin and Ziehl-Neelsen stains. The clinical and pathologic features were analyzed with review of the literature. The patients included 26 male and 21 female, with mean age 47.1 years (range 14-84 years). There were three sinonasal TB, 19 nasopharyngeal TB, two oropharyngeal TB, 18 laryngeal TB, four middle ear TB, one salivary gland TB and one laryngeal TB complicating laryngeal cancer. The initial symptoms were nasal obstruction, mucopurulent rhinorrhea, epistaxis, snoring, hoarseness, dysphagia, odynophagia, serous otitis, hearing loss, tinnitus, and otalgia. Physical examination result was variable, from an apparently normal mucosa, to an evident mass, or a mucosa with an adenotic or swollen appearance, ulcers, leukoplakic areas, and various combinations thereof. CT and MRI findings included diffuse thickening, a soft-tissue mass, calcification within the mass and bone destruction resembling malignancy. Histologic examination showed granulomas with a central necrotic focus surrounded by epithelioid histiocytes and multinucleated Langhan's giant cells. Acid-fast bacilli were difficult to demonstrate but found in 13/45 cases. Follow-up data were available in 42 patients. Primary TB arising in the head and neck mucosa is rare. It may mimic or co-exist with other conditions. The characteristic histopathology is a granuloma with central caseous necrosis and Langhans'giant cells. Identification of acid-fast bacilli and bacteriologic culture confirm the diagnosis of mycobacterial disease.

Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis.

PubMed

Xing, Zhou; McFarland, Christine T; Sallenave, Jean-Michel; Izzo, Angelo; Wang, Jun; McMurray, David N

2009-06-10

Recombinant adenovirus-vectored (Ad) tuberculosis (TB) vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. Specific pathogen-free guinea pigs were immunized with BCG, AdAg85A intranasally (i.n), AdAg85A intramuscularly (i.m), BCG boosted with AdAg85A i.n, BCG boosted with AdAg85A i.m, or treated only with saline. The animals were then infected by a low-dose aerosol of M. tuberculosis (M.tb). At the specified times, the animals were sacrificed and the levels of infection in the lung and spleen were assessed. In separate studies, the long-term disease outcome of infected animals was monitored until the termination of this study. Immunization with Ad vaccine alone had minimal beneficial effects. Immunization with BCG alone and BCG prime-Ad vaccine boost regimens significantly reduced the level of M.tb infection in the tissues to a similar extent. However, while BCG alone prolonged the survival of infected guinea pigs, the majority of BCG-immunized animals succumbed by 53 weeks post-M.tb challenge. In contrast, intranasal or intramuscular Ad vaccine boosting of BCG-primed animals markedly improved the survival rate with 60% of BCG/Ad i.n- and 40% of BCG/Ad i.m-immunized guinea pigs still surviving by 74 weeks post-aerosol challenge. Boosting, particularly via the intranasal mucosal route, with AdAg85A vaccine is able to significantly enhance the long-term survival of BCG-primed guinea pigs following pulmonary M.tb challenge. Our results thus support further evaluation of this viral-vectored TB vaccine in clinical trials.