TB Summit 2014

PubMed Central

Maitra, Arundhati; Bhakta, Sanjib

2014-01-01

World TB Day commemorates Dr Robert Koch’s first announcement on March 24, 1882, that the bacterium Mycobacterium tuberculosis is the causative agent of tuberculosis. Currently, the event comprises of several conferences, meetings and activities held all over the world with the singular intention of raising public awareness about the global health emergency. In spite of having discovered the etiological agent of tuberculosis more than a century ago, a sizeable population still contract the disease every year and fall prey to it. In 2012, an estimated 8.6 million people developed the disease with 1.3 million succumbing to it. The number of TB deaths in children is unacceptably large, given that most are preventable. However, the challenge appears to be shifting toward attempts to control the rise and spread of the drug resistant variants of the microbe. To achieve this, a concerted effort from academia, clinical practice, and industry has been put forth. The TB Summit 2014 attempted to raise awareness as well as bring together experts involved in different aspects of tuberculosis research to help establish a more collective approach to battle this age-old disease. PMID:25003368

T-SPOT.TB in Detection of Active Tuberculosis During Pregnancy: A Retrospective Study in China.

PubMed

Chen, Qiaopei; Guo, Xuxiao; Wang, Xinfeng; Wang, Maoshui

2016-01-06

Interferon-gamma release assays have not been validated in active TB among pregnant women. Therefore, the objective of this retrospective study was to estimate the diagnostic value of T-SPOT.TB in active TB among pregnant women. Between May 2012 and May 2015, 26 consecutive pregnant women with suspected TB were enrolled in our study. The clinicopathological characteristics and T-SPOT.TB results were reviewed and analyzed. Pregnant patients were divided into a TB group (n=21) and a Non-TB group (n=5). In the TB group, 5 patients had pulmonary TB, 5 had pulmonary TB+ extrapulmonary TB, and 11 had exclusively extrapulmonary TB. The most common site of extrapulmonary TB was pleural (n=11). Statistical analysis showed that the lymphocyte count in the TB group was lower than in the Non-TB group (P<0.05). For detection of active TB during pregnancy, T-SPOT.TB had a high sensitivity of 100.0% (84.5%-100.0%) and a specificity of 80.0% (37.6-96.4%). T-SPOT.TB shows good performance in detection of active tuberculosis during pregnancy. Interferon gamma release assay for TB screening of pregnant women is recommended in clinical practice because it may be a more appropriate diagnostic tool than the tuberculin skin test.

Multiplex analysis of plasma cytokines/chemokines showing different immune responses in active TB patients, latent TB infection and healthy participants.

PubMed

Yao, Xiangyang; Liu, Yongliang; Liu, Yang; Liu, Wei; Ye, Zhizhong; Zheng, Chao; Ge, Shengxiang

2017-12-01

Interferon gamma release assays (IGRAs) have been widely used to diagnose Mycobacterium tuberculosis (MTB) infection. However, IGRAs cannot discriminate between active TB patients and latent TB infection (LTBI), and the sensitivity of IGRAs for MTB infection is suboptimal. Here, we analyzed cytokines/chemokines in MTB antigen-stimulated and -unstimulated plasma samples to identify host biomarkers that are associated with active TB and MTB infection. Active TB patients, subjects with LTBI and healthy participants were recruited. Seventy-one soluble cytokines and chemokines were tested using Luminex liquid array-based multiplexed immunoassays. For the 71 examined factors, our results indicated that the unstimulated levels of IL-8 Nil , IP-10 Nil , MIP-1a Nil , and sIL-2Ra Nil and the antigen stimulated levels of IL-8 (Ag-Nil) , VEGF (Ag-Nil) , and MCP-3 (Ag-Nil) were potential biomarkers for differentiating between active TB and LTBI, with AUCs of 0.8, 0.86, 0.755, 0.845, 0.825, 0.812 and 0.75, respectively. The G-CSF (Ag-Nil) , GM-CSF (Ag-Nil) , IL-1a (Ag-Nil) , IL-2 (Ag-Nil) , IP-10 (Ag-Nil) , BCA-1 (Ag-Nil) and Eotaxin-1 (Ag-Nil) responses were significantly higher in patients with active TB and LTBI compared with healthy participants (p < 0.05), with AUCs of 0.922, 0.902, 0.908, 1.0, 0.937, 0.919 and 0.935, respectively. Our preliminary data suggest that unstimulated or stimulated levels of cytokines and chemokines could be used as host biomarkers for diagnosing active TB as well as additional biomarkers, except IFN-γ, for MTB infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India

PubMed Central

Bapat, Prachi R.; Satav, Ashish R.; Husain, Aliabbas A.; Shekhawat, Seema D.; Kawle, Anuja P.; Chu, Justin J.; Purohit, Hemant J.; Daginawala, Hatim F.; Taori, Girdhar M.; Kashyap, Rajpal S.

2015-01-01

Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis. PMID:26241963

The risk factor of false-negative and false-positive for T-SPOT.TB in active tuberculosis.

PubMed

Di, Li; Li, Yan

2018-02-01

T-SPOT.TB is a promising diagnosis tool to identify both pulmonary tuberculosis and extrapulmonary tuberculosis, as well as latent tuberculosis; however, the factors that affect the results of T-SPOT.TB remains unclear. In this study, we aim to figure out the risk factor of T-SPOT.TB for active TB. A total of 349 patients were recruited between January 1st, 2016 and January 22st, 2017 at Renmin Hospital of Wuhan University, including 98 subjects with TB and 251 subjects with non-TB disease, and received T-SPOT.TB (Oxford Immunotec Ltd). Statistics were analyzed by SPSS 19.0 using logistic regression. The overall specificity and sensitivity of the T-SPOT.TB was 92.83% (233/251; 95%CI 0.8872-0.9557) and 83.67% (82/98; 95%CI 0.7454-0.9010), respectively. Patients with tuberculous meningitis were more likely to have false-negative results (OR 17.4, 95%CI 3.068-98.671; P<.001) while patients with cured TB tended to induce false-positive results (OR 30.297; 95%CI 7.069-129.849; P<.001). The results were not affected by sex, age, onset time, smoke, alcohol, treatment, allergic history, co-morbidity, TB (exclude tuberculous meningitis) (P>.05). Tuberculous meningitis was a risk factor of false-negative for T-SPOT.TB, while cured TB was a risk factor of false-positive. © 2017 Wiley Periodicals, Inc.

Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

PubMed

Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

2016-01-01

India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Tuberculosis Facts - Exposure to TB

MedlinePlus

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

Tuberculosis Facts - Testing for TB

MedlinePlus

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

Screening contacts of patients with extrapulmonary TB for latent TB infection.

PubMed

Humphreys, Anna; Abbara, Aula; Williams, Sion; John, Laurence; Corrah, Tumena; McGregor, Alastair; Davidson, Robert N

2018-03-01

2016 TB National Institute for Health and Care Excellence (NICE) guidelines imply that contacts of extrapulmonary TB do not require screening for latent TB infection. At our high TB prevalence site, we identified 189 active cases of TB for whom there were 698 close contacts. 29.1% of the contacts of pulmonary TB and 10.7% of the contacts of extrapulmonary TB had active or latent TB infection. This supports screening contacts of extrapulmonary TB at our site and presents a way to access high-risk individuals. We propose to continue to screen the contacts of our patients with extrapulmonary TB and recommend other TB units audit their local results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Tuberculosis Facts - TB Can Be Treated

MedlinePlus

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

Tuberculosis Facts - You Can Prevent TB

MedlinePlus

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

HIV and Tuberculosis (TB)

MedlinePlus

... or brain. If not treated, TB disease can cause death. HIV weakens the immune system , increasing the risk ... spine, or brain. If not treated, TB can cause death. How does TB spread from person to person? ...

Tuberculosis Facts - TB and HIV/AIDS

MedlinePlus

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

PEPFAR support for the scaling up of collaborative TB/HIV activities.

PubMed

Howard, Andrea A; Gasana, Michel; Getahun, Haileyesus; Harries, Anthony; Lawn, Stephen D; Miller, Bess; Nelson, Lisa; Sitienei, Joseph; Coggin, William L

2012-08-15

The US President's Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR's TB/HIV programming is based on the World Health Organization's 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result, PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR's support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy, intensified case finding, and infection control. Issues to be addressed by future programming include accelerating implementation of isoniazid preventive therapy, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation.

PEPFAR Support for the Scaling Up of Collaborative TB/HIV Activities

PubMed Central

Howard, Andrea A.; Gasana, Michel; Getahun, Haileyesus; Harries, Anthony; Lawn, Stephen D.; Miller, Bess; Nelson, Lisa; Sitienei, Joseph; Coggin, William L.

2014-01-01

The US President’s Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR’s TB/HIV programming is based on the World Health Organization 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR’s support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy (IPT), intensified case finding and infection control. Issues to be addressed by future programming include accelerating implementation of IPT, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation. PMID:22797735

TB & HIV: the deadly intersection.

PubMed

MacDougall, D S

1999-05-01

About 2 billion people worldwide are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). TB is the leading cause of premature death in less industrialized countries, and 8 million more people become infected every year. The World Health Organization (WHO) declared TB a global emergency in 1993 and launched a series of prevention and vaccination programs. In spite of effective drug therapy and a vaccine, tuberculosis remains a major public health problem. The TB and HIV epidemics are closely intertwined, and the risk of TB disease progression is 100 times greater in HIV-positive individuals. TB is the leading cause of death among HIV-infected people worldwide, and virologic evidence suggests that the host immune response to TB may enhance HIV replication and accelerate the progression of HIV infection. The interaction between the two diseases was the subject of a conference called TB & HIV: Applying Advances to the Clinic, Public Health, and the World. Charts and tables show reported TB cases in the U.S., trends in TB cases among foreign-born persons in the U.S., and the country of origin for foreign-born persons with TB in the U.S. Several poster sessions from the conference are summarized. Strategies for dealing with the TB epidemic are outlined.

Challenges with diagnosing and investigating suspected active tuberculosis disease in military trainees.

PubMed

Chang, David; Webber, Bryant J; Hetrick, Steven M; Owen, Jerry B; Blasi, Audra A; Steele, Bernadette M; Yun, Heather C

2017-08-01

Between 1 January 2010 and 31 December 2016, a total of 14 U.S. and international military personnel in training at Joint Base San Antonio-Lackland, TX, were hospitalized due to suspected pulmonary tuberculosis (TB); of these, five personnel were diagnosed with active TB disease. Only one TB case had pulmonary symptoms, but these symptoms were not suggestive of TB. The incidence rate in the training population was 1.89 per 100,000 population (95% CI: 0.81, 4.42), with a higher rate when restricted to international military students attending the Defense Language Institute English Language Center. No instances of TB transmission were identified. The variety of atypical presentations and their resulting diagnostic and public health challenges prompted this retrospective review of all hospitalized cases. This case series highlights both the importance of a high index of clinical suspicion when TB is being considered in close congregate settings as well as the risk of overreliance on acid-fast bacilli staining and nucleic acid amplification testing for ruling out active pulmonary disease in young, otherwise healthy trainees. Practical solutions are suggested.

Staying on Track with TB Medicine

MedlinePlus

... medicines. If you have TB disease , you must remember that TB germs die very slowly. Even if you feel better after a few weeks on the TB medicines, it does not mean all the TB germs are dead. Treating TB takes months. Staying on your medicine the ... points to remember: • Anyone can breathe in TB germs and get ...

Evaluation of risk factors for false-negative results with an antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT®. TB) in the diagnosis of active tuberculosis: A large-scale retrospective study in China.

PubMed

Yang, Chi; Zhang, Shaojun; Yao, Lan; Fan, Lin

2018-05-01

Objective To investigate the diagnostic efficacy of an interferon-γ release assay, T-SPOT ® . TB, for diagnosing active tuberculosis (TB) and to identify risk factors for false-negative results. Methods This retrospective study enrolled consecutive patients with active TB and with non-TB respiratory diseases to evaluate the risk factors for false-negative results when using the T-SPOT ® . TB assay for the diagnosis of active TB. Patients with active TB were categorized as having confirmed pulmonary TB, clinically diagnosed pulmonary TB or extrapulmonary TB (EPTB). Results This study analysed 4964 consecutive patients; 2425 with active TB and 2539 with non-TB respiratory diseases. Multivariate logistic regression analyses identified the following five factors that were all associated with an increased false-negative rate with the T-SPOT ® . TB assay: increased age (odds ratio [OR] 1.018; 95% confidence interval [CI] 1.013, 1.024); decreased CD8+ count (OR 0.307; 95% CI 0.117, 0.803); negative sputum acid-fast bacilli (AFB) smear staining (OR 1.821; 95% CI 1.338, 2.477); negative mycobacterial cultures (OR 1.379; 95% CI 1.043, 1.824); and absence of EPTB (OR 1.291; 95% CI 1.026, 1.623). Conclusions Increased age, decreased CD8+ count, negative sputum AFB smear results, negative sputum mycobacterial cultures and absence of EPTB might lead to an increased false-negative rate when using the T-SPOT ® . TB assay.

Are TB control programmes in South Asia ignoring children with disease? A situational analysis.

PubMed

Shakoor, Sadia; Qamar, Farah Naz; Mir, Fatima; Zaidi, Anita; Hasan, Rumina

2015-02-01

Paediatric tuberculosis (TB) has long been an evasive entity for public health practitioners striving to control the disease. Owing to difficulty in diagnosis of paediatric TB, incidence estimates based on current case detection fall short of actual rates. The four high-burden countries in South Asia (SA-HBC)-Afghanistan, Pakistan, India and Bangladesh-alone account for >75% of missed TB cases worldwide. It follows that these countries are also responsible for a large although unmeasured proportion of missed paediatric cases. In view of current Millennium Development Goals recommending a scale-up of paediatric TB detection and management globally, there is a dire need to improve paediatric TB programmes in these high-burden countries. Inherent problems with diagnosis of paediatric TB are compounded by programmatic and social barriers in SA-HBC. We have reviewed the current situation of TB control programmes in SA-HBC countries based on published statistics and performed a strengths, weaknesses, opportunities and threats situational analysis with a view towards identifying critical issues operant in the region posing barriers to improving paediatric TB control. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Optimal treatment interruptions control of TB transmission model

NASA Astrophysics Data System (ADS)

Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.

2018-03-01

A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.

Hierarchy Low CD4+/CD8+ T-Cell Counts and IFN-γ Responses in HIV-1+ Individuals Correlate with Active TB and/or M.tb Co-Infection.

PubMed

Shao, Lingyun; Zhang, Xinyun; Gao, Yan; Xu, Yunya; Zhang, Shu; Yu, Shenglei; Weng, Xinhua; Shen, Hongbo; Chen, Zheng W; Jiang, Weimin; Zhang, Wenhong

2016-01-01

Detailed studies of correlation between HIV-M.tb co-infection and hierarchy declines of CD8+/CD4+ T-cell counts and IFN-γ responses have not been done. We conducted case-control studies to address this issue. 164 HIV-1-infected individuals comprised of HIV-1+ATB, HIV-1+LTB and HIV-1+TB- groups were evaluated. Immune phenotyping and complete blood count (CBC) were employed to measure CD4+ and CD8+ T-cell counts; T.SPOT.TB and intracellular cytokine staining (ICS) were utilized to detect ESAT6, CFP10 or PPD-specific IFN-γ responses. There were significant differences in median CD4+ T-cell counts between HIV-1+ATB (164/μL), HIV-1+LTB (447/μL) and HIV-1+TB- (329/μL) groups. Hierarchy low CD4+ T-cell counts (<200/μL, 200-500/μL, >500/μL) were correlated significantly with active TB but not M.tb co-infection. Interestingly, hierarchy low CD8+ T-cell counts were not only associated significantly with active TB but also with M.tb co-infection (P<0.001). Immunologically, HIV-1+ATB group showed significantly lower numbers of ESAT-6-/CFP-10-specific IFN-γ+ T cells than HIV-1+LTB group. Consistently, PPD-specific IFN-γ+CD4+/CD8+ T effector cells in HIV-1+ATB group were significantly lower than those in HIV-1+LTB group (P<0.001). Hierarchy low CD8+ T-cell counts and effector function in HIV-1-infected individuals are correlated with both M.tb co-infection and active TB. Hierarchy low CD4+ T-cell counts and Th1 effector function in HIV-1+ individuals are associated with increased frequencies of active TB, but not M.tb co-infection.

Opportunities and challenges for HIV care in overlapping HIV and TB epidemics.

PubMed

Havlir, Diane V; Getahun, Haileyesus; Sanne, Ian; Nunn, Paul

2008-07-23

Tuberculosis (TB) and the emerging multidrug-resistant TB epidemic represent major challenges to human immunodeficiency virus (HIV) care and treatment programs in resource-limited settings. Tuberculosis is a major cause of mortality among patients with HIV and poses a risk throughout the course of HIV disease, even after successful initiation of antiretroviral therapy (ART). Progress in the implementation of activities directed at reducing TB burden in the HIV population lags far behind global targets. HIV programs designed for longitudinal care are ideally suited to implement TB control measures and have no option but to address TB vigorously to save patient lives, to safeguard the massive investment in HIV treatment, and to curb the global TB burden. We propose a framework of strategic actions for HIV care programs to optimally integrate TB into their services. The core activities of this framework include intensified TB case finding, treatment of TB, isoniazid preventive treatment, infection control, administration of ART, TB recording and reporting, and joint efforts of HIV and TB programs at the national and local levels.

Performance of the QuantiFERON-TB Gold Assay Among HIV-infected Children With Active Tuberculosis in France.

PubMed

Hormi, Myriam; Guérin-El Khourouj, Valérie; Pommelet, Virginie; Jeljeli, Mohamed; Pédron, Béatrice; Diana, Jean-Sébastien; Faye, Albert; Sterkers, Ghislaine

2018-04-01

Data regarding the use of QuantiFERON to assist the diagnosis of active tuberculosis (TB) in HIV-infected children are limited, especially in countries with low incidence of TB/HIV coinfection. QuantiFERON results were analyzed in 63 HIV-infected children who presented to our hospital in Paris, France. Seventeen HIV-uninfected children with active TB (4 culture-confirmed) were included for comparison. The 63 HIV-infected children (median age: 11 yr) had 113 QuantiFERON tests. Thirty-four (54%) were born in sub-Saharan Africa. Vertical HIV transmission was documented for 50 of 52 (96%) and stage III HIV-infection for 30 of 50 children (60%). Over the study period, active TB was diagnosed in 7 of 63 HIV-infected children (3 culture-confirmed). Additional ongoing or previous opportunistic infections were present in 4 of 7. QuantiFERON results were positive in 2 of 7 HIV-infected children with active TB (sensitivity: 29%) and 16 of 17 HIV-uninfected children with active TB (sensitivity: 94%). At initial QuantiFERON testing of the 63 HIV-infected children, 8 (13%) had positive results (1, active TB; 5, latent TB; 2, previous TB) and 51 (81%) had negative results. Of 33 children with repeat testing after an initially positive or negative result, the only change was one conversion from a negative to a positive result at the onset of active TB. The 4 children (6%) with indeterminate quantiFERON results had a concomitant opportunistic infection. Results of repeat testing after clinical stabilization were negative in all 4. QuantiFERON testing performed poorly for active TB diagnosis in this series of children with advanced HIV infection.

Multicenter study of QuantiFERON®-TB Gold Plus in patients with active tuberculosis.

PubMed

Horne, D J; Jones, B E; Kamada, A; Fukushima, K; Winthrop, K L; Siegel, S A R; Kovacs, A; Anthony, P; Meekin, K A; Bhat, S; Kerndt, P; Chang, A; Koelle, D M; Narita, M

2018-06-01

QuantiFERON®-TB Gold Plus (QFT-Plus), recently approved for use in the United States, is a new-generation QuantiFERON assay that differs from its predecessors in that it uses an additional antigen tube containing peptides to elicit both CD8+ and CD4+ T-lymphocyte responses. To assess the sensitivity of QFT-Plus compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) in participants with active TB. Adult patients with active TB at three US and two Japanese sites were eligible for this study if they had culture-confirmed TB and were either untreated or had received 14 days of anti-tuberculosis treatment. We enrolled 164 participants, nine of whom had indeterminate results. Excluding indeterminate values, there were 150 QFT-GIT-positive results among 159 tests and 146 QFT-Plus-positive results among 157 tests, with sensitivities of respectively 94.3% (95%CI 89.5-97.4) and 93.02% (95%CI 87.8-96.5%). The estimated sensitivities for the two tests were not significantly different (P = 0.16). Overall test agreement was 98.7%, with a κ statistic of 0.89 (95%CI 0.75-1.00). In this multisite study, we found that QFT-Plus had similar sensitivity to QFT-GIT in adult patients with active TB.

Antituberculosis IgG Antibodies as a Marker of Active Mycobacterium tuberculosis Disease

PubMed Central

Welch, Ryan J.; Lawless, Kathleen M.

2012-01-01

Anti-Mycobacterium tuberculosis IgG antibodies may aid in the diagnosis of active M. tuberculosis disease. We studied whether anti-M. tuberculosis IgG antibodies are elevated in active M. tuberculosis disease and assessed factors contributing to false-positive and -negative results. A retrospective study of 2,150 individuals tested by the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was conducted at the University of Utah, ARUP Laboratories, November 2008 to December 2010. All samples were tested with the InBios Active TbDetect antituberculosis (anti-TB) IgG antibody assay. Of 1,044 patients with a positive QFT-GIT, 59 (5.7%) were positive for M. tuberculosis antibodies. Fourteen of 1,106 (1.3%) with a negative or indeterminate QFT-GIT were positive for M. tuberculosis antibodies. M. tuberculosis antibody tests were positive in 61.5% with confirmed active M. tuberculosis disease and other mycobacterial infections. Over half of the false-negative M. tuberculosis antibody tests occurred in patients ≥90 years of age. False positives were seen in 12.9% of autoimmune patients. The odds ratio of being positive by the QFT-GIT and the InBios TB IgG assay increased with confirmed M. tuberculosis disease or highly suspected M. tuberculosis disease and was 86.7 (95% confidence interval [CI], 34.4 to 218.5) in these two groups compared to patients negative by both tests. Although anti-M. tuberculosis antibodies can be detected in patients with active M. tuberculosis disease, caution should be used with patients where immunoglobulin levels may be decreased or patients with autoantibodies. PMID:22301692

The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.

PubMed

Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie

2016-01-01

Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clearing the smoke around the TB-HIV syndemic: smoking as a critical issue for TB and HIV treatment and care

PubMed Central

Jackson-Morris, A.; Fujiwara, P. I.; Pevzner, E.

2016-01-01

SUMMARY The collision of the tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics has been described as a ‘syndemic’ due to the synergistic impact on the burden of both diseases. This paper explains the urgent need for practitioners and policy makers to address a third epidemic that exacerbates TB, HIV and TB-HIV. Tobacco use is the leading cause of preventable death worldwide. Smoking is more prevalent among persons diagnosed with TB or HIV. Smoking is associated with tuberculous infection, TB disease and poorer anti-tuberculosis treatment outcomes. It is also associated with an increased risk of smoking-related diseases among people living with HIV, and smoking may also inhibit the effectiveness of life-saving ART. In this paper, we propose integrating into TB and HIV programmes evidence-based strategies from the ‘MPO-WER’ package recommended by the World Health Organization’s Framework Convention on Tobacco Control. Specific actions that can be readily incorporated into current practice are recommended to improve TB and HIV outcomes and care, and reduce the unnecessary burden of death and disease due to smoking. PMID:26260816

Decreased serum 5-oxoproline in TB patients is associated with pathological damage of the lung.

PubMed

Che, Nanying; Cheng, Jianhua; Li, Haijing; Zhang, Zhiguo; Zhang, Xuxia; Ding, Zhixin; Dong, Fangting; Li, Chuanyou

2013-08-23

Tuberculosis (TB) is a serious world-wide health problem, causing millions of deaths every year. Metabolomics is a relatively new approach to identify disease specific biomarkers. However, there is little information available on metabolite biomarkers in TB. In this study, we used gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS) to identify serum metabolite biomarkers associated with the active state of TB. Potential biomarkers were selected by comparing serum metabolites in 10 healthy donors with 10TB patients, and in 6TB patients before and after treatment. Selected biomarkers were then validated using a larger population of samples from 120 healthy donors and 120TB patients derived from different clinical backgrounds The 5-oxoproline level was consistently low in patients with active TB. Further validation in larger population of clinical samples showed that 5-oxoproline was associated with pathological damage of the lung but not with age, sex, or bacterial burden in TB patients. Serum 5-oxoproline may be a useful biomarker for active TB and pathological damage of the lung. Copyright © 2013 Elsevier B.V. All rights reserved.

Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA.

PubMed

van Rensburg, Ilana C; Wagman, Chandre; Stanley, Kim; Beltran, Caroline; Ronacher, Katharina; Walzl, Gerhard; Loxton, Andre G

2017-01-10

Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment).We show that FASLG, IL5RA, CD38 and IL4 expression was lower in B-cells from TB cases compared to healthy controls. The changes in expression levels of CD38 may be due to a reduced activation of B-cells from TB cases at diagnosis. By month 2 of treatment, there was a significant increase in the expression of APRIL and IL5RA in TB cases. Furthermore, after 6 months of treatment, APRIL, FASLG, IL5RA and CD19 were upregulated in B-cells from TB cases. The increase in the expression of APRIL and CD19 suggests that there may be restored activation of B-cells following anti-TB treatment. The upregulation of FASLG and IL5RA indicates that B-cells expressing regulatory genes may play an important role in the protective immunity against M.tb infection. Our results show that increased activation of B-cells is present following successful TB treatment, and that the expression of FASLG and IL5RA could potentially be utilised as a signature to monitor treatment response.

The prevalence and determinants of active tuberculosis among diabetes patients in Cape Town, South Africa, a high HIV/TB burden setting.

PubMed

Berkowitz, Natacha; Okorie, Adaeze; Goliath, Rene; Levitt, Naomi; Wilkinson, Robert J; Oni, Tolu

2018-04-01

Studies addressing the association between diabetes mellitus (DM) and tuberculosis (TB) in sub-Saharan Africa are limited. We assessed the prevalence of active TB among DM patients at a primary care clinic, and identified risk factors for prevalent TB. A cross-sectional study was conducted in adult DM patients attending a clinic in Khayelitsha, Cape Town. Participants were screened for active TB (symptom screening and microbiological diagnosis) and HIV. Among 440 DM patients screened, the active TB prevalence was 3.0% (95% CI 1.72-5.03). Of the 13 prevalent TB cases, 53.9% (n = 7; 95% CI 27.20-78.50) had no TB symptoms, and 61.5% (n = 8; 95% CI 33.30-83.70) were HIV-1 co-infected. There were no significant differences in either fasting plasma glucose or HbA 1c levels between TB and non-TB participants. On multivariate analysis, HIV-1 infection (OR 11.3, 95% CI 3.26-39.42) and hemoptysis (OR 31.4, 95% CI 3.62-273.35) were strongly associated with prevalent active TB, with no differences in this association by age or gender. The prevalence of active TB among DM patients was 4-fold higher than the national prevalence; suggesting the need for active TB screening, particularly if hemoptysis is reported. Our results highlight the importance of HIV screening in this older population group. The high prevalence of sub-clinical TB among those diagnosed with TB highlights the need for further research to determine how best to screen for active TB in high-risk TB/HIV population groups and settings. Copyright © 2018. Published by Elsevier B.V.

Determination of dehydroepiandrosterone and its biologically active oxygenated metabolites in human plasma evinces a hormonal imbalance during HIV-TB coinfection.

PubMed

Vecchione, María Belén; Eiras, Javier; Suarez, Guadalupe Verónica; Angerami, Matías Tomás; Marquez, Cecilia; Sued, Omar; Ben, Graciela; Pérez, Héctor Miguel; Gonzalez, Diego; Maidana, Patricia; Mesch, Viviana; Quiroga, María Florencia; Bruttomesso, Andrea Claudia

2018-04-27

An estimated one third of the world's population is affected by latent tuberculosis (TB), which once active represents a leading cause of death among infectious diseases. Human immunodeficiency virus (HIV) infection is a main predisposing factor to TB reactivation. Individuals HIV-TB co-infected develop a chronic state of inflammation associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. This results in a hormonal imbalance, disturbing the physiological levels of cortisol and dehydroepiandrosterone (DHEA). DHEA and its oxygenated metabolites androstenediol (AED), androstenetriol (AET) and 7-oxo-DHEA are immunomodulatory compounds that may regulate physiopathology in HIV-TB co-infection. In order to study possible changes in plasma levels of these hormones, we developed an approach based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). To our knowledge, this represents the first report of their simultaneous measurement in HIV-TB individuals and the comparison with healthy donors, obtaining statistically higher plasma levels of DHEA, AET and 7-oxo-DHEA in patients. Moreover, we found that concentrations of 7-oxo-DHEA positively correlated with absolute CD4+ T cell counts, nadir CD4+ T cell values and with individuals who presented TB restricted to the lungs. This research contributes to understanding the role of these hormones in HIV-TB and emphasizes the importance of deepening their study in this context.

Limitations on human rights: are they justifiable to reduce the burden of TB in the era of MDR- and XDR-TB?

PubMed

Boggio, Andrea; Zignol, Matteo; Jaramillo, Ernesto; Nunn, Paul; Pinet, Geneviève; Raviglione, Mario

2008-01-01

Tuberculosis, in all its forms, poses a serious, demonstrable threat to the health of countless individuals as well as to health as a public good. MDR-TB and, in particular, the emergence of XDR-TB, have re-opened the debate on the importance, and nature, of treatment supervision for basic TB control and the management of drug-resistant TB. Enforcing compulsory measures regarding TB patients raises questions of respect for human rights. Yet, international law provides for rights-limiting principles, which would justify enforcing compulsory measures against TB patients who refuse to have diagnostic procedures or who refuse to be monitored and treated once disease is confirmed. This article analyzes under what circumstances compulsory measures for TB patients may be enforced under international law. Compulsory measures for TB patients may, in fact, be justified on legal grounds provided that these measures are foreseen in the law, that they are used as a last resort, and that safeguards are in place to protect affected individuals. The deadly nature of the disease, its epidemiology, the high case fatality rate, and the speed at which the disease leads to death when associated with HIV are proven.

Fluorometric determination of the activity of alkaline phosphatase based on the competitive binding of gold nanoparticles and pyrophosphate to CePO4:Tb nanorods.

PubMed

Xu, Ai-Zhen; Zhang, Li; Zeng, Hui-Hui; Liang, Ru-Ping; Qiu, Jian-Ding

2018-05-09

A fluorometric method is described for the determination of the activity of alkaline phosphatase (ALP). It relies on the competition between gold nanoparticles (AuNPs) and pyrophosphate (PPi) for the coordination sites on the surface of CePO 4 :Tb nanorods. The green fluorescence of the CePO 4 :Tb is reduced in the presence of AuNPs due to fluorescence resonance energy transfer (FRET), but can be restored on addition of PPi due to the stronger affinity of PPi to the CePO 4 :Tb. In the presence of ALP, PPi is hydrolyzed to form phosphate which has much weaker affinity for the CePO 4 :Tb. Hence, the AuNPs will reassemble on the CePO 4 :Tb, and fluorescence is reduced. Fluorescence drops linearly in the 0.2 to 100 U·L -1 activity range, and the detection limit is 60 mU·L -1 (at S/N = 3). The method does not require any modification of the surface of the CePO 4 :Tb and is highly sensitive and selective. The inhibition of ALP activity by Na 3 VO 4 was also studied. In our perception, the method may find application in the diagnosis of ALP-related diseases, in screening for inhibitors, and in studies on ALP-related functions in biological systems. Graphical abstract A assay for the detection of alkaline phosphatase is proposed based on the fluorescence resonance energy transfer between CePO 4 :Tb and AuNPs. It relies on the competitive binding of AuNPs and pyrophosphate (PPi) to CePO 4 :Tb and the hydrolysis of PPi by ALP.

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.

Immune TB Antibody Phage Display Library as a Tool To Study B Cell Immunity in TB Infections.

PubMed

Hamidon, Nurul Hamizah; Suraiya, Siti; Sarmiento, Maria E; Acosta, Armando; Norazmi, Mohd Nor; Lim, Theam Soon

2018-03-01

B cells and in particular antibodies has always played second fiddle to cellular immunity in regard to tuberculosis (TB). However, recent studies has helped position humoral immunity especially antibodies back into the foray in relation to TB immunity. Therefore, the ability to correlate the natural antibody responses of infected individuals toward TB antigens would help strengthen this concept. Phage display is an intriguing approach that can be utilized to study antibody-mediated responses against a particular infection via harvesting the B cell repertoire from infected individuals. The development of disease-specific antibody libraries or immune libraries is useful to better understand antibody-mediated immune responses against specific disease antigens. This study describes the generation of an immune single-chain variable fragment (scFv) library derived from TB-infected individuals. The immune library with an estimated diversity of 10 9 independent clones was then applied for the identification of monoclonal antibodies against Mycobacterium tuberculosis α-crystalline as a model antigen. Biopanning of the library isolated three monoclonal antibodies with unique gene usage. This strengthens the role of antibodies in TB immunity in addition to the role played by cellular immunity. The developed library can be applied against other TB antigens and aid antibody-derived TB immunity studies in the future.

A world of cities and the end of TB

PubMed Central

Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

2016-01-01

The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. PMID:26884491

Accelerating TB notification from the private health sector in Delhi, India.

PubMed

Kundu, Debashish; Chopra, Kamal; Khanna, Ashwani; Babbar, Neeti; Padmini, T J

2016-01-01

In India, almost half of all patients with tuberculosis (TB) seek care in the private sector as the first point of care. The national programme is unable to support such TB patients and facilitate effective treatment, as there is no information on TB and Multi or Extensively Drug Resistant TB (M/XDR-TB) diagnosis and treatment in private sector. To improve this situation, Government of India declared TB a notifiable disease for establishing TB surveillance system, to extend supportive mechanism for TB treatment adherence and standardised practices in the private sector. But TB notification from the private sector is a challenge and still a lot needs to be done to accelerate TB notification. Delhi State TB Control Programme had taken initiatives for improving notification of TB cases from the private sector in 2014. Key steps taken were to constitute a state level TB notification committee to oversee the progress of TB notification efforts in the state and direct 'one to one' sensitisation of private practitioners (PPs) (in single PP's clinic, corporate hospitals and laboratories) by the state notification teams with the help of available tools for sensitising the PP on TB notification - TB Notification Government Order, Guidance Tool for TB Notification and Standards of TB Care in India. As a result of focussed state level interventions, without much external support, there was an accelerated notification of TB cases from the private sector. TB notification cases from the private sector rose from 341 (in 2013) to 4049 (by the end of March 2015). Active state level initiatives have led to increase in TB case notification. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

HIV screening among TB patients and co-trimoxazole preventive therapy for TB/HIV patients in Addis Ababa: facility based descriptive study.

PubMed

Denegetu, Amenu Wesen; Dolamo, Bethabile Lovely

2014-01-01

Collaborative TB/HIV management is essential to ensure that HIV positive TB patients are identified and treated appropriately, and to prevent tuberculosis (TB) in HIV positive patients. The purpose of this study was to assess HIV case finding among TB patients and Co-trimoxazole Preventive Therapy (CPT) for HIV/TB patients in Addis Ababa. A descriptive cross-sectional, facility-based survey was conducted between June and July 2011. Data was collected by interviewing 834 TB patients from ten health facilities in Addis Ababa. Both descriptive and inferential statistics were used to summarize and analyze findings. The proportion of TB patients who (self reported) were offered for HIV test, tested for HIV and tested HIV positive during their anti-TB treatment follow-up were; 87.4%, 69.4% and 20.2%; respectively. Eighty seven HIV positive patients were identified, who knew their status before diagnosed for the current TB disease, bringing the cumulative prevalence of HIV among TB patients to 24.5%. Hence, the proportion of TB patients who knew their HIV status becomes 79.9%. The study revealed that 43.6% of those newly identified HIV positives during anti-TB treatment follow-up were actually treated with CPT. However, the commutative proportion of HIV positive TB patients who were ever treated with CPT was 54.4%; both those treated before the current TB disease and during anti-TB treatment follow-up. HIV case finding among TB patients and provision of CPT for TB/HIV co-infected patients needs boosting. Hence, routine offering of HIV test and provision of CPT for PLHIV should be strengthened in-line with the national guidelines.

Tuberculosis after liver transplantation in a large center in New York City: QuantiFERON® -TB Gold-based pre-transplant screening performance and active tuberculosis post-transplant.

PubMed

Hand, Jonathan; Sigel, Keith; Huprikar, Shirish; Hamula, Camille; Rana, Meena

2018-04-01

Pre-transplant screening for latent tuberculosis infection (LTBI) is a complex consideration that varies by institution. Inconsistent performance of interferon-gamma release assay (IGRA) further complicates screening. Data regarding LTBI screening outcomes and test characteristics in a large, foreign-born pre-transplant population within the United States are limited. In this retrospective study, patients who received QuantiFERON ® -TB Gold (QFT) prior to liver transplantation (LT) were included. Characteristics of patients were compared by QFT result, and predictors of indeterminate results were evaluated. Similar comparisons were performed between patients who developed active TB and those who did not. Of 148 patients screened, the rate of positive, indeterminate, and negative testing was 13.5% (20/148), 27% (40/148), and 59% (88/148), respectively. An indeterminate QFT result was more than 16 times more likely in patients with a Model for End-stage Liver Disease score >25 (odds ratio [OR] 16.7; 95% confidence interval [CI], 2.1-132.0; P = .008) and more than 4 times when performed in our institution's lab compared with commercial lab (OR 4.1; 95% CI, 1.34-12.44; P = .013). The overall TB incidence was 1102/100 000 transplant cases. No patient who developed active TB had a positive QFT. All were born outside of the United States (P = .06) and had pre-transplantation chest imaging demonstrating granulomatous disease (P = .006). Our experience further highlights the challenges of LTBI screening prior to LT and suggests that QFT may be a poor predictor of active TB in higher risk pre-transplant populations. Candidates should be screened as early as possible to optimize QFT performance, and local epidemiological data should be used to create institution-specific screening protocols in areas with large populations from TB-endemic regions. Management should consider TB risk factors, QFT, and imaging instead of reliance on QFT testing alone. © 2018 John Wiley

Progress and challenges in TB vaccine development

PubMed Central

Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H.E.; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

2018-01-01

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development. PMID:29568497

Progress and challenges in TB vaccine development.

PubMed

Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H E; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

2018-01-01

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our "failed" trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

Exploring workplace TB interventions with foreign-born Latino workers.

PubMed

Eggerth, Donald E; Keller, Brenna M; Flynn, Michael A

2018-05-15

Persons born outside the United States are more likely to be diagnosed with tuberculosis disease (TB) than native-born individuals. Foreign-born Latinos at risk of TB may be difficult to reach with public health interventions due to cultural and institutional barriers. Workplaces employing large concentrations of foreign-born Latinos may be useful locations for TB interventions targeting this high-risk population. This study used a two-phase approach to investigate the feasibility of workplace TB interventions. The first phase investigated employer knowledge of TB and receptiveness to allowing TB interventions in their businesses through 5 structured interviews. The second phase investigated foreign-born workers' knowledge of TB and their receptiveness to receiving TB interventions in their places of employment through 12 focus groups stratified by gender and education. Phase 1: Only 1 of the 5 employers interviewed had a high level of knowledge about TB, and three had no knowledge other than that TB was a disease that involved coughing. They were receptive to workplace TB interventions, but were concerned about lost productivity and customers finding out if an employee had TB. Phase 2: There was no observed differences in responses between gender and between the bottom two education groups, so the final analysis took place between a gender-combined lower education group and higher education group. The higher education group tended to have knowledge that was more accurate and to view TB as a disease associated with poverty. The lower education group tended to have more misconceptions about TB and more often expressed concern that their employers would not support worksite interventions. The results from both phases indicate that more TB education is needed among both foreign-born Latino workers and their employers. Obstacles to implementing workplace TB interventions include knowledge, potential productivity loss, employer liability, and perceived customer response

Addressing diabetes mellitus as part of the strategy for ending TB

PubMed Central

Harries, Anthony D.; Kumar, Ajay M.V.; Satyanarayana, Srinath; Lin, Yan; Zachariah, Rony; Lönnroth, Knut; Kapur, Anil

2016-01-01

As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases. PMID:26884497

Survey on medicinal plants traditionally used in Senegal for the treatment of tuberculosis (TB) and assessment of their antimycobacterial activity.

PubMed

Diop, ElHadji Assane; Queiroz, Emerson Ferreira; Kicka, Sébastien; Rudaz, Serge; Diop, Tahir; Soldati, Thierry; Wolfender, Jean-Luc

2018-04-24

In West Africa, populations are used to taking traditional medicine as a first aid against common health problems. In this aspect, many plants are claimed to be effective in the treatment of Tuberculosis (TB), which according to the World Health Organization (WHO) remains one of the world's deadliest communicable diseases. The main aim of this study was to identify plants used to treat TB-symptoms by the population of Senegal and to evaluate their possible concomitant use with clinically approved TB-drugs. This approach allowed the selection of plants effectively used in traditional medicine. In order to verify if the usage of some of these plants can be rationalized, the activity of their traditional preparations was assessed with both an intracellular and extracellular antimycobacterial host-pathogen assays. An ethnopharmacological survey conducted on 117 TB-patients and 30 healers in Senegal from March to May 2014. The questionnaires were focused on the use of medicinal plants to treat common TB -symptoms (cough longer than 2 weeks, fever, night sweats, weight loss and bloody sputum). Local plant names, utilized organs (herbal drugs) and traditional formulations of the plants were recorded. Extracts were prepared by mimicking the traditional decoction in boiling water and screened for their antimycobacterial activity using Mycobacterium marinum, as a validated TB surrogate, and an Acanthamoeba castellanii - M. marinum whole-cell based host-pathogen assay, to detect anti-infective activities. By the end of the survey, nearly 30 plants were cited and the 12 most cited herbal drugs were collected and their usage documented by extensive literature search. Extracts of the chosen herbs were screened with the described assays; with a main focus on traditional formulas (mainly herbal decoctions). Two of the water extracts from Combretum aculeatum and Guiera senegalensis showed significant antimycobacterial activities when compared to the positive control drug (rifampin

[USE OF QuantiFERON-TB Gold in Tube AND T-SPOT.TB FOR DIAGNOSING PATIENTS WITH SUSPECTED PULMONARY TUBERCULOSIS].

PubMed

Okimoto, Niro; Kurihara, Takeyuki; Miyashita, Naoyuki

2016-04-01

We analyzed the use of QFT-TB Gold in Tube and T-SPOT.TB in diagnosing patients with suspected pulmonary tuberculosis. We evaluated 122 patients with suspected pulmonary tuberculosis (where chest X-ray showed consolidation or. tumor shadow in predilection sites of pulmonary tuberculosis and through contact investigation). QFT-TB Gold and T-SPOT.TB were performed for all the patients. The positive response rate and history of pulmonary tuberculosis in patients who showed positive results for the tests were evaluated. Ninteen patients showed positive results for QFT-TB Gold, and 9, for T-SPOT.TB. Four patients showed positive results for QFT-TB Gold, and 3, for T-SPOT.TB in 4 patients with active tuberculosis. The patients without active tuberculosis whose IGRAs were positive (old pulmonary tuberculosis, Mycobacterium avium cmplex, pneumonia, lung cancer, pulmonary sequestration, bronchiectasis) had a past history of pulmonary tuberculosis. The positive result rate of QFT?-TB Gold was higher than that of T-SPOT.TB in the subjects with suspected pulmonary tuberculosis. We think that QFT-TB Gold reflected the past history of pulmonary tuberculosis.

Anaemia in patients with HIV-associated TB: relative contributions of anaemia of chronic disease and iron deficiency.

PubMed

Kerkhoff, A D; Meintjes, G; Opie, J; Vogt, M; Jhilmeet, N; Wood, R; Lawn, S D

2016-02-01

Anaemia commonly complicates both human immunodeficiency virus (HIV) infection and tuberculosis (TB), contributing substantially to morbidity and mortality. The mechanisms underlying anaemia and corresponding treatments in co-infected patients are poorly defined. To determine the relative contributions of anaemia of chronic disease (ACD) and iron deficiency to anaemia in patients with HIV-associated TB. Consecutively recruited hospitalised (n = 102) and matched ambulatory patients (n = 51) with microbiologically confirmed HIV-associated TB in Cape Town, South Africa, were included. Haemoglobin levels, iron status markers, hepcidin and pro-inflammatory cytokines in blood were measured. We determined the prevalence of ACD and iron-deficiency anaemia (IDA) using seven different published definitions of IDA. More than 80% of enrolled HIV-associated TB patients were anaemic, and anaemia was more severe among in-patients. Over 95% of anaemic HIV-associated TB patients had ACD, whereas the proportion with IDA using a range of seven different definitions was low overall (median <3%, range 0-32.6) in both patient groups. The proportion with IDA and hepcidin concentration ⩿ 20.0 ng/ml (predictive of responsiveness to oral iron supplementation) was also very low (median <3%, range 0-15.1). ACD was the predominant cause underlying anaemia in HIV-associated TB patients, and IDA was very uncommon in this setting. The majority of anaemic HIV-associated TB patients were unlikely to benefit from oral iron supplementation.

A world of cities and the end of TB.

PubMed

Prasad, Amit; Ross, Alex; Rosenberg, Paul; Dye, Christopher

2016-03-01

The WHO's End TB Strategy aims to reduce TB deaths by 95% and incidence by 90% between 2015 and 2035. As the world rapidly urbanizes, more people could have access to better infrastructure and services to help combat poverty and infectious diseases, including TB. And yet large numbers of people now live in overcrowded slums, with poor access to urban health services, amplifying the burden of TB. An alignment of the Sustainable Development Goals (SDGs) for health and for urban development provides an opportunity to accelerate the overall decline in infection and disease, and to create cities free of TB. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

More significance of TB-IGRA except for the diagnose of tuberculosis.

PubMed

Xu, Jun-Chi; Li, Ze-Yi; Chen, Xin-Nian; Shi, Cui-Lin; Wu, Mei-Ying; Chen, Hui; Zhu, Xiao-Yan; Song, Hua-Feng; Wu, Min-Juan; Xu, Ping

2018-01-01

Tuberculosis (TB)-interferon gamma release assay (IGRA) test has the characteristics of short time, high specificity, and high sensitivity, but it lacks the correlation research between TB-IGRA test results and body's immune cells, disease progression and prognosis, which is explored in this study. A retrospective study was carried out on positive TB-IGRA patients who were infected with TB and diagnosed at our hospital from January 2014 to June 2015. The TB-IGRA, routine blood test, T-cell subgroup data were collected for statistical analysis. TB-IGRA results were in positive proportion to the lymphocytes, CD4 + T cells and CD4 + CD28 + T cells, whereas negative to the Treg cells. Patient with unilateral pulmonary lesion had higher TB-IGRA than those with bilateral pulmonary lesions. After the stimulation of TB-specific antigen, the proportion of CD4 + IFN-γ + and CD8 + IFN-γ + T Tcells were both increased and the CD4 + IFN-γ + T had positive correlation with the value of TB-IGRA. IFN-γ was tested with TB-IGRA in patients with TB by the specific TB T cells and correlated with the lymphocytes, while the lymphocytes also closely related to the host's anti-TB immunity and disease outcome. Hence the result of TB-IGRA could reflect the specific anti-TB immunity ability of the host, disease progression and prognosis. This study further expands the application scope of TB-IGRA technology in the diagnosis of TB and lays a foundation for clinical practice to understand the immunity state of the patients with TB and the application of auxiliary clinical immunity regulators. © 2017 Wiley Periodicals, Inc.

Analysis of Factors Influencing Diagnostic Accuracy of T-SPOT.TB for Active Tuberculosis in Clinical Practice.

PubMed

Zhang, Lifan; Shi, Xiaochun; Zhang, Yueqiu; Zhang, Yao; Huo, Feifei; Zhou, Baotong; Deng, Guohua; Liu, Xiaoqing

2017-08-10

T-SPOT.TB didn't perform a perfect diagnosis for active tuberculosis (ATB), and some factors may influence the results. We did this study to evaluate possible factors associated with the sensitivity and specificity of T-SPOT.TB, and the diagnostic parameters under varied conditions. Patients with suspected ATB were enrolled prospectively. Influencing factors of the sensitivity and specificity of T-SPOT.TB were evaluated using logistic regression models. Sensitivity, specificity, predictive values (PV), and likelihood ratios (LR) were calculated with consideration of relevant factors. Of the 865 participants, 205 (23.7%) had ATB, including 58 (28.3%) microbiologically confirmed TB and 147 (71.7%) clinically diagnosed TB. 615 (71.7%) were non-TB. 45 (5.2%) cases were clinically indeterminate and excluded from the final analysis. In multivariate analysis, serous effusion was the only independent risk factor related to lower sensitivity (OR = 0.39, 95% CI: 0.18-0.81) among patients with ATB. Among non-TB patients, age, TB history, immunosuppressive agents/glucocorticoid treatment and lymphocyte count were the independent risk factors related to specificity of T-SPOT.TB. Sensitivity, specificity, PV+, PV-, LR+ and LR- of T-SPOT.TB for diagnosis of ATB were 78.5%, 74.1%, 50.3%, 91.2%, 3.0 and 0.3, respectively. This study suggests that influencing factors of sensitivity and specificity of T-SPOT.TB should be considered for interpretation of T-SPOT.TB results.

Integrated Source Case Investigation for Tuberculosis (TB) and HIV in the Caregivers and Household Contacts of Hospitalised Young Children Diagnosed with TB in South Africa: An Observational Study

PubMed Central

Lala, Sanjay G.; Little, Kristen M.; Tshabangu, Nkeko; Moore, David P.; Msandiwa, Reginah; van der Watt, Martin; Chaisson, Richard E.; Martinson, Neil A.

2015-01-01

Background Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. Methods Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. Results Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. Conclusion In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed

High Incidence of Tuberculosis Infection in Rheumatic Diseases and Impact for Chemoprophylactic Prevention of Tuberculosis Activation during Biologics Therapy

PubMed Central

Bai, Fengmin; Zhang, Shu; Jiang, Ting; Shen, Jie; Zhu, Qi; Yue, Tao; Shao, Lingyun; Gao, Yan; Feng, Yun; Weng, Xinhua; Zou, Hejian; Zhang, Ying

2013-01-01

We conducted a long-term follow-up study in patients with rheumatic diseases who were candidates for biologics treatment to evaluate the effects of biologic agents on the risk of tuberculosis infection and the effect of prophylactic treatment on tuberculosis activation. One hundred one patients with rheumatic diseases who were candidates for biologics treatment were recruited, and 57 healthy subjects were recruited as controls. Tuberculin skin test (TST) and the T-SPOT.TB test were performed for all subjects at baseline. Follow-up testing by the T-SPOT.TB assay was performed every 6 months in patients with rheumatic diseases and at 2 years of recruitment in the healthy controls. In patients with rheumatic diseases and healthy controls, the TST-positive (induration, ≥10 mm) rates were 37.6% (38/101) and 34.0% (18/53), respectively (P > 0.05), while the T-SPOT.TB-positive rates were 46.5% (47/101) and 21.1 (12/57), respectively (P = 0.0019). Fifty-two patients were followed up at month 6 with a T-SPOT.TB-positive rate of 40.4%, and 49 were followed up for ≥12 months with a T-SPOT.TB-positive rate of 36.7%, with no significant difference in the positive rate at different time points including baseline (P > 0.05). Long-term follow-up revealed that conversion to T-SPOT.TB positivity occurred only in the biologics treatment group, with a positive conversion rate of 11.2% (4/38). Most importantly, no latent tuberculosis developed into active tuberculosis during follow-up with T-SPOT.TB screening and preemptive treatment with isoniazid. Biologics treatment appears to increase the risk of tuberculosis infection. However, tuberculosis activation could be prevented by preemptive isoniazid treatment in patients with latent tuberculosis infection while receiving biologics therapy. PMID:23554465

New drugs and regimens for treatment of TB

PubMed Central

Leibert, Eric; Rom, William N

2013-01-01

Tools for effective TB control have been available for years. Case finding, active medications, case management and directly observed therapy are the foundations for the management of TB. The current TB epidemic, centered in resource-limited settings is fueled by the HIV-1 epidemic. Lack of ability to diagnose and treat drug-resistant TB has led to development of more extensive patterns of resistance. Among the currently available drugs, there is reason to hope that rifamycins paired with fluoroquinolones will lead to shorter treatment regimens for drug-susceptible TB. As the result of novel public-private collaborations and investments of resources, new drugs are being developed. These include TMC207, already shown to have activity early in the treatment of multidrug-resistant TB and others that are likely to be active against persistor organisms, and have the prospect to dramatically shorten treatment courses for active and latent TB. Given that these drugs have novel mechanisms of action, combinations have the prospect to be highly active even against multidrug-resistant organisms. PMID:20586565

Electrocatalysis of carbon black- or poly(diallyldimethylammonium chloride)-functionalized activated carbon nanotubes-supported Pd-Tb towards methanol oxidation in alkaline media

NASA Astrophysics Data System (ADS)

Wang, Li; Wang, Yi; Li, An; Yang, Yunshang; Tang, Qinghu; Cao, Hongbin; Qi, Tao; Li, Changming

2014-07-01

The Pd-Tb/C catalysts with different Pd/Tb ratios were synthesized by a simple simultaneous reduction reaction with sodium borohydride in aqueous solution. The structure and morphology of those catalysts had been characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The electrocatalytic performance of those catalysts for methanol oxidation in alkaline media was investigated using cyclic voltammetry (CV), linear sweep voltammetry (LSV) and CO stripping experiments. It is found that the 20%Pd-1%Tb/C catalyst has a higher catalytic activity than the 20%Pd/C catalyst, but the effect of Tb cannot be explained by a bi-functional mechanism. According to the X-Ray photoelectron spectroscopy (XPS) analyses, it is suggested that the higher content of metallic Pd caused by the addition of Tb contributes to the better catalytic activity of 20%Pd-1%Tb/C. Based on the good electrocatalytic performance of 20%Pd-1%Tb/C, the 20%Pd-1%Tb catalyst supported on poly(diallyldimethylammonium chloride) (PDDA)-functionalized activated carbon nanotubes was prepared, and it exhibits a better catalytic activity. The improvement mainly results from the further increase of metallic Pd due to the presence of PDDA.

Killer (FASL regulatory) B cells are present during latent TB and are induced by BCG stimulation in participants with and without latent tuberculosis.

PubMed

van Rensburg, Ilana C; Loxton, Andre G

2018-01-01

Regulatory B cells (Bregs) have been shown to be present during several disease states. The phenotype of the cells is not completely defined and the function of these cells differ between disease. The presence of FASL expressing (killer) B cells during latent and successfully treated TB disease have been shown but whether these cells are similar to regulatory B cells remain unclear. We assessed the receptor expression of FASL/IL5 (killer B cells), CD24/CD38 (regulatory B cells) on whole peripheral blood of participants with untreated active TB and healthy controls. We then isolated B cells from a second cohort of M.tb exposed (Quantiferon (QFN) positive) and unexposed (Quantiferon negative) HIV negative participants, and evaluated the frequency of killer B cells induced following stimulation with BCG and/or CD40 and IL5. Our data reveal no difference in the expression on CD24 and CD38 between participants with active TB and the controls. There was also no difference in the frequency of regulatory B cells measured in the peripheral blood mononuclear cells (PBMC) fraction between latent TB and uninfected controls. We did however notice that regulatory B cells (CD24hiCD38hi) population express the FASL receptor. The expression of killer B cell phenotype (CD178+IL5RA+) was significantly higher in controls compared to those with active TB disease (1,06% vs 0,455%). Furthermore, we found that BCG restimulation significantly induced the FASL/IL5RA B cells but this was only evident in the QFN positive group. Our data suggest that both regulatory and killer B cells are present during latent and active TB disease but that the frequency of these populations are increased during latent disease. We also show that the FASL+IL5RA+ B killer B cells are induced in latent TB infection following BCG restimulation but whether these cells are indicative of protection remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dynamic Changes in Pro- and Anti-Inflammatory Cytokine Profiles and Gamma Interferon Receptor Signaling Integrity Correlate with Tuberculosis Disease Activity and Response to Curative Treatment▿

PubMed Central

Sahiratmadja, Edhyana; Alisjahbana, Bachti; de Boer, Tjitske; Adnan, Iskandar; Maya, Anugrah; Danusantoso, Halim; Nelwan, Ronald H. H.; Marzuki, Sangkot; van der Meer, Jos W. M.; van Crevel, Reinout; van de Vosse, Esther; Ottenhoff, Tom H. M.

2007-01-01

Pro- and anti-inflammatory cytokines and their signaling pathways play key roles in protection from and pathogenesis of mycobacterial infection, and their balance and dynamic changes may control or predict clinical outcome. Peripheral blood cells' capacity to produce proinflammatory (tumor necrosis factor alpha [TNF-α], interleukin-12/23p40 [IL-12/23p40], and gamma interferon [IFN-γ]) and anti-inflammatory (IL-10) cytokines in response to Mycobacterium tuberculosis or unrelated stimuli (lipopolysaccharide, phytohemagglutinin) was studied in 93 pulmonary tuberculosis (TB) patients and 127 healthy controls from Indonesia. Their cells' ability to respond to IFN-γ was examined to investigate whether M. tuberculosis infection can also inhibit IFN-γ receptor (IFN-γR) signaling. Although there was interindividual variability in the observed responses, the overall results revealed that M. tuberculosis-induced TNF-α and IFN-γ levels showed opposite trends. Whereas TNF-α production was higher in active-TB patients than in controls, IFN-γ production was strongly depressed during active TB, correlated inversely with TB disease severity, and increased during therapy. By contrast, mitogen-induced IFN-γ production, although lower in patients than in controls, did not change during treatment, suggesting an M. tuberculosis-specific and reversible component in the depression of IFN-γ. Depressed IFN-γ production was not due to decreased IL-12/IL-23 production. Importantly, IFN-γ-inducible responses were also significantly depressed during active TB and normalized during treatment, revealing disease activity-related and reversible impairment in IFN-γR signaling in TB. Finally, IFN-γ/IL-10 ratios significantly correlated with TB cure. Taken together, these results show that M. tuberculosis-specific stimulation of IFN-γ (but not TNF-α) production and IFN-γR signaling are significantly depressed in active TB, correlate with TB disease severity and activity, and

An intervention of active TB case finding among smokers attending routine primary care facilities in China: an exploratory study.

PubMed

Wei, Xiaolin; Zou, Guangyan; Chong, Marc Kc; Xu, Lin

2015-09-01

Smoking is an important risk factor of TB. However, no studies have been conducted to identify TB cases from smokers. We assessed the process and initial impact of active case finding among smokers at primary care facilities in a setting with high smoking rates and TB burden. A prospective quasi-experimental study was conducted in para-urban communities in Yunnan China between September 2013 and June 2014. Smokers attending primary care facilities in the intervention group were prescribed chest X-rays if they had diabetes or TB symptoms, or were elders or close contacts of TB patients. Those with X-rays suggestive of TB were referred to TB dispensaries for diagnosis. Passive case finding was practiced in the control group. In the intervention group, we screened 471 smokers with high risks of TB, of whom 73% took chest X-ray examinations. Eight TB cases were diagnosed, reflecting a 1.7% yield rate of all screened smokers. Smokers with diabetes (OR 6.003, 95% CI 1.057-34.075) were more likely to have TB compared with those without. In total, the intervention group reported significantly higher TB notification rate compared with the control group (38.6 vs 22.9 per 100 000, p=0.016). Active case finding among smokers with high risks of TB was feasible and contributed to improved notification rates. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Framework of behavioral indicators evaluating TB health promotion outcomes: a modified Delphi study of TB policymakers and health workers.

PubMed

Li, Ying; Ehiri, John; Hu, Daiyu; Oren, Eyal; Cao, Jia

2015-12-15

Although TB health promotion directed at policy makers and healthcare workers (HCWs) is considered important to tuberculosis (TB) control, no indicators currently assess the impact of such promotional activities. This article is the second in a series of papers that seek to establish a framework of behavioral indicators for outcome evaluation of TB health promotion, using the Delphi method. In the first article, we sought to establish a framework of behavioral indicators for outcome evaluation of TB health promotion among TB suspects and patients. The objective of this second article is to present an indicator framework that can be used to assess behavioral outcomes of TB health promotion directed at policy makers and HCWs. A two-round, modified Delphi method was used to establish the indicators. Sixteen experts who were knowledgeable and experienced in the field of TB control were consulted in Delphi surveys. A questionnaire was developed following 4 steps, and involved ranking indicators on a five-point Likert scale. The consensus level was 70 %. Median, mode, and Coefficient of variation (CV) were used to describe expert responses. An authority coefficient (Cr) was used to assess the degree of each expert's authority. Consensus was achieved following the two survey rounds and several iterations among the experts. For TB health-promotion activities directed at policymakers, the experts reached consensus on 2 domains ("Resource inputs" and "Policymaking and monitoring behaviors"), 4 subdomains ("Human resources" among others), and 13 indicators ("Human resources per 100,000 person" among others). For TB health-promotion activities directed at HCWs, the experts reached consensus on 5 domains ("Self-protective behaviors" among others), 6 sub-domains ("Preventing infection" among others), and 15 indicators ("Average hours of daily workplace disinfection by ultraviolet radiation" among others). This study identified a conceptual framework of core behavioral indicators

TB tracer teams in South Africa: knowledge, practices and challenges of tracing TB patients to improve adherence.

PubMed

Bristow, Claire C; Podewils, Laura Jean; Bronner, Liza Ellen; Bantubani, Nonkqubela; Walt, Martie van der; Peters, Annatjie; Mametja, David

2013-09-04

In 2008-2009 the South African National Tuberculosis (TB) Program (NTP) implemented a national pilot project, the TB Tracer Project, aiming to decrease default rates and improve patient outcomes. The current study aimed to inform the NTP by describing the knowledge, attitudes, and practices of TB program personnel involved with tracing activities. A self-administered written questionnaire was sent to TB staff, managers and tracer team leaders to assess basic TB knowledge, attitudes and practices. Descriptive statistics were used to summarize results and the chi-squared statistic was used to compare responses of staff at facilities that participated in the TB Tracer Project (tracer) and those that followed standard NTP care (non-tracer). Of 560 total questionnaires distributed, 270 were completed and returned (response rate 48%). Total TB knowledge ranged from 70.8-86.3% correct across all response groups. However, just over half (range 50-59.3%) of each respondent group was able to correctly identify the four components of a DOT encounter. A patient no longer feeling sick was cited by 72.1% of respondents as the reason patients fail to adhere to treatment. Tracer teams were viewed as an effective means to get patients to return to treatment by 96.3% of health facility level respondents. Tracer team leaders reported concerns including lack of logistical support (41.7%), insufficient physical safety precautions (41.7%), and inadequate protection from contracting TB (39.1%). Upon patients returning to treatment at the clinic, facilities included in the TB Tracer Project were significantly more likely to discuss alternate DOTS arrangements than non-tracer facilities (79.2 vs. 66.4%, p = 0.03). This study identified key components of knowledge, attitudes, and practices regarding TB patient tracing activities in South Africa. Educating patients on the essential need to complete treatment irrespective of clinical symptoms may help improve treatment adherence. Future

TB tracer teams in South Africa: knowledge, practices and challenges of tracing TB patients to improve adherence

PubMed Central

2013-01-01

Background In 2008–2009 the South African National Tuberculosis (TB) Program (NTP) implemented a national pilot project, the TB Tracer Project, aiming to decrease default rates and improve patient outcomes. The current study aimed to inform the NTP by describing the knowledge, attitudes, and practices of TB program personnel involved with tracing activities. Methods A self-administered written questionnaire was sent to TB staff, managers and tracer team leaders to assess basic TB knowledge, attitudes and practices. Descriptive statistics were used to summarize results and the chi-squared statistic was used to compare responses of staff at facilities that participated in the TB Tracer Project (tracer) and those that followed standard NTP care (non-tracer). Results Of 560 total questionnaires distributed, 270 were completed and returned (response rate 48%). Total TB knowledge ranged from 70.8-86.3% correct across all response groups. However, just over half (range 50–59.3%) of each respondent group was able to correctly identify the four components of a DOT encounter. A patient no longer feeling sick was cited by 72.1% of respondents as the reason patients fail to adhere to treatment. Tracer teams were viewed as an effective means to get patients to return to treatment by 96.3% of health facility level respondents. Tracer team leaders reported concerns including lack of logistical support (41.7%), insufficient physical safety precautions (41.7%), and inadequate protection from contracting TB (39.1%). Upon patients returning to treatment at the clinic, facilities included in the TB Tracer Project were significantly more likely to discuss alternate DOTS arrangements than non-tracer facilities (79.2 vs. 66.4%, p = 0.03). Conclusions This study identified key components of knowledge, attitudes, and practices regarding TB patient tracing activities in South Africa. Educating patients on the essential need to complete treatment irrespective of clinical symptoms may

Migration, TB control and elimination: Whom to screen and treat.

PubMed

Rendon, A; Centis, R; Zellweger, J-P; Solovic, I; Torres-Duque, C A; Robalo Cordeiro, C; de Queiroz Mello, F C; Manissero, D; Sotgiu, G

Tuberculosis (TB) in migrants represents an important clinical and public health threat, particularly in low TB incidence countries. The current review is aimed to assess issues related to screening and treatment of migrants with latent TB infection or TB disease. Copyright © 2017 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.

Outbreak column 21: Tuberculosis (TB): Still a nosocomial threat.

PubMed

Curran, Evonne T

2018-05-01

This outbreak column explores the epidemiology and infection prevention guidance on tuberculosis (TB) in the UK. The column finds that, at present, national guidance leaves UK hospitals ill-prepared to prevent nosocomial TB transmission. Reasons for this conclusion are as follows: (1) while TB is predominantly a disease that affects people with 'social ills', it has the potential to infect anyone who is sufficiently exposed; (2) nosocomial transmission is documented throughout history; (3) future nosocomial exposures may involve less treatable disease; and (4) current UK guidance is insufficient to prevent nosocomial transmission and is less than that advocated by the World Health Organization and the Centers for Disease Control and Prevention.

"The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" - Meeting report.

PubMed

Boggiano, Cesar; Eichelberg, Katrin; Ramachandra, Lakshmi; Shea, Jaqueline; Ramakrishnan, Lalita; Behar, Samuel; Ernst, Joel D; Porcelli, Steven A; Maeurer, Markus; Kornfeld, Hardy

2017-06-14

Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission. Copyright © 2017.

Multidrug-Resistant TB

PubMed Central

Cox, Helen; Coomans, Fons

2016-01-01

Abstract The right to enjoy the benefits of scientific progress (REBSP) is a little-known but potentially valuable right that can contribute to rights-based approaches to addressing multidrug-resistant TB (MDR-TB). We argue that better understanding of the REBSP may help to advance legal and civil society action for health rights. While the REBSP does not provide an individual entitlement to have a new drug developed for MDR-TB, it sets up entitlements to expect a state to establish a legislative and policy framework aimed at developing scientific capacity to address the most important health issues and at disseminating the outcomes of scientific research. By making scientific findings available and accessible, people can be enabled to claim the use of science for social benefits. Inasmuch as the market fails to address neglected diseases such as MDR-TB, the REBSP provides a potential counterbalance to frame a positive obligation on states to both marshal their own resources and to coordinate the actions of multiple other actors towards this goal, including non-state actors. While the latter do not hold the same level of accountability as states, the REBSP can still enable the recognition of obligations at a level of “soft law” responsibilities. PMID:27780997

Deterministic SLIR model for tuberculosis disease mapping

NASA Astrophysics Data System (ADS)

Aziz, Nazrina; Diah, Ijlal Mohd; Ahmad, Nazihah; Kasim, Maznah Mat

2017-11-01

Tuberculosis (TB) occurs worldwide. It can be transmitted to others directly through air when active TB persons sneeze, cough or spit. In Malaysia, it was reported that TB cases had been recognized as one of the most infectious disease that lead to death. Disease mapping is one of the methods that can be used as the prevention strategies since it can displays clear picture for the high-low risk areas. Important thing that need to be considered when studying the disease occurrence is relative risk estimation. The transmission of TB disease is studied through mathematical model. Therefore, in this study, deterministic SLIR models are used to estimate relative risk for TB disease transmission.

Understanding social context on TB cases

NASA Astrophysics Data System (ADS)

Ariyanto, Y.; Wati, D. M.

2017-01-01

Tuberculosis (TB) nowadays still becomes one of the world’s deadliest communicable disease. More than half were in South-East Asia and Western Pacific Regions, including Indonesia. As developing country, Indonesia remains classic problems in overcoming TB, that is discontinuation on treatment. Most of discontinuation on treatment among TB patients are affected by diagnostic delay that caused by patient delay. These phenomena occur in many areas, rural to suburb, coastal to plantation, and so on, and they are related with social context among community that could be social capital for each community to deal with TB. Jember as one of county in East Java is known as plantation area. It also has a high prevalence of TB. This study focused on understanding about social context among community, especially on plantation area. This cross-sectional study involved in three districts of Jember, those are Tanggul, Pakusari, and Kalisat. The data were obtained directly from the TB patients, local community, and Primary Health Care (PHC) where the patients recorded. Spatial analysis and social network analysis (SNA) were applied to obtain health seeking behavior pattern among the TB patients coincide the community. Most of TB patients had already chosen health professionals to lead the treatment, although some of them remained to choose self-medication. Meanwhile, SNA showed that religious leader was considered as main part of countermeasures of TB. But they didn’t ever become central figures. So it can be concluded that there are other parts among community who can contribute due to combatting on TB.

TB in Vulnerable Populations

PubMed Central

Ugarte-Gil, César; Caro, Godofredo; Aylas, Rula; Castro, César; Lema, Claudia

2016-01-01

Abstract This article analyzes the factors associated with vulnerability of the Ashaninka, the most populous indigenous Peruvian Amazonian people, to tuberculosis (TB). By applying a human rights-based analytical framework that assesses public policy against human rights standards and principles, and by offering a step-by-step framework for a full assessment of compliance, it provides evidence of the relationship between the incidence of TB among the Ashaninka and Peru’s poor level of compliance with its human rights obligations. The article argues that one of the main reasons for the historical vulnerability of the Ashaninka to diseases such as TB is a lack of political will on the part of the national government to increase public health spending, ensure that resources reach the most vulnerable population, and adopt and invest in a culturally appropriate health system. PMID:27780999

Cough Due to TB and Other Chronic Infections: CHEST Guideline and Expert Panel Report.

PubMed

Field, Stephen K; Escalante, Patricio; Fisher, Dina A; Ireland, Belinda; Irwin, Richard S

2018-02-01

Cough is common in pulmonary TB and other chronic respiratory infections. Identifying features that predict whether pulmonary TB is the cause would help target appropriate individuals for rapid and cost-effective screening, potentially limiting disease progression and preventing transmission to others. A systematic literature search for individual studies to answer eight key questions (KQs) was conducted according to established Chest Organization methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014. Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search was undertaken in March 2017. Even where TB prevalence is greatest, most individuals with cough do not have pulmonary TB. There was no evidence that 1, 3, or 4 weeks' duration were better predictors than cough lasting ≥ 2 weeks to screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever, night sweats, hemoptysis, and/or weight loss in addition to cough (any World Health Organization [WHO]-endorsed symptom) increases the diagnostic sensitivity for TB. Although the diagnostic accuracy of symptom-based screening remains low, the negative predictive value of the WHO-endorsed symptom screen in PLWHIV may help to risk-stratify individuals who are not close TB contacts and who do not require further testing for pulmonary TB in resource-limited settings. However, pregnant PLWHIV are more likely to be asymptomatic, and the WHO-endorsed symptom screen is not sensitive enough to be reliable. Combined with passive case finding (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and possibly when less advanced. Whether outcomes are improved or transmission is reduced is unclear. Screening asymptomatic patients is cost-effective only in populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is more cost-effective than

Pattern of socio-economic and health aspects among TB patients and controls.

PubMed

Kapoor, A K; Deepani, Vijit; Dhall, Meenal; Kapoor, Satwanti

2016-10-01

Socio-economic and health-related factors have a significant impact on tuberculosis (TB) incidence among population residing in resource-scare settings. To evaluate the pattern of socio-economic and health-related factors among TB patients and control in Delhi, India. The present cross-sectional study was performed among 893 TB patients (or cases) and 333 healthy disease-free controls. The data for the present study was obtained from several district TB centres in north, west and south Delhi. The collected data was edited, coded and statistical analysed with the help of SPSS 20.0 version. Illiteracy and primary education were significant risk factors being associated with a TB. Rented housing condition had an odds ratio (OR) of 1.4 (95% confidence interval [CI]: 1.09-1.89) compared to owned housing condition. 3-5 individuals per room were 3 times more likely to be associated with a case of TB (95% CI: 2.49-4.41). Migrant individuals were 13 times more likely to be associated with a case of TB (95% CI: 8.77-19.78) in comparison to settled population. Daily consumption of non-vegetarian food also significantly contributed to case of TB with an OR of 3.4 (95% CI: 2.51-4.72). Loss of appetite and family TB served as significant health-related factors associated with TB risk. Lower educational status, rented household, individuals per room (as a measure of overcrowding) and migratory status served as prominent risk factors for TB disease. Preference and frequency of non-vegetarian food being consumed, night sweating, weight loss, loss of appetite, earlier TB and family TB were principle health-related risk factors associated with TB disease. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

TB Terms

MedlinePlus

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TB control programmes: the challenges for Africa.

PubMed

Harries, T

1996-11-01

Governmental neglect of tuberculosis (TB), inadequately managed and inaccurately designed TB control programs, population growth, and the HIV epidemic account for the resurgence of TB in sub-Saharan Africa. The World Health Organization and the International Union against TB and Lung Disease have developed a TB control strategy that aims to reduce mortality, morbidity, and transmission of TB. It aims for an 85% cure rate among detected new cases of smear-positive TB and a 70% rate of detecting existing smear-positive TB cases. The strategy involves the provision of short-course chemotherapy (SCC) to all identified smear-positive TB cases through directly observed treatment (DOTS). SCC treatment regimens for smear-positive pulmonary TB recommended for sub-Saharan African countries are: initial phase = daily administration over 2 months of streptomycin, rifampicin, isoniazid, and pyrazinamide; continuation phase = 3 doses over 4 months of isoniazid and rifampicin or daily administration of thiacetazone and isoniazid or of ethambutol and isoniazid. A TB control policy must be implemented to bring about effective TB control. The essential elements of this policy include political commitment, case detection through passive case-finding, SCC, a regular supply of essential drugs, and a monitoring and evaluation system. Political commitment involves establishing a National TB Control Program to be integrated into the existing health structure. Increased awareness of TB in the community and among health workers and a reference laboratory are needed to make case finding successful. A distribution and logistics system is needed to ensure uninterrupted intake of drugs throughout treatment. These regimens have been very successful and cost-effective but pose several disadvantages (e.g., heavy workload of recommended 3 sputum smear tests). A simplified approach involves 1 initial sputum smear for 6 months; 6-months, intermittent rifampicin-based therapy, 100% DOTS throughout

Development of Diazaquinomycin Class Antibiotics for the Treatment of Drug-Resistant TB Infections

DTIC Science & Technology

2016-10-01

exhibited weak antibacterial activity by targeting thymidylate synthase, though no reports of their anti-TB activity existed and our studies have suggested...Murphy, B. T. Diaza-anthracene antibiotics from a freshwater-derived actinomycete with selective antibacterial activity toward M. tuberculosis. ACS Inf...freshwater-derived actinomycete with selective antibacterial activity toward M. tuberculosis. ACS Infectious Diseases, 2015. 1: p. 168-174. (17) Mullowney

Proteomic profiling of eccrine sweat reveals its potential as a diagnostic biofluid for active tuberculosis.

PubMed

Adewole, Olanisun Olufemi; Erhabor, Greg Efosa; Adewole, Temitayo Oluwatoyin; Ojo, Abiodun Oluwasesan; Oshokoya, Harriet; Wolfe, Lisa M; Prenni, Jessica E

2016-05-01

Excessive sweating is a common symptom of the disease and an unexplored biofluid for TB diagnosis; we conducted a proof-of-concept study to identify potential diagnostic biomarkers of active TB in eccrine sweat. We performed a global proteomic profile of eccrine sweat sampled from patients with active pulmonary TB, other lung diseases (non-TB disease), and healthy controls. A comparison of proteomics between Active-TB, Non-TB, and Healthy Controls was done in search for potential biomarkers of active TB. Sweat specimens were pooled from 32 active TB patients, 27 patients with non-TB diseases, and 24 apparently healthy controls, all were negative for HIV. Over 100 unique proteins were identified in the eccrine sweat of all three groups. Twenty-six proteins were exclusively detected in the sweat of patients with active TB while the remaining detected proteins overlapped between three groups. Gene ontology evaluation indicated that the proteins detected uniquely in sweat of active TB patients were involved in immune response and auxiliary protein transport. Gene products for cellular components (e.g. ribosomes) were detected only in active TB patients. Data are available via ProteomeXchange with identifier PXD003224. Proteomics of sweat from active TB patients is a viable approach for biomarker identification, which could be used to develop a nonsputum-based test for detection of active TB. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interleukin-1 receptor antagonist, a biomarker of response to anti-TB treatment in HIV/TB co-infected patients.

PubMed

Nouhin, Janin; Pean, Polidy; Madec, Yoann; Chevalier, Mathieu F; Didier, Celine; Borand, Laurence; Blanc, François-Xavier; Scott-Algara, Daniel; Laureillard, Didier; Weiss, Laurence

2017-05-01

Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment. Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time. At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)). None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infected patients. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

TIME Impact - a new user-friendly tuberculosis (TB) model to inform TB policy decisions.

PubMed

Houben, R M G J; Lalli, M; Sumner, T; Hamilton, M; Pedrazzoli, D; Bonsu, F; Hippner, P; Pillay, Y; Kimerling, M; Ahmedov, S; Pretorius, C; White, R G

2016-03-24

Tuberculosis (TB) is the leading cause of death from infectious disease worldwide, predominantly affecting low- and middle-income countries (LMICs), where resources are limited. As such, countries need to be able to choose the most efficient interventions for their respective setting. Mathematical models can be valuable tools to inform rational policy decisions and improve resource allocation, but are often unavailable or inaccessible for LMICs, particularly in TB. We developed TIME Impact, a user-friendly TB model that enables local capacity building and strengthens country-specific policy discussions to inform support funding applications at the (sub-)national level (e.g. Ministry of Finance) or to international donors (e.g. the Global Fund to Fight AIDS, Tuberculosis and Malaria).TIME Impact is an epidemiological transmission model nested in TIME, a set of TB modelling tools available for free download within the widely-used Spectrum software. The TIME Impact model reflects key aspects of the natural history of TB, with additional structure for HIV/ART, drug resistance, treatment history and age. TIME Impact enables national TB programmes (NTPs) and other TB policymakers to better understand their own TB epidemic, plan their response, apply for funding and evaluate the implementation of the response.The explicit aim of TIME Impact's user-friendly interface is to enable training of local and international TB experts towards independent use. During application of TIME Impact, close involvement of the NTPs and other local partners also builds critical understanding of the modelling methods, assumptions and limitations inherent to modelling. This is essential to generate broad country-level ownership of the modelling data inputs and results. In turn, it stimulates discussions and a review of the current evidence and assumptions, strengthening the decision-making process in general.TIME Impact has been effectively applied in a variety of settings. In South Africa, it

Common patterns and disease-related signatures in tuberculosis and sarcoidosis.

PubMed

Maertzdorf, Jeroen; Weiner, January; Mollenkopf, Hans-Joachim; Bauer, Torsten; Prasse, Antje; Müller-Quernheim, Joachim; Kaufmann, Stefan H E

2012-05-15

In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.

Potential Function of Granulysin, Other Related Effector Molecules and Lymphocyte Subsets in Patients with TB and HIV/TB Coinfection

PubMed Central

Pitabut, Nada; Sakurada, Shinsaku; Tanaka, Takahiro; Ridruechai, Chutharut; Tanuma, Junko; Aoki, Takahiro; Kantipong, Pacharee; Piyaworawong, Surachai; Kobayashi, Nobuyuki; Dhepakson, Panadda; Yanai, Hideki; Yamada, Norio; Oka, Shinichi; Okada, Masaji; Khusmith, Srisin; Keicho, Naoto

2013-01-01

Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy. Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9+Vδ2+ T cells, CD4+ T cells and CD8+ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection. Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry. Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8+ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed. Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection. PMID:23801887

Effectiveness of TB sensitization initiatives in improving the involvement of self help group members in rural TB control in south India.

PubMed

Thomas, Beena; Priscilla Rebecca, B; Dhanalakshmi, A; Rani, S; Deepa Lakshmi, A; Watson, Basilea; Vijayalakshmi, R; Muniyandi, M; Karikalan, N

2016-12-01

The 'End TB strategy' has highlighted the importance of inter-sectoral collaboration and community mobilization for achieving zero TB deaths by 2020. The aim of the study was to develop and test a model TB sensitization programme involving self help groups (SHGs). This experimental study was conducted in two blocks (intervention and control), in Tiruvallur district. The intervention content included short-lecture, musical story telling activity, role play, short film on TB. The impact was compared at baseline, third and sixth months in terms of SHGs' awareness, promotion of awareness, identification and referral of presumptive TB cases and provision of TB treatment. A total of 764 vs 796 SHGs were enrolled in control and intervention groups, respectively. The knowledge attitude, and practice score (lower score indicated a better attitude and practice), from baseline to 6 months was significantly reduced (29 to 24) in the intervention group. Similarly, a significant difference was observed in identification and referral of chest symptomatics in the intervention group at 3 and 6 months. During the 3 month follow-up a significantly higher proportion of SHG members were involved in TB awareness activities in the intervention (623/748 [83.3%]) vs control group (471/728 [64.7%]; p<0.001). Findings from this study highlight the feasibility of involving SHGs through a model TB sensitization program for strengthening TB prevention and control activities. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Litigation as TB Rights Advocacy

PubMed Central

2016-01-01

Abstract One thousand people die every day in India as a result of TB, a preventable and treatable disease, even though the Constitution of India, government schemes, and international law guarantee available, accessible, acceptable, quality health care. Failure to address the spread of TB and to provide quality treatment to all affected populations constitutes a public health and human rights emergency that demands action and accountability. As part of a broader strategy, health activists in India employ Public Interest Litigation (PIL) to hold the state accountable for rights violations and to demand new legislation, standards for patient care, accountability for under-spending, improvements in services at individual facilities, and access to government entitlements in marginalized communities. Taking inspiration from right to health PIL cases (PILs), lawyers in a New Delhi-based rights organization used desk research, fact-findings, and the Right To Information Act to build a TB PIL for the Delhi High Court, Sanjai Sharma v. NCT of Delhi and Others (2015). The case argues that inadequate implementation of government TB schemes violates the Constitutional rights to life, health, food, and equality. Although PILs face substantial challenges, this paper concludes that litigation can be a crucial advocacy and accountability tool for people living with TB and their allies. PMID:27781000

Tracking and Treating Mobile Populations. The TB Net System. Migrant Clinicians Network Monograph Series. = El Sistema de Red para la TB.

ERIC Educational Resources Information Center

Migrant Clinicians Network, Inc., Austin, TX.

A comprehensive tracking and referral network that helps provide continuity of care for mobile populations with active tuberculosis (TB) or TB infection is considered essential for effective treatment of TB. However, the interstate referral system that exists between state health departments has been highly inefficient for serving migrant…

Low Yield of Chest Radiography in General Inpatients and Outpatients with "Positive PPD" Results in a Country with Low Prevalence of TB.

PubMed

Eisenberg, Ronald L; Heidinger, Benedikt H

2017-07-01

The purpose of this study was to assess the frequency and spectrum of abnormalities on routine screening chest radiographs among inpatients and outpatients with "positive purified protein derivative (PPD)" in a large tertiary care academic medical center in a country with low prevalence of tuberculosis (TB). The reports of all chest radiographs of general inpatients and outpatients referred for positive PPD (2010-2014) were evaluated for the frequency of evidence of active or latent TB and the spectrum of imaging findings. The results of additional chest radiographs and computed tomography scans were recorded, as were additional relevant clinical histories and symptoms. Of the 2518 patients who underwent chest radiography for positive PPD, the radiographs were normal in 91.3%. The vast majority of the abnormal radiographs demonstrated findings consistent with old tuberculous disease. There were three cases (0.1%) of active TB, all of which were either recent immigrants from an endemic area or had other relevant histories or clinical symptoms suggestive of the disease. Universal chest radiography in general inpatient and outpatient populations referred for positive PPD is of low yield for detecting active disease in a country with low prevalence of TB. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Performance of QuantiFERON®-TB Gold In-Tube assay in children receiving disease modifying anti-rheumatic drugs.

PubMed

Gabriele, Francesca; Trachana, Maria; Simitsopoulou, Maria; Pratsidou-Gertsi, Polixeni; Iosifidis, Elias; Pana, Zoi Dorothea; Roilides, Emmanuel

2017-10-01

To evaluate the performance of the Quantiferon ® -TB Gold In-Tube (QFT-IT) interferon (IFN)-γ assay for the detection of latent tuberculosis infection (LTBI) in children receiving anti-rheumatic treatment in a tertiary referral hospital of Northern Greece. A total of 79 consecutive children receiving anti-rheumatic treatment [of which 18 screened prior to antitumor necrosis factor (TNF)-α treatment] were tested using Mantoux tuberculin skin test (TST) and QFT-IT. Association of both tests with risk factors for latent tuberculosis and Bacillus Calmette-Guerin immunization was determined. Influence of age, TNF-α inhibitors, systemic corticosteroids, conventional disease modifying anti-rheumatic drugs (DMARDs) and total duration of therapy on the QFT-IT mitogen-induced response was evaluated. Agreement between TST and QFT-IT results was moderate (k=0.38). Frequency of QFT-IT indeterminate results was low (2.5%). In patients with risk factors for LTBI, the odds of a positive IFN-γ assay was increased by a factor of 27.6 (P=0.002), whereas there was no positive TST. There was a significant difference in the mitogen-induced IFN-γ secretion among various treatments (P=0.038). TNF-α inhibitors were associated with increased mitogen-induced IFN-γ secretion compared to monotherapy with conventional DMARDs (P=0.008). All children screened prior to anti-TNF-α treatment exhibited a negative QFT-IT and no active TB disease was detected during a 2-year follow-up. QFT-IT may be a more reliable test than TST for detection of LTBI in children with rheumatic diseases receiving anti-rheumatic treatment. Drug regimen might influence the mitogen-induced IFN-γ secretion and the effect of TNF-α inhibitors might vary according to the specific agent administered.

Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age.

PubMed

Bae, Won; Park, Kyoung Un; Song, Eun Young; Kim, Se Joong; Lee, Yeon Joo; Park, Jong Sun; Cho, Young-Jae; Yoon, Ho Il; Yim, Jae-Joon; Lee, Choon-Taek; Lee, Jae Ho

2016-01-01

Currently, there are two types of interferon-gamma release assays (IGRAs) in use for the detection of tuberculosis (TB) infection, the QuantiFERON-TB Gold In-Tube test (GFT-GIT) and T-SPOT.TB. Owing to contradictory reports regarding whether the results of these IGRAs are affected by the age of the patient, we aimed to determine if these two tests have age-related differences in sensitivity. We retrospectively reviewed the medical records of diagnosed TB patients who were tested using either QFT-GIT or T-SPOT.TB from February 2008 to December 2013. The positivity of the two tests was analyzed and compared with true TB infection, which was defined as active TB based on either a positive Mycobacterium culture or a positive TB polymerase chain reaction. The QFT-GIT group included 192 TB patients, and the T-SPOT.TB group included 212 TB patients. Of the patients with pulmonary TB, 76 (39.6%) were in the QFT-GIT group and 143 (67.5%) in the T-SPOT.TB group. The overall sensitivity was 80.2% for QFT-GIT and 91.0% for T.SPOT.TB. The sensitivities of QFT-GIT and T-SPOT.TB according to age group were as follows: <29 years, 93.3% and 96.7%; 30-49 years, 86.5% and 94.7%; 50-69 years, 76.8% and 87.5%; and >70 years, 68.3% and 85.7%, respectively. The trend of age-related changes in sensitivity was significant for both QFT-GIT (p = 0.004) and T.SPOT.TB (p = 0.039). However, only QFT-GIT was significantly related to age in the multivariate analysis. QFT-GIT, but not T-SPOT.TB, was significantly affected by patient age.

Processing of metacaspase 2 from Trypanosoma brucei (TbMCA2) broadens its substrate specificity.

PubMed

Gilio, Joyce M; Marcondes, Marcelo F; Ferrari, Débora; Juliano, Maria A; Juliano, Luiz; Oliveira, Vitor; Machado, Maurício F M

2017-04-01

Metacaspases are members of the cysteine peptidase family and may be implicated in programmed cell death in plants and lower eukaryotes. These proteases exhibit calcium-dependent activity and specificity for arginine residues at P 1 . In contrast to caspases, they do not require processing or dimerization for activity. Indeed, unprocessed metacaspase-2 of Trypanosoma brucei (TbMCA2) is active; however, it has been shown that cleavages at Lys 55 and Lys 268 increase TbMCA2 hydrolytic activity on synthetic substrates. The processed TbMCA2 comprises 3 polypeptide chains that remain attached by non-covalent bonds. Replacement of Lys 55 and Lys 268 with Gly via site-directed mutagenesis results in non-processed but enzymatically active mutant, TbMCA2 K55/268G. To investigate the importance of this processing for the activity and specificity of TbMCA2, we performed activity assays comparing the non-processed mutant (TbMCA2 K55/268G) with the processed TbMCA2 form. Significant differences between TbMCA2 WT (processed form) and TbMCA2 K55/268G (non-processed form) were observed. Specifically, we verified that although non-processed TbMCA2 is active when assayed with small synthetic substrates, the TbMCA2 form does not exhibit hydrolytic activity on large substrates such as azocasein, while processed TbMCA2 is able to readily digest this protein. Such differences can be relevant for understanding the physiological regulation and function of TbMCA2. Copyright © 2017 Elsevier B.V. All rights reserved.

Purity-activity relationships of natural products: the case of anti-TB active ursolic acid.

PubMed

Jaki, Birgit U; Franzblau, Scott G; Chadwick, Lucas R; Lankin, David C; Zhang, Fangqiu; Wang, Yuehong; Pauli, Guido F

2008-10-01

The present study explores the variability of biological responses from the perspective of sample purity and introduces the concept of purity-activity relationships (PARs) in natural product research. The abundant plant triterpene ursolic acid (1) was selected as an exemplary natural product due to the overwhelming number yet inconsistent nature of its approximate 120 reported biological activities, which include anti-TB potential. Nine different samples of ursolic acid with purity certifications were obtained, and their purity was independently assessed by means of quantitative 1H NMR (qHNMR). Biological evaluation consisted of determining MICs against two strains of virulent Mycobacterium tuberculosis and IC50 values in Vero cells. Ab initio structure elucidation provided unequivocal structural confirmation and included an extensive 1H NMR spin system analysis, determination of nearly all J couplings and the complete NOE pattern, and led to the revision of earlier reports. As a net result, a sigmoid PAR profile of 1 was obtained, demonstrating the inverse correlation of purity and anti-TB bioactivity. The results imply that synergistic effects of 1 and its varying impurities are the likely cause of previously reported antimycobacterial potential. Generating PARs is a powerful extension of the routinely performed quantitative correlation of structure and activity ([Q]SAR). Advanced by the use of primary analytical methods such as qHNMR, PARs enable the elucidation of cases like 1 when increasing purity voids biological activity. This underlines the potential of PARs as a tool in drug discovery and synergy research and accentuates the need to routinely combine biological testing with purity assessment.

Analogues of the Frog-skin Antimicrobial Peptide Temporin 1Tb Exhibit a Wider Spectrum of Activity and a Stronger Antibiofilm Potential as Compared to the Parental Peptide

NASA Astrophysics Data System (ADS)

Grassi, Lucia; Maisetta, Giuseppantonio; Maccari, Giuseppe; Esin, Semih; Batoni, Giovanna

2017-04-01

The frog skin-derived peptide Temporin 1Tb (TB) has gained increasing attention as novel antimicrobial agent for the treatment of antibiotic-resistant and/or biofilm-mediated infections. Nevertheless, such a peptide possesses a preferential spectrum of action against Gram-positive bacteria. In order to improve the therapeutic potential of TB, the present study evaluated the antibacterial and antibiofilm activities of two TB analogues against medically relevant bacterial species. Of the two analogues, TB_KKG6A has been previously described in the literature, while TB_L1FK is a new analogue designed by us through statistical-based computational strategies. Both TB analogues displayed a faster and stronger bactericidal activity than the parental peptide, especially against Gram-negative bacteria in planktonic form. Differently from the parental peptide, TB_KKG6A and TB_L1FK were able to inhibit the formation of Staphylococcus aureus biofilms by more than 50% at 12 μM, while only TB_KKG6A prevented the formation of Pseudomonas aeruginosa biofilms at 24 μM. A marked antibiofilm activity against preformed biofilms of both bacterial species was observed for the two TB analogues when used in combination with EDTA. Analysis of synergism at the cellular level suggested that the antibiofilm activity exerted by the peptide-EDTA combinations against mature biofilms might be due mainly to a disaggregating effect on the extracellular matrix in the case of S. aureus, and to a direct activity on biofilm-embedded cells in the case of P. aeruginosa. Both analogues displayed a low hemolytic effect at the active concentrations and, overall, TB_L1FK resulted less cytotoxic towards mammalian cells. Collectively, the results obtained demonstrated that subtle changes in the primary sequence of TB may provide TB analogues that, used alone or in combination with adjuvant molecules such as EDTA, exhibit promising features against both planktonic and biofilm cells of medically relevant

Low Indeterminate Rates Associated With Use of the QuantiFERON-TB Gold In-Tube Test in Children With Inflammatory Bowel Disease on Long-term Infliximab.

PubMed

Vortia, Eugene; Uko, Victor E; Yen-Lieberman, Belinda; Frawley, Jill; Worley, Sarah E; Danziger-Isakov, Lara; Kaplan, Barbara; Mahajan, Lori

2018-03-19

Tumor necrosis factor alpha (TNF-α) inhibitors are linked with increased risk of reactivation of active tuberculosis. The QuantiFERON-TB Gold In-Tube test is approved for screening latent tuberculosis infection in children and adults. There are limited data on the test performance in children on long-term treatment with TNF-α inhibitors. The objective of this study was to assess the proportion of indeterminate results for the QuantiFERON-TB Gold In-Tube in children with inflammatory bowel disease (IBD) on long-term infliximab treatment and to evaluate the range of interferon-γ responses to mitogen. A single-center prospective study of children 5 to 19 years of age with IBD on long-term infliximab treatment (>3 months). Each child was assessed for tuberculosis exposure risk and had blood drawn for the QuantiFERON-TB Gold In-Tube. Data on the range of interferon-γ responses and final QuantiFERON-TB Gold In-Tube test results were collected. Ninety-three children were included, with a median age of 16 years. The median total duration of infliximab therapy was 34 months (range, 3-119 months). The QuantiFERON-TB Gold In-Tube was indeterminate in 1 patient (1.1%), positive in 2 patients, and negative in 90 patients. The maximum interferon-γ response to mitogen (10 IU/mL) was observed in 82 patients (88%), with only 1 patient having an inadequate response. The proportion of indeterminate results was significantly lower than the prospectively hypothesized rate of 8%, based on prior studies in nonimmunosuppressed patients (P = 0.004). Pediatric patients with IBD on long-term treatment with infliximab had an adequate interferon-γ response to mitogen and a low indeterminate rate when assessed with the QuantiFERON-TB Gold In-Tube test. This study demonstrates a robust interferon gamma response to phytohemagglutinin stimulation in a pediatric population on long-term therapy with infliximab. The QuantiFERON-TB Gold In-Tube test may therefore be useful as a periodic

Epidemiology of HIV-TB in Asia.

PubMed

Narain, Jai P; Lo, Ying-Ru

2004-10-01

Tuberculosis (TB) has, for centuries, continued to remain a public health problem of enormous importance, particularly in the developing world, taking a heavy toll of those at their prime of life. The emergence of human immunodeficiency virus (HIV infection) and its close association with TB poses an even greater challenge to the health systems in general and TB programmes in particular, in African and Asian countries. HIV is considered to be the most potent risk factor for progression to active TB among those infected both with TB and HIV; as a result, TB is the most common life threatening opportunistic infection associated with HIV, and biggest cause of death among patients with acquired immunodeficiency syndrome (AIDS). In areas hard-hit by HIV, TB is increasing, leading to greater case load, thereby overstretching the already fragile health infrastructure. The deadly relationship between HIV and TB, each potentiating the effect of the other, requires a clearly defined strategy taking into consideration the natural history of the co-infection and its progression to clinical TB (and AIDS). It is clear that the only way to fight this is by bringing the two programmes to join forces and work creatively and innovatively. The strategy should include not only preventing HIV through community-based behavioural interventions and limiting progression to clinical TB through the use of isoniazid preventive therapy, but also early diagnosis and treatment of HIV-associated TB and AIDS using DOTS strategy and combination antiretroviral therapy respectively. The strategy probably would not succeed unless both the programmes are first strengthened before attempting to forge collaboration based on mutual strengths and comparative advantages. In addition, mobilizing national and international response, building partnerships and mobilizing resources will help a great deal in mounting an appropriate and effective response to HIV/TB in the Asian context.

Enhancing TB case detection: experience in offering upfront Xpert MTB/RIF testing to pediatric presumptive TB and DR TB cases for early rapid diagnosis of drug sensitive and drug resistant TB.

PubMed

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Nair, Sreenivas Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shayam; Thakur, Rahul; Parmar, Malik; Gray, Christen; Ramachandran, Ranjani; Vadera, Bhavin; Ekka, Shobha; Dhawan, Shikha; Babre, Ameet; Ghedia, Mayank; Alavadi, Umesh; Dewan, Puneet; Khetrapal, Mini; Khanna, Ashwini; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2014-01-01

Diagnosis of pulmonary tuberculosis (PTB) in children is challenging due to difficulties in obtaining good quality sputum specimens as well as the paucibacillary nature of disease. Globally a large proportion of pediatric tuberculosis (TB) cases are diagnosed based only on clinical findings. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents the results from pediatric groups taking part in a large demonstration study wherein Xpert MTB/RIF testing replaced smear microscopy for all presumptive PTB cases in public health facilities across India. The study covered a population of 8.8 million across 18 programmatic sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each study TU. Pediatric presumptive PTB cases (both TB and Drug Resistant TB (DR-TB)) accessing any public health facilities in study area were prospectively enrolled and tested on Xpert MTB/RIF following a standardized diagnostic algorithm. 4,600 pediatric presumptive pulmonary TB cases were enrolled. 590 (12.8%, CI 11.8-13.8) pediatric PTB were diagnosed. Overall 10.4% (CI 9.5-11.2) of presumptive PTB cases had positive results by Xpert MTB/RIF, compared with 4.8% (CI 4.2-5.4) who had smear-positive results. Upfront Xpert MTB/RIF testing of presumptive PTB and presumptive DR-TB cases resulted in diagnosis of 79 and 12 rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high (98%, CI 90.1-99.9), with no statistically significant variation with respect to past history of treatment. Upfront access to Xpert MTB/RIF testing in pediatric presumptive PTB cases was associated with a two-fold increase in bacteriologically-confirmed PTB, and increased detection of rifampicin-resistant TB cases under routine operational conditions across India. These results suggest that routine Xpert MTB/RIF testing is a promising solution to

Strategies for halting the rise of multidrug resistant TB epidemics: assessing the effect of early case detection and isolation.

PubMed

Espindola, Aquino L; Varughese, Marie; Laskowski, Marek; Shoukat, Affan; Heffernan, Jane M; Moghadas, Seyed M

2017-03-01

The increasing rates of multidrug resistant TB (MDR-TB) have posed the question of whether control programs under enhanced directly observed treatment, short-course (DOTS-Plus) are sufficient or implemented optimally. Despite enhanced efforts on early case detection and improved treatment regimens, direct transmission of MDR-TB remains a major hurdle for global TB control. We developed an agent-based simulation model of TB dynamics to evaluate the effect of transmission reduction measures on the incidence of MDR-TB. We implemented a 15-day isolation period following the start of treatment in active TB cases. The model was parameterized with the latest estimates derived from the published literature. We found that if high rates (over 90%) of TB case identification are achieved within 4 weeks of developing active TB, then a 15-day patient isolation strategy with 50% effectiveness in interrupting disease transmission leads to 10% reduction in the incidence of MDR-TB over 10 years. If transmission is fully prevented, the rise of MDR-TB can be halted within 10 years, but the temporal reduction of MDR-TB incidence remains below 20% in this period. The impact of transmission reduction measures on the TB incidence depends critically on the rates and timelines of case identification. The high costs and adverse effects associated with MDR-TB treatment warrant increased efforts and investments on measures that can interrupt direct transmission through early case detection. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Provider-initiated HIV testing and counselling for TB patients and suspects in Nairobi, Kenya.

PubMed

Odhiambo, J; Kizito, W; Njoroge, A; Wambua, N; Nganga, L; Mburu, M; Mansoer, J; Marum, L; Phillips, E; Chakaya, J; De Cock, K M

2008-03-01

Integrated tuberculosis (TB) and human immunodeficiency virus (HIV) services in a resource-constrained setting. Pilot provider-initiated HIV testing and counselling (PITC) for TB patients and suspects. Through partnerships, resources were mobilised to establish and support services. After community sensitisation and staff training, PITC was introduced to TB patients and then to TB suspects from December 2003 to December 2005. Of 5457 TB suspects who received PITC, 89% underwent HIV testing. Although not statistically significant, TB suspects with TB disease had an HIV prevalence of 61% compared to 63% for those without. Of the 614 suspects who declined HIV testing, 402 (65%) had TB disease. Of 2283 patients referred for cotrimoxazole prophylaxis, 1951 (86%) were enrolled, and of 1727 patients assessed for antiretroviral treatment (ART), 1618 (94%) were eligible and 1441 (83%) started treatment. PITC represents a paradigm shift and is feasible and acceptable to TB patients and TB suspects. Clear directives are nevertheless required to change practice. When offered to TB suspects, PITC identifies large numbers of persons requiring HIV care. Community sensitisation, staff training, multitasking and access to HIV care contributed to a high acceptance of HIV testing. Kenya is using this experience to inform national response and advocate wide PITC implementation in settings faced with the TB-HIV epidemic.

Economic burden of HIV and TB/HIV coinfection in a middle-income country: a costing analysis alongside a pragmatic clinical trial in Brazil.

PubMed

Teixeira de Siqueira-Filha, Noemia; Militao de Albuquerque, Maria de Fatima; Cunha Rodrigues, Laura; Legood, Rosa; Costa Santos, Andreia

2018-03-15

The objective of this study was to measure the costs of people living with HIV (PLHIV) as well as active tuberculosis (TB/HIV), latent tuberculosis infection (LTBI/HIV) or without TB (HIV/AIDS). We analysed the costs through the entire pathway of care during the prediagnosis and treatment periods from the Brazilian public health system perspective. We applied a combination of bottom-up and top-down approaches to capture and estimate direct medical and non-medical costs. We measured the mean cost per patient per type of care (inpatient, outpatient and emergency care) and disease category (HIV/AIDS, HIV/AIDS death, TB/HIV, TB/HIV death and LTBI/HIV). Between March 2014 and March 2016 we recruited 239 PLHIV. During the follow-up 26 patients were diagnosed and treated for TB and 5 received chemoprophylaxis for LTBI. During the prediagnosis and treatment period, the mean total costs for HIV or AIDS and AIDS death categories were US$1558 and US$2828, respectively. The mean total costs for TB/HIV and TB/HIV death categories were US$5289.0 and US$8281, respectively. The mean total cost for the LTBI/HIV category was US$882. Patients with TB/HIV impose a higher economic burden on the health system than HIV/AIDS and LTBI/HIV. Patients with LTBI/HIV were the lowest cost group among all disease categories, indicating that preventive TB treatment can avoid the further costs treating active TB. RBR-22t943, Results. © 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.

Mapping sites of high TB transmission risk: Integrating the shared air and social behaviour of TB cases and adolescents in a South African township.

PubMed

Patterson, Benjamin; Morrow, Carl D; Kohls, Daniel; Deignan, Caroline; Ginsburg, Samuel; Wood, Robin

2017-04-01

Tuberculosis remains a major public health problem in poverty-stricken areas of the world. Communal gathering places account for the majority of TB transmission in high burden settings. To investigate the social behaviour patterns of individuals who have developed TB disease and adolescents at risk of infection. To develop a cheap and effective method to locate transmission hot spots in high burden communities. Portable, combined CO 2 /GIS monitors and location diaries were given to individuals from a South African township. The three groups: newly diagnosed TB patients, recently treated TB patients and adolescents recorded their activities over a median of two days. Rebreathed air volumes (RAVs) at all GIS locations were calculated from CO 2 levels using the Rudnick-Milton variant of the Wells-Riley TB transmission model. Hot spot analysis was performed to determine the communal buildings which correspond to spatially clustered high RAVs. Analysis of diaries found that the adolescent group spent greater time in congregate settings compared with the other two groups driven by time spent in school/work (new TB: 1%, recent TB: 8%, and adolescents: 23%). Adolescents also changed their location more frequently (9.0, 6.0, 14.3 changes per day; p<0.001). The RAVs reflected this divergence between the groups (44, 40, 127l; p<0.001). Communal buildings associated with high RAVs were found to be a clinic, two schools and a library. Hot spot analysis revealed the most intense clustering of high RAVs at a community school. Our study demonstrates a new methodology to uncover TB transmission hot spots using a technique that avoids the need to pre-select locations. Investigation of a South African township highlighted the high risk potential of schools and high risk social behaviour of adolescents. Consequently the targeting of transmission reduction strategies to schools may prove highly efficacious in high burden settings. Copyright © 2017 The Authors. Published by Elsevier B

Tuberculosis Comorbidity with Communicable and Noncommunicable Diseases

PubMed Central

Bates, Matthew; Marais, Ben J.; Zumla, Alimuddin

2015-01-01

The 18th WHO Global Tuberculosis Annual Report indicates that there were an estimated 8.6 million incident cases of tuberculosis (TB) in 2012, which included 2.9 million women and 530,000 children. TB caused 1.3 million deaths including 320,000 human immunodeficiency virus (HIV)-infected people; three-quarters of deaths occurred in Africa and Southeast Asia. With one-third of the world’s population latently infected with Mycobacterium tuberculosis (Mtb), active TB disease is primarily associated with a break down in immune surveillance. This explains the strong link between active TB disease and other communicable diseases (CDs) or noncommunicable diseases (NCDs) that exert a toll on the immune system. Comorbid NCD risk factors include diabetes, smoking, malnutrition, and chronic lung disease, all of which have increased relentlessly over the past decade in developing countries. The huge overlap between killer infections such as TB, HIV, malaria, and severe viral infections with NCDs, results in a “double burden of disease” in developing countries. The current focus on vertical disease programs fails to recognize comorbidities or to encourage joint management approaches. This review highlights major disease overlaps and discusses the rationale for better integration of tuberculosis care with services for NCDs and other infectious diseases to enhance the overall efficiency of the public health responses. PMID:25659380

The association between ARV and TB drug resistance on TB treatment outcome among Kazakh TB/HIV patients.

PubMed

Mishkin, Kathryn; Alaei, Kamiar; Alikeyeva, Elmira; Paynter, Christopher; Aringazina, Altyn; Alaei, Arash

2018-02-26

TB drug resistance poses a serious threat to the public health of Kazakhstan. This paper presents findings related to TB treatment outcome and drug resistant status among people coinfected with HIV and TB in Kazakhstan. Cohort study using data were provided by the Kazakhstan Ministry of Health's National Tuberculosis Program for 2014 and 2015. Chi-square and logistical regression were performed to understand factors associated with drug resistant TB status and TB treatment outcome. In bivariate analysis, drug resistant status was significantly associated with year of TB diagnosis (p=0.001) viral load (p=0.03). TB treatment outcome was significantly associated with age at diagnosis (p=01), ARV treatment (p <0.0001), and TB drug resistant status (p=0.02). In adjusted analysis, drug resistance was associated with increased odds of successful completion of treatment with successful result compared to treatment failure (OR 6.94, 95% CI: 1.39-34.44) CONCLUSIONS: Our results suggest that being drug resistant is associated with higher odds of completing treatment with successful outcome, even when controlling for receipt of ARV therapy. Copyright © 2018. Published by Elsevier Ltd.

[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

Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253.

PubMed

Shiboski, C H; Chen, H; Ghannoum, M A; Komarow, L; Evans, S; Mukherjee, P K; Isham, N; Katzenstein, D; Asmelash, A; Omozoarhe, A E; Gengiah, S; Allen, R; Tripathy, S; Swindells, S

2014-06-01

To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm(3). Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95%CI 1.2-4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22-48) and the specificity 85% (95%CI 81-88). We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding.

Framework of behavioral indicators for outcome evaluation of TB health promotion: a Delphi study of TB suspects and Tb patients.

PubMed

Li, Ying; Ehiri, John; Hu, Daiyu; Zhang, Yanqi; Wang, Qingya; Zhang, Shun; Cao, Jia

2014-05-16

Health promotion for prevention and control of Tuberculosis (TB) is implemented worldwide because of its importance, but few reports have evaluated its impact on behavior due to a lack of standard outcome indicators. The objective of this study was to establish a framework of behavioral indicators for outcome evaluation of TB health promotion among TB suspects and patients. A two-round modified Delphi method involving sixteen TB control experts was used to establish a framework of behavioral indicators for outcome evaluation of TB health promotion targeted at TB suspects and patients. Sixteen of seventeen invited experts in TB control (authority score of 0.91 on a 1.0 scale) participated in round 1 survey. All sixteen experts also participated in a second round survey. After two rounds of surveys and several iterations among the experts, there was consensus on a framework of indicators for measuring outcomes of TB health promotion for TB suspects and patients. For TB suspects, the experts reached consensus on 2 domains ("Healthcare seeking behavior" and "Transmission prevention"), 3 subdomains ("Seeking care after onset of TB symptoms", "Pathways of seeking care" and "Interpersonal contact etiquette"), and 8 indicators (including among others, "Length of patient delay"). For TB patients, consensus was reached on 3 domains ("Adherence to treatment", "Healthy lifestyle" and "Transmission prevention"), 8 subdomains (including among others, "Adherence to their medication"), and 14 indicators (including "Percentage of patients who adhered to their medication"). Operational definitions and data sources were provided for each indicator. The findings of this study provide the basis for debate among international experts on a framework for achieving global consensus on outcome indicators for TB health promotion interventions targeted at TB patients and suspects. Such consensus will help to increase effectiveness of TB health promotion, while ensuring international

Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis

PubMed Central

Petruccioli, Elisa; Scriba, Thomas J.; Petrone, Linda; Hatherill, Mark; Cirillo, Daniela M.; Joosten, Simone A.; Ottenhoff, Tom H.; Denkinger, Claudia M.; Goletti, Delia

2016-01-01

New approaches to control the spread of tuberculosis (TB) are needed, including tools to predict development of active TB from latent TB infection (LTBI). Recent studies have described potential correlates of risk, in order to inform the development of prognostic tests for TB disease progression. These efforts have included unbiased approaches employing “omics” technologies, as well as more directed, hypothesis-driven approaches assessing a small set or even individual selected markers as candidate correlates of TB risk. Unbiased high-throughput screening of blood RNAseq profiles identified signatures of active TB risk in individuals with LTBI, ≥1 year before diagnosis. A recent infant vaccination study identified enhanced expression of T-cell activation markers as a correlate of risk prior to developing TB; conversely, high levels of Ag85A antibodies and high frequencies of interferon (IFN)-γ specific T-cells were associated with reduced risk of disease. Others have described CD27−IFN-γ+CD4+ T-cells as possibly predictive markers of TB disease. T-cell responses to TB latency antigens, including heparin-binding haemagglutinin and DosR-regulon-encoded antigens have also been correlated with protection. Further studies are needed to determine whether correlates of risk can be used to prevent active TB through targeted prophylactic treatment, or to allow targeted enrolment into efficacy trials of new TB vaccines and therapeutic drugs. PMID:27836953

OSHA TB standard adds teeth to CDC guidelines. Occupational Safety and Health Administration. Centers for Disease Control and Prevention.

PubMed

1997-12-01

The Occupational Safety and Health Administration (OSHA) has published a proposed standard to provide health care workers with more protection against tuberculosis (TB). With one-quarter of new TB cases occurring in HIV-infected people, 5.3 million workers treating AIDS patients and working with at-risk populations need to be aware of the proposed guidelines. OSHA estimates that the new standard could eliminate most work-related TB infections and save up to $116 million in medical costs and lost production. The OSHA standards vary from those of the Centers for Disease Control (CDC) in several ways. CDC guidelines are voluntary, whereas OSHA standards are enforceable and facilities can be fined for violations. Although OSHA standards have incorporated basic elements of the CDC recommendations, OSHA standards also would require employers to conduct exposure assessments, require six-month skin testing, and call for respirator use in more instances. OSHA officials expect broad participation at public hearings on the new standard, scheduled to begin in February 1998.

Understanding Market Size and Reporting Gaps for Paediatric TB in Indonesia, Nigeria and Pakistan: Supporting Improved Treatment of Childhood TB in the Advent of New Medicines.

PubMed

Coghlan, Renia; Gardiner, Elizabeth; Amanullah, Farhana; Ihekweazu, Chikwe; Triasih, Rina; Grzemska, Malgorzata; Sismanidis, Charalambos

2015-01-01

We sought to understand gaps in reporting childhood TB cases among public and private sector health facilities (dubbed "non-NTP" facilities) outside the network of national TB control programmes, and the resulting impact of under-reporting on estimates of paediatric disease burden and market demand for new medicines. Exploratory assessments were carried out in Indonesia, Nigeria and Pakistan, reaching a range of facility types in two selected areas of each country. Record reviews and interviews of healthcare providers were carried out to assess numbers of unreported paediatric TB cases, diagnostic pathways followed and treatment regimens prescribed. A total of 985 unreported diagnosed paediatric TB cases were identified over a three month period in 2013 in Indonesia from 64 facilities, 463 in Pakistan from 35 facilities and 24 in Nigeria from 20 facilities. These represent an absolute additional annualised yield to 2013 notifications reported to WHO of 15% for Indonesia, 2% for Nigeria and 7% for Pakistan. Only 12% of all facilities provided age and sex-disaggregated data. Findings highlight the challenges of confirming childhood TB. Diagnosis patterns in Nigeria highlight a very low suspicion for childhood TB. Providers note the need for paediatric medicines aligned to WHO recommendations. This study emphasises the impact of incomplete reporting on the estimation of disease burden and potential market size of paediatric TB medicines. Further studies on "hubs" (facilities treating large numbers of childhood TB cases) will improve our understanding of the epidemic, support introduction efforts for new treatments and better measure markets for new paediatric medicines.

Primary lung cancer coexisting with active pulmonary tuberculosis.

PubMed

Varol, Y; Varol, U; Unlu, M; Kayaalp, I; Ayranci, A; Dereli, M S; Guclu, S Z

2014-09-01

Lung cancer and pulmonary tuberculosis (TB) comorbidity is a clinical problem that presents a challenge for the diagnosis and treatment of both diseases. To clarify the clinical and survival characteristics of cases with both lung cancer and active pulmonary TB. From 2008 to 2013, 3350 TB patients admitted to the TB Department of the Chest Diseases Hospital of Izmir, Turkey, were evaluated. In 38 (1.1%) male patients, lung cancer and TB were found to coexist. Almost all of the patients were diagnosed at Stage III (n = 14, 36.8%) or IV (n = 17, 44.7%) lung cancer, whereas four (10.6%) had Stage II and three (7.9%) had Stage I disease. Squamous cell lung cancer was the predominant histology (n = 23, 60.7%). The median overall survival among patients was 13.4 months (95%CI 8.09-18.8). One-year survival rates for patients with Stages I, II, III and IV were respectively 100%, 75%, 57% and 40%. The present study demonstrates that lung cancer combined with active pulmonary TB most frequently presents as squamous cell carcinoma, with a male predominance. The overall survival of lung cancer patients did not change even with concomitant active TB.

Role of oral candidiasis in TB and HIV co-infection: AIDS Clinical Trial Group Protocol A5253

PubMed Central

Shiboski, C. H.; Chen, H.; Ghannoum, M. A.; Komarow, L.; Evans, S.; Mukherjee, P. K.; Isham, N.; Katzenstein, D.; Asmelash, A.; Omozoarhe, A. E.; Gengiah, S.; Allen, R.; Tripathy, S.; Swindells, S.

2014-01-01

SUMMARY OBJECTIVE To evaluate the association between oral candidiasis and tuberculosis (TB) in human immunodeficiency virus (HIV) infected individuals in sub-Saharan Africa, and to investigate oral candidiasis as a potential tool for TB case finding. METHODS Protocol A5253 was a cross-sectional study designed to improve the diagnosis of pulmonary TB in HIV-infected adults in high TB prevalence countries. Participants received an oral examination to detect oral candidiasis. We estimated the association between TB disease and oral candidiasis using logistic regression, and sensitivity, specificity and predictive values. RESULTS Of 454 participants with TB culture results enrolled in African sites, the median age was 33 years, 71% were female and the median CD4 count was 257 cells/mm3. Fifty-four (12%) had TB disease; the prevalence of oral candidiasis was significantly higher among TB cases (35%) than among non-TB cases (16%, P < 0.001). The odds of having TB was 2.4 times higher among those with oral candidiasis when controlling for CD4 count and antifungals (95%CI 1.2–4.7, P = 0.01). The sensitivity of oral candidiasis as a predictor of TB was 35% (95%CI 22–48) and the specificity 85% (95%CI 81–88). CONCLUSION We found a strong association between oral candidiasis and TB disease, independent of CD4 count, suggesting that in resource-limited settings, oral candidiasis may provide clinical evidence for increased risk of TB and contribute to TB case finding. PMID:24903939

Considerations for biomarker-targeted intervention strategies for tuberculosis disease prevention.

PubMed

Fiore-Gartland, Andrew; Carpp, Lindsay N; Naidoo, Kogieleum; Thompson, Ethan; Zak, Daniel E; Self, Steve; Churchyard, Gavin; Walzl, Gerhard; Penn-Nicholson, Adam; Scriba, Thomas J; Hatherill, Mark

2018-03-01

Current diagnostic tests for Mycobacterium tuberculosis (MTB) infection have low prognostic specificity for identifying individuals who will develop tuberculosis (TB) disease, making mass preventive therapy strategies targeting all MTB-infected individuals impractical in high-burden TB countries. Here we discuss general considerations for a risk-targeted test-and-treat strategy based on a highly specific transcriptomic biomarker that can identify individuals who are most likely to progress to active TB disease as well as individuals with TB disease who have not yet presented for medical care. Such risk-targeted strategies may offer a rapid, ethical and cost-effective path towards decreasing the burden of TB disease and interrupting transmission and would also be critical to achieving TB elimination in countries nearing elimination. We also discuss design considerations for a Correlate of Risk Targeted Intervention Study (CORTIS), which could provide proof-of-concept for the strategy. One such study in South Africa is currently enrolling 1500 high-risk and 1700 low-risk individuals, as defined by biomarker status, and is randomizing high-risk participants to TB preventive therapy or standard of care treatment. All participants are monitored for progression to active TB with primary objectives to assess efficacy of the treatment and performance of the biomarker. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Framework of behavioral indicators for outcome evaluation of TB health promotion: a Delphi study of TB suspects and Tb patients

PubMed Central

2014-01-01

Background Health promotion for prevention and control of Tuberculosis (TB) is implemented worldwide because of its importance, but few reports have evaluated its impact on behavior due to a lack of standard outcome indicators. The objective of this study was to establish a framework of behavioral indicators for outcome evaluation of TB health promotion among TB suspects and patients. Methods A two-round modified Delphi method involving sixteen TB control experts was used to establish a framework of behavioral indicators for outcome evaluation of TB health promotion targeted at TB suspects and patients. Results Sixteen of seventeen invited experts in TB control (authority score of 0.91 on a 1.0 scale) participated in round 1 survey. All sixteen experts also participated in a second round survey. After two rounds of surveys and several iterations among the experts, there was consensus on a framework of indicators for measuring outcomes of TB health promotion for TB suspects and patients. For TB suspects, the experts reached consensus on 2 domains (“Healthcare seeking behavior” and “Transmission prevention”), 3 subdomains (“Seeking care after onset of TB symptoms”, “Pathways of seeking care” and “Interpersonal contact etiquette”), and 8 indicators (including among others, “Length of patient delay”). For TB patients, consensus was reached on 3 domains (“Adherence to treatment”, “Healthy lifestyle” and “Transmission prevention”), 8 subdomains (including among others, “Adherence to their medication”), and 14 indicators (including “Percentage of patients who adhered to their medication”). Operational definitions and data sources were provided for each indicator. Conclusions The findings of this study provide the basis for debate among international experts on a framework for achieving global consensus on outcome indicators for TB health promotion interventions targeted at TB patients and suspects. Such consensus will help to

[CLINICAL UTILITY OF T-SPOT.TB ASSAY WITH T-Cell Xtend REAGENT FOR ACTIVE TUBERCULOSIS DIAGNOSIS IN THE FIELD TEST AT OUR HOSPITAL].

PubMed

Nemoto, Kenji; Oh-ishi, Shuji; Taguchi, Masato; Hyodo, Kentaro; Kanazawa, Jun; Miura, Yukiko; Takaku, Takio; Usui, Shingo; Hayashihara, Kenji; Saito, Takefumi

2016-04-01

T-SPOT.TB (T-SPOT), an interferon-gamma release assay, has shown promise as a diagnostic tool for active tuberculosis (TB), and its use is expanding. Addition of the T-Cell Xtend (TCX) reagent may allow delayed processing, and this characteristic is important for using this test in the field. However, limited data is available on the usefulness of T-SPOT with TCX as a field test for diagnosing active TB. To investigate the clinical utility of T-SPOT with TCX and the risk factors for a false-negative result in patients with active TB. A total of 57 patients with active TB who underwent the T-SPOT test with TCX prior to treatment were enrolled between May 2013 and May 2015. One patient with an indeterminate result for T-SPOT was excluded; therefore, the data of 56 patients were eventually included in the final analysis. The basic characteristics and clinical findings were compared between the true-positive and false-negative T-SPOT groups. Of the 56 patients, 40 (71.4%), 13 (23.2%), 3 (5.4%) had true-positive, false-negative, and borderline T-SPOT results, respectively. This study did not reveal any significant risk factors for a false-negative T-SPOT result. In this clinical study, the proportion of patients with a false-negative result for T-SPOT with TCX for active TB was higher than that reported previously. Therefore, careful interpretation of a negative result for T-SPOT with TCX is necessary, regardless of the patient's background.

Inhibitory effect of Xenorhabdus nematophila TB on plant pathogens Phytophthora capsici and Botrytis cinerea in vitro and in planta

PubMed Central

Fang, Xiangling; Zhang, Manrang; Tang, Qian; Wang, Yonghong; Zhang, Xing

2014-01-01

Entomopathogenic bacteria Xenorhabdus spp. produce secondary metabolites with potential antimicrobial activity for use in agricultural productions. This study evaluated the inhibitory effect of X. nematophila TB culture on plant pathogens Botrytis cinerea and Phytophthora capsici. The cell-free filtrate of TB culture showed strong inhibitory effects (>90%) on mycelial growth of both pathogens. The methanol-extracted bioactive compounds (methanol extract) of TB culture also had strong inhibitory effects on mycelial growth and spore germinations of both pathogens. The methanol extract (1000 μg/mL) and cell-free filtrate both showed strong therapeutic and protective effects (>70%) on grey mold both in detached tomato fruits and plants, and leaf scorch in pepper plants. This study demonstrates X. nematophila TB produces antimicrobial metabolites of strong activity on plant pathogens, with great potential for controlling tomato grey mold and pepper leaf scorch and being used in integrated disease control to reduce chemical application. PMID:24599183

Inhibitory effect of Xenorhabdus nematophila TB on plant pathogens Phytophthora capsici and Botrytis cinerea in vitro and in planta.

PubMed

Fang, Xiangling; Zhang, Manrang; Tang, Qian; Wang, Yonghong; Zhang, Xing

2014-03-06

Entomopathogenic bacteria Xenorhabdus spp. produce secondary metabolites with potential antimicrobial activity for use in agricultural productions. This study evaluated the inhibitory effect of X. nematophila TB culture on plant pathogens Botrytis cinerea and Phytophthora capsici. The cell-free filtrate of TB culture showed strong inhibitory effects (>90%) on mycelial growth of both pathogens. The methanol-extracted bioactive compounds (methanol extract) of TB culture also had strong inhibitory effects on mycelial growth and spore germinations of both pathogens. The methanol extract (1000 μg/mL) and cell-free filtrate both showed strong therapeutic and protective effects (>70%) on grey mold both in detached tomato fruits and plants, and leaf scorch in pepper plants. This study demonstrates X. nematophila TB produces antimicrobial metabolites of strong activity on plant pathogens, with great potential for controlling tomato grey mold and pepper leaf scorch and being used in integrated disease control to reduce chemical application.

Lithium-aluminum-zinc phosphate glasses activated with Tb3+ and Tb3+/Eu3+ for green laser medium, reddish-orange and white phosphor applications

NASA Astrophysics Data System (ADS)

Francisco-Rodriguez, H. I.; Lira, A.; Soriano-Romero, O.; Meza-Rocha, A. N.; Bordignon, S.; Speghini, A.; Lozada-Morales, R.; Caldiño, U.

2018-05-01

A spectroscopic analysis of Tb3+ and Tb3+/Eu3+ doped lithium-aluminum-zinc phosphate glasses is performed through their absorbance and photoluminescence spectra, and decay time profiles. Laser parameter values (stimulated emission cross section, effective bandwidth, gain bandwidth and optical gain) were obtained for the terbium 5D4 → 7F5 green emission from the Tb3+ singly-doped glass (LAZT) excited at 350 nm to judge the suitability of the glass phosphor for fiber lasers. A quantum yield of (47.68 ± 0.49)% was measured for the 5D4 level luminescence. Upon 350 nm excitation the LAZT glass phosphor emits green light with a color purity of 65.6% and chromaticity coordinates (0.285, 0.585) very close to those (0.29, 0.60) of European Broadcasting Union illuminant green. The Tb3+/Eu3+codoped glass emission color can be tuned from reddish-orange of 1865 K upon 318 nm excitation to warm white of 3599 K and neutral white of 4049 K upon 359 and 340 nm excitations, respectively. Upon Tb3+ excitation at 340 nm Eu3+ is sensitized by Tb3+ through a non-radiative energy transfer with an efficiency of 0.23-0.26. An electric dipole-dipole interaction might be the dominant mechanism in the Tb3+ to Eu3+ energy transfer taking place into Tb3+ - Eu3+ clusters.

Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network.

PubMed

Suwanpimolkul, Gompol; Kawkitinarong, Kamon; Manosuthi, Weerawat; Sophonphan, Jiratchaya; Gatechompol, Sivaporn; Ohata, Pirapon June; Ubolyam, Sasiwimol; Iampornsin, Thatri; Katerattanakul, Pairaj; Avihingsanon, Anchalee; Ruxrungtham, Kiat

2017-06-01

To evaluate the applicability and accuracy of the urine lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and HIV-negative patients with disseminated TB. Frozen urine samples obtained at baseline from patients in the TB research cohort with proven culture-positive TB were selected for blinded urine LAM testing. One hundred and nine patients were categorized into four groups: (1) HIV-positive patients with TB; (2) HIV-negative patients with disseminated TB; (3) HIV-negative immunocompromised patients with TB; and (4) patients with diseases other than TB. The sensitivity of urine LAM testing for culture-positive TB, specificity of urine LAM testing for patients without TB, positive predictive value (PPV), and negative predictive value (NPV) were assessed. The sensitivity of the urine LAM test in group 1 patients with a CD4 T-cell count of >100, ≤100, and ≤50 cells/mm 3 was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2 and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A positive urine LAM test result was significantly associated with death. This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Is TB in Your Curriculum?

ERIC Educational Resources Information Center

Kerr, Joanne; Elwell, Jack

2002-01-01

Points out the importance of effective health education to fight against tuberculosis (TB) which is the number one fatal infectious disease around the world. Describes a science curriculum on tuberculosis that includes information on the facts about tuberculosis, a forum on tuberculosis, and evaluation. (Contains 17 references.) (YDS)

Understanding Market Size and Reporting Gaps for Paediatric TB in Indonesia, Nigeria and Pakistan: Supporting Improved Treatment of Childhood TB in the Advent of New Medicines

PubMed Central

2015-01-01

Objective of the Study We sought to understand gaps in reporting childhood TB cases among public and private sector health facilities (dubbed “non-NTP” facilities) outside the network of national TB control programmes, and the resulting impact of under-reporting on estimates of paediatric disease burden and market demand for new medicines. Methodology Exploratory assessments were carried out in Indonesia, Nigeria and Pakistan, reaching a range of facility types in two selected areas of each country. Record reviews and interviews of healthcare providers were carried out to assess numbers of unreported paediatric TB cases, diagnostic pathways followed and treatment regimens prescribed. Main Findings A total of 985 unreported diagnosed paediatric TB cases were identified over a three month period in 2013 in Indonesia from 64 facilities, 463 in Pakistan from 35 facilities and 24 in Nigeria from 20 facilities. These represent an absolute additional annualised yield to 2013 notifications reported to WHO of 15% for Indonesia, 2% for Nigeria and 7% for Pakistan. Only 12% of all facilities provided age and sex-disaggregated data. Findings highlight the challenges of confirming childhood TB. Diagnosis patterns in Nigeria highlight a very low suspicion for childhood TB. Providers note the need for paediatric medicines aligned to WHO recommendations. Conclusion: How Market Data Can Support Better Public Health Interventions This study emphasises the impact of incomplete reporting on the estimation of disease burden and potential market size of paediatric TB medicines. Further studies on “hubs” (facilities treating large numbers of childhood TB cases) will improve our understanding of the epidemic, support introduction efforts for new treatments and better measure markets for new paediatric medicines. PMID:26460607

Testing for TB Infection

MedlinePlus

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

Dr Mario Raviglione, director of the Stop TB Department World Health Organization. Interview by Christo Hall.

PubMed

Raviglione, Mario

2012-03-01

Tuberculosis (TB) is a very global disease; there are over 9 million new incidences of TB every year with the vast majority of cases emerging in the developing world. As one of three major diseases associated with poverty it affects the areas where poverty is most prevalent, notably Asia and Africa. While the incidence rate has been slowly declining in the developed world it continues to pose a major health threat to even the most developed nations. To demonstrate the global, and persistent, nature of TB we asked Dr Mario Raviglione, Director of the World Health Organization's Stop TB Department to provide an analysis on the current TB situation in the United Kingdom and comment on what measures should be taken to alleviate the issue of TB in one of the world's richest countries.

Indoor air pollution from secondhand tobacco smoke, solid fuels, and kerosene in homes with active tuberculosis disease in South Africa.

PubMed

Elf, Jessica L; Eke, Onyinyechi; Rakgokong, Modiehi; Variava, Ebrahim; Baliram, Yudesh; Motlhaoleng, Katlego; Lebina, Limakatso; Shapiro, Adrienne E; Breysse, Patrick N; Golub, Jonathan E; Martinson, Neil

2017-11-13

Secondhand tobacco smoke (SHS), use of solid fuels, and kerosene may play an important role in perpetuating the tuberculosis (TB) epidemic. The purpose of this study was to explore the prevalence of household air pollution (HAP) from these sources in homes of someone with TB in a high HIV-prevalence setting. A convenience sample of homes and household members participating in an ongoing active case-finding study in Matlosana district townships surrounding Klerksdorp, South Africa were included. We found a high prevalence of air pollution from SHS, solid fuels, and kerosene among individuals in homes with a case of prevalent active TB disease in Klerksdorp, South Africa. Adults in 40% of homes reported a daily smoker in the home, and 70% of homes had detectable air nicotine. In homes with a history of previous TB (prior to but not including the index case) as compared to those without previous TB, both SHS (83% vs. 65%, respectively) and solid/kerosene fuel use for more than 1 h/day (27% vs. 21%, respectively) were more prevalent. Larger studies are needed to estimate the risk of TB from these types of air pollution in HIV infected individuals and settings with high HIV prevalence.

Evaluation of accessory cell heterogeneity. I. Differential accessory cell requirement for T helper cell activation and for T-B cooperation.

PubMed

Ramila, G; Studer, S; Kennedy, M; Sklenar, I; Erb, P

1985-01-01

Several Ia+ tumor cell lines and peritoneal exudate macrophages were tested as accessory cells (AC) for the activation of antigen-specific T cells and for T-B cooperation. The macrophages and all the Ia+ tumor lines tested induced the release of lymphokines from T cells in a major histocompatibility complex (MHC)-restricted fashion and reconstituted the antibody responses of AC-depleted spleen cells or of purified T and B cells. However, only the normal macrophages but none of the tumor lines induced carrier-specific T helper (Th) cells which help B cells for specific antihapten antibody responses by linked recognition. For T-B cooperation accessory cells were also required, but in contrast to Th cell activation any type of Ia+ AC (e.g. macrophage or tumor line) was effective. Strong MHC-restriction between the lymphocytes and the AC was seen if antigen-pulsed AC were added into the AC-depleted T-B cooperation cultures. If the AC and antigen were concomitantly added to the AC-depleted T-B cultures, MHC-restriction was less obvious. Concanavalin A supernatant reconstituted the response of AC-depleted T-B cultures provided antigen-specific Th cells and the hapten-carrier conjugate were present. If, however, tumor line-activated T cells were added instead of macrophage-induced Th cells, no cooperation with B cells took place even in the presence of Con A supernatant. The results obtained demonstrate a differential AC requirement for the induction of Th cells depending on the differentiation stage of the Th cells.

Hit Generation in TB Drug Discovery: From Genome to Granuloma

PubMed Central

2018-01-01

Current tuberculosis (TB) drug development efforts are not sufficient to end the global TB epidemic. Recent efforts have focused on the development of whole-cell screening assays because biochemical, target-based inhibitor screens during the last two decades have not delivered new TB drugs. Mycobacterium tuberculosis (Mtb), the causative agent of TB, encounters diverse microenvironments and can be found in a variety of metabolic states in the human host. Due to the complexity and heterogeneity of Mtb infection, no single model can fully recapitulate the in vivo conditions in which Mtb is found in TB patients, and there is no single “standard” screening condition to generate hit compounds for TB drug development. However, current screening assays have become more sophisticated as researchers attempt to mirror the complexity of TB disease in the laboratory. In this review, we describe efforts using surrogates and engineered strains of Mtb to focus screens on specific targets. We explain model culture systems ranging from carbon starvation to hypoxia, and combinations thereof, designed to represent the microenvironment which Mtb encounters in the human body. We outline ongoing efforts to model Mtb infection in the lung granuloma. We assess these different models, their ability to generate hit compounds, and needs for further TB drug development, to provide direction for future TB drug discovery. PMID:29384369

Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

PubMed Central

Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

2012-01-01

Background Significant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings. Methods Médecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE. Results Between May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen. Conclusions AE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays

Prevalence and Risk factors for Drug Resistance among Hospitalized TB Patients in Georgia

PubMed Central

Vashakidze, L; Salakaia, A.; Shubladze, N.; Cynamon, M.; Barbakadze, K.; Kikvidze, M.; Papitashvili, L.; Nonikashvili, M.; Solomonia, N.; Bejanishvili, N.; Khurtsilava, I.

2010-01-01

SUMMARY Background Tuberculosis control in Georgia follows the WHO recommended DOTS strategy and has reached Global TB Control targets in treatment of sensitive TB, but the management of drug resistant forms of TB still represents a serious problem. A country-wide Drug Resistance Survey (DRS) found that the prevalence of MDR-TB was 6.8% in new and 27.4% in previously treated TB cases. Objective To determine prevalence and risk factors for drug resistance among TB patients in order to improve DR-TB case management and control. Methods Extensive social, clinical and bacteriological data were collected from hospitalized patients (National Centre for Tuberculosis and Lung Diseases, Georgia, 2005–2007). Results Out of 605 patients DR-TB was found in 491 (81.2%) cases, MDR-TB was observed in 261(43.1%) [51 (23%) out of 222 New cases and 210 (55%) out of 383 Previously treated cases], mono-DR-TB in 130 (21.5%), poly-DR-TB in 67 (11.1%) and XDR-TB in 33 (5.5%) cases. Study showed that female gender, living in densely populated capital, family TB contact and previous TB treatment are associated with risk for having MDR-TB. Conclusions Findings confirm the necessity of improvement of infection control measures and availability of standardized treatment for DR-TB patients. PMID:19723406

The Soluble Plasminogen Activator Receptor as a Biomarker on Monitoring the Therapy Progress of Pulmonary TB-AFB(+) Patients

PubMed Central

Mardining Raras, Tri Yudani; Noor Chozin, Iin

2010-01-01

The role of soluble soluble urokinase-type plasminogen activator receptor (suPAR) as a biological marker for TB treatment efficacy on active pulmonary TB-AFB(+) patients was investigated. Twenty pulmonary TB-AFB(+) patients participated in a cohort study for six months. The plasma suPAR level was measured using ELISA method before treatment, two months, four months and six months after treatment. At the same time clinical parameters were also measured. Results indicated that all patients (n = 20) showed highest plasma suPAR levels before treatment (median 12.775 ng/mL) and significantly decreased ( P = .0001<.05, R 2 = .890) after 2 months (median 8.019 ng/mL) and 4 months (median 5.771 ng/mL) of treatment, respectively. However, only slightly declined after 6 months therapy (median 5.009 ng/mL), near control group level (median 4.772 ng/mL). Interestingly, the significant reduced of suPAR level was parallel to treatment efficacy and correlated with other clinical and laboratory parameters, that is, decreasing of patients' complaints, increasing of BMI (r = −0.281), thoracic imaging improvement, sputum conversion, decreasing of ESR (r = 0.577) and monocytes count (r = 0.536) with exception the width of lesion in thoracic imaging. In conclusion, the suPAR level in could reflect the progress of TB therapy. PMID:22567258

Validation of the BrockTB Stat-Pak Assay for Detection of Tuberculosis in Eurasian Badgers (Meles meles) and Influence of Disease Severity on Diagnostic Accuracy▿

PubMed Central

Chambers, Mark A.; Crawshaw, Tim; Waterhouse, Sue; Delahay, Richard; Hewinson, R. Glyn; Lyashchenko, Konstantin P.

2008-01-01

A lateral-flow immunoassay (BrockTB Stat-Pak) for detecting tuberculosis in Eurasian badgers was 49% sensitive and 93% specific against culture for M. bovis (n = 1,464) at necropsy. However, the sensitivity was significantly higher (66 to 78%) in animals with more severe tuberculosis, indicating that the BrockTB Stat-Pak may be useful for the detection of badgers with the greatest risk of transmitting disease. PMID:18272706

Interdisciplinary Public Health Intervention in a Multigenerational Tuberculosis (TB) Outbreak in Harris County, Texas: A Case Study with Implications for Disease Control Process Improvement and Transmission Cycle Interruption

PubMed Central

Haynie, Aisha; Plasencia, Carlos; Fields, Kimberly; Nesbitt, Elna; Lovings-Clark, Audrey; Scott, Mary; Wiltz-Beckham, Dana; Reed, Brian; Shah, Umair A

2017-01-01

Abstract Background Harris County Public Health (HCPH) is the health department for Harris County, Texas jurisdiction. Harris County as a whole is the nation’s third most populous county, with 4.3 million residents, and a TB case rate more than double that of the USA. (7.6 cases per 100,000 pop). A total, 327 individuals were diagnosed with TB in Harris County during 2015, over two-thirds occurring in foreign-born individuals. In 2016, HCPH treated an immigrant female with active TB. Initial contact investigation (CI) yielded five household contacts (HHC). Two tested positive, but refused subsequent clinical evaluation by HCPH. Two months later, HCPH was notified of a HHC hospitalized with TB. After hospital discharge, the sick HHC moved into a motel in attempts to self-isolate, but refused evaluation of additional HHC in the home, and banned home access, precluding adequate CI. After numerous phone calls, visits to motel and home, and multiple rescheduled appointments, legal action appeared inevitable. Days later, HCPH was notified of another HHC diagnosed with active TB. Methods With alarm regarding the family’s adherence to control orders, TB staff implemented an innovative multidisciplinary team-based intervention in hopes of avoiding legal action. A site visit was paid to the motel by a local health authority, two TB staff, a county public investigator, and a refugee clinic outreach worker fluent in the family’s language. Patients were presented with letters requesting immediate cooperation to avoid court filings. Questions were answered, misinformation corrected, and education provided. Results Intermediary on-site intervention using a compassionate, firm multidisciplinary team approach resulted in 16 additional family members tested, yielding an infant with active TB (Case 4) and 8 with TB Infection (TBI). Isolation breaches were also discovered. Most importantly, TB transmission cycle was interrupted. Cultural and economic barriers hindering

Research Advances: New Weapon in War on TB

ERIC Educational Resources Information Center

King, Angela G.

2005-01-01

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis, which usually attacks the lung and is spread through the air from one person to another. Researchers from Johnson & Johnson Pharmaceutical Research and Development, the Swedish Institute for Infectious Disease Control and The Pitie-Salpetriere School of Medicine began their…

The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome

PubMed Central

Manabe, Yukari C.; Kesavan, Anup K.; Lopez-Molina, Javier; Hatem, Christine L.; Brooks, Megan; Fujiwara, Ricardo; Hochstein, Karl; Pitt, M. Louise M.; Tufariello, JoAnn; Chan, John; McMurray, David N.; Bishai, William R.; Dannenberg, Arthur M.; Mendez, Susana

2015-01-01

The large reservoir of human latent tuberculosis (TB) contributes to the global success of the pathogen, Mycobacterium tuberculosis (Mtb). We sought to test whether aerosol infection of rabbits with Mtb H37Rv could model paucibacillary human latent TB. The lung burden of infection peaked at 5 weeks after aerosol infection followed by host containment of infection that was achieved in all rabbits. One-third of rabbits had at least one caseous granuloma with culturable bacilli at 36 weeks after infection suggesting persistent paucibacillary infection. Corticosteroid-induced immunosuppression initiated after disease containment resulted in reactivation of disease. Seventy-two percent of rabbits had culturable bacilli in the right upper lung lobe homogenates compared to none of the untreated controls. Discontinuation of dexamethasone led to predictable lymphoid recovery, with a proportion of rabbits developing multicentric large caseous granuloma. The development and severity of the immune reconstitution inflammatory syndrome (IRIS) was dependent on the antigen load at the time of immunosuppression and subsequent bacillary replication during corticosteroid-induced immunosuppression. Clinically, many aspects were similar to IRIS in severely immunosuppressed HIV-infected patients who have functional restoration of T cells in response to effective (highly active) antiretroviral therapy. This corticosteroid model is the only animal model of the IRIS. Further study of the rabbit model of TB latency, reactivation and IRIS may be important in understanding the immunopathogenesis of these poorly modeled states as well as for improved diagnostics for specific stages of disease. PMID:18068491

Nitroimidazoles for the treatment of TB: past, present and future

PubMed Central

Mukherjee, Tathagata; Boshoff, Helena

2011-01-01

Tuberculosis remains a leading cause of death resulting from an infectious agent, and the spread of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis poses a threat to management of global health. New drugs that effectively shorten the duration of treatment and are active against drug-resistant strains of this pathogen are urgently required to develop effective chemotherapies to combat this disease. Two nitroimidazoles, PA-824 and OPC-67683, are currently in Phase II clinical trials for the treatment of TB and the outcome of these may determine the future directions of drug development for anti-tubercular nitroimidazoles. In this review we summarize the development of these nitroimidazoles and alternative analogs in these series that may offer attractive alternatives to PA-824 and OPC-67683 for further development in the drug-discovery pipeline. Lastly, the potential pitfalls in the development of nitroimidazoles as drugs for TB are discussed. PMID:21879846

Prevalence of pulmonary TB and spoligotype pattern of Mycobacterium tuberculosis among TB suspects in a rural community in Southwest Ethiopia

PubMed Central

2012-01-01

Background In Ethiopia where there is no strong surveillance system and state of the art diagnostic facilities are limited, the real burden of tuberculosis (TB) is not well known. We conducted a community based survey to estimate the prevalence of pulmonary TB and spoligotype pattern of the Mycobacterium tuberculosis isolates in Southwest Ethiopia. Methods A total of 30040 adults in 10882 households were screened for pulmonary TB in Gilgel Gibe field research centre in Southwest Ethiopia. A total of 482 TB suspects were identified and smear microscopy and culture was done for 428 TB suspects. Counseling and testing for HIV/AIDS was done for all TB suspects. Spoligotyping was done to characterize the Mycobacterium tuberculosis isolates. Results Majority of the TB suspects were females (60.7%) and non-literates (83.6%). Using smear microscopy, a total of 5 new and 4 old cases of pulmonary TB cases were identified making the prevalence of TB 30 per 100,000. However, using the culture method, we identified 17 new cases with a prevalence of 76.1 per 100,000. There were 4.3 undiagnosed pulmonary TB cases for every TB case who was diagnosed through the passive case detection mechanism in the health facility. Eleven isolates (64.7%) belonged to the six previously known spoligotypes: T, Haarlem and Central-Asian (CAS). Six new spoligotype patterns of Mycobacterium tuberculosis, not present in the international database (SpolDB4) were identified. None of the rural residents was HIV infected and only 5 (5.5%) of the urban TB suspects were positive for HIV. Conclusion The prevalence of TB in the rural community of Southwest Ethiopia is low. There are large numbers of undiagnosed TB cases in the community. However, the number of sputum smear-positive cases was very low and therefore the risk of transmitting the infection to others may be limited. Active case finding through health extension workers in the community can improve the low case detection rate in Ethiopia. A large

Perception of stigma towards TB among patients on DOTS & patients attending general OPD in Delhi.

PubMed

Anand, Tanu; Kumar, D Arun; Sharma, Nandini; Saha, Renuka; Krishnamurthy, Laxmi; Singh, S V; Ingle, G K

2014-01-01

In India, Tuberculosis (TB) continues to be a public health problem. One of the key reasons for it is the stigma associated with the disease which affects the treatment seeking behaviour and hence the outcome. To assess the perceived and enacted stigma among TB patients and perceptions of other patients related to TB in Central Delhi. A cross-sectional study conducted in urban field practice area of a medical college of Delhi, using a pre-designed questionnaire containing items for assessment of stigma being faced by a TB patient in family, social life and workplace. It also contained questions pertaining to reaction of patients from general OPD to a family member who develops TB. A total of 100 patients on DOTS and 200 patients from general OPD were interviewed. There were 21 patients who reported to have delayed treatment seeking due to stigma. Nearly one third patients (n=34; 34%) noted negative changes in the behaviour of their family members towards them while 40% were isolated on being diagnosed with the disease. Out of the 36 employed TB patients, 65.5% (n=23) experienced negative change in the behaviour of their colleagues. In general OPD patients, significantly higher proportion of female patients said that they would not disclose the disease status of a family member suffering from TB to their neighbours (p<0.001). Perception of stigmatizing effect of Tuberculosis was high both amongst TB and other patients. Behaviour Change Communication (BCC) strategies are needed to address the effects of stigma like delayed treatment seeking.

Public-private mix for TB and TB-HIV care in Lagos, Nigeria.

PubMed

Daniel, O J; Adedeji Adejumo, O; Abdur-Razzaq, H A; Ngozi Adejumo, E; Salako, A A

2013-09-01

Private and public tuberculosis (TB) treatment centres in Lagos State, Nigeria. To assess the contribution of private health care providers to TB and TB-HIV (human immunodeficiency virus) case finding in Lagos State. A retrospective review of programme data submitted to the Lagos State TB and Leprosy Control Programme in 2011 by public, private for-profit (PFP) and private not-for-profit (PNFP) health care providers. A total of 8425 TB cases were notified by 31 private (11 PFP and 20 PNFP) and 99 public health facilities in Lagos State. Overall, the private facilities were responsible for 10.3% (866/8425) of the total TB cases notified. The proportion of TB patients tested for HIV was respectively 86.2%, 53.1% and 96.5% among public, PFP and PNFP facilities. Overall, 22.4% of the TB patients were HIV-positive. The HIV positivity rate among public, PFP and PNFP facilities was respectively 23.8%, 7.8% and 9.9%. Uptake of cotrimoxazole preventive therapy was respectively 69.6%, 25% and 38.2% among public, PFP and PNFP facilities, while that of antiretroviral therapy was respectively 23.8%, 8.3% and 9.1% in public, PFP and PNFP facilities. There is a need to scale up collaboration with the private sector, and particularly PNFP health providers.

Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility in a murine M.tb infection model

PubMed Central

Harrington-Kandt, Rachel; Stylianou, Elena; Eddowes, Lucy A.; Lim, Pei Jin; Stockdale, Lisa; Pinpathomrat, Nawamin; Bull, Naomi; Pasricha, Janet; Ulaszewska, Marta; Beglov, Yulia; Vaulont, Sophie

2018-01-01

Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection. Here, we investigated hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of iron-responsive genes was measured by qRT-PCR and bacterial burden determined in organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post-infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1 knockout mice did not have a significantly altered M.tb mycobacterial load in either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not robustly affect disease outcome despite causing iron deficiency anaemia. Taken together, our data indicate that unlike with many other infections, hepcidin is decreased following M.tb infection, and show that hepcidin ablation does not influence M.tb growth in vivo. Furthermore, because even severe iron deficiency did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses to scavenge iron from the host must be extremely efficient, and may therefore represent potential targets for drugs and vaccines. PMID:29324800

Global evidence directing regional preventive strategies in Southeast Asia for fighting TB/HIV.

PubMed

Aung, Myo Nyein; Moolphate, Saiyud; Paudel, Damodar; Jayathunge Ph, Mangalasiri; Duangrithi, Duangjai; Wangdi, Kinley; Aung, Thin Nyein Nyein; Lorga, Thaworn; Higuchi, Kazue

2013-03-14

Tuberculosis (TB) and human immunodeficiency virus (HIV) co-epidemics form a huge burden of disease in the Southeast Asia region. Five out of eleven nations in this region are high TB/HIV burden countries: Myanmar, Thailand, India, Indonesia and Nepal. The trends of TB incidence in these countries have been rising in recent years, in contrast to a falling global trend. Experts in the field of TB control and health service providers have been perplexed by the association of TB and HIV infections which causes a mosaic clinical presentation, a unique course with poor treatment outcomes including death. We conducted a review of contemporary evidence relating to TB/HIV control with the aims of assisting integrated health system responses in Southeast Asia and demystifying current evidence to facilitate translating it into practice.

Poor continuity of care for TB diagnosis and treatment in Zambian Prisons: a situation analysis.

PubMed

Hatwiinda, S; Topp, S M; Siyambango, M; Harris, J B; Maggard, K R; Chileshe, C; Kapata, N; Reid, S E; Henostroza, G

2018-02-01

Prisons act as infectious disease reservoirs. We aimed to explore the challenges of TB control and continuity of care in prisons in Zambia. We evaluated treatment outcomes for a cohort of inmates diagnosed with TB during a TB REACH funded screening programme initiated by the Zambia Prisons Service and the Centre for Infectious Disease Research in Zambia. Between October 2010 and September 2011, 6282 inmates from six prisons were screened for TB, of whom 374 (6.0%) were diagnosed. TB treatment was initiated in 345 of 374 (92%) inmates. Of those, 66% were cured or completed treatment, 5% died and 29% were lost to follow-up. Among those lost to follow-up, 11% were released into the community and 13% were transferred to other prisons. Weak health systems within the Zambian prison service currently undermines continuity of care, despite intensive TB screening and case-finding interventions. To prevent TB transmission and the development of drug resistance, we need sufficient numbers of competent staff for health care, reliable health information systems including electronic record keeping for prison facilities, and standard operating procedures to guide surveillance, case-finding and timely treatment initiation and completion. © 2017 John Wiley & Sons Ltd.

Linkage to HIV, TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town, South Africa

PubMed Central

Govindasamy, Darshini; Kranzer, Katharina; van Schaik, Nienke; Noubary, Farzad; Wood, Robin; Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.; Bekker, Linda-Gail

2013-01-01

Background HIV counseling and testing may serve as an entry point for non-communicable disease screening. Objectives To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. Methods A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. Results Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. Conclusion Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care. PMID:24236170

Systematic review on tuberculosis transmission on aircraft and update of the European Centre for Disease Prevention and Control risk assessment guidelines for tuberculosis transmitted on aircraft (RAGIDA-TB).

PubMed

Kotila, Saara M; Payne Hallström, Lara; Jansen, Niesje; Helbling, Peter; Abubakar, Ibrahim

2016-01-01

As a setting for potential tuberculosis (TB) transmission and contact tracing, aircraft pose specific challenges. Evidence-based guidelines are needed to support the related-risk assessment and contact-tracing efforts. In this study evidence of TB transmission on aircraft was identified to update the Risk Assessment Guidelines for TB Transmitted on Aircraft (RAGIDA-TB) of the European Centre for Disease Prevention and Control (ECDC). Electronic searches were undertaken from Medline (Pubmed), Embase and Cochrane Library until 19 July 2013. Eligible records were identified by a two-stage screening process and data on flight and index case characteristics as well as contact tracing strategies extracted. The systematic literature review retrieved 21 records. Ten of these records were available only after the previous version of the RAGIDA guidelines (2009) and World Health Organization guidelines on TB and air travel (2008) were published. Seven of the 21 records presented some evidence of possible in-flight transmission, but only one record provided substantial evidence of TB transmission on an aircraft. The data indicate that overall risk of TB transmission on aircraft is very low. The updated ECDC guidelines for TB transmission on aircraft have global implications due to inevitable need for international collaboration in contract tracing and risk assessment.

Recent developments of coumarin-containing derivatives and their anti-tubercular activity.

PubMed

Hu, Yuan-Qiang; Xu, Zhi; Zhang, Shu; Wu, Xiang; Ding, Jun-Wei; Lv, Zao-Sheng; Feng, Lian-Shun

2017-08-18

Tuberculosis (TB) is a lift-threatening chronic deadliest infectious disease caused predominantly by Mycobacterium tuberculosis (MTB) which affects primarily the lungs (pulmonary TB) apart from other vital organs. The emergence of drug-resistant TB (DR-TB), multidrug-resistant TB (MDR-TB), extensively drug-resistant TB (XDR-TB) and the recently cases of totally drug resistant (TDR) towards currently accessible standard drugs was increased up to alarming level in the recent decades. In pursuit of searching new anti-TB agents, numerous of derivatives have been synthesized and screened for their anti-TB activity. Coumarins are one of the most important classes of natural products that exhibited various biological activities, and their derivatives regarded as a new class of effective anti-TB candidates owing to their potential anti-TB activity. Thus, coumarin skeleton has attracted great interest in the development of new anti-TB agents. This review outlines the advances in the application of coumarin-containing derivatives as anti-TB agents and the critical aspects of design and structure-activity relationship of these derivatives. Published by Elsevier Masson SAS.

A Systematic Review of the Epidemiology, Immunopathogenesis, Diagnosis, and Treatment of Pleural TB in HIV- Infected Patients

PubMed Central

Aljohaney, A.; Amjadi, K.; Alvarez, G. G.

2012-01-01

Background. High HIV burden countries have experienced a high burden of pleural TB in HIV-infected patients. Objective. To review the epidemiology, immunopathogenesis, diagnosis, and treatment of pleural TB in HIV-infected patients. Methods. A literature search from 1950 to June 2011 in MEDLINE was conducted. Results. Two-hundred and ninety-nine studies were identified, of which 30 met the inclusion criteria. The immunopathogenesis as denoted by cells and cytokine profiles is distinctly different between HIV and HIV-uninfected pleural TB disease. Adenosine deaminase and interferon gamma are good markers of pleural TB disease even in HIV-infected patients. HIV-uninfected TB suspects with pleural effusions commonly have a low yield of TB organisms however the evidence suggests that in dually infected patients smear and cultures have a higher yield. The Gene Xpert MTB/RIF assay has significant potential to improve the diagnosis of pleural TB in HIV-positive patients. Conclusions. Pleural TB in HIV-infected patients has a different immunopathogenesis than HIV-uninfected pleural TB and these findings in part support the differences noted in this systematic review. Research should focus on developing an interferon gamma-based point of care diagnostic test and expansion of the role of Gene Xpert in the diagnosis of pleural TB. PMID:22474483

Yellow to orange-reddish glass phosphors: Sm3+, Tb3+ and Sm3+/Tb3+ in zinc tellurite-germanate glasses

NASA Astrophysics Data System (ADS)

Alvarez-Ramos, M. E.; Alvarado-Rivera, J.; Zayas, Ma. E.; Caldiño, U.; Hernández-Paredes, J.

2018-01-01

An optical spectroscopy analysis of TeO-GeO2-ZnO glass co-activating Sm3+/Tb3+ ions was carried out through Raman, photoluminescence spectra and decay time profiles as a function of Sm3+ concentration. According to the estimated CIE1931 chromaticity coordinates, the color of the emission can be adjusted from the yellow light region (0.4883, 0.4774), towards the reddish light region (0.5194,0.4144) by increasing the Sm3+ content from 1, 3, 5% mol, co-doped with 1% mol Tb3+ under co-excitation of Sm3+ and Tb3+ at 378 nm. The color temperatures are in the range of 1379-2804 K. Such photoluminescence is generated by the 4G 5/2 → 4H 5/2, 4H 7/2, 4H9/2 emissions of Sm3+ in addition to the 5D4→7F6,5,4,3 emissions of Tb3+; the single doped Sm3+ glass displayed an intense orange light. Meanwhile, co-doped Sm3+/Tb3+ glasses excited at 378 nm showed a significant reduction in Tb3+ emission, with a simultaneous increment in the reddish-orange emission of Sm3+, due to a non-radiative resonant energy transfer from Tb3+ to Sm3+. Decay time profile analysis of the Tb3+ emission as function of Sm3+ ion content suggests that an electric dipole-dipole interaction into Tb3+-Sm3+ clusters might dominate in the energy transfer process, with an efficiency and probability of 0.22, 0.27, 0.38 and 122.8, 327.6, 522.7 s-1, respectively.

Mini epidemic of isoniazide resistant TB in rural TN: a need for supervised preventive therapy.

PubMed

Mehta, Jay; Keith, Rob; Al Hasan, Muhannad; Ryland, Byrd; Roy, Thomas

2009-08-01

With the resurgence of tuberculosis (TB) in the late 1980s, multi-drug-resistant TB (MDR-TB) also became a serious challenge to the TB control programs across the United States (US). While the incidence of TB resumed a downward trend in the mid 1900s, drug-resistant TB continues to be a national and international problem. We reviewed the public health data of drug-resistant TB cases (1996-2002) in Greene County, TN, with a detailed analysis of their contact investigation. Our study included demographic data of age, sex, race, human immunodeficiency virus (HIV) status and other known risk factors for drug-resistant TB. Contact investigation of two patients with isoniazide-resistant active pulmonary TB led to the discovery of two additional cases of active pulmonary tuberculosis, one of them being a 14-month-old child. All four of the patients were U.S. born, had negative HIV tests, and lacked other risk factors for drug-resistant TB. In all four cases, the Mycobacterium tuberculosis isolates were resistant to isoniazide, three were streptomycin resistant, and was ethambutol resistant. A total of 65 close contacts were identified, 11 of whom had a positive purified protein derivative (PPD) skin test indicating latent TB infection. Based on the American Thoracic Society's recommendations, the contacts with a positive PPD were prescribed rifampin for chemo-prevention rather than INH. However, one active case was detected from this infected contact who had failed to comply with chemo-preventive therapy. The second active case was a child who developed active pulmonary TB before chemoprevention could be initiated. Drug culture profile and DNA analysis (RFLP) confirmed the same source for TB transmission. The 11/65 (16.5 percent) infection rate among the contact was comparable to the state average (p < 0.05), but the case rate of 4/65 (6.15 percent) was high. In two out of four active cases, who were family members of the known cases, active infection could have been

The Risk of Depressive Disorder Among Contacts of Tuberculosis Patients in a TB-endemic Area

PubMed Central

Pan, Sheng-Wei; Yen, Yung-Feng; Feng, Jia-Yih; Su, Vincent Yi-Fong; Kou, Yu Ru; Su, Wei-Juin

2015-01-01

Abstract Tuberculosis (TB) disease may be transmitted to close contacts of index cases, causing physical illness. No studies have investigated the risk of developing depressive disorder among TB contacts in a TB-endemic area. Adult participants with a new diagnosis of TB contact (ICD-9-CM codes V01.1 plus chest radiographic order) since January 1, 2008, were identified from the National Health Insurance Research Database in Taiwan. A control cohort matched for age (±5 y), sex, enrolled years, and income level was selected. These 2 cohorts were followed until December 31, 2012, and observed for the development of depressive disorder. The Kaplan-Meier method and the log-rank test were used to examine the difference in cumulative incidences of depressive disorder between groups. Cox proportional-hazard models were used to calculate adjusted hazard ratios (aHRs) for depressive disorder. The TB contact cohort consisted of 9046 patients and matched controls of 36,184 ones. The mean age of TB contacts was 44.7 years, and 56.0% of them were women. During a mean follow-up period of 2.5 years, 127 (1.40%) TB contacts and 521 (1.44%) matched controls developed depressive disorder. TB exposure was found to be an independent risk factor of depressive disorder in women (aHR 1.34, 95% confidence interval [CI] 1.07–1.68), but not in men (aHR 0.71, 95% CI 0.48–1.06) after adjusting for age, comorbidities, and income levels. The risk of depression was significantly higher for female TB contacts than for matched controls in the first and second years (aHR 1.49, 95% CI 1.03–2.14; and aHR 1.53, 95% CI 1.05–2.23, respectively), but not thereafter. Of note, 67 (0.74%) TB contacts and 88 (0.24%) matched controls developed active TB, but none of them had subsequent depressive disorder during follow-up periods. Female TB contacts had an increased risk of depression within the first 2 years after exposure. Clinicians should consider conducting depression evaluations in addition to

Questions and Answers about TB

MedlinePlus

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

Knowledge and attitude of key community members towards tuberculosis: mixed method study from BRAC TB control areas in Bangladesh.

PubMed

Paul, Sukanta; Akter, Rahima; Aftab, Afzal; Khan, Antora M; Barua, Mrittika; Islam, Shayla; Islam, Akramul; Husain, Ashaque; Sarker, Malabika

2015-01-31

Bangladesh National Tuberculosis (TB) Control Programme adopted a number of strategies to facilitate TB diagnosis and treatment. 'Advocacy, Communication and Social Mobilization' (ACSM) was one of the key strategies implemented by BRAC (Bangladesh Rural Advancement Committee, a non-governmental development organization) TB control program. The purpose of this study is to assess the knowledge and attitudes of the key community members (KCMs) participated in ACSM in BRAC TB control areas. This study combined quantitative and qualitative methods using a mixed method approach. KCMs in three districts with low TB case detection rates were targeted to assess the ACSM program. The quantitative survey using a multi-stage random-sampling strategy was conducted among 432 participants. The qualitative study included in-depth interviews (IDIs) of a sub sample of 48 respondents. For quantitative analysis, descriptive statistics were reported using frequencies, percentages, and Chi square tests, while thematic analysis was used for qualitative part. Most (99%) of the participants had heard about TB, and almost all knew that TB is a contagious yet curable disease. More than half (53%) of the KCMs had good knowledge regarding TB, but BRAC workers were found to be more knowledgeable compared to other KCMs. However, considerable knowledge gaps were observed among BRAC community health workers. Qualitative results revealed that the majority of the KCMs were aware about the signs, symptoms and transmission pathways of TB and believed that smoking and addiction were the prime causes of transmission of TB. The knowledge about child TB was poor even among BRAC health workers. Stigma associated with TB was not uncommon. Almost all respondents expressed that young girls diagnosed with TB. This study finding has revealed varying levels of knowledge and mixed attitudes about TB among the KCMs. It also provides insight on the poor knowledge regarding child TB and indicate that despite the

Implementing the End TB Strategy in the Western Pacific Region: Translating vision into reality.

PubMed

Rahevar, Kalpeshsinh; Fujiwara, Paula I; Ahmadova, Shalala; Morishita, Fukushi; Reichman, Lee B

2018-04-12

The End TB Strategy aims to end the global tuberculosis (TB) epidemic by 2035 in line with the sustainable development goals targets and has been implemented in the World Health Organization (WHO) Western Pacific Region since 2015. Significant progress has been made in implementing this strategy. However, several challenges still remain. In 2016, an estimated 1.8 million people developed TB in the region, and of these about 20% were missed by national TB programmes. The gap in diagnosis and enrolment as well as treatment completion is greater with drug-resistant TB. Many TB-affected families face catastrophic costs due to the disease. Sustaining financing for TB care is a long-term challenge in many countries. This article emphasizes targeted interventions in high-risk populations, including systematic screening and patient-centred TB care. Several other approaches including improving TB diagnostic tools and algorithm, and engaging all care providers are suggested to find missing TB patients. Drug-resistant TB requires additional resourcing for laboratories, enrolment and patient support. Specific measures are required at different levels to mitigate financial burden due to TB including linking TB to overall social protection schemes. The Moscow Ministerial conference in 2017 and upcoming United Nations (UN) 2018 high-level meeting provide an opportunity to raise TB higher on the global agenda, forge partnerships and move towards universal health coverage. © 2018 Asian Pacific Society of Respirology.

Pastoralism and delay in diagnosis of TB in Ethiopia

PubMed Central

Gele, Abdi A; Bjune, Gunnar; Abebe, Fekadu

2009-01-01

the only observed predictor for health care providers' delay (aOR. 3.39, CI 1.68–6.83). Conclusion Patient delay observed among pastoralist TB patients in SRS is one of the highest reported so far from developing countries, exceeding two years in some patients. This long patient delay appears to be associated with patient's inadequate knowledge of the disease and distance to health care facility with nomadic pastoralists being the most affected. Regional TB control programmes need to consider the exceptional circumstances of pastoralists, to maximise their access to TB services. PMID:19128498

Challenges and solutions for a rational vaccine design for TB-endemic regions.

PubMed

Gowthaman, Uthaman; Mushtaq, Khurram; Tan, Amabel C; Rai, Pradeep K; Jackson, David C; Agrewala, Javed N

2015-01-01

Vaccines have been successful for global eradication or control of dreaded diseases such as smallpox, diphtheria, tetanus, yellow fever, whooping cough, polio, and measles. Unfortunately, this success has not been achieved for controlling tuberculosis (TB) worldwide. Bacillus Calmette Guérin (BCG) is the only available vaccine against TB. Paradoxically, BCG has deciphered success in the Western world but has failed in TB-endemic areas. In this article, we highlight and discuss the aspects of immunity responsible for controlling Mycobacterium tuberculosis infection and factors responsible for the failure of BCG in TB-endemic countries. In addition, we also suggest strategies that contribute toward the development of successful vaccine in protecting populations where BCG has failed.

Should sputum-negative presumptive TB patients be actively followed to identify missing cases in India?

PubMed

Waikar, S; Pathak, A; Ghule, V; Kapoor, A; Sagili, K; Babu, E R; Chadha, S

2017-12-21

Setting: Sputum smear microscopy, the primary diagnostic tool used for diagnosis of tuberculosis (TB) in India's Revised National TB Control Programme (RNTCP), has low sensitivity, resulting in a significant number of TB cases reported as sputum-negative. As the revised guidelines pose challenges in implementation, sputum-negative presumptive TB (SNPT) patients are subjected to 2 weeks of antibiotics, followed by chest X-ray (CXR), resulting in significant loss to care among these cases. Objective: To determine whether reducing delays in CXR would yield additional TB cases and reduce initial loss to follow-up for diagnosis among SNPT cases. Methods: In an ongoing intervention in five districts of Maharashtra, SNPT patients were offered upfront CXR. Results: Of 119 male and 116 female SNPT patients with a mean age of 45 years who were tested by CXR, 32 (14%) were reported with CXR suggestive of TB. Administering upfront CXR in SNPT patients yielded twice as many additional cases, doubling the proportion of cases detected among all those tested as against administering CXR 2 weeks after smear examination. Conclusion: Our interventional study showed that the yield of TB cases was significantly greater when upfront CXR examination was undertaken without waiting for a 2-week antibiotic trial.

Effect of host diversity and species assemblage composition on bovine tuberculosis (bTB) risk in Ethiopian cattle.

PubMed

Sintayehu, Dejene W; Heitkönig, Ignas M A; Prins, Herbert H T; Tessema, Zewdu K; DE Boer, Willem F

2017-05-01

Current theories on diversity-disease relationships describe host species diversity and species identity as important factors influencing disease risk, either diluting or amplifying disease prevalence in a community. Whereas the simple term 'diversity' embodies a set of animal community characteristics, it is not clear how different measures of species diversity are correlated with disease risk. We therefore tested the effects of species richness, Pielou's evenness and Shannon's diversity on bovine tuberculosis (bTB) risk in cattle in the Afar Region and Awash National Park between November 2013 and April 2015. We also analysed the identity effect of a particular species and the effect of host habitat use overlap on bTB risk. We used the comparative intradermal tuberculin test to assess the number of bTB-infected cattle. Our results suggested a dilution effect through species evenness. We found that the identity effect of greater kudu - a maintenance host - confounded the dilution effect of species diversity on bTB risk. bTB infection was positively correlated with habitat use overlap between greater kudu and cattle. Different diversity indices have to be considered together for assessing diversity-disease relationships, for understanding the underlying causal mechanisms. We posit that unpacking diversity metrics is also relevant for formulating disease control strategies to manage cattle in ecosystems characterized by seasonally limited resources and intense wildlife-livestock interactions.

QuantiFERON-TB Gold In-tube test for the diagnosis of active and latent tuberculosis in selected health facilities of Addis Ababa, Ethiopia.

PubMed

Niguse, Selam; Desta, Kassu; Gebremichael, Gebremdihin; Gebrezgeaxier, Atsebeha; Getahun, Mulluwork; Kassa, Desta

2018-05-11

To determine the performance of QuantiFERON-TB IN-Gold for the diagnosis active tuberculosis and latent tuberculosis. A total of 213 participants (136 tuberculosis suspects, 66 latently infected) were enrolled. Of 213, 21 (15.4%) of the tuberculosis suspects and 3 (4.5%) of the latent tuberculosis groups were human immunodeficiency virus infected. The sensitivity, specificity, positive and negative predictive value of QuantiFERON-TB IN-Gold for the diagnosis of active tuberculosis was 70.3% (26/37), 49.5% (49/99), 34.7% (26/75) and 83.1% (49/59) respectively. A kappa value of 0.316 (p = 0.001, 95% CI 1.605-1.609) between QuantiFERON-TB IN-Gold and tuberculin skin test were found.

Review of policy and status of implementation of collaborative HIV-TB activities in 23 high-burden countries.

PubMed

Gupta, S; Granich, R; Date, A; Lepere, P; Hersh, B; Gouws, E; Samb, B

2014-10-01

Issuance of national policy guidance is a critical step to ensure quality HIV-TB (human immunodeficiency virus-tuberculosis) coordination and programme implementation. From the database of the Joint United Nations Programme on HIV/AIDS (UNAIDS), we reviewed 62 national HIV and TB guidelines from 23 high-burden countries for recommendations on HIV testing for TB patients, criteria for initiating antiretroviral therapy (ART) and the Three I's for HIV/TB (isoniazid preventive treatment [IPT], intensified TB case finding and TB infection control). We used UNAIDS country-level programme data to determine the status of implementation of existing guidance. Of the 23 countries representing 89% of the global HIV-TB burden, Brazil recommends ART irrespective of CD4 count for all people living with HIV, and four (17%) countries recommend ART at the World Health Organization (WHO) 2013 guidelines level of CD4 count ⩿500 cells/mm(3) for asymptomatic persons. Nineteen (83%) countries are consistent with WHO 2013 guidelines and recommend ART for HIV-positive TB patients irrespective of CD4 count. IPT is recommended by 16 (70%) countries, representing 67% of the HIV-TB burden; 12 recommend symptom-based screening alone for IPT initiation. Guidelines from 15 (65%) countries with 79% of the world's HIV-TB burden include recommendations on HIV testing and counselling for TB patients. Although uptake of ART, HIV testing for TB patients, TB screening for people living with HIV and IPT have increased significantly, progress is still limited in many countries. There is considerable variance in the timing and content of national policies compared with WHO guidelines. Missed opportunities to implement new scientific evidence and delayed adaptation of existing WHO guidance remains a key challenge for many countries.

Early diagnosis and effective treatment regimens are the keys to tackle antimicrobial resistance in tuberculosis (TB): A report from Euroscicon's international TB Summit 2016

PubMed Central

Shaik, Monisha; Danquah, Cynthia Amaning

2017-01-01

ABSTRACT To say that tuberculosis (TB) has regained a strong foothold in the global human health and wellbeing scenario would be an understatement. Ranking alongside HIV/AIDS as the top reason for mortality due to a single infectious disease, the impact of TB extends far into socio-economic context worldwide. As global efforts led by experts and political bodies converge to mitigate the predicted outcome of growing antimicrobial resistance, the academic community of students, practitioners and researchers have mobilised to develop integrated, inter-disciplinary programmes to bring the plans of the former to fruition. Enabling this crucial requirement for unimpeded dissemination of scientific discovery was the TB Summit 2016, held in London, United Kingdom. This report critically discusses the recent breakthroughs made in diagnostics and treatment while bringing to light the major hurdles in the control of the disease as discussed in the course of the 3-day international event. Conferences and symposia such as these are the breeding grounds for successful local and global collaborations and therefore must be supported to expand the understanding and outreach of basic science research. PMID:27813702

Targeting the human macrophage with combinations of drugs and inhibitors of Ca2+ and K+ transport to enhance the killing of intracellular multi-drug resistant Mycobacterium tuberculosis (MDR-TB)--a novel, patentable approach to limit the emergence of XDR-TB.

PubMed

Martins, Marta

2011-05-01

The emergence of resistance in tuberculosis has become a serious problem for the control of this disease. For that reason, new therapeutic strategies that can be implemented in the clinical setting are urgently needed. The design of new compounds active against mycobacteria must take into account that tuberculosis is mainly an intracellular infection of the alveolar macrophage and therefore must maintain activity within the host cells. An alternative therapeutic approach will be described in this review, focusing on the activation of the phagocytic cell and the subsequent killing of the internalized bacteria. This approach explores the combined use of antibiotics and phenothiazines, or Ca(2+) and K(+) flux inhibitors, in the infected macrophage. Targeting the infected macrophage and not the internalized bacteria could overcome the problem of bacterial multi-drug resistance. This will potentially eliminate the appearance of new multi-drug resistant tuberculosis (MDR-TB) cases and subsequently prevent the emergence of extensively-drug resistant tuberculosis (XDR-TB). Patents resulting from this novel and innovative approach could be extremely valuable if they can be implemented in the clinical setting. Other patents will also be discussed such as the treatment of TB using immunomodulator compounds (for example: betaglycans).

Conducting efficacy trials in children with MDR-TB: what is the rationale and how should they be done?

PubMed

Seddon, J A; Weld, E D; Schaaf, H S; Garcia-Prats, A J; Kim, S; Hesseling, A C

2018-05-01

Paediatric anti-tuberculosis treatment trials have traditionally been limited to Phase I/II studies evaluating the drug pharmacokinetics and safety in children, with assumptions about efficacy made by extrapolating data from adults. However, it is increasingly being recognised that, in some circumstances, efficacy trials are required in children. The current treatment for children with multidrug-resistant tuberculosis (MDR-TB) is long and toxic; shorter, safer regimens, using novel agents, require urgent evaluation. Given the changing pattern of drug metabolism, disease spectrum and rates of TB disease confirmation with age, decisions around inclusion criteria require careful consideration. The most straightforward MDR-TB efficacy trial would include only children with confirmed MDR-TB and no additional drug resistance. Given that it may be unclear at the time treatment is initiated whether the diagnosis will ultimately be confirmed and what the final drug resistance profile will be, this presents a unique challenge in children. Recruiting only these children would, however, limit the generalisability of such a trial, as in reality the majority of children with TB do not have bacteriologically confirmed disease. Given the good existing treatment outcomes with current routine regimens for children with MDR-TB, conducting a superiority trial may not be the optimal design. Demonstrating non-inferiority of efficacy, but superiority with regard to safety, would be an alternative strategy. Using standardised control and experimental MDR-TB treatment regimens is challenging given the wide spectrum of paediatric disease. However, using variable regimens would make interpretation challenging. A paediatric MDR-TB efficacy trial is urgently needed, and with global collaboration and capacity building, is highly feasible.

Preparation and luminescence properties of Ce3+ and Ce3+/Tb(3+)-activated Y4Si2O7N2 phosphors.

PubMed

Xia, Zhiguo; Wu, Weiwei

2013-09-28

Ce(3+) and Ce(3+)/Tb(3+)-activated Y4Si2O7N2 phosphors are synthesized by the solid-state method, which can be efficiently excited by near ultraviolet (UV) light emitting diode (LED) chips. The PL spectrum of Y4Si2O7N2:Ce(3+) shows a broad hump between 380 and 650 nm, assigned to the electron transition from the 4f energy level to different 5d sub levels of the Ce(3+) ions at different Y(3+) sites. The color of the Y4Si2O7N2:Ce(3+) phosphor can shift from blue to green by introducing Tb(3+). In addition, the energy transfer process from Ce(3+) to Tb(3+) in the Y4Si2O7N2 host was investigated and discussed in terms of both the luminescence spectra and decay curves. The energy transfer critical distance has been calculated and evaluated by the concentration quenching method. Therefore, the Ce(3+) and Ce(3+)/Tb(3+)-activated Y4Si2O7N2 phosphors can serve as key materials for phosphor-converted white-light UV-LEDs.

Presumed latent ocular tuberculosis diagnosed with the positive quantiFERON-TB Gold In-Tube Test in a HLA-A29-positive patient.

PubMed

Rangel, Carlos Mario; Atencia, Cesar; Merayo-Lloves, Jesus; Fernandez-Vega Sanz, Alvaro

2015-06-04

A 59-year-old Hispanic woman presented with a 3-year history of floaters associated with bilateral reduced visual acuity. Her best-corrected visual acuity (BCVA) was 20/40. Both anterior segments were without inflammation, but fundoscopy showed mild vitreous inflammation and multiple inflammatory choroidal lesions. Tests for inflammatory and infectious diseases were negative except for human leucocyte antigen A29. The patient was diagnosed with birdshot choroidoretinopathy, and treatment was initiated with cyclosporine A 2.5 mg/kg/day. One year after treatment, the patient reported systemic symptoms with no improvement in visual acuity. Fundus findings remained with vitreal inflammation. QuantiFERON-TB Gold In-Tube Test was positive, and a diagnosis of presumed latent ocular tuberculosis (TB) was made. We initiated anti-TB treatment for 9 months. At 6 months of anti-TB therapy, there was no active inflammation. The patient was followed for 2 years with no medications and no active inflammation. Her final BCVA was 20/25. 2015 BMJ Publishing Group Ltd.

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study.

PubMed

Efsen, A M W; Schultze, A; Miller, R F; Panteleev, A; Skrahin, A; Podlekareva, D N; Miro, J M; Girardi, E; Furrer, H; Losso, M H; Toibaro, J; Caylà, J A; Mocroft, A; Lundgren, J D; Post, F A; Kirk, O

2018-01-01

Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5-74.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis.

PubMed

Monin, Leticia; Griffiths, Kristin L; Lam, Wing Y; Gopal, Radha; Kang, Dongwan D; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K; Mitreva, Makedonka; Rosa, Bruce A; Ramos-Payan, Rosalio; Morrison, Thomas E; Murray, Peter J; Rangel-Moreno, Javier; Pearce, Edward J; Khader, Shabaana A

2015-12-01

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1-expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1-expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.

[Preparation and luminescent properties of CaMoO4:Tb3+].

PubMed

Wang, Xi-gui; Bo, Su-ling; Na, Mi-la; Qi, Xia

2010-01-01

The precursor of the sample CaMoO4:Tb3+ was prepared by the coprecipitation method. TG-DTA spectra show that there is, at 850 degrees C, an energy absorption peak, suggesting that the sample reaches the activation spot of its response. The XRD pattern of the roasted sample shows that CaMoO4:Tb3+, in the single phase, is a representative scheelite structure of CaMoO4, but the peaks shift toward right, implying that tiny crystal defect in the crystal is produced. The defect is likely to be formed by the formation of the holes as two Tb3+ replace three Ca2+ in a cell. The excitation and emission spectra of the sample were investigated and revealed that the defect structure of the sample is in favor of the energy transfer of the characteristic peak (488 nm) of the MoO4(2-) effectively to Tb3+, and makes the 4f electrons of the Tb3+ transit, especially the (7)F6-->(5)D4 electronic transition (488 nm) of the Tb3+, to be greatly strengthened. As a result, the emission spectra with lamdaex=488 nm show that the emission intensity of the spontaneously activated fluorescence MoO4(2-) is greatly weakened, while the green light luminescence intensity of the (5)D4-->(7)F5 transition (544 nm) of the Tb3+ is greatly enhanced. This suggests that the sample CaMoO4:Tb3+ will become the luminescence material with potentially great application value.

The high burden of tuberculosis (TB) and human immunodeficiency virus (HIV) in a large Zambian prison: a public health alert.

PubMed

Henostroza, German; Topp, Stephanie M; Hatwiinda, Sisa; Maggard, Katie R; Phiri, Winifreda; Harris, Jennifer B; Krüüner, Annika; Kapata, Nathan; Ayles, Helen; Chileshe, Chisela; Reid, Stewart E

2013-01-01

Tuberculosis (TB) and human immunodeficiency virus (HIV) represent two of the greatest health threats in African prisons. In 2010, collaboration between the Centre for Infectious Disease Research in Zambia, the Zambia Prisons Service, and the National TB Program established a TB and HIV screening program in six Zambian prisons. We report data on the prevalence of TB and HIV in one of the largest facilities: Lusaka Central Prison. Between November 2010 and April 2011, we assessed the prevalence of TB and HIV amongst inmates entering, residing, and exiting the prison, as well as in the surrounding community. The screening protocol included complete history and physical exam, digital radiography, opt-out HIV counseling and testing, sputum smear and culture. A TB case was defined as either bacteriologically confirmed or clinically diagnosed. A total of 2323 participants completed screening. A majority (88%) were male, median age 31 years and body mass index 21.9. TB symptoms were found in 1430 (62%). TB was diagnosed in 176 (7.6%) individuals and 52 people were already on TB treatment at time of screening. TB was bacteriologically confirmed in 88 cases (3.8%) and clinically diagnosed in 88 cases (3.8%). Confirmed TB at entry and exit interventions were 4.6% and 5.3% respectively. Smear was positive in only 25% (n = 22) of bacteriologically confirmed cases. HIV prevalence among inmates currently residing in prison was 27.4%. Ineffective TB and HIV screening programs deter successful disease control strategies in prison facilities and their surrounding communities. We found rates of TB and HIV in Lusaka Central Prison that are substantially higher than the Zambian average, with a trend towards concentration and potential transmission of both diseases within the facility and to the general population. Investment in institutional and criminal justice reform as well as prison-specific health systems is urgently required.

Combined IFN-γ and TNF-α release assay for differentiating active tuberculosis from latent tuberculosis infection.

PubMed

Kim, Ji Yeun; Park, Joung Ha; Kim, Min-Chul; Cha, Hye Hee; Jeon, Na-Young; Park, Seong Yeon; Kim, Min-Jae; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2018-05-08

The IFN-γ-release assay (IGRA) cannot differentiate active tuberculosis (TB) from latent TB infection (LTBI). We hypothesized that the TNF-α-release assay (TARA) combined with IGRA might discriminate active TB from not active TB without LTBI. Adult patients with suspected TB, and with unrelated diseases such as herpes zoster as controls, were enrolled in an intermediate TB-burden country. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as those having not active TB with and without LTBI based on IGRA results. The IGRA and TARA by using ELISPOT assays were performed on peripheral mononuclear cells. Thirty six patients with active TB and 53 patients including 18 not active TB with LTBI and 35 not active TB without LTBI were finally included. The sensitivity and specificity of the IGRA for those patients found to have active TB were 94% (CI, 80-99) and 66% (CI 52-78), respectively. Combining the IGRA and the TARA substantially increased the specificity for active TB (93%, CI, 82-98; P = 0.001) compared with the IGRA only, without compromising sensitivity (89%, CI, 73-96; P = 0.67). Combining the IGRA and TARA appears to be useful for diagnosing active TB. Copyright © 2018. Published by Elsevier Ltd.

The Prevention and Control of HIV/AIDS, TB and Vector-borne Diseases in Informal Settlements: Challenges, Opportunities and Insights

PubMed Central

Mercado, Susan P.; Becker, Daniel; Edmundo, Katia; Mugisha, Frederick

2007-01-01

Today’s urban settings are redefining the field of public health. The complex dynamics of cities, with their concentration of the poorest and most vulnerable (even within the developed world) pose an urgent challenge to the health community. While retaining fidelity to the core principles of disease prevention and control, major adjustments are needed in the systems and approaches to effectively reach those with the greatest health risks (and the least resilience) within today’s urban environment. This is particularly relevant to infectious disease prevention and control. Controlling and preventing HIV/AIDS, tuberculosis and vector-borne diseases like malaria are among the key global health priorities, particularly in poor urban settings. The challenge in slums and informal settlements is not in identifying which interventions work, but rather in ensuring that informal settlers: (1) are captured in health statistics that define disease epidemiology and (2) are provided opportunities equal to the rest of the population to access proven interventions. Growing international attention to the plight of slum dwellers and informal settlers, embodied by Goal 7 Target 11 of the Millennium Development Goals, and the considerable resources being mobilized by the Global Fund to fight AIDS, TB and malaria, among others, provide an unprecedented potential opportunity for countries to seriously address the structural and intermediate determinants of poor health in these settings. Viewed within the framework of the “social determinants of disease” model, preventing and controlling HIV/AIDS, TB and vector-borne diseases requires broad and integrated interventions that address the underlying causes of inequity that result in poorer health and worse health outcomes for the urban poor. We examine insights into effective approaches to disease control and prevention within poor urban settings under a comprehensive social development agenda. PMID:17431796

Thermally stimulated properties in ZnSe:Tb and ZnSe:(Mn, Tb) phosphors

NASA Astrophysics Data System (ADS)

Mishra, A. K.; Mishra, S. K.; Pandey, S. P.; Lakshmi Mishra, Kshama

2018-02-01

Thermoluminescence studies were performed of ZnSe:Tb and ZnSe:(Mn, Tb) phosphors. A method of preparation for ZnSe phosphors doped with Tb and (Mn, Tb) has been discussed. The thermoluminescence (TL) properties of these phosphors have been studied from 100 to 370 K temperature after exciting by UV radiation (365 nm) at three uniform heating rates 0.4, 0.6 and 0.9 K/s. The trapping parameters like trap depth, lifetime of electrons and capture cross-section have also been determined using various methods.

The sensitivity of the QuantiFERON®-TB Gold Plus assay in Zambian adults with active tuberculosis.

PubMed

Telisinghe, L; Amofa-Sekyi, M; Maluzi, K; Kaluba-Milimo, D; Cheeba-Lengwe, M; Chiwele, K; Kosloff, B; Floyd, S; Bailey, S-L; Ayles, H

2017-06-01

To investigate the sensitivity of the new interferon-gamma release assay (IGRA), QuantiFERON®-TB Gold Plus (QFT-Plus), for active TB (used as a surrogate for latent tuberculous infection) in a Zambian TB clinic. Consecutive smear or Xpert® MTB/RIF-positive adult (age 18 years) pulmonary TB patients were recruited between June 2015 and March 2016. Venous blood was tested using QFT-Plus. The sensitivity was defined as the number positive divided by the total number tested. Using logistic regression, factors associated with positive QFT-Plus results were explored. Of 108 patients (median age 32 years, interquartile range 27-38; 73% male; 63% human immunodeficiency virus [HIV] positive), 90 were QFT-Plus-positive, 11 were negative and seven had indeterminate results; sensitivity was 83% (95%CI 75-90). There was no difference in sensitivity by HIV status (HIV-positive 85%, 95%CI 75-93; n = 68 vs. HIV-negative 80%, 95%CI 64-91; n = 40; P = 0.59). In models adjusted for age alone, CD4 cell count <100 cells/μl (OR 0.15, 95%CI 0.02-0.96; P = 0.05) and body mass index <18.5 kg/m2 (OR 0.27, 95%CI 0.08-0.91; P = 0.02) were associated with decreased odds of positive QFT-Plus results. Overall, the sensitivity of QFT-Plus is similar to that of the tuberculin skin test and other IGRAs. While overall sensitivity is not affected by HIV status, QFT-Plus sensitivity was lower among people living with HIV/acquired immune-deficiency syndrome with severe immunosuppression.

Fine mapping of powdery mildew resistance genes PmTb7A.1 and PmTb7A.2 in Triticum boeoticum (Boiss.) using the shotgun sequence assembly of chromosome 7AL.

PubMed

Chhuneja, Parveen; Yadav, Bharat; Stirnweis, Daniel; Hurni, Severine; Kaur, Satinder; Elkot, Ahmed Fawzy; Keller, Beat; Wicker, Thomas; Sehgal, Sunish; Gill, Bikram S; Singh, Kuldeep

2015-10-01

A novel powdery mildew resistance gene and a new allele of Pm1 were identified and fine mapped. DNA markers suitable for marker-assisted selection have been identified. Powdery mildew caused by Blumeria graminis is one of the most important foliar diseases of wheat and causes significant yield losses worldwide. Diploid A genome species are an important genetic resource for disease resistance genes. Two powdery mildew resistance genes, identified in Triticum boeoticum (A(b)A(b)) accession pau5088, PmTb7A.1 and PmTb7A.2 were mapped on chromosome 7AL. In the present study, shotgun sequence assembly data for chromosome 7AL were utilised for fine mapping of these Pm resistance genes. Forty SSR, 73 resistance gene analogue-based sequence-tagged sites (RGA-STS) and 36 single nucleotide polymorphism markers were designed for fine mapping of PmTb7A.1 and PmTb7A.2. Twenty-one RGA-STS, 8 SSR and 13 SNP markers were mapped to 7AL. RGA-STS markers Ta7AL-4556232 and 7AL-4426363 were linked to the PmTb7A.1 and PmTb7A.2, at a genetic distance of 0.6 and 6.0 cM, respectively. The present investigation established that PmTb7A.1 is a new powdery mildew resistance gene that confers resistance to a broad range of Bgt isolates, whereas PmTb7A.2 most probably is a new allele of Pm1 based on chromosomal location and screening with Bgt isolates showing differential reaction on lines with different Pm1 alleles. The markers identified to be linked to the two Pm resistance genes are robust and can be used for marker-assisted introgression of these genes to hexaploid wheat.

TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo.

PubMed

Kaboru, Berthollet Bwira; Ogwang, Brenda A; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

2013-09-01

HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases' control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region.

Illness perception of tuberculosis (TB) and health seeking practice among urban slum residents of Bangladesh: a qualitative study.

PubMed

Bam, Kiran; Bhatt, Lokesh Prasad; Thapa, Rajshree; Dossajee, Hussein Karimjee; Angdembe, Mirak Raj

2014-08-27

Combating tuberculosis (TB) in urban slums is more complex than in rural areas due to reasons such as over-crowding, unhygienic living conditions and poverty. This study aimed to assess illness perception of TB and identify barriers and facilitators for health seeking practice among the residents of Badda slum, Dhaka, Bangladesh. The Badda slum was purposively selected. Convenience sampling was carried out to select participants aged 18 years and above. Twenty two in-depth interviews, two key informants' interviews and participatory rapid appraisal (PRA) were conducted. Data were analyzed manually by using defined a priori codes and color coding of the quotes in data matrix table. TB was commonly recognized as Jokkha (pulmonary TB), Sas rog (disease associated to breathing) followed by TB. More females than males had knowledge about TB related illness. Very few perceived of being at risk of TB despite the high risk behavior and environment. Prime barriers for health seeking practice of TB were cost along with other barriers like prevailing stigma on TB, lack of information on service sites and unavailability of accompanying person. Training and orientation to community organizations and people, awareness on TB and free treatment through advertisements/media, community level diagnostic and home based care were identified as the facilitators for the health seeking practice of TB. Perceptions of TB and knowledge associated with the disease shape the health seeking practice, therefore promotion of media awareness campaign, targeting the people of urban slums for reducing misconceptions and promotion of home based service is needed to encourage health seeking practice in the future.

Luminescence Properties of Ca19Ce(PO4)14:A (A = Eu3+/Tb3+/Mn2+) Phosphors with Abundant Colors: Abnormal Coexistence of Ce4+/3+-Eu3+ and Energy Transfer of Ce3+ → Tb3+/Mn2+ and Tb3+-Mn2.

PubMed

Shang, Mengmeng; Liang, Sisi; Lian, Hongzhou; Lin, Jun

2017-06-05

A series of Eu 3+ /Tb 3+ /Mn 2+ -ion-doped Ca 19 Ce(PO 4 ) 14 (CCPO) phosphors have been prepared via the conventional high-temperature solid-state reaction process. Under UV radiation, the CCPO host presents a broad blue emission band from Ce 3+ ions, which are generated during the preparation process because of the formation of deficiency. The Eu 3+ -doped CCPO phosphors can exhibit magenta to red-orange emission as a result of the abnormal coexistence of Ce 3+ /Ce 4+ /Eu 3+ and the metal-metal charge-transfer (MMCT) effect between Ce 3+ and Eu 3+ . When Tb 3+ /Mn 2+ are doped into the hosts, the samples excited with 300 nm UV light present multicolor emissions due to energy transfer (ET) from the host (Ce 3+ ) to the activators with increasing activator concentrations. The emitting colors of CCPO:Tb 3+ phosphors can be tuned from blue to green, and the CCPO:Mn 2+ phosphors can emit red light. The ET mechanism from the host (Ce 3+ ) to Tb 3+ /Mn 2+ is demonstrated to be a dipole-quadrapole interaction for Ce 3+ → Tb 3+ and an exchange interaction for Ce 3+ → Mn 2+ in CCPO:Tb 3+ /Mn 2+ . Abundant emission colors containing white emission were obtained in the Tb 3+ - and Mn 2+ -codoped CCPO phosphors through control of the levels of doped Tb 3+ and Mn 2+ ions. The white-emitted CCPO:Tb 3+ /Mn 2+ phosphor exhibited excellent thermal stability. The photoluminescence properties have shown that these materials might have potential for UV-pumped white-light-emitting diodes.

Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a Function of Tuberculosis Disease History.

PubMed

Scriba, Thomas J; Carpenter, Chelsea; Pro, Sebastian Carrasco; Sidney, John; Musvosvi, Munyaradzi; Rozot, Virginie; Seumois, Grégory; Rosales, Sandy L; Vijayanand, Pandurangan; Goletti, Delia; Makgotlho, Edward; Hanekom, Willem; Hatherill, Mark; Peters, Bjoern; Sette, Alessandro; Arlehamn, Cecilia S Lindestam

2017-09-15

Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining. We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.

The prevalence of HIV among adults with pulmonary TB at a population level in Zambia.

PubMed

Chanda-Kapata, Pascalina; Kapata, Nathan; Klinkenberg, Eveline; Grobusch, Martin P; Cobelens, Frank

2017-03-29

Tuberculosis and HIV co-infection is one of the main drivers of poor outcome for both diseases in Zambia. HIV infection has been found to predict TB infection/disease and TB has been reported as a major cause of death among individuals with HIV. Improving case detection of TB/HIV co-infection has the potential to lead to early treatment of both conditions and can impact positively on treatment outcomes. This study was conducted in order to determine the HIV prevalence among adults with tuberculosis in a national prevalence survey setting in Zambia, 2013-2014. A countrywide cross sectional survey was conducted in 2013/2014 using stratified cluster sampling, proportional to population size for rural and urban populations. Each of the 66 countrywide clusters represented one census supervisory area with cluster size averaging 825 individuals. Socio-demographic characteristics were collected during a household visit by trained survey staff. A standard symptom-screening questionnaire was administered to 46,099 eligible individuals across all clusters, followed by chest x-ray reading for all eligible. Those symptomatic or with x-ray abnormalities were confirmed or ruled out as TB case by either liquid culture or Xpert MTBRif performed at the three central reference laboratories. HIV testing was offered to all participants at the survey site following the national testing algorithm with rapid tests. The prevalence was expressed as the proportion of HIV among TB cases with 95% confidence limits. A total of 265/6123 (4.3%) participants were confirmed of having tuberculosis. Thirty-six of 151 TB survey cases who accepted HIV testing were HIV-seropositive (23.8%; 95% CI 17.2-31.4). The mean age of the TB/HIV cases was 37.6 years (range 24-70). The majority of the TB/HIV cases had some chest x-ray abnormality (88.9%); were smear positive (50.0%), and/or had a positive culture result (94.4%). None of the 36 detected TB/HIV cases were already on TB treatment, and 5/36 (13

Quantitative genetic analysis of the bTB diagnostic single intradermal comparative cervical test (SICCT).

PubMed

Tsairidou, Smaragda; Brotherstone, Susan; Coffey, Mike; Bishop, Stephen C; Woolliams, John A

2016-11-24

Bovine tuberculosis (bTB) is a disease of significant economic importance and is a persistent animal health problem with implications for public health worldwide. Control of bTB in the UK has relied on diagnosis through the single intradermal comparative cervical test (SICCT). However, limitations in the sensitivity of this test hinder successful eradication and the control of bTB remains a major challenge. Genetic selection for cattle that are more resistant to bTB infection can assist in bTB control. The aim of this study was to conduct a quantitative genetic analysis of SICCT measurements collected during bTB herd testing. Genetic selection for bTB resistance will be partially informed by SICCT-based diagnosis; therefore it is important to know whether, in addition to increasing bTB resistance, this might also alter genetically the epidemiological characteristics of SICCT. Our main findings are that: (1) the SICCT test is robust at the genetic level, since its hierarchy and comparative nature provide substantial protection against random genetic changes that arise from genetic drift and from correlated responses among its components due to either natural or artificial selection; (2) the comparative nature of SICCT provides effective control for initial skin thickness and age-dependent differences; and (3) continuous variation in SICCT is only lowly heritable and has a weak correlation with SICCT positivity among healthy animals which was not significantly different from zero (P > 0.05). These emerging results demonstrate that genetic selection for bTB resistance is unlikely to change the probability of correctly identifying non-infected animals, i.e. the test's specificity, while reducing the overall number of cases. This study cannot exclude all theoretical risks from selection on resistance to bTB infection but the role of SICCT in disease control is unlikely to be rapidly undermined, with any adverse correlated responses expected to be weak and slow, which

Patient Reported Delays in Seeking Treatment for Tuberculosis among Adult and Pediatric TB Patients and TB Patients Co-Infected with HIV in Lima, Peru: A Qualitative Study

PubMed Central

Paz-Soldan, Valerie A.; Alban, Rebecca E.; Dimos Jones, Christy; Powell, Amy R.; Oberhelman, Richard A.

2014-01-01

Introduction: Tuberculosis (TB) remains a significant public health challenge worldwide, and particularly in Peru with one of the highest incidence rates in Latin America. TB patient behavior has a direct influence on whether a patient will receive timely diagnosis and successful treatment of their illness. Objectives: The objective was to understand the complex factors that can impact TB patient health seeking behavior. Methods: In-depth interviews were conducted with adult and parents of pediatric patients receiving TB treatment (n = 43), within that group a sub-group was also co-infected with HIV (n = 11). Results: Almost all of the study participants recognized delays in seeking either their child’s or their own diagnosis of their TB symptoms. The principal reasons for treatment-seeking delays were lack of knowledge and confusion of TB symptoms, fear and embarrassment of receiving a TB diagnosis, and a patient tendency to self-medicate prior to seeking formal medical attention. Conclusion: Health promotion activities that target patient delays have the potential to improve individual patient outcomes and mitigate the spread of TB at a community level. PMID:25566523

Study of crystal-field excitations and infrared active phonons in TbMnO3

NASA Astrophysics Data System (ADS)

Mansouri, S.; Jandl, S.; Balli, M.; Fournier, P.; Mukhin, A. A.; Ivanov, V. Yu; Balbashov, A.; Orlita, M.

2018-05-01

The Tb3+ (4f 8) crystal-field (CF) excitations and the infrared phonons in TbMnO3 are studied as a function of temperature and under an applied magnetic field. The phonon energy shifts reflect local displacement of the oxygen ions that contribute to the CF energy level shifts below 120 K and under magnetic field. The CF polarized transmission spectra provide interesting information about the debated nature of the excitations at 41, 65, 130 cm‑1. We also evaluate the contribution of the charge transfer mechanism to the magnetoelectric process in TbMnO3 under magnetic field.

Effect of tuberculosis on the survival of HIV-infected men in a country with low TB incidence

PubMed Central

López-Gatell, H; Cole, SR; Margolick, JB; Witt, MD; Martinson, J; Phair, JP; Jacobson, LP

2010-01-01

Evidence regarding the effect of tuberculosis disease (TB) on HIV disease progression at the population level remains inconclusive. We estimated the effect of incident TB on time to acquired immunodeficiency syndrome (AIDS)-related death, using a marginal structural Cox model. Between 1984 and 2005, 2,882 HIV-infected men in the Multicenter AIDS Cohort Study contributed 21,914 person-years while followed for a median of 5.4 years. At study entry, the median CD4 cell count and HIV-1 RNA viral load were 533 cells/mm3 (interquartile range [IQR], 365 – 737) and 12,953 copies/ml (IQR, 2,453 – 48,540), respectively. This study was performed in a setting with a modest exposure to HAART; 8,295 of 23,801 (35%) person-years were followed during the HAART era. Fifteen men incurred incident TB, yielding a TB incidence of 7 (95% confidence interval [CI]: 4, 14) per 10,000 person-years, and 1,072 died of AIDS-related causes. Accounting for potential confounders, including CD4 cell count and viral load, the hazard of AIDS-related death was 2.4 times larger for the person-time with TB, compared to the person-time without TB (95% CI: 1.2, 4.7). Results underscore the importance of avoiding TB by using preventive interventions, such as treatment of latent TB infection, particularly in populations with a large prevalence of HIV/TB co-infected individuals. PMID:18753866

[Duties of institutions and heads of health care centers in the area of infection control, information, assessment, registration and financing of benefits provided to TB patients].

PubMed

Zielonka, Tadeusz M

2015-01-01

The Act on preventing and counteracting infections and infectious diseases in humans effective in Poland requires the heads of health care outlets and institutions to counteract spreading of TB in units under their management. They are, by all means, responsible for monitoring infections in their respective units, including development, implementation and monitoring of the implementation of procedures into practice, aiming at limiting the dissemination of TB in hospitals and outpatient clinics. Medical service unit managers are also responsible for providing members of their staff with means of individual protection against infection with Mycobacterium tuberculosis bacillus. Their duties also include reporting all of the recognized TB cases in their respective units. TB is an infectious diseases included in the occupational disease list. Assessment of TB as an occupational disease is the responsibility of provincial TB prevention clinics. The Act also provides principles of financing of individual benefits available for the insured TB patients as well as those not insured.

[Duties of institutions and heads of health care centers in the area of infection control, information, assessment, registration and financing of benefits provided to TB patients].

PubMed

Zielonka, Tadeusz M

2011-01-01

The Act on preventing and counteracting infections and infectious diseases in humans effective in Poland provides for the duty of the heads of health care outlets and institutions to counteract spreading of TB in units under their management. They are, by all means, responsible for monitoring infections in their respective units, involving development, implementation and monitoring of practical implementation of procedures aiming at limiting dissemination of TB in hospitals and outpatient clinics. Medical service unit managers are also responsible for providing members of their staffs with means of individual protection against infection with Mycobacterium tuberculosis bacillus. Their duties also include notification of all recognized TB cases in their respective units. TB is an infectious diseases included in the occupational disease list. Assessment of TB as occupational disease is the responsibility of provincial TB prevention clinics. The Act also provides for principles of financing of individual benefits available for the insured TB patients and those not insured.

The experience of implementing a 'TB village' for a pastoralist population in Cherrati, Ethiopia.

PubMed

Tayler-Smith, K; Khogali, M; Keiluhu, K; Jemmy, J-P; Ayada, L; Weyeyso, T; Issa, A M; De Maio, G; Harries, A D; Zachariah, R

2011-10-01

In Cherrati District, Somali Regional State (SRS), Ethiopia, despite a high burden of tuberculosis (TB), TB control activities are virtually absent. The majority of the population is pastoralist with a mobile lifestyle. TB care and treatment were offered using a 'TB village' approach that included traditional style residential care, community empowerment and awareness raising, provision of essential social amenities and essential food and non-food items. To describe 1) key aspects of the implementation of the TB village approach, 2) TB treatment outcomes and 3) the lessons learnt during implementation. Descriptive study. A total of 297 patients entered the TB village between September 2006 and October 2008; 271 (91%) patients were treated successfully, nine (3%) defaulted and 13 (4%) died. For pastoralist populations, a TB village approach may be effective for improving access to TB care, ensuring proper adherence to treatment and achieving good overall TB outcomes. The successes and challenges of this approach are discussed.

[Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (ii): Prophylaxis and treatment].

PubMed

Baquero-Artigao, F; Mellado Peña, M J; del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

2015-10-01

In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Lessons learnt from TB screening in closed immigration centres in Italy

PubMed Central

Crepet, Anna; Repetto, Ernestina; Al Rousan, Ahmad; Sané Schepisi, Monica; Girardi, Enrico; Prestileo, Tullio; Codecasa, Luigi; Garelli, Silvia; Corrao, Salvatore; Ippolito, Giuseppe; Decroo, Tom; Maccagno, Barbara

2016-01-01

Background Between June 2012 and December 2013 Médecins Sans Frontières launched a pilot project with the aim of testing a strategy for improving timely diagnosis of active pulmonary TB among migrants hosted in four centres of identification and expulsion (CIE) in Italy. Methods This is a descriptive study. For active TB case finding we used an active symptom screening approach among migrants at admission in four CIE's. Here we describe the feasibility and the yield of this programme. Results Overall, 3588 migrants were screened, among whom 87 (2.4%) had a positive questionnaire. Out of 30 migrants referred for further investigations, three were diagnosed as having TB, or 0.1% out of 3588 individuals that underwent screening. Twenty-five (29%, 25/87) migrants with positive questionnaires were not referred for further investigation, following the doctors' decision; however, for 32 (37%, 32/87) migrants the diagnostic work-out was not completed. In multivariate analyses, being over 35 years (OR 1.7; 95% CI 1.1–2.6) and being transgender (OR 4.9; 95% CI 2.1–11.7), was associated with a positive questionnaire. Conclusions TB screening with symptom screening questionnaires of migrants at admission in closed centres is feasible. However, to improve the yield, follow-up of patients with symptoms or signs suggestive for TB needs to be improved. PMID:27208040

The sensitivity of the QuantiFERON®-TB Gold Plus assay in Zambian adults with active tuberculosis

PubMed Central

Amofa-Sekyi, M.; Maluzi, K.; Kaluba-Milimo, D.; Cheeba-Lengwe, M.; Chiwele, K.; Kosloff, B.; Floyd, S.; Bailey, S-L.; Ayles, H.

2017-01-01

SUMMARY SETTING AND OBJECTIVE: To investigate the sensitivity of the new interferon-gamma release assay (IGRA), QuantiFERON®-TB Gold Plus (QFT-Plus), for active TB (used as a surrogate for latent tuberculous infection) in a Zambian TB clinic. DESIGN: Consecutive smear or Xpert® MTB/RIF-positive adult (age ⩾18 years) pulmonary TB patients were recruited between June 2015 and March 2016. Venous blood was tested using QFT-Plus. The sensitivity was defined as the number positive divided by the total number tested. Using logistic regression, factors associated with positive QFT-Plus results were explored. RESULTS: Of 108 patients (median age 32 years, interquartile range 27–38; 73% male; 63% human immunodeficiency virus [HIV] positive), 90 were QFT-Plus-positive, 11 were negative and seven had indeterminate results; sensitivity was 83% (95%CI 75–90). There was no difference in sensitivity by HIV status (HIV-positive 85%, 95%CI 75–93; n = 68 vs. HIV-negative 80%, 95%CI 64–91; n = 40; P = 0.59). In models adjusted for age alone, CD4 cell count <100 cells/μl (OR 0.15, 95%CI 0.02–0.96; P=0.05) and body mass index <18.5 kg/m2 (OR 0.27, 95%CI 0.08–0.91; P = 0.02) were associated with decreased odds of positive QFT-Plus results. CONCLUSION: Overall, the sensitivity of QFT-Plus is similar to that of the tuberculin skin test and other IGRAs. While overall sensitivity is not affected by HIV status, QFT-Plus sensitivity was lower among people living with HIV/acquired immune-deficiency syndrome with severe immunosuppression. PMID:28482964

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

PubMed Central

Monin, Leticia; Griffiths, Kristin L.; Lam, Wing Y.; Gopal, Radha; Kang, Dongwan D.; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K.; Mitreva, Makedonka; Rosa, Bruce A.; Ramos-Payan, Rosalio; Morrison, Thomas E.; Murray, Peter J.; Rangel-Moreno, Javier; Pearce, Edward J.; Khader, Shabaana A.

2015-01-01

Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB. PMID:26571397

[Human resource capacity building on TB laboratory work for TB control program--through the experience of international TB laboratory training course for TB control at the Research Institute of Tuberculosis, JATA, Japan].

PubMed

Fujiki, Akiko; Kato, Seiya

2008-06-01

The international training course on TB laboratory work for national tuberculosis program (NTP) has been conducted at the Research Institute of Tuberculosis since 1975 funded by Japan International Cooperation Agency in collaboration with WHO Western Pacific Regional Office. The aim of the course is to train key personnel in TB laboratory field for NTP in resource-limited countries. The course has trained 265 national key personnel in TB laboratory service from 57 resource-limited countries in the last 33 years. The number of participants trained may sound too small in the fight against the large TB problem in resource-limited countries. However, every participant is playing an important role as a core and catalyst for the TB control program in his/her own country when they were back home. The curriculum is composed of technical aspects on TB examination, mainly sputum microscopy in addition since microscopy service is provided at many centers that are deployed in a widely spread area, the managerial aspect of maintaining quality TB laboratory work at the field laboratory is another component of the curriculum. Effective teaching methods using materials such as artificial sputum, which is useful for panel slide preparation, and technical manuals with illustrations and pictures of training procedure have been developed through the experience of the course. These manuals are highly appreciated and widely used by the front line TB workers. The course has also contributed to the expansion of EQA (External Quality Assessment) system on AFB microscopy for the improvement of the quality of TB laboratory service of NTP. The course is well-known for not only having a long history, but also for its unique learning method emphasizing "Participatory Training", particularly for practicum sessions to master the skills on AFB microscopy. The method in learning AFB microscopy, which was developed by the course, was published as a training manual by IUATLD, RIT and USAID. As it is

Virologic and immunologic outcome of HAART in Human Immunodeficiency Virus (HIV)-1 infected patients with and without tuberculosis (TB) and latent TB infection (LTBI) in Addis Ababa, Ethiopia.

PubMed

Kassa, Desta; Gebremichael, Gebremedhin; Alemayehu, Yodit; Wolday, Dawit; Messele, Tsehaynesh; van Baarle, Debbie

2013-01-01

HIV/TB coinfection remains a major challenge even after the initiation of HAART. Little is known about Mycobacterium tuberculosis (Mtb) specific immune restoration in relation to immunologic and virologic outcomes after long-term HAART during co-infections with latent and active TB. A total of 232 adults, including 59 HIV patients with clinical TB (HIV + TB+), 125 HIV patients without clinical TB (HIV + TB-), 13 HIV negative active TB patients (HIV-TB+), and 10 HIV negative Tuberculin Skin TST positive (HIV-TST+), and 25 HIV-TST- individuals were recruited. HAART was initiated in 113 HIV + patients (28 TB + and 85 TB-), and anti-TB treatment for all TB cases. CD4+ T-cell count, HIV RNA load, and IFN-γ responses to ESAT-6/CFP-10 were measured at baseline, 6 months (M6), 18 months (M18) and 24 months (M24) after HAART initiation. The majority of HIV + TB- (70%, 81%, 84%) as well as HIV + TB + patients (60%, 77%, 80%) had virologic success (HIV RNA < 50 copies/ml) by M6, M18 and M24, respectively. HAART also significantly increased CD4+ T-cell counts at 2 years in HIV + TB + (from 110.3 to 289.9 cells/μl), HIV + TB- patients (197.8 to 332.3 cells/μl), HIV + TST- (199 to 347 cells/μl) and HIV + TST + individuals (195 to 319 cells/μl). Overall, there was no significant difference in the percentage of patients that achieved virologic success and in total CD4+ counts increased between HIV patients with and without TB or LTBI. The Mtb specific IFN-γ response at baseline was significantly lower in HIV + TB + (3.6 pg/ml) compared to HIV-TB + patients (34.4 pg/ml) and HIV + TST + (46.3 pg/ml) individuals; and in HIV-TB + patients compared to HIV-TST + individuals (491.2 pg/ml). By M18 on HAART, the IFN-γ response remained impaired in HIV + TB + patients (18.1 pg/ml) while it normalized in HIV + TST + individuals (from 46.3 to 414.2 pg/ml). Our data show that

The High Burden of Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) in a Large Zambian Prison: A Public Health Alert

PubMed Central

Henostroza, German; Topp, Stephanie M.; Hatwiinda, Sisa; Maggard, Katie R.; Phiri, Winifreda; Harris, Jennifer B.; Krüüner, Annika; Kapata, Nathan; Ayles, Helen; Chileshe, Chisela; Reid, Stewart E.

2013-01-01

Background Tuberculosis (TB) and human immunodeficiency virus (HIV) represent two of the greatest health threats in African prisons. In 2010, collaboration between the Centre for Infectious Disease Research in Zambia, the Zambia Prisons Service, and the National TB Program established a TB and HIV screening program in six Zambian prisons. We report data on the prevalence of TB and HIV in one of the largest facilities: Lusaka Central Prison. Methods Between November 2010 and April 2011, we assessed the prevalence of TB and HIV amongst inmates entering, residing, and exiting the prison, as well as in the surrounding community. The screening protocol included complete history and physical exam, digital radiography, opt-out HIV counseling and testing, sputum smear and culture. A TB case was defined as either bacteriologically confirmed or clinically diagnosed. Results A total of 2323 participants completed screening. A majority (88%) were male, median age 31 years and body mass index 21.9. TB symptoms were found in 1430 (62%). TB was diagnosed in 176 (7.6%) individuals and 52 people were already on TB treatment at time of screening. TB was bacteriologically confirmed in 88 cases (3.8%) and clinically diagnosed in 88 cases (3.8%). Confirmed TB at entry and exit interventions were 4.6% and 5.3% respectively. Smear was positive in only 25% (n = 22) of bacteriologically confirmed cases. HIV prevalence among inmates currently residing in prison was 27.4%. Conclusion Ineffective TB and HIV screening programs deter successful disease control strategies in prison facilities and their surrounding communities. We found rates of TB and HIV in Lusaka Central Prison that are substantially higher than the Zambian average, with a trend towards concentration and potential transmission of both diseases within the facility and to the general population. Investment in institutional and criminal justice reform as well as prison-specific health systems is urgently required. PMID

Litigation as TB Rights Advocacy: A New Delhi Case Study.

PubMed

McBroom, Kerry

2016-06-01

One thousand people die every day in India as a result of TB, a preventable and treatable disease, even though the Constitution of India, government schemes, and international law guarantee available, accessible, acceptable, quality health care. Failure to address the spread of TB and to provide quality treatment to all affected populations constitutes a public health and human rights emergency that demands action and accountability. As part of a broader strategy, health activists in India employ Public Interest Litigation (PIL) to hold the state accountable for rights violations and to demand new legislation, standards for patient care, accountability for under-spending, improvements in services at individual facilities, and access to government entitlements in marginalized communities. Taking inspiration from right to health PIL cases (PILs), lawyers in a New Delhi-based rights organization used desk research, fact-findings, and the Right To Information Act to build a TB PIL for the Delhi High Court, Sanjai Sharma v. NCT of Delhi and Others (2015). The case argues that inadequate implementation of government TB schemes violates the Constitutional rights to life, health, food, and equality. Although PILs face substantial challenges, this paper concludes that litigation can be a crucial advocacy and accountability tool for people living with TB and their allies.

TB Is Back.

ERIC Educational Resources Information Center

Natale, Jo Anna

1992-01-01

The reemergence of tuberculosis, particularly of new drug-resistant strains, points up the need for well-coordinated school health programs. Immigration effects, growing populations of HIV-infected persons, and relaxed screening procedures are partly responsible for TB's reemergence. Two sidebars offer advice on coping with TB at school and…

Role of routine abdominal ultrasonography in intensified tuberculosis case finding algorithms at HIV clinics in high TB burden settings.

PubMed

Spalgais, Sonam; Agarwal, Upasna; Sarin, Rohit; Chauhan, Devesh; Yadav, Anita; Jaiswal, Anand

2017-05-18

High proportion of TB in people living with HIV (PLHIV) is undiagnosed. Due to this active TB case finding is recommended for HIV clinics in high TB burden countries. Presently sputum examination and chest radiography are frontline tests recommended for HIV infected TB presumptives. Abdominal TB which occurs frequently in PLHIV may be missed even by existing programmatic intensified case finding protocols. This study evaluated the routine use of ultrasonography (USG) for active case finding of abdominal TB in HIV clinics. Retrospective analysis of eight years' data from an HIV Clinic in a TB hospital in India. Patients underwent chest x-ray, sputum examination, USG abdomen and routine blood tests at entry to HIV care. Case forms were scrutinized for diagnosis of TB, USG findings and CD4 cell counts. Abdominal TB was classified as probable or possible TB. Probable TB was based on presence of two major USG (abdomen) findings suggestive of active TB, or one major USG finding with at least two minor USG findings or at least two symptoms, or any USG finding with microbiologically confirmed active TB at another site. Possible TB was based on the presence of one major USG finding, or the presence of two minor USG findings with at least two symptoms. Bacteriological confirmation was not obtained. Eight hundred and eighty-nine people PLHIV underwent a baseline USG abdomen. One hundred and thirteen of 340 cases already diagnosed with TB and 87 of the 91 newly diagnosed with TB at time of HIV clinic registration had abdominal TB. Non-abdominal symptoms like weight loss, fever and cough were seen in 53% and 22% cases had no symptoms at all. Enlarged abdominal lymph nodes with central caseation, ascitis, splenic microabsesses, bowel thickening and hepatosplenomegaly were the USG findings in these cases. Abdominal TB is a frequent TB site in PLHIV presenting with non-abdominal symptoms. It can be easily detected on basis of features seen on a simple abdominal ultrasound

Development of a POC Test for TB Based on Multiple Immunodominant Epitopes of M. tuberculosis Specific Cell-Wall Proteins

PubMed Central

Gonzalez, Jesus M.; Francis, Bryan; Burda, Sherri; Hess, Kaitlyn; Behera, Digamber; Gupta, Dheeraj; Agarwal, Ashutosh Nath; Verma, Indu; Verma, Ajoy; Myneedu, Vithal Prasad; Niedbala, Sam; Laal, Suman

2014-01-01

The need for an accurate, rapid, simple and affordable point-of-care (POC) test for Tuberculosis (TB) that can be implemented in microscopy centers and other peripheral health-care settings in the TB-endemic countries remains unmet. This manuscript describes preliminary results of a new prototype rapid lateral flow TB test based on detection of antibodies to immunodominant epitopes (peptides) derived from carefully selected, highly immunogenic M. tuberculosis cell-wall proteins. Peptide selection was initially based on recognition by antibodies in sera from TB patients but not in PPD-/PPD+/BCG-vaccinated individuals from TB-endemic settings. The peptides were conjugated to BSA; the purified peptide-BSA conjugates striped onto nitrocellulose membrane and adsorbed onto colloidal gold particles to devise the prototype test, and evaluated for reactivity with sera from 3 PPD-, 29 PPD+, 15 PPD-unknown healthy subjects, 10 patients with non-TB lung disease and 124 smear-positive TB patients. The assay parameters were adjusted to determine positive/negative status within 15 minutes via visual or instrumented assessment. There was minimal or no reactivity of sera from non-TB subjects with the striped BSA-peptides demonstrating the lack of anti-peptide antibodies in subjects with latent TB and/or BCG vaccination. Sera from most TB patients demonstrated reactivity with one or more peptides. The sensitivity of antibody detection ranged from 28–85% with the 9 BSA-peptides. Three peptides were further evaluated with sera from 400 subjects, including additional PPD-/PPD+/PPD-unknown healthy contacts, close hospital contacts and household contacts of untreated TB patients, patients with non-TB lung disease, and HIV+TB- patients. Combination of the 3 peptides provided sensitivity and specificity>90%. While the final fully optimized lateral flow POC test for TB is under development, these preliminary results demonstrate that an antibody-detection based rapid POC lateral flow test

Prognostic score to predict mortality during TB treatment in TB/HIV co-infected patients.

PubMed

Nguyen, Duc T; Jenkins, Helen E; Graviss, Edward A

2018-01-01

Estimating mortality risk during TB treatment in HIV co-infected patients is challenging for health professionals, especially in a low TB prevalence population, due to the lack of a standardized prognostic system. The current study aimed to develop and validate a simple mortality prognostic scoring system for TB/HIV co-infected patients. Using data from the CDC's Tuberculosis Genotyping Information Management System of TB patients in Texas reported from 01/2010 through 12/2016, age ≥15 years, HIV(+), and outcome being "completed" or "died", we developed and internally validated a mortality prognostic score using multiple logistic regression. Model discrimination was determined by the area under the receiver operating characteristic (ROC) curve (AUC). The model's good calibration was determined by a non-significant Hosmer-Lemeshow's goodness of fit test. Among the 450 patients included in the analysis, 57 (12.7%) died during TB treatment. The final prognostic score used six characteristics (age, residence in long-term care facility, meningeal TB, chest x-ray, culture positive, and culture not converted/unknown), which are routinely collected by TB programs. Prognostic scores were categorized into three groups that predicted mortality: low-risk (<20 points), medium-risk (20-25 points) and high-risk (>25 points). The model had good discrimination and calibration (AUC = 0.82; 0.80 in bootstrap validation), and a non-significant Hosmer-Lemeshow test p = 0.71. Our simple validated mortality prognostic scoring system can be a practical tool for health professionals in identifying TB/HIV co-infected patients with high mortality risk.

A Beneficial Effect of Low-Dose Aspirin in a Murine Model of Active Tuberculosis

PubMed Central

Kroesen, Vera Marie; Rodríguez-Martínez, Paula; García, Eric; Rosales, Yaiza; Díaz, Jorge; Martín-Céspedes, Montse; Tapia, Gustavo; Sarrias, Maria Rosa; Cardona, Pere-Joan; Vilaplana, Cristina

2018-01-01

An excessive, non-productive host-immune response is detrimental in active, chronic tuberculosis (TB) disease as it typically leads to tissue damage. Given their anti-inflammatory effect, non-steroidal anti-inflammatory drugs can potentially attenuate excessive inflammation in active TB disease. As such, we investigated the prophylactic and therapeutic effect of low-dose aspirin (LDA) (3 mg/kg/day), either alone or in combination with common anti-TB treatment or BCG vaccination, on disease outcome in an experimental murine model of active TB. Survival rate, bacillary load (BL) in lungs, and lung pathology were measured. The possible mechanism of action of LDA on the host’s immune response was also evaluated by measuring levels of CD5L/AIM, selected cytokines/chemokines and other inflammatory markers in serum and lung tissue. LDA increased survival, had anti-inflammatory effects, reduced lung pathology, and decreased bacillary load in late-stage TB disease. Moreover, in combination with common anti-TB treatment, LDA enhanced survival and reduced lung pathology. Results from the immunological studies suggest the anti-inflammatory action of LDA at both a local and a systemic level. Our results showed a systemic decrease in neutrophilic recruitment, decreased levels of acute-phase reaction cytokines (IL-6, IL-1β, and TNF-α) at late stage and a delay in the decrease in T cell response (in terms of IFN-γ, IL-2, and IL-10 serum levels) that occurs during the course of Mycobacterium tuberculosis infection. An anti-inflammatory milieu was detected in the lung, with less neutrophil recruitment and lower levels of tissue factor. In conclusion, LDA may be beneficial as an adjunct to standard anti-TB treatment in the later stage of active TB by reducing excess, non-productive inflammation, while enhancing Th1-cell responses for elimination of the bacilli. PMID:29740435

Screening for latent and active tuberculosis infection in the elderly at admission to residential care homes: A cost-effectiveness analysis in an intermediate disease burden area.

PubMed

Li, Jun; Yip, Benjamin H K; Leung, Chichiu; Chung, Wankyo; Kwok, Kin On; Chan, Emily Y Y; Yeoh, Engkiong; Chung, Puihong

2018-01-01

Tuberculosis (TB) in the elderly remains a challenge in intermediate disease burden areas like Hong Kong. Given a higher TB burden in the elderly and limited impact of current case-finding strategy by patient-initiated pathway, proactive screening approaches for the high-risk group could be optimal and increasingly need targeted economic evaluations. In this study, we examined whether and under what circumstance the screening strategies are cost-effective compared with no screening strategy for the elderly at admission to residential care homes. A decision analytic process based on Markov model was adopted to evaluate the cost-effectiveness of four strategies: (i) no screening, (ii) TB screening (CXR) and (iii) TB screening (Xpert) represent screening for TB in symptomatic elderly by chest X-ray and Xpert® MTB/RIF respectively, and (iv) LTBI/TB screening represents screening for latent and active TB infection by QuantiFERON®-TB Gold In-Tube and chest X-ray. The target population was a hypothetical cohort of 65-year-old people, using a health service provider perspective and a time horizon of 20 years. The outcomes were direct medical costs, life-years and quality-adjusted life-years (QALYs) measured by incremental cost-effectiveness ratio (ICER). In the base-case analysis, no screening was the most cost-saving; TB screening (CXR) was dominated by TB screening (Xpert); LTBI/TB screening resulted in more life-years and QALYs accrued. The ICERs of LTBI/TB screening were US$19,712 and US$29,951 per QALY gained compared with no screening and TB screening (Xpert), respectively. At the willingness-to-pay threshold of US$50,000 per QALY gained, LTBI/TB screening was the most cost-effective when the probability of annual LTBI reactivation was greater than 0.155% and acceptability of LTBI/TB screening was greater than 38%. In 1,000 iterations of Monte Carlo simulation, the probabilities of no screening, TB screening (CXR), TB screening (Xpert), and LTBI/TB screening to be

Analysis of 161Tb by radiochemical separation and liquid scintillation counting

DOE PAGES

Jiang, J.; Davies, A.; Arrigo, L.; ...

2015-12-05

The determination of 161Tb activity is problematic due to its very low fission yield, short half-life, and the complication of its gamma spectrum. At AWE, radiochemically purified 161Tb solution was measured on a PerkinElmer 1220 Quantulus TM Liquid Scintillation Spectrometer. Since there was no 161Tb certified standard solution available commercially, the counting efficiency was determined by the CIEMAT/NIST Efficiency Tracing method. The method was validated during a recent inter-laboratory comparison exercise involving the analysis of a uranium sample irradiated with thermal neutrons. Lastly, the measured 161Tb result was in excellent agreement with the result using gamma spectrometry and the resultmore » obtained by Pacific Northwest National Laboratory.« less

The prevalence of human immunodeficiency virus infection among TB patients in Port Harcourt Nigeria

PubMed Central

Erhabor, O; Jeremiah, Z A; Adias, T C; Okere, CE

2010-01-01

The joint statement by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America recommends that all patients with tuberculosis (TB) undergo testing for human immunodeficiency virus (HIV) infection after counseling. In this study, we investigated the prevalence of HIV infection among 120 patients diagnosed with microbiologically proven TB aged 18 to 54 years with a mean age of 39.5 years (standard deviation 6.75). The subjects studied were 36 male (30%) and 84 females (70%). Enzyme-linked immunosorbent assay methods were used to screen for HIV infection among the subjects. Of the 120 TB patients tested 30 (25%) were positive for HIV infection. The prevalence of HIV was higher in females 24 (80%) compared to males 6 (20%) and among singles (66.7%) compared to married subjects (33.3%) (χ2 = 83.5 and χ2 = 126.2, respectively P = 0.001). HIV-1 was the predominant viral subtype. HIV prevalence was significantly higher in subjects in the 38–47 year and 28–37 year age groups (both 40%) followed by the 18–28 year age group (20%) (χ2 = 42.6, P = 0.05). The mean CD4 lymphocyte count of the HIV-infected TB subjects was significantly lower (195 ± 40.5 cells/μL) compared to the non-HIV infected (288 ± 35.25 cells/μL P = 0.01). This study has shown a high prevalence of HIV among TB patients. Reactivation of TB among people living with HIV can be reduced by TB preventive therapy and by universal access to antiretroviral therapy. PMID:22096379

Risk factors associated with multidrug-resistant tuberculosis (MDR-TB) in a tertiary armed force referral and teaching hospital, Ethiopia.

PubMed

Demile, Biresaw; Zenebu, Amare; Shewaye, Haile; Xia, Siqing; Guadie, Awoke

2018-05-31

Ethiopia is one of the world health organization defined higher tuberculosis (TB) burden countries where the disease remains a massive public health threat. This study aimed to identify the prevalence and associated factors of multidrug-resistant tuberculosis (MDR-TB) using all armed force and civilian TB attendants in a tertiary level armed force hospital, where data for MDR-TB are previously unpublished. Cross-sectional study was conducted from September 2014 to August 2015 in a tertiary level Armed Force Referral and Teaching Hospital (AFRTH), Ethiopia. Armed force members (n = 251) and civilians (n = 130) which has been undergone TB diagnosis at AFRTH were included. All the specimens collected were subjected to microscopic smear observation, culture growth and drug susceptibility testing. Data were analyzed using statistical package for social sciences following binary logistic regression and Chi-square. P-values < 0.05 were considered statistically significant. Among 381 TB patients, 355 (93.2%) new and 26 (6.8%) retreatment cases were identified. Culture and smear positive TB cases were identified in 297 (77.9%) and 252 (66.1%) patients, respectively. The overall prevalence of MDR-TB in AFRTH was found 1.8% (1.3% for armed force members and 0.5% for civilian patients) all of which were previously TB treated cases. The entire treatment success rates were 92.6% achieved highest in the armed force (active and pension) than the civilian patients. The failure and dead cases were also found 2.5 and 4.6%, respectively. Using bivariate analysis, category of attendants and TB contact history were strong predictors of MDR-TB in armed force and civilian patients. Moreover, human immunodeficiency virus (HIV) infection also identified a significant (OR = 14.6; 95% CI = 2.3-92.1; p = 0.004) predicting factor for MDR-TB in armed force members. However, sex, age and body mass index were not associated factor for MDR-TB. In AFRTH, lower prevalence of

Stratification by interferon-γ release assay level predicts risk of incident TB.

PubMed

Winje, Brita Askeland; White, Richard; Syre, Heidi; Skutlaberg, Dag Harald; Oftung, Fredrik; Mengshoel, Anne Torunn; Blix, Hege Salvesen; Brantsæter, Arne Broch; Holter, Ellen Kristine; Handal, Nina; Simonsen, Gunnar Skov; Afset, Jan Egil; Bakken Kran, Anne Marte

2018-04-05

Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI. © 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.

Including the third dimension: a spatial analysis of TB cases in Houston Harris County.

PubMed

Feske, Marsha L; Teeter, Larry D; Musser, James M; Graviss, Edward A

2011-12-01

To reach the tuberculosis (TB) elimination goals established by the Institute of Medicine (IOM) and the Centers for Disease Control and Prevention (CDC), measures must be taken to speed the currently stagnant TB elimination rate and curtail a future peak in TB incidence. Increases in TB incidence have historically coincided with immigration, poverty, and joblessness; all situations that are currently occurring worldwide. Effective TB elimination strategies will require the geographical elucidation of areas within the U.S. that have endemic TB, and systematic surveillance of the locations and location-based risk factors associated with TB transmission. Surveillance data was used to assess the spatial distribution of cases, the yearly TB incidence by census tract, and the statistical significance of case clustering. The analysis revealed that there are neighborhoods within Houston/Harris County that had a heavy TB burden. The maximum yearly incidence varied from 245/100,000-754/100,000 and was not exclusively dependent of the number of cases reported. Geographically weighted regression identified risk factors associated with the spatial distribution of cases such as: poverty, age, Black race, and foreign birth. Public transportation was also associated with the spatial distribution of cases and census tracts identified as high incidence were found to be irregularly clustered within communities of varied SES. Copyright © 2011 Elsevier Ltd. All rights reserved.

Lessons learnt from TB screening in closed immigration centres in Italy.

PubMed

Crepet, Anna; Repetto, Ernestina; Al Rousan, Ahmad; Sané Schepisi, Monica; Girardi, Enrico; Prestileo, Tullio; Codecasa, Luigi; Garelli, Silvia; Corrao, Salvatore; Ippolito, Giuseppe; Decroo, Tom; Maccagno, Barbara

2016-09-01

Between June 2012 and December 2013 Médecins Sans Frontières launched a pilot project with the aim of testing a strategy for improving timely diagnosis of active pulmonary TB among migrants hosted in four centres of identification and expulsion (CIE) in Italy. This is a descriptive study. For active TB case finding we used an active symptom screening approach among migrants at admission in four CIE's. Here we describe the feasibility and the yield of this programme. Overall, 3588 migrants were screened, among whom 87 (2.4%) had a positive questionnaire. Out of 30 migrants referred for further investigations, three were diagnosed as having TB, or 0.1% out of 3588 individuals that underwent screening. Twenty-five (29%, 25/87) migrants with positive questionnaires were not referred for further investigation, following the doctors' decision; however, for 32 (37%, 32/87) migrants the diagnostic work-out was not completed. In multivariate analyses, being over 35 years (OR 1.7; 95% CI 1.1-2.6) and being transgender (OR 4.9; 95% CI 2.1-11.7), was associated with a positive questionnaire. TB screening with symptom screening questionnaires of migrants at admission in closed centres is feasible. However, to improve the yield, follow-up of patients with symptoms or signs suggestive for TB needs to be improved. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Extensively Drug-resistant Tuberculosis (XDR-TB): A daunting challenge to the current End TB Strategy and policy recommendations.

PubMed

Rahman, Md Arifur; Sarkar, Atanu

2017-07-01

Extensively Drug-resistant Tuberculosis (XDR-TB) has emerged as one of the most formidable challenges to the End TB Strategy that has targeted a 95% reduction in TB deaths and 90% reduction in cases by 2035. Globally, there were an estimated 55,100 new XDR-TB cases in 2015 in 117 countries. However, only one in 30 XDR-TB cases had been reported so far. Drug susceptibility test (DST) is the mainstay for diagnosing XDR-TB, but the lack of laboratory facilities in the resource-limited endemic countries limit its uses. A few new drugs including bedaquiline and delamanid, have the potential to improve the efficiency of XDR-TB treatment, but the drugs have been included in 39 countries only. The costs of XDR-TB treatment are several folds higher than that of the MDR-TB. Despite the financing from the donors, there is an urgent need to fill the current funding gap of US$ 2 billion to ensure effective treatment and robust surveillance. In the review article we have addressed current update on XDR-TB, including surveillance, diagnosis and the interventions needed to treat and limit its spread, emphasis on extensive financial support for implementing of current recommendations to meet the goals of End TB Strategy. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

A Serum Circulating miRNA Signature for Short-Term Risk of Progression to Active Tuberculosis Among Household Contacts.

PubMed

Duffy, Fergal J; Thompson, Ethan; Downing, Katrina; Suliman, Sara; Mayanja-Kizza, Harriet; Boom, W Henry; Thiel, Bonnie; Weiner Iii, January; Kaufmann, Stefan H E; Dover, Drew; Tabb, David L; Dockrell, Hazel M; Ottenhoff, Tom H M; Tromp, Gerard; Scriba, Thomas J; Zak, Daniel E; Walzl, Gerhard

2018-01-01

Biomarkers that predict who among recently Mycobacterium tuberculosis (MTB)-exposed individuals will progress to active tuberculosis are urgently needed. Intracellular microRNAs (miRNAs) regulate the host response to MTB and circulating miRNAs (c-miRNAs) have been developed as biomarkers for other diseases. We performed machine-learning analysis of c-miRNA measurements in the serum of adult household contacts (HHCs) of TB index cases from South Africa and Uganda and developed a c-miRNA-based signature of risk for progression to active TB. This c-miRNA-based signature significantly discriminated HHCs within 6 months of progression to active disease from HHCs that remained healthy in an independent test set [ROC area under the ROC curve (AUC) 0.74, progressors < 6 Mo to active TB and ROC AUC 0.66, up to 24 Mo to active TB], and complements the predictions of a previous cellular mRNA-based signature of TB risk.

Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-γ and IL-17 production in blood from TB + patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras.

PubMed

Alvarez-Corrales, Nancy; Ahmed, Raija K; Rodriguez, Carol A; Balaji, Kithiganahalli N; Rivera, Rebeca; Sompallae, Ramakrishna; Vudattu, Nalini K; Hoffner, Sven E; Zumla, Alimuddin; Pineda-Garcia, Lelany; Maeurer, Markus

2013-03-06

A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-γ and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-γ production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. The pattern of immune target recognition is different in regard to IFN-γ and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.

Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America.

PubMed

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

2015-01-01

Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00-4.09), prior anti-TB treatment (3.42 (1.88-6.22)), and living in EE (7.19 (3.28-15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90-96% in other regions (p<0.0001). In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART.

Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America

PubMed Central

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

2015-01-01

Objectives Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Design and Methods Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Results Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00–4.09), prior anti-TB treatment (3.42 (1.88–6.22)), and living in EE (7.19 (3.28–15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90–96% in other regions (p<0.0001). Conclusions In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART. PMID:26716686

A model of population dynamics of TB in a prison system and application to South Africa.

PubMed

Witbooi, Peter; Vyambwera, Sibaliwe Maku

2017-11-29

Tuberculosis (TB) continues to spread in South African prisons in particular, as prisons are over-capacitated and have poor ventilation. The awaiting trial detainees are not screened on admission and are at high risk of getting infected with TB. We propose a compartmental model to describe the population dynamics of TB disease in prisons. Our model considers the inflow of susceptible, exposed and TB infectives into the prison population. Removal of individuals out of the prison population can be either by death or by being released from prison, as compared to a general population in which removal is only by death. We describe conditions, including non-inflow of infectives into the prison, which will ensure that TB can be eradicated from the prison population. The model is calibrated for the South African prison system, by using data in existing literature. The model can be used to make quantitative projections of TB prevalence and to measure the effect of interventions. Illustrative simulations in this regard are presented. The model can be used for other prison populations too, if data is available to calculate the model parameters. Various simulations generated with our model serve to illustrate how it can be utilized in making future projections of the levels of prevalence of TB, and to quantify the effect of interventions such as screening, treatment or reduction of transmission parameter values through improved living conditions for inmates. This makes it particularly useful as there are various targets set by the World Health Organization and by governments, for reduction of TB prevalence and ultimately its eradication. Towards eradication of TB from a prison system, the theorem on global stability of the disease-free state is a useful indicator.

Comparison of TST and IGRA in Diagnosis of Latent Tuberculosis Infection in a High TB-Burden Setting.

PubMed

Sharma, Surendra K; Vashishtha, Richa; Chauhan, L S; Sreenivas, V; Seth, Divya

2017-01-01

There are currently two tests for diagnosing latent tuberculosis infection (LTBI); TST and IGRA. However, it is still unclear that which one of these tests performs better in high TB-burden settings. 1511 household contacts of pulmonary TB patients were enrolled to compare the performance of TST and IGRA for LTBI. At baseline all participant underwent testing for IGRA [QuantiFERON-TB® Gold In-tube (QFT-GIT) assay] and TST [2 tuberculin unit (TU), purified protein derivative (PPD), RT23, Staten Serum Institute (SSI), Copenhagen, Denmark]. All the household contacts were followed-up for two years for incident TB cases. Active TB was diagnosed in 76 household contacts at an incidence rate of 2.14 per 1000 person-years. Both, TST [Hazard Ratio (HR): 1.14, 95% confidence interval (CI): 0.72-1.79, p = 0.57], as well as QFT-GIT assay (HR: 1.66, 95% CI: 0.97-2.84, p = 0.06) results at baseline were not significantly associated with subsequent development of active TB among household contacts of pulmonary TB patients. Neither TST nor IGRA predicted subsequent development of active TB among household contacts of pulmonary TB patients during follow-up. However, keeping in view the cost, and other logistics, TST remains the most preferred method for LTBI diagnosis in resource-limited, high TB-burden settings.

Collaborative drug discovery for More Medicines for Tuberculosis (MM4TB)

PubMed Central

Ekins, Sean; Spektor, Anna Coulon; Clark, Alex M.; Dole, Krishna; Bunin, Barry A.

2016-01-01

Neglected disease drug discovery is generally poorly funded compared with major diseases and hence there is an increasing focus on collaboration and precompetitive efforts such as public–private partnerships (PPPs). The More Medicines for Tuberculosis (MM4TB) project is one such collaboration funded by the EU with the goal of discovering new drugs for tuberculosis. Collaborative Drug Discovery has provided a commercial web-based platform called CDD Vault which is a hosted collaborative solution for securely sharing diverse chemistry and biology data. Using CDD Vault alongside other commercial and free cheminformatics tools has enabled support of this and other large collaborative projects, aiding drug discovery efforts and fostering collaboration. We will describe CDD's efforts in assisting with the MM4TB project. PMID:27884746

Use of Activity Space in a Tuberculosis Outbreak: Bringing Homeless Persons Into Spatial Analyses.

PubMed

Worrell, Mary Claire; Kramer, Michael; Yamin, Aliya; Ray, Susan M; Goswami, Neela D

2017-01-01

Tuberculosis (TB) causes significant morbidity and mortality in US cities, particularly in poor, transient populations. During a TB outbreak in Fulton County, Atlanta, GA, we aimed to determine whether local maps created from multiple locations of personal activity per case would differ significantly from traditional maps created from single residential address. Data were abstracted for patients with TB disease diagnosed in 2008-2014 and receiving care at the Fulton County Health Department. Clinical and activity location data were abstracted from charts. Kernel density methods, activity space analysis, and overlay with homeless shelter locations were used to characterize case spatial distribution when using single versus multiple addresses. Data were collected for 198 TB cases, with over 30% homeless US-born cases included. Greater spatial dispersion of cases was found when utilizing multiple versus single addresses per case. Activity spaces of homeless and isoniazid (INH)-resistant cases were more spatially congruent with one another than non-homeless and INH-susceptible cases ( P < .0001 and P < .0001, respectively). Innovative spatial methods allowed us to more comprehensively capture the geography of TB-infected homeless persons, who made up a large portion of the Fulton County outbreak. We demonstrate how activity space analysis, prominent in exposure science and chronic disease, supports that routine capture of multiple location TB data may facilitate spatially different public health interventions than traditional surveillance maps. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Activities of the Korean Institute of Tuberculosis

PubMed Central

Ryoo, Sungweon; Kim, Hee Jin

2014-01-01

The Korean National Tuberculosis Association (KNTA) set up the Korean Institute of Tuberculosis (KIT) in 1970 to foster research and technical activities pertaining to tuberculosis (TB). The KNTA/KIT had successfully conducted a countrywide TB prevalence survey from 1965 to 1995 at 5-year intervals. The survey results (decline in TB rates) established Korea as a country that had successfully implemented national control programs for TB. The KIT developed the Korea Tuberculosis Surveillance System and the Laboratory Management Information System, both of which were transferred to the Korea Centers for Disease Control and Prevention after its establishment. The KIT functions as a central and supranational reference TB laboratory for microbiological and epidemiological research and provides training and education for health-care workers and medical practitioners. Recently, the KIT has expanded its activities to countries such as Ethiopia, Laos, and Timor-Leste to support TB control and prevention. The KIT will continue to support research activities and provide technical assistance in diagnosing the infection until it is completely eliminated in Korea. PMID:25861580

Energy transfer from Tb{sup 3+} to Eu{sup 2+} in Ga{sub 2}S{sub 3}:(Eu{sup 2+}, Tb{sup 3+}) crystals

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

Tagiev, O. B., E-mail: Oktay58@mail.ru; Ganbarova, Kh. B.

2015-04-15

The photoluminescence of Ga{sub 2}S{sub 3} crystals activated with Eu{sup 2+} and Tb{sup 3+} ions separately and with ions of both types is studied in the temperature range 77–300 K. It is established that, in the range 77–300 K, the observed broadband photoluminescence in (Ga{sub 2}S{sub 3}){sub 0.95}:(Eu{sub 2}O{sub 3}){sub 0.05} crystals with a peak at 545 nm is defined by 4f{sup 6}5d-4f{sup 7}({sup 8}S{sub 7/2}) intracenter transitions in Eu{sup 2+} ions and the photoluminescence with peaks at 492, 544, 584, 625, and 680 nm in (Ga{sub 2}S{sub 3}){sub 0.99}(Tb{sub 2}O{sub 3}){sub 0.01} crystals is due to the 5d →more » {sup 2}F{sub j} (j = 6−2) intracenter transitions in Tb{sup 3+} ions. It is shown that the photoluminescence bands of Tb{sup 3+} ions in the (Ga{sub 2}S{sub 3}){sub 0.94}(Eu{sub 2}O{sub 3}){sub 0.05}(Tb{sub 2}O{sub 3}){sub 0.01} crystals disappears because of excitation energy transfer from Tb{sup 3+} ions to Eu{sup 2+} ions; i.e., the Tb{sup 3+} ion is a sensitizer of the photoluminescence of the Eu{sup 2+} ion.« less

TB in Children in the United States

MedlinePlus

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

TB control: challenges and opportunities for India.

PubMed

Pai, Madhukar; Daftary, Amrita; Satyanarayana, Srinath

2016-03-01

India's TB control programme has treated over 19 million patients, but the incidence of TB continues to be high. TB is a major killer and drug-resistant TB is a growing threat. There are several likely reasons, including social conditions and co-morbidities that fuel the TB epidemic: under-investment by the government, weak programme implementation and management, suboptimal quality of care in the private sector, and insufficient advocacy around TB. Fortunately, India possesses the technical know-how, competence and resources to address these challenges. The End TB Strategy by WHO offers India an excellent blueprint to advance the agenda of TB control. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Spanish Society for Pediatric Infectious Diseases guidelines on tuberculosis in pregnant women and neonates (i): Epidemiology and diagnosis. Congenital tuberculosis].

PubMed

Baquero-Artigao, F; Mellado Peña, M J; Del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L

2015-10-01

Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Risk factors for false-negative T-SPOT.TB assay results in patients with pulmonary and extra-pulmonary TB.

PubMed

Pan, Liping; Jia, Hongyan; Liu, Fei; Sun, Huishan; Gao, Mengqiu; Du, Fengjiao; Xing, Aiying; Du, Boping; Sun, Qi; Wei, Rongrong; Gu, Shuxiang; Zhang, Zongde

2015-04-01

To investigate the risk factors for false-negative T-SPOT.TB results in patients with pulmonary TB (PTB) and extra-pulmonary TB (EPTB). Patients with suspected TB who underwent valid T-SPOT.TB tests were prospectively enrolled at Beijing Chest Hospital between November 2012 and November 2013. Basic characters and clinical laboratory findings were compared between true-positive and false-negative T-SPOT.TB groups. Of 1928 suspected TB patients, 774 (530 PTB and 244 EPTB) microbiologically/histopathogenically-confirmed patients (636 culture-confirmed) were analyzed. Forty-six PTB patients (8.7%) and 32 EPTB patients (13.1%) had negative T-SPOT.TB results. Multivariate analysis showed that increased age [odds radio (OR) 2.26, 95% confidence interval (CI) 1.11-4.58], over-weight (BMI ≥ 25 kg/m(2), OR 2.43, 95% CI 1.05-5.63), and a longer period of illness before hospitalization (>6 months, OR 2.46, 95% CI 1.24-4.92) were independent risk factors for false-negative T-SPOT.TB results in PTB patients. In EPTB patients, increased age (OR 2.42, 95% CI 1.09-5.35) also showed an independent association with false-negative T-SPOT.TB results. Careful interpretation of negative T-SPOT.TB results is necessary in older patients with suspected PTB or EPTB, and in PTB patients who are over-weight or have had longer periods of illness before hospitalization. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

TB Mobile: a mobile app for anti-tuberculosis molecules with known targets

PubMed Central

2013-01-01

Background An increasing number of researchers are focused on strategies for developing inhibitors of Mycobacterium tuberculosis (Mtb) as tuberculosis (TB) drugs. Results In order to learn from prior work we have collated information on molecules screened versus Mtb and their targets which has been made available in the Collaborative Drug Discovery (CDD) database. This dataset contains published data on target, essentiality, links to PubMed, TBDB, TBCyc (which provides a pathway-based visualization of the entire cellular biochemical network) and human homolog information. The development of mobile cheminformatics apps could lower the barrier to drug discovery and promote collaboration. Therefore we have used this set of over 700 molecules screened versus Mtb and their targets to create a free mobile app (TB Mobile) that displays molecule structures and links to the bioinformatics data. By input of a molecular structures and performing a similarity search within the app we can infer potential targets or search by targets to retrieve compounds known to be active. Conclusions TB Mobile may assist researchers as part of their workflow in identifying potential targets for hits generated from phenotypic screening and in prioritizing them for further follow-up. The app is designed to lower the barriers to accessing this information, so that all researchers with an interest in combatting this deadly disease can use it freely to the benefit of their own efforts. PMID:23497706

TB/HIV Co-Infection Care in Conflict-Affected Settings: A Mapping of Health Facilities in the Goma Area, Democratic Republic of Congo

PubMed Central

Kaboru, Berthollet Bwira; Ogwang, Brenda. A.; Namegabe, Edmond Ntabe; Mbasa, Ndemo; Kabunga, Deka Kambale; Karafuli, Kambale

2013-01-01

Background: HIV/AIDS and Tuberculosis (TB) are major contributors to the burden of disease in sub-Saharan Africa. The two diseases have been described as a harmful synergy as they are biologically and epidemiologically linked. Control of TB/HIV co-infection is an integral and most challenging part of both national TB and national HIV control programmes, especially in contexts of instability where health systems are suffering from political and social strife. This study aimed at assessing the provision of HIV/TB co-infection services in health facilities in the conflict-ridden region of Goma in Democratic Republic of Congo. Methods: A cross-sectional survey of health facilities that provide either HIV or TB services or both was carried out. A semi-structured questionnaire was used to collect the data which was analysed using descriptive statistics. Results: Eighty facilities were identified, of which 64 facilities were publicly owned. TB care was more available than HIV care (in 61% vs. 9% of facilities). Twenty-three facilities (29%) offered services to co-infected patients. TB/HIV co-infection rates among patients were unknown in 82% of the facilities. Only 19 facilities (24%) reported some coordination with and support from concerned diseases’ control programmes. HIV and TB services are largely fragmented, indicating imbalances and poor coordination by disease control programmes. Conclusion: HIV and TB control appear not to be the focus of health interventions in this crisis affected region, despite the high risks of TB and HIV infection in the setting. Comprehensive public health response to this setting calls for reforms that promote joint TB/HIV co-infection control, including improved leadership by the HIV programmes that accuse weaknesses in this conflict-ridden region. PMID:24596866

HIV, multidrug-resistant TB and depressive symptoms: when three conditions collide.

PubMed

Das, Mrinalini; Isaakidis, Petros; Van den Bergh, Rafael; Kumar, Ajay M V; Nagaraja, Sharath Burugina; Valikayath, Asmaa; Jha, Santosh; Jadhav, Bindoo; Ladomirska, Joanna

2014-01-01

Management of multidrug-resistant TB (MDR-TB) patients co-infected with human immunodeficiency virus (HIV) is highly challenging. Such patients are subject to long and potentially toxic treatments and may develop a number of different psychiatric illnesses such as anxiety and depressive disorders. A mental health assessment before MDR-TB treatment initiation may assist in early diagnosis and better management of psychiatric illnesses in patients already having two stigmatising and debilitating diseases. To address limited evidence on the baseline psychiatric conditions of HIV-infected MDR-TB patients, we aimed to document the levels of depressive symptoms at baseline, and any alteration following individualized clinical and psychological support during MDR-TB therapy, using the Patient Health Questionnaire-9 (PHQ-9) tool, among HIV-infected patients. This was a retrospective review of the medical records of an adult (aged >15 years) HIV/MDR-TB cohort registered for care during the period of August 2012 through to March 2014. A total of 45 HIV/MDR-TB patients underwent baseline assessment using the PHQ-9 tool, and seven (16%) were found to have depressive symptoms. Of these, four patients had moderate to severe depressive symptoms. Individualized psychological and clinical support was administered to these patients. Reassessments were carried out for all patients after 3 months of follow-up, except one, who died during the period. Among these 44 patients, three with baseline depressive symptoms still had depressive symptoms. However, improvements were observed in all but one after 3 months of follow-up. Psychiatric illnesses, including depressive symptoms, during MDR-TB treatment demand attention. Routine administration of baseline mental health assessments by trained staff has the potential to assist in determining appropriate measures for the management of depressive symptoms during MDR-TB treatment, and help in improving overall treatment outcomes. We recommend

Hospitalized care for MDR-TB in Port Harcourt, Nigeria: a qualitative study.

PubMed

Bieh, Kingsley Lezor; Weigel, Ralf; Smith, Helen

2017-01-10

In Nigeria multidrug-resistant tuberculosis (MDR-TB) is prevalent in 2.9% of new TB cases and 14% of retreatment cases, and the country is one of 27 with high disease burden globally. Patients are admitted and confined to one of ten MDR-TB treatment facilities throughout the initial 8 months of treatment. The perspectives of MDR-TB patients shared on social media and in academic research and those of providers are limited to experiences of home-based care. In this study we explored the views of hospitalised MDR-TB patients and providers in one treatment facility in Nigeria, and describe how their experiences are linked to accessibility of care and support services, in line with international goals. We aimed to explore the physical, social and psychological needs of hospitalized MDR TB patients, examine providers' perceptions about the hospital based model and discuss the model's advantages and disadvantages from the patient and the provider perspective. We conducted two gender distinct focus group discussions and 11 in-depth interviews with recently discharged MDR-TB patients from one MDR-TB treatment facility in Nigeria. We triangulated this with the views of four providers who played key roles in the management of MDR-TB patients via key informant interviews. Transcribed data was thematically analysed, using an iterative process to constantly compare and contrast emerging themes across the data set for deeper understanding of the full range of participants' views. The study findings demonstrate the psycho-social impacts of prolonged isolation and the coping mechanisms of patients in the facility. The dislocation of patients from their normal social networks and the detachment between providers and patients created the need for interdependence of patients for emotional and physical support. Providers' fears of infection contributed to stigma and hindered accessibility of care and support services. The current trend towards discharging patients after culture

Regulatory T Cells Subvert Mycobacterial Containment in Patients Failing Extensively Drug-resistant TB Treatment.

PubMed

Davids, Malika; Pooran, Anil S; Pietersen, Elize; Wainwright, Helen C; Binder, Anke; Warren, Robin; Dheda, Keertan

2018-02-09

The advent of extensively (XDR-TB) and totally drug-resistant TB, with limited or no treatment options, has facilitated renewed interest in host directed immunotherapy, particularly for therapeutically destitute patients. However, the selection and utility of such approaches depend upon understanding the host immune response in XDR-TB, which hitherto remains unexplored. To determine the host immunological profile in patients with XDR-TB, compared to drug-sensitive TB, using peripheral blood and explanted lung tissue. Blood and explanted lung tissue were obtained from patients with XDR-TB (n=31), drug-sensitive TB (DS-TB, n=20) and presumed latent-TB infection (LTBI, n=20). T-cell phenotype (Th1/Th2/Th17/Tregs) was evaluated in all patient groups, and Treg function assessed in XDR-TB non-responders by co-culturing PPD pre-primed effector T-cells with H37Rv-infected monocyte-derived macrophages, with or without autologous Tregs. Mycobacterial containment was evaluated by counting colony-forming units. Patients failing XDR-TB treatment had an altered immuno-phenotype characterized by a substantial increase in the frequency (median; IQR) of CD4+CD25+FoxP3+ regulatory T-cells (11.5; 5.9-15.2) compared to DS-TB (3.4 %; 1.6-5.73; p < 0.001) and presumed LTBI (1.8 % 1.2-2.3; p < 0.001), which was unrelated to disease duration. Tregs isolated from XDR-TB patients suppressed T-cell proliferation (up to 90%) and subverted containment of H37Rv-infected monocyte-derived macrophages (by 30%; p= 0.03) by impairing effector T-cell function through a mechanism independent of direct cell-to-cell contact, IL-10, TGF-beta and CTLA-4. Collectively, these data suggest that Tregs may be contributing to immune dysfunction, and bacterial persistence, in patients with XDR-TB. The relevant cellular pathways may serve as potential targets for immunotherapeutic intervention.

Dihydrolipoamide dehydrogenase-Lpd (Rv0462)-specific T cell recall responses are higher in healthy household contacts of TB: a novel immunodominant antigen from M. tuberculosis.

PubMed

Devasundaram, Santhi; Raja, Alamelu

2017-07-01

The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates. Multicolor flow cytometry analysis of whole-blood cultures showed higher Lpd-specific Th1 recall response (IFN-γ, TNF-α, and IL-2; P = 0.0006) and memory CD4 + and CD8 + T cells (CCR7 + CD45RA - and CCR7 - CD45RA - ) in healthy household contacts (HHC) of TB ( P < 0.0001), which is comparable with or higher than the standard antigens, ESAT-6 and CFP-10. The frequency of Lpd-specific multifunctional T cells was higher in HHC compared with PTB patients. However, there is no significant statistical correlation. Regulatory T cell (T reg ) analysis of HHCs and active TB patients demonstrated very low Lpd-specific CD4 + T regs relative to ESAT-6 and CFP-10. Our study demonstrates that the Lpd antigen induces a strong cellular immune response in healthy mycobacteria-infected individuals. In consideration of this population having demonstrated immunologic protection against active TB disease development, our data are encouraging about the possible use of Lpd as a target for further TB subunit vaccine development. © Society for Leukocyte Biology.

Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam.

PubMed

Phuong, N T M; Nhung, N V; Hoa, N B; Thuy, H T; Takarinda, K C; Tayler-Smith, K; Harries, A D

2016-03-21

The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010-2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010-2012. A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection-currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation.

HIV-TB Coinfection among 57 Million Pregnant Women, Obstetric Complications, Alcohol Use, Drug Abuse, and Depression.

PubMed

Fernandez, Dorian; Salami, Imoleayo; Davis, Janelle; Mbah, Florence; Kazeem, Aisha; Ash, Abreah; Babino, Justin; Carter, Laquiesha; Salemi, Jason L; Spooner, Kiara K; Olaleye, Omonike A; Salihu, Hamisu M

2018-01-01

HIV and tuberculosis represent diseases of major public health importance worldwide. Very little is known about HIV-TB coinfection among pregnant women, especially from industrialized settings. In this study, we examined the association between TB, HIV, and HIV-TB coinfection among pregnant mothers and obstetric complications, alcohol use, drug abuse, and depression. We examined inpatient hospital discharges in the United States from January 1, 2002, through December 31, 2014. We employed multivariable survey logistic regression to generate adjusted estimates for the association between infection status and study outcomes. We analyzed approximately 57 million records of pregnant women and their delivery information. HIV-TB coinfection was associated with the highest risks for several obstetric complications, alcohol use, and drug abuse. The risk for alcohol abuse was more than twice as high among HIV-monoinfected as compared to TB-monoinfected mothers. That risk gap more than doubled with HIV-TB coinfection. Both HIV-monoinfected and HIV-TB coinfected mothers experienced similarly increased risks for depression. Mothers with HIV-TB coinfection experienced relatively heightened risks for obstetric complications, alcohol use, and drug abuse. The findings of this study underscore the importance of augmenting and enhancing social and structural support systems for HIV-TB coinfected pregnant women.

Social, economic, and psychological impacts of MDR-TB treatment in Tijuana, Mexico: a patient's perspective.

PubMed

Morris, M D; Quezada, L; Bhat, P; Moser, K; Smith, J; Perez, H; Laniado-Laborin, R; Estrada-Guzman, J; Rodwell, T C

2013-07-01

The State of Baja California, Mexico, had the highest prevalence of multidrug-resistant tuberculosis (MDR-TB) in Mexico in 2009. To understand the socio-economic burden of MDR-TB disease and its treatment on patients in Tijuana and Mexicali, Mexico. From July to November 2009, qualitative interviews were conducted with 12 patients enrolled in a US-Mexico binational MDR-TB treatment program, Puentes de Esperanza (Bridges of Hope), which was designed to support MDR-TB patients. In-depth interviews were coded to identify major themes in patient experiences of MDR-TB diagnosis and care. While some patients were able to maintain their pre-MDR-TB lives to a limited extent, most patients reported losing their sense of identity due to their inability to work, social isolation, and stigmatization from family and friends. The majority of participants expressed appreciation for Puentes' role in 'saving their lives'. Being diagnosed with MDR-TB and undergoing treatment imposes significant psychological, social and economic stress on patients. Strong social support elements within Puentes helped alleviate these burdens. Improvements to the program might include peer-support groups for patients undergoing treatment and transitioning back into the community after treatment.

The Risk of Depressive Disorder Among Contacts of Tuberculosis Patients in a TB-endemic Area: A Population-based Cohort Study.

PubMed

Pan, Sheng-Wei; Yen, Yung-Feng; Feng, Jia-Yih; Su, Vincent Yi-Fong; Kou, Yu Ru; Su, Wei-Juin

2015-10-01

Tuberculosis (TB) disease may be transmitted to close contacts of index cases, causing physical illness. No studies have investigated the risk of developing depressive disorder among TB contacts in a TB-endemic area.Adult participants with a new diagnosis of TB contact (ICD-9-CM codes V01.1 plus chest radiographic order) since January 1, 2008, were identified from the National Health Insurance Research Database in Taiwan. A control cohort matched for age (±5 y), sex, enrolled years, and income level was selected. These 2 cohorts were followed until December 31, 2012, and observed for the development of depressive disorder. The Kaplan-Meier method and the log-rank test were used to examine the difference in cumulative incidences of depressive disorder between groups. Cox proportional-hazard models were used to calculate adjusted hazard ratios (aHRs) for depressive disorder.The TB contact cohort consisted of 9046 patients and matched controls of 36,184 ones. The mean age of TB contacts was 44.7 years, and 56.0% of them were women. During a mean follow-up period of 2.5 years, 127 (1.40%) TB contacts and 521 (1.44%) matched controls developed depressive disorder. TB exposure was found to be an independent risk factor of depressive disorder in women (aHR 1.34, 95% confidence interval [CI] 1.07-1.68), but not in men (aHR 0.71, 95% CI 0.48-1.06) after adjusting for age, comorbidities, and income levels. The risk of depression was significantly higher for female TB contacts than for matched controls in the first and second years (aHR 1.49, 95% CI 1.03-2.14; and aHR 1.53, 95% CI 1.05-2.23, respectively), but not thereafter. Of note, 67 (0.74%) TB contacts and 88 (0.24%) matched controls developed active TB, but none of them had subsequent depressive disorder during follow-up periods.Female TB contacts had an increased risk of depression within the first 2 years after exposure. Clinicians should consider conducting depression evaluations in addition to routine TB contact

Granzyme A as a potential biomarker of Mycobacterium tuberculosis infection and disease.

PubMed

Guggino, Giuliana; Orlando, Valentina; Cutrera, Stella; La Manna, Marco P; Di Liberto, Diana; Vanini, Valentina; Petruccioli, Elisa; Dieli, Francesco; Goletti, Delia; Caccamo, Nadia

2015-08-01

Cytotoxic molecules such as granulysin, perforin and granzymes produced by cytolytic T cells directly contribute to immune defense against tuberculosis (TB). In search for novel TB biomarkers, we have evaluated the levels of granzyme A in plasma obtained from QuantiFERON-TB Gold In tube (QFT-IT) assays from patients with active TB disease and subjects with latent TB infection (LTBI). Granzyme A serum levels in TB patients were significantly lower than values found in LTBI subjects even after subtraction of the unstimulated levels from the antigen-stimulated responses. The receiver operator characteristics (ROC) curve analysis comparing TB patients and LTBI groups, showed that at a cut-off value of granzyme A of <3.425pg/ml, the sensitivity and the specificity of the assay were 29.41% and 94.74%, respectively. Our results suggest that granzyme A could be considered another biomarker of TB, that can be used, other than IFN-γ, to discriminate between patients with active TB and LTBI subjects in a well characterized cohort of confirmed Mycobacterium tuberculosis-infected individuals. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia--an observational cohort study.

PubMed

Meressa, Daniel; Hurtado, Rocío M; Andrews, Jason R; Diro, Ermias; Abato, Kassim; Daniel, Tewodros; Prasad, Paritosh; Prasad, Rebekah; Fekade, Bekele; Tedla, Yared; Yusuf, Hanan; Tadesse, Melaku; Tefera, Dawit; Ashenafi, Abraham; Desta, Girma; Aderaye, Getachew; Olson, Kristian; Thim, Sok; Goldfeld, Anne E

2015-12-01

In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients. A standardised second-line drug (SLD) regimen was used in a non-governmental organisation-Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24 months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models. From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ≥ 24 months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m(2), p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death. We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

E-health systems for management of MDR-TB in resource-poor environments: a decade of experience and recommendations for future work.

PubMed

Fraser, Hamish S F; Habib, Ali; Goodrich, Mark; Thomas, David; Blaya, Joaquin A; Fils-Aime, Joseph Reginald; Jazayeri, Darius; Seaton, Michael; Khan, Aamir J; Choi, Sharon S; Kerrison, Foster; Falzon, Dennis; Becerra, Mercedes C

2013-01-01

Multi-drug resistant TB (MDR-TB) is a complex infectious disease that is a growing threat to global health. It requires lengthy treatment with multiple drugs and specialized laboratory testing. To effectively scale up treatment to thousands of patients requires good information systems to support clinical care, reporting, drug forecasting, supply chain management and monitoring. Over the last decade we have developed the PIH-EMR electronic medical record system, and subsequently OpenMRS-TB, to support the treatment of MDR-TB in Peru, Haiti, Pakistan, and other resource-poor environments. We describe here the experience with implementing these systems and evaluating many aspects of their performance, and review other systems for MDR-TB management. We recommend a new approach to information systems to address the barriers to scale up MDR-TB treatment, particularly access to the appropriate drugs and lab data. We propose moving away from fragmented, vertical systems to focus on common platforms, addressing all stages of TB care, support for open data standards and interoperability, care for a wide range of diseases including HIV, integration with mHealth applications, and ability to function in resource-poor environments.

Genome-wide association study of ancestry-specific TB risk in the South African Coloured population

PubMed Central

Chimusa, Emile R.; Zaitlen, Noah; Daya, Michelle; Möller, Marlo; van Helden, Paul D.; Mulder, Nicola J.; Price, Alkes L.; Hoal, Eileen G.

2014-01-01

The worldwide burden of tuberculosis (TB) remains an enormous problem, and is particularly severe in the admixed South African Coloured (SAC) population residing in the Western Cape. Despite evidence from twin studies suggesting a strong genetic component to TB resistance, only a few loci have been identified to date. In this work, we conduct a genome-wide association study (GWAS), meta-analysis and trans-ethnic fine mapping to attempt the replication of previously identified TB susceptibility loci. Our GWAS results confirm the WT1 chr11 susceptibility locus (rs2057178: odds ratio = 0.62, P = 2.71e−06) previously identified by Thye et al., but fail to replicate previously identified polymorphisms in the TLR8 gene and locus 18q11.2. Our study demonstrates that the genetic contribution to TB risk varies between continental populations, and illustrates the value of including admixed populations in studies of TB risk and other complex phenotypes. Our evaluation of local ancestry based on the real and simulated data demonstrates that case-only admixture mapping is currently impractical in multi-way admixed populations, such as the SAC, due to spurious deviations in average local ancestry generated by current local ancestry inference methods. This study provides insights into identifying disease genes and ancestry-specific disease risk in multi-way admixed populations. PMID:24057671

Evaluation of a TB infection control implementation initiative in out-patient HIV clinics in Zambia and Botswana.

PubMed

Emerson, C; Lipke, V; Kapata, N; Mwananyambe, N; Mwinga, A; Garekwe, M; Lanje, S; Moshe, Y; Pals, S L; Nakashima, A K; Miller, B

2016-07-01

Out-patient human immunodeficiency virus (HIV) care and treatment clinics in Zambia and Botswana, countries with a high burden of HIV and TB infection. To develop a tuberculosis infection control (TB IC) training and implementation package and evaluate the implementation of TB IC activities in facilities implementing the package. Prospective program evaluation of a TB IC training and implementation package using a standardized facility risk assessment tool, qualitative interviews with facility health care workers and measures of pre- and post-test performance. A composite measure of facility performance in TB IC improved from 32% at baseline to 50% at 1 year among eight facilities in Zambia, and from 27% to 80% at 6 months among 10 facilities in Botswana. Although there was marked improvement in indicators of managerial, administrative and environmental controls, key ongoing challenges remained in ensuring access to personal protective equipment and implementing TB screening in health care workers. TB IC activities at out-patient HIV clinics in Zambia and Botswana improved after training using the implementation package. Continued infrastructure support, as well as monitoring and evaluation, are needed to support the scale-up and sustainability of TB IC programs in facilities in low-resource countries.

Coordination ability determined transition metal ions substitution of Tb in Tb-Asp fluorescent nanocrystals and a facile ions-detection approach.

PubMed

Duan, Jiazhi; Ma, Baojin; Liu, Feng; Zhang, Shan; Wang, Shicai; Kong, Ying; Du, Min; Han, Lin; Wang, Jianjun; Sang, Yuanhua; Liu, Hong

2018-04-26

Although the synthesis and fluorescent properties of lanthanide-amino acid complex nanostructures have been investigated extensively, limited studies have been reported on metal ions' substitution ability for the lanthanide ions in the complex and their effect on the fluorescent property. In this study, taking biocompatible Tb-aspartic acid (Tb-Asp) complex nanocrystals as a model, the substitution mechanism of metal ions, particularly transition metals, for Tb ions in Tb-Asp nanocrystals and the change in the fluorescent property of the Tb-Asp nanocrystals after substitution were systematically investigated. The experimental results illustrated that metal ions with higher electronegativity, higher valence, and smaller radius possess stronger ability for Tb ions' substitution in Tb-Asp nanocrystals. Based on the effect of substituting ions' concentration on the fluorescent property of Tb-Asp, a facile method for copper ions detection with high sensitivity was proposed by measuring the fluorescent intensity of Tb-Asp nanocrystals' suspensions containing different concentrations of copper ions. The good biocompatibility, great convenience of synthesis and sensitive detection ability make Tb-Asp nanocrystals a very low cost and effective material for metal ions detection, which also opens a new door for practical applications of metal-Asp coordinated nanocrystals.

TB in healthcare workers in the UK: a cohort analysis 2009-2013.

PubMed

Davidson, Jennifer A; Lalor, Maeve K; Anderson, Laura F; Tamne, Surinder; Abubakar, Ibrahim; Thomas, H Lucy

2017-07-01

To describe the burden of TB in healthcare workers (HCWs) in the UK and determine whether HCWs are at increased risk of TB due to occupational exposure. Retrospective cohort analysis of national UK TB surveillance and genotyping data between 2009 and 2013. The rate of TB in HCWs compared with non-HCWs to calculate incidence rate ratios stratified by country of birth. 2320 cases of TB in HCWs were notified in the study period, 85% were born abroad. The TB rate in HCWs was 23.4 (95% CI 22.5 to 24.4) per 100 000 compared with 16.2 (95% CI 16.0 to 16.3) per 100 000 in non-HCWs. After stratifying by country of birth, there was not an increased TB incidence in HCWs for the majority of countries of birth, including in the UK-born. Using combined genotyping and epidemiological data, only 10 confirmed nosocomial transmission events involving HCWs were identified between 2010 and 2012. Of these, only two involved transmission to patients. The lack of an increased risk of TB after stratifying by country of birth, and the very few transmission events involving nosocomial transmission in the UK suggests that TB in HCWs in the UK is not generally acquired through UK occupational exposure. The majority of cases in foreign-born HCWs are likely to result from reactivation of latent TB infection (LTBI) acquired abroad, and is not likely to be prevented by BCG vaccination in the UK. Testing and treatment of LTBI in HCWs with exposure to high TB burden countries should be the focus of occupational health prevention activities. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Heme Oxygenase-1 Regulation of Matrix Metalloproteinase-1 Expression Underlies Distinct Disease Profiles in Tuberculosis

PubMed Central

Andrade, Bruno B.; Kumar, Nathella Pavan; Amaral, Eduardo P.; Riteau, Nicolas; Mayer-Barber, Katrin D.; Tosh, Kevin W.; Maier, Nolan; Conceição, Elisabete L.; Kubler, Andre; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Barbosa, Theolis; Manganiello, Vincent C.; Moss, Joel; Fontana, Joseph R.; Marciano, Beatriz E.; Sampaio, Elizabeth P.; Olivier, Kenneth N.; Holland, Steven M.; Jackson, Sharon H.; Moayeri, Mahtab; Leppla, Stephen; Sereti, Irini; Barber, Daniel L.; Nutman, Thomas B.; Babu, Subash; Sher, Alan

2015-01-01

Pulmonary tuberculosis (TB) is characterized by oxidative stress and lung tissue destruction by matrix metalloproteinases (MMP). The interplay between these distinct pathological processes and the implications for TB diagnosis and disease staging are poorly understood. Heme oxygenase-1 (HO-1) levels have been shown to distinguish active from latent as well as successfully treated Mycobacterium tuberculosis (Mtb) infection. MMP-1 expression is also associated with active TB. Here, we measured plasma levels of these two important biomarkers in distinct TB cohorts from India and Brazil. Patients with active TB expressed either very high levels of HO-1 and low levels of MMP-1 or the converse. Moreover, TB patients with either high HO-1 or MMP-1 levels displayed distinct clinical presentations as well as plasma inflammatory marker profiles. In contrast, in an exploratory North American study, inversely correlated expression of HO-1 and MMP-1 was not observed in patients with other non-tuberculous lung diseases. To assess possible regulatory interactions in the biosynthesis of these two enzymes at the cellular level, we studied expression of HO-1 and MMP-1 in Mtb-infected human and murine macrophages. We found that infection of macrophages with live virulent Mtb is required for robust induction of high levels of HO-1, but not MMP-1. In addition, we observed that carbon monoxide, a product of Mtb induced HO-1 activity, inhibits MMP-1 expression by suppressing c-Jun/AP-1 activation. These findings reveal a mechanistic link between oxidative stress and tissue remodeling that may find applicability in the clinical staging of TB patients. PMID:26268658

Drug permeation and metabolism in Mycobacterium tuberculosis: Prioritising local exposure as essential criterion in new TB drug development.

PubMed

Tanner, Lloyd; Denti, Paolo; Wiesner, Lubbe; Warner, Digby F

2018-06-22

Anti-tuberculosis (TB) drugs possess diverse abilities to penetrate the different host tissues and cell types in which infecting Mycobacterium tuberculosis bacilli are located during active disease. This is important since there is increasing evidence that the respective "lesion-penetrating" properties of the front-line TB drugs appear to correlate well with their specific activity in standard combination therapy. In turn, these observations suggest that rational efforts to discover novel treatment-shortening drugs and drug combinations should incorporate knowledge about the comparative abilities of both existing and experimental anti-TB agents to access bacilli in defined physiological states at different sites of infection, as well as avoid elimination by efflux or inactivation by host or bacterial metabolism. However, while there is a fundamental requirement to understand the mode of action and pharmacological properties of any current or experimental anti-TB agent within the context of the obligate human host, this is complex and, until recently, has been severely limited by the available methodologies and models. Here, we discuss advances in analytical models and technologies which have enabled investigations of drug metabolism and pharmacokinetics (DMPK) for new TB drug development. In particular, we consider the potential to shift the focus of traditional pharmacokinetic-pharmacodynamic analyses away from plasma to a more specific "site of action" drug exposure as an essential criterion for drug development and the design of dosing strategies. Moreover, in summarising approaches to determine DMPK data for the "unit of infection" comprising host macrophage and intracellular bacillus, we evaluate the potential benefits of including these analyses at an early stage in the preclinical drug development algorithm. © 2018 IUBMB Life, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Fluorescence properties of Tb{sup 3+} and Sm{sup 3+} activated novel LiAl{sub 7}B{sub 4}O{sub 17} host via solution combustion synthesis

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

Palaspagar, R.S., E-mail: rspalaspagar@gmail.com; Gawande, A.B., E-mail: gawandeab@gmail.com; Sonekar, R.P., E-mail: sonekar_rp@yahoo.com

2015-12-15

Graphical abstract: - Highlights: • New LiAl{sub 7}B{sub 4}O{sub 17}:Tb{sup 3+}, Sm{sup 3+} phosphors were synthesized first time by solution combustion method. • The LiAl{sub 7}B{sub 4}O{sub 17}:Tb{sup 3+} emissions; 489, 544, 586 and 623 nm (λ{sub ex} = 234 nm). • Also for LiAl{sub 7}B{sub 4}O{sub 17}:Sm{sup 3+}; 564, 601 and 649 nm (λ{sub ex} = 403 nm). • Synthesized materials were characterized by powder XRD, FE-SEM. • Concentration quenching mechanism and critical transfer distance of Tb{sup 3+} and Sm{sup 3+} in the prepared sample has been investigated. - Abstract: Novel LiAl{sub 7}B{sub 4}O{sub 17} (LABO) phosphor activated withmore » trivalent rare earth ions (RE = Tb, Sm) was synthesized by using solution combustion synthesis. The powder X-ray diffraction (XRD), field emission-scanning electron microscope (FE-SEM), photoluminescence (PL), critical transfer distance (R{sub c}) and quenching mechanism studies were employed to characterize the samples. Under ultraviolet irradiation of the LiAl{sub 7}B{sub 4}O{sub 17}: Tb{sup 3+}, Sm{sup 3+} phosphors exhibit the typical green ({sup 5}D{sub 4} → {sup 7}F{sub j} = 6, 5, 4 and 3) emission band of the Tb{sup 3+} ions, as well as an orange-red and red ({sup 4}G{sub 5/2} → {sup 6}H{sub J=5/2,} {sub 7/2,} {sub 9/2}) emission bands of the Sm{sup 3+} ions. These results suggest that Tb{sup 3+} and Sm{sup 3+} activated LABO phosphor could be promising in vision of the necessity for solid state lighting applications.« less

Rational use of Xpert testing in patients with presumptive TB: clinicians should be encouraged to use the test-treat threshold.

PubMed

Decroo, Tom; Henríquez-Trujillo, Aquiles R; De Weggheleire, Anja; Lynen, Lutgarde

2017-10-11

A recently published Ugandan study on tuberculosis (TB) diagnosis in HIV-positive patients with presumptive smear-negative TB, which showed that out of 90 patients who started TB treatment, 20% (18/90) had a positive Xpert MTB/RIF (Xpert) test, 24% (22/90) had a negative Xpert test, and 56% (50/90) were started without Xpert testing. Although Xpert testing was available, clinicians did not use it systematically. Here we aim to show more objectively the process of clinical decision-making. First, we estimated that pre-test probability of TB, or the prevalence of TB in smear-negative HIV infected patients with signs of presumptive TB in Uganda, was 17%. Second, we argue that the treatment threshold, the probability of disease at which the utility of treating and not treating is the same, and above which treatment should be started, should be determined. In Uganda, the treatment threshold was not yet formally established. In Rwanda, the calculated treatment threshold was 12%. Hence, one could argue that the threshold was reached without even considering additional tests. Still, Xpert testing can be useful when the probability of disease is above the treatment threshold, but only when a negative Xpert result can lower the probability of disease enough to cross the treatment threshold. This occurs when the pre-test probability is lower than the test-treat threshold, the probability of disease at which the utility of testing and the utility of treating without testing is the same. We estimated that the test-treatment threshold was 28%. Finally, to show the effect of the presence or absence of arguments on the probability of TB, we use confirming and excluding power, and a log10 odds scale to combine arguments. If the pre-test probability is above the test-treat threshold, empirical treatment is justified, because even a negative Xpert will not lower the post-test probability below the treatment threshold. However, Xpert testing for the diagnosis of TB should be performed

Performance evaluation of Xpert MTB/RIF in a moderate tuberculosis incidence compared with TaqMan MTB and TRCRapid M.TB.

PubMed

Tsuyuguchi, Kazunari; Nagai, Hideaki; Ogawa, Kenji; Matsumoto, Tomoshige; Morimoto, Kozo; Takaki, Akiko; Mitarai, Satoshi

2017-02-01

Xpert MTB/RIF is an automated nucleic acid amplification test (NAT) that can detect the presence of Mycobacterium tuberculosis complex (MTC) in clinical specimens as well as rifampicin (RIF) resistance resulting from rpoB mutation. Despite its high sensitivity and specificity for diagnosing tuberculosis (TB) with or without RIF resistance, the clinical performance of the test is variable. In this study, we evaluated the performance of Xpert MTB/RIF in a setting of moderate TB burden and high medical resources. A total of 427 sputum specimens were obtained from 237 suspected TB cases. Of these, 159 were identified as active TB, while the other 78 were non-TB diseases. The overall sensitivity and specificity of MTC detection by Xpert MTB/RIF using culture results as a reference were 86.8% [95% confidence interval (CI): 81.8%-90.6%] and 96.8% (95% CI: 93.1%-98.5%), respectively. Among MTC-positive culture specimens, Xpert MTB/RIF positivity was 95.2% (95% CI: 91.2%-97.5%) in smear-positive and 44.7% (95% CI 30.1-60.3) in smear-negative specimens. Xpert MTB/RIF was similar to other NATs (TaqMan MTB and TRCRapid M.TB) in terms of performance. Xpert MTB/RIF detected 25 RIF-resistant isolates as compared to 22 with the mycobacterial growth indicator tube antimicrobial susceptibility testing system, yielding a sensitivity of 100% (95% CI: 85.1%-100%) and specificity of 98.3% (95% CI: 95.1%-99.4%). These results indicate that although sensitivity in smear-negative/culture-positive specimens was relatively low, Xpert MTB/RIF is a useful diagnostic tool for detecting TB and RIF resistance even in settings of moderate TB burden. Copyright © 2016. Published by Elsevier Ltd.

Taking forward the World TB Day 2016 theme 'Unite to End Tuberculosis' for the WHO Africa Region.

PubMed

Ntoumi, Francine; Kaleebu, Pontiano; Macete, Eusebio; Mfinanga, Sayoki; Chakaya, Jeremiah; Yeboah-Manu, Dorothy; Bates, Matthew; Mwaba, Peter; Maeurer, Markus; Petersen, Eskild; Zumla, Alimuddin

2016-05-01

Tuberculosis (TB) remains a global emergency, with an estimated 9.6 million new TB cases worldwide reported in 2014. Twenty-eight percent of these cases were in the World Health Organization (WHO) Africa Region, where the annual case detection rate was 281 per 100000 population-more than double the global average of 133 per 100000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive, and the Africa Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480000 had multidrug-resistant TB (MDR-TB). Whilst of the African countries, only South Africa has reported a high prevalence of MDR-TB, it is likely that all of Sub-Saharan Africa has an unreported high load of drug-resistant TB. Tragically, in 2014, only 48% of individuals diagnosed with MDR-TB had successful treatment and an estimated 190000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the Africa Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life-expectancy and demographic profile of many countries in Sub-Saharan Africa. The theme designated for this year's World TB Day, March 24, 2016, is 'Unite to End TB'. From the Africa Region, there is an urgent need to seriously address the political, economic, and social factors that influence host-Mycobacterium tuberculosis interactions and result in disease. Recent political and funder initiatives that provide renewed hope for the alleviation of Africa's TB and TB/HIV problems are discussed. Copyright © 2016. Published by Elsevier Ltd.

Na3Tb(PO4)2: Synthesis, crystal structure and greenish emitting properties

NASA Astrophysics Data System (ADS)

Zhao, Dan; Ma, Zhao; Liu, Bao-Zhong; Zhang, Rui-Juan; Wu, Zhi-Qiang; Wang, Jian; Duan, Pei-Gao

2018-03-01

A anhydrous orthoborate Na3Tb(PO4)2 has been prepared and its crystal structure was determined by X-Ray diffraction of a non-merohedral twinned single crystal. The results show that the compound crystallizes in monoclinic space group C2/c and the structure features a 3D framework containing PO4, NaO6, NaO7, NaO8 and TbO8 polyhedra. Under near-UV excitation (370 nm), Na3Tb(PO4)2 shows intense characteristic emission bands of Tb3+ (490 nm, 543 nm, 585 nm and 620 nm) with the CIE coordinate of (0.3062, 0.5901), corresponding to greenish color. The excitation spectrum covers a wide range from 340 nm to 390 nm, which indicates that phosphor Na3Tb(PO4)2 can be efficiently activated by near-UV LED ship.

Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam

PubMed Central

Nhung, N. V.; Hoa, N. B.; Thuy, H. T.; Takarinda, K. C.; Tayler-Smith, K.; Harries, A. D.

2016-01-01

Setting: The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. Objectives: To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010–2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010–2012. Design: A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. Results: The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. Conclusion: Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection—currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation. PMID:27051608

Snapshot of Quantiferon TB gold testing in Northern Mexico.

PubMed

González-Salazar, F; Vargas-Villarreal, J; Garcialuna-Martínez, F J; Rivera, G; Moreno-Treviño, M G; Montfort-Gardeazabal, J M; Garcialuna-Martínez, E

2011-12-01

Most people infected with Mycobacterium tuberculosis have an asymptomatic condition named latent tuberculosis. These people do not have bacilli in the corporal secretions and are hard to diagnose by conventional laboratory tests. Diagnosis of latent tuberculosis infection (LTBI) in México is based on the tuberculin skin test (TST). This test has disadvantages, principally because the vaccine containing the Bacille Calmette-Guérin (BCG) is applied to 99% of this population and causes false positive TST outcomes. Recently, interferon-gamma release assays (IGRA) have been demonstrated to be a good test to detect latent tuberculosis with equal or better sensitivity to TST and without interference from BCG. However, in México the IGRA are an uncommon test due to the higher cost compared to TST. The main objective of this work was demonstrate the potential utility of the Quantiferon TB(®) gold in tube (QTB(®)-GIT) test to detect latent TB in a population from northern México. Samples from 106 subjects with close contact, or without contact, with actively infected TB patients were tested to detect LTBI. Our results show a significant difference between individuals in close contact with active TB patients (39.7%) compared to those without contact (3.2%), p < 0.01. The concordance between TST and QTB(®)-GIT was poor (κ = 0.31). Our preliminary results show that the QTB(®)-GIT has better capacity than TST to detect latent tuberculosis infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Recombinant ESAT-6-CFP10 Fusion Protein Induction of Th1/Th2 Cytokines and FoxP3 Expressing Treg Cells in Pulmonary TB.

PubMed

Jackson-Sillah, Dolly; Cliff, Jacqueline M; Mensah, Gloria Ivy; Dickson, Emmanuel; Sowah, Sandra; Tetteh, John K A; Addo, Kwasi K; Ottenhoff, Tom H M; Bothamley, Graham; Dockrell, Hazel M

2013-01-01

Early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are Mycobacterium tuberculosis (Mtb)-specific antigens that are secreted by actively metabolising bacteria and contribute to the virulence of the bacteria. Their ability to induce Treg and Th2 responses, particularly during the first two weeks of treatment, has not been comprehensively examined to date. The purpose of this work was to characterise Th1, Th2 and Treg responses to rESAT-6-CFP10 fusion protein in TB patients before and during the intensive phase of treatment and in healthy M.bovis BCG vaccinated donors. Forty-six newly diagnosed, HIV-negative, smear-positive pulmonary TB patients and 20 healthy donors were recruited in the UK and Ghana. Their peripheral blood mononuclear cells (PBMC) were used in ex vivo ELISPOT and in vitro cultures to identify immunological parameters of interest. The study confirmed that protective immune responses to rESAT-6-CFP10 are impaired in active TB but improved during treatment: circulating antigen-specific IL-4-producing T-cells were increased in untreated TB but declined by two weeks of treatment while the circulating antigen-specific IFN-γ producing T cells which showed a transient rise at one week of treatment, persisted at baseline levels at two months of treatment. In vitro T cell proliferation and IFN-γ production were reduced, while IL-4 and CD4(+)FoxP3(+)CD25(hi) cell expression were increased in response to rESAT-6-CFP10 fusion protein in untreated TB. These responses were reversed during early treatment of TB. These observations support further investigations into the possible utility of these parameters as markers of active disease and favourable treatment outcomes.

Recombinant ESAT-6-CFP10 Fusion Protein Induction of Th1/Th2 Cytokines and FoxP3 Expressing Treg Cells in Pulmonary TB

PubMed Central

Jackson-Sillah, Dolly; Cliff, Jacqueline M.; Mensah, Gloria Ivy; Dickson, Emmanuel; Sowah, Sandra; Tetteh, John K A.; Addo, Kwasi K.; Ottenhoff, Tom H. M.; Bothamley, Graham; Dockrell, Hazel M.

2013-01-01

Background Early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are Mycobacterium tuberculosis (Mtb)–specific antigens that are secreted by actively metabolising bacteria and contribute to the virulence of the bacteria. Their ability to induce Treg and Th2 responses, particularly during the first two weeks of treatment, has not been comprehensively examined to date. The purpose of this work was to characterise Th1, Th2 and Treg responses to rESAT-6-CFP10 fusion protein in TB patients before and during the intensive phase of treatment and in healthy M.bovis BCG vaccinated donors. Methods Forty-six newly diagnosed, HIV-negative, smear-positive pulmonary TB patients and 20 healthy donors were recruited in the UK and Ghana. Their peripheral blood mononuclear cells (PBMC) were used in ex vivo ELISPOT and in vitro cultures to identify immunological parameters of interest. Results The study confirmed that protective immune responses to rESAT-6-CFP10 are impaired in active TB but improved during treatment: circulating antigen-specific IL-4-producing T-cells were increased in untreated TB but declined by two weeks of treatment while the circulating antigen-specific IFN-γ producing T cells which showed a transient rise at one week of treatment, persisted at baseline levels at two months of treatment. In vitro T cell proliferation and IFN-γ production were reduced, while IL-4 and CD4+FoxP3+CD25hi cell expression were increased in response to rESAT-6-CFP10 fusion protein in untreated TB. These responses were reversed during early treatment of TB. Conclusions These observations support further investigations into the possible utility of these parameters as markers of active disease and favourable treatment outcomes. PMID:23826366

Usefulness of interferon-γ release assay for the diagnosis of sputum smear-negative pulmonary and extra-pulmonary TB in Zhejiang Province, China.

PubMed

Ji, Lei; Lou, Yong-Liang; Wu, Zhong-Xiu; Jiang, Jin-Qin; Fan, Xing-Li; Wang, Li-Fang; Liu, Xiao-Xiang; Du, Peng; Yan, Jie; Sun, Ai-Hua

2017-09-01

Quick diagnosis of smear-negative pulmonary tuberculosis (TB) and extra-pulmonary TB are urgently needed in clinical diagnosis. Our research aims to investigate the usefulness of the interferon-γ release assay (IGRA) for the diagnosis of smear-negative pulmonary and extra-pulmonary TB. We performed TB antibody and TB-IGRA tests on 389 pulmonary TB patients (including 120 smear-positive pulmonary TB patients and 269 smear-negative pulmonary TB patients), 113 extra-pulmonary TB patients, 81 patients with other pulmonary diseases and 100 healthy controls. Blood samples for the TB-Ab test and the TB-IGRA were collected, processed, and interpreted according to the manufacturer's protocol. The detection ratio of smear-positive pulmonary TB patients and smear-negative pulmonary TB patients were 90.8% (109 of 120) and 89.6% (241 of 269), respectively. There was no statistically significant difference of its performance between these two sample sets (P > 0.05). The detection ratio of positive TB patients and extra-pulmonary TB patients were 90.0% (350 of 389) and 87.6% (99 of 113), respectively, which was not significantly different (P > 0.05). In this work, the total detection ratio using TB-IGRA was 89.4%, therefore TB-IGRA has diagnostic values in smear-negative pulmonary TB and extra-pulmonary TB diagnosis.

HIV and TB co-infection in Indian context.

PubMed

Mahyoub, E M; Garg, Suneela; Singh, M M; Agarwal, Paras; Gupta, V K; Gupta, Naresh

2013-01-01

This study was carried out in a Anti-Retroviral Therapy Clinic and TB center of a tertiary level hospital to find out socio-demographic correlates of HIV/TB individuals and risk factors of HIV/TB co-infection in Indian context. It is a case-control study comprising 420 subjects, 3 groups of 140 each. For a case group of HIV-TB co-infected subjects, two control groups, one comprising HIV patients (not having TB), and the other TB patients (not having HIV). Majority 267 (63.6%) males, 100 (71.4%) in case group (HIV/ TB), 74 (52.9%) in control group 1 (TB) and 93 (66.4%) in control group 2 (HIV). Mean (+/-SD) age of case-group was 34.91 (+/- 8.57) years. New TB cases were 213 (76.1%), more among control-group 1, compared to case-group. Multivariate analysis showed that risk of co-infection was 1.94 times higher among individuals aged >35 years. Difference statistically significant amongst those who were not on ART than who were on ART (p < 0.001). Those with CD4 counts <200 had 1.85 times risk of TB. Smokers had 1.92 times risk of TB. Co-infection higher in males, in age group 35-44 years, urban area, lower educational status and lower socioeconomic class. Current history of smoking significantly associated with co-infection. HIV status during TB infection was detected in 1/4th of study subjects. History of TB symptoms in family significantly associated with co-infection.

Social, Economic, and Psychological Impacts of MDR-TB Treatment in Tijuana, Mexico: A Patient's Perspective

PubMed Central

Morris, Meghan D.; Quezada, Liliana; Bhat, Priya; Moser, Kathleen; Smith, Jennifer; Perez, Hector; Laniado-Laborin, Rafael; Estrada-Guzman, Julia; Rodwell, Timothy C.

2013-01-01

Setting The state of Baja California, Mexico had the highest prevalence of multidrug-resistant tuberculosis (MDR-TB) in Mexico in 2009. Objective To understand the socioeconomic burdens of MDR-TB disease and its treatment on patients in Tijuana and Mexicali, Mexico. Design From July to November 2009, qualitative interviews were conducted with 12 patients who were enrolled in a US-Mexico binational MDR-TB treatment program called “Puentes de Esperanza” (Bridges of Hope), which was designed to support MDR-TB patients. In-depth interviews were coded to identify major themes in patient experiences of MDR-TB diagnosis and care. Results While some patients were able to maintain their pre-MDR-TB lives to a limited extent, most patients reported losing their sense of identity due to their inability to work, social isolation, and stigmatization from family and friends. The majority of participants expressed appreciation for Puentes’ role in “saving their life.” Conclusion Being diagnosed with MDR-TB and undergoing treatment imposes significant psychological, social, and economic stress on patients. Strong social support elements within Puentes helped ameliorate these burdens. Improvements to the program might include peer-support groups for patients undergoing treatment and transitioning back into the community after treatment. PMID:23743315

Implementing the global plan to stop TB, 2011-2015--optimizing allocations and the Global Fund's contribution: a scenario projections study.

PubMed

Korenromp, Eline L; Glaziou, Philippe; Fitzpatrick, Christopher; Floyd, Katherine; Hosseini, Mehran; Raviglione, Mario; Atun, Rifat; Williams, Brian

2012-01-01

The Global Plan to Stop TB estimates funding required in low- and middle-income countries to achieve TB control targets set by the Stop TB Partnership within the context of the Millennium Development Goals. We estimate the contribution and impact of Global Fund investments under various scenarios of allocations across interventions and regions. Using Global Plan assumptions on expected cases and mortality, we estimate treatment costs and mortality impact for diagnosis and treatment for drug-sensitive and multidrug-resistant TB (MDR-TB), including antiretroviral treatment (ART) during DOTS for HIV-co-infected patients, for four country groups, overall and for the Global Fund investments. In 2015, China and India account for 24% of funding need, Eastern Europe and Central Asia (EECA) for 33%, sub-Saharan Africa (SSA) for 20%, and other low- and middle-income countries for 24%. Scale-up of MDR-TB treatment, especially in EECA, drives an increasing global TB funding need--an essential investment to contain the mortality burden associated with MDR-TB and future disease costs. Funding needs rise fastest in SSA, reflecting increasing coverage need of improved TB/HIV management, which saves most lives per dollar spent in the short term. The Global Fund is expected to finance 8-12% of Global Plan implementation costs annually. Lives saved through Global Fund TB support within the available funding envelope could increase 37% if allocations shifted from current regional demand patterns to a prioritized scale-up of improved TB/HIV treatment and secondly DOTS, both mainly in Africa--with EECA region, which has disproportionately high per-patient costs, funded from alternative resources. These findings, alongside country funding gaps, domestic funding and implementation capacity and equity considerations, should inform strategies and policies for international donors, national governments and disease control programs to implement a more optimal investment approach focusing on

Air Travel and TB: an airline perspective.

PubMed

Dowdall, Nigel P; Evans, Anthony D; Thibeault, Claude

2010-03-01

The commercial airline industry in the 21st century is a global business, able to transport large numbers of people to almost any part of the world within a few hours. There has long been concern in public health circles about the potential for transmission of communicable diseases, such as TB, on board aircraft. The recent threats from novel and emerging infectious diseases including SARS and pandemic flu has facilitated unprecedented levels of cooperation between international industry representatives, regulators and public health authorities in addressing the issues of air travel and communicable disease. This paper reviews the regulatory environment, ways in which the risks are mitigated through aspects of aircraft design, opportunities for prevention by identifying individuals who may be suffering from a communicable disease prior to flight and the approach used in managing suspected cases of communicable disease on board aircraft.

Active Tuberculosis among Homeless Persons, Toronto, Ontario, Canada, 1998–2007

PubMed Central

Rea, Elizabeth; McDermaid, Cameron; Stuart, Rebecca; Chambers, Catharine; Wang, Jun; Chan, Angie; Gardam, Michael; Jamieson, Frances; Yang, Jae; Hwang, Stephen W.

2011-01-01

While tuberculosis (TB) in Canadian cities is increasingly affecting foreign-born persons, homeless persons remain at high risk. To assess trends in TB, we studied all homeless persons in Toronto who had a diagnosis of active TB during 1998–2007. We compared Canada-born and foreign-born homeless persons and assessed changes over time. We identified 91 homeless persons with active TB; they typically had highly contagious, advanced disease, and 19% died within 12 months of diagnosis. The proportion of homeless persons who were foreign-born increased from 24% in 1998–2002 to 39% in 2003–2007. Among foreign-born homeless persons with TB, 56% of infections were caused by strains not known to circulate among homeless persons in Toronto. Only 2% of infections were resistant to first-line TB medications. The rise in foreign-born homeless persons with TB strains likely acquired overseas suggests that the risk for drug-resistant strains entering the homeless shelter system may be escalating. PMID:21392424

TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites.

PubMed

Ammerman, Michelle L; Presnyak, Vladimir; Fisk, John C; Foda, Bardees M; Read, Laurie K

2010-11-01

TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5' ends of pan-edited RNAs than at their 3' ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3' to 5' progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3' ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA-RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3' to 5' progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs.

Working towards TB elimination the WHO Regional Strategic Plan (2006-2015).

PubMed

Nair, Nani; Cooreman, Erwin

2006-03-01

DOTS has expanded rapidly in the South-East Asia Region over the period of the Partnership's first Global Plan (2001-2005), with almost 100% geographical coverage achieved in 2005. All countries have made impressive progress in improving coverage and quality. This progress has been made possible through strong political commitment and large investments in TB control for improved infrastructure, reliable drug supply, increased staffing, improved laboratory services, and intensified training and supervision. Accomplishing the objectives outlined in this document will require sustaining the progress in all countries and particularly in the five high burden countries for achieving major regional and global impact. National TB programmes will need to be supported to maintain or surpass the 70% case detection and 85% treatment success rates. The achievement of the TB-related targets linked to the MDGs will also depend on how effectively initiatives such as DOTS-Plus, PPM DOTS and interventions for TB/ HIV among others, are implemented. National governments and development partners must fulfill their commitments to mobilizing and sustaining adequate resources to support the full range of activities envisaged. The benefits of full and effective implementation of all the planned interventions would be substantial. These will result in 20 to 25 million TB cases being treated in DOTS program mes and more than 150 000 drug-resistant cases receiving treatment through DOTS-Plus during the period 2006-2015. In addition, at least 250 000 HIV-infected TB patients may also receive anti-retroviral therapy. As a consequence, the prevalence of TB is expected to fall below 175/100 000 and the number of TB deaths is expected to fall to between 100 000 and 150 000 per year. There would also be substantial economic benefits given that TB disproportionately affects adults in their most productive years. Considering these aspects, it is expected that the TB incidence will decline

Novel tunable green-red-emitting oxynitride phosphors co-activated with Ce3+, Tb3+, and Eu3+: photoluminescence and energy transfer.

PubMed

Huo, Jiansheng; Dong, Langping; Lü, Wei; Shao, Baiqi; You, Hongpeng

2017-07-14

A series of novel Ce 3+ , Tb 3+ and Eu 3+ ion doped Y 4 SiAlO 8 N-based oxynitride phosphors were synthesized by the solid-state method and characterized by X-ray powder diffraction, scanning electron microscopy, photoluminescence, lifetimes and thermo-luminescence. The excitation of the Ce 3+ /Tb 3+ co-doped and Ce 3+ /Tb 3+ /Eu 3+ tri-doped phosphor with near-UV radiation results in strong linear Tb 3+ green and Eu 3+ red emission. The occurrence of Ce 3+ -Tb 3+ and Ce 3+ -Tb 3+ -Eu 3+ energy transfer processes is responsible for the bright green or red luminescence. The Tb 3+ ion acting as an energy transfer bridge can alleviate MMCT quenching between the Ce 3+ -Eu 3+ ion pairs. The lifetime measurements demonstrated that the energy-transfer mechanisms of Ce 3+ → Tb 3+ and Tb 3+ → Eu 3+ are dipole-quadrupole and quadrupole-quadrupole interactions, respectively. The temperature dependent luminescence measurements showed that as-prepared green/red phosphors have good thermal stability against temperature quenching. The obtained results indicate that these phosphors might serve as promising candidates for n-UV LEDs.

Gene mutations in Mycobacterium tuberculosis: multidrug-resistant TB as an emerging global public health crisis.

PubMed

Mishra, Rahul; Shukla, Priyanka; Huang, Wei; Hu, Ning

2015-01-01

Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. TB poses formidable challenges to the global health at the public health and scientific level by acquiring gene mutation into anti TB drugs specially rifampin and isoniazid which leads resistant to drug regime and treatment forms. Our tools to combat MDR (multidrug resistant) TB are dangerously out of date and ineffective. Besides new tools (TB drugs, vaccines, diagnostics), we also need new strategies to identify key Mycobacterium tuberculosis and human host interaction. It is all equally important that we build up high quality clinical trial capacity and bio banks for TB biomarkers identification. But most important is global commitment at all levels to roll back TB before it expose us again. Rapid development of drug resistance caused by M. tuberculosis has lead to measure resistance accurately and easily. This knowledge will certainly help us to understand how to prevent the occurrence of drug resistance as well as identifying genes associated with new drug resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigation of Tb 3+ ion fluorescence properties in γ-irradiated poly(ethylene oxide)-TbCl 3 blended systems

NASA Astrophysics Data System (ADS)

Cho, Myung D.; Okamoto, Yoshiyuki

1995-05-01

Degradation of polymers by γ-irradiation using Tb 3+ ion as a fluorescence probe was investigated. When poly(ethylene oxide) blended with TbCl 3 films were γ-irradiated in air, the fluorescence intensity of Tb 3+ was found to be greatly increased and the molecular weights of PEO were decreased. These results suggest that radiolysis caused chain degradation of PEO and produced carbonyl groups at the end of the cleaved polymer chain. The chromophore moiety produced transfers energy to Tb 3+ ion located within the non-irradiative energy trasfer distance. It is suggested that blended films of PEO with Tb 3+ may be used as convenient and fast detectors of γ-irradiation doses.

TB preventive therapy for people living with HIV: key considerations for scale-up in resource-limited settings.

PubMed

Pathmanathan, I; Ahmedov, S; Pevzner, E; Anyalechi, G; Modi, S; Kirking, H; Cavanaugh, J S

2018-06-01

Tuberculosis (TB) is the leading cause of death for persons living with the human immunodeficiency virus (PLHIV). TB preventive therapy (TPT) works synergistically with, and independently of, antiretroviral therapy to reduce TB morbidity, mortality and incidence among PLHIV. However, although TPT is a crucial and cost-effective component of HIV care for adults and children and has been recommended as an international standard of care for over a decade, it remains highly underutilized. If we are to end the global TB epidemic, we must address the significant reservoir of tuberculous infection, especially in those, such as PLHIV, who are most likely to progress to TB disease. To do so, we must confront the pervasive perception that barriers to TPT scale-up are insurmountable in resource-limited settings. Here we review available evidence to address several commonly stated obstacles to TPT scale-up, including the need for the tuberculin skin test, limited diagnostic capacity to reliably exclude TB disease, concerns about creating drug resistance, suboptimal patient adherence to therapy, inability to monitor for and prevent adverse events, a 'one size fits all' option for TPT regimen and duration, and uncertainty about TPT use in children, adolescents, and pregnant women. We also discuss TPT delivery in the era of differentiated care for PLHIV, how best to tackle advanced planning for drug procurement and supply chain management, and how to create an enabling environment for TPT scale-up success.

Photoluminescence properties of Li2SrGeO4:RE3+ (RE = Ce/Tb/Dy) phosphors and enhanced luminescence through energy transfer between Ce3+ and Tb3+/Dy3+

NASA Astrophysics Data System (ADS)

Huang, Shuai; Li, Guogang

2014-07-01

Li2SrGeO4:RE3+ (RE = Tb/Dy/Ce) phosphors were prepared by the conventional solid-state reaction. X-ray diffraction (XRD), photoluminescence (PL) spectra, and lifetimes were utilized to characterize samples. Under the excitation of ultraviolet (231 nm for Tb3+ and 351 nm for Dy3+), the Li2SrGeO4:Tb3+ and Li2SrGeO4:Dy3+ phosphors show their respective characteristic emissions of Tb3+ (5D3,4 → 7FJ‧, J‧ = 3, 4, 5, 6) and Dy3+ (4F9/2 → 6H15/2 and 4F9/2 → 6H13/2), respectively. Ce3+ activated Li2SrGeO4 phosphors exhibit broad band blue emission due to the 5d-4f transition of Ce3+. Co-doping Ce3+ into the LSG: Ce3+/Dy3+ samples enhances the luminescence intensity of Tb3+ and Dy3+ significantly under the excitation wavelength at 340 nm through energy transfer from Ce3+ to Tb3+/Dy3+. In addition, the energy transfer mechanism between Ce3+ and Tb3+/Dy3+ has been demonstrated to be a resonant type via a dipole-quadrupole interaction.

Wavelength dependence of Verdet constant of Tb{sup 3+}:Y{sub 2}O{sub 3} ceramics

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

Snetkov, I. L., E-mail: snetkov@appl.sci-nnov.ru; Palashov, O. V.; Permin, D. A.

2016-04-18

Samples of the magneto-active material—Tb{sup 3+}:Y{sub 2}O{sub 3} ceramics with Tb{sup 3+} ion concentrations of 10%, 20%, 30%, and 100% (Tb{sub 2}O{sub 3})—were prepared and studied. The wavelength dependence of Verdet constant in the 380 nm–1750 nm range was approximated for all investigated ceramic samples and was predicted for a pure Tb{sub 2}O{sub 3} material. Tb{sub 2}O{sub 3} ceramics demonstrates a more than three times higher Verdet constant in comparison with terbium gallium garnet crystal or ceramics. The linear dependence of the Verdet constant on Tb{sup 3+} ion concentration in the Tb{sup 3+}:Y{sub 2}O{sub 3} ceramics was demonstrated. The obtained data willmore » be useful for fabricating magneto-optical elements of Faraday devices based on Tb{sup 3+}:Y{sub 2}O{sub 3} with arbitrary Tb{sup 3+} ion concentration operating at room temperature in the wavelength range of 380 nm–1750 nm.« less

Determining Mycobacterium tuberculosis Infection among BCG-Immunised Ugandan Children by T-SPOT.TB and Tuberculin Skin Testing

PubMed Central

Nkurunungi, Gyaviira; Lutangira, Jimreeves E.; Lule, Swaib A.; Akurut, Hellen; Kizindo, Robert; Fitchett, Joseph R.; Kizito, Dennison; Sebina, Ismail; Muhangi, Lawrence; Webb, Emily L.; Cose, Stephen; Elliott, Alison M.

2012-01-01

Background Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population. Methodology/Principal Findings We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens. Conclusions/Significance We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of

Alternative medicine: an ethnographic study of how practitioners of Indian medical systems manage TB in Mumbai.

PubMed

McDowell, Andrew; Pai, Madhukar

2016-03-01

Mumbai is a hot spot for drug-resistant TB, and private practitioners trained in AYUSH systems (Ayurveda, yoga, Unani, Siddha and homeopathy) are major healthcare providers. It is important to understand how AYUSH practitioners manage patients with TB or presumptive TB. We conducted semi-structured interviews of 175 Mumbai slum-based practitioners holding degrees in Ayurveda, homeopathy and Unani. Most providers gave multiple interviews. We observed 10 providers in clinical interactions, documenting: clinical examinations, symptoms, history taking, prescriptions and diagnostic tests. No practitioners exclusively used his or her system of training. The practice of biomedicine is frequent, with practitioners often using biomedical disease categories and diagnostics. The use of homeopathy was rare (only 4% of consultations with homeopaths resulted in homeopathic remedies) and Ayurveda rarer (3% of consultations). For TB, all mentioned chest x-ray while 31 (17.7%) mentioned sputum smear as a TB test. One hundred and sixty-four practitioners (93.7%) reported referring TB patients to a public hospital or chest physician. Eleven practitioners (6.3%) reported treating patients with TB. Nine (5.1%) reported treating patients with drug-susceptible TB with at least one second-line drug. Important sources of health care in Mumbai's slums, AYUSH physicians frequently use biomedical therapies and most refer patients with TB to chest physicians or the public sector. They are integral to TB care and control. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Latently and uninfected healthcare workers exposed to TB make protective antibodies against Mycobacterium tuberculosis.

PubMed

Li, Hao; Wang, Xing-Xing; Wang, Bin; Fu, Lei; Liu, Guan; Lu, Yu; Cao, Min; Huang, Hairong; Javid, Babak

2017-05-09

The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.

Rolling Out Xpert® MTB/RIF for TB Detection in HIV-Infected Populations:An Opportunity for Systems Strengthening.

PubMed

Pathmanathan, Ishani; Date, Anand; Coggin, William L; Nkengasong, John; Piatek, Amy S; Alexander, Heather

2017-03-31

To eliminate preventable deaths, disease and suffering due to tuberculosis (TB), improved diagnostic capacity is critical. The Cepheid Xpert ® MTB/RIF assay is recommended by the World Health Organization as the initial diagnostic test for people with suspected HIV-associated TB. However, despite high expectations, its scale-up in real-world settings has faced challenges, often due to the systems that support it. In this commentary we discuss needs and opportunities for systems strengthening to support widespread scale-up of Xpert ® MTB/RIF as they relate to each step within the TB diagnostic cascade, from finding presumptive patients, to collecting, transporting and testing sputum specimens, to reporting and receiving results, to initiating and monitoring treatment and, ultimately, to ensuring successful and timely treatment and cure. Investments in evidence-based interventions at each step along the cascade and within the system as a whole will augment not only the utility of Xpert ® MTB/RIF, but also the successful implementation of future diagnostic tests. Xpert ® MTB/RIF will only improve patient outcomes if optimally implemented within the context of strong TB programs and systems. Roll-out of this technology to people living with HIV and others in resource-limited settings offers the opportunity to leverage current TB and HIV laboratory, diagnostic and programmatic investments, while also addressing challenges and strengthening coordination between laboratory systems, laboratory-program interfaces, and TB-HIV program interfaces. If successful, the benefits of this tool could extend beyond progress towards global End TB Strategy goals, to improve system-wide capacity for global disease detection and control.

TbRGG2 facilitates kinetoplastid RNA editing initiation and progression past intrinsic pause sites

PubMed Central

Ammerman, Michelle L.; Presnyak, Vladimir; Fisk, John C.; Foda, Bardees M.; Read, Laurie K.

2010-01-01

TbRGG2 is an essential kinetoplastid RNA editing accessory factor that acts specifically on pan-edited RNAs. To understand the mechanism of TbRGG2 action, we undertook an in-depth analysis of edited RNA populations in TbRGG2 knockdown cells and an in vitro examination of the biochemical activities of the protein. We demonstrate that TbRGG2 down-regulation more severely impacts editing at the 5′ ends of pan-edited RNAs than at their 3′ ends. The initiation of editing is reduced to some extent in TbRGG2 knockdown cells. In addition, TbRGG2 plays a post-initiation role as editing becomes stalled in TbRGG2-depleted cells, resulting in an overall decrease in the 3′ to 5′ progression of editing. Detailed analyses of edited RNAs from wild-type and TbRGG2-depleted cells reveal that TbRGG2 facilitates progression of editing past intrinsic pause sites that often correspond to the 3′ ends of cognate guide RNAs (gRNAs). In addition, noncanonically edited junction regions are either absent or significantly shortened in TbRGG2-depleted cells, consistent with impaired gRNA transitions. Sequence analysis further suggests that TbRGG2 facilitates complete utilization of certain gRNAs. In vitro RNA annealing and in vivo RNA unwinding assays demonstrate that TbRGG2 can modulate RNA–RNA interactions. Collectively, these data are consistent with a model in which TbRGG2 facilitates initiation and 3′ to 5′ progression of editing through its ability to affect gRNA utilization, both during the transition between specific gRNAs and during usage of certain gRNAs. PMID:20855539

Hemostasis and Lipoprotein Indices Signify Exacerbated Lung Injury in TB With Diabetes Comorbidity.

PubMed

Dong, Zhengwei; Shi, Jingyun; Dorhoi, Anca; Zhang, Jie; Soodeen-Lalloo, Adiilah K; Tan, WenLing; Yin, Hongyun; Sha, Wei; Li, Weitong; Zheng, Ruijuan; Liu, Zhonghua; Yang, Hua; Qin, Lianhua; Wang, Jie; Huang, Xiaochen; Wu, Chunyan; Kaufmann, Stefan H E; Feng, Yonghong

2018-05-01

Exacerbated immunopathology is a frequent consequence of TB that is complicated by diabetes mellitus (DM); however, the underlying mechanisms are still poorly defined. In the two groups of age- and sex-matched patients with TB and DM (DM-TB) and with TB and without DM, we microscopically evaluated the areas of caseous necrosis and graded the extent of perinecrotic fibrosis in lung biopsies from the sputum smear-negative (SN) patients. We scored acid-fast bacilli in sputum smear-positive (SP) patients and compiled CT scan data from both the SN and SP patients. We compared inflammatory biomarkers and routine hematologic and biochemical parameters. Binary logistic regression analyses were applied to define the indices associated with the extent of lung injury. Enlarged caseous necrotic areas with exacerbated fibrotic encapsulations were found in SN patients with DM-TB, consistent with the higher ratio of thick-walled cavities and more bacilli in the sputum from SP patients with DM-TB. Larger necrotic foci were detected in men compared with women within the SN TB groups. Significantly higher fibrinogen and lower high-density lipoprotein cholesterol (HDL-C) were observed in SN patients with DM-TB. Regression analyses revealed that diabetes, activation of the coagulation pathway (shown by increased platelet distribution width, decreased mean platelet volume, and shortened prothrombin time), and dyslipidemia (shown by decreased low-density lipoprotein cholesterol, HDL-C, and apolipoprotein A) are risk factors for severe lung lesions in both SN and SP patients with TB. Hemostasis and dyslipidemia are associated with granuloma necrosis and fibroplasia leading to exacerbated lung damage in TB, especially in patients with DM-TB. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

[Duties of physicians or other healthcare workers connected with diagnosis, treatment, dissemination of information, assessment and registration of TB patients].

PubMed

Zielonka, Tadeusz M

2015-01-01

Effective laws provide a series of duties to be performed by physicians and other medical personnel associated with TB. Every TB case and death resulting from TB as well as any case of undesirable result of BCG test requires notification and filling in of a special form. The physician has a duty to inform TB patients their legal guardians, close relatives or friends about the need to undergo sanitary and diagnostic procedure, treatment or vaccination, as well as on how to prevent disease from spreading. Persons failing to comply with the relevant numerous legal requirements in this respect are subject to a fine.TB patients can use special sick benefits extending up to 270 days. There is a requirement to use appropriate codes to define TB irrespective of LCD-10 classification.

Malnutrition associated with unfavorable outcome and death among South African MDR-TB and HIV co-infected children.

PubMed

Hicks, R M; Padayatchi, N; Shah, N S; Wolf, A; Werner, L; Sunkari, V B; O'Donnell, M R

2014-09-01

Pediatric multidrug-resistant tuberculosis (MDR-TB) is complicated by difficult diagnosis, complex treatment, and high mortality. In South Africa, these challenges are amplified by human immunodeficiency virus (HIV) co-infection; however, evidence on treatment outcomes among co-infected children is limited. Using conventional and new pediatric definitions, to describe treatment outcomes and identify risk factors for unfavorable outcome and mortality in children aged <15 years with MDR-TB or extensively drug-resistant TB (XDR-TB) in KwaZulu-Natal, South Africa. Retrospective cohort study in a regional TB referral hospital. From January 2009 to June 2010, 84 children (median age 8 years, IQR 4-12) with MDR-TB (n = 78) or XDR-TB (n = 6) initiated treatment. Sixty-four (77%) were HIV-positive and 62 (97%) received antiretroviral therapy. Sixty-six (79%) achieved favorable treatment outcomes. Overall mortality was 11% (n = 9) at 18 months after initiation of treatment. Malnutrition (aOR 27.4, 95%CI 2.7-278.7) and severe radiographic findings (aOR 4.68, 95%CI 1.01-21.9) were associated with unfavorable outcome. New pediatric outcome definitions increased the proportion classified as cured. It is possible to successfully treat pediatric MDR-TB-HIV even in resource-poor settings. Malnutrition is a marker for severe TB-HIV disease, and is a potential target for future interventions in these patients.

Circulating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus: Association with Disease Activity

PubMed Central

Choi, Jin-Young; Ho, John Hsi-en; Pasoto, Sandra G; Bunin, Viviane; Kim, Sangtaek; Carrasco, Solange; Borba, Eduardo F; Gonçalves, Celio R; Costa, Priscila R; Kallas, Esper G; Bonfa, Eloisa; Craft, Joe

2015-01-01

Objective To assess circulating follicular helper-like CD4+ T (cTfh-like) cells in systemic lupus erythematosus (SLE) and determine their relationship to disease activity. Methods We analyzed blood samples from SLE patients, and as controls, Behçet’s disease (BD) patients and healthy individuals. We used flow cytometry to enumerate cTfh-like cells using as markers the C-X-C chemokine receptor type 5 (CXCR5), inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PCDC1, PD-1), and secretion of interleukin-21 (IL-21). We compared the frequency of cTfh-like cells with that of circulating plasmablasts (CD19+IgD−CD38+) and evaluated their possible association with disease activity. Results cTfh-like T cells, identified as CXCR5hiICOShiPD-1hi, were expanded in the blood of SLE patients compared to BD and healthy controls. Such cells produced IL-21 with lower expression of CCR7, compared to circulating CXCR5hi central memory (Tcm) cells, enabling their distinction. PD-1, not ICOS or CXCR5, expression was significantly elevated in cTfh-like cells from SLE patients compared to controls. PD-1 expression among CXCR5hi cTfh-like cells correlated with disease activity, circulating plasmablasts, and anti-dsDNA antibody positivity, but not disease duration nor past organ injury; rather, it reflected current active disease. Conclusion We found that cTfh-like cells are associated with disease activity in SLE, suggesting that their presence indicates abnormal homeostasis of T-B cell collaboration with a causal relationship central to disease pathogenesis. These findings also suggest that cTfh-like cells provide a surrogate for aberrant GC activity in SLE, and that their PD-1 expression offers a tool for following disease activity and response to therapies. PMID:25581113

Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity.

PubMed

Kwon, Yong-Soo; Cho, Young-Nan; Kim, Moon-Ju; Jin, Hye-Mi; Jung, Hyun-Ju; Kang, Jeong-Hwa; Park, Ki-Jeong; Kim, Tae-Jong; Kee, Hae Jin; Kim, Nacksung; Kee, Seung-Jung; Park, Yong-Wook

2015-05-01

Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. The aims of this study were to examine the levels of MAIT cells in pulmonary tuberculosis (TB) and nontuberculous mycobacteria (NTM) lung disease patients, to evaluate the clinical relevance of MAIT cell levels, and to investigate the functions of MAIT cells. Patients with pulmonary TB (n = 35), NTM (n = 29), and healthy controls (n = 75) were enrolled in the study. MAIT cell levels and functions were measured by flow cytometry. Circluating MAIT cell levels were found to be reduced in TB and NTM patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAIT cell numbers were significantly correlated with sputum AFB positivity, extent of disease, hemoglobin levels, lymphocyte counts, CRP and ESR levels. MAIT cells in TB patients failed to produce interferon-γ irrespective of the mode of stimulation, whereas NTM patients displayed a defect in MR1-dependent signaling pathway. Notably, an elevated expression of programmed death-1 was also associated with MAIT cell deficiency in TB. This study shows that MAIT cells are numerically and functionally deficient in TB and NTM patients and these deficiencies could contribute to immune system dysreguation in mycobacterial infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Understanding the gender aspects of tuberculosis: a narrative analysis of the lived experiences of women with TB in slums of Delhi, India.

PubMed

Khan, Koushambhi Basu

2012-01-01

There have been few ethnographic studies on gender aspects of tuberculosis (TB). In this article, drawing on a qualitative study on TB in Delhi slums and through an intersectional analysis of group interviews and personal narratives of women living with TB, I bring forth the "genderization" of TB and the associated sufferings for women. With my findings I demonstrate how gender, in conjunction with other social forces, influences the disease outcomes and stigmatizes women, how lives in slums are uniquely organized by multiple discourses that contribute to the gender makings of TB, and, finally, how women strategize to reduce their burden of illness.

inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis

PubMed Central

2013-01-01

Background Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. Results We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research

inTB - a data integration platform for molecular and clinical epidemiological analysis of tuberculosis.

PubMed

Soares, Patrícia; Alves, Renato J; Abecasis, Ana B; Penha-Gonçalves, Carlos; Gomes, M Gabriela M; Pereira-Leal, José B

2013-08-30

Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research laboratories, hospitals or

Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in Trypanosoma brucei

PubMed Central

Smith, Joseph T.; Singha, Ujjal K.; Misra, Smita

2018-01-01

ABSTRACT The small Tim proteins belong to a group of mitochondrial intermembrane space chaperones that aid in the import of mitochondrial inner membrane proteins with internal targeting signals. Trypanosoma brucei, the protozoan parasite that causes African trypanosomiasis, possesses multiple small Tim proteins that include homologues of T. brucei Tim9 (TbTim9) and Tim10 (TbTim10) and a unique small Tim that shares homology with both Tim8 and Tim13 (TbTim8/13). Here, we found that these three small TbTims are expressed as soluble mitochondrial intermembrane space proteins. Coimmunoprecipitation and mass spectrometry analysis showed that the small TbTims stably associated with each other and with TbTim17, the major component of the mitochondrial inner membrane translocase in T. brucei. Yeast two-hybrid analysis indicated direct interactions among the small TbTims; however, their interaction patterns appeared to be different from those of their counterparts in yeast and humans. Knockdown of the small TbTims reduced cell growth and decreased the steady-state level of TbTim17 and T. brucei ADP/ATP carrier (TbAAC), two polytopic mitochondrial inner membrane proteins. Knockdown of small TbTims also reduced the matured complexes of TbTim17 in mitochondria. Depletion of any of the small TbTims reduced TbTim17 import moderately but greatly hampered the stability of the TbTim17 complexes in T. brucei. Altogether, our results revealed that TbTim9, TbTim10, and TbTim8/13 interact with each other, associate with TbTim17, and play a crucial role in the integrity and maintenance of the levels of TbTim17 complexes. IMPORTANCE Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite’s mitochondrion represents a useful source for potential chemotherapeutic targets. Similarly to yeast and humans, mitochondrial functions depend on the import of proteins that are encoded in the nucleus and made in the cytosol. Even though the machinery involved in this

Divergent Small Tim Homologues Are Associated with TbTim17 and Critical for the Biogenesis of TbTim17 Protein Complexes in Trypanosoma brucei.

PubMed

Smith, Joseph T; Singha, Ujjal K; Misra, Smita; Chaudhuri, Minu

2018-06-27

The small Tim proteins belong to a group of mitochondrial intermembrane space chaperones that aid in the import of mitochondrial inner membrane proteins with internal targeting signals. Trypanosoma brucei , the protozoan parasite that causes African trypanosomiasis, possesses multiple small Tim proteins that include homologues of T. brucei Tim9 (TbTim9) and Tim10 (TbTim10) and a unique small Tim that shares homology with both Tim8 and Tim13 (TbTim8/13). Here, we found that these three small TbTims are expressed as soluble mitochondrial intermembrane space proteins. Coimmunoprecipitation and mass spectrometry analysis showed that the small TbTims stably associated with each other and with TbTim17, the major component of the mitochondrial inner membrane translocase in T. brucei Yeast two-hybrid analysis indicated direct interactions among the small TbTims; however, their interaction patterns appeared to be different from those of their counterparts in yeast and humans. Knockdown of the small TbTims reduced cell growth and decreased the steady-state level of TbTim17 and T. brucei ADP/ATP carrier (TbAAC), two polytopic mitochondrial inner membrane proteins. Knockdown of small TbTims also reduced the matured complexes of TbTim17 in mitochondria. Depletion of any of the small TbTims reduced TbTim17 import moderately but greatly hampered the stability of the TbTim17 complexes in T. brucei Altogether, our results revealed that TbTim9, TbTim10, and TbTim8/13 interact with each other, associate with TbTim17, and play a crucial role in the integrity and maintenance of the levels of TbTim17 complexes. IMPORTANCE Trypanosoma brucei is the causative agent of African sleeping sickness. The parasite's mitochondrion represents a useful source for potential chemotherapeutic targets. Similarly to yeast and humans, mitochondrial functions depend on the import of proteins that are encoded in the nucleus and made in the cytosol. Even though the machinery involved in this

TB-IRIS and remodelling of the T cell compartment in highly immunosuppressed HIV+ patients with TB: the CAPRI T (ANRS-12614) study

PubMed Central

Haridas, V.; Pean, P.; Jasenosky, L.D.; Madec, Y.; Laureillard, D.; Sok, T.; Sath, S.; Borand, L.; Marcy, O.; Chan, S.; Tsitsikov, E.; Delfraissy, J.-F.; Blanc, F.-X.; Goldfeld, A.E.

2015-01-01

Objective To investigate the impact of tuberculosis (TB)-associated immune reconstitution syndrome (IRIS) upon immunological recovery and the T cell compartment after initiation of TB and antiretroviral therapy (ART). Design and methods We prospectively evaluated T cell immunophenotypes by flow cytometry and cytokines by Luminex assays in a subset (n=154) of highly immunosuppressed HIV+ patients with TB from the CAMELIA randomized clinical trial. We compared findings from patients who developed TB-IRIS to findings from patients who did not develop TB-IRIS. Data were evaluated with mixed effect linear regression, Kaplan-Meier estimates, and Wilcoxon rank sum tests, and q-values were calculated to control for multiple comparisons. Results Development of TB-IRIS was associated with significantly greater pre-ART frequencies of HLA-DR+CD45RO+CD4+, CCR5+CD4+, OX40+CD4+, and Fas+ effector memory (EM) CD8+ T cells, and significantly elevated levels of plasma IL-6, IL-1β, IL-8, and IL-10 and viral load. Post-ART initiation, EM CD4+ and Fas+ EM CD4+ T cell frequencies significantly expanded, and central memory (CM) CD4+ T cell frequencies significantly contracted in patients who experienced TB-IRIS. By week 34 post-TB treatment initiation, EM/CM CD4+ T cell ratios were markedly higher in TB-IRIS versus non-TB-IRIS patients. Conclusions A distinct pattern of pre-ART T cell and cytokine markers appear to poise the immune response to develop TB-IRIS. Experience of TB-IRIS is then associated with long-term remodeling of the CD4+ T cell memory compartment towards an EM-dominated phenotype. We speculate that these pre- and post-ART TB-IRIS-associated immune parameters may contribute to superior immune control of TB/HIV co-infection and better clinical outcome. PMID:25486415

An intervention to stop smoking among patients suspected of TB - evaluation of an integrated approach

PubMed Central

2010-01-01

Background In many low- and middle-income countries, where tobacco use is common, tuberculosis is also a major problem. Tobacco use increases the risk of developing tuberculosis, secondary mortality, poor treatment compliance and relapses. In countries with TB epidemic, even a modest relative risk leads to a significant attributable risk. Treating tobacco dependence, therefore, is likely to have benefits for controlling tuberculosis in addition to reducing the non-communicable disease burden associated with smoking. In poorly resourced health systems which face a dual burden of disease secondary to tuberculosis and tobacco, an integrated approach to tackle tobacco dependence in TB control could be economically desirable. During TB screening, health professionals come across large numbers of patients with respiratory symptoms, a significant proportion of which are likely to be tobacco users. These clinical encounters, considered to be "teachable moments", provide a window of opportunity to offer treatment for tobacco dependence. Methods/Design We aim to develop and trial a complex intervention to reduce tobacco dependence among TB suspects based on the WHO 'five steps to quit' model. This model relies on assessing personal motivation to quit tobacco use and uses it as the basis for assessing suitability for the different therapeutic options for tobacco dependence. We will use the Medical Research Council framework approach for evaluating complex interventions to: (a) design an evidence-based treatment package (likely to consist of training materials for health professionals and education tools for patients); (b) pilot the package to determine the delivery modalities in TB programme (c) assess the incremental cost-effectiveness of the package compared to usual care using a cluster RCT design; (d) to determine barriers and drivers to the provision of treatment of tobacco dependence within TB programmes; and (e) support long term implementation. The main outcomes to

An intervention to stop smoking among patients suspected of TB--evaluation of an integrated approach.

PubMed

Siddiqi, Kamran; Khan, Amir; Ahmad, Maqsood; Shafiq-ur-Rehman

2010-03-25

In many low- and middle-income countries, where tobacco use is common, tuberculosis is also a major problem. Tobacco use increases the risk of developing tuberculosis, secondary mortality, poor treatment compliance and relapses. In countries with TB epidemic, even a modest relative risk leads to a significant attributable risk. Treating tobacco dependence, therefore, is likely to have benefits for controlling tuberculosis in addition to reducing the non-communicable disease burden associated with smoking. In poorly resourced health systems which face a dual burden of disease secondary to tuberculosis and tobacco, an integrated approach to tackle tobacco dependence in TB control could be economically desirable. During TB screening, health professionals come across large numbers of patients with respiratory symptoms, a significant proportion of which are likely to be tobacco users. These clinical encounters, considered to be "teachable moments", provide a window of opportunity to offer treatment for tobacco dependence. We aim to develop and trial a complex intervention to reduce tobacco dependence among TB suspects based on the WHO 'five steps to quit' model. This model relies on assessing personal motivation to quit tobacco use and uses it as the basis for assessing suitability for the different therapeutic options for tobacco dependence.We will use the Medical Research Council framework approach for evaluating complex interventions to: (a) design an evidence-based treatment package (likely to consist of training materials for health professionals and education tools for patients); (b) pilot the package to determine the delivery modalities in TB programme (c) assess the incremental cost-effectiveness of the package compared to usual care using a cluster RCT design; (d) to determine barriers and drivers to the provision of treatment of tobacco dependence within TB programmes; and (e) support long term implementation. The main outcomes to assess the effectiveness

Predictive value of serum bradykinin and desArg9-bradykinin levels for chemotherapeutic responses in active tuberculosis patients: A retrospective case series.

PubMed

Qian, Xu; Nguyen, Duc T M; Li, Yaojun; Lyu, Jianxin; Graviss, Edward A; Hu, Tony Y

2016-12-01

There is an urgent need for methods that can rapidly and accurately assess therapeutic responses in patients with active tuberculosis (TB) in order to predict treatment outcomes. Exposure to bacterial pathogens can rapidly activate the plasma contact system, triggering the release of bradykinin (BK) and its metabolite desArg 9 -bradykinin (DABK) to induce inflammation and innate immune responses. We hypothesized that serum BK and DABK levels might act as sensitive immune response signatures for changes in Mycobacterium tuberculosis (Mtb) burden, and therefore examined how serum levels of these markers corresponded with anti-TB therapy in a small cohort of active TB cases. Nanotrap Mass-Spectrometry (MS) was used to analyze serial blood specimens from 13 HIV-negative adults with microbiologically confirmed active TB who were treated with first-line anti-TB chemotherapy. MS signal for BK (m/z 1060.5) and DABK (m/z 904.5) serum peptides were evaluated at multiple time-points (before, during, and after treatment) to evaluate how BK and DABK levels corresponded with disease status. Serum BK levels declined from pretreatment baseline levels during the early stage anti-TB therapy (induction phase) and tended to remain below baseline levels during extended treatment (consolidation phase) and after therapy completion. BK levels were consistent with induction phase sputum culture conversions indicative of decreased Mtb burden reflecting good treatment responses. Serum DABK levels tended to increase during the induction phase and decrease at consolidation and post-therapy time points, which may indicate a shift from active disease to chronic inflammation to a disease free state. Elevated BK and DABK levels after treatment completion in one patient may be related to the subsequent recurrent TB disease. Our pilot data suggests that changes in the circulating BK and DABK levels in adult TB patients can be used as potential surrogate markers of the host response both early and

HIV screening among newly diagnosed TB patients: a cross sectional study in Lima, Peru.

PubMed

Ramírez, Suzanne; Mejía, Fernando; Rojas, Marlene; Seas, Carlos; Van der Stuyft, Patrick; Gotuzzo, Eduardo; Otero, Larissa

2018-03-20

Since 2006, the Peruvian National TB program (NTP) recommends voluntary counseling and testing (VCT) for all tuberculosis (TB) patients. Responding to the differential burden of both diseases in Peru, TB is managed in peripheral health facilities while HIV is managed in referral centers. This study aims to determine the coverage of HIV screening among TB patients and the characteristics of persons not screened. From March 2010 to December 2011 we enrolled new smear-positive pulmonary TB adults in 34 health facilities in a district in Lima. NTP staff offered VCT to all TB patients. Patients with an HIV positive result were referred for confirmation tests and management. We interviewed patients to collect their demographic and clinical characteristics and registered if patients opted in or out of the screening. Of the 1295 enrolled TB patients, nine had a known HIV diagnosis. Of the remaining, 76.1% (979) were screened for HIV. Among the 23.9% (307) not screened, 38.4% (118) opted out of the screening. TB patients at one of the health care facilities of the higher areas of the district (OR = 3.38, CI 95% 2.17-5.28 for the highest area and OR = 2.82, CI 95% 1.78-4.49 for the high area) as well as those reporting illegal drug consumption (OR = 1.65, CI 95% 1.15-2.37) were more likely not to be screened. Twenty-four were HIV positive (1.9% of all patients 1295, or 2.4% of those screened). Of 15 patients diagnosed with HIV during the TB episode, ten were enrolled in an HIV program. The median time between the result of the HIV screening and the first consultation at the HIV program was 82 days (IQR, 32-414). The median time between the result of the HIV screening and antiretroviral initiation was 148.5 days (IQR 32-500). An acceptable proportion of TB patients were screened for HIV in Lima. Referral systems of HIV positive patients should be strengthened for timely ART initiation.

Towards earlier inclusion of Children in Tuberculosis (TB) drugs trials: Consensus statements from an Expert Panel

PubMed Central

Nachman, Sharon; Ahmed, Amina; Amanullah, Farhana; Becerra, Mercedes C; Botgros, Radu; Brigden, Grania; Browning, Renee; Gardiner, Elizabeth; Hafner, Richard; Hesseling, Anneke; How, Cleotilde; Jean-Philippe, Patrick; Lessem, Erica; Makhene, Mamodikoe; Mbelle, Nontombi; Marais, Ben; McIlleron, Helen; Mc Neeley, David F; Mendel, Carl; Murray, Stephen; Navarro, Eileen; Oramasionwu, Gloria E; Porcalla, Ariel R; Powell, Clydette; Powell, Mair; Rigaud, Mona; Rouzier, Vanessa; Samson, Pearl; Schaaf, H. Simon; Shah, Seema; Starke, Jeff; Swaminathan, Soumya; Wobudeya, Eric; Worrell, Carol

2015-01-01

Children represent a significant proportion of the global tuberculosis (TB) burden, and may be disproportionately more affected by its most severe clinical manifestations. Currently available treatments for pediatric drug-susceptible (DS) and drug-resistant (DR) TB, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxicities, and an overall lack of suitable, child-friendly formulations. The complex and burdensome nature of administering the existing regimens to treat DS TB also contributes to the rise of DR TB strains. Despite the availability and use of these therapies for decades, a dearth of dosing evidence in children underscores the importance of sustained efforts for TB drug development to better meet the treatment needs of children with TB. Several new TB drugs and regimens with promising activity against both DS and DR TB strains have recently entered clinical development and are in various phases of clinical evaluation in adults or have received marketing authorization for adults. However, initiation of clinical trials to evaluate these drugs in children is often deferred, pending the availability of complete safety and efficacy data in adults or after drug approval. This document summarizes consensus statements from an international panel of childhood TB opinion leaders which support the initiation of evaluation of new TB drugs and regimens in children at earlier phases of the TB Drug development cycle. PMID:25957923

Mind the gap: TB trends in the USA and the UK, 2000-2011.

PubMed

Nnadi, Chimeremma D; Anderson, Laura F; Armstrong, Lori R; Stagg, Helen R; Pedrazzoli, Debora; Pratt, Robert; Heilig, Charles M; Abubakar, Ibrahim; Moonan, Patrick K

2016-04-01

TB remains a major public health concern, even in low-incidence countries like the USA and the UK. Over the last two decades, cases of TB reported in the USA have declined, while they have increased substantially in the UK. We examined factors associated with this divergence in TB trends between the two countries. We analysed all cases of TB reported to the US and UK national TB surveillance systems from 1 January 2000 through 31 December 2011. Negative binominal regression was used to assess potential demographic, clinical and risk factor variables associated with differences in observed trends. A total of 259,609 cases were reported. From 2000 to 2011, annual TB incidence rates declined from 5.8 to 3.4 cases per 100,000 in the USA, whereas in the UK, TB incidence increased from 11.4 to 14.4 cases per 100,000. The majority of cases in both the USA (56%) and the UK (64%) were among foreign-born persons. The number of foreign-born cases reported in the USA declined by 15% (7731 in 2000 to 6564 in 2011) while native-born cases fell by 54% (8442 in 2000 to 3883 in 2011). In contrast, the number of foreign-born cases reported in the UK increased by 80% (3380 in 2000 to 6088 in 2011), while the number of native-born cases remained largely unchanged (2158 in 2000 to 2137 in 2011). In an adjusted negative binomial regression model, significant differences in trend were associated with sex, age, race/ethnicity, site of disease, HIV status and previous history of TB (p<0.01). Among the foreign-born, significant differences in trend were also associated with time since UK or US entry (p<0.01). To achieve TB elimination in the UK, a re-evaluation of current TB control policies and practices with a focus on foreign-born are needed. In the USA, maintaining and strengthening control practices are necessary to sustain the progress made over the last 20 years. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please

Ocular inflammatory disease and ocular tuberculosis in a cohort of patients co-infected with HIV and multidrug-resistant tuberculosis in Mumbai, India: a cross-sectional study

PubMed Central

2013-01-01

Background The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART). Methods Lilavati Hospital and Research Center and Médecins Sans Frontières (MSF) organized a cross-sectional ophthalmological evaluation of HIV/MDR-TB co-infected patients followed in an MSF-run HIV-clinic in Mumbai, India, which included measuring visual acuity, and slit lamp and dilated fundus examinations. Results Between February and April 2012, 47 HIV/MDR-TB co-infected patients (including three patients with extensively drug-resistant TB) were evaluated. Sixty-four per cent were male, mean age was 39 years (standard deviation: 8.7) and their median (IQR) CD4 count at the time of evaluation was 264 cells/μL (158–361). Thirteen patients (27%) had detectable levels of HIV viremia (>20 copies/ml). Overall, examination of the anterior segments was normal in 45/47 patients (96%). A dilated fundus examination revealed active ocular inflammatory disease in seven eyes of seven patients (15.5%, 95% Confidence Intervals (CI); 5.1-25.8%). ‘These included five eyes of five patients (10%) with choroidal tubercles, one eye of one patient (2%) with presumed tubercular chorioretinitis and one eye of one patient (2%) with evidence of presumed active CMV retinitis. Presumed ocular tuberculosis was thus seen in a total of six patients (12.7%, 95% CI; 3.2-22.2%). Two patients who had completed anti-TB treatment had active ocular inflammatory disease, in the form of choroidal tubercles (two eyes of two patients). Inactive scars were seen in three eyes of three patients (6%). Patients with extrapulmonary TB and patients <39 years old were at significantly higher risk of having ocular TB [Risk Ratio: 13.65 (95% CI: 2.4-78.5) and 6.38 (95% CI: 1.05-38.8) respectively]. Conclusions Ocular

Acceptability and effectiveness of the storekeeper-based TB referral system for TB suspects in sub-districts of Lilongwe in Malawi.

PubMed

Simwaka, Bertha Nhlema; Theobald, Sally; Willets, Annie; Salaniponi, Felix M L; Nkhonjera, Patnice; Bello, George; Squire, Stephen Bertel

2012-01-01

Early access to tuberculosis diagnosis and treatment remains a challenge in developing countries. General use of informal providers such as storekeepers is common. The aim of this study was to determine the effectiveness and acceptability of a storekeeper-based referral system for TB suspects in urban settings of Lilongwe, Malawi. The referral system intervention was implemented in two sub-districts. This was evaluated using a pre and post comparison as well as comparison with a third sub-district designated as the control. The intervention included training of storekeepers to detect and refer clients with chronic cough using predesigned referral letters along with monitoring and supervision. Data from a community based chronic cough survey and an audit of health centre records were used to measure its effectiveness. Focus group discussions and in-depth interviews were carried out to document acceptability of the intervention with the different stakeholders. Following the intervention, the mean patient delay appeared lower in the intervention than comparison areas (2.14 weeks (SD 5.8) vs 8.8 weeks (SD 15.1)). However, after adjusting for confounding variables this difference was not significant (p = 0.07). After the intervention the proportion of the population diagnosed with smear positive TB in the intervention sites (1.2 per 1000) was significantly higher than in the comparison area (0.6 per 1000, p<0.01) even after adjusting for sex and age. Qualitative findings suggested that (a) the referral letters triggered health workers to ask patients to submit sputum for TB diagnosis (b) the approach may be sustainable as the referral role was linked to the livelihood of the storekeepers. The study suggests that the referral system with storekeepers is sustainable and effective in increasing smear positive TB case notification. Studies that assess this approach for control of other diseases along with collection of specimens by storekeepers or similar providers are

TB epidemiology: where are the young women? Know your tuberculosis epidemic, know your response.

PubMed

Perumal, Rubeshan; Naidoo, Kogieleum; Padayatchi, Nesri

2018-03-27

The global predominance of tuberculosis in men has received significant attention. However, epidemiological studies now demonstrate that there is an increased representation of young women with tuberculosis, especially in high HIV burden settings where young women bear a disproportionate burden of HIV. The role of the HIV epidemic, as well as changes in behavioural, biological, and structural risk factors are explored as potential explanations for the increasing burden of tuberculosis in young women. As young women are particularly vulnerable to HIV infection in sub-Saharan Africa, it is unsurprising that the TB epidemic in this setting has become increasingly feminised. This age-sex trend of TB in South Africa is similar to WHO estimates for other countries with a high HIV prevalence where there are more female than male cases notified up to the age of 25 years. The high prevalence of anaemia of chronic disease in young women with HIV is an additional potential reason for their increased TB risk. The widespread use of injectable medroxyprogesterone acetate contraception, which has been shown to possess selective glucocorticoid effect and oestrogen suppression, in young women may be an important emerging biological risk factor for tuberculosis in young women. Behavioural factors such as alcohol use and tobacco smoking patterns are further factors which may be responsible for the narrowing of the sex gap in TB epidemiology. In comparison to the significantly higher alcohol consumption rates in men globally, there is a narrowing gap in alcohol consumption between the sexes in South Africa with alarming rates of alcohol abuse in young women. There is a similar narrowing of the tobacco smoking gap between the sexes in South Africa, with increasing smoking prevalence in young women. With nearly 70% of all TB patients being co-infected with HIV in our setting, it is not surprising that the age and sex distribution of TB is increasingly resembling the distribution of HIV

Implementation and outcomes of an active defaulter tracing system for HIV, prevention of mother to child transmission of HIV (PMTCT), and TB patients in Kibera, Nairobi, Kenya.

PubMed

Thomson, Kerry A; Cheti, Erastus O; Reid, Tony

2011-06-01

Retention of patients in long term care and adherence to treatment regimens are a constant challenge for HIV, prevention of mother to child transmission of HIV (PMTCT), and TB programmes in sub-Saharan Africa. This study describes the implementation and outcomes of an active defaulter tracing system used to reduce loss to follow-up (LTFU) among HIV, PMTCT, TB, and HIV/TB co-infected patients receiving treatment at three Médecins Sans Frontières clinics in the informal settlement of Kibera, Nairobi, Kenya. Patients are routinely contacted by a social worker via telephone, in-person visit, or both very soon after they miss an appointment. Patient outcomes identified through 1066 tracing activities conducted between 1 April 2008 and 31 March 2009 included: 59.4% returned to the clinic, 9.0% unable to return to clinic, 6.3% died, 4.7% refused to return to clinic, 4.5% went to a different clinic, and 0.8% were hospitalized. Fifteen percent of patients identified for tracing could not be contacted. LTFU among all HIV patients decreased from 21.2% in 2006 to 11.5% in 2009. An active defaulter tracing system is feasible in a resource poor setting, solicits feedback from patients, retains a mobile population of patients in care, and reduces LTFU among HIV, PMTCT, and TB patients. Copyright © 2011 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Alveolar Epithelial Cells in Mycobacterium tuberculosis Infection: Active Players or Innocent Bystanders?

PubMed

Scordo, Julia M; Knoell, Daren L; Torrelles, Jordi B

2016-01-01

Tuberculosis (TB) is a disease that kills one person every 18 s. TB remains a global threat due to the emergence of drug-resistant Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following seroconversion, and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure, which influence the extent of infection. We further discuss how the M.tb-alveolar epithelium interaction instigates cell-to-cell crosstalk that regulates the immune balance between a proinflammatory and an immunoregulatory state, thereby prohibiting or allowing the establishment of infection. We propose that consideration of alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. © 2015 S. Karger AG, Basel.

Alveolar epithelial cells in Mycobacterium tuberculosis infection: Active Players or Innocent Bystanders

PubMed Central

Scordo, Julia M.; Knoell, Daren L.; Torrelles, Jordi B.

2015-01-01

Tuberculosis (TB) is a disease that kills one person every 18 seconds. TB remains a global threat due to the emergence of drug resistance Mycobacterium tuberculosis (M.tb) strains and the lack of an efficient vaccine. The ability of M.tb to persist in latency, evade recognition following sero-conversion and establish resistance in vulnerable populations warrants closer examination. Past and current research has primarily focused on examination of the role of alveolar macrophages and dendritic cells during M.tb infection, which are critical in the establishment of the host response during infection. However, emerging evidence indicates that the alveolar epithelium is a harbor for M.tb and critical during progression to active disease. Here we evaluate the relatively unexplored role of the alveolar epithelium as a reservoir and also its capacity to secrete soluble mediators upon M.tb exposure that influence the extent of infection. We further discuss how the M.tb-alveolar epithelia interaction instigate cell to cell crosstalk that regulates immune balance between a pro-inflammatory or immunoregulatory state thereby prohibiting or allowing the establishment of infection. We propose that consideration of the alveolar epithelia provides a more comprehensive understanding of the lung environment in vivo in the context of host defense against M.tb. PMID:26384325

Epidemiological Characteristics and Clinical Outcome of HIV-Related Tuberculosis in a Population of TB Patients in South-western Nigeria.

PubMed

Olowe, Olugbenga A; Makanjuola, Olufunmilola B; Adekanmi, Adeniyi S; Adefioye, Olusola J; Olowe, Rita A

2017-06-01

Tuberculosis (TB) is the second leading cause of death from infectious disease globally with its impact more dramatic in resource limited settings. Individuals with human immunodeficiency virus (HIV) infection who also develop tuberculosis represent a significant challenge to TB control. This study was carried out to determine the prevalence of TB-HIV coinfection and pattern of infection among TB patients. We also compared treatment outcome among coinfected patients with those not coinfected. A six-year retrospective review of records of patients managed at the Tuberculosis Treatment Center of the LAUTECH Teaching Hospital, South-Western Nigeria from January 2009 to December 2014 was carried out. One hundred and five (26.3%) of the 399 TB patients seen in the study period were coinfected with HIV. About 10% of the subjects had extrapulmonary tuberculosis. Treatment failure was significantly worse among patients who had both HIV and TB compared with those who had TB only (49.5% vs. 32%, p = 0.001). Death rate was also higher in the coinfected individuals implying a poorer clinical outcome. High prevalence of TB-HIV coinfection and poor treatment outcome in this group of individuals, though predictable, calls for a more concerted effort in the management of TB-HIV coinfection.

Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections.

PubMed

Roy, Upal; Barber, Paul; Tse-Dinh, Yuk-Ching; Batrakova, Elena V; Mondal, Debasis; Nair, Madhavan

2015-01-01

Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

Extensively drug-resistant tuberculosis (XDR-TB) in Morocco.

PubMed

Ennassiri, Wifak; Jaouhari, Sanae; Cherki, Wafa; Charof, Reda; Filali-Maltouf, Abdelkarim; Lahlou, Ouafae

2017-12-01

Extensively drug-resistant tuberculosis (XDR-TB) has recently been identified as a major global health threat. The aim of this study was to evaluate the presence of XDR-TB among Mycobacterium tuberculosis isolates in Morocco and its association with demographic, clinical and epidemiological features. A total of 524 patients from the Moroccan National Tuberculosis Reference Laboratory, representative of all of the geographic regions, were subject to first-line drug susceptibility testing (DST). Subsequently, 155 isolates found to be multidrug-resistant tuberculosis (MDR-TB) underwent second-line DST. Moreover, to enhance our understanding of the genetic basis of these drug-resistant strains, drug resistance-associated mutations were investigated in isolates either identified as pre-XDR- and XDR-TB or suspected resistant using the GenoType ® MTBDRsl V1.0 assay. In this study, 4 (2.6%) XDR-TB and 18 (11.6%) pre-XDR-TB isolates were identified. Agreement between the MTBDRsl assay results and phenotypic DST was 95.2% for ofloxacin, 81.0% for kanamycin and 95.2% for amikacin. To the best of our knowledge, this is the first study to evaluate the frequency of XDR-TB in Morocco. These results highlight the need to reinforce the TB management policy in Morocco with regard to control and detection strategies in order to prevent further spread of XDR-TB isolates. Copyright © 2017. Published by Elsevier Ltd.

World TB Day 2018: The Challenge of Drug Resistant Tuberculosis.

PubMed

Gupta-Wright, Ankur; Tomlinson, Gillian S; Rangaka, Molebogeng X; Fletcher, Helen A

2018-01-01

On 24th March, the world commemorates the day in 1882 when Dr Robert Koch announced his discovery of Mycobacterium tuberculosis (MTB). Over 130 years later, tuberculosis (TB) continues to affect individuals, communities, and entire health systems and economies. Koch unsuccessfully tried to 'cure' TB, and despite major advances in other areas of medicine, control of TB remains elusive- in 2016 TB was the leading infectious cause of death. The STOP TB partnership and World Health Organization (WHO) have announced their theme for World TB Day 2018 "Wanted: Leaders for a TB-Free World. You can make history. End TB." This theme recognizes that TB is much larger than any one person, institute or discipline of research, and provides an opportunity for us to reflect on the major challenges and consider how we, as a scientific community, can work together and take the lead to address the global crisis of drug-resistant TB (DR-TB).

Colworth prize lecture 2016: exploiting new biological targets from a whole-cell phenotypic screening campaign for TB drug discovery.

PubMed

Moynihan, Patrick Joseph; Besra, Gurdyal S

2017-10-01

Mycobacterium tuberculosis is the aetiological agent of tuberculosis (TB) and is the leading bacterial cause of mortality and morbidity in the world. One third of the world's population is infected with TB, and in conjunction with HIV represents a serious problem that urgently needs addressing. TB is a disease of poverty and mostly affects young adults in their productive years, primarily in the developing world. The most recent report from the World Health Organisation states that 8 million new cases of TB were reported and that ~1.5 million people died from TB. The efficacy of treatment is threatened by the emergence of multi-drug and extensively drug-resistant strains of M. tuberculosis. It can be argued that, globally, M. tuberculosis is the single most important infectious agent affecting mankind. Our research aims to establish an academic-industrial partnership with the goal of discovering new drug targets and hit-to-lead new chemical entities for TB drug discovery.

Double Standards in Global Health: Medicine, Human Rights Law and Multidrug-Resistant TB Treatment Policy.

PubMed

Nicholson, Thomas; Admay, Catherine; Shakow, Aaron; Keshavjee, Salmaan

2016-06-01

The human rights arguments that underpinned the fight against HIV over the last three decades were poised, but ultimately failed, to provide a similar foundation for success against multidrug-resistant TB (MDR-TB) and other diseases of the poor. With more than 1.5 million deaths since 2000 attributed to strains of MDR-TB, and with half a million new, and mostly untreated, MDR-TB cases in the world each year, the stakes could not be higher. The World Health Organization (WHO), whose mandate is to champion the attainment by all peoples of the highest possible level of health, recommended unsound medical treatment for MDR-TB patients in resource-poor settings from 1993-2002. Citing cost considerations, WHO did not recommend the available standard of care that had been successfully used to contain and defeat MDR-TB in rich countries. By acting as a strategic gatekeeper in its technical advisory role to donor agencies and countries, it also facilitated the global implementation of a double standard for TB care in low- and middle-income countries (LMICs), upending important legal and scientific priorities. This raises serious questions about whether the organization violated international human rights standards and those established in its own constitution. While calling for additional analysis and discussion on this topic, the authors propose that policymakers should reject double standards of this kind and instead embrace the challenge of implementing the highest standard of care on a global level.

Quality of life of pulmonary TB patients after intensive phase treatmentin the health centers of Medan city, Indonesia

NASA Astrophysics Data System (ADS)

Wahyuni, A. S.; Soeroso, N.; Harahap, J.; Amelia, R.; Alona, I.

2018-03-01

Tuberculosis (TB) is one of the chronic diseases that has become a long major health problem in the world, as well as in Indonesia. TB treatment takes a long time (6-9 months) to cover both intensive and advanced phases. TB patients experience significant disruptions in their social life, exposed to stigma and discrimination. The purpose of this study was to determine the quality of life of TB patients after two months of TB intensive treatment phase. We conducted a quantitative study through cross-sectional design. This research recruited 100 TB patients aged > 18 years old and Category I with AFB(+) result. We involved patients from 7 Health Centers in Medan City. We utilised SF 36 instrument to assess the patients quality of lifein the interview. To analyse the collected data, we performed Independent t-analysis. The result of this study was that the quality of life of TB patients who had undergone initial treatment phase wasina low category with a score of 63.9. The two best-measured aspects of quality of life among the eight dimensions assessed in the instrument were pain and physical function.

DNA topoisomerase I and DNA gyrase as targets for TB therapy.

PubMed

Nagaraja, Valakunja; Godbole, Adwait A; Henderson, Sara R; Maxwell, Anthony

2017-03-01

Tuberculosis (TB) is the deadliest bacterial disease in the world. New therapeutic agents are urgently needed to replace existing drugs for which resistance is a significant problem. DNA topoisomerases are well-validated targets for antimicrobial and anticancer chemotherapies. Although bacterial topoisomerase I has yet to be exploited as a target for clinical antibiotics, DNA gyrase has been extensively targeted, including the highly clinically successful fluoroquinolones, which have been utilized in TB therapy. Here, we review the exploitation of topoisomerases as antibacterial targets and summarize progress in developing new agents to target DNA topoisomerase I and DNA gyrase from Mycobacterium tuberculosis. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Technology and tuberculosis control: the OUT-TB Web experience.

PubMed

Guthrie, Jennifer L; Alexander, David C; Marchand-Austin, Alex; Lam, Karen; Whelan, Michael; Lee, Brenda; Furness, Colin; Rea, Elizabeth; Stuart, Rebecca; Lechner, Julia; Varia, Monali; McLean, Jennifer; Jamieson, Frances B

2017-04-01

Develop a tool to disseminate integrated laboratory, clinical, and demographic case data necessary for improved contact tracing and outbreak detection of tuberculosis (TB). In 2007, the Public Health Ontario Laboratories implemented a universal genotyping program to monitor the spread of TB strains within Ontario. Ontario Universal Typing of TB (OUT-TB) Web utilizes geographic information system (GIS) technology with a relational database platform, allowing TB control staff to visualize genotyping matches and microbiological data within the context of relevant epidemiological and demographic data. OUT-TB Web is currently available to the 8 health units responsible for >85% of Ontario's TB cases and is a valuable tool for TB case investigation. Users identified key features to implement for application enhancements, including an e-mail alert function, customizable heat maps for visualizing TB and drug-resistant cases, socioeconomic map layers, a dashboard providing TB surveillance metrics, and a feature for animating the geographic spread of strains over time. OUT-TB Web has proven to be an award-winning application and a useful tool. Developed and enhanced using regular user feedback, future versions will include additional data sources, enhanced map and line-list filter capabilities, and development of a mobile app. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India.

PubMed

Raizada, Neeraj; Khaparde, Sunil D; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M; Singh, Varinder; Umadevi, K R; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C H Surya; Mall, Shalini; Singh, Pooja; Saha, B K; Denkinger, Claudia M; Boehme, Catharina; Sarin, Sanjay

2018-01-01

Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65-8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9-9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India

PubMed Central

Raizada, Neeraj; Khaparde, Sunil D.; Salhotra, Virender Singh; Rao, Raghuram; Kalra, Aakshi; Swaminathan, Soumya; Khanna, Ashwani; Chopra, Kamal Kishore; Hanif, M.; Singh, Varinder; Umadevi, K. R.; Nair, Sreenivas Achuthan; Huddart, Sophie; Prakash, C. H. Surya; Mall, Shalini; Singh, Pooja; Saha, B. K.; Denkinger, Claudia M.; Boehme, Catharina

2018-01-01

Background Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. Methods A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0–14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. Results The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65–8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9–9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. Conclusion The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest

Can Australia eliminate TB? Modelling immigration strategies for reaching MDG targets in a low-transmission setting.

PubMed

Denholm, Justin T; McBryde, Emma S

2014-02-01

The 2050 Millennium Development Goals (MDG) for tuberculosis (TB) aim for elimination of TB as a public health issue. We used a mathematical modelling approach to evaluate the feasibility of this target in a low-prevalence setting with immigration-related strategies directed at latent tuberculosis. We used a stochastic individual-based model to simulate tuberculosis disease among immigrants to Victoria, Australia; a representative low-transmission setting. A variety of screening and treatment approaches aimed at preventing reactivation of latent infection were applied to evaluate overall tuberculosis incidence reduction and rates of multidrug resistant disease. Without additional intervention, tuberculosis incidence was predicted to reach 34.5 cases/million by 2050. Strategies involving the introduction of an available screening/treatment combination reduced TB incidence to between 16.9-23.8 cases/million, and required screening of 136-427 new arrivals for each case of TB prevented. Limiting screening to higher incidence regions of origin was less effective but more efficient. Public health strategies targeting latent tuberculosis infection in immigrants may substantially reduce tuberculosis incidence in a low prevalence region. However, immigration-focused strategies cannot achieve the 2050 MDG and alternative or complementary approaches are required. © 2014 The Authors. ANZJPH © 2014 Public Health Association of Australia.

Designing and implementing a socioeconomic intervention to enhance TB control: operational evidence from the CRESIPT project in Peru.

PubMed

Wingfield, Tom; Boccia, Delia; Tovar, Marco A; Huff, Doug; Montoya, Rosario; Lewis, James J; Gilman, Robert H; Evans, Carlton A

2015-08-21

Cash transfers are key interventions in the World Health Organisation's post-2015 global TB policy. However, evidence guiding TB-specific cash transfer implementation is limited. We designed, implemented and refined a novel TB-specific socioeconomic intervention that included cash transfers, which aimed to support TB prevention and cure in resource-constrained shantytowns in Lima, Peru for: the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project. Newly-diagnosed TB patients from study-site healthposts were eligible to receive the intervention consisting of economic and social support. Economic support was provided to patient households through cash transfers on meeting the following conditions: screening for TB in household contacts and MDR TB in patients; adhering to TB treatment and chemoprophylaxis; and engaging with CRESIPT social support (household visits and community meetings). To evaluate project acceptability, quantitative and qualitative feedback was collected using a mixed-methods approach during formative activities. Formative activities included consultations, focus group discussions and questionnaires conducted with the project team, project participants, civil society and stakeholders. Over 7 months, 135 randomly-selected patients and their 647 household contacts were recruited from 32 impoverished shantytown communities. Of 1299 potential cash transfers, 964 (74 %) were achieved, 259 (19 %) were not achieved, and 76 (7 %) were yet to be achieved. Of those achieved, 885/964 (92 %) were achieved optimally and 79/964 (8 %) sub-optimally. Key project successes were identified during 135 formative activities and included: strong multi-sectorial collaboration; generation of new evidence for TB-specific cash transfer; and the project being perceived as patient-centred and empowering. Challenges included: participant confidence being eroded through cash transfer delays, hidden account-charges and stigma; access to

Magnetic and thermal properties of amorphous TbFeCo alloy films

NASA Astrophysics Data System (ADS)

Wang, Ke; Dong, Shuo; Huang, Ya; Qiu, Yuzhen

2017-07-01

Amorphous TbFeCo material with perpendicular magnetic anisotropy is currently attracting more attention for potential applications in spintronic devices and logic memories. We systematically investigate magnetic, structural, thermal, optical and electrical properties of TbFeCo alloy films. It shows out-of-plane easy axis of the films turns into in-plane orientation after annealing. Significant increase in saturation magnetization in the temperature range between 400 and 450 °C is revealed by thermomagnetic measurements. The occurrence of crystallization and oxidation at high temperatures is confirmed by X-ray diffraction measurements. Pronounced changes in optical reflectance and sheet resistance are observed with temperature, in line with structural relaxation and change. The activation barriers for crystallization and oxidation are determined to be 1.01 eV and 0.83 eV, respectively, for FeCo-rich and Tb-rich samples. Better thermal stability against crystallization and oxidation is demonstrated in the FeCo-rich sample than the Tb-rich type. Our results provide some useful information for the alloy used in device fabrication.

Preparation and characterization of Tb3+ ions doped zincborophosphate glasses for green emission

NASA Astrophysics Data System (ADS)

Bindu, S. Hima; Raju, D. Siva; Krishna, V. Vinay; Raju, Ch. Linga

2017-06-01

The present study reports the preparation of various concentrations of Tb3+ ions doped zincborophosphate glasses and analysis by XRD, FTIR, optical, emission and decay curve spectras. The effect of borate groups on the phosphate was evidenced by FTIR spectroscopy. The JO intensity parameters was calculated using Judd-Offlet theory. The fluroscence spectra of Tb3+ doped zincborophosphate glasses revealed the efficient blue and green emissions due to 5D3 and 5D4 excited levels to 7Fj ground state respectively. The decay curves exhibits single exponential curves for all the Tb3+ ion concentrations. Various radiative and fluorescence parameters are calculated using JO intensity parameters. Based on the results obtained in the present study, the Tb3+ ions doped zincborophosphate glasses behaves as a efficient laser active materials for highintensity emissions in the green region.

IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after antituberculosis treatment.

PubMed

Yang, Qianting; Cai, Yi; Zhao, Wei; Wu, Fan; Zhang, Mingxia; Luo, Kai; Zhang, Yan; Liu, Haiying; Zhou, Boping; Kornfeld, Hardy; Chen, Xinchun

2014-12-01

The diagnosis of active tuberculosis (TB) disease remains a challenge, especially in high-burden settings. Cytokines and chemokines are important in the pathogenesis of TB. Here we investigate the usefulness of circulating and compartmentalized cytokines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF), and cerebrospinal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 and MIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG for distinguishing TB from LTBI. However, IP-10 and MIG levels in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 and MIG in the PF and CSF showed promising diagnostic values in discriminating TB and non-TB pleural effusion (AUC = 0.87 for IP-10 and 0.93 for MIG), as well as TB meningitis and non-TB meningitis (AUC = 0.9 for IP-10 and 0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, granulocyte colony-stimulating factor (G-CSF), and gamma interferon (IFN-γ) decreased, while the levels of MCP-1/CCL2 and eotaxin-1/CCL11 increased, after successful treatment of TB. Our findings provide a practical methodology for discriminating active TB from LTBI by sequential IFN-γ release assays (IGRAs) and plasma IP-10 testing, while increased IP-10 and MIG at the site of infection (PF or CSF) can be used as a marker for distinguishing pleural effusion and meningitis caused by TB from those of non-TB origins. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Role of TAF12 in the Increased VDR Activity in Paget’s Disease of Bone

DTIC Science & Technology

2014-10-01

DRIP205) and VDR interacting with the histone acetyltransferases (SRC1, CBBP etc) that control entry and activity of RNA polymerase II for TAF12...bone volume fraction (BV/TV, %), trabecular number (Tb.N, N /mm2), trabecular thickness (Tb.Th, mm), and trabecular bone spacing (Tb.Sp, mm). Cortical...mean SD ( n ¼ 4); p< 0.01, significantly different from OCLs formed with the same treatment in WT mouse cultures. (B) OCL formation by treatment of

A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis

PubMed Central

Schnippel, Kathryn; Sharp, Alana

2016-01-01

Objective Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. Methods We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Findings Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low

A Data-Driven Evaluation of the Stop TB Global Partnership Strategy of Targeting Key Populations at Greater Risk for Tuberculosis.

PubMed

McLaren, Zoë M; Schnippel, Kathryn; Sharp, Alana

2016-01-01

Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low-income households (β1 = -0

Targeted screening and treatment for latent tuberculosis infection using QuantiFERON-TB Gold is cost-effective in Mexico.

PubMed

Burgos, J L; Kahn, J G; Strathdee, S A; Valencia-Mendoza, A; Bautista-Arredondo, S; Laniado-Laborin, R; Castañeda, R; Deiss, R; Garfein, R S

2009-08-01

To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective.

Multifunctional G-Rich and RRM-Containing Domains of TbRGG2 Perform Separate yet Essential Functions in Trypanosome RNA Editing

PubMed Central

Foda, Bardees M.; Downey, Kurtis M.; Fisk, John C.

2012-01-01

Efficient editing of Trypanosoma brucei mitochondrial RNAs involves the actions of multiple accessory factors. T. brucei RGG2 (TbRGG2) is an essential protein crucial for initiation and 3′-to-5′ progression of editing. TbRGG2 comprises an N-terminal G-rich region containing GWG and RG repeats and a C-terminal RNA recognition motif (RRM)-containing domain. Here, we perform in vitro and in vivo separation-of-function studies to interrogate the mechanism of TbRGG2 action in RNA editing. TbRGG2 preferentially binds preedited mRNA in vitro with high affinity attributable to its G-rich region. RNA-annealing and -melting activities are separable, carried out primarily by the G-rich and RRM domains, respectively. In vivo, the G-rich domain partially complements TbRGG2 knockdown, but the RRM domain is also required. Notably, TbRGG2's RNA-melting activity is dispensable for RNA editing in vivo. Interactions between TbRGG2 and MRB1 complex proteins are mediated by both G-rich and RRM-containing domains, depending on the binding partner. Overall, our results are consistent with a model in which the high-affinity RNA binding and RNA-annealing activities of the G-rich domain are essential for RNA editing in vivo. The RRM domain may have key functions involving interactions with the MRB1 complex and/or regulation of the activities of the G-rich domain. PMID:22798390

Spectroscopy and energy transfer in lead borate glasses doubly doped with Dy(3)(+)-Tb(3+) and Tb(3)(+)-Eu(3+) ions.

PubMed

Pisarska, Joanna; Kos, Agnieszka; Pisarski, Wojciech A

2014-08-14

Lead borate glasses doubly doped with Dy(3)(+)-Tb(3+) and Tb(3+)-Eu(3+) were investigated using optical spectroscopy. Luminescence spectra of rare earths were detected under various excitation wavelengths. The main green emission band due to (5)D4→(7)F5 transition of Tb(3+) is observed under excitation of Dy(3+), whereas the main red emission band related to (5)D0→(7)F2 transition of Eu(3+) is successfully observed under direct excitation of Tb(3+). In both cases, the energy transfer processes from Dy(3+) to Tb(3+) and from Tb(3+) to Eu(3+) in lead borate glasses occur through a nonradiative processes with efficiencies up to 16% and 18%, respectively. The presence of energy transfer process was also confirmed by excitation spectra measurements. Copyright © 2014 Elsevier B.V. All rights reserved.

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India.

PubMed

Sachdeva, Kuldeep Singh; Raizada, Neeraj; Sreenivas, Achuthan; Van't Hoog, Anna H; van den Hof, Susan; Dewan, Puneet K; Thakur, Rahul; Gupta, R S; Kulsange, Shubhangi; Vadera, Bhavin; Babre, Ameet; Gray, Christen; Parmar, Malik; Ghedia, Mayank; Ramachandran, Ranjani; Alavadi, Umesh; Arinaminpathy, Nimalan; Denkinger, Claudia; Boehme, Catharina; Paramasivan, C N

2015-01-01

Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

PubMed Central

Sachdeva, Kuldeep Singh; Raizada, Neeraj; Sreenivas, Achuthan; van't Hoog, Anna H.; van den Hof, Susan; Dewan, Puneet K.; Thakur, Rahul; Gupta, R. S.; Kulsange, Shubhangi; Vadera, Bhavin; Babre, Ameet; Gray, Christen; Parmar, Malik; Ghedia, Mayank; Ramachandran, Ranjani; Alavadi, Umesh; Arinaminpathy, Nimalan; Denkinger, Claudia; Boehme, Catharina; Paramasivan, C. N.

2015-01-01

Background Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. Methods This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. Results In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Conclusion Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased

Assessing spatial heterogeneity of MDR-TB in a high burden country

PubMed Central

Jenkins, Helen E.; Plesca, Valeriu; Ciobanu, Anisoara; Crudu, Valeriu; Galusca, Irina; Soltan, Viorel; Serbulenco, Aliona; Zignol, Matteo; Dadu, Andrei; Dara, Masoud; Cohen, Ted

2013-01-01

Multidrug-resistant tuberculosis (MDR-TB) is a major concern in countries of the former Soviet Union. The reported risk of resistance among TB cases in the Republic of Moldova is among the highest in the world. We aimed to produce high-resolution spatial maps of MDR-TB risk and burden in this setting. We analyzed national TB surveillance data collected between 2007 and 2010 in Moldova. High drug susceptibility testing coverage and detailed location data permitted identification of sub-regional areas of higher MDR-TB risk. We investigated whether the distribution of cases with MDR-TB risk factors could explain this observed spatial variation in MDR-TB. 3,447 MDR-TB cases were notified during this period; 24% of new and 62% of previously treated patients had MDR-TB. Nationally, the estimated annual MDR-TB incidence was 54 cases/100,000 persons and >1,000 cases/100,000 persons within penitentiaries. We identified substantial geographic variation in MDR-TB burden and hotspots of MDR-TB. Locations with a higher percentage of previously incarcerated TB cases were at greater risk of being MDR-TB hotspots. Spatial analyses revealed striking geographic heterogeneity of MDR-TB. Methods to identify locations of high MDR-TB risk and burden should allow for better resource allocation and more appropriate targeting of studies to understand local mechanisms driving resistance. PMID:23100496

High variability of TB, HIV, hepatitis C treatment and opioid substitution therapy among prisoners in Germany.

PubMed

Müller, Jana; Schmidt, Daniel; Kollan, Christian; Lehmann, Marc; Bremer, Viviane; Zimmermann, Ruth

2017-10-25

In Germany, medical care of prisoners is completely separated from extramural health care. The extent and quality of medical care among prisoners in Germany are therefore largely unknown. We performed a secondary data analysis of pharmacy sales data for tuberculosis (TB), HIV, hepatitis C (HCV) and opioid substitution treatment (OST) delivered to prisons in 11 federal states (FS) in Germany between 01/2012 and 03/2013. The aims of this study were to assess (i) the treatment availability for the selected diseases and OST in German prisons, (ii) the proportion of prisoners treated per FS and overall for TB, HIV, HCV and OST during the study period. Substances unique to or typically used for the treatment of each disease were defined as marker substances with defined daily doses (DDD). For each marker substance we assessed the cumulative number of DDD, the average daily number of DDD (DDD d ) and average treatment prevalence per day in percent (adTP). Accordingly, the DDD d represents one person treated per day and the adTP means the proportion of prisoners treated per day. We compared the adTP of the diseases with previously measured prevalences. We obtained data from pharmacies supplying prisons in 11 of 16 German FS. Of the included prisons, 41% were supplied with medicines for TB, 71% for HIV and 58% for HCV and OST. Twice as many delivered marker substances for TB were indicated for the continuation phase and chemoprevention than the intensive phase. The HIV adTP ranged from 0.06% to 0.94%, HCV adTP ranged from 0.03% to 0.59% and OST adTP ranged from 0% to 7.90%. The overall adTP for the respective treatment was 0.39% for HIV, 0.12% for HCV and 2.18% for OST. According to our findings treatment rates for TB were consistent with the expected TB prevalence, at least in Berlin. HIV treatment seems to be offered to an adequate proportion of estimated infected prisoners. In contrast, the HCV treatment prevalence was low. High variation among FS in provision of all

Neutron spectroscopic study of crystal field excitations in Tb 2Ti 2O 7 and Tb 2Sn 2O 7

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

Zhang, J.; Fritsch, Katharina; Hao, Z.

2014-04-01

We present time-of-flight inelastic neutron scattering measurements at low temperature on powder samples of the magnetic pyrochlore oxides Tb 2Ti 2O 7 and Tb 2Sn 2O 7. These two materials possess related, but different ground states, with Tb 2Sn 2O 7 displaying "soft" spin ice order below T N approx 0.87 K, while Tb 2Ti 2O 7 enters a hybrid, glassy-spin ice state below T g approx 0.2 K. Our neutron measurements, performed at T = 1.5 K and 30 K, probe the crystal field states associated with the J = 6 states of Tb 3+ within the appropriate Fd3-barmmore » pyrochlore environment. These crystal field states determine the size and anisotropy of the Tb 3+ magnetic moment in each material's ground state, information that is an essential starting point for any description of the low temperature phase behavior and spin dynamics in Tb 2Ti 2O 7 and Tb 2Sn 2O 7. While these two materials have much in common, the cubic stanate lattice is expanded compared to the cubic titanate lattice. As our measurements show, this translates into a factor of approx 2 increase in the crystal field bandwidth of the 2J +1 = 13 states in Tb 2Ti 2O 7 compared with Tb 2Sn 2O 7. Our results are consistent with previous measurements on crystal field states in Tb 2Sn 2O 7, wherein the ground state doublet corresponds primarily to mJ = {vert_bar}+-5> and the first excited state doublet to mJ = {vert_bar}+-4>. In contrast, our results on Tb 2Ti 2O 7 differ markedly from earlier studies, showing that the ground state doublet corresponds to a significant mixture of mJ = {vert_bar}+-5>, mJ = {vert_bar}+-4> and mJ = {vert_bar}+-2>, while the first excited state doublet corresponds to a mixture of mJ = {vert_bar}+-4>, mJ = {vert_bar}+-5> and mJ = {vert_bar}+-1>. We discuss these results in the context of proposed mechanisms for the failure of Tb 2Ti 2O 7 to develop conventional long range order down to 50 mK.« less

Diagnostic usefulness of the QuantiFERON-TB gold in-tube test (QFT-GIT) for tuberculous vertebral osteomyelitis.

PubMed

Choi, Sungim; Jung, Kyung Hwa; Son, Hyo-Ju; Lee, Seung Hyun; Hong, Jung Min; Kim, Min Chul; Kim, Min Jae; Chong, Yong Pil; Sung, Heungsup; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2018-05-01

Interferon (IFN)-γ-releasing assay for diagnosing tuberculosis (TB) has shown promise; however, there are only a few reports on usefulness of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral osteomyelitis. All patients presenting at a tertiary hospital between January 2010 and July 2016 with suspected TB vertebral osteomyelitis were retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We used QFT-GIT to measure the IFN-γ response to ESAT-6, CFP-10 and TB7.7. A total of 141 patients were enrolled; 32 (23%) were categorized as having confirmed TB, (1%) as probable TB, 14 (10%) as possible TB and 93 (66%) as not TB. Of these, 16 patients with probable and possible TB were excluded from the final analysis. Chronic granulomas with/without necrosis, acid-fast bacilli stain, M. tuberculosis polymerase chain reaction and cultures for M. tuberculosis were positive in 14 (44%), 12 (38%), 22 (69%) and 28 (88%) patients, respectively, among the 32 patients with confirmed TB. The overall sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive result, and likelihood ratio for a negative result of the QFT-GIT for TB vertebral osteomyelitis were 91% (95% confidence interval [CI], 75-98%), 65% (95% CI, 54-75%), 50% (95% CI, 42-58%), 95% (95% CI, 86-98%), 2.59 (95% CI, 1.89-3.55) and 0.14 (95% CI, 0.05-0.43), respectively. The QFT-GIT appears to be a useful adjunct test for diagnosing TB vertebral osteomyelitis because the negative test results may be useful for excluding a diagnosis of active TB vertebral osteomyelitis.

New diagnostics for latent and active tuberculosis: state of the art and future prospects.

PubMed

Pai, Madhukar; O'Brien, Richard

2008-10-01

Tuberculosis (TB) continues to be the world's most important infectious cause of morbidity and mortality among adults. Nearly 9 million people develop TB disease each year, and an estimated 1.6 million die from the disease. Despite this enormous global burden, case detection rates are low, posing serious hurdles for TB control. Conventional TB diagnosis continues to rely on antiquated tests such as sputum smear microscopy, culture, tuberculin skin test, and chest radiography. These tests have several limitations and perform poorly in populations affected by the HIV epidemic. Conventional tests for detection of drug resistance are time consuming, tedious, and inaccessible in most settings. In this review, we describe recent advances in the diagnosis of latent and active TB, and detection of drug resistance. Although the perfect test will not be ready for large-scale roll-out and integration into routine TB care services for some time, substantial progress has been made in expanding the TB diagnostic product pipeline. With the resurgence of interest in the development of new tools for TB control, and the recent influx of funding and political support, it is likely that the next few years will see the introduction of new diagnostic tools into routine TB control programs.

Local level epidemiological analysis of TB in people from a high incidence country of birth.

PubMed

Massey, Peter D; Durrheim, David N; Stephens, Nicola; Christensen, Amanda

2013-01-22

The setting for this analysis is the low tuberculosis (TB) incidence state of New South Wales (NSW), Australia. Local level analysis of TB epidemiology in people from high incidence countries-of-birth (HIC) in a low incidence setting has not been conducted in Australia and has not been widely reported. Local level analysis could inform measures such as active case finding and targeted earlier diagnosis. The aim of this study was to use a novel approach to identify local areas in an Australian state that have higher TB rates given the local areas' country of birth profiles. TB notification data for the three year period 2006-2008 were analysed by grouping the population into those from a high-incidence country-of-birth and the remainder. During the study period there were 1401 notified TB cases in the state of NSW. Of these TB cases 76.5% were born in a high-incidence country. The annualised TB notification rate for the high-incidence country-of-birth group was 61.2/100,000 population and for the remainder of the population was 1.8/100,000. Of the 152 Local Government Areas (LGA) in NSW, nine had higher and four had lower TB notification rates in their high-incidence country-of-birth populations when compared with the high-incidence country-of-birth population for the rest of NSW. The nine areas had a higher proportion of the population with a country of birth where TB notification rates are >100/100,000. Those notified with TB in the nine areas also had a shorter length of stay in Australia than the rest of the state. The areas with higher TB notification rates were all in the capital city, Sydney. Among LGAs with higher TB notification rates, four had higher rates in both people with a high-incidence country of birth and people not born in a high-incidence country. The age distribution of the HIC population was similar across all areas, and the highest differential in TB rates across areas was in the 5-19 years age group. Analysing local area TB rates and possible

Severe hypovitaminosis D in active tuberculosis patients and its predictors.

PubMed

Wang, Qiuzhen; Liu, Yufeng; Ma, Yan; Han, Lei; Dou, Mei; Zou, Yue; Sun, Limei; Tian, Hong; Li, Tongxia; Jiang, Guofeng; Du, Baoli; Kou, Tingyan; Song, Jiaqi; Kok, Frans J; Schouten, Evert G

2018-06-01

Tuberculosis (TB) patients have a significant vitamin D deficiency (VDD) endemic, which may be closely related to the onset and progress of the disease. The comorbidity of diabetes (DM) and TB has posed an increasing challenge in recent years. However, the influence of DM on TB and the possible mechanism are still uncertain. We carried out this study to identify the nutritional status of vitamin D (VD) in TB patients in a northern city in China (latitude 36° N) and investigate the possible predictors of severe vitamin D deficiency (SVDD). A cross-sectional study including 461 active TB patients (192 with and 269 without DM) were randomly selected from Qingdao Chest Hospital from June 2015 to August 2016. We measured serum 25 hydroxyvitamin D [25(OH)D], and investigated the association between sociodemographic, dietary intake, DM, body mass index (BMI), severity of initial TB signs and symptoms (TB score) and VD status. Multivariate logistic regression analysis was used to define the possible predictors of SVDD. The median serum 25(OH)D concentration was 8.50 ng/mL. Of the 461 TB patients included, 383 (83.1%) had VDD [25(OH)D < 20 ng/mL], and 217 (47.1%) had SVDD [25(OH)D < 8 ng/mL]. The variables associated with serum 25(OH)D concentrations were DM, outdoor activity level, TB score and BMI (p < 0.05). Patients with severe TB score had nearly 5 fold higher risk of having SVDD compared with those in mild subgroup [OR (95% CI) = 4.919 (2.644-9.150), p < 0.001]. Low outdoor activity level also increased the odds of SVDD, while DM and high fish consumption showed protect effects. Severe hypovitaminosis D is prevalent in active TB patients, and the main predictors of SVDD were severe TB score, low outdoor activity, inadequate fish consumption. Lowered serum 25(OH)D may be associated with increased risk of TB in DM. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Special report. TB and health care workers: the challenge for hospitals and their safety directors.

PubMed

1994-06-01

New federal regulations seeking to prevent tubercular infection of health care workers have created conflicts between unions and hospital administrators over the best and cheapest methods of reducing the threat. Though there has been dispute over the particulars, there has been little argument that some steps must be taken, particularly in urban areas, to control the spread of a disease that has rebounded in new and deadly forms in recent years. Most agree that one of the most effective ways to avoid infection is to train employees to identify new hospital arrivals who are likely to have active cases of TB.

Evaluation of coexistence of cancer and active tuberculosis; 16 case series.

PubMed

Çakar, Beyhan; Çiledağ, Aydın

2018-01-01

Tuberculosis is an important risk factor for cancer. Pulmonary TB and lung cancer(LC) may mimic each other especially in the aspect of the clinical and radiological features. The aim of the study was to evaluate the features and risk factors of cases with coexistence cancer and active TB. We retrospectively reviewed the medical records of patients with coexisting TB and cancer a period from 2009 to 2014. We evaluated demographic data, the ways diagnosis of TB cases, the location of TB and cancer, TB treatment results of the cases. We recorded 374 TB cases in our dyspensary at this study period. In 16 (4%) of these cases, a coexistence of cancer and TB was detected. The male/female ratio was 12/4. The mean age was 62,12 ± 15,13 years. There were TST results except three cases. There were ten pulmonary TB and six extra-pulmonary TB (four peripheral lymphadenopathy TB, one abdominal TB lymphadenopathy and one salivary gland TB). Cancer types were as follows; eight lung cancer, two breast cancer, one base of tongue, one endometrium cancer, one hypopharyngeal cancer, one stomach cancer, one bladder cancer and one maxillary cancer. Diagnosis of all cases was confirmed by bacteriologic and/or histopathological examination. Squamous cell carcinoma was the most common type of cancers. This rate was 9/16. All TB cases were new. There were risk factors out of two case in the cases. Five cases were died during TB treatment. Others completed TB treatment without any complication. In our study, the coexistence of LC and pulmonary TB was more common. The local immunity is deteriorated in cancer cases. If there is pulmonary infiltrates in lung or peripheral lymphadenopathy, we must search tuberculosis too out of metastatic lesion and other infectious diseases. We should not make delay in the diagnosis of active TB in cancer cases.

Vitamin D status and TB treatment outcomes in adult patients in Tanzania: a cohort study.

PubMed

Mehta, Saurabh; Mugusi, Ferdinand M; Bosch, Ronald J; Aboud, Said; Urassa, Willy; Villamor, Eduardo; Fawzi, Wafaie W

2013-11-18

Vitamin D is an immunomodulator and can alter response to tuberculosis (TB) treatment, though randomised trials have been inconclusive to date. We present one of the first comprehensive analysis of the associations between vitamin D status and TB treatment, T-cell counts and nutritional outcomes by HIV status. Cohort study. Outpatient clinics in Tanzania. 25-hydroxyvitamin D levels were assessed in a cohort of 677 patients with TB (344 HIV infected) initiating anti-TB treatment at enrolment in a multivitamin supplementation (excluding vitamin D) trial (Clinicaltrials.gov identifier: NCT00197704). Information on treatment outcomes such as failure and relapse, HIV disease progression, T-cell counts and anthropometry was collected routinely, with a median follow-up of 52 and 30 months for HIV-uninfected and HIV-infected patients, respectively. Cox and binomial regression, and generalised estimating equations were used to assess the association of vitamin D status with these outcomes. Mean 25-hydroxyvitamin D concentrations at enrolment were 69.8 (±21.5) nmol/L (27.9 (±8.6) ng/mL). Vitamin D insufficiency (<75 nmol/L) was associated with a 66% higher risk of relapse (95% CI 4% to 164%; 133% higher risk in HIV-uninfected patients). Each unit higher 25-hydroxyvitamin D levels at baseline were associated with a decrease of 3 (p=0.004) CD8 and 3 (p=0.01) CD3 T-cells/µL during follow-up in patients with HIV infection. Vitamin D insufficiency was also associated with a greater decrease of body mass index (BMI; -0.21 kg/m(2); 95% CI -0.39 to -0.02), during the first 8 months of follow-up. No association was observed for vitamin D status with mortality or HIV disease progression. Adequate vitamin D status is associated with a lower risk of relapse and with improved nutritional indicators such as BMI in patients with TB, with or without HIV infection. Further research is needed to determine the optimal dose of vitamin D and effectiveness of daily vitamin D supplementation

Steps on a journey to TB control in Solomon Islands: a cross-sectional, mixed methods pre-post evaluation of a local language DVD.

PubMed

Massey, Peter D; Asugeni, Rowena; Wakageni, John; Kekeubata, Esau; Maena'aadi, John; Laete'esafi, John; Waneagea, Jackson; Asugeni, Vunivesi; MacLaren, David; Speare, Richard

2015-02-03

In Solomon Islands many people with Tuberculosis (TB) have challenges in accessing services because of socio-cultural, geographic and health service reasons, resulting in delays in TB treatment and low detection rates. The purpose of this project was to (i) develop a local language audio-visual resource (DVD) about TB (ii) share this resource with people in remote villages and (iii) evaluate the process and outcomes. The project involved the development and evaluation of a DVD in local Kwaio language. The DVD included five short videos based on the Australian Respiratory Council TB Education Flipchart. The DVD also included short videos of: traditional music/chanting (ai'imae); drama that presented an allegory of TB; and a short documentary on the redevelopment of the local TB Ward. A mixed-methods approach evaluated changes in TB knowledge and investigated the impact of the DVD. The DVD was recorded and produced in March-June 2013 and screened in 41 villages and hamlets. The pre-post DVD survey was completed by 64% (255/400) of people who viewed the DVD in the villages. Pre-DVD survey responses showed a moderate to high knowledge about TB signs, symptoms and treatment but 76/255 (30%) stated TB was caused by sorcery and 85/255 (33%) incorrectly stated that TB medication should be stopped when a patient feels better. The post-DVD survey showed a significant increase in people in coastal villages reporting (i) a 3-week cough would trigger a medical assessment and (ii) TB is mainly spread through the air. Statements that TB is not caused by sorcery increased post-DVD in both coastal and mountain villages, however belief in sorcery in mountain villages remained high at 20/70 (29%). The local DVD resource was developed within local cultural understandings and oral traditions of Kwaio people. Using modern but accessible DVD technology generated a lot of interest about the disease and the stories. The project evaluation indicates that current delays in seeking treatment

Enthalpy of Mixing in Al–Tb Liquid

DOE PAGES

Zhou, Shihuai; Tackes, Carl; Napolitano, Ralph

2017-06-21

The liquid-phase enthalpy of mixing for Al$-$Tb alloys is measured for 3, 5, 8, 10, and 20 at% Tb at selected temperatures in the range from 1364 to 1439 K. Methods include isothermal solution calorimetry and isoperibolic electromagnetic levitation drop calorimetry. Mixing enthalpy is determined relative to the unmixed pure (Al and Tb) components. The required formation enthalpy for the Al3Tb phase is computed from first-principles calculations. Finally, based on our measurements, three different semi-empirical solution models are offered for the excess free energy of the liquid, including regular, subregular, and associate model formulations. These models are also compared withmore » the Miedema model prediction of mixing enthalpy.« less

Targeted screening and treatment for latent tuberculosis infection using QuantiFERON®-TB Gold is cost-effective in Mexico

PubMed Central

Burgos, J. L.; Kahn, J. G.; Strathdee, S. A.; Valencia-Mendoza, A.; Bautista-Arredondo, S.; Laniado-Laborin, R.; Castañeda, R.; Deiss, R.; Garfein, R. S.

2009-01-01

SUMMARY OBJECTIVE To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. DESIGN We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON®-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. RESULTS Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. CONCLUSIONS In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective. PMID:19723375

Socio-demographic and AIDS-related factors associated with tuberculosis stigma in southern Thailand: a quantitative, cross-sectional study of stigma among patients with TB and healthy community members

PubMed Central

2011-01-01

Background Tuberculosis (TB) remains one of the most important infectious diseases worldwide. A comprehensive approach towards disease control that addresses social factors including stigma is now advocated. Patients with TB report fears of isolation and rejection that may lead to delays in seeking care and could affect treatment adherence. Qualitative studies have identified socio-demographic, TB knowledge, and clinical determinants of TB stigma, but only one prior study has quantified these associations using formally developed and validated stigma scales. The purpose of this study was to measure TB stigma and identify factors associated with TB stigma among patients and healthy community members. Methods A cross-sectional study was performed in southern Thailand among two different groups of participants: 480 patients with TB and 300 healthy community members. Data were collected on socio-demographic characteristics, TB knowledge, and clinical factors. Scales measuring perceived TB stigma, experienced/felt TB stigma, and perceived AIDS stigma were administered to patients with TB. Community members responded to a community TB stigma and community AIDS stigma scale, which contained the same items as the perceived stigma scales given to patients. Stigma scores could range from zero to 30, 33, or 36 depending on the scale. Three separate multivariable linear regressions were performed among patients with TB (perceived and experience/felt stigma) and community members (community stigma) to determine which factors were associated with higher mean TB stigma scores. Results Only low level of education, belief that TB increases the chance of getting AIDS, and AIDS stigma were associated with higher TB stigma scores in all three analyses. Co-infection with HIV was associated with higher TB stigma among patients. All differences in mean stigma scores between index and referent levels of each factor were less than two points, except for incorrectly believing that TB